#37688

[leomacgivena]

山猫だぶ㌠さんはTwitterを使っています：「記載者がツイ廃だからじゃないですかね」

[nuadox]

Innovative molecular biology technique allows for discovery of novel targets for candidate vaccines against schistosomiasis

- By Luciana Constantino , Agência FAPESP -

Researchers in Brazil have used an innovative technique in molecular biology to identify targets for candidate vaccines against Schistosoma mansoni, the parasite that causes schistosomiasis.

Considered one of the world’s 17 neglected tropical diseases (NTDs), schistosomiasis affects some 200 million people in 74 countries, according to the World Health Organization (WHO). Six million are estimated to be infected in Brazil, mainly in the Northeast region and Minas Gerais state.

The scientists used phage display, the study of protein interactions using bacteriophages, viruses that infect bacteria, to screen 99.6% of 119,747 DNA sequences encoding the proteins known to be expressed across all life-cycle stages of the parasite, achieving comprehensive coverage of its proteome.

The results of the study are reported in an article in NPJ Vaccines, an open-access journal published by the Springer Nature group. 

They follow on from those of a previous study that revealed the mechanism whereby the Rhesus macaque Macaca mulatta naturally develops a lasting immune response against schistosomiasis by inhibiting certain of the parasite’s genes so that it cannot multiply in the host organism. This immune response leads to self-cure after first contact with S. mansoni and enables the animal to react faster to a second infection (read more at: agencia.fapesp.br/37688).

“Phage display had never been deployed for this purpose in research on parasitic diseases, which normally involves preselection of a few targets for testing of candidate vaccines. In this study, we screened 12,000 proteins of S. mansoni at the same time to identify which ones were targeted by the macaque’s antibodies, both after initial infection and reinfection and after reinfection and self-cure, a key innovation. Both the technique and the model for the study were innovative,” said Murilo Sena Amaral, a researcher at Butantan Institute’s Laboratory of Cell Cycle.

Amaral is the penultimate author of the article. The last author, as principal investigator for the study, is Sergio Verjovski-Almeida, also a researcher at Butantan Institute and a professor at the University of São Paulo’s Institute of Chemistry (IQ-USP).

Both are supported by FAPESP (15/06366-2 and 20/01917-9), which has also funded scholarships for other researchers in the group (18/18117-5, 19/02305-0 and 16/10046-6), including a PhD scholarship for first author Daisy Woellner Santos.

Methodology

The researchers investigated the immune response of ten macaques infected by S. mansoni during the stages of self-cure and resistance to reinfection using a recently developed technique called peptide library-based phage immunoprecipitation sequencing (PhIP-Seq). They constructed a phage display library that comprised 119,747 DNA sequences encoding 11,641 known proteins from S. mansoni in all stages of its life cycle. The library was incubated with antibodies collected from rhesus macaques in a previous study at different points during the process of self-cure and resistance to reinfection. The aim was to isolate and identify specific targets of the animal’s immune response to the parasite.

The study involved rhesus macaques, which naturally develop a lasting immune response to the disease (photo: researcher’s archive)

Library screening with antibodies from the early phase of parasite infection identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the host’s digestive tract, shifting toward intracellular proteins during the late phase of parasite clearance (released owing to its death). Epitope refers to the specific target against which an individual antibody binds. When an antibody binds to a protein, it bonds not to the entire protein but to a segment known as an epitope.

The enriched peptides were analyzed with bioinformatics tools to identify potential candidates for vaccines. The most promising candidates were tested in a pilot vaccination assay, in which mice were immunized with a selected pool of PhIP-Seq-enriched phage-displayed peptides. The result was a significant reduction of worm burden in the immunized mice.

“You often hear the argument that a schistosomiasis vaccine isn’t feasible, but our discoveries have revealed a great deal of the immune response and opened up promising prospects for the development of an effective vaccine. We worked with the 12,000 proteins key to all stages of the parasite’s life cycle and succeeded in identifying the most reactive targets,” Verjovski-Almeida told Agência FAPESP. The technique can be used for other types of parasite, he added.

In an article published in May 2023, the group described their discovery of a way to “separate” male and female parasites so as to prevent reproduction and egg release. Male-female pairing, with the female living inside the male, is essential to their survival. Without it, they die. In the study, the researchers showed that male-female separation could be obtained by silencing specific long noncoding RNAs (lncRNAs), which are therefore a promising target for treatment of the disease (read more at: agencia.fapesp.br/41908). 

Female inside male of Schistosoma mansoni (photo: researcher’s archive)

How the worm works

Schistosomiasis is a parasitic disease associated with poor hygiene and a lack of basic sanitation. It is transmitted when an infected person excretes feces containing schistosome eggs into the environment. The eggs hatch in freshwater, releasing larvae that infect snails. The snails are intermediate hosts, while humans are definitive hosts.

After four weeks, the larvae leave the snail as cercariae, the free-swimming larval stage. When humans come into contact with contaminated water, they acquire the disease via active skin penetration by cercariae.

In the human bloodstream, the cercariae progress to the schistosomule stage, eventually becoming adult worms that lodge in the veins of the intestines. The first symptoms of the disease appear two to six weeks after infection.

The disease is diagnosed by laboratory analysis of feces. Simple cases can be treated by a single dose of praziquantel, a drug discovered in the 1970s and distributed in Brazil by the national health system (Sistema Único de Saúde, SUS). However, it does not assure continuous protection. Patients taking it can be reinfected, and there are reports of parasite drug resistance.

“The next step is to develop a suitable vaccine formulation containing adjuvants and a novel mechanism for delivery of these antigens so that they produce better protection in the host. We have some targets with higher response levels,” Verjovski-Amaral explained. Butantan Institute has applied for a patent on the group’s discoveries linked to possible vaccine targets.

Oswaldo Cruz Foundation (FIOCRUZ), an arm of the Brazilian Health Ministry, has been working for years on what could be the world’s first schistosomiasis vaccine. Called Schistovac, it is in the testing stage and contains a modified version of the Sm14 protein found in S. mansoni. The protein normally plays a key role in trafficking fatty acids, which are essential to the parasite’s cellular functions. The modified version is designed to prevent proliferation.

The article “Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques” is at: www.nature.com/articles/s41541-023-00803-x.  

This text was originally published by FAPESP Agency according to Creative Commons license CC-BY-NC-ND. Read the original here.

--

Header image: This micrograph reveals four Schistosoma mansoni trematodes, a pair (left), a female (center), and a male (right). Credit: CDC/Wikimedia Commons. Ed note: A slight blue filter has been applied.

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[wutbju]

Thomas Strickler Newcomer, 81, husband of Janet Marie Huntington Newcomer, was gently led home by his heavenly Father on Saturday, August 26, 2023 at his home in Mountain City, TN.

If you could summarize a lifetime in a few words, Tom’s would include faithfulness, love, family, discipleship and soul winning. A man of few spoken words, he expressed his thoughts, prayers, and aspirations in poetry.

Tom was born on January 1, 1942, in Winter Garden, FL, to John Gilson and Grace Hope Newcomer. He was the ninth of ten children.

Tom earned his B.A in English and his M.A. in Educational Administration at Bob Jones University in Greenville, SC. He administered and taught in Christian schools over the years. He and his wife owned and managed reupholstery and commercial cleaning businesses. He enjoyed reading, family hikes in the mountains, singing the old hymns of the faith and writing poetry. His ample library includes countless treasured and well-marked Bibles.

In addition to his loving wife of 59 years, he is survived by his daughters Loretta Newcomer, Belinda (Ryan) Parker, and Rebecca Ring; his grandchildren; his sister Mary (Glen) Wiedenhaupt; and brothers Joseph (Patricia), and David (Beverly) Newcomer.

He was preceded in death by his parents John and Grace Newcomer; his son John Newcomer; his siblings Loranna Wright, James Newcomer, Charlotte Newcomer, Jessie Auer, Charlee Jackson and John Newcomer.

A graveside service will be held on Saturday, September 2, 2023, at 10:00 a.m. at the Shady Valley Memorial Gardens with Pastor Bob Jones to officiate, 9727 U.S. 421, Shady Valley, TN, 37688. Pallbearers will be Tom's grandsons.

[ilgiomba]

Non cambierò. E non ce n'è motivo!

Non cambierò. E non ce n'è motivo! Che si metta il cuore in pace chiunque pensa che basti qualche stupida invettiva per farmi cambiare idea!

LEGGI TUTTO L'ARTICOLO AL LINK https://www.ilgiomba.it/non-cambiero-e-non-ce-ne-motivo/37688

[guerrerense]

Wetex por Stapleton Road Por Flickr: Last night we had high winds and torrential rain on the coast in Devon. As the sun rose the rain abated but the winds from the east increased, this means stormy seas. High tide was at 1335 in Dawlish which more or less coincided with the arrival of what would have been in old money an ADEX (advertised day excursion) that being the 1Z45 0600 York to Paignton hauled by 37688 and 37521 with 47828 on the back. What a day for it.

[ginsterphotography]

the sad sight at Healey Mills yard in West Yorkshire, 09/09/2005, withdrawn locos waiting for the scrap man, I think a few made it out alive, notably front left, 37688.

[saskia-stefan-unterwegs]

Weserbergland 9.0

5.5.22 - 8.5.22

Endlich wieder....eine Motorradtour mit Freunden.  Anreise: Donnerstag, 5. Mai / Abreise: Sonntag: 8. Mai Unterkunft: Landhotel Weserblick, Kasseler Straße 2, 37688 Beverungen Teilnehmer: Chapter Nord (Jörg, Kai-Erik, Sonja, Sven), Chapter West (Saskia, Stefan), Chapter Süd (Gabi, Lucia, Rolf) Treff Chapter West & Süd: ca. 13h im Saustall in Wetterburg Treff alle Chapter: ca. 15h30 im Biergarten an der Unterkunft "Weserblick"

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37688 - Dorsley Park Farm, Totnes. by Nathan S Via Flickr: An almost entire withdrawal of GWR's IET fleet over the weekend lead the operator looking around for suitable stock to cover. At the time of this photograph just two IETs were available for traffic due to cracks in the fleets yaw dampers and/or lifting points. Locomotive Services Limited have provided five ex EMR HST trailers for GWR to pair with their own power cars to help provide some capacity. The Mk3 trailers are seen here climbing Rattery behind 37688 on transfer from Crewe to Laira.

[ifallininlovewithyou]

[mansheb]

I'm not gay: #IdolsSA judge Somizi reveals his tlof tlof preferences to Dineo Ranaka (WATCH VIDEO)

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I'm not gay: #IdolsSA judge Somizi reveals his tlof tlof preferences to Dineo Ranaka (WATCH VIDEO)

Media personality, author, and choreographer Somizi Mhlongo says he does not want to be "boxed" about his seexxuality. Mhlongo said this during a recent interview with Dineo Ranaka and Sol Phenduka during the Kaya Breakfast on Kaya 959. The breakfast show hosts said they were "decoding" the veteran entertainer. "I don't want to be boxed," […] Read more on I'm not gay: #IdolsSA judge Somizi reveals his tlof tlof preferences to Dineo Ranaka (WATCH VIDEO)

[interestingasfuckreddit]

Lurker, ink and acrylic painting https://t.me/InterestingasfuckBackup/37688 #interestingasfuck #rinterestingasfuck #interestingasfuckreddit #interestingasfucksubreddit #r_interestingasfuck

[guerrerense]

I Don't Believe It ! por Stapleton Road Por Flickr: youtu.be/iDFDAv_mdOg In true Victor Meldrew style I was incredulous this morning as I stood in a freezing sleet and snow shower to photograph the 0901 TRO -PLM LSL tour. The train was running pretty much 20 minutes late, had it been on time then I would have been bathed in glorious April sunshine. As it turned out the temperature was just above freezing and the heavens dumped a chuffin massive cloud full of sleet and snow on top of me. So.....bringing up the rear of said service is 37688 racing through Lostwithiel. For the record, I managed to get ahead of it at the Royal Albert Bridge. Stay tuned.

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LA Clippers' Kawhi Leonard remains out for Game 4 vs. Phoenix Suns, Marcus Morris a game-time decision PLAYA VISTA, Calif. -- Kawhi Leonard sta... Read the rest on our site with the url below https://worldwidetweets.com/la-clippers-kawhi-leonard-remains-out-for-game-4-vs-phoenix-suns-marcus-morris-a-game-time-decision/?feed_id=37688&_unique_id=60d7dee9b9610 #IvicaZubac #KawhiLeonard #LAClippers #MarcusMorrisSr. #nba #News #PhoenixSuns #TeranceMann