#reactive oxygen species

[existennialmemes]

[oxygen atom voice] I'm essential to survival! I keep your cells healthy! But if you're not careful, I will also rip those cells apart looking for stealable electrons. Tee Hee! Best of luck, bitch.

[bpod-bpod]

ROS vs Bacteria

Inducing lung lining cells to produce bacteria-killing reactive oxygen species (highly reactive chemicals that can cause oxidative damage) protects against pneumonia without reliance on antibiotics

Read the published research paper here

Image from work by Yongxing Wang and colleagues

Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in PLOS Pathogens, September 2023

You can also follow BPoD on Instagram, Twitter and Facebook

[medicomunicare]

DNA repair going APE and strand breaks fixing with ATM: please no cash, just redox and contact bases

New research from a team of genome scientists and DNA damage response (DDR) experts breaks new ground in understanding the function of a protein currently limited in clinical trials for cancer treatments. The new investigaton shows how ATM-mediated signaling is induced by DNA single-strand breaks (SSBs) for DNA damage repair – illuminating the distinct mechanisms of SSB-induced ATM kinase and…

[whats-in-a-sentence]

ROS detoxification enzymes and antioxidants function in cells as a network supported by various antioxidant recycling systems that replenish the level of reduced antioxidants (Figure 24.20).

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[tenth-sentence]

Target proteins include transcription factors, various protein kinases, Ca²+-ATPases, enzymes producing reactive oxygen species (ROS), and ion channels.

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[blueoaknx]

Mitochondrial Dysfunction in mtARS Disorders

Introduction

Mitochondria are indispensable organelles that facilitate cellular bioenergetics, predominantly through oxidative phosphorylation (OXPHOS). Mitochondrial aminoacyl-tRNA synthetases (mtARS) are essential for the fidelity of mitochondrial translation, catalyzing the ligation of amino acids to their cognate tRNAs. Mutations in mtARS genes precipitate a spectrum of mitochondrial disorders, culminating in dysfunctional protein synthesis and aberrant mitochondrial bioenergetics. This review delves into the molecular pathogenesis of mitochondrial dysfunction in mtARS disorders, elucidating their biochemical perturbations, clinical phenotypes, and emerging therapeutic paradigms.

Molecular Pathophysiology of mtARS Disorders

MtARS enzymes ensure translational accuracy by charging mitochondrial tRNAs with their respective amino acids, a prerequisite for mitochondrial protein biosynthesis. Pathogenic variants in mtARS genes result in defective aminoacylation, perturbing mitochondrial translation and compromising the integrity of the electron transport chain (ETC). These perturbations induce bioenergetic deficits, increased reactive oxygen species (ROS) production, and secondary mitochondrial stress responses, leading to cellular demise.

Genetic Etiology of mtARS Mutations

Dysfunctional mtARS genes such as DARS2, AARS2, RARS2, and YARS2 have been implicated in autosomal recessive mitochondrial disorders. These mutations exhibit tissue-specific phenotypic heterogeneity, with neurological, muscular, and systemic manifestations. For instance, DARS2 mutations drive leukoencephalopathy with brainstem and spinal cord involvement, whereas AARS2 defects result in a constellation of neurodegenerative and ovarian pathologies.

Biochemical and Cellular Consequences

Dysfunctional mtARS enzymes manifest in multifaceted mitochondrial deficits, including impaired translation, defective OXPHOS, and dysregulated mitochondrial proteostasis.

Disruption of Mitochondrial Translation

Impaired aminoacylation abrogates the synthesis of mitochondrially encoded proteins, undermining the assembly of ETC complexes. This translational arrest culminates in defective ATP synthesis and precipitates a systemic energy deficit.

Electron Transport Chain Dysfunction and Bioenergetic Failure

Pathogenic mtARS mutations lead to OXPHOS inefficiencies, reducing mitochondrial membrane potential (Δψm) and ATP output. Perturbed electron flux exacerbates ROS accumulation, instigating oxidative damage and apoptotic cascades.

Mitochondrial Unfolded Protein Response (UPRmt) Activation

Cellular compensatory mechanisms, including UPRmt, are upregulated in response to mitochondrial translation failure. UPRmt mitigates proteotoxic stress via chaperone-mediated protein refolding and degradation pathways. However, chronic UPRmt activation fosters maladaptive stress responses, contributing to progressive cellular degeneration.

Clinical Manifestations

mtARS disorders exhibit phenotypic variability, spanning from mild neuromuscular impairment to severe multisystemic involvement. The pathophysiological hallmark includes disrupted neurological, muscular, and cardiac function.

Neurological Dysfunction

Neurodegeneration is a predominant feature of mtARS disorders, manifesting as ataxia, seizures, intellectual disability, and progressive leukoencephalopathy. Magnetic resonance imaging (MRI) frequently reveals white matter abnormalities, indicative of compromised oligodendrocyte function.

Myopathy and Metabolic Dysregulation

Muscle tissue, with its high ATP demand, is particularly susceptible to mitochondrial dysfunction. Clinical hallmarks include hypotonia, muscle weakness, and exercise intolerance, often concomitant with metabolic anomalies such as lactic acidosis and elevated pyruvate-to-lactate ratios.

Cardiomyopathy and Mitochondrial Energetics

Hypertrophic cardiomyopathy has been observed in YARS2-associated mitochondrial disorders, wherein compromised ATP synthesis in cardiomyocytes disrupts contractile function and electrophysiological stability.

Diagnostic and Functional Evaluation

A combination of genomic, biochemical, and imaging modalities facilitates the diagnosis of mtARS disorders.

Genomic and Transcriptomic Analysis

Whole-exome sequencing (WES) and whole-genome sequencing (WGS) are pivotal for identifying pathogenic mtARS variants. Transcriptomic profiling elucidates perturbations in mitochondrial gene expression networks, further refining diagnostic accuracy.

Functional Mitochondrial Assays

Biochemical assays, including high-resolution respirometry, ATP quantification, and ETC enzymatic profiling, provide insights into mitochondrial bioenergetics. Patient-derived fibroblasts and induced pluripotent stem cells (iPSCs) serve as valuable models for functional interrogation.

Neuroimaging and Biomarker Identification

Advanced imaging modalities such as MR spectroscopy (MRS) detect metabolic derangements, including lactate accumulation in affected brain regions. Circulating mitochondrial-derived peptides and metabolomic signatures are emerging as potential diagnostic biomarkers.

Emerging Therapeutic Strategies

Despite the absence of curative therapies, multiple avenues are under investigation to ameliorate mitochondrial dysfunction in mtARS disorders.

Mitochondria-Directed Antioxidants

Therapeutic compounds such as MitoQ, idebenone, and edaravone aim to attenuate oxidative stress and preserve mitochondrial integrity.

Genetic and RNA-Based Interventions

Gene therapy strategies utilizing adeno-associated virus (AAV)-mediated delivery and CRISPR-based genome editing are being explored for genetic correction of mtARS mutations. Additionally, RNA-based approaches, including antisense oligonucleotides (ASOs) and mRNA replacement therapy, hold promise in restoring mtARS functionality.

Metabolic Modulation and Supportive Therapies

Ketogenic diets, NAD+ precursors (e.g., nicotinamide riboside), and mitochondrial biogenesis activators (e.g., PGC-1α modulators) are under investigation to enhance cellular energy metabolism. Supportive interventions, including physical therapy and neuromuscular rehabilitation, remain integral to patient management.

Conclusion and Future Directions

Mitochondrial dysfunction in mtARS disorders arises from defective mitochondrial translation, OXPHOS perturbation, and maladaptive stress responses. Advances in genomic medicine, mitochondrial therapeutics, and precision medicine approaches are poised to transform the diagnostic and therapeutic landscape. Continued research into mtARS pathobiology, coupled with translational innovations, will be instrumental in developing targeted interventions for affected individuals.

[icpa]

The role of antioxidants in periodontal health | ICPA Health Products Ltd.

Periodontal disease is a persistent inflammatory condition that impacts the tissues encircling our teeth. This condition arises from an imbalance between oral biofilms and the body’s immune response, potentially leading to the loss of tooth-supporting tissues. When this inflammation is confined to the protective periodontium, it’s termed gingivitis. However, when it extends to the periodontal supporting structures, it’s recognized as periodontitis. This prevalent oral disease, affecting 10%-15% of adults, is primarily driven by bacterial plaque microorganisms. Additionally, factors such as systemic health, oral hygiene, age, gender, and smoking play significant roles in its development.

The double-edged sword of Reactive Oxygen Species (ROS)

Reactive oxygen species (ROS) serve as crucial players in our body’s defense against invading pathogens. These molecules have antimicrobial properties that help combat infections in the oral cavity. However, ROS can be a “double-edged sword” since an excessive presence of these molecules can become cytotoxic to our own cells. ROS plays pivotal roles in cell signaling, gene regulation, and antimicrobial defense. An overabundance of ROS, coupled with inadequate antioxidant capacity, can result in oxidative stress within the affected periodontal tissues. This, in turn, leads to pathological changes and the destruction of host tissues, ultimately culminating in the loss of teeth as their supporting structures degrade. Inside cells, ROS can inflict damage on biomolecules and cell membranes, further exacerbating the situation.

The link between oxidative stress and periodontal disease

Emerging research has elucidated the connection between oxidative stress and periodontal disease. In the early stages of periodontal disease, especially in the case of periodontitis, a prominent oxidative process unfolds, characterized by elevated levels of reactive oxygen and nitrogen species (ROS and RNS). This oxidative onslaught can upset the balance of the body’s response, triggering changes in biomolecules, especially lipids, proteins, and nucleic acids, ultimately leading to damage to periodontal tissues.

The role of antioxidants

To counteract the deleterious effects of excessive free radicals generated during oxidative stress, our bodies possess an antioxidant defense system. Antioxidants can inhibit and reduce the damage caused by these harmful molecules. These natural antioxidants are found in various sources, including foods, teas, vitamins, minerals, and more. They are also used in auxiliary treatments for conditions such as cardiovascular diseases, pulmonary diseases, aging, and atherosclerosis, all of which share physiological links with periodontal diseases. This suggests that the application of antioxidants might also yield benefits in managing periodontal health.

Promising results

Recent scientific inquiry supports the idea that antioxidants can play a pivotal role in the treatment of periodontitis. A meta-analysis comprising fifteen clinical trials demonstrated uniformly positive outcomes associated with antioxidant supplementation during periodontitis treatment. These findings offer hope and promise for those seeking alternative therapies to complement traditional periodontal treatments.

Conclusion

As we delve deeper into the intricacies of periodontal disease, the role of oxidative stress and antioxidants emerges as a significant area of interest. Oxidative stress appears to be a key contributor to the development and progression of periodontal

diseases. Antioxidants, with their ability to neutralize harmful free radicals, hold promise as adjunct therapies in managing and mitigating the effects of periodontal disease. With ongoing research in this field, we are one step closer to a more comprehensive understanding of periodontal health and the potential for novel treatments that can preserve our smiles for years to come.

[reasonsforhope]

"A new study evaluated a low-cost yet effective way to combat bacterial resistance using curcumin–the natural yellow plant compound in turmeric.

In 2017, a tragic death in a Nevada hospital was linked to a new strain of bacteria that had developed a resistance to 26 different antibiotics. Called ‘superbugs’, such antibiotic-resistant bacteria (including MRSA) remains a pressing public health threat.

Now researchers at Texas A&M University have shown that curcumin, the compound that gives turmeric its characteristic bright yellow color, can be used to reduce this antibiotic resistance.

They showed that when curcumin is intentionally given to bacteria as food, and then activated by light, it can trigger deleterious reactions within these microbes, eventually killing them. They demonstrated that this process reduces the number of antibiotic-resistant strains and renders conventional antibiotics effective again.

The results of the study were published this week in the journal Scientific Reports.

“We need alternative ways to either kill the superbugs or find a novel way to modify natural processes within the bacteria so that antibiotics start to act again,” said Dr. Vanderlei Bagnato, professor in the Department of Biomedical Engineering and senior author on the study.

Photodynamic inactivation, a technique that has shown promise in combating bacterial resistance, uses light and light-sensitive molecules, called photosensitizers, to produce reactive oxygen species that can kill microorganisms by disrupting their metabolic processes.

In the new experiments, the team used curcumin, which is also a natural food for bacteria. They tested this technique on strains of Staphylococcus aureus (MRSA) that are resistant to amoxicillin, erythromycin, and gentamicin.

The researchers exposed the bacteria to many cycles of light exposure and then compared the minimum concentration of antibiotics needed to kill the bacteria after light exposure versus those that did not get light exposure.

���When we have a mixed population of bacteria where some are resistant, we can use photodynamic inactivation to narrow the bacterial distribution, leaving behind strains that are more or less similar in their response to antibiotics,” Bagnato told Texas A&M News.

“It’s much easier now to predict the precise antibiotic dose needed to remove the infection.”

MORE PROGRESS ON SUPERBUGS: • The Humble Potato Could Hold Key to Beating Hospital Superbugs and Crop Diseases • Compounds in Amber Could Help Fight Drug-Resistant Bacteria Superbugs, Say Scientists • When Antibiotics Failed, She Found a Natural Enemy of the Superbug to Save Husband’s Life

The team noted that photodynamic inactivation using curcumin has tremendous potential as an adjuvant or additional therapy with antibiotics for diseases, like pneumonia, caused by antibiotic-resistant bacteria.

“Photodynamic inactivation offers a cost-effective treatment option, which is crucial for reducing medical expenses not only in developing countries but also in the United States,” said Dr. Vladislav Yakovlev, professor in the Department of Biomedical Engineering and author on the study..."

-via Good News Network, February 8, 2025

[comicaurora]

If you were a sci-fi writer, how would you solve the Fermi paradox? That being the discrepancy between evidence for alien life, versus the likelihood of their existence? (basically. If alien so likely, why we not see?) The Dead Space series has an amazing cosmic horror solution, but i'm curious what you're brain could come up with!

There's a lot of possibilities, some more interesting than others.

The speed of light and the distance between inhabited stars makes it prohibitively slow to detect, make contact with, or reach any star with alien life. It doesn't matter if we're not alone, our corner of Space Reachable Within A Human Lifetime is so comparatively small that we may as well be. We're all blindly wandering through an infinite desert, calling into the void. Space exploration is a long game, and on that timescale, even whole civilizations blink out very quickly. If we manage to catch a signal and follow it, we might find nothing on the other end but ruins - or an asteroid field where a planet's orbit used to be.

The universe is too young for us to find anyone else out there. We're the first. How will we shape the galaxy to make life better for those who come after us?

The life that formed on Earth is terrifyingly invasive. The atmosphere and ocean is choked with monocellular life, and its surface is coated with a mass of multicellular organisms finding new ways to devour one another. Even extinction events don't keep down the biomass for long. If life on other planets looks anything like us, the problem isn't going to be detecting it. It'll have gotten everywhere. The problem is going to be not immediately getting colonized and eaten alive by it. And if life on other planets DOESN'T look like us, our whole planet is probably a class 1 biohazard and contamination risk. Multicellular earth organisms contain microcosmic ecosystems that proliferate explosively when they die. If anything inside them can find ANYTHING to eat, it's over.

Life evolves frequently, but always in oceans. It is extremely rare for any alien life to leave that ocean and adapt to life on land. Without this step, the jump to space exploration - even space contemplation - becomes infinitely more unlikely.

Monocellular life is seeded on planets from an outside source and allowed to self-cultivate and grow until the biomass reaches a certain volume. Then the farmers return to harvest it.

There is not a single other species on our entire planet that humans can actually reliably communicate with. It takes tremendous amounts of training to make an animal capable of recognizing even a handful of words, and very few of them can use them. Humans can't even communicate with other humans with 100% clarity, even if they're using the same language. When we find alien life, if we even recognize it as anything resembling life as we know it, we have absolutely no way of communicating.

Space colonialism has been disallowed by the space geneva conventions due to massive past tragedies, parasitic exploitation of worlds and senseless loss of life. Human expeditionary efforts are being watched warily through targeting sights.

We've known about radio communication for less than 200 years. We haven't yet figured out the medium through which all advanced civilizations communicate.

Alien life exists in abundance, but the vast majority of it is extremely tiny. We wouldn't spot an anthill on a satellite photo, and none of their ships are large enough to survive passage through our atmosphere.

Earth's oxygen atmosphere is an anomaly, and our first and most enduring extinction event. The explosive proloferation of cyanobacteria and their oxygen photosynthesis irreparably altered the planet's prebiotic atmosphere and wiped out everything that couldn't handle the sudden massive increase in a highly reactive and flammable gas. Earth is considered highly toxic and unstable, though recently detected increases in methane and CO2 might signal that nature is finally beginning to heal.

[jpitha]

The Oxygen Breathers

I thought I posted this one here, but it looks like I didn’t, so here you go!

It was always an event when the Humans visited.

They'd arrive in their sleek, smooth, thick ships; completely at odds with the other ships of the Coalition. Human ships always looked like they were grown rather than built. People would whisper how the Humans made their ships as tough as they were. How human ships could go atmospheric and land on the ground.

It was nonsense of course, no ship - human or otherwise - could do that. Kre'kk figured that the Humans probably spread that rumor themselves.

After they'd arrive, they would come out of the docking umbilical in their small, highly polished suits. They were a rare class of sapient indeed.

The Oxygen Breathers.

Most 'civilized' people in the Coalition came from worlds with manganese sulfur atmospheres. The humans with their oxidizer for a breathing gas were seen as brash, reckless folks who make decisions without proper consideration. Given the reactive nature of their atmosphere, it's practically a given that they too are more reactive in their choices.

Kre'kk stands at attention at the end of the umbilical ready to welcome the humans for their - hopefully - short visit. They come from a high gravity world with a single massive moon - fully a quarter of the size of their own planet itself - so their environmental defaults are... somewhat extreme compared to the rest of the Coalition. The never fail to mention the moon.

As they approached, they reach one half unit away from Kre'kk and stop. He looked down at them - they were about half his height - and he made the Universal Gesture of welcome. The humans reciprocate and Kre'kk’s head frill rustles.

"Welcome to Coalition Orbital 43559 - known to the Lemilar as 'Habilamen.' I am Administrator Kre'kk and I welcome you as equals for you visit."

The human at the head of the group is wearing a slightly different suit. Still polished and reflective, but where the rest of the humans are wearing suits of pitch black - darker than interstellar space - this one is a deep vermillion red. Kre'kk is drawn to the color. It's so rich! It almost looks wet.

When they begin to speak, a simplified icon of a human face is projected onto the smooth polished surface of the helmet. It seems that the humans have taken some care to make themselves look less frightening in their environmental suits. "Thank you for the greeting, Administrator Kre'kk. I am Captain Margaret Kellerman and this is my crew." She gestures behind her. "We plan on staying only for three cycles demi in order to take on a load of Ribanium and trade with any interested parties. I will share with you a manifest of what we have available to trade." She gestures on her arm, and the file appears on Kre'kk's pad.

Kre'kk is taken aback at her voice. It's so clear. She seems to be speaking through a translator, but it is getting the nuance and overtones of the Lemilar Trade Language perfectly. She could have a career as an entertainer or storyteller easily if she was a difference species. Kre’kk swallows. "Uh, thank you Captain, I have received your file and will distribute it. Please make use of our facilities during your stay."

Captain Kellerman's helmet flashed a icon of a face, smiling - without their teeth - broadly. "Thank you Administrator Kre'kk, we shall."

For two cycles, Kre'kk held out hope that the human's visit would be without incident. They came in quietly, did some minor trading, loaded their Ribanium and spent a… reasonable amount of money on entertainment and refreshments - suitable for their systems - while on board. Kre'kk felt they were trying very hard to be model visitors. Apparently they knew humans had a reputation in the Coalition for being... rowdy.

On the last demi cycle before the Humans were scheduled to depart a group of Felimen came over, angry. They had spent the entire two cycles previous loudly complaining that the humans shouldn't be here, and that they had captured Felimen colonies long ago and had begun the process of 'poisoning them' to be more suitable to them. The Human authorities maintain - and have the receipts to prove - that they purchased the planets legally from the Felimen, and never attempted to hide their goals of colonization and geoengineering. Regardless, a long, bloody war had followed and the humans had pushed the Felimen to capitulate and were currently engaged in a Cold War with each other.

Kre'kk was alerted as soon as the shouts started. The Felimen seemed to come to the humans wanting to cause trouble. For their part, the humans tried their best to talk the Felimen down. Their helmet icons were looking sad and quiet and they gestured in ways to try and reduce tension. The Felimen were having none of it though.

As Kre'kk undulated over to try and calm them, one of the Felimen in the back had wheeled out a battle rifle. Kre'kk had no idea how they had snuck it in, but it was completely banned on the Orbital and was cause for immediate expulsion. Before he could sound the alarm and get the Orbital authorities to come, they fired at the group of humans.

It proved to be a fatal error in judgement.

One of the humans in the front of the group was struck directly in their center of mass. They staggered back, and their suit showed significant damage. Luckily for them the suit was not penitrated. The humans reputation for building strong was well earned apparently.

Faster than Kre'kk could follow and only confirmed by viewing the security footage after the fact, three of the humans brought massive slug throwers to bear. Kre’kk knew that the Coalition sapient races find chemical powered metal slug throwers to be far too heavy to be hand weapons. If they are used, they're tripod or vehicle mounted. The humans are apparently experts in their manufacture and use, and can swing them around like they weigh nothing.

The noise of the slug throwers in the hall was deafening. Kre'kk winced as his active noise cancellation dampened the noise and wondered how the humans could take the noise without being injured, but he assumed they must also have some kind of noise cancelling built into their environmental suits.

They fired for a short time indeed, but it was more than enough. All of the Felimen were dead, with the ones in the front unrecognizable. The silence in the hall after they finished firing weighed heavy. It felt like an eternity after they had stopped before the station alarms sounded.

Kre'kk moved over to the humans. They were checking eachothers suits and cleaning up the small yellow colored pieces of metal that come flying out of their throwers when they fire. "Brass" is what they call it. Kre'kk gestured an apology. "I'm sorry. Battle weapons are banned here. You're going to have to leave now."

Captain Kellerman's icon showed pure fury. Her gauntlet covered hand pointed at him accusingly. "You're going to take their side, Administrator? You were here, you saw them. They shot first! They damaged the suit of one of my crew! It was through the luck of Forturne herself that his suit was not pierced!”

Kre'kk slid back one half unit unconsciously. "Be that as it may, you responded with… disproportionate force to their attack. It was uncalled for."

Captain Kellerman sputtered, her melodic voice taking on frightening undertones as the translator worked overtime to relay her fury to Kre'kk. "Uncalled for!? Administrator Kre'kk with all due respect you are out of line. You know about the war I assume, but do you know what they did to our colonies? They dropped nanobombs on our legally purchased colonies. They weren't trying to take back land, they were trying to obliterate us. I was there, I saw it with my own eyes."

Kre'kk was taken aback. This was not part of the standard narrative about the war. "I did not know that no, the Felimen-"

"The Felimen tell their own version of the war in order to garner support and sympathy against 'the aggressor human' I'm sure." Captain Kellerman sounded bitter in the translated voice. "Kre'kk. Your people border the Felimen opposite us do you not?"

"Yes, our territory borders theirs but-"

"And have you by any chance heard of some border worlds coming under some kind of unknown trouble? Maybe a strange illness, or unusually strong weather on the worlds?"

Kre'kk's frill rippled worriedly and he said nothing. He had heard about things like that.

Captain Kellerman cleared her helmet. Suddenly, Kre'kk saw her clearly. Small, with bilateral symmetry, close set binocular eyes and a small mouth, this was the first time Kre'kk saw a human as they are, not as their icons show them. They are predators. They are hunters.

They are terrifying.

Kre'kk unconsciously made a gesture of fear and slid back another half unit. Captain Kellerman's face contorted into a snarl. "Know this Kre'kk. It's only a matter of time before they do to you what they attempted - and failed - to do to us. Think hard about who your friends are and who in the Coalition you can come to for help when they start dropping nanobombs on your worlds." Just as suddenly as it had cleared, her helmet darkened again, and the cartoon icon of her face returned. It felt like a mockery to Kre'kk now.

The humans picked up the rest of their debris and freed their weapons. Faster than Kre'kk could ripple, they were all carrying slug throwers. "We're leaving, Administrator Kre'kk. If any Felimen even come within 5 units of us-" The people behind her cycled a round into their rifles for emphasis "-we will take it as a provocation and will respond with 'disproportionate' force."

"Y-yes Captain. I will relay this information."

"Oh and Administrator Kre'kk? Your Station will be added to the list of Orbitals where humans will not go. We will do no trading, sell no wares, and offer no defense. You and yours will do well to consider your stance vis-a-vis us and the Felimen."

Without another word, the group of humans turned and marched towards their ship. Shaking, Kre'kk signaled that they were not to be interrupted and made sure their warning about Felimen was relayed.

After they left and the mess was cleaned up, Kre'kk sat in his quarters and stared out the window at the planet below a long time. One of his creche mates was living on a newly founded colony bordering Felimen space. He began composing a message to beam to her asking if she had any plans about moving back.

[b1asho]

Round one of the species introduction!!!!

Prectikar Master Post:

Here's some info on them, and if you want to see some other drawings I've done of them (albeit some occasionally older n crustier ones), check out my deviantart: https://www.deviantart.com/blasho

Anyway let's get into a terribly long string of paragraphs about some of their info:

Prectikar are a large sentient species, usually standing at around 8-9 feet tall when fully upright and weighing anywhere close to or upwards if 1000 pounds

They are covered in feather-like fur (or is it fur-like feathers? They're occasionally branched like feathers, and all have quills, but some are more hairlike) due to the cold climate they evolved in, though length and thickness of it now varies by region.

They are omnivorous, and while they have many traits to help them hunt and kill, most of their diet tends to be plants.

Originally rush-down predators, they use their considerable strength to move in quick bursts and their specialized tusks to either ram prey to death or gouge into it as they grapple it.

Their jaw strength is also insane,with their skull actually sacrificing brain space in favor of it, which helps them eat pretty much anything they come across. They pay a lot of attention to food and cooking because of their high calorie needs and very sensitive nose/tongue.

They have manganese as an oxygen carrier is a result of the scarcity of other metals in their environment and potentially because of its general affinity for oxygen.

This causes their blood to be an amber/orange brown and shades of pink depending on its exposure to oxygen.

Through a network of cooperative bonding and other adaptations (like better oxygen retention in muscles and the easily carried size and longevity of the molecule) they’ve managed to bring this manganese transport molecule close to hemoglobin in terms of effectiveness, though they can also make use of manganese’s catalyst properties to temporarily push it to bring lots more oxygen to their tissues at a time (used for short bursts of speed and strength that allow them to take down large prey and plants for food).

their large body size (selected by their colder environment) lets them use their own high body heat to keep the O2 fixation and liberation going in their highly effective lungs.

An extensive understanding of their internal chemistry is unknown (aka gatekept by their colonizers/"uplifters" who ill get to later) but it seems like they also have a network of bacteria in their body just to manage the more reactive and damaging oxides that form, and to remove/convert the spent manganese into connective tissue and aid in bone maintenance.

They have higher calorie needs from keeping up the body temp and recycling/removing all that stuff, alongside just being big in general. Alongside a lot of sleeping, they also basically just eat all the time (compared to other species) to compensate, though their mammal-like fat retention and other metabolic adaptations for scarcity mean that they can handle long periods without resources(though this causes increasingly compounded problems for them)

Some other downsides include low tolerance of changes in oxygen levels (particularly low) and temperature levels, and poor adaptation to environments outside of their biosphere/without all the microorganisms since these things upset their delicate balance.

(part of why so many tribes were nomadic was/is to chase temperate and ‘warm’ seasons, even though to us that’s still cold. Prectikar living in human dominated areas often just take a lot of supplements with beneficial bacteria in them to cope with thr lack of that in their environent, and any food printers need an 'ink' cartridge containing these things or else theyre basically useless.),

They also experience faster general wear and tear from having constant complex and intensive chemical reactions(sometimes with dangerous chemicals) going on in their bloodstream and tissues.

( I’m not a biochemist, so if there’s any glaring issues with this then just explain it away to yourself with ‘they have a gland for that’ or ‘just don’t think about it actually’ which is what I did. I just wanted the fun color with a metal that can reversibly bond with oxygen :). )

They have one nasal passageway for smell/air and a second, bigger cavity for just vocalization (which they can’t breathe in from as easily).

This second cavity is between their first set of eyes, and has a phonic lip structure inside to produce higher pitched sounds.

The upper nasal opening has muscled nostrils that act as lips to further help control sound. The noise coming from here sounds very high to them, but to us it sounds like a nasally human voice, broken uobhere and there with squeaks, buzzes, and clicks).

They can pitch this nose voice very high, closer to dolphin-like clicking noises but not quite echolocation level.

Their throat vocal cords by their air sac are very long and thick, used for making very deep noises that carry long distances.

However, the vocal control they have through their mouth is very poor due to this and the inarticulate lips and tongue they have, and due to the more limited air they can bring in and out of it, so when speaking only through their mouth they sound a lot like seals or dogs and can only really go in short bursts before having to refill the sac.

Most of their languages are spoken with the nose and mouth sounds in tandem, where the high and low mix to make a more even sounding voice.

It’s fairly easy to understand them, but nearly impossible for us to truly speak any of their native languages, and if they wanted to they could also just start making sounds we cant hear.

They see it as strange that humans and other species speak with a single tone without difficulty.

The red flaps pictured on the drawing of their mouth and nasal passages can be moved to seal off the passage and direct airflow elsewhere.

The big red one in their throat acts as a “diaphragm” to fill and empty the air sac (which is left over from when their digestive and respiratory tracts were more connected like ours, but time in the water heavily shifted it to a more ‘blowhole’ type outline to help them breathe and vocalize from the surface).

The other flap by the air sac and its vocal cords moves upwards to block off the digestive tract whenever the mouth or nose is opened to allow air to be drawn in by this diaphragm.

The two red flaps making a pinched shape can move independently or with the other red flap, but never at the same time with each other. The main airway is always separate from the digestive tract, though the flap to the middle, non vocal nasal passage can be moved so that it’s a part of either the vocal nasal passage to draw in air or the air sac part to act as another resonance chamber.

Air can be drawn in by the diaphragm via open mouth and through the nose via open top red flap at the same time, and can be released at the same time, resulting in their near continuous double speak sound they use for their own language.

Their characteristic large tusks are retractable and housed in a cone-shaped bony socket on the side of their jaw.

A muscle is attached to the bony root of the tooth, and pushes it out. As it slides towards the front of the mouth, the cone socket narrows and wedges a protrusion on the tooth into a hole in the socket, and then the muscle stiffens, locking it in there.

When the tusk retracts, the muscle quickly jimmies the tooth forward then draws it back to get it out of the hole, and then pulls it back into the wider part of the socket.

This is mainly because their tusks are ever growing (but very slowly) but not great at self sharpening, and are their main weapon in self defense and hunting,so it seems this just happened to keep them safe.

If a tusk is broken, as long as it was not cracked at the root, it can be regrown with extensive time in the socket, but otherwise they stay safely stowed in da socket where the majority of its sharp edge can stay protected from chewing and other mouth stuff. Tusks won't start growing in until their teenage years.

They are primarily bipedal/ quadrupedal and switch between the two occasionally.

Knuckle walking helps distribute their top-heavy weight and give them more balance for long and short distance, while walking upright gives them better visibility, less stress on their neck/upper back, and quicker but unsteadier movement.

Their gallop/sprint utilizes both arms and legs to propel them forward in a gait halfway between a bear and a gorilla (since their big mid arms are set like a bears) to overtake prey after an ambush or drive them into the rest of the pack waiting elsewhere. Quad walking also helps them get around in buildings meant for species half their size.

Their hands are some of their only places without hair, but as they age, they loose it on their arms and face too.

Prectikar have different uses for each of their pairs of limbs, and have for all stages of their evolution.

The front ones specialized for grappling prey and grabbing things, and so have a ‘sprawling’ shoulder position like humans and have hands with relatively nimble fingers, the outer two are angled inwards but can also move in a pamprodactyl ish fashion (which acts as their version of a thumb, and lets them switch from big to little grabbing motions) .

Their mid limbs used to be wings with hands, and still have a basically zygodactyl finger position that was helpful for holding onto branches (with the backwards facing finger), but over time they have been converted into terrestrial knuckle-walking limbs, with the one that swings back and forth being brought forwards to walk or swung back to adjust grip on big things they want to move or for balance on unstable terrain like ice . The fingers on this one are big and clumsy, pretty much only useful for digging, walking, or slashing.

Their back limbs also used to be for grasping but were mainly counterbalances, but have now turned into plantigrade walking limbs (and much like humans, that’s pretty much all they use them for). All have nonretractable claws.

Prectikar are viviparous and usually give birth to litters of up to 8.

They have a specific mating season, where their dimorphic traits will become more pronounced.

Males in rut will shed the feathers on their throat sac region and it will become a bright ambery yellow color, and they will also grow in longer feathers on their butt region (in a fan shape for display purposes. The dont have a true post anal tail like humans).

They will also develop some of that pinkish orange/yellow on their chest skin. Females go throguh estrus cycles and will also grow a more prominent butt feather crest, as well as some very long feathers around their neck, shoulders, and abdomen for babies to hold onto.

Their skin patches turn a much brighter shade of yellow to help direct newborns to where they can feed from. Once they give birth, they will start making an oily and thick secretion across the skin patch which is collected into a divot which the infant licks from. Part of why the babies hold onto them is so they can constantly lick the 'milk'so they can grow.

Newborns come out blind and hairless, but quickly grow in a thick down and open their eyes so they can climb on mom.

Once they're weaned, they'll drop off and use the muscles they gained hanging on and climbing to start moving with the adults. They grow very fast, and canes are a common sight in teens to help deal with the rapid bone and muscle growth.

Usually, it is only during this season where chest/skin related nudity standards change to be more conservative, since showing those colors means youre down to fuck and so doing that is usually restricted to in private with their partner or for bachelors.

They have very strict binaries for sex and gender based on this seasonal divide and religion.

Most tribes show gender identity through a piercing on their lower nose for male or chin for female (so dont worry, the main guy up there is showing some male presenting chest outside of the mating season, so hes fine).

Normally, only some cultures pierce their ears, which are like if owls had a little mobile flap of outer ear to swivel I stead of their whole head. Very little of it is actually flesh, and the sound is mainly captured by the feathers around it.

While they have a reputation otherwise, Prectikar are highly social within their tribal/family groups.

They regularly allogroom, greet each other with hugs, and usually travel in sibling groups. Households are multi generational.

They have a reputation as standoffish or irritable because they take things very differently and have other standards/specific body language truggers. also most other species treat them differently/with fear by default.

their upper pair of eyes is larger and focused on long distance vision while their lower pair is for close up vision, creatign a bifocal effect for them when using both at once.

Aaaaaand that oretty much everything, I think. I'll post some other arts related to them soon, but consider this the Master Post on the things you should know about them!!

[whats-in-a-sentence]

Rapid SSA responses to different abiotic stress conditions, including heat, cold, salinity, and high light intensity, have been demonstrated to be mediated by a self-propagating wave of ROS production, which travels at a rate of approximately 8.4 cm min^-1 and is dependent on the presence of a specific NADPH oxidase, respiratory burst oxidase homolog D (RBOHD), which is located on the plasma membrane (Figure 24.14).

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[blueoaknx]

Mitochondrial Dysfunction in Type 2 Diabetes

Introduction

Mitochondria, essential for cellular energy metabolism, play a crucial role in bioenergetics and metabolic homeostasis. Mitochondrial dysfunction has been implicated as a key pathophysiological factor in Type 2 Diabetes Mellitus (T2DM), contributing to insulin resistance, metabolic inflexibility, and beta-cell dysfunction. This review explores the intricate mechanisms underlying mitochondrial impairments in T2DM, including defective oxidative phosphorylation, disrupted mitochondrial dynamics, impaired mitophagy, and excessive reactive oxygen species (ROS) generation, with a focus on potential therapeutic interventions targeting mitochondrial pathways.

Mechanistic Insights into Mitochondrial Dysfunction in T2DM

1. Defective Oxidative Phosphorylation and ATP Synthesis

Mitochondrial oxidative phosphorylation (OXPHOS) occurs through the electron transport chain (ETC), comprising Complexes I-IV and ATP synthase (Complex V). In T2DM, evidence suggests a downregulation of mitochondrial ETC activity, particularly in Complex I (NADH:ubiquinone oxidoreductase) and Complex III (cytochrome bc1 complex), leading to reduced ATP synthesis. This dysfunction is often linked to compromised NADH oxidation and inefficient proton gradient formation, resulting in cellular energy deficits and impaired insulin-stimulated glucose uptake.

2. Elevated Reactive Oxygen Species (ROS) and Oxidative Stress

Mitochondria are a primary source of ROS, predominantly generated at Complex I and Complex III during electron leakage. In T2DM, excess substrate influx due to hyperglycemia leads to mitochondrial overactivation, driving excessive ROS production. Elevated ROS induces oxidative damage to mitochondrial DNA (mtDNA), lipids, and proteins, disrupting mitochondrial integrity and function. Oxidative stress further impairs insulin signaling by activating stress-responsive kinases such as c-Jun N-terminal kinase (JNK) and IκB kinase (IKK), contributing to systemic insulin resistance.

3. Mitochondrial Biogenesis and Transcriptional Dysregulation

Mitochondrial biogenesis is regulated by the transcriptional coactivator Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), which modulates downstream transcription factors such as Nuclear Respiratory Factors (NRF-1/NRF-2) and Mitochondrial Transcription Factor A (TFAM). In T2DM, PGC-1α expression is downregulated, impairing mitochondrial biogenesis and reducing mitochondrial density, leading to decreased oxidative capacity in metabolically active tissues like skeletal muscle and liver.

4. Disrupted Mitochondrial Dynamics and Mitophagy

Mitochondrial quality control is maintained through dynamic fission and fusion processes. Fission, mediated by Dynamin-related protein 1 (Drp1), is necessary for mitochondrial fragmentation and mitophagy, while fusion, regulated by Mitofusin 1/2 (Mfn1/2) and Optic Atrophy 1 (OPA1), maintains mitochondrial integrity. In T2DM, an imbalance favoring excessive fission leads to mitochondrial fragmentation, impairing energy metabolism and exacerbating insulin resistance. Moreover, defective mitophagy, regulated by PTEN-induced kinase 1 (PINK1) and Parkin, results in the accumulation of dysfunctional mitochondria, further aggravating metabolic dysfunction.

Implications of Mitochondrial Dysfunction in T2DM Pathophysiology

1. Skeletal Muscle Insulin Resistance

Skeletal muscle accounts for ~80% of postprandial glucose uptake, relying on mitochondrial ATP production for insulin-mediated glucose transport. Impaired mitochondrial function in muscle cells reduces oxidative phosphorylation efficiency, promoting a shift towards glycolysis and lipid accumulation, ultimately leading to insulin resistance.

2. Pancreatic Beta-Cell Dysfunction

Mitochondrial ATP production is essential for insulin secretion in pancreatic beta cells. ATP-sensitive potassium channels (K_ATP) regulate glucose-stimulated insulin secretion (GSIS), with ATP/ADP ratios dictating channel closure and depolarization-induced insulin exocytosis. In T2DM, mitochondrial dysfunction leads to inadequate ATP generation, impairing GSIS and reducing insulin secretion capacity. Additionally, oxidative stress-induced beta-cell apoptosis contributes to progressive loss of beta-cell mass.

3. Hepatic Mitochondrial Dysfunction and Lipid Dysregulation

Mitochondrial dysfunction in hepatocytes contributes to hepatic insulin resistance and non-alcoholic fatty liver disease (NAFLD). Impaired fatty acid oxidation due to dysfunctional mitochondria leads to lipid accumulation, exacerbating hepatic insulin resistance and systemic metabolic dysregulation.

Therapeutic Strategies Targeting Mitochondrial Dysfunction

1. Exercise-Induced Mitochondrial Adaptation

Physical activity upregulates PGC-1α expression, enhancing mitochondrial biogenesis and oxidative metabolism. High-intensity interval training (HIIT) and endurance exercise improve mitochondrial efficiency and reduce oxidative stress, mitigating insulin resistance in T2DM patients.

2. Pharmacological Modulation of Mitochondrial Function

Metformin: Enhances mitochondrial complex I activity, reducing hepatic gluconeogenesis and oxidative stress.

Thiazolidinediones (TZDs): Activate PPAR-γ, promoting mitochondrial biogenesis and improving insulin sensitivity.

Mitochondria-targeted Antioxidants: Agents like MitoQ, SkQ1, and SS-31 reduce mitochondrial ROS, preventing oxidative damage and preserving mitochondrial function.

3. Nutritional and Metabolic Interventions

Ketogenic and Low-Carb Diets: Enhance mitochondrial fatty acid oxidation, reducing lipid accumulation and improving metabolic flexibility.

Intermittent Fasting: Induces mitochondrial biogenesis and autophagy, improving metabolic homeostasis.

Nutraceuticals: Coenzyme Q10, resveratrol, and nicotinamide riboside (NR) enhance mitochondrial function and energy metabolism.

4. Emerging Gene and Cellular Therapies

Gene Therapy: Targeted upregulation of PGC-1α and TFAM to restore mitochondrial function.

Mitochondrial Transplantation: Direct transfer of healthy mitochondria to replace dysfunctional ones, an emerging frontier in metabolic disease management.

Conclusion

Mitochondrial dysfunction is a central determinant in the pathogenesis of T2DM, affecting insulin signaling, glucose metabolism, and lipid homeostasis. Targeting mitochondrial pathways through exercise, pharmacological agents, dietary modifications, and emerging gene therapies offers promising avenues for improving metabolic health in T2DM. 

[covid-safer-hotties]

Also preserved in our archive

Listen at the first link!

The GIST

Recent studies suggest that a hypermetabolic state that damages the mitochondria results in a hypometabolic state in chronic fatigue syndrome (ME/CFS), long COVID, and fibromyalgia (FM). They also suggest that something in the blood, serum, or plasma is damaging the mitochondria in these diseases.

We’re not done with the mitochondria, though – far from it! Now we look at a bevy of recent long-COVID mitochondrial studies suggesting that mitochondrial dysfunction affects more than energy production and which illuminate what may have gone wrong in the mitochondria.

Muscle biopsies of 120 long-COVID patients who had ended up in the ICU found that a year later their muscles had higher levels of immune cells involved in tissue repair and reduced activity of the 2nd and fourth mitochondrial complexes. The authors concluded that there was “aberrant repair and altered mitochondrial activity in skeletal muscle.”

They couldn’t explain how a respiratory illness affected the muscles but a subsequent study did. A hamster model found that the coronavirus suppressed the genes associated with the muscle fibers, protein production, both sides of the mitochondrial energy production process (Krebs cycle and electron transport chain), and fat breakdown.

As it was doing that, it unleashed a barrage of inflammatory factors (IFN-α, IFN-γ, and TNF-α) which triggered a shift from relying mostly on aerobic energy production to the less effective process of anaerobic energy production (glycolysis).

The authors concluded that using treatments “that can boost mitochondrial functions, enhance protein synthesis, and inhibit protein degradation” may be useful for treating muscle fatigue in long COVID.

Next, a muscle study assessing “maximal fatty acid oxidation (MFO)” (i.e. energy produced by the breakdown of fats during exercise) found significantly reduced levels of fatty acid oxidation in long COVID and a “premature shift” from relying on fats to carbohydrates to powering their cells.

This was important because the body prefers to burn fats during exercise and because fats play key roles in both parts of the mitochondrial energy production process. The finding wasn’t so surprising, though. Problems with carnitine – which transports fatty acids into the mitochondria – have popped up in both long COVID and ME/CFS – suggesting that the fatty acids that power the mitochondria during exercise may not be getting into them.

A review paper asserted that increased free radical production (reactive oxygen species (ROS)) by the mitochondria both pushes the cell into a state of anaerobic energy production but also pushes the immune system to activate the inflammatory or innate immune response and away from the adaptive immune response that targets pathogens. This benefits the viruses by providing the substrates they need to grow and allows them to escape from the immune system.

Several researchers, including Avindra Nath, believe that the immune system tries to compensate for the impaired adaptive immune defense by ramping up the innate immune response. Nath believes this shift plays a central role in ME/CFS.

They proposed that treatments to boost mitochondrial functioning and reduce the production of mitochondrial reactive oxygen species (ROS) (free radicals) will be beneficial.

Lastly, a review asserted that the predominant view of the mitochondria as the main energy producers of the cell is misguided and incomplete. Harkening back to Naviaux’s characterization of the mitochondria as the primary threat-sensing part of the cell, the authors believe the mitochondria regulate the “physiological processes at the level of the cell, organ and organism”; i.e. the mitochondrial problems affect much more than low energy levels and fatigue.

A blog on red light/infrared light therapy – which could both boost mitochondrial health and antioxidant defenses – is coming up.

Full text at either link! There's a lot more than the gist