#a mouse modified for cancer research’s purpose is to be used in cancer research

[ookaookaooka]

continuing on the tags on the last post, the idea of loving the thing that will one day eat you because it has spent your whole life feeding and caring for you is so important to me

[freefartexpert]

Mice Model Market to be Worth $2.48 Billion by 2030 - Exclusive Report by Meticulous Research®

According to a new market research report titled, ‘Mice Model Market by Mice Type (Inbred, Hybrid), Services (Breeding, Cryopreservation, Quarantine), Technology (CRISPR, Nuclear Transfer), Application (Oncology, Cardiology, Neuro), End User (Research, Academia, Pharmaceutical) - Global Forecast to 2030,' published by Meticulous Research®, the mice model market is projected to reach $2.48 billion by 2030 at a CAGR of 6.5% from 2023 to 2030.

Mice models are laboratory mice that are used as experimental models in scientific research studies. These mice are bred and genetically modified in such a way that it mimics the pathophysiology of human diseases. They are used for a wide range of research purposes, such as drug discovery, cancer research, immunology, and neurology. Mouse models are especially important in drug discovery & testing of new drugs as they give valuable insights into the absorption, distribution, metabolism, and excretions of drug molecules.

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The diseases in mice have a similar pathophysiological characteristics as humans. In addition, the genomic composition of mice is largely similar to humans. Hence, mice models are widely preferred as an ideal candidate for experimental research studies.

The mice model market is driven by factors such as the advantages of mice as an animal model for studying human diseases, the rising prevalence of cancer, the increasing number of grants for research studies, and the rising demand for personalized medicine. Furthermore, the technological advancements & innovations in mice models are expected to provide significant opportunities for the growth of this market.

However, ethical concerns and regulatory restrictions are expected to hinder the growth of this market to a certain extent. In addition, factors such as the lack of skilled personnel for performing animal studies and the high cost of mice models are the major challenges to market growth.

Rising Demand for Personalized Medicine to Drive Mice Model Market

Currently, personalized medicines are highly preferred for treating many genetic diseases. Mice models help facilitate the development of personalized medicines. Humanized mice models are also gaining popularity in the study of personalized medicines. Especially in cancer research, personalized mice models can be created by implanting a piece of the patient’s tumor in the immune-compromised mice. The mice can then be tested for response to various personalized cancer drugs. These studies yield promising personalized drug therapies for cancer. Pharmaceutical companies have also been reported to use mouse models derived from cancer cell lines to test and improve the effectiveness of new anticancer drugs. The rising demand for personalized medicines would thus drive the demand for mice models in research studies.

The report includes an extensive assessment of the market based on mice type, service, technology, application, end user, and geography. The study also provides valuable insights into the key growth strategies adopted by major market players in the last three to four years.

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The mice model market is segmented based on mice type, services, technology, mode, application, end user, and geography. The study also evaluates industry competitors and analyzes the market at the regional and country levels.

Based on mice type, in 2023, the inbred mice segment is expected to account for the largest share of the mice model market. The large market share of this segment is attributed to the advantages of the inbred mice for conducting scientific studies, such as a high degree of genetic homogeneity and consistency, they are easy-to-produce and cost-effective compared to other mice types, and have a wide range of application areas in research.

Based on service, in 2023, the breeding segment is expected to account for the largest share of the mice model market. The large market share of this segment is attributed to the high demand for breeding services to produce customized solutions based on research needs and higher quality & consistency of the mice, which can lead to reliable and reproducible experimental results.

Based on technology, in 2023, the CRISPR/CAS9 segment is expected to account for the largest share of the mice model market. The large market share of this segment is attributed to the advantages of the technology to provide precise, targeted specific gene modifications in mice in a cost-effective manner compared to other genetic engineering techniques and its ability to create genetically modified mice models quickly and efficiently.

Based on mode, in 2023, the outsourced segment is expected to account for the largest share of the mice model market. The large market share of this segment is attributed to the increased preference by research organizations to outsource animal research to service providers to save operational costs, reduce labor requirements and get access to specialized expertise.

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Based on application, in 2023, the oncology studies segment is expected to account for the largest share of the mice model market. The large market share of this segment is attributed to the increased demand for mice models for oncology studies to test the efficacy and safety of potential cancer therapies, increased demand for personalized medicines, and increased funding for cancer research.

Based on end user, in 2023, the pharmaceutical & biotechnology companies segment is expected to account for the largest share of the mice model market. The large market share of this segment is attributed to the increased use of mice models in the pharmaceutical & biotechnology companies for preclinical drug development studies, increased pharmaceutical R&D expenditure, and growing demand to rapidly develop new personalized medicines.

Based on geography, in 2023, North America is expected to account for the largest share of the mice model market, followed by Europe, and Asia-Pacific. North America’s large market share is primarily attributed to its high R&D expenditure and research funding in the region, robust infrastructure for conducting research, favorable government initiatives, and presence of key market players in the region. However, Asia-Pacific is slated to record the highest CAGR in the mice model market during the forecast period. The growth of this market is driven by the rapidly growing pharmaceutical & biotechnology industry in the region, increasing R&D expenditure, and increasing government funding for research projects, especially in China and India.

Some of the key players operating in this market are Charles River Laboratories International, Inc. (U.S.), The Jackson Laboratory (U.S.), Laboratory Corporation of America Holdings (U.S.), Horizon Discovery Group plc (U.K.), Trans Genic Inc. (Japan), GenOway S.A. (France), Taconic Biosciences, Inc.(U.S.), Envigo Ltd (U.S.), Janvier Labs (France), ingenious targeting laboratory (U.S.), Harbour Antibodies B.V. (China) (Subsidiary of HBM Holdings), Crescendo Biologics Ltd. (U.K.), Deltagen Inc. (U.S.), and ImmunoGenes Kft. (Hungary).

To gain more insights into the market with a detailed table of content and figures, click here: https://www.meticulousresearch.com/product/mice-model-market-4151

Scope of the Report:

Mice Model Market, by Mice Type

Inbred Mice

Genetically Engineered Mice

Outbred Mice

Hybrid/Congenic Mice

Conditioned/Surgically Modified Mice

Spontaneous Mutant Mice

Other Types

(Other types majorly include knockout mice model, carcinogen-induced mice model, and transplantation mice model) Mice Model Market, by Service

Breeding

Cryopreservation

Model-in Licensing

Genetic Testing

Quarantine

Other Services

(Other Services majorly include in-vivo & in-vitro pharmacology, rederivation, and genetically engineered model services) Mice Model Market, by Technology

CRISPR/CAS9

Embryonic Stem Cell Injection

Nuclear Transfer

Other Technologies

(Other Technologies majorly include microinjection and chemical mutagenesis)

Mice Model Market, by Mode

Outsourced

In-house 

Mice Model Market, by Application

Oncology Studies

Cardiovascular Studies

Genetic Studies

Endocrine Metabolic Studies

Neurological Studies

Immunology & Inflammation studies

Other Applications

(Other applications include infectious disease studies, fibrosis, and regenerative medicine)

Mice Model Market, by End User

Pharmaceutical & Biotechnology Companies

Academic & Research Institutes

Contract Research Organizations

Other End Users

Other end users majorly include cosmetic companies, government agencies, etc.

Mice Model Market, by Geography

North America

U.S.

Canada

Europe

Germany

France

U.K.

Italy

Spain

Rest of Europe (RoE)

Asia-Pacific

China

Japan

India

Rest of Asia-Pacific (RoAPAC)

Latin America

Brazil

Mexico

Rest of Latin America (RoLATAM)

Middle East & Africa

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https://www.meticulousresearch.com/product/genetic-testing-market-5370 About Meticulous Research®

Meticulous Research® was founded in 2010 and incorporated as Meticulous Market Research Pvt. Ltd. in 2013 as a private limited company under the Companies Act, 1956. Since its incorporation, the company has become the leading provider of premium market intelligence in North America, Europe, Asia-Pacific, Latin America, and the Middle East & Africa.

The name of our company defines our services, strengths, and values. Since the inception, we have only thrived to research, analyze, and present the critical market data with great attention to details. With the meticulous primary and secondary research techniques, we have built strong capabilities in data collection, interpretation, and analysis of data including qualitative and quantitative research with the finest team of analysts. We design our meticulously analyzed intelligent and value-driven syndicate market research reports, custom studies, quick turnaround research, and consulting solutions to address business challenges of sustainable growth.

Contact: Mr. Khushal Bombe Meticulous Market Research Inc. 1267 Willis St, Ste 200 Redding,  California, 96001, U.S. USA: +1-646-781-8004 Europe : +44-203-868-8738 APAC: +91 744-7780008 Email- sales@meticulousresearch.com  Visit Our Website: https://www.meticulousresearch.com/ Connect with us on LinkedIn- https://www.linkedin.com/company/meticulous-research Content Source: https://www.meticulousresearch.com/pressrelease/309/mice-model-market-2030

[juniperpublishers-jdvs]

Review on Applications of Genetic Engineering And Cloning in Farm animals-Juniper Publishers

JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF DAIRY & VETERINARY SCIENCES

Abstract

Genetic engineering involves producing transgenic animal’s models by using different techniques such as exogenous pronuclear DNA microinjection in zygotes, injection of genetically modified embryonic stem cells into blastocysts and retrovirus mediated gene transfer. It is highly applicable and crucial technology which involves increasing animal production and productivity, increases animal disease resistance and biomedical application. Cloning involves the production of animals that are genetically identical to the donor nucleus. The most commonly applied and recent technique is somatic cell nuclear transfer in which the nucleus from body cell is transferred to an egg cell to create an embryo that is virtually identical to the donor nucleus. There are different applications of cloning which includes: rapid multiplication of desired livestock, animal conservation and research model. However, at present it is an inefficient process due to parturition difficulties, placental abnormalities and post-natal viabilities. Beside to this Food safety, animal welfare, public and social acceptance and religious institutions are the most common challenges for the development of this technology. In developing country including Ethiopia the science is not yet conceived and the concerned body should pay great attention to such valuable aspects of biotechnological advancements.

Keywords:   Cloning; Genetic engineering; Nuclear transfer; Transgenic animal; Animal welfare

Abbreviations:   DNA: Deoxy ribose Nucleic Acid; SCNT: Somatic Cell Nuclear Transfer; ES: Embryonic stem; EGF: Epidermal Growth factor; TGF: Transforming Growth Factor; MMA: Mastitis Metritis Agalactia; NT: Nuclear Transfer; FDA: Food and Drug Administration; MAS: Marker-Assisted Selection; MHC: Major Histocompatibility Complex

Introduction

Biotechnology has contributed to the genetic improvement of farm animals for decades, through artificial insemination and embryo transfers. The advent of modern biotechnology provides new avenues for genetic improvement in the production of farm animals. During the past decades, however, the term biotechnology has come to be associated more with molecular- based technologies, such as gene cloning and genetic engineering [1]. Now a days, biotechnology typically genetic engineering and cloning play an important role on both basic and applied research becoming an essential tool for the understanding of the biology and development of animal biotechnology. Such technology presents a wide range of applications, such as the production of biopharmaceuticals, studies on gene expression and its regulation, the improvement of animal production, production of herds resistant to specific diseases and many other biomedical and medical purposes [2].

Through the biotechnology of gene therapy, scientists are making efforts at curing genetic diseases by attempting to replace defective genes with the correct version and also used to produce more effective and efficient vaccines, therapeutic antibodies, antibiotics and other pharmaceuticals. There are more than 370 drug products and vaccines obtained through biotechnology currently in clinical trials, targeting more than 200 diseases including various cancers, Alzheimer’s disease, heart disease, diabetes, multiple sclerosis and arthritis [3].

A genetically engineered or transgenic animal is an animal that carries a known sequence of recombinant Deoxy ribose Nucleic Acid (DNA) in its cells, and which passes that DNA onto its offspring [4]. Recombinant DNA refers to DNA fragments that have been joined together in a laboratory. The resultant recombinant DNA construct is usually designed to express the  proteins that are encoded by the genes included in the construct, when present in the genome of a transgenic animal. Because the genetic code for all organisms is made up of the same four nucleotide building blocks, this means that a gene makes the same protein whether it is made in an animal, a plant or a microbe. Proteins that have been expressed in transgenic animals include therapeutic proteins for the treatment of human diseases [5]; proteins that enable animals to better resist disease and proteins that result in the production of more healthful animal products (milk, eggs or meat) for consumers [6].

Cloning refers to producing genetically identical individual to donor cells and copying gene, which involves the creation of an animal or individual that derives its genes from a single other individual; it is also referred as asexual reproduction [7]. Cloned offspring in human and farm animals sometimes produced in nature when early embryo splits in to two (or sometime, more) species of just a few days after fertilization, before the cells have become too specialized. However, there are a number of artificial methods to produce genetically identical mammals. Of these, the nuclear cloning technology is considered to have the greatest potential application for animal agriculture and medicine [8].

Scientists have been attempting to clone animals through nuclear transfer of somatic cell (SCNT) for several decades. SCNT is an efficient way to create herds of genetically modified cloned animals, preservation of endangered species, production of human therapeutic proteins in genetically modified clone animals, use of genetically modified cloned animals as a source of organs for human transplantation, gaining a better understanding of cellular differentiation and reprogramming capabilities that could be the basis for human cellular therapies, and better models to study new treatments for human disease. However, SCNT cloning thus far has been very inefficient process and cloned animals have exhibited serious health problems [9].

The genetic engineering of animals has increased significantly in recent years, and the use of this technology brings with it ethical issues, some of which relate to animal welfare defined by the World Organization for Animal Health [10]. It is important to try to reflect societal values within scientific practice and emerging technology, especially publicly funded efforts that aim to provide societal benefits, but that may be deemed ethically contentious [11]. Even though, genetic engineering and cloning are interesting sciences with wide range of application, they have also some uncertainties and challenges and further investigation are needed to develop the technology. Therefore the objectives of this seminar paper area follow

• To review the application of genetic engineering and cloning,

• To highlight the concepts, techniques and challenges of genetic engineering and cloning.

Literature Review

Review History of genetic engineering and cloning time line

Genetic modification caused by human activity has been occurring since around 12,000 BC, when humans first began to domesticate organisms. Genetic engineering is the direct manipulation of an organism’s genome using certain biotechnology techniques that have only existed since the 1970s. Genetic engineering as the direct transfer of DNA from one organism to another was first accomplished by Herbert Boyer and Stanley Cohen in 1973 [12].

Human directed genetic manipulation was occurring much earlier, beginning with the domestication of plants and animals through artificial selection. The dog is believed to be the first animal domesticated, possibly arising from a common ancestor of the wolf. The first genetically modified animal was a mouse created in 1973 by Rudolf Jahnish [12]. Cloning research has been underway since the 1890s.The first animal cloning research was an attempt to produce identical organisms by splitting animal embryos at early stages of development. Work continued in the field of animal cloning and in 1952 the nuclear transfer procedure was invented. Work with nuclear transfer resulted in the successful cloning of many species from embryonic nuclei. In the 1980’s, nuclear transfer was used to clone cattle and sheep using cells taken directly from early embryos [13].

In 1995, living lambs, named Megan and Morag, were created for the first time from cultured cells. However, prior to 1997 the word clone conjured up images of creatures from Jurassic Park or other works of science fiction in the minds of most people. In July of 1996, Scottish scientists created the first animal cloned from an adult cell. On July 5, 1996, Dolly the sheep was born at the Rollin Institute in Edinburgh Scotland. The announcement of her birth in early 1997 shocked the scientific community and stirred debate over the possibility of cloning humans [14]. A process known as cell nuclear replacement created Dolly by transferring a mammary cell of a six-year-old white Welsh Mountain sheep into the egg cell of a Scottish blackface ewe. Since Dolly's birth, several other species have successfully been cloned including: mice, cattle, sheep, pigs, goats, rabbits and a cat [15] (Table 1).

Genetic engineering (transgenic animal) model

Genetic engineering is the name of a group of techniques used for direct genetic modification of organisms or population of organisms using recombination of DNA. These procedures are of use to identify, replicate, modify and transfer the genetic material of cells, tissues or complete organisms. Most techniques are related to the direct manipulation of DNA oriented to the expression of particular genes [16].

In a broader sense, genetic engineering involves the incorporation of DNA markers for selection (marker-assisted selection, MAS), to increase the efficiency of the so called traditional methods of breeding based on phenotypic information [17]. Transgenic animals can be created to gain knowledge of gene function and further decipher the genetic code, study gene control in complex organisms, build genetic disease models, improve animal production traits, and produce new animal products [18].

Technique of genetic engineering

Exogenous pronuclear DNA microinjection in zygotes:

Micro-injection is the first successful approach for the creation of transgenic animals based on the injection of a foreign DNA construct into a fertilized oocyte. The construct integrates randomly into the host oocyte genome, subsequently the zygote continues embryonic development and the embryo is transferred to a foster mother and eventually develops to a transgenic animal. However, this method has strong limitations: on average, less than 1% of embryos injected and 10% of animals born are transgenic, genes can only be added, not replaced or deleted, and multiple copies of the transgene are inserted at random, hindering the correct regulation of gene expression and possibly interfering with endogenous gene function. This requires large amounts of oocytes to be injected, as the overall efficiency of the process is very low [19].

Injection of genetically modified embryonic stem (ES) cells into blastocysts

Embryonic stem cells are derived from embryos at a very early stage (the blastula), and possess the important characteristic of pluripotency. Pluripotency is the ability of these cells to differentiate to any of the cell types and tissues found in the adult organism. Embryonic stem cells can be grown in culture for many passages and can be subjected to transformation with transgene constructs, resulting in modifications of their genome. The constructs used not only permit the selection of successfully transformed cells, but also allow gene targeting to be accomplished. Thus, genes can be specifically introduced, replaced or deleted (so-called knock-ins and knock-outs) [20].

Injection of genetically modified embryonic stem (ES) cells into blastocysts, mainly through the feature of gene targeting, allows a broad variety of genetic modifications to be introduced. For many years, several laboratories worldwide have tried to produce ES cells from farm animals, and although some success has been claimed, no robust and reproducible method has been published. Indeed, even in mice the production of ES cells is a costly and labor-intensive technology [18].

Retrovirus mediated gene transfer

Transgenesis may also be accomplished by employing virus- derived vectors, namely vectors based on the retrovirus-class of lenti viruses [21]. Genes that are essential for viral replication are deleted from the viral genome, maintaining only the capacity for integration of the viral genome into the host genome. The parts of the viral genes can replaced by the transgene of interest, then Viruses carrying the modified gene are produced in-vitro and subsequently injected into the perivitelline space of the zygote, resulting in infection of the zygote and integration of the viral genome into the host genome. Transgenesis rates reaching up to 100% of injected embryos have been described [22].

Major drawbacks of this method are a limited transgene size and random transgene integration. Random and possibly multiple transgene integration may lead to position effects, disturbance of the host genome and dose effects, as is the case with pronuclear injection. Solving these problems holds great promise for the further development and application of lentiviral vectors [22].

Uses of animal genetic engineering

Increase animal disease resistance

Genetic engineering of agricultural animals has the potential to improve disease resistance by introducing specific genes into livestock. Identification of single genes in the major histocompatibility complex (MHC), which influence the immune response, was instrumental in the recognition of the genetic basis of disease resistance/susceptibility [23]. The application of transgenic technology to specific aspects of the immune system should provide opportunities to genetically engineer livestock that are healthier and have superior disease resistance. One specific example where transgenesis has been applied to disease resistance in livestock is the attempt to produce cattle resistant to mastitis. Lysostaphin is an antimicrobial peptide that protects mammary glands against Staphylococcus aurous infection by killing the bacteria in a dose-dependent manner. Transgenic dairy cows that secrete lysostaphin into their milk have been produced to address the mastitis issue. The application of nuclear transfer technology, or cloning, will enable the augmentation of beneficial alleles and/or the removal (via gene knock-out) of undesirable alleles associated with disease resistance or susceptibility. By knocking-out the intestinal receptor for the K88 antigen lead to the absence of this antigen has been shown to confer resistance to infection of K88-positive E. coli [24].

Enhance growth and meat trait

Altering the fat or cholesterol composition of the carcass is valuable benefit that can be delivered via genetic engineering. By changing the metabolism or uptake of cholesterol and/ or fatty acids, the content of fat and cholesterol of meats, eggs and cheeses could be lowered. There is also the possibility of introducing beneficial fats such as the omega-3 fatty lipoprotein receptor gene and hormones like leptin are also potential targets that would decrease fat and cholesterol in animal products [6].

The use of genetic engineering to improve feed efficiency and/or appetite could profoundly impact livestock production and deliver significant benefits to producers, processors, and consumers. Increased uptake of nutrients in the digestive tract, by alteration of the enzyme profiles in the gut, could increase feed efficiency. The ability to introduce enzymes such as Phytase or xylanase into the gut of species where they are not normally present, such as swine or poultry, is particularly attractive [25].

The introduction of phytase would increase the bioavailability of phosphorus from phytic acid in corn and soy products. Golovan and his colleagues reported that the production of transgenic pigs expressing salivary phytase as early as seven days of age. The salivary phytase provided essentially complete digestion of the dietary phytate phosphorus in addition to reducing phosphorus output in waste by up to 75%. Furthermore, transgenic pigs required almost no inorganic phosphorus supplementation to the diet to achieve normal growth. The use of phytase transgenic pigs in commercial pork production could result in significantly decreased environmental phosphorus pollution from livestock operations [25].

Improve wool production

The control of the quality, color, yield and ease of harvest of hair, wool and fiber for fabric and yarn production has been an area of focus for genetic engineering in livestock. The manipulation of the quality, length, fineness and crimp of the wool and hair fiber from sheep and goats has been examined using transgenic methods. Transgenic methods also allow improvements to fiber elasticity, surface and strength. Decreasing the surface interactions between fibers could decrease shrinkage of garments made from such fibers [26].

Desired milk yield and composition

Advances in recombinant DNA technology have provided the opportunity either to improve the composition of milk or to produce entirely novel proteins in milk. These changes may add value to, as well as increase, the potential uses of milk. The improvement of livestock growth or survivability through the modification of milk composition requires production of genetically engineered animals that:

1) Produce a greater quantity of milk,

2) Produce milk of higher nutrient protein content. The major nutrients in milk are protein, fat and lactose.

Elevation of these components can improve growth and health of the developing offspring that consumer the enhanced milk [27].

Changing milk composition may improve animal growth is the addition or supplementation of beneficial naturally occurring hormones, growth factors or bioactive factors to the milk through the use of genetic engineering. It has been suggested that bioactive substances in milk possess important functions in the neonate with regard to regulation of growth, development and maturation of the gut, immune system and endocrine organs [28]. Transgenic alteration of milk composition has the potential to enhance the production of certain proteins and/or growth factors that are deficient in milk. The increased expression of a number of these proteins in milk may improve growth, development, health and survivability of the developing offspring. Some of these factors are insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), transforming growth factor (TGF) and lactoferrin [29].

The properties’ of milk that bear consideration for modification are those that affect human and animal health. It has been shown that specific antibodies can be produced in genetically engineered animals. It is possible to produce antibodies in the mammary gland that are capable of preventing mastitis in cattle, sheep and goats and mastitis metritis agalactia (MMA) in pigs, and/or antibodies that aid in the prevention of domestic animal or human diseases. Other role is to increase proteins that have physiological roles within the mammary gland itself such as lactalbumin, lysozyme, lysostaphin or other antimicrobial peptides.

It is important to consider the use of transgenics to increase specific components, which are already present in milk for manufacturing purposes. An example might be to increase one of the casein components in milk. This could increase the value of milk in manufacturing processes such as production of cheese or yogurt. One might also alter the physical properties of a protein such as casein [30].

Human cell-based therapies

Direct applications of Nuclear Transfer (NT) technology in human therapies, principally therapeutic cloning as opposed to human reproductive cloning [31]. Patients with diseases or disorders in tissues like insulin-dependent diabetes, muscular dystrophy, spinal cord injury, certain cancers and various neurological disorders, including Parkinson’s disease could potentially generate their own immunologically compatible cells for transplantation, which would offer lifelong treatment without tissue rejection [32]. Initially, this approach could employ human NT and embryonic stem cells but, the use of this technique in human is controversial. In the longer term, however, fundamental understanding of reprogramming will enable one cell type to be directly trans-differentiated into another cell type specifically required for cell-based therapy [33].

One major application of animal transgenesis is the production of pharmaceutical products, also known as animal pharming. Since many human proteins cannot be produced in microorganisms and production in cell culture is often laborintensive with low yields, the production of biopharmaceuticals in transgenic animal bioreactors is an attractive alternative [34]. Many human proteins cannot be produced in micro-organisms, since they lack post-translational modification mechanisms that are essential for the correct function of many human proteins. Pharmaceutical proteins or other compounds can be produced in a variety of body fluids, including milk, urine, blood, saliva, chicken egg white and seminal fluid, depending on the use of tissue-specific promoters [35].

Protein based drug

Protein-based drugs differ from protein products synthesized in the blood in that they are produced in-vivo by other organs. This technology is even being applied to the development of complex proteins such as monoclonal antibodies as well as many other important human replacement proteins and protein drugs such as polyclonal antibodies and plasminogen activator [3]. Researchers recently created a line of transgenic swine that produce recombinant human erythropoietin a naturally occurring human hormone that boosts the body’s production of red blood cells. The transgenic swine produced the hormone in their milk through a potentially more efficient and lower cost process than traditional methods patients with diseased kidneys no longer able to produce the protein, as well as cancer patients being treated with chemotherapy who develop anemia as a consequence of bone marrow depletion from their cancer drug regimens. Erythropoetin-based drugs are some of the most widely used protein-based drugs, and are expensive to manufacture [36].

Xenotransplantation

Xenotransplantation is the transplantation of organs or cells from one species to another. Human to human transplantation are sometimes difficult due to scarcity of donor organ. Pig is considered the preferred candidate for xenotransplantation because of physiological compatibility and breeding characteristics. Large numbers of pathogen free pigs can be raised to provide organs for transplantation in to humans [37]. However, one of the problems associated with using pig organs for xenotransplantation is that the immune system of the human recipient attacks the transplanted organ, causing transplant rejection. Pigs naturally produce a sugar, called a1, 3-galactosyltransferase (aGalT) on the surface of their cells, which the human immune system recognizes as foreign [38]. The human immune system then forms antibodies to attack the cells which produce that sugar, resulting in tissue rejection. Through the use of genetic engineering and cloning, scientists have created pigs which are deficient for aGalT and do not produce it on the surface of their cells. Transfer of these genetically engineered tissues and organs into baboon recipients has increased the length of time before the organs are rejected by the recipient’s immune system.

Techniques of cloning

Cloning is a powerful technique by producing genetically identical individuals and potentially it could be used for multiplication of elite animals and minimizes the genetic variation in experimental animals. It can be used for the conservation as well as propagation of endangered species. It may be used also as a tool for the production of stem cells for therapeutic purposes, as therapeutic cloning. Cloning using somatic cells offers opportunities to select and multiply animals of specific merits. Cloned offspring in humans and animals are sometimes produced in nature when the early embryo splits in two (or sometimes, more) pieces just a few days after fertilization, before the cells have become too specialized. However, there are also a number of artificial methods to produce genetically identical mammals. Of these, the nuclear cloning methodology is considered to have the greatest potential application for animal agriculture and medicine [8].

Somatic Cell Nuclear Transfer (SCNT)

The transfer of a cell nucleus from a body cell into an egg from which the chromosomes have been removed or inactivated; is method used for cloning of organisms. Once the genome transferred with the egg cell then one cell embryo is created and the process of cloning is completed and further development of the clone can occur [39] (Figure 1).

Embryo splitting (embryo twining)

Embryo splitting may be considered the first true cloning procedure involving human intervention, and was first described by Willesden and Polge in 1981, when monozygotic twin calves were produced. Embryo splitting or the mechanical separation of cells can be used in very early embryos. Two-cell embryos derived from either in vitro fertilization or embryo rescue following in vivo fertilization are held in place with micropipettes under a microscope.

The zonapellucida (the clear layer of protein surrounding the oocyte and fertilized ovum) of these embryos is opened, and the two-celled embryo is then split into individual cells with a finely drawn needle or pipette. One of the cells is left in the original zonapellucida and the other is either placed into an empty zonapellucida or allowed to develop without a zonapellucida. These so-called demi-embryos can be cultured in vitro for a few days, inspected for appropriate growth and then transferred directly to synchronized recipient dams or frozen for future use (Figure 2).

Application of cloning

Rapid multiplication of desired livestock: Cloning could enable the rapid dissemination of superior genotypes from nucleus breeding flocks and herds, directly to commercial farmers. Genotypes could be provided that are ideally suited for specific product characteristics, disease resistance, or environmental conditions. Cloning could be extremely useful in multiplying outstanding F1 crossbred animals, or composite breeds, to maximize the benefits of both heterosis and potential uniformity within the colonal family [8]. These genetic gains could be achieved through the controlled release of selected lines of elite live animals or cloned embryos. More appropriately, given that cloning is not particularly efficient at present: a niche opportunity exists in the production of small numbers of cloned animals with superior genetics for breeding. These could be clones of performance tested animals, especially sires. This would be particularly relevant in the sheep and beef industries, where cloned sires could be used in widespread natural mating to provide an effective means of disseminating their superior genetics. This could be used as a substitute for artificial insemination, which in these more extensive industries is often expensive and inconvenient [40].

Animal conservation: Cloning can be used along with other forms of assisted reproduction to help preserve indigenous breeds of livestock, which have production traits and adaptability to local environments that should not be lost from the global gene pool. In some situations, inter-species NT and embryo transfer may be used to aid the conservation of some exotic species. At the very least, it is appropriate to consider the cryopreservation of somatic cells from these endangered animals as insurance against further Research model losses in diversity. Cryobanking of somatic cells from rare and endangered birds and animals against further losses of diversity or possible extinction of Wildlife to preserve endangered indigenous breeds of livestock adapted to particular environments [41].

Research model

Sets of cloned animals could be effectively used to reduce genetic variability and reduce the numbers of animals needed for some experimental studies. This could be conducted on a larger scale than is currently possible with naturally occurring genetically identical twins [42]. Lambs cloned from sheep selected either for resistance or susceptibility to nematode worms will be useful in studies aimed at discovering novel genes and regulatory pathways in immunology [43].

Problems and prospects of animal cloning

Placental abnormalities: A failure of the placenta to develop and function correctly is a common feature amongst clones. The majority of early pregnancy failures, before placentome formation, are attributed to an inadequate transition from yolk sac to allantoic-derived nutrition, with poor allantoic vascularisation in sheep [44]. Furthermore, there is reported evidence of immunological rejection contributing to early embryonic loss. Typically in cattle, 50% to 70% of pregnancies at day 50 are lost throughout the remainder of gestation and up to term. This is in stark contrast to only 0% to 5% loss with artificial insemination or natural mating over the same period. In extreme cases, placentomes are entirely absent at day 50. Shortly thereafter, these pregnancies fail. More commonly, cloned placentae only have half the normal number of placentomes, display compensatory overgrowth and are oedematous. Of particular concern are the losses in the second half of gestation; especially the occurrence of hydroallantois, i.e. the excess accumulation of fluid within the allantoises [45].

Post-natal viability: The viability of cloned offspring at delivery and up to weaning is reduced compared to normal, and this is despite greater than usual veterinary care. Data from our group shows that around 80% of cloned calves delivered at term are alive after 24hours [46]. Two-thirds of the mortality within this period is due to a spinal fracture syndrome through the cranial epiphyseal plate of the first lumbar vertebrae or to deaths that occurred either in utero or from dystocia. Surviving newborn clones have altered neonatal metabolism and physiology, possibly due to placental abnormalities, and it takes time for these processes to adjust to normal [47].

At Agriculture Research, typically an additional 15% of calves initially born alive die before weaning. In our experience, the most common mortality factors during this period are gastroenteritis and umbilical infections. Other abnormalities noted include defects in the cardiovascular, musculoskeletal and neurological systems, as well as susceptibility to lung infections and digestive disorders. Hydronephrosis is particularly common in sheep, with correspondingly elevated serum urea levels in some surviving clones.

Parturition difficulties: Intervention is often deemed necessary to deliver cloned offspring, as intervention gestation length in NT pregnancies is typically prolonged and the birth weight of cloned calves may be 25% heavier than normal. Newborn cloned calves display adrenal glands, so this extended gestation may be due to failure of the placentae to respond to foetal cortisol near term or to a lack of adreno corticotropic hormone release from the foetus. Oversized cloned offspring add to the birth complications. They are larger than artificially inseminated or naturally-mated controls. It has been reported that somatic cloned calves are heavier than embryonic clones. At Agriculture Research, the occurrence of prolonged gestation and the risk of dystocia initially prompted the delivery of clones by elective caesarean-section, following a brief exposure to exogenous corticosteroids.

Public opinion and food safety to genetically engineered and cloned animal: Public opinion against cloning is apparent throughout the world. According to The Euro Barometer poll conducted in 2008, 84% of European Union citizens feel that the long-term effects of animal cloning on nature were unknown. The same poll also revealed that 61% European Union citizens of citizens believe the cloning of animals to be morally wrong (The Gallup Organization, 2008). A2005 Pew Initiative on Food and Biotechnology poll found that two-thirds of United States consumers indicated that they are uncomfortable with animal cloning in general. An earlier Gallup poll reportedly found that two-thirds considered animal cloning morally wrong [48].

Cloning has given rise to a massive ethical debate, including reports by bioethics committees and many books and articles. There are few enthusiastic advocates of cloning, but a number of bioethicists have tried to show that popular responses and even the more sophisticated philosophical arguments against cloning are naïve, and cannot be sustained. These commentators have argued that people's opposition to cloning is a Yuk reaction, which cannot stand up to reasoned argument. In a similar, defensive way, liberals have argued that while cloning may not be very desirable, it should not stop other people from doing it, because that would interfere with freedom [49].

The composition of food products derived from clones have found that they have the same composition as milk or meat from conventionally-produced animals [50]. Milk and meat from clones produced by embryo splitting and nuclear transfer of embryonic cells have been entering the human food supply for over 20 years with no evidence of problems. However, in 2001, the Center for Veterinary Medicine at the Food and Drug Administration (FDA) determined that it should undertake a comprehensive risk assessment to identify hazards and characterize food consumption risks that may result from Somatic cell nuclear transfer (SCNT) animal clones and therefore asked companies not to introduce these cloned animals, their progeny, or their food products (milk or meat) into the human or animal food supply. As there is no fundamental reason to suspect that clones will produce novel toxins or allergens, the main underlying food safety concern was whether the Somatic cell nuclear transfer (SCNT) cloning process results in subtle changes in the composition of animal food products [43].

Although the amount of data describing the health of the progeny of clones is more limited than the amount describing the health of animal clones themselves, there is an underlying biological assumption behind the predicted health and resultant food safety of the sexually-produced progeny of clones. The genetic remodeling process that occurs during gametogenesis (i.e. the production of eggs and sperm), is thought to naturally reset any epigenetic anomalies that might result from the cloning process. Sexual reproduction effectively corrects any programming errors that may have been introduced into the cloned parent’s DNA, thereby resulting in the production of normal gametes and offspring. This assumption is supported by a study in mice where it has been observed that abnormalities present in cloned mice are not passed on to their sexually- derived progeny. In addition, observations on the relatively small number of progeny of bovine and swine clones that have been born support the premise of normal development [51].

Ethical issue of genetic engineering and cloning in respect to animal welfare

Some scientific, governmental and religious organizations oppose reproductive cloning since serious ethical concerns have been raised by the future possibility of harvesting organs from clones [51]. The majority of religious organizations distinguish between reproductive and therapeutic cloning. Since cloning is an unnatural born of an individual, no one has the right to undertake it except God. Many embryos develop abnormally and die in utero, while others may be infertile or born with developmental defects, some of which are attributable to these so-called insertional problems [52]. Still other health issues may not become apparent until later in life. Transgenic animals often exhibit variable or uncontrolled expression of the inserted gene, resulting in illness and death [53]. In one study, ten transgenic piglets were followed from birth through puberty. Half of the animals died or had to be euthanized due to severe health problems during the investigation, indicating a high mortality rate among genetically engineered piglets. In addition, three of the surviving piglets showed decreased cardiac output [54].

The genetic modification of sheep containing an extra copy of a growth hormone gene resulted in animals who reportedly grew faster, leaner, and larger than those conventionally bred; produced more wool; or produced milk for prolonged periods. Developing more economically profitable sheep reportedly resulted in negative welfare side effects from the excess growth hormone, including increased incidences of diabetes and susceptibility to parasites [55]. Cloning research also reveals abnormalities and high failure rates, problems widely acknowledged by scientists in the field and potentially indicative of poor animal welfare [56]. Seemingly healthy bioengineered animals are at risk for a variety of defects. All cloned babies have some sort of error. The list of problems from which clones have suffered is extensive, including diabetes, enlarged tongues, malformed faces, intestinal blockages, shortened tendons, deformed feet, weakened immune systems, respiratory distress, circulatory problems, and dysfunctional hearts, brains, livers, and kidneys.

Future perspectives of transgenesis

The techniques for obtaining transgenic animals in species of agricultural interest are still inefficient. Some approaches that may overcome this problem are based on cloning techniques. Using these techniques it is feasible to reduce to less than 50% the number of embryo receptor females, which is one of the most important economic limiting factor in domestic species. It would also facilitate the further proliferation of transgenic animals. Recent results relate these techniques with still low success rates [57], high rates of perinatal mortality and variable transgenic expression that requires to be evaluated before generalizing their application. Considerable effort and time is required to propagate the transgenic animal genetics into commercial dairy herds. Rapid dissemination of the genetics of the parental animals by nuclear transfer could result in the generation of mini herds in two to three years. However, the existing inefficiencies in nuclear transfer make this a difficult undertaking. It is noteworthy that the genetic merit of the 'cloned’ animals can be fixed, while continuous genetic improvements is introduced in commercial herds by using artificial insemination breeding programs [58].

In an alternative scenario of herd expansion, semen homozygous for the transgene may be available in four to five years. Extensive breeding programs will be critical in studying the interaction and co-adaptation of the transgene(s), with the background polygenes controlling milk production and composition. Controlling inbreeding and confirming the absence of deleterious traits so that the immediate genetic variability introduced by transgenesis is transformed into the greatest possible genetic progress is equally critical.

Cloning in Africa

The first healthy cloned calf in South Africa in 2003 was successful called Futhi [59]. It is African's first cloned (nuclear transferred) healthy calf, produced with handmade cloning. In situations regarding our country, there is no any reliable research conducted on genetic engineering and cloning. It is also difficult to perform or apply the technology not only because of technological insufficiency and financial limitation but also lack of skill and knowledge [60-62].

Conclusion and Recommendation

Genetic engineering is the processes of producing genetically modified animals by using different techniques such as exogenous pronuclear DNA microinjection in zygotes, injection of genetically modified embryonic stem cells into blastocysts and retrovirus mediated gene transfer. It has advanced application in various sectors including increased animal production and productivity, increase animal disease resistance and biomedical application. Cloning is the process of producing genetically identical individual to the donor cells by using different techniques such as somatic cell nuclear transfer and embryo splitting [63-65]. It has various applications such as rapid multiplication of desired livestock, animal conservation and research model [66,67]. Even if, transgenic and cloned animals have wide range application and the science is very interesting and valuable, many challenges from the food safety, animal welfare, public and social acceptance points of view, socio-cultural and religious obstacles and technical inefficiency are headache for the technology [68].

In most of developing country including Ethiopia have no attempt of animal genetic engineering and cloning which could be attributed to lack of knowledge and skill, technological insufficiency as well as financial limitation. Therefore; based on the above conclusion the following recommendations are forwarded:

a. Further study and research are needed to be conducted to improve the techniques and increase the successes rate of genetic engineering and cloning.

b. Much work is to be done on creating public awareness on genetic engineering and animal cloning to avert the sociocultural and religious problems facing this technological advancement.

c. Veterinarian should acquire basic knowledge about the application and techniques of animal genetic engineering and cloning and this should be part of the academic curriculum.

d. Concerned organizations/institution in developing country including Ethiopia should be involved in technology transfer researches and make use of the advantages of animal genetic engineering and cloning.

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[cancerbiophd]

hi julia! could you expand a little bit on how you use an excel spreadsheet to summarize papers you're reading? idk if im too tired to function but i dont understand how you do it. :[ do you use different sheets per paper or one sheet for all of them? thanks!

Hi there! And sure!

There are a few formats you could start off with, and then let change as you see fit. The beauty of doing all this on excel is you can copy and paste and drag and delete and basically modify the formats for what works best for you as time goes by. 

Format 1: Super general. You just want to have a “cheatsheet” of sorts of all the papers you’re reading. You can keep it all on one sheet, or break the sheets up into separate topics or classes. 

These can be your column headings:

Authors (shortened; can just keep it as first author et al)

Link to paper (ex. on PubMed, for future reference)

Short title

Main hypothesis/research question/purpose of paper

Any important/unique methods to remember (ex. in vitro vs in vivo models)

Figure 1 notes - Can just copy and paste the figure 1 title if you want, or can shorten as you see fit

Figure 2 notes

Etc

Conclusion

Any other notes

It’s definitely going to be a suuuper wide excel sheet, so maybe not suitable for printing, but you can make adjust the row height as necessary to make it a bit more manageable on screen. 

Another option is to have all the headings as rows, so it’s easier to print. Then have each paper be its own column or sheet, as you see fit. 

If each paper has its own Sheet, you can have Sheet #1 be a table of contents, so you can quickly find which paper summary you want to pull up. 

Format 2: More specific. Say you’re writing a paper for a specific topic, and want to keep all your readings in a row. 

Now you can organize your sheets into specific sub-topics, like if you need some references for the Intro, and others for each Subheading. Or maybe even papers that support your argument, and papers that counter it. Etc. 

Your headings could go something like this:

Authors (shortened; can just keep it as first author et al)

Link to paper (ex. on PubMed, for future reference)

Short title

And then pertinent details

Here’s one of mine as an example. I was writing a paper on estrogen’s effects on mouse bone in the context of breast cancer bone metastasis model, and needed to reference what was known:

I know it’s hard to see, but my headings are: Authors, Link to paper, Short title, Lesions, Cells, Mouse, OVX?, E2 pellet, E2 duration, Author comments on E2 effects on bone, JC comments (my own notes/interpretations). I then color-coded some cells/phrases to further group them so I can quickly tell which ones are similar at a glance. 

I have 2 sheets in this file: one for ER+ breast cancer, the other for ER- breast cancer. 

I hope this helps to get you started!

[newmarketplace]

What Would Be The Scope Of The Humanized Mice Model Market In The Next 10 Years?

Persistence Market Research (PMR) has published a new research report on humanized mice model. The report has been titled, “Humanized Mice Model Market: Global Industry Key Analysis, Size, Share, Growth, Trends and Forecast 2017 – 2026.” In order to extemporize pre-clinical studies, humanized mice models surface as a better solution. With further development in genomic analysis, there is also a chance of refinement in the mouse models.

Humanized mice models have been in use mice for better understanding of the disease, in order to design effective therapies, create accurate models of drug metabolism and improve the understanding of mammalian and human genome function. Market players are incessantly competing for a significant value share and expansion of their global outreach by investing in technologies.

Get Sample Copy of Report @ https://www.persistencemarketresearch.com/samples/22714

Company Profiles

THE JACKSON LABORATORY

Taconic Biosciences, Inc.

Genoway S.A.

Yecuris Corporation

Charles River Laboratories, Inc.

Crown Bioscience Inc.

Ingenious Targeting Laboratory Inc.

orizon Discovery Group plc

HuMurine Technologies

Trans Genic Inc., Ltd.

Get To Know Methodology of Report @ https://www.persistencemarketresearch.com/methodology/22714  

With growing need to develop better varieties of humanized mice model and improve the quality and outcome of research studies, the demand for humanized mice models is increasing. However, various technical restrictions may pose as a challenge for the development of the market. Some of the leading companies operating in the market are The Jackson Laboratory, Crown Bioscience Inc. (JSR Life Science), Charles River Laboratories International, Inc., Taconic Biosciences, Inc., Ingenious Targeting Laboratory Inc., Trans Genic Inc., Ltd., GenOway, Creative Animodel, and Horizon Discovery Group plc.

According to the report, the global humanized mice model market is projected to exhibit a CAGR of 6.0% from 2017 to 2026. In 2017, the market was worth US$ 67.5 Mn and it has been estimated that it will touch a valuation of US$ 113.5 Mn by the end of 2026.

Technological Development to Trigger Demand for Humanized Mice Models

Novel technologies are being developed with each passing day, which permit robust genetic modification of mice, which accelerates the development of new immune deficient mice models for capitalizing on the discovery of novel approaches to enhance the engraftment of human cells or tissues.

Moreover, speedy technological advancements have been witnessed in the last 20 years, which comprise the genetic engineering of mouse genome such as the development of knock-out mouse, knock-in mouse as well as the transgenic mouse.

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The aptitude to engraft mouse liver with human hepatocytes and mouse bone marrow with human hematopoietic stem cells is also foreseen to provide new opportunities, proliferating the market growth. These models also overcome the limitations of xenograft models as they elucidate disease etiology, tumor progression and metastasis.

Moreover, humanized mice strains provide better research models than working with mutant mouse protein. They are considered as more realistic models for tumor studies than the dish-grown cancer cells, and are also used for safety evaluation when neither normal mice nor rats can be used in particular biologics.

Availability of Substitutes to Hinder Market Growth

In addition to mice, other genetically modified species that can be used as models are being carefully measured for research purpose. Lately, knockout of CFTR gene has been stated in the pig as it is similar in size to humans and may be a superior model for the research on cardiovascular and metabolic diseases. Experimental advancements employing computer simulation, in silico, in vitro, and other non-animal approaches are also being taken up for the replacement of animal studies.

About us:

Persistence Market Research (PMR), as a 3rd-party research organization, does operate through an exclusive amalgamation of market research and data analytics for helping businesses ride high, irrespective of the turbulence faced on the account of financial/natural crunches.

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[mariebenz]

Protein Critical for Skin Barrier Function Identified

MedicalResearch.com Interview with:

Dr. Millar Sarah E. Millar, Ph.D. Director, Black Family Stem Cell Institute Professor, Departments of Cell, Developmental and Regenerative Biology and Dermatology Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: One of the major roles of the skin is to serve as a protective barrier, both preventing external insults, such as toxins and pathogens, from entering the body, and helping to retain moisture. The mechanisms required for appropriate skin barrier formation remain incompletely understood. Elucidating these processes is important for understanding and developing improved treatments for dermatological diseases in which the skin barrier is dysfunctional, such as eczema and psoriasis. Understanding epigenetic regulators, proteins that modify the structure of genetic material, is an area of scientific interest, as many new drugs target these proteins. Importantly, multiple epigenetic regulators have been shown to be important in skin development. My lab has focused on one group of epigenetic regulators, histone deacetylases (HDACs), because HDAC inhibitors show promise for treating several different cancers and other disorders in which cell proliferation is poorly controlled. We previously showed that HDACs 1 and 2 are required for normal skin development. In the current study, we investigated whether the related protein HDAC3 is also important in establishing the skin barrier. 

Dermnet NZ image MedicalResearch.com: What are the main findings? What role might this protein play in epidermal barrier disorders such as ichthyosis, bullous disorders, eczema or other cutaneous diseases? Response: Using genetically engineered mouse models, we deleted HDAC3 in the epidermis, the outermost layer of the skin, and found that the mutant mice failed to survive due to barrier dysfunction. Our data show that HDAC3 modulates diverse biological processes required for normal skin development, and indicate that HDAC3 interacts with multiple DNA-binding proteins to regulate its target genes.y65 Given its critical role in barrier establishment, HDAC3’s activity may be disrupted in skin disorders in which the barrier does not function properly. Interestingly, we found that mice lacking epidermal HDAC3 have a very different phenotype from mice lacking epidermal HDACs 1 and 2, demonstrating that these related proteins have distinct functions in regulating skin development. Additionally, we found that while HDAC1/2-mediated regulation of epidermal gene expression is dependent on enzymatic activity, HDAC3 appears to act in an enzyme-independent fashion. This has important implications for the use of HDAC inhibitors, as these drugs specifically target HDAC enzymatic function. Our findings suggest that use of HDAC inhibitors might recapitulate loss of HDAC1/2, but not loss of HDAC3. MedicalResearch.com: What should readers take away from your report?  Response: HDAC3 is critical for epidermal development and establishment of the skin barrier. Our data suggest that it accomplishes its gene regulatory activities primarily as a scaffolding protein, in concert with diverse DNA-binding proteins.  MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: An important area of future investigation will be to characterize the role of HDAC3 in models of skin disease. It will be interesting to determine whether loss of HDAC3 activity plays a role in disorders such as eczema and psoriasis. We have no competing interests to disclose.  Citation: Katherine M. Szigety, Fang Liu, Chase Y. Yuan, Deborah J. Moran, Jeremy Horrell, Heather R. Gochnauer, Ronald N. Cohen, Jonathan P. Katz, Klaus H. Kaestner, John T. Seykora, John W. Tobias, Mitchell A. Lazar, Mingang Xu, Sarah E. Millar. HDAC3 ensures stepwise epidermal stratification via NCoR/SMRT-reliant mechanisms independent of its histone deacetylase activity. Genes & Development, 2020; DOI: 10.1101/gad.333674.119  The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

[kidkei]

On the Horizon: Hemangiosarcoma Studies

© William Wise | Dreamstime.com

Every veterinarian who has handled a dog with HSA needs for higher early diagnostics and simpler therapies to cease the progress of the HSA tumors. “The wish list for every veterinary oncologist starts with trying to find some way to deal with hemangiosarcoma,” says Rodney Page, DVM, MS, Professor of Oncology, Director of the Flint Animal Cancer Center, and Principal Investigator for the Golden Retriever Lifetime Study. “It’s a tumor that’s relatively unique to dogs and has completely evaded all attempts to understand what’s going on in a way that’s able to be modified in the patient. It’s a rapidly fatal cancer and one that desperately needs better diagnostic tools and treatments.” (Quoted from “Cancer Research: Looking Back, Moving Forward,” morrisanimalfoundation.org, March 27, 2019.) Fortunately, analysis on HSA is going down in lots of places: 

Ethos Veterinary Health’s Canine Hemangiosarcoma Molecular Profiling (CHAMP) undertaking is a multi-faceted potential research of canine splenic HSA. One of its first undertakings was to evaluate the worth of customized medication in canines with HSA after which validate the usefulness of a doubtlessly prognostic take a look at. Through a collaboration between Ethos and the Translational Genomics Research Institute (TGen), the molecular characterization of genomic alterations in HSA was not too long ago accomplished. CHAMP hopes to establish canines with distinct prognoses and develop molecularly focused therapies for every affected person.

Ethos Discovery (a division of Ethos Veterinary Health, LLC) is evaluating Rapamycin to find out whether or not it might probably enhance therapy outcomes for canines with HSA and to achieve an understanding of which HSA genotypes could profit most from its use. Rapamycin is understood to have an immunosuppressive that gives vital anticancer exercise and has been accredited to be used in treating a number of human cancers.

At the Flint Animal Cancer Center at Colorado State University in Fort Collins, researchers are evaluating the effectiveness of VDC-597 administered orally to canines with Stage I and II splenic HSA who’ve undergone splenectomy. VDC-597 is an oral agent that has antitumor and antimeta-static exercise in human and mouse most cancers fashions in addition to in canine HSA cell strains.

The Veterinary Clinical Investigations Center at the University of Pennsylvania in Philadelphia, in partnership with NovaVive, are in the follow-up stage of a research on the efficacy of treating canine splenic hemangiosarcoma with intravenous Immunocidin, the mycobacterial cell wall fraction derived from non-pathogenic Mycobacterium phlei, stimulating anti-tumor exercise. It is at the moment accredited for the therapy of mammary most cancers in canines.

The University of Minnesota Veterinary Medical Center, Purdue University, and University of Pennsylvania are collaborating on a research to find out whether or not propranolol (a blood stress treatment) utilized in mixture with standard-of-care doxorubicin chemotherapy can enhance outcomes for canines with HSA. Propranolol can kill HSA cells in the laboratory; it has additionally been efficient in decreasing illness development and growing survival time in people with angiosarcoma (which has similarities to canine HSA).

A research at the New York State College of Veterinary Medicine at Cornell University goals to seek out and take a look at new medicine that may forestall tumor progress. The long-term targets of this undertaking are to establish higher procedures and medicines to deal with canine HSA in addition to to check the capacity of newer focused medicine in stopping tumor progress or recurrence.

The Shine On Project, led by Jaime Modiano, VMD, PHD, at the University of Minnesota College of Veterinary Medicine, is designed to detect HSA cells in the blood at the earliest onset by means of a brand new, focused drug referred to as eBAT. The drug was developed at the University of Minnesota with the purpose of destroying the cells accountable for tumor formation, thereby stopping the formation of malignancies. The course of “will use a blood test to look for the cells responsible for establishing and maintaining the disease, and then use an experimental drug treatment that attacks those same cells in order to prevent development of the tumor.” Researchers at the school have been finding out the biology and the habits of HSA for greater than 10 years.

A latest retrospective multicenter observational cohort research of 406 canines decided that the threat of HSA analysis in canines presenting with blood accumulation in the stomach could possibly be predicted utilizing a easy threat rating modeled on 4 predictors: physique weight, whole plasma protein, platelet depend, and thoracic radiograph discovering. This analysis course of may support in figuring out and treating canines at decrease threat for this analysis. (“Development and validation of a hemangiosarcoma likelihood prediction model in dogs presenting with spontaneous hemoabdomen: The HeLP score,” Schick et al, Journal of Veterinary Emergency and Critical Care, Volume 29, Issue 3, 17 April 2019.)

Michigan-based Metta Pets is at the moment enrolling canines at choose referral facilities round the United States for a medical trial, “Investigation of a traditional Chinese medicine herbal therapy protocol for treatment of dogs with Stage II splenic hemangiosarcoma after splenectomy.” They will consider the influence of a standardized bupleurum-based natural formulation administered with vitamin D supplementation, Yunnan Pai Yao, and coriolus mushroom granular extract in canine sufferers recognized with stage II splenic HSA following splenectomy. To date, no toxicities from the therapy have been famous, together with one dog who obtained a major repeated overdose on account of shopper non-compliance. Preliminary information recommend improved survival occasions when in comparison with chemotherapy therapy and a rise in the variety of sufferers residing to 1 yr or extra. This research will help in figuring out if these promising findings are repeatable when a bigger variety of sufferers are evaluated.

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[nafjohannahairas]

University Of Cambridge And Animal Testing

Animal research plays an essential role in our understanding of health and disease and in the development of modern medicines and surgical techniques. Without the use of animals, we would not have many of the modern medicines, antibiotics, vaccines and surgical techniques that we take for granted in both human and veterinary medicine. Some of the important and pioneering work for which Cambridge is best known and which has led to major improvements in people’s lives was only possible using animals, from the development of IVF techniques through to human monoclonal antibodies. They say that they place good welfare at the centre of all our animal research and aim to meet the highest standards: good animal welfare and good science go hand-in-hand. Their research is scrutinised by the Animal Welfare and Ethical Review Body, who strive to reduce the number of animals used. Although animals will play a role in biomedical research for the foreseeable future, we strive to use the minimum number possible. Our researchers are actively looking at techniques to refine their experiments and help us reduce – and ultimately replace – their use. 

What types of animal are used at Cambridge?

The majority of the animals they use are mice and zebrafish – they make up 97% of all procedures at Cambridge. Where these species are not suitable, they use a small number of other animals, such as xenopus frogs, rats and sheep, as well as non-human primates, namely marmosets and macaques. 

What types of animal research do they carry out?

Some of the work carried out is fundamental research, aimed at understanding how humans and animals develop and how our immune systems and brains work, for example. This knowledge is essential for underpinning our understanding of health and disease for both medical and veterinary purposes. 

Other work is aimed at tackling specific diseases, for example in helping us understand how Parkinson’s disease affects the brain and motor system and how it might be tackled, or in developing new treatments for autoimmune diseases such as type 1 diabetes and multiple sclerosis.

Why has the number of procedures in the UK increased year upon year?

Whilst every attempt is made to minimise the number of procedures undertaken in research, there has been an overall increase over the last decade due to the use of genetically-modified (GM) mice. If these breeding figures were to be excluded, the total number of procedures carried out year upon year would decrease slightly.

How severe were these procedures? When applying to use animals for research purposes, researchers must assign a severity classification to the procedures they plan to undertake before authority to do the work is authorised by the Home Office.  Once their licence has been granted they must also record the actual level of suffering, i.e. severity experienced by each animal during the course of a procedure.

The prospective severity classification of a procedure is determined by the degree of pain, suffering, distress or lasting harm expected to be experienced by an individual animal during the course of the procedure.  After an experiment has been completed the researcher must record the actual level of suffering experienced by each animal.  The prospective severity classifications are defined by the EU Directive as Non-recovery, Mild, Moderate and Severe, examples of which are provided below.

Non-recovery Procedures, which are performed entirely under general anaesthesia from which the animal shall not recover consciousness.

Mild Procedures on animals as a result of which the animals are likely to experience short term mild pain, suffering or distress, as well as procedures with no significant impairment of the wellbeing or general condition of the animals.

Mild procedures include:

anaesthesia

non-invasive imaging, like and MRI scan

short-term social isolation

taking a blood sample

superficial non-surgical procedures e.g. ear biopsies in mice and non-surgical implantation of recording devices and minipumps

Moderate Procedures on animals as a result of which the animals are likely to experience short term moderate pain, suffering or distress, or long-lasting mild pain, suffering or distress as well as procedures that are likely to cause moderate impairment of the wellbeing or general condition of the animals.

Moderate procedures include:

invasive surgery under general anaesthetic e.g. surgical implantation of a catheter into a blood vessel for long term drug delivery

causing cancer in an animal where the tumour growth impairs normal behaviour

feeding a modified diet which is deficient in an essential nutrient such that it affects the health of the animal

exposing the animal to something that they would normally run away from, without enabling them to run away

the breeding of genetically altered animals where the animals health is affected, e.g. genetic models of diabetes.

Severe Procedures on animals as a result of which the animals are likely to experience severe pain, suffering or distress, or long-lasting moderate pain, suffering or distress as well as procedures, that are likely to cause severe impairment of the wellbeing or general condition of the animals.

any test where death is the end-point or where deaths are expected and it is not easy to determine when an animal is likely to die, e.g. models of aortic aneurysm

testing a device that could cause pain/death if it were to fail, e.g. testing devices designed to support patients at risk of heart disease

inescapable electric shock treatments, e.g. to induce a model of learned helplessness

breeding animals with genetic disorders that are expected to experience severe and persistent impairment of general condition, for example Huntington’s disease, and muscular dystrophy

Actual severity: The above definitions and examples also provide a good insight into what animals could have experienced when undergoing procedures and so reflect how actual severity is determined.  The only difference is that in the UK the Home Office introduced a further actual severity classification known as sub-threshold.  This classification therefore appears when UK annual returns of procedures are published.

Sub-threshold This is for procedures which were originally assigned an above-threshold pain or suffering classification, but when the work was undertaken the actual level of suffering was below that which would exceed the threshold at which procedures are licenced under the Act.

Sub-threshold procedures include:

breeding of genetically altered animals under project licence authority but without a harmful phenotype

dosing with a compound in feed where the animals ate normally and suffered no consequences of being dosed

Finally, any animals that are undergoing experimental procedures that are found dead and death could have been procedure related will be automatically classified as Severe unless the researcher can proved that the death was not procedure related.

How do they ensure high standards of animal welfare? They believe that good science and good animal welfare go hand in hand. The UK has the most rigorous animal welfare regulations in the world, and they consider adherence to these regulations as a minimum and will continue to aim for the highest possible standards of animal care.

They strongly agree with, and rigidly follow, the guiding principles emphasised by the Home Office on the need to refine protocols, keep the numbers of animals used to a minimum and replace the use of animals with other methods where possible. To this end, they encourage all staff involved in animal research and husbandry to continuously develop and improve on existing welfare standards, offering incentives to those that contribute, and rewarding those that are recognised by the laboratory animal welfare organisations.

Are they looking for alternatives to animal use? They are committed to refining, reducing and replacing the use of animals in research - known as the 3Rs. Animals are only used where no alternatives are viable. Cambridge scientists are also leading research looking at finding viable alternatives. For example, in 2014, Dr Meritxell Huch from the Gurdon Institute won the UK’s international prize for the scientific and technological advance with the most potential to achieve the 3Rs for work to grow “mini-livers” from adult mouse stem cells.

Do they test cosmetics and household products on animals? No. It is not permitted anywhere within the UK or the European Union to test cosmetics or household products on animals.

[bharatiyamedia-blog]

Serving to transplanted stem cells stick round and do their jobs

http://tinyurl.com/y4bt9wem Credit score: CC0 Public Area Bone marrow transplants of hematopoietic stem cells have develop into commonplace therapy for a number of situations together with cancers of the blood and lymphatic methods, sickle cell anemia, inherited metabolic issues, and radiation harm. Sadly, many bone marrow transplants fail resulting from rejection by the affected person’s immune system or graft-versus-host illness (through which the transplanted marrow cells assault the affected person’s wholesome cells), each of which will be deadly. Mesenchymal stromal cells (MSCs) are identified to secrete compounds that modulate the immune system and have proven promise in mitigating these issues in animal trials. Nevertheless, medical outcomes with MSCs have been disappointing to date, as they’re quickly cleared from the physique and may draw assault from sufferers’ immune methods, and efforts to encapsulate MSCs in protecting biomaterials have resulted in giant, cumbersome hydrogels that can not be given intravenously and compromise the cells’ features. Immediately, in a scientific first, researchers from the Wyss Institute for Biologically Impressed Engineering, Harvard’s John A. Paulson Faculty of Engineering and Utilized Sciences (SEAS), and the Harvard Stem Cell Initiative (HSCI) display a single-cell encapsulation expertise that successfully protects transplanted MSCs from clearance and immune assault and improves the success of bone marrow transplants in mice. The work is revealed in PNAS. “To our information, that is the primary instance of single-cell encapsulation getting used to enhance cell therapies, which have gotten extra widespread as therapies for quite a few illnesses,” stated first writer Angelo Mao, Ph.D., a former graduate scholar within the lab of Wyss Core College member and lead of the Wyss Immuno-Supplies Platform David Mooney, Ph.D. who’s now a postdoc with Wyss Core College member James Collins, Ph.D. “And, our encapsulated cells will be frozen and thawed with minimal influence on the cells’ efficiency, which is essential within the context of hospitals and different therapy facilities.” This advance builds on a way the group beforehand developed that makes use of a microfluidic system to coat particular person residing cells with a skinny layer of an alginate-based hydrogel, creating what they time period “microgels.” The method encapsulates cells with 90% effectivity, and the ensuing microgels are sufficiently small that they are often delivered intravenously, not like the cumbersome hydrogels created by different strategies. When injected into mice, MSCs encapsulated utilizing this system remained within the animals’ lungs ten occasions longer than “naked” MSCs, and remained viable for as much as three days. As a result of a considerable amount of MSCs’ medical attraction lies of their secretion of compounds that modulate the physique’s immune system, the researchers wanted to check how microgel encapsulation impacts MSCs’ capability to operate and resist immune assault. They modified their authentic alginate microgel by including one other compound that cross-links to the alginate and makes the microgel stiffer and higher in a position to withstand the physique’s immune system and clearance mechanisms. In addition they cultured the MSCs after encapsulation to encourage them to divide and produce extra cells. When these new microgels had been injected into mice, their persistence elevated five-fold over the earlier microgel design and an order of magnitude over naked MSCs. To induce an immune response in opposition to the MSCs, the group incubated encapsulated cells in a medium containing fetal bovine serum, which is acknowledged by the physique as international, earlier than introducing them into mice. Whereas the clearance fee of the encapsulated MSCs was increased than that noticed with out immune activation, it was nonetheless 5 occasions decrease than that of naked MSCs. The microgels additionally outperformed naked MSCs when injected into mice that had a preexisting immune reminiscence response in opposition to MSCs, which mimics human sufferers who’re given a number of infusions of stem cells. MSCs uncovered to inflammatory cytokines reply by growing their expression of immune-modulating genes and proteins, so the researchers subsequent examined whether or not encapsulation of their new microgels impacted this response. They discovered that naked and encapsulated MSCs had comparable ranges of gene expression when uncovered to the identical cytokines, demonstrating that the microgels didn’t impair MSC efficiency. For his or her pièce de résistance, the group injected their MSC-containing microgels into mice together with transplanted bone marrow, half of which was immune-compatible with the recipient mouse and half of which was allogeneic, or an immune mismatch. Mice that obtained encapsulated MSCs had greater than double the fraction of allogeneic bone marrow cells of their marrow and blood after 9 days in contrast with mice that didn’t obtain MSCs. Encapsulated MSCs additionally led to a better diploma of engraftment of the allogeneic cells into the host bone marrow in comparison with naked MSCs. “One of many robust factors of this work is that it makes use of a very non-genetic strategy to dramatically enhance cell survival in transplant contexts, the place it is sorely wanted,” stated Mooney, who can be the Robert P. Pinkas Household Professor of Bioengineering at SEAS. “This expertise properly enhances genetic engineering approaches, and actually may very well be extra environment friendly than making an attempt to straight modify immune cells themselves.” The Wyss Institute’s Validation Venture Program is supporting development of this strategy as a attainable therapy for ischemia (narrowing of blood vessels) in human sufferers, and hopes to display medical viability within the close to future. Validation Tasks are applied sciences with potential high-impact purposes which have efficiently progressed via important idea refinement and meet predefined technical, product improvement, and mental property standards. “This expertise concurrently resolves a number of points with bone marrow transplants and stem cell therapies utilizing a sublime, biomaterials-based strategy that represents the sort of cross-disciplinary considering that we worth so significantly on the Wyss Institute,” stated Wyss Founding Director Donald Ingber, M.D., Ph.D., who can be the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Kids’s Hospital, in addition to Professor of Bioengineering at SEAS. “We’re excited to help this mission because it strikes towards medical validation, and we look ahead to different potential purposes of microencapsulation to deal with drug and cell supply issues.” How to engineer a stronger immune system Extra data: Angelo S. Mao el al., “Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation,” PNAS (2019). www.pnas.org/cgi/doi/10.1073/pnas.1819415116 Supplied by Harvard University Quotation: Serving to transplanted stem cells stick round and do their jobs (2019, July 15) retrieved 15 July 2019 from https://medicalxpress.com/information/2019-07-transplanted-stem-cells-jobs.html This doc is topic to copyright. Other than any truthful dealing for the aim of personal examine or analysis, no half could also be reproduced with out the written permission. The content material is supplied for data functions solely. Source link

[jerrytackettca]

Genetic Editing of Animals Has Horrible Side Effects

Would you eat a burger made from a cow with lab-altered DNA? How about a potato or a piece of salmon that was similarly tweaked? Gene-editing technologies are here, and they're already being used to alter the food supply.

For instance, gene-edited crops, in which DNA is tweaked or snipped out at a precise location, include soybeans with altered fatty acid profiles, potatoes that take longer to turn brown and potatoes that remain fresher longer and do not produce carcinogens when fried.

Genetically engineered (GE) salmon, dubbed “frankenfish,” which are engineered to grow about twice as fast as typical farm-raised salmon, not only exist but are already being sold and eaten in Canada, to the tune of 5 tons in 2017 alone (none of which was labeled as such).1

The next step that biotech companies are racing to bring to the not-so-proverbial table is gene-edited farm animals. Unlike GE foods, which may have genes from other species inserted, gene editing involves altering an organism's DNA. Like GE foods, however, gene-edited foods come with unknown risks to the animals and the people who eat them.

Gene Editing Led to Enlarged Tongues, Extra Vertebrae and Other Side Effects

While scientists have made great strides in mapping out genomes of entire organisms, much remains unknown about the purpose of individual genes and how they interact with one another. As such, making tweaks to genes, even those intended to be precise, often lead to surprising and unintended consequences.

In the case of livestock, researchers have used CRISPR-Cas9 and other gene-editing technologies to create cows that can tolerate warmer temperatures (so they can be raised in the tropics), goats with longer cashmere wool and rabbits and pigs with bigger, leaner muscles. Serious side effects resulted, however, including enlarged tongues in the rabbits.2,3

Among pigs that were altered by deleting the myostatin (MSTN) gene, which limits muscle growth, the larger muscles came along with an extra vertebra in 20 percent of the gene-edited animals.

“This result provides us a new insight to better understand MSTN’s function in both skeletal and muscle formation and development in the future studies,” the researchers noted, adding, “This phenomenon has never been reported in other MSTN-mutant animals."4 And therein lies the problem.

Genetic tweaking is not an exact science, and often researchers don’t know the extent of a gene’s functions until something like an extra vertebra reveals itself. Lisa Moses, an animal bioethicist at Harvard Medical School’s Center for Bioethics, told The Wall Street Journal:5

"Humans have a very long history of messing around in nature with all kinds of unintended consequences … It's really hubris of us to assume that we know what we're doing and that we can predict what kinds of bad things can happen."

Gene Editing Is Being Used to Alter Physical Traits, Puberty and Diseases in Animals

Along with altering DNA to create meatier or more temperature-tolerant animals, researchers have snipped out a section of pig DNA intended to prevent Porcine Reproductive and Respiratory Syndrome (PRRS) — a common and often fatal ailment among CAFO (concentrated animal feeding operation) pigs.6 Such edits are permanent and passed down to other generations.

In another project, this one funded by the U.S. Department of Agriculture, researchers have added the SRY gene to cattle, which results in female cows that turn into males, complete with larger muscles, a penis and testicles, but no ability to make sperm.7 Male (or male-like) cattle are more valuable to the beef industry because they get bigger, faster, allowing companies to make greater profits in less time.

Other biotech companies have taken to targeting genes intended to ease animal suffering, which they believe may soften regulators and consumers who are wary of the technology. "It's a better story to tell," Tammy Lee, CEO of Recombinetics, told the New York Post.8

The company has snipped out the genes responsible for growing horns in dairy cows, for instance, which means they wouldn't be subjected to the inhumane ways the horns are currently removed (with no pain relief).

Currently, cows born with the hornless trait are being raised at the University of California, Davis, with plans to eventually test their milk for any oddities. The company is also working on editing genes so pigs don't go through puberty. This would make castrating pigs — an inhumane procedure currently done (also without painkillers) to prevent meat from gaining an unpleasant odor — unnecessary.9

Recombinetics and other biotech companies don't want gene-edited foods to come with any warnings or additional regulations, which could hamper the technology's progress and acceptance by farmers. Once this occurs, though, it's likely that gene-editing will be used less for humanity's sake and more to create larger profits, such as via gene-editing to increase litter size.10

What Are the Consequences of Eating Gene-Edited Foods?

Foods produced via gene-editing are not subject to regulation by the U.S. Department of Agriculture (USDA) — although an advisory board recommended gene-edited foods could not be labeled organic — or other regulatory agencies.11

In fact, in March 2018, the USDA released a statement noting that it would not regulate CRISPR-edited crops, noting, "With this approach, USDA seeks to allow innovation when there is no risk present."12

Gene editing, with its loose regulation, accessibility and quick results, has been called the next "food revolution,"13 at least for plant foods, but it's unclear whether the same will hold true for animals. In the U.S., it's been proposed that gene-edited foods do not need to be labeled, either, but the European Union ruled that they should be regulated the same as genetically modified organisms (GMOs).

Jaydee Hanson, an analyst at advocacy group the Center for Food Safety, told National Geographic that this may be closer to reality. "This is the new kind of genetic engineering, whether you call it transgenic [GMO] or not. It should be adequately regulated. We're not saying it should be stopped — we should know what has been done."14

As for what the health effects of eating gene-edited foods may be, no one knows. In an interview with GM Watch, Michael Antoniou, a London-based molecular geneticist, explained that significant changes could occur due to genetic editing, in both agricultural and medical contexts, necessitating long-term safety and toxicity studies. He explained:15

"Many of the genome editing-induced off-target mutations, as well as those induced by the tissue culture, will no doubt be benign in terms of effects on gene function. However, many will not be benign and their effects can carry through to the final marketed product, whether it be plant or animal …

Thus not only is it necessary to conduct whole genome sequencing to identify all off-target mutations from CRISPR-based genome editing, but it is also essential to ascertain the effects of these unintended changes on global patterns of gene function.

… In addition, it is important to acknowledge that the targeted intended change in a given gene may also have unintended effects. For example, the total disruption or modification of an enzyme function can lead to unexpected or unpredictable biochemical side-reactions that can markedly alter the composition of an organism, such as a food crop.

The compositional alterations in food products produced with genome editing techniques will not be fully revealed by the molecular profiling methods due to the current inherent limitations of these techniques. So it is still necessary to conduct long-term toxicity studies in established animal model systems. In the absence of these analyses, to claim that genome editing is precise and predictable is based on faith rather than science."

Gene Editing May Not Be as Precise as It Seems

Researchers at the U.K.'s Wellcome Sanger Institute systematically studied mutations from CRISPR-Cas9 in mouse and human cells, focusing on the gene-editing target site. Large genetic rearrangements were observed, including DNA deletions and insertions, that were spotted near the target site.

They were far enough away, however, that standard tests looking for CRISPR-related DNA damage would miss them. The DNA deletions could end up activating genes that should stay "off," such as cancer-causing genes, as well as silencing those that should be "on."16

CRISPR-Cas9 also leads to the activation of the p53 gene, which works to either repair the DNA break or kill off the CRISPR-edited cell.17 CRISPR actually has a low efficacy rate for this reason, and CRISPR-edited cells that survive are able to do so because of a dysfunctional p53.

The problem is that p53 dysfunction is also linked to cancer (including close to half of ovarian and colorectal cancers and a sizable portion of lung, pancreatic, stomach, breast and liver cancers as well).18

In one recent study, researchers were able to boost average insertion or deletion efficiency to greater than 80 percent, but that was because of a dysfunctional p53 gene,19 which would mean the cells could be predisposed to cancer. The fact remains that while these new technologies are fascinating with enormous potential to change the world, they're highly experimental and the stakes are high.

In 2018, He Jiankui, a Chinese scientist, claimed to have created the world's first gene-edited babies. Although the claims haven't been vetted, Jiankui says he modified the DNA of human embryos during in vitro fertilization by disabling a gene called CCR5, which could potentially make the babies resistant to infection with HIV.20

Americans Don't Want Frankenfish — Why Would They Want 'Frankenmeat'?

In the U.S., negative public opinion has been instrumental in keeping GE fish off store shelves. In 2013, a New York Times poll revealed that 75 percent of respondents would not eat GE fish and 93 percent said such foods should be labeled as such.21

The argument for gene-edited foods has been that they’re somehow more natural than GE foods, as they don’t have foreign genes inserted, only tweaks to already existing DNA. But is a meat from a mutant pig with extra muscle and vertebrae really the same as meat from a wild pig?

The U.S. Food and Drug Administration (FDA) proposed to classify animals with edited or engineered DNA as drugs, prompting backlash from the biotech industry,22 but the fact remains that we're dealing with a whole new world when it comes to food from gene-edited animals — and consumers deserve to know what they're eating.

Only then can you make an informed decision about whether or not to consume gene-edited or GE foods. Without a label, however, if such foods come to the market they'll blend right into the food chain with unknown consequences, just as has been done with GMOs in the past.

Further, since the genetic alterations are permanent and capable of being passed on to new generations, the technology has lasting ramifications for the environment and the natural world should the altered traits enter surrounding ecosystems. While such advancements in technology will undoubtedly be explored, it should be done with an abundance of caution and full disclosure to consumers.

from http://articles.mercola.com/sites/articles/archive/2019/03/12/genetic-editing-of-animals-has-side-effects.aspx

source http://niapurenaturecom.weebly.com/blog/genetic-editing-of-animals-has-horrible-side-effects

[paullassiterca]

Genetic Editing of Animals Has Horrible Side Effects

Would you eat a burger made from a cow with lab-altered DNA? How about a potato or a piece of salmon that was similarly tweaked? Gene-editing technologies are here, and they’re already being used to alter the food supply.

For instance, gene-edited crops, in which DNA is tweaked or snipped out at a precise location, include soybeans with altered fatty acid profiles, potatoes that take longer to turn brown and potatoes that remain fresher longer and do not produce carcinogens when fried.

Genetically engineered (GE) salmon, dubbed “frankenfish,” which are engineered to grow about twice as fast as typical farm-raised salmon, not only exist but are already being sold and eaten in Canada, to the tune of 5 tons in 2017 alone (none of which was labeled as such).1

The next step that biotech companies are racing to bring to the not-so-proverbial table is gene-edited farm animals. Unlike GE foods, which may have genes from other species inserted, gene editing involves altering an organism’s DNA. Like GE foods, however, gene-edited foods come with unknown risks to the animals and the people who eat them.

Gene Editing Led to Enlarged Tongues, Extra Vertebrae and Other Side Effects

While scientists have made great strides in mapping out genomes of entire organisms, much remains unknown about the purpose of individual genes and how they interact with one another. As such, making tweaks to genes, even those intended to be precise, often lead to surprising and unintended consequences.

In the case of livestock, researchers have used CRISPR-Cas9 and other gene-editing technologies to create cows that can tolerate warmer temperatures (so they can be raised in the tropics), goats with longer cashmere wool and rabbits and pigs with bigger, leaner muscles. Serious side effects resulted, however, including enlarged tongues in the rabbits.2,3

Among pigs that were altered by deleting the myostatin (MSTN) gene, which limits muscle growth, the larger muscles came along with an extra vertebra in 20 percent of the gene-edited animals.

“This result provides us a new insight to better understand MSTN’s function in both skeletal and muscle formation and development in the future studies,” the researchers noted, adding, “This phenomenon has never been reported in other MSTN-mutant animals.“4 And therein lies the problem.

Genetic tweaking is not an exact science, and often researchers don’t know the extent of a gene’s functions until something like an extra vertebra reveals itself. Lisa Moses, an animal bioethicist at Harvard Medical School’s Center for Bioethics, told The Wall Street Journal:5

"Humans have a very long history of messing around in nature with all kinds of unintended consequences … It’s really hubris of us to assume that we know what we’re doing and that we can predict what kinds of bad things can happen.”

Gene Editing Is Being Used to Alter Physical Traits, Puberty and Diseases in Animals

Along with altering DNA to create meatier or more temperature-tolerant animals, researchers have snipped out a section of pig DNA intended to prevent Porcine Reproductive and Respiratory Syndrome (PRRS) — a common and often fatal ailment among CAFO (concentrated animal feeding operation) pigs.6 Such edits are permanent and passed down to other generations.

In another project, this one funded by the U.S. Department of Agriculture, researchers have added the SRY gene to cattle, which results in female cows that turn into males, complete with larger muscles, a penis and testicles, but no ability to make sperm.7 Male (or male-like) cattle are more valuable to the beef industry because they get bigger, faster, allowing companies to make greater profits in less time.

Other biotech companies have taken to targeting genes intended to ease animal suffering, which they believe may soften regulators and consumers who are wary of the technology. “It’s a better story to tell,” Tammy Lee, CEO of Recombinetics, told the New York Post.8

The company has snipped out the genes responsible for growing horns in dairy cows, for instance, which means they wouldn’t be subjected to the inhumane ways the horns are currently removed (with no pain relief).

Currently, cows born with the hornless trait are being raised at the University of California, Davis, with plans to eventually test their milk for any oddities. The company is also working on editing genes so pigs don’t go through puberty. This would make castrating pigs — an inhumane procedure currently done (also without painkillers) to prevent meat from gaining an unpleasant odor — unnecessary.9

Recombinetics and other biotech companies don’t want gene-edited foods to come with any warnings or additional regulations, which could hamper the technology’s progress and acceptance by farmers. Once this occurs, though, it’s likely that gene-editing will be used less for humanity’s sake and more to create larger profits, such as via gene-editing to increase litter size.10

What Are the Consequences of Eating Gene-Edited Foods?

Foods produced via gene-editing are not subject to regulation by the U.S. Department of Agriculture (USDA) — although an advisory board recommended gene-edited foods could not be labeled organic — or other regulatory agencies.11

In fact, in March 2018, the USDA released a statement noting that it would not regulate CRISPR-edited crops, noting, “With this approach, USDA seeks to allow innovation when there is no risk present.”12

Gene editing, with its loose regulation, accessibility and quick results, has been called the next “food revolution,”13 at least for plant foods, but it’s unclear whether the same will hold true for animals. In the U.S., it’s been proposed that gene-edited foods do not need to be labeled, either, but the European Union ruled that they should be regulated the same as genetically modified organisms (GMOs).

Jaydee Hanson, an analyst at advocacy group the Center for Food Safety, told National Geographic that this may be closer to reality. “This is the new kind of genetic engineering, whether you call it transgenic [GMO] or not. It should be adequately regulated. We’re not saying it should be stopped — we should know what has been done.”14

As for what the health effects of eating gene-edited foods may be, no one knows. In an interview with GM Watch, Michael Antoniou, a London-based molecular geneticist, explained that significant changes could occur due to genetic editing, in both agricultural and medical contexts, necessitating long-term safety and toxicity studies. He explained:15

“Many of the genome editing-induced off-target mutations, as well as those induced by the tissue culture, will no doubt be benign in terms of effects on gene function. However, many will not be benign and their effects can carry through to the final marketed product, whether it be plant or animal …

Thus not only is it necessary to conduct whole genome sequencing to identify all off-target mutations from CRISPR-based genome editing, but it is also essential to ascertain the effects of these unintended changes on global patterns of gene function.

… In addition, it is important to acknowledge that the targeted intended change in a given gene may also have unintended effects. For example, the total disruption or modification of an enzyme function can lead to unexpected or unpredictable biochemical side-reactions that can markedly alter the composition of an organism, such as a food crop.

The compositional alterations in food products produced with genome editing techniques will not be fully revealed by the molecular profiling methods due to the current inherent limitations of these techniques. So it is still necessary to conduct long-term toxicity studies in established animal model systems. In the absence of these analyses, to claim that genome editing is precise and predictable is based on faith rather than science.”

Gene Editing May Not Be as Precise as It Seems

Researchers at the U.K.’s Wellcome Sanger Institute systematically studied mutations from CRISPR-Cas9 in mouse and human cells, focusing on the gene-editing target site. Large genetic rearrangements were observed, including DNA deletions and insertions, that were spotted near the target site.

They were far enough away, however, that standard tests looking for CRISPR-related DNA damage would miss them. The DNA deletions could end up activating genes that should stay “off,” such as cancer-causing genes, as well as silencing those that should be “on.”16

CRISPR-Cas9 also leads to the activation of the p53 gene, which works to either repair the DNA break or kill off the CRISPR-edited cell.17 CRISPR actually has a low efficacy rate for this reason, and CRISPR-edited cells that survive are able to do so because of a dysfunctional p53.

The problem is that p53 dysfunction is also linked to cancer (including close to half of ovarian and colorectal cancers and a sizable portion of lung, pancreatic, stomach, breast and liver cancers as well).18

In one recent study, researchers were able to boost average insertion or deletion efficiency to greater than 80 percent, but that was because of a dysfunctional p53 gene,19 which would mean the cells could be predisposed to cancer. The fact remains that while these new technologies are fascinating with enormous potential to change the world, they’re highly experimental and the stakes are high.

In 2018, He Jiankui, a Chinese scientist, claimed to have created the world’s first gene-edited babies. Although the claims haven’t been vetted, Jiankui says he modified the DNA of human embryos during in vitro fertilization by disabling a gene called CCR5, which could potentially make the babies resistant to infection with HIV.20

Americans Don’t Want Frankenfish — Why Would They Want ‘Frankenmeat’?

In the U.S., negative public opinion has been instrumental in keeping GE fish off store shelves. In 2013, a New York Times poll revealed that 75 percent of respondents would not eat GE fish and 93 percent said such foods should be labeled as such.21

The argument for gene-edited foods has been that they’re somehow more natural than GE foods, as they don’t have foreign genes inserted, only tweaks to already existing DNA. But is a meat from a mutant pig with extra muscle and vertebrae really the same as meat from a wild pig?

The U.S. Food and Drug Administration (FDA) proposed to classify animals with edited or engineered DNA as drugs, prompting backlash from the biotech industry,22 but the fact remains that we’re dealing with a whole new world when it comes to food from gene-edited animals — and consumers deserve to know what they’re eating.

Only then can you make an informed decision about whether or not to consume gene-edited or GE foods. Without a label, however, if such foods come to the market they’ll blend right into the food chain with unknown consequences, just as has been done with GMOs in the past.

Further, since the genetic alterations are permanent and capable of being passed on to new generations, the technology has lasting ramifications for the environment and the natural world should the altered traits enter surrounding ecosystems. While such advancements in technology will undoubtedly be explored, it should be done with an abundance of caution and full disclosure to consumers.

from Articles http://articles.mercola.com/sites/articles/archive/2019/03/12/genetic-editing-of-animals-has-side-effects.aspx source https://niapurenaturecom.tumblr.com/post/183396986291

[battybat-boss]

Research Confirms that Curcumin, the Active Ingredient of Turmeric, Heals Cancer

by Paul Fassa Health Impact News

Over 2,000 studies have been done over the past decade or so that indicate and confirm the ability of curcumin, the active ingredient of turmeric, to act as a healing agent for cancer. 

The prestigious University of Texas MD Anderson Cancer Center's research determined, in 2011, that curcumin was able to create apoptosis in cancer cells that normally resist apoptosis, without endangering normal cells. (Source)

An earlier human clinical trial at the MD Anderson Cancer Center was conducted in 2008, involving 25 patients with pancreatic cancer, the most difficult and lethal cancer to put into remission. Their oral curcumin was not so bio-available, as blood levels were not commiserating with the amounts consumed.

Even with that poor bio-availability, two patients' tumors did shrink while the others demonstrated positive biological markers conducive to increased immune system activity against their pancreatic cancers with diminishing biological markers that promoted cancer's spread. There were no adverse side effects. (Source)

But it wasn't until the summer of this year, 2018, that the precise primary biochemical dynamic that made turmeric's active ingredient curcumin effective against cancer was isolated by researchers in San Diego with cooperating academic medical researchers in China. 

Crystal Structure Analysis Reveals Curcumin Enzyme Responsible for Cancer Cell Demise

The actual study was first published online in the journal PNAS (Proceedings of the National Academy of Science) on July 9, 2018, and put into hard copy print on August 7th of the same year.

The researchers used X-ray crystallography, a technique for determining the three-dimensional structure of molecules by diffracting X-rays from crystalized molecules to collect data for reconstructing the electronic density and assembly of atoms or molecules within that crystal. (Source)

The resulting report was titled: Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2.

We need to decode that some. 

26S proteasome:

… proteasome function is essential for protein homeostasis and influences the regulation of most cellular processes, and inhibitors of the proteasome have proven to be very valuable research tools and therapeutic agents that have prolonged the lives of thousands of patients with multiple myeloma. (Source with details)

Dual specificity tyrosine phosphorylation regulated kinase 2 as DYRK2:

A gene on chromosome 12q15 [which is found in several types of cancer tumors] that encodes a dual specificity kinase involved in the control of mitotic transition and the regulation of cellular growth and/or development by phosphorylation of … [several genetic, protein components, and enzymes with cells]. (Source)

From the study's text:

In the current study, we provide evidence that curcumin is a specific and potent inhibitor of DYRK2 and regulates the proteasome activity via DYRK2 inhibition. Cocrystal structure of curcumin with DYRK2 reveals that curcumin binds potently to the active site of DYRK2 via hydrophobic and hydrogen bonds.

Furthermore, curcumin was found to not affect the proteasome activity of cells with DYRK2 deletion.

Notably, curcumin treatment significantly reduced tumor volume in a TNBC mouse xenograft model, and the tumor volume was comparable to DYRK2-depleted tumors. The results establish that the inhibition of the DYRK2–proteasome axis is the primary mode of action of curcumin with expanded therapeutic utility in proteasome inhibitor-resistant cancer burdens. (Source)

The following graphic representation with explanation below is from the study:

Structure of DYRK2 is in complex with curcumin. (A) The Fo–Fc difference electron density map (2.5 σ) calculated before curcumin was modeled is shown as a green mesh, revealing the presence of curcumin. (B) Curcumin occupies the ATP-binding pocket of DYRK2. Curcumin atoms are shown as yellow and red spheres. DYRK2 is shown in a surface representation. (C) Detailed interactions between DYRK2 and curcumin. Hydrogen bonds are shown as dashed lines.

Commentary on the Study

Some pharmaceutical industry compounds have already been developed to inhibit DYRK2, but they create toxic side effects. The researchers acknowledged pharmaceutical drugs' toxic side effects and intended to look for a safer substitute. 

They already knew that curcumin can play a solid role in conquering cancers, even if relegated only to serve as an adjunct, and that it was a safe compound used for both cuisine and medical purposes for over 2,000 years.

It has been used with certain chemotherapeutic drugs as an adjunct, resulting in less damage to non-cancerous cells and increased efficacy with tumor cells.

It was commonly considered that curcumin would not be effective for cancer by itself due to its limited bio-availability when consumed orally. It's known that curcumin's bio-availability is hampered by digestive gastric juices and these researchers also claim that curcumin is expelled from the bloodstream too rapidly as well.

The UC San Diego researchers confided to Science Daily: 

“Our primary focus is to develop a [pharmaceutical] chemical compound that can target DYRK2 in patients with these cancers”, explained UC San Diego professor Jack E. Dixon, Ph.D.

“In general, curcumin is expelled from the body quite fast,” added UC San Diego pharmacologist Sourav Banerjee.

“For curcumin to be an effective drug, it needs to be modified to enter the bloodstream and stay in the body long enough to target the cancer. Owing to various chemical drawbacks, curcumin on its own may not be sufficient to completely reverse cancer in human patients.” (Source) 

This strongly suggests that the results of this research are meant to be exploited by Big Pharma and mainstream oncology for financial benefits while creating harm from side effects to patients with patented synthetic molecules that offer negligible health benefits at very high prices.

How You Can Get Optimum Bio-availability from Curcumin

Traditional techniques involve combining turmeric with saturated fat and piperine (the active ingredient of black pepper) while cooking over heat. The saturated fat protects curcumin from gastric juices to allow its penetration into small intestines where it can be absorbed into the blood. Black pepper's piperine enhances curcumin's cellular absorption. 

First, make turmeric paste using purified water and turmeric powder with a ratio of two parts water to one part non-irradiated, preferably organic, turmeric powder over heat. Stir until a thick paste with uniform consistency occurs, adding water or turmeric as needed. 

Allow it to cool off. Then take whatever paste you want to make Golden Milk and heat it with the best whole milk you can find while stirring in a pan over low heat. Too many Golden Milk advocates insist on non-dairy milk, but you can watch their cooking and blending techniques on YouTube videos.  

Add a dollop of virgin coconut oil with around a teaspoonful of freshly ground black pepper. Stir until you get a consistency that you're able to drink.

After refrigerating, you may have to warm it up some again or put it into a blender to liquefy the coconut oil that hardens when refrigerated. It's not rocket science. What's important is combining the key ingredients with heat.

There are other solutions that involve much less labor. Curcumin extracts are sometimes sold in enteric-coated capsules that protect the curcumin from gastric juices. They may also contain piperine. Those are the best types of convenient curcumin supplements sold over the counter.

You can also go online and find liposomal curcumin. Liposomal encapsulation technology (LET) not only protects the curcumin from gastric juices, but it also enables the lipid encapsulated curcumin molecules to penetrate fatty cell walls. 

This is pricier than the other options. But it may be the most effective and convenient. 

  <!--//<![CDATA[ var m3_u = (location.protocol=='https:'?'https://network.sophiamedia.com/openx/www/delivery/ajs.php':'http://network.sophiamedia.com/openx/www/delivery/ajs.php'); var m3_r = Math.floor(Math.random()*99999999999); if (!document.MAX_used) document.MAX_used = ','; document.write ("<scr"+"ipt type='text/javascript' src='"+m3_u); document.write ("?zoneid=3&target=_blank"); document.write ('&cb=' + m3_r); if (document.MAX_used != ',') document.write ("&exclude=" + document.MAX_used); document.write (document.charset ? '&charset='+document.charset : (document.characterSet ? '&charset='+document.characterSet : '')); document.write ("&loc=" + escape(window.location)); if (document.referrer) document.write ("&referer=" + escape(document.referrer)); if (document.context) document.write ("&context=" + escape(document.context)); if (document.mmm_fo) document.write ("&mmm_fo=1"); document.write ("'><\/scr"+"ipt>"); //]]>-->

[lopezdorothy70-blog]

Research Confirms that Curcumin, the Active Ingredient of Turmeric, Heals Cancer

by Paul Fassa Health Impact News

Over 2,000 studies have been done over the past decade or so that indicate and confirm the ability of curcumin, the active ingredient of turmeric, to act as a healing agent for cancer. 

The prestigious University of Texas MD Anderson Cancer Center's research determined, in 2011, that curcumin was able to create apoptosis in cancer cells that normally resist apoptosis, without endangering normal cells. (Source)

An earlier human clinical trial at the MD Anderson Cancer Center was conducted in 2008, involving 25 patients with pancreatic cancer, the most difficult and lethal cancer to put into remission. Their oral curcumin was not so bio-available, as blood levels were not commiserating with the amounts consumed.

Even with that poor bio-availability, two patients' tumors did shrink while the others demonstrated positive biological markers conducive to increased immune system activity against their pancreatic cancers with diminishing biological markers that promoted cancer's spread. There were no adverse side effects. (Source)

But it wasn't until the summer of this year, 2018, that the precise primary biochemical dynamic that made turmeric's active ingredient curcumin effective against cancer was isolated by researchers in San Diego with cooperating academic medical researchers in China. 

Crystal Structure Analysis Reveals Curcumin Enzyme Responsible for Cancer Cell Demise

The actual study was first published online in the journal PNAS (Proceedings of the National Academy of Science) on July 9, 2018, and put into hard copy print on August 7th of the same year.

The researchers used X-ray crystallography, a technique for determining the three-dimensional structure of molecules by diffracting X-rays from crystalized molecules to collect data for reconstructing the electronic density and assembly of atoms or molecules within that crystal. (Source)

The resulting report was titled: Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2.

We need to decode that some. 

26S proteasome:

… proteasome function is essential for protein homeostasis and influences the regulation of most cellular processes, and inhibitors of the proteasome have proven to be very valuable research tools and therapeutic agents that have prolonged the lives of thousands of patients with multiple myeloma. (Source with details)

Dual specificity tyrosine phosphorylation regulated kinase 2 as DYRK2:

A gene on chromosome 12q15 [which is found in several types of cancer tumors] that encodes a dual specificity kinase involved in the control of mitotic transition and the regulation of cellular growth and/or development by phosphorylation of … [several genetic, protein components, and enzymes with cells]. (Source)

From the study's text:

In the current study, we provide evidence that curcumin is a specific and potent inhibitor of DYRK2 and regulates the proteasome activity via DYRK2 inhibition. Cocrystal structure of curcumin with DYRK2 reveals that curcumin binds potently to the active site of DYRK2 via hydrophobic and hydrogen bonds.

Furthermore, curcumin was found to not affect the proteasome activity of cells with DYRK2 deletion.

Notably, curcumin treatment significantly reduced tumor volume in a TNBC mouse xenograft model, and the tumor volume was comparable to DYRK2-depleted tumors. The results establish that the inhibition of the DYRK2–proteasome axis is the primary mode of action of curcumin with expanded therapeutic utility in proteasome inhibitor-resistant cancer burdens. (Source)

The following graphic representation with explanation below is from the study:

Structure of DYRK2 is in complex with curcumin. (A) The Fo–Fc difference electron density map (2.5 σ) calculated before curcumin was modeled is shown as a green mesh, revealing the presence of curcumin. (B) Curcumin occupies the ATP-binding pocket of DYRK2. Curcumin atoms are shown as yellow and red spheres. DYRK2 is shown in a surface representation. (C) Detailed interactions between DYRK2 and curcumin. Hydrogen bonds are shown as dashed lines.

Commentary on the Study

Some pharmaceutical industry compounds have already been developed to inhibit DYRK2, but they create toxic side effects. The researchers acknowledged pharmaceutical drugs' toxic side effects and intended to look for a safer substitute. 

They already knew that curcumin can play a solid role in conquering cancers, even if relegated only to serve as an adjunct, and that it was a safe compound used for both cuisine and medical purposes for over 2,000 years.

It has been used with certain chemotherapeutic drugs as an adjunct, resulting in less damage to non-cancerous cells and increased efficacy with tumor cells.

It was commonly considered that curcumin would not be effective for cancer by itself due to its limited bio-availability when consumed orally. It's known that curcumin's bio-availability is hampered by digestive gastric juices and these researchers also claim that curcumin is expelled from the bloodstream too rapidly as well.

The UC San Diego researchers confided to Science Daily: 

“Our primary focus is to develop a [pharmaceutical] chemical compound that can target DYRK2 in patients with these cancers”, explained UC San Diego professor Jack E. Dixon, Ph.D.

“In general, curcumin is expelled from the body quite fast,” added UC San Diego pharmacologist Sourav Banerjee.

“For curcumin to be an effective drug, it needs to be modified to enter the bloodstream and stay in the body long enough to target the cancer. Owing to various chemical drawbacks, curcumin on its own may not be sufficient to completely reverse cancer in human patients.” (Source) 

This strongly suggests that the results of this research are meant to be exploited by Big Pharma and mainstream oncology for financial benefits while creating harm from side effects to patients with patented synthetic molecules that offer negligible health benefits at very high prices.

How You Can Get Optimum Bio-availability from Curcumin

Traditional techniques involve combining turmeric with saturated fat and piperine (the active ingredient of black pepper) while cooking over heat. The saturated fat protects curcumin from gastric juices to allow its penetration into small intestines where it can be absorbed into the blood. Black pepper's piperine enhances curcumin's cellular absorption. 

First, make turmeric paste using purified water and turmeric powder with a ratio of two parts water to one part non-irradiated, preferably organic, turmeric powder over heat. Stir until a thick paste with uniform consistency occurs, adding water or turmeric as needed. 

Allow it to cool off. Then take whatever paste you want to make Golden Milk and heat it with the best whole milk you can find while stirring in a pan over low heat. Too many Golden Milk advocates insist on non-dairy milk, but you can watch their cooking and blending techniques on YouTube videos.  

Add a dollop of virgin coconut oil with around a teaspoonful of freshly ground black pepper. Stir until you get a consistency that you're able to drink.

After refrigerating, you may have to warm it up some again or put it into a blender to liquefy the coconut oil that hardens when refrigerated. It's not rocket science. What's important is combining the key ingredients with heat.

There are other solutions that involve much less labor. Curcumin extracts are sometimes sold in enteric-coated capsules that protect the curcumin from gastric juices. They may also contain piperine. Those are the best types of convenient curcumin supplements sold over the counter.

You can also go online and find liposomal curcumin. Liposomal encapsulation technology (LET) not only protects the curcumin from gastric juices, but it also enables the lipid encapsulated curcumin molecules to penetrate fatty cell walls. 

This is pricier than the other options. But it may be the most effective and convenient. 

  <!--//<![CDATA[ var m3_u = (location.protocol=='https:'?'https://network.sophiamedia.com/openx/www/delivery/ajs.php':'http://network.sophiamedia.com/openx/www/delivery/ajs.php'); var m3_r = Math.floor(Math.random()*99999999999); if (!document.MAX_used) document.MAX_used = ','; document.write ("<scr"+"ipt type='text/javascript' src='"+m3_u); document.write ("?zoneid=3&target=_blank"); document.write ('&cb=' + m3_r); if (document.MAX_used != ',') document.write ("&exclude=" + document.MAX_used); document.write (document.charset ? '&charset='+document.charset : (document.characterSet ? '&charset='+document.characterSet : '')); document.write ("&loc=" + escape(window.location)); if (document.referrer) document.write ("&referer=" + escape(document.referrer)); if (document.context) document.write ("&context=" + escape(document.context)); if (document.mmm_fo) document.write ("&mmm_fo=1"); document.write ("'><\/scr"+"ipt>"); //]]>-->

[technicaldr]

Fix the EHR!

After a blizzard of hype surrounding the electronic health record (EHR), health professionals are now in full backlash mode against this complex new tool. They are rightly seen as a major cause of professional burnout among physicians and nurses: Clinicians are spending almost half their professional time typing, clicking, and checking boxes on electronic records. They can and must be made into useful, easy-to-use tools that liberate, rather than oppress, clinicians.

  Performing several tasks, badly. The EHR is a lot more than merely an electronic version of the patient’s chart. It has also become the control panel for managing the clinical encounter through clinician order entry. Moreover, through billing and regulatory compliance, it has also become a focal point of quality-improvement efforts. While some of these efforts actually have improved quality and patient safety, many others served merely to “buff up the note” to make the clinician look good on “process” measures, and simply maximize billing.

  Mashing up all these functions — charting, clinical ordering, billing/compliance and quality improvement — inside the EHR has been a disaster for the clinical user, in large part because the billing/compliance function has dominated. The pressure from angry physician users has produced a medieval solution: Hospital and clinics have hired tens of thousands of scribes literally to follow clinicians around and record their notes and orders into the EHR. Only in health care, it seems, could we find a way to “automate” that ended up adding staff and costs!

  As bad as the regulatory and documentation requirements are, they are not the largest problem. The electronic system's hospitals have adopted at huge expense are fronted by user interfaces out of the mid-1990s: Windows 95-style screens and drop-down menus, data input by typing and navigation by point and click. These antiquated user interfaces are astonishingly difficult to navigate. Clinical information vital for care decisions is sometimes entombed dozens of clicks beneath the user-facing pages of the patient’s chart.

  Paint a picture of the patient. For EHRs to become truly useful tools and liberate clinicians from the busywork, a revolution in usability is required. Care of the patient must become the EHR’s central function. At its center should be a portrait of the patient’s medical situation at the moment, including the diagnosis, major clinical risks and trajectory, and the specific problems the clinical team must resolve. This ���uber-assessment” should be written in plain English and have a discrete character limit like those imposed by Twitter, forcing clinicians to tighten their assessment.

  The patient portrait should be updated frequently, such as at a change in clinical shifts. Decision rules determining precisely who has responsibility for painting this portrait will be essential. In the inpatient setting, the main author may be a hospitalist, primary surgeon, or senior resident. In the outpatient setting, it’s likely to be the primary care physician or non-physician provider. While one individual should take the lead, this assessment should be curated collaboratively, a la Wikipedia.

  This clinical portrait must become the rallying point of the team caring for the patient. To accomplish this, the EHR needs to become “groupware” for the clinical team, enabling continuous communication among team members. The patient portrait should function as the “wall” on which team members add their own observations of changes in the patient’s condition, actions they have taken, and questions they are trying to address. This group effort should convey an accurate picture (portrait plus updates) for new clinicians starting their shifts or joining the team as consultants.

  The tests, medications or procedures ordered, and test results and monitoring system readings should all be added (automatically) to the patient’s chart. But here, too, a major redesign is needed. In reimagining the patient’s chart, we need to modify today’s importing function, which encourages users indiscriminately to overwhelm the clinical narrative with mountains of extraneous data. The minute-by-minute team comments on the wall should erase within a day or two, like images in SnapChat, and not enter and complicate the permanent record.

  Typing and point and click must go. Voice and gesture-based interfaces must replace the unsanitary and clunky keyboard and mouse as the method of building and be interacting with the record. Both documenting the clinical encounter and ordering should be done by voice command, confirmed by screen touch. Orders should display both the major risks and cost of the tests or procedures ordered before the order can be confirmed. Several companies, including Google and Microsoft, are already piloting “digital” scribes that convert the core conversation between doctor and patient into a digital clinical note.

  Moreover, interactive data visualization must replace the time-wasting click storm presently required to unearth patient data. Results of voice searches of the patient’s record should be available for display in the nursing station and the physicians’ ready room. It should also be presentable to patients on interactive whiteboards in patient rooms. Physicians should be able to say things like: “Show me Jeff’s glucose and creatinine values graphed back to the beginning of this hospital stay” or “Show me all of Bob’s abdominal CT scans performed pre- and postoperatively.” The physician should also be able to prescribe by voice command everything from a new medication to a programmed reminder to be delivered to the patient’s iPhone at regular intervals.

  Population health data and research findings should also be available by voice command. For example, a doctor should be able to say: “Show me all the published data on the side-effect risks associated with use of pembrolizumab in lung cancer patients, ranked from highest to lowest,” or “Show me the prevalence of postoperative complications by type of complication in the past thousand patients who have had knee replacements in our health system, stratified by patient age.”

  AI must make the clinical system smarter. EHRs already have rudimentary artificial intelligence (AI) systems to help with billing, coding, and regulatory compliance. But the primitive state of AI in EHRs is a major barrier to effective care. Clinical record systems must become a lot smarter if clinical care is to predominate, in particular by reducing needless and duplicative documentation requirements. Revisiting Medicare payment policy, beginning with the absurdly detailed data requirements for Evaluation and Management visits (E&M), would be a great place to start.

  The patient’s role should also be enhanced by the EHR and associated tools. Patients should be able to enter their history, medications, and family history remotely, reducing demands on the care team and its supporting cast. Patient data should also flow automatically from clinical laboratories, as well as data from instrumentation attached to the patient, directly to the record, without the need for human data entry.

  Of course, a new clinical workflow will be needed to curate all of this patient-generated data and respond accordingly. It cannot be permitted to clutter the wall or be “mainlined” to the primary clinical team; rather, it must be prioritized according to patient risk/benefit and delivered via a workflow designed expressly for this purpose. AI algorithms must also be used to scrape from the EHR the information needed to assign acuity scores and suggest diagnoses that accurately reflect the patient’s current state.

  Given how today’s clinical alert systems inundate frontline caregivers, it is unsurprising that most alerts are ignored. It is crucial that the EHR be able to prioritize alerts that address only immediate threats to the patient’s health in real time. Health care can learn a lot from the sensible rigor and discipline of the alert process in the airline cockpit. Clinical alerts should be presented in an easy-to-read, hard-to-ignore color-coded format. Similarly, hard stops — system-driven halts in medication or other therapies — must be intelligent; that is, they must be related to the present reality of the patient’s condition and limited to clinical actions that truly threaten the health or life of the patient.

  From prisoners to advocates. The failure of EHRs thus far to achieve the goals of improving healthcare productivity, outcomes, and clinician satisfaction is the result both of immature technology and the failure of their architects to fully respect the complexity of converting the massive health care system from one way of doing work to another. Today, one can see a path to turning the EHR into a well-designed and useful partner to clinicians and patients in the care process. To do this, we must use AI, vastly improved data visualization, and modern interface design to improve usability. When this has been accomplished, we believe that clinicians will be converted from surly prisoners of poorly realized technology to advocates of the systems themselves and enthusiastic leaders of efforts to further improve them.

Technical Dr. Inc.'s insight:

Contact Details :

inquiry@technicaldr.com or 877-910-0004 www.technicaldr.com

[sherristockman]

CRISPR: Crispy Fries Your DNA Dr. Mercola By Dr. Mercola CRISPR gene-editing technology brought science fiction to life with its ability to cut and paste DNA fragments, potentially eliminating serious inherited diseases. CRISPR-Cas9, in particular, has gotten scientists excited because,1 by modifying an enzyme called Cas9, the gene-editing capabilities are significantly improved. That's not to say they're perfect, however, as evidenced by a recent study that showed CRISPR may have significant unintended consequences to your DNA, including large deletions and complex rearrangements.2 Many of the concerns to date regarding CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeat, technology have centered on off-target mutations. The featured study, published in Nature Biotechnology, looked at on-target mutations at the site of the "cuts," revealing potentially dangerous changes that could increase the risk of chronic diseases like cancer. Is CRISPR Scrambling DNA? Researchers at the U.K.'s Wellcome Sanger Institute systematically studied mutations from CRISPR-Cas9 in mouse and human cells, focusing on the gene-editing target site. Large genetic rearrangements were observed, including DNA deletions and insertions, that were spotted near the target site. They were far enough away, however, that standard tests looking for CRISPR-related DNA damage would miss them. The DNA deletions could end up activating genes that should stay "off," such as cancer-causing genes, as well as silencing those that should be "on." One of the study's authors, professor Allan Bradley, said in a statement:3 "This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects." The deletions detected were at a scale of "thousands of bases," which is more than previously thought and enough to affect adjacent genes. For instance, deletions equivalent to thousands of DNA letters were revealed. "In one case, genomes in about two-thirds of the CRISPR'd cells showed the expected small-scale inadvertent havoc, but 21 percent had DNA deletions of more than 250 bases and up to 6,000 bases long," Scientific American reported.4 The cells targeted by CRISPR try to "stitch things back together," according to Bradley, "But it doesn't really know what bits of DNA lie adjacent to each other." As a result, the DNA may be rearranged, previously distant DNA sequences may become attached, or unrelated sections could be incorporated into the chromosome.5 Cas9, a bacteria enzyme that acts as the "scissors" in CRISPR, actually remains in the body for a period of hours to weeks. Even after the initial DNA segment had been cut out and a new section "pasted" into the gap to repair it, Cas9 continued to make cuts into the DNA. "[T]he scissors continued to cut the DNA over and over again. They found significant areas near the cut site where DNA had been removed, rearranged or inverted," The Conversation reported.6 Does This Mean CRISPR Isn't Safe? It's too soon to say what the long-term effects of gene-editing technology will be, and there are many variables to the safety equation. The findings likely only apply to CRISPR-Cas9, which cuts through the DNA's double strand. Other CRISPR technologies exist that may alter only a single strand or not involve cutting at all, instead swapping DNA letters. There are also CRISPR systems that target RNA instead of DNA and those that could potentially involve only cells isolated from the body, such as white blood cells, which could then be analyzed for potential mutations before being put back into the body.7 The Nature study did make waves in the industry, though, such that within the first 20 minutes of the results being made public three CRISPR companies lost more than $300 million in value.8 Some companies using CRISPR have said they're already on the lookout for large and small DNA deletions (including one company using the technology to make pig organs that could be transplanted into humans). One company also claims it hasn't found large deletions in their work on cells that do not divide often (the Nature study used actively dividing cells).9 The researchers are standing by their findings, however, which the journal took one year to publish. During that time, Bradley says, he was asked to conduct additional experiments and "the results all held up."10 Past studies have also found unexpected mutations, including one based on a study that used CRISPR-Cas9 to restore sight in blind mice by correcting a genetic mutation. The researchers sequenced the entire genome of the CRISPR-edited mice to search for mutations. In addition to the intended genetic edit, they found more than 100 additional deletions and insertions along with more than 1,500 single-nucleotide mutations.11 The study was later retracted, however, due to insufficient data and a need for more research to confirm the results.12 CRISPR-Edited Cells Could Cause Cancer Revealing the many complexities of gene editing, CRISPR-Cas9 also leads to the activation of the p53 gene, which works to either repair the DNA break or kill off the CRISPR-edited cell.13 CRISPR actually has a low efficacy rate for this reason, and CRISPR-edited cells that survive are able to do so because of a dysfunctional p53. The problem is that p53 dysfunction is also linked to cancer (including close to half of ovarian and colorectal cancers and a sizable portion of lung, pancreatic, stomach, breast and liver cancers as well).14 In one recent study, researchers were able to boost average insertion or deletion efficiency to greater than 80 percent, but that was because of a dysfunctional p53 gene,15 which would mean the cells could be predisposed to cancer. The researchers noted, " … it will be critical to ensure that [CRISPR-edited cells] have a functional p53 before and after engineering."16 A second study, this one by the Karolinska Institute in Sweden, found similar results and concluded, " … p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9."17 Some have suggested that if CRISPR could cure one chronic or terminal disease at the "cost" of an increased cancer risk later,18 it could still be a beneficial technology, but most agree that more work is needed and caution warranted. A CRISPR clinical trial in people with cancer is already underway in China, and the technology has been used to edit human embryos made from sperm from men carrying inherited disease mutations. The researchers successfully altered the DNA in a way that would eliminate or correct the genes causing the inherited disease.19 If the embryos were implanted into a womb and allowed to grow, the process, which is known as germline engineering, would result in the first genetically modified children — and any engineered changes would be passed on to their own children. A February 2017 report issued by the U.S. National Academies of Sciences (NAS) basically set the stage for allowing research on germline modification (such as embryos, eggs and sperm) and CRISPR, but only for the purpose of eliminating serious diseases. In the U.S., a first of its kind human trial involving CRISPR is currently recruiting participants with certain types of cancer. The trial is going to attempt to use CRISPR to modify immune cells to make them attack tumor cells more effectively. As far as risks from potential mutations, it's anyone's guess, but lead researcher Dr. Edward Stadtmauer of the University of Pennsylvania told Scientific American, "We are doing extensive testing of the final cellular product as well as the cells within the patient."20 Are 'Designer Babies' Next? It's easy to argue for the merits of CRISPR when you put it in the context of curing deafness, inherited diseases or cancer, and at least 17 clinical trials using gene-editing technologies to tackle everything from gastrointestinal cancer to tumors of the central nervous system to sickle cell disease have been registered in the U.S.21 Another use of the technology entirely is the creation of "designer babies" with a certain eye color or increased intelligence. About 40 countries have already banned the genetic engineering of human embryos and 15 of 22 European countries prohibit germ line modification.22 In the U.S., the NAS report specifically said research into CRISPR and germline modification could not be for "enhancing traits or abilities beyond ordinary health." Still, using gene editing to create designer babies is a question of when, not if, with some experts saying it could occur in a matter of decades.23 There are both safety and ethical considerations to think about. With some proponents saying it would be unethical not to use the technology. For instance, Julian Savulescu, an ethicist at the University of Oxford, told Science News he believes parents would be morally obligated to use gene-editing technology to keep their children healthy. "If CRISPR could … improve impulse control and give a child a greater range of opportunities, then I'd have to say we have the same moral obligation to use CRISPR as we do to provide education, to provide an adequate diet …"24 Others have suggested CRISPR could represent a new form of eugenics, especially since it can only be done via in vitro fertilization (IVF), putting it out of reach of many people financially and potentially expanding inequality gaps. On the other hand, some argue that countries with national health care could provide free coverage for gene editing, possibly helping to reduce inequalities.25 It's questions like these that make determining the safety of CRISPR and other gene-editing technology more important now than ever before. What Does a CRISPR-Enabled Future Hold? We've already entered the era of genetic engineering and CRISPR represents just one piece of the puzzle. It's an exciting time that could lead to major advances in diseases such as sickle-cell anemia, certain forms of blindness, muscular dystrophy, HIV and cancer, but also one that brings the potential for serious harm. In addition to work in human and animal cells, gene-edited crops, in which DNA is tweaked or snipped out at a precise location, have already been created — and eaten. To date, the technology has been used to produce soybeans with altered fatty acid profiles, potatoes that take longer to turn brown and potatoes that remain fresher longer and do not produce carcinogens when fried. The latter could be sold as early as 2019. The gene-editing science, in both plants and animals, is progressing far faster than long-term effects can be fully realized or understood. There are many opportunities for advancement to be had, but they must come with the understanding that unintended mutations with potentially irreversible effects could be part of the package.

[kristinsimmons]

Making Electronic Health Records Great Again

By ROBERT WACHTER and JEFF GOLDSMITH

After a blizzard of hype surrounding the electronic health record (EHR), health professionals are now in full backlash mode against this complex new tool. They are rightly seen as a major cause of professional burnout among physicians and nurses: Clinicians are spending almost half their professional time typing, clicking, and checking boxes on electronic records. They can and must be made into useful, easy-to-use tools that liberate, rather than oppress, clinicians.

Performing several tasks, badly. The EHR is a lot more than merely an electronic version of the patient’s chart. It has also become the control panel for managing the clinical encounter through clinician order entry. Moreover, through billing and regulatory compliance, it has also become a focal point of quality-improvement efforts. While some of these efforts actually have improved quality and patient safety, many others served merely to “buff up the note” to make the clinician look good on “process” measures, and simply maximize billing.

Mashing up all these functions — charting, clinical ordering, billing/compliance and quality improvement — inside the EHR has been a disaster for the clinical user, in large part because the billing/compliance function has dominated. The pressure from angry physician users has produced a medieval solution: Hospital and clinics have hired tens of thousands of scribes literally to follow clinicians around and record their notes and orders into the EHR. Only in health care, it seems, could we find a way to “automate” that ended up adding staff and costs!

As bad as the regulatory and documentation requirements are, they are not the largest problem. The electronic systems hospitals have adopted at huge expense are fronted by user interfaces out of the mid-1990s: Windows 95-style screens and dropdown menus, data input by typing and navigation by point and click. These antiquated user interfaces are astonishingly difficult to navigate. Clinical information vital for care decisions is sometimes entombed dozens of clicks beneath the user-facing pages of the patient’s chart.

Paint a picture of the patient. For EHRs to become truly useful tools and liberate clinicians from the busywork, a revolution in usability is required. Care of the patient must become the EHR’s central function. At its center should be a portrait of the patient’s medical situation at the moment, including the diagnosis, major clinical risks and trajectory, and the specific problems the clinical team must resolve. This “uber-assessment” should be written in plain English and have a discrete character limit like those imposed by Twitter, forcing clinicians to tighten their assessment.

The patient portrait should be updated frequently, such as at a change in clinical shifts. Decision rules determining precisely who has responsibility for painting this portrait will be essential. In the inpatient setting, the main author may be a hospitalist, primary surgeon, or senior resident. In the outpatient setting, it’s likely to be the primary care physician or non-physician provider. While one individual should take the lead, this assessment should be curated collaboratively, a la Wikipedia.

This clinical portrait must become the rallying point of the team caring for the patient. To accomplish this, the EHR needs to become “groupware” for the clinical team, enabling continuous communication among team members. The patient portrait should function as the “wall” on which team members add their own observations of changes in the patient’s condition, actions they have taken, and questions they are trying to address. This group effort should convey an accurate picture (portrait plus updates) for new clinicians starting their shifts or joining the team as consultants.

The tests, medications or procedures ordered, and test results and monitoring system readings should all be added (automatically) to the patient’s chart. But here, too, major redesign is needed. In reimagining the patient’s chart, we need to modify today’s importing function, which encourages users indiscriminately to overwhelm the clinical narrative with mountains of extraneous data. The minute-by-minute team comments on the wall should erase within a day or two, like images in SnapChat, and not enter and complicate the permanent record.

Typing and point and click must go. Voice and gesture-based interfaces must replace the unsanitary and clunky keyboard and mouse as the method of building and interacting with the record. Both documenting the clinical encounter and ordering should be done by voice command, confirmed by screen touch. Orders should display both the major risks and cost of the tests or procedures ordered before the order can be confirmed. Several companies, including Google and Microsoft, are already piloting “digital” scribes that convert the core conversation between doctor and patient into a digital clinical note.

Moreover, interactive data visualization must replace the time-wasting click storm presently required to unearth patient data. Results of voice searches of the patient’s record should be available for display in the nursing station and the physicians’ ready room. It should also be presentable to patients on interactive white boards in patient rooms. Physicians should be able to say things like: “Show me Jeff’s glucose and creatinine values graphed back to the beginning of this hospital stay” or “Show me all of Bob’s abdominal CT scans performed pre- and postoperatively.” The physician should also be able to prescribe by voice command everything from a new medication to a programmed reminder to be delivered to the patient’s iPhone at regular intervals.

Population health data and research findings should also be available by voice command. For example, a doctor should be able to say: “Show me all the published data on the side-effect risks associated with use of pembrolizumab in lung cancer patients, ranked from highest to lowest,” or “Show me the prevalence of postoperative complications by type of complication in the past thousand patients who have had knee replacements in our health system, stratified by patient age.”

AI must make the clinical system smarter. EHRs already have rudimentary artificial intelligence (AI) systems to help with billing, coding, and regulatory compliance. But the primitive state of AI in EHRs is a major barrier to efficient care. Clinical record systems must become a lot smarter if clinical care is to predominate, in particular by reducing needless and duplicative documentation requirements. Revisiting Medicare payment policy, beginning with the absurdly detailed data requirements for Evaluation and Management visits (E&M), would be a great place to start.

The patient’s role should also be enhanced by the EHR and associated tools. Patients should be able to enter their history, medications, and family history remotely, reducing demands on the care team and its supporting cast. Patient data should also flow automatically from clinical laboratories, as well as data from instrumentation attached to the patient, directly to the record, without the need for human data entry.

Of course, a new clinical workflow will be needed to curate all of this patient-generated data and respond accordingly. It cannot be permitted to clutter the wall or be “mainlined” to the primary clinical team; rather, it must be prioritized according to patient risk/benefit and delivered via a workflow designed expressly for this purpose. AI algorithms must also be used to scrape from the EHR the information needed to assign acuity scores and suggest diagnoses that accurately reflect the patient’s current state.

Given how today’s clinical alert systems inundate frontline caregivers, it is unsurprising that most alerts are ignored. It is crucial that the EHR be able to prioritize alerts that address only immediate threats to the patient’s health in real time. Health care can learn a lot from the sensible rigor and discipline of the alert process in the airline cockpit. Clinical alerts should be presented in an easy-to-read, hard-to-ignore color-coded format. Similarly, hard stops — system-driven halts in medication or other therapies — must be intelligent; that is, they must be related to the present reality of the patient’s condition and limited to clinical actions that truly threaten the health or life of the patient.

From prisoners to advocates. The failure of EHRs thus far to achieve the goals of improving health care productivity, outcomes, and clinician satisfaction is the result both of immature technology and the failure of their architects to fully respect the complexity of converting the massive health care system from one way of doing work to another. Today, one can see a path to turning the EHR into a well-designed and useful partner to clinicians and patients in the care process. To do this, we must use AI, vastly improved data visualization, and modern interface design to improve usability. When this has been accomplished, we believe that clinicians will be converted from surly prisoners of poorly realized technology to advocates of the systems themselves and enthusiastic leaders of efforts to further improve them.

Robert Wachter, MD is chair of the Department of Medicine at the University of California, San Francisco.

Jeff Goldsmith is national adviser to Navigant Consulting and an associate professor of public health sciences at the University of Virginia.

This post first appeared in Harvard Business Review.

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