#mitochondrial signaling

[bsahely]

The Spiral of Syntony: A Unified Theory of Flow and Healing Across Biological, Bioelectrical, and Subtle Energy Systems | ChatGPT4o

[Download Full Document (PDF)] The document presents The Spiral of Syntony, a comprehensive framework for understanding healing and regeneration across various systems, including biological, emotional, and energetic dimensions. It posits that healing follows a seven-phase spiral of coherence: Sensing, Polarization, Structuring, Signaling, Meaning-Making, Action, and Feedback. This model…

[blueoaknx]

The Connection Between Damaged Mitochondria and Arthritis

Mitochondria are integral organelles responsible for various critical cellular functions, primarily energy production through oxidative phosphorylation. They are involved in maintaining cellular homeostasis, regulating metabolism, modulating calcium levels, and controlling apoptosis. Emerging evidence has highlighted mitochondrial dysfunction as a key contributor to a variety of diseases, including arthritis. This formal overview aims to explore the complex relationship between damaged mitochondria and arthritis, focusing on the molecular mechanisms that link mitochondrial dysfunction to the pathogenesis of inflammatory joint diseases, particularly rheumatoid arthritis (RA) and osteoarthritis (OA).

Mitochondrial Structure and Function

Mitochondria are double-membraned organelles found in eukaryotic cells, and they are crucial for cellular energy metabolism. Their primary role is the production of adenosine triphosphate (ATP) via oxidative phosphorylation, a process that takes place in the inner mitochondrial membrane. During this process, the electron transport chain (ETC) generates a proton gradient across the inner membrane, which drives ATP synthesis through ATP synthase. However, this process also generates reactive oxygen species (ROS) as byproducts, primarily from complexes I and III of the ETC. Under normal physiological conditions, ROS are neutralized by antioxidants, including superoxide dismutase (SOD), catalase, and glutathione. However, under pathological conditions, excessive ROS production can lead to oxidative stress, contributing to cellular damage and dysfunction.

In addition to ATP production, mitochondria have essential roles in calcium buffering, apoptosis regulation, and the maintenance of cellular integrity. Damage to these organelles disrupts these functions, contributing to various diseases, including arthritis.

Mitochondrial Dysfunction in Arthritis

Arthritis is a group of diseases characterized by inflammation and degeneration of the joints. It includes conditions like rheumatoid arthritis (RA), an autoimmune disease, and osteoarthritis (OA), a degenerative disease. In both types of arthritis, mitochondrial dysfunction has been identified as a critical factor that exacerbates disease progression through several mechanisms, including increased oxidative stress, immune activation, and tissue damage.

1. Oxidative Stress and Mitochondrial Damage

Oxidative stress is a hallmark of both RA and OA, and mitochondria are central to its production. In these conditions, mitochondrial dysfunction results in an increase in ROS production, overwhelming the cell’s antioxidant defenses. This oxidative stress leads to the modification of cellular structures, including proteins, lipids, and DNA, causing further mitochondrial damage. In RA, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) stimulate immune cells like macrophages and neutrophils to release large amounts of ROS. These ROS contribute to the local inflammatory environment and accelerate joint destruction by damaging mitochondria and amplifying oxidative stress.

Mitochondrial damage results in a feedback loop where impaired mitochondrial function generates more ROS, further promoting inflammation. For instance, in RA, markers of oxidative damage such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) have been found to correlate with disease activity, suggesting a direct relationship between mitochondrial dysfunction and disease severity.

2. Mitochondrial DNA Damage and Inflammatory Signaling

Mitochondrial DNA (mtDNA) is particularly vulnerable to oxidative damage due to its proximity to the ETC, where ROS are produced during ATP synthesis. Unlike nuclear DNA, mtDNA is not protected by histones and has limited repair mechanisms, making it prone to mutations. Damage to mtDNA impairs mitochondrial function and can lead to the release of mtDNA fragments into the cytoplasm or extracellular space.

In the context of arthritis, mtDNA damage has been implicated in immune activation. When damaged mtDNA is released into the cytoplasm, it is recognized by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), on immune cells. TLRs, particularly TLR9, activate downstream inflammatory signaling pathways that lead to the production of pro-inflammatory cytokines such as TNF-α and IL-6. This further exacerbates the inflammatory response in joints and contributes to the progression of arthritis. Studies have shown that the presence of mtDNA fragments in the serum of RA patients correlates with disease activity, indicating the role of mtDNA in driving inflammation.

3. Mitochondrial Dynamics and Arthritis Pathogenesis

Mitochondrial dynamics refer to the continuous processes of mitochondrial fission (division) and fusion (joining), which maintain mitochondrial function and integrity. Fission allows for the removal of damaged mitochondria, while fusion helps to integrate mitochondrial contents and maintain a healthy mitochondrial pool. Imbalance between fission and fusion is associated with several diseases, including arthritis.

In the case of RA, excessive mitochondrial fission and reduced fusion have been observed. This imbalance results in mitochondrial fragmentation, which impairs mitochondrial function, increases ROS production, and contributes to cellular stress. Fission is regulated by proteins such as dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1), while fusion is controlled by mitofusins (Mfn1 and Mfn2) and optic atrophy 1 (OPA1). Dysregulation of these proteins in RA leads to a fragmented mitochondrial network, which exacerbates oxidative stress and inflammation in synovial tissues.

4. Mitochondrial-Dependent Cell Death

Mitochondria are also central regulators of programmed cell death, particularly apoptosis. In the pathogenesis of arthritis, excessive or dysregulated apoptosis contributes to joint destruction. Mitochondrial dysfunction plays a critical role in the intrinsic apoptotic pathway by releasing pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF). These factors activate caspase-dependent and caspase-independent pathways, leading to the death of synovial cells and cartilage cells, which contributes to the progressive tissue damage observed in both RA and OA.

Furthermore, mitochondrial permeability transition pore (mPTP) opening, which is induced by oxidative stress, can lead to necrosis, a form of uncontrolled cell death. Necrotic cell death in the joints increases inflammation and tissue degradation, particularly in OA, where cartilage breakdown is a hallmark feature.

Therapeutic Approaches Targeting Mitochondrial Dysfunction in Arthritis

Given the significant role of mitochondrial dysfunction in the pathogenesis of arthritis, various therapeutic strategies aimed at improving mitochondrial function are under investigation.

1. Mitochondrial Antioxidants

Mitochondrial-targeted antioxidants, such as MitoQ and MitoTEMPO, have been developed to selectively accumulate in mitochondria, where they can neutralize ROS and reduce oxidative stress. These compounds have shown promise in preclinical models of arthritis, where they help to reduce inflammation, protect mitochondrial function, and limit joint damage. The use of mitochondrial antioxidants could be an effective strategy to mitigate oxidative stress in arthritic conditions.

2. Mitochondrial Biogenesis Enhancement

Another potential therapeutic approach is the activation of mitochondrial biogenesis, the process by which new mitochondria are formed to compensate for damaged mitochondria. Agents that activate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a key regulator of mitochondrial biogenesis, could help restore mitochondrial function in arthritic tissues. Compounds such as resveratrol and NAD+ precursors are under investigation for their ability to promote mitochondrial biogenesis and improve cellular metabolism in arthritis.

3. Mitochondrial Dynamics Modulation

Restoring the balance between mitochondrial fission and fusion is another therapeutic strategy. Inhibiting excessive mitochondrial fission or promoting mitochondrial fusion may help maintain mitochondrial integrity and reduce inflammation in arthritis. Drugs targeting Drp1 or enhancing Mfn1/Mfn2 activity are potential candidates for modulating mitochondrial dynamics in arthritic diseases.

4. Mitophagy Enhancement

Mitophagy, the selective autophagic degradation of damaged mitochondria, is essential for maintaining mitochondrial quality. Enhancing mitophagy through the use of compounds like spermidine or activators of the PINK1/PARK2 pathway could help eliminate dysfunctional mitochondria and reduce inflammation, making it a promising therapeutic approach in arthritis.

Conclusion

Mitochondrial dysfunction plays a critical role in the pathogenesis of arthritis, contributing to oxidative stress, inflammation, and joint damage. The intricate relationship between damaged mitochondria and immune activation highlights the importance of targeting mitochondrial health in the treatment of arthritis. Emerging therapeutic strategies aimed at restoring mitochondrial function, reducing oxidative stress, and modulating mitochondrial dynamics hold promise for improving the management of arthritis and preventing joint destruction. Further research into mitochondrial biology and its role in arthritis is essential for the development of more effective, targeted therapies for these debilitating conditions.

[calina-alda]

give me your post-viral wesker physical/bodily hcs please. what's he look like in there... do you have any pg67 function headcanons. the masses must know! (if you want to share, of course... i saw biology and i ran in here)

Okay so first of all congratulations, because with this question you accidentally triggered two of my fixations, resident evil lore and biology. So naturally I spent way too much time thinking about this at a molecular level, and emerged with a little manifesto on 'what the virus does to Wesker'.

Okay, lets get into it!

The virus inserts viral DNA directly into the host’s genome, permanently altering Wesker's genetic code. It targets specific stem cell populations to overwrite genetic instructions. These new genes code for synthetic proteins that give his body enhanced abilities. The virus functions similarly to an engineered gene therapy vector, but instead of fixing a mutation, it adds entirely new capabilities:

Healing Factor

• Wesker’s body heals stupidly fast. Bullet wounds seal up in real time. It’s not just fast, it’s efficient. No scar, no bruise, just gone. That’s because of proteins, that promote extreme tissue regeneration by accelerating transcription of growth factors.

• The viral DNA triggers production of proteins that upregulate mitochondrial efficiency. So his cells are constantly in overdrive, replicating and regenerating at insane speeds. That kind of process would literally melt a normal person from the inside out, but the virus keeps him juuuuust stable enough to survive it.

• That means he burns through nutrients and energy at an insane rate. But he still eats very little because his body has learned to metabolize efficiently.

• Because of this, he doesn’t get sick. Like, ever. No flu, no fever, nothing. His immune system probably nukes bacteria before they finish replicating.

Strength

• A key viral protein might mimic myostatin inhibitors, increasing muscle mass without bulk, think insane strength in a lean frame.

• He could punch a hole in reinforced steel if he wanted to, but the scary part is that he doesn’t. He holds back all the time. He can crack a man’s ribs with one hand, or gently zip up your jacket without pulling the tab off.

• His control is off the charts. He’s not just strong, he’s precise. Every movement is calculated.

Eyesight & Senses

• He sees more than most people. Infrared, low light, motion trails, his vision is layered. The world probably looks like a high-contrast heatmap half the time.

• That’s why he wears sunglasses 24/7. Not just for the aesthetic (though let’s be real, it’s working), but to help with light sensitivity. Without them, he’d probably get visual overload in a well-lit room. (Okay, Gojo Satoru)

• His hearing is sharp too. Not supernatural, but he can pick up your heartbeat if you're close enough. It makes sneaking up on him borderline impossible.

The PG67A/W Serum

• The serum is a lifeline. The virus is unstable on its own, the host cells try to over-replicate or misfire signals, leading to cellular death or mutation.

• PG67A/W likely acts as a suppressor or regulator, binding to specific viral receptors or feedback loops, controlling gene expression and inhibitory enzyme systems to keep certain proteins from overexpressing.

• He doses every 6 to 8 hours. He keeps spares on him at all times. If he’s on a mission, he builds his entire schedule around those injections.

• He hides injection sites on his inner thigh, shoulder, or hip, places easy to reach but not visible.

Body Temperature

• His body runs hot. Like, unnaturally warm to the touch, like 39°C on a normal day. You could probably use him as a space heater.

• He doesn’t sweat much, but if he’s pushing his limits, the heat builds up fast. He’ll disappear for a cold shower or just stand in front of an AC vent for five minutes without saying anything.

• Resting heart rate? Low. Like athlete-low, sometimes around 40 bpm. But if he moves into combat mode, it spikes instantly. Controlled tachycardia, probably tied to the virus.

Time Perception & Reflexes

• The virus likely alters neurotransmitter uptake and synaptic plasticity, enhancing reaction time and cognition. It increases dopamine and norepinephrine sensitivity, creating hyper-alertness without overstimulation.

• Neural conduction speed may be boosted by: enhanced myelination of neurons. Modified ion channels that allow faster action potential firing.

• The result? Time feels slower to him. His brain processes information so fast that everything else seems like it’s moving in slow motion. That’s why he reacts before you even finish blinking.

• But it’s also exhausting in a subtle way. Conversations feel slow. Meetings drag. He lives in a world that’s slightly out of sync.

Mutation Risk

• He’s constantly on the edge. The virus wants to take over, it wants him to evolve into something monstrous. He keeps that in check with raw willpower and serum, but it’s always there.

• He has nightmares about it. Not dying, mutating. Losing himself.

Aging

• The virus triggers production of novel proteins that tabilize telomeres.

• His aging basically stopped. He should be pushing 50, but he still looks like he’s in his late 30s at most.

Touch & Intimacy

• His body doesn’t regulate hormones quite the same anymore. He can feel arousal, desire, etc., but it’s slower to build and hits harder when it does.

• And his stamina...He doesn’t get tired, doesn’t lose focus, and has total control over his body. He can go for hours without so much as breaking a sweat, and he’s frustratingly composed the whole time

Pain Response

• The virus likely alters his nervous system, especially the nociceptors.

• Instead of fully shutting off pain, it modulates the intensity, filtering it through a “useful or not” lens.

• So he still feels pain, but it’s dulled. A knife wound feels like pressure. A gunshot is just an annoyance.

• He can weaponize it too. Take a hit, stay standing, stare you down without even flinching, smile on his face, it’s terrifying. And he knows it.

Anyway. That’s the gist of what I think is going on inside Wesker’s terrifyingly efficient, (incredibly attractive) body. Please note:

• I did have microbiology, but I’m studying environmental science.

• I am not a virologist or Umbrella scientist (tragic, I know), just someone who thinks too hard about fictional men with god complexes.

• Also, I had to use a translator for like 40% of the fancy terms because my English science vocab just noped out halfway through. So if something sounds too text book, blame the language barrier

Thank you for enabling me, lol

[nshtn]

[ UV Albert Wesker Uroboros & PG67 HCs ]

These take after the knowledge that PG67 contains hastily-added leech genes. This is full of medical jargon related to virology and genetics. It's hard sci-fi styled!

tags: medical:genetic;neurology (hardly);virology;needles (PG67-A/W), cannibalism mention, childhood trauma, body horror, mental decay

Such a far cry from his beginnings... he's truly taken after the man he hates the most.

Unfortunately for Wesker, adding Uroboros in intensely massive quantities to an existing Progenitor-67 infection is a poor choice that makes him spend much of his fight with Chris alternating between pouncing him like a rabid animal and curling like the death throes of a dying spider.

And unfortunately for Chris, Wesker doesn't die when he's left at the volcano to stew in a puddle of himself. Even with the awakened lack of thermophilic qualities as a result of the genetic influence of G, there is enough local flora and fauna to keep him alive... albeit in a subdued state.

Physiological:

Uroboros, combined on the initial foundation of Progenitor 67, takes after Progenitor 67's metabolic inefficiency and drives that far higher than it was ever meant to go in an attempt to sow compatibility.

Due to this, Wesker needs a truly ridiculous amount of calories (~6,000 - ~9,000 kcal/d) to remain fully intelligent.

A lesser amount will generally retain him, though he will experience a plethora of negative symptoms related to starvation (~3,500 - ~5,500 kcal/d).

The very brink of his sanity and humanity will find him lacking if he consumes the average human male's daily caloric intake (~1,800 - ~3,000 kcal/d).

Wesker cannot digest iron bound to salt or any organic chelates except heme (or hemeprotein) as a result of initial Progenitor 67 infection.

Progenitor 67 epigenetically alters his enterocytes. The genes involved with this are the upregulation of HCP1 and the downregulation of DMT1 and, less intensely, Dcytb, and is a result of both Progenitors' own natural leaning and, primarily, the hasty introduction of leech genes when microinjection became available.

This ultimately means that, as time drags on, he begins to find his palate shifts from a lot of power smoothies to meat.

But there is something crucial here: 67% or more of heme iron is lost when you cook meat. That means...

↑ He slowly slips into preferring his meat blue or raw, otherwise he won't be able to properly supplement his need for heme iron.

↑ With the addition of Uroboros, which dethrones and replaces Progenitor, this change persists and couples roughly with his modified caloric needs.

Usually present in brown adipocytes, UCP1 and UCP2 are both overactive as a result of the improper inclusion of Uroboros' gene signalling.

As a result of this, Wesker's natural temperature is hotter than a normal human being's.

He's probably uncomfortably warm to others - almost naturally feverish.

UCP1 and UCP2 cause proton leakage across the mitochondrial membrane - UCP1 being the primary uncoupler regarded in thermogenesis.

↑ As a result of this leak, ATP use is less efficient. This exacerbates his metabolic disorder.

↑ The inclusion of UCP2 upregulation alongside UCP1 was done out of an abundance of caution.

The gluconeogenesis enzyme PEPCK-C, involved in the burning of fat to produce glucose, is overexpressed in dual infection.

While this gives Wesker higher stamina and physical endurance, it comes at the expense of contributing to insulin resistance and is a key player in his bodies' teetering metabolic imbalance.

↑ This is because Uroboros doesn't upregulate and express PEPCK-C in just skeletal muscular cells - it does so where it is already present, too; this is a personal oversight.

↑ PEPCK-M was personally avoided in its' development because it is a popular oncogene.

Uroboros; a monster that eats itself continually without end. It physically presents a sign of Wesker's malingering, endless need to consume across his skin.

Patches of necrotizing, hardening skin and flesh form across his arms and legs in uneven patterns.

Scaly, itchy lesions creep along his cheekbones and the sides of his neck like a corrupted skin flush.

These are a weaker, useless vestigial presentation of the hardening of skin he undergoes when he's being flash-fried by high temperatures.

They're positive for many of the proto-oncogenes related to melanomas and are undoubtedly at least oncogenetic, but aren't strictly cancerous; instead, they're a misguided attempt at defense that vacillates 'on' without facing heat danger.

One of the scars of Wesker's infection and subsequent mutative transformation are hypermelanotic deposits that coat previously-mutated skin in a dark fade.

They start strongest at his fingertips and weaken at the base of his shoulders.

They are also strongest in the center of his chest where his macronuclei is present and taper off approaching his shoulders and abdomen.

His face has some of the same tinting in uneven splotches descending strongest from where he was burned.

Uroboros enhances the strength of many of his bones - more potent the closer to the surface of his body - by fortifying them with calcium and double-thickening them.

As a feature of the beginning stages of Uroboros' starvation, it will begin to leach calcium out of bones and the deposits it creates.

↑ These deposits are not found in the brain or the skull.

When resources are threateningly low, the bones will be stripped for the calcium they uniformly contain, causing him to experience an effect similar to calcium gout / pseudoarthritis, malaise, and brittling.

This leaching undoes itself and becomes re-fortifying under the duress of stress hormones like cholecystokinin and epinephrine. Less specific but still counted in re-fortification is cortisol and norepinephrine.

↑ Re-fortifying can be triggered accidentally through rigorous & sustained physical exercise or copulation.

Epigenetic changes brought on by Progenitor physiologically are stacked upon inappropriately and pseudorandomly by Uroboros like re-patchwork, which leads to a general instability and accidental incorporation of Progenitor's physical defense mechanisms.

This is what ultimately enables him to survive the events of RE5.

Neurological:

Progenitor infection spiraling into his temporal lobes, brain stem, and, minorly, his frontal lobes as years progress are the cause of his irritation and aggression in RE5.

It does this because it has no antimutagenic properties unlike the more developed t-Virus, slowly mutating out of control into a dysfunctional beast as Wesker experiences more and more stress and trauma.

A bit like G in this regard...

His SERT is disrupted by its' presence in the midbrain raphe nuclei along the brain stem.

This causes elevated extracellular serotonin levels initially, followed by receptor downregulation and eventual serotonin deficiency.

The lack of available serotonin leads him to experience, at first, heightened periods of aggression. Later, this becomes mania and even delirium if he forfeits sleep or a PG/67 shot, because...

As time ticks on, his dopamine begins to become dysregulated as well.

This imbalance contributes to mood swings, aggression, and impaired decision-making.

It also leads to a loss of the ability to feel pleasure or joy in things, making him manic and paranoid, taking risks uncharacteristically to feel something, anything.

As Progenitor 67 degrades brain function, particularly areas involved in impulse control and aggression, Wesker experiences the uncontrollable urge to consume.

This leads him to cannibalize interns and people he calculates won't be missed, as well as people who piss him off enough. During this time it does change - and become true - that a misplaced boop! or headpat! might get you killed.

His ego begins to vacillate and strengthen itself in an effort to maintain itself despite his decline. If he can just finish Uroboros, everything will be okay again, he can fix himself...

His brain practically relies on his PG67-A/W dose before he gains Uroboros.

A rapid decline in cognitive and emotional stability when he’s off the dose is present.

It's not unlike sundowning...

You would not want to see his MRIs during this time. They look awful - his brain has lesions and there are parts that are grossly overgrown; there are tiny black specks where Progenitor has gnawed holes in the fabric of him. If he hadn't roped it in, he would probably end up eventually going completely feral from his brain swelling up against the sides of his skull; he'd just become another victim of Cannibal Disease and turn, simply painfully slowly.

Uroboros is not supposed to crawl into the brain. It's supposed to leave it unaffected - but Progenitor having already curdled and spread unchecked into it gives it an opening for opportunistic infection.

It attempts to knit the holes and tamp down overgrown regions, but in doing this, it feeds from a sort of 'genetic template' that restores Wesker's ability to feel and feel greatly. This includes the reactivation (and reanimation) of the greatly disordered regions of his brain responsible for empathy, sleep regulation, attachment, and guilt.

It also cannot perfectly recreate lost tissue or resurrect memories from dead, liquefied tissue, so he retains some of his symptoms, like mood swings.

Rage becomes consuming, hunger becomes voracious, and guilt becomes haunting; he is plagued with an unfortunate (to him) tendency to consider others.

He finds it a prying weakness, but he can no longer tamp it down into nonexistence as he did; he is, essentially, thermally reduced to his Arklay days in behavior. He’s still intelligent and cunning, but he must now wrestle with intense emotional responses that don’t align with his goals at all...

Guilt and empathy are so foreign to him they are nearly out-of-body; he views them clinically and tries to rationalize them away, but his inability becomes the stake that impales him and imparts a malingering sense of conflict.

...and he must take a good, hard, long look at his goals and how far they've diverted from their initial precedence.

... what is he now? What use does he serve in this world - to what master does he heel, clearly dethroned from his position? These questions and more are things he asks himself now.

Is he doomed to roam aimlessly without purpose until he perishes?

[covid-safer-hotties]

Also preserved in our archive

"Just a cold" that could potentially cause cancer.

By Jo Cavallo

It’s not news that some viruses, including human papillomavirus, human immunodeficiency virus, Epstein-Barr, and hepatitis B, can cause or accelerate the development of cancer. But a recent story in The Washington Post about rare cancers being diagnosed in individuals who had previously been infected by the coronavirus has raised the specter of whether acute respiratory syndrome coronavirus (SARS–CoV-2) could also be an instigator in the initiation of cancer.1

Although the devastating short-term severe impact of SARS–CoV-2 is evidenced by the more than 7,000,000 reported coronavirus-related deaths worldwide since the outbreak of COVID-19 was declared a pandemic by the World Health Organization, in 2020,2 the long-term implications on health are just starting to be investigated.

According to Afshin Beheshti, PhD, President of the COVID-19 International Research Team and Professor of Surgery and Computational and Systems Biology, Director of the Space Biomedicine Program, and Associate Director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, it is hypothesized that SARS–CoV-2 may have long-term, life-threatening complications, including the acceleration of cancer, but these cancer-related effects may take several years to manifest. In this interview with The ASCO Post, Dr. Beheshti discussed how SARS–CoV-2could be a risk factor in cancer development.

Mechanisms of COVID That May Lead to Cancer Development

Reports are starting to emerge about a possible link between the coronavirus and the acceleration of the development of cancers. Is severe SARS–CoV-2 an oncogenic agent? Could the virus be implicated in causing cancer?

All we have right now is preliminary and indirect evidence of a potential causal link between SARS–CoV-2 and cancer. When there is an injury to the body or an infection, there may be short-term cancer-related signals that go up, but they dissipate quickly. What we are seeing in some patients with long COVID is that these cancer-related signals, such as inflammatory factors and mitochondrial dysfunction, are persistent. This makes us hypothesize that SARS–CoV-2 may be an oncogenic type of virus. But if so, we don’t know whether it is an initiator of cancer or a driver of cancer progression.

There is a good study in preprint showing a connection between respiratory viral infections and the awakening of dormant metastatic breast cancer cells in the lungs.3 In this study, the researchers infected mice with SARS–CoV-2 or the influenza virus to understand the mechanisms that disrupt the quiescence of dormant disseminated cancer cells that may lead to metastatic progression. What they found is that both the influenza virus and SARS–CoV-2 increased breast disseminated cancer cell expansion in the lungs after infection. When the researchers expanded their findings to human observational data, they observed that cancer survivors who had contracted SARS–CoV-2 infection had a substantially increased risk of lung metastatic progression and cancer-related death compared with cancer survivors who had not developed SARS–CoV-2.3

So, in a sense, maybe SARS–CoV-2 creates a different landscape in the lungs, in this case, to make the cancer more susceptible to progress or for the dormant cells to become active. My colleague, Kashyap Patel, MD, Chief Executive Officer of Carolina Blood and Cancer Care Associates, is seeing rare and lethal cancers popping up in his patients after they have contracted the coronavirus, so he has a strong suspicion—but no hard evidence—that there is a link between the virus and the development of cancer.1 We are working together to figure out whether the virus is causing dormant tumors to become reactivated, or it is causing an initiation. We want to bring attention to this issue before it’s too late.

Lingering Coronavirus Fragments and Long-Term Immune Responses

Is it possible that the coronavirus, rather than disappearing from the body after it infects an individual, lingers, potentially initiating cancer?

That is one of the concerns in patients who have had long COVID infection. So far, we have not seen the virus replicating in the body 15 or 20 days after infection. But researchers studying the impact of long COVID on the body have found that fragments of SARS–CoV-2 left behind after infection may continue to trigger immune responses.4 Whether that triggers cancer mechanisms is a hypothesis we should look into.

Focusing Research on SARS–CoV-2 and the Risk for Cancer Development

What are you learning about how COVID, especially long COVID, impacts the body in terms of prematurely aging tissue? Could that process spark the development of cancer?

We don’t know the answers to those questions. Emerging evidence has pointed to mitochondrial dysfunction or mitochondria suppression as a potential underpinning mechanism contributing to the persistence of long-COVID symptoms.5 That could mean there is a long-term impact on how cells transform energy.

In cancer development, malignant cells produce energy in a unique way that supports their rapid growth and spread. Known as the Warburg effect, this process could potentially play a role in the increased risk of cancer in patients with long COVID, because their cells may experience changes that make it easier for cancer to develop and thrive.

There is also long-lasting immune activation present in patients with long COVID, which can go on for 2 to 3 years after active infection. We know that consistent upper respiratory inflammation in the body can cause cancer progression.

A lot of the research underway now in long COVID is not yet focused on cancer development and the potential for SARS–CoV-2 to cause cancer, but it’s a question researchers should investigate.

DISCLOSURE: Dr. Beheshti is on the advisory board for Tevogen Bio.

REFERENCES

1. Cha AE: ‘Unusual’ cancers emerged after the pandemic. Doctors ask if covid is to blame. The Washington Post, June 6, 2024.

2. Worldometer: Coronavirus Death Toll. Available at www.worldometers.info/coronavirus/coronavirus-death-toll. Accessed November 18, 2024.

3. Chia SB, Johnson BJ, Hu J, et al: Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs. Res Sq [Preprint] rs.3.rs-4210090, 2024.

4. Doctrow B: SARS–CoV-2 fragments may cause problems after infection. National Institutes of Health, February 27, 2024. Available at www.nih.gov/news-events/nih-research-matters/sars-cov-2-fragments-may-cause-problems-after-infection. Accessed November 18, 2024.

5. Molnar T, Lehoczki A, Fekete M, et al: Mitochondrial dysfunction in long COVID: Mechanisms, consequences, and potential therapeutic approaches. GeroScience 46:5267-5286, 2024.

[transgenderer]

So I'm birds the heterogamous sex is the female, males have ZZ chromosomes and females have ZW chromosomes. Some of the key respiratory proteins are on the Z chromosome, so all the genes for them come from the father, but the mitochondria come from the mother. Therefore, the mother must be unusually selective in mates, if she picks a mate with bad respiratory proteins, or proteins that don't match her mitochondria, her female offspring will all die. And it seems this might explain bright plumage in male birds! Plumage patterns are sensitive to differences between groups, signalling mismatch, and it turns out bright red color reflects mitochondria functionality!

[darkmaga-returns]

Story at-a-glance

Suppression of mitochondrial ATP production prevents apoptosis and activates the NLRP3 inflammasome, a key player in inflammation and disease

Inhibitors of oxidative phosphorylation (OXPHOS) lead to changes in mitochondrial cristae structure and retention of cytochrome c, which is necessary for NLRP3 activation but not sufficient on its own

Activation of the NLRP3 inflammasome requires two signals, one of which is mitochondrial, highlighting the complexity of its regulation

Diverse NLRP3 activators share the ability to suppress apoptosis, allowing damaged cells to survive and contributing to chronic inflammation and cancer

Mitochondrial dysfunction is closely linked to inflammation and various diseases, emphasizing the importance of understanding these mechanisms for optimal health

[longhaulerbear]

THE GIST

• When we look back, 2024 might just be perceived as a year of fundamental progress. In study after study, two general themes popped up again and again. ME/CFS patients’ cells across their bodies are exhausted and exhibit a “failure to respond” when exposed to stress.
 • An early study, for instance, found – in what the authors stated constituted a “profound disruption” – that important signaling factors called extracellular vesicles became activated about 1/3rd as much as the healthy controls did after exercise.
 • Next, a UK/Australian B-cell study demonstrated that when asked to proliferate – something that happens during an infection – the B-cells of the ME/CFS patients displayed their own kind of “profound disruption”; i.e. they produced fewer mitochondria and turned to a dirty and inefficient fuel – amino acids – to try to produce energy.
 • Talk about “profound” … Avindra Nath’s finding that B-cells were stuck in an immature stage bothered him so much that he concluded they were “the primary defect” (in ME/CFS). He believes they produce immune exhaustion and, via activation of innate immune responses, inflammation.
 • For his part, Anthony Komaroff spoke of an immune system that seemed to be spinning and spinning – causing it to eventually burn itself out.
 • Vishnu Shankar of Stanford agreed. His finding of high rates of reactive oxygen species (free radicals) linked to T-cell hyperproliferation suggested that a chronically activated immune system was using up so much energy that it had created an energy sink for the rest of the body.
 • Exhaustion was the linchpin of a metabolomic study that proposed that as their mitochondrial resources were exhausted, females, in particular, became more prone to coming down with ME/CFS.
 • Meanwhile, the Simmaron Research Foundation found that low oxygen (i.e. low energy levels) produced a melange of familiar problems (increased oxidative stress, impaired lipid synthesis, problems with tissue repair, and pathogen killing).
 • ME/CFS patients’ brains appeared to be in a similar fix as blood oxygen levels suggested that the brain’s voracious appetite for energy was causing it to strip as much oxygen from the blood as possible.
 • Another seconded that notion when it showed that instead of adapting to a task and using less energy like the healthy controls did – the ME/CFS patients’ brains actually used more energy to accomplish the same task; i.e. when given a task, their brains appeared to be in a hypermetabolic state that would lead to a crash.
 • Cellular exhaustion reared its head again when Younger found elevated lactate levels throughout the brain in a subset of ME/CFS patients, suggesting the brain had exhausted its resources, run out of oxygen, and was burning other fuels to keep it going.
 • Nath’s findings of reduced cerebrospinal levels of dopamine metabolites and a serotonin precursor (DHPG) hit at yet another potential metabolic issue – decreased catecholamine biosynthesis – once again suggesting that the brain was running low on vital resources.
 • With that, it appeared that both the brains and immune cells of ME/CFS patients had fallen prey to the same problem: both were running out of resources and had resorted to operating anaerobically and/or using inefficient fuels to fuel them.
 • An African Green Monkey virus suggested how this may be happening. It found that the energy demands of people with “long-African Monkey virus syndrome” soared in the early stages of the infection, creating a “hypermetabolic state” in their immune cells.
 • Patients whose immune cells couldn’t meet the metabolic demands were forced to turn to alternative anaerobic energy pathways (glycolysis/pyruvate metabolism) to generate energy – and were sicker. Indeed, 30 days after the pathogen had apparently been vanquished, an “energy maladjustment” had occurred, leaving them in a state of “metabolic insufficiency”.
 • The conclusion – an inability to produce enough energy during the infection overloaded the mitochondria – damaging them – and leaving their cells in a low-energy state.

[anumberofhobbies]

I wonder what the status of this from last year is now?

To see if WASF3 dysfunction might be involved in ME/CFS, the team compared muscle tissue samples taken from 14 people with ME/CFS to samples from 10 healthy volunteers. They found substantially higher levels of WASF3 in most of the people with ME/CFS. This dysfunctional increase in WASF3 seemed to be linked to impairment of a cellular signaling pathway called the ER stress pathway. When the team treated human muscle cells with a compound known to increase ER stress, they saw a corresponding harmful increase in WASF3. The researchers treated cells from the initial study participant with an experimental drug, called salubrinal, known to reduce ER stress. After this treatment, WASF3 levels decreased in the cells, more mitochondrial energy complexes formed, and energy production improved. “We hope to embark on clinical studies to investigate whether this type of strategy can also work in patients to improve energy levels,” Hwang says. Mitochondrial dysfunction has been found in some people with Long COVID and other conditions that include fatigue. More research is needed to understand whether targeting ER stress may also be a promising approach for these conditions.

[kaylinalexanderbooks]

Happy STS round 2! What level of medical knowledge exists in Alium?

Thanks again!

A lot of medical knowledge, due to advanced tech because, well, they have healers as a decent part of their population (the fifth most common).

Healers can sense what's wrong in someone who's sick. Even if they don't have the medical expertise, they would be able to tell where the problem was, and a general idea of what's going on, even if they don't know the exact terminology. Most healers are encouraged to study medicine due to their abilities, for better or worse.

Healers can also, of course, heal to varying degrees. For example, Level-1 healers would be able to close up wounds and prevent blood loss, but wouldn't be able to heal more cell damage, such as burns. Level-2 healers can heal burns, and Level-3 healers can prevent scarring.

The way powered-healing works is that they have significantly higher macrophages, which healers are encouraged to donate, and those can be used to create antidotes, medications, vaccines, etc. Healers also have the ability to boost mitochondrial energy production and regeneration, more ATP energy, and enhanced cell signalling to repair the damaged cells. With the proper samples, technology did develop to semi-replicate this ability in for relatively minor injuries. Does this make Level-1 healers feel obsolete? Yeah. It does, thanks for asking.

In summary, Alium has higher medical tech due to healers being common enough.

Thanks!

TSP intro

TSP tag list (ask to be +/-): @thepeculiarbird @illarian-rambling @televisionjester @finchwrites

[bsahely]

From Systems to Cells: A Regenerative Model of Healing and Health | ChatGPT4o

[Download Full Document (PDF)] This document presents a comprehensive exploration of a regenerative model of healing and health, emphasizing the interconnectedness of biological, psychological, social, and ecological systems. The introduction highlights the crisis of coherence within living systems, proposing that health is defined not just by the absence of disease but by the presence of…

[giulliadella]

WE HAVE SOLVED THE MYSTERY OF WHY CELLS HATE NEUTROPHILS SO MUCH IN CAW

So, last night, my boyfriend and I got into some random discussion about programmed cell death and some new breakthroughs in medicine, you know, the usual things you talk about with your boyfriend at 1 AM. It is well known that leftover bodies of dead cells are phagocytosed (literally consumed) by macrophages. And that’s why I always wondered why aren’t cells scared of macrophages as much as they are of neutrophils, since neutrophils don’t consume the dead cells. With my limited understanding of immunity (which we technically don’t learn a lot about in biology) I thought that neutrophils only consumed invader bacteria and fungi.

And OH BOY was I wrong about that.

Because (and yes I have spent whole night researching this, I’ll provide the links to papers in the end lol) neutrophils are little freaks and not only do they phagocytose leftovers of cells they actually cause them to die in the first place. This happens during infections, especially with viruses that cause the excess release of cytokines (like Coronaviridae). Cytokines activate neutrophils who basically just follow the signal towards the infection site and there all hell breaks loose. Neutrophils phagocytose bacteria and virions (those are viruses that haven’t infected a cell yet) which is fine, but they also degranulate and NETose. I’ll explain this in simple terms to my best ability.

Degranulation is when granulocytes (neutrophils, eosinophils, basophils and mastocytes are all different granulocytes) release their granules which are kind of like little sacks inside their cytoplasm which contain various chemicals. Releasing these chemicals happens when the cell receives appropriate stimulus, the little granules expel their contents out of the cell’s interior. In the case of neutrophils, granules contain very toxic compounds that cause the formation of free radicals which damage DNA and proteins of the surrounding cells, as well as granules filled with digestive enzymes which, well, digest the surrounding tissues.

NETosis is a special type of cell death specific to neutrophils in which they literally degranulate pieces of their own, or their mitochondrial DNA together with more toxic compounds. This creates a net of DNA strands called chromatin which entangles invading bacteria and severely damages them and also marks them for phagocytosis by macrophages. But this process is not well controlled and some of that chromatin and toxic compounds can land onto neighboring cells which is, as you can conclude, very bad for them.

With these two abilities at hand, neutrophils are very well equipped to kill cells and destroy tissue. Which is good in cases when the cells are infected and the tissue is damaged, but their quite aggressive methods can damage healthy cells in the area as well, some of them will die and neutrophils will phagocytose their dead particles. 

Basically, to neutrophils every infection is a huge kill and eat all you can buffet. They literally phagocytose until they physically cannot anymore and then go to the spleen or bone marrow to die. They also allow macrophages to consume them and thus pass on the antigens for antigen presentation which influences further immune response. But they can also cause a lot of damage, especially if cytokine storm happens and they completely lose control. This is what causes SARS and it can kill you if it’s severe enough. 

Biologically speaking, neutrophils are very important because they are the first ones to come to the sight of infection and their crazy methods usually finish the things before they get too severe. They themselves produce cytokines that mobilize macrophages and dendritic cells so that more immune cells can join and help them. They also have a role in repairing the tissues they damaged.

However, other immune cells, including macrophages and killer T cells, simply don’t cause as much damage. Neutrophils just go all out, which is why they live for such a short period of time compared to their colleagues (they live for only few days, compared to macrophages who can live up to a month and lymphocytes who can live for months, even years).

So, yeah, my boyfriend and I have concluded (at 4AM this morning) that neutrophils are so feared because they damage tissue, go crazy and violently kill healthy cells by accident, then consume them and that’s not by accident, it’s a mechanism to repair tissues.

I can’t believe I wasted whole night just for this. My boyfriend is also disappointed. But I hope that we finally have an explanation for this mystery. Tell me what you think lol.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589350/

https://www.nature.com/articles/nri.2017.105

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820392/#:~:text=Neutrophils%20contribute%20to%20tissue%20injury,detail%20here%20(Kruger%20et%20al.

[anulithots]

go ahead & talk about caspases

So I'm using this article for my ramblings (I annotated it and went feral): Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis - PubMed (nih.gov)

The research article, and how to storyfy it

SO the crux of this article - being called the ‘paradoxical functions of caspases’ and all - is that capase-3’s cause cell proliferation and cleavage in more than just apoptosis, implying that their function is widespread throughout the cell.

Now that sounded formal. Here’s how I’ll story-fy it. So Cassiah the Caspase-3 wants to not be attached to the world because their purpose is to destroy it. If death lies at the end of this then why suffer the pain of wanting something from this? However, because of thrill life offered after the Caspase-9 first awoke them, they want their life to mean something. They want their life to be so full of meaning and fulfillment at every moment that death wouldn’t matter much anyways.

So with the dual purposes of caspase-3’s, the question of whether Cassiah is meant to cause apoptosis or something else is uncertain. What Cassiah knows is that they want to fulfil their itches and urges to kill/cleave proteins

(We’ll have cleaving be a sort of ‘blood transformation’. So they must be cut in a certain way… similar to those blood sigil things)

They know that cleaving other proteins would give their buzzing energy in a search for more a rest, that would be the moment they finally are content.

Now the Caspase-9 that awoke Cassiah believes that Cassiah must meet the expectations of their purpose. Don’t ask questions. If Cassiah is meant to cause the death of the cell then so be it. Attempting to avoid this fate would only cause more heartache. ‘This is real. If you get caught in dreams of grandeur, as you, as a caspase… then I can only wish that you realize the truth before the end.’

Casapse-9/intrinsic pathway activation (this one involves cytochrome-c from the mitochondria, fun fun):

In essence, external growth factors cease, the outside world doesn’t want anything from this cell anymore. Stressors such as ‘viral infections, hypoxia, hyperthermia, oxidative stress, and intrinsically detected stress signals resulting from exposure to toxic chemical or radiation exposure’. So the outside world is cut off, something on the inside is wrong.

As far as signaling goes, I imagine something akin to carrier pigeons? … I still have to figure out what sort of style of world this is, but honestly I’m leaning more and more towards ‘biology first then the rest melds around that’. So either more sentient ‘carrier pigeon’ types or little floating things (magic sparkles of sorts) that land upon certain proteins or other receptors that cause some sort of shift or change. In this case. Stress signals. They cause certain alarms to go off, such as this pathway. So is everyone aware that the world might end? Yes and no. It depends on who you are, and given that cell signaling is complex, I imagine that everyone has their own idea/awareness of what is going on. If a protein goes about their day and recognizes a little signal floating around among the slew, the hustle and bustle of things floating around, then that might be a cause for concern.

From here the signals cause the mitochondrial membrane to be more permeable.

Now for membranes, their built of this ‘ramen type thing’ (similar to how people build all sorts of things with ramen… but more magical and fancy and such )

… so we’re going with magical absurdism here.

Anywho, so the phospholipid bilayer… would probably look around the same? Heads facing the outside, so it’s bumpy, along with the inside looking like stringy ramen. So that becomes looser…

and things

begin

to

leak.

SUCH AS CYTOCHROME C!

I forget what this was used for in cellular respiration because…. cellular respiration… I’d need to review some of that. If I remember correctly, it was part of oxidative phosphorylation… the electron transport chain?

So that starts bleeding into the surrounding space, which forms a apoptosomal complex that includes caspase-9.

Storyfying wise - Caspase-9 has lied dormant in this biomechanical machine (sci-fi is slowly but surely becoming more intriguing to me), waking rarely, always a hush hush if they do. For that, everyone knows (at least everyone in the know knows) that could end in disaster.

So the cytochrome c causes that biomechanical mass to awaken, a sore and tired and… dread-filled caspase-9 within.

(We’re going to be looser with personalities needing backstories to explain every facet here for my own sanity)

This caspase-9 then - still shaking off the aches of dormancy - awakens their ‘younger sibling who will cause the end of the world’

And here, they feel a touch of pity. It’s not fair. Really. It’s not fair yet this is what it is, how the Caspase-9 wishes it didn’t have to do this, but the universe itself is against any rebellion, and they don’t want any pain unto themself.

Caspase-3s’s are these little caspase-3 assassins that kill off caspase-3’s. The way this whole thing with all the opposing signals works here is that… this is an entire world here. IN order to have the ‘right thing’ done, there must be conflict, someone who wins out in the end, it’s a fragile balance.

So the Caspase-9… now here’s the part where I’m still figuring it out… it’s okay but it could be better…

The caspase-9 manages to save only one of the caspase-3’s from the caspase-3s, Cassiah, who does seem a little shaken from the whole ordeal, and a little hesitant to follow their whole purpose, they don’t leave immediately… In fact, they aren’t really shaken, they are thrilled.

Oh. What an issue.

The Caspase-9 easily forgets the other caspase-3’s, and this more than anything frightens Cassiah, while the Caspase-9 tells them that this, whatever this is, they just escaped with their lives here. They could’ve easily been killed as well, then the Caspase-9 would need other caspase-3’s to replace Cassiah. THe world doesn’t care. There’s no solace outside of the promise of being useful. Any attempt otherwise ends in heartache.

Now here Cassiah wonders what would’ve happened if they had died right then, before they got the chance to fully experience something, it wouldn’t have been such a pain then. It would’ve been like sleeping more after a brief interruption.

Does the world care? Is there a meaning to this?

Perhaps not.

But they want a meaning to this. To their life. They want to live and savor every moment of it so even if they had died in the next, they could’ve died fulfilled, full, with a meaning to even death.

So Casaiah’s really fighting against their own desire to live well with the promise of a meaningless but purposeful existence, one that is guaranteed not to hurt, to be satisfying in the end, as long as they don’t resist.

(Sigh I won’t really get this until I start writing Cassiah prose)

the dual purpose of caspase-3

Caspase-3’s cleave other proteins, inhibitors, and such. Again, I imagine this would involve a high-stakes kidnapping a blood-sigil-type-thing where Cassiah cuts just so for the protein to change purpose/activate or deactivate.

Now part of what they do is cut inhibitors, for instance, they cut an inhibitor that keeps DNA from fragmenting. An inhibitor inhibits caspase-activated DNAse, once Caspse-3 removed the inhibitor, caspase-activated DNAse condenses and cleaves DNA at ‘interneucleosomal linker sites between nucleosomes’

OTHER RESULTS: so, because of Caspase-3’s other downstream targets ‘phosphatidylserine from the inner layer of the plasma membrane’ leaks from the membrane to the outside of the cell. It binds to the cell surface and calls phagocytes to the cell to consume it. This is a preliminary sign of apoptosis

~Storyfying this - So BLOOD SIGILS CARVED INTO THE FLESH.

ANd I doubt articles will have the specific targets because cell signaling is…. complicated so say the least, so I have some creative liberty here.

In Cassiah’s little adventures around the cell, they have sudden thoughts to do the deed. They will have to kidnap them, take them somewhere private and carve the sigil into flesh, they will change shape as a result.

As far as their morals go with this, they don’t want to be forgotten, so they are perfectly fine with doing the deed itself (what’s more memorable than a life-changing event?) however apoptosis is possible. Apoptosis, in which everything will be forgotten. It wouldn’t have mattered if Cassiah existed or not, their life wouldn’t have meant anything, and that scares them more than anything .

So despite their desire to do the whole blood sigil thing, they avoid it, they even save others for the sake of avoiding apoptosis.

other things:

Caspase-3 activity causes ‘nonautomatous and cell autonomous (or direct) mechanisms of initiation and execution’

nonautomatous refers to the adjacent cells proliferating to replace the apoptotic cell

Caspase-3 activates pathways, starts pathways, interferes with pathways that can lead to tissue growth and wound healing. (nonautonomous) Which is not so fun for tumors and such…

cell autonomous refers to the apoptotic cell itself and how Capase-3

capase-3’s are also known to cleave substrates during the M to G1 transition step in mitosis even when apoptosis will not occur

“This has been explained by caspse-3 mediating the cleavage of p21 (the cyclin-dependent kinase [CDK] inhibitor) at its C terminus, thereby disrupting the ability of p21 to interact with proliferating cell nuclear antigen (PCNA) leading to cell cycle inhibition” ←- basically Caspase-3 can start the cell cycle which IS CRAZY TO ME AAAAAAAAAAAAAAAAAAAAAA

SO STORY WISE

There will definitely be an episode in which Cassiah finds out that they could be involved in mitosis rather than apoptosis. So they spend time around cyclin-dependent kinases for the day and see if they feel any ‘blood sigil urges’

The nonautomnous parts of this are fun, but since they are outside the scope of the cell, I am unsure of if I can include them, but it would be fun if I could because it’s peak angst. (being replaced and such.)

ALSO ALSO

procaspase-3 affects MITOCHONDRIAL REGULATION

“In this case, the suppression of Caspase-3 expression led to mitochondrial dysfunction, accumulation of damaged mitochondria, and downregulation of key transcriptional activators of mitochondrial biogenesis”

PEOPLE POEPLE SKJDSKLFJKDLSJ AAAAAAAAAAAa

SO BASICALLY

I was wrong that procaspases float in a void and are deactivated. They actually work to regulate the mitochondria. KLJDFKJDSLKF but here’s the thing. I built Cassiah’s character off of existing first as floating within the void. If that’s not the case, then I need to change thier entire character to fit around this more. Hopefully it will be easier… maybe…. sighhhh

Now as fun as researching about caspases has been, it’s really for the purpose of character building, now I want to look more into diving deeper on all the AP bio topics and fully fleshing out this world and the themes.

ANd now I also have to rework Cassiah’s character after finding out about this mitochrondria thing…. sigh sigh I should’ve finished the article before I started.

ERM... yes. OKAY SO biology taglist... you do not have to read all this.

The lovely biology taglist: @vamp4ever @bonesbeetle @neurospicy-salsa @sea-dwelling-wizard

[nutritioneducationwithlsfitness]

ICMR NUTRITION GUIDELINES 2024 BREAKDOWN : LSFITNESS

Statement 1 : Some protein powders, marketed in packages as protein supplements, contain protein from multiple sources. Protein powders may also contain added sugars, non-caloric sweeteners and additives such as artificial flavoring, hence, are not advisable to be consumed on a regular basis.

My Take: Protein powders that contain proteins from multiple sources are known as protein blends. These blends often include whey protein, casein protein, albumin, and others. Protein blends are completely safe for use if they are manufactured and processed in facilities that adhere to strict safety standards, such as those following HACCP (Hazard Analysis and Critical Control Points) guidelines.

Statement 2 : Protein powders may also contain added sugars, non-caloric sweeteners and additives such as artificial flavoring, hence, are not advisable to be consumed on a regular basis.

My Take: Protein powders may contain added sugars, non-caloric sweeteners, and artificial flavorings. However, these additives are commonplace in many foods we consume today. Rather than casting a negative light on whey protein supplements, it would be more beneficial to implement strict regulations that limit the use of added sugars. Additionally, encouraging the use of healthier non-caloric sweeteners, such as Fructo-oligosaccharides (FOS), and replacing artificial flavorings with natural ones could improve the nutritional quality of these supplements.

Statement 3 : Whey protein is rich in branched chain amino acids (BCAAs). Recent evidence suggests that BCAAs may increase the risk of certain non-communicable diseases (NCDs). As mentioned above, adequate non-protein energy from carbohydrate and fat is essential for dietary proteins/AA to be utilized for protein synthesis and for related functions in the body. Consuming high level of protein, especially in the form of protein supplement powders, is therefore not advisable.

My Take: Whey protein is indeed rich in branched-chain amino acids (BCAAs): leucine, isoleucine, and valine. Recent evidence has shown a direct correlation between elevated plasma levels of BCAAs and insulin resistance, but this does not necessarily mean it is caused solely by high consumption of BCAAs. The condition may also be due to dysfunctional BCAA catabolism, existing insulin resistance, or being overweight or obese.

Elevated plasma BCAA levels have been observed in individuals who are overweight or obese and exhibit insulin resistance, and these levels are higher compared to healthy individuals. Observational studies have found that plasma BCAA levels are also elevated in patients with Type 2 diabetes when compared to age and BMI-matched controls without diabetes.

Insulin plays a critical role in the metabolism of BCAAs. Results from Mendelian randomization studies indicate that insulin resistance drives higher plasma BCAA levels, and large-scale genetic studies suggest a causal role of diminished BCAA catabolism in underlying insulin resistance.

Dysfunctional BCAA catabolism may lead to the accumulation of a number of BCAA catabolic metabolites in the plasma of insulin-resistant individuals with obesity or Type 2 diabetes, including BCAA-derived acylcarnitines, 3-HIB, 2-HB, and 2-KB. These can have toxic effects on cellular functions. It has been shown that acylcarnitines can cause mitochondrial dysfunction in several tissues and anaplerotic stress, thus dysregulating glucose and fat oxidation.

While there is evidence that elevated BCAA levels can impair insulin signaling pathways, it remains unclear whether elevated BCAA levels are a cause or a consequence of insulin resistance. Most studies measure plasma BCAA levels rather than in peripheral tissues, so future research focusing on peripheral tissues could provide a better perspective on tissue-specific BCAA catabolism.

Statement 4 : Most athletes can get the recommended amount of protein through food alone, without the use of supplements. Protein powders are not required. Moreover, prolonged intake of a large amount of protein is associated with potential dangers, such as bone mineral loss and kidney damage.

My Take: Athletes can obtain the recommended amount of protein through their diet alone, depending on what they eat.

For example, a non-vegetarian athlete can easily meet protein needs from sources such as chicken breast, mutton, and whole eggs while maintaining overall caloric intake, as these sources contain fewer ancillary calories.

Conversely, let's consider an athlete who follows a vegan diet. Major vegan protein sources like tofu, cereals and millets, and pulses and legumes do provide some protein. However, if an athlete relies solely on these foods without supplements, the total calorie count may exceed caloric requirements due to the additional carbohydrates and fats in these protein sources.

Regarding the safety of protein consumption, prolonged intake of a significant amount of protein—ranging from 25-75 grams daily—has not been associated with potential dangers such as bone mineral loss and kidney damage. In fact, studies have shown a positive impact on bone mineral density.

The European Society on Parenteral and Enteral Nutrition (ESPEN) advocates for a higher protein intake of 1.0–1.5 g/kg/day to help slow age-related muscle loss.

There is no evidence to suggest that a high protein diet can cause kidney damage in individuals with healthy renal function. However, those with kidney disease, such as chronic kidney disease (CKD), should limit their protein intake.

[carolinemeinicke]

BrainFit for Life: A User's Guide to Life-Long Brain Health and Fitness.

Brain Fitness is quickly gaining momentum in the media and business worlds. Most of the current focus is on 'brain-training' programs to boost cognitive function. While this is a positive movement, we must not lose focus that the physical visit site here health of the brain is required for cognitive health. We must not ignore all the data regarding the cognitive benefits of a health diet, physical exercise and optimal sleep.

As the Brain Fitness industry continues to gain momentum, and people explore all the incredible brain-training tools being developed, we hope that enthusiasts don't take their eye off the importance of the physical health of the brain and all the systems it communicates with. The brain is unique in that it houses our cognitive and emotional capacities in the form of the mind. It is a 'cognitive' organ that hungers for stimulation from new experiences and challenges. Many brain fitness programs strive to satisfy this need. Yet the brain is also a physical organ that plays by many of the same rules as the heart, lungs, liver and kidneys. To stay healthy and perform optimally it requires quality nutrition, physical activity and optimal sleep. The brain, especially, relies on a healthy vascular system to efficiently deliver oxygen and key nutrients and remove waste. In fact, the brain uses approximately 20% of the oxygen we breathe to satisfy its high-energy demands. Given that the brain only weighs about 2% of the body, we can consider it an energy hog and we must cater to its needs very carefully.

Nutrients play key roles in brain function. Several have shown efficacy in clinical trials treating cases of mood disorders, cognitive decline and of course benefiting the physical health of the brain. Nutrients are both the raw materials employed in creating new neural connections and important components in regulating the activity of genes involved in these processes. Specific nutrients involved in mitochondrial efficiency, the energy factories of brain and body cells, are particularly important for many aspects of brain function. Other nutrients are involved in the inner workings of neuronal membranes, responsible for ensuring that electrochemical signals, which make up our thoughts, transmit efficiently and reliably. Finally, antioxidants, important throughout the body, are especially important in the brain due to its high energy production rates and concurrent high capacity for free radical leakage. Keeping this in mind, it is readily apparent that nutrition provides the building blocks for our brain's structure and function, and therefore cannot be ignored.

Exercise is a clearly established component for promoting brain health as well. No longer can we think that the brain is completely separate from the brawn. Human studies have shown the value of exercise in controlling stress and maintaining positive mood states; in improving cognitive function, including performance on memory and executive tasks; and in improving the brain's two-way communication streams with the rest of the body. Some of these benefits are likely due to the positive effects of exercise on neurovascular health, which parallel cardiovascular health. Other benefits seem due to increased grey matter in 'front office' functions of the cortex; and neuronal birth, or neurogenesis, in the hippocampus, a brain region that controls aspects of memory and mood regulation. Whatever the mechanism, giving your body a workout will produce substantial benefits in terms of brain health. Remember, a body in motion tends to stay in motion, and your brain and body will be together your whole life.

Mental activity is an obvious, and critical, ingredient for optimizing and maintaining brain function. Studies have established relationships between the degree of life-time mental activity and late-life cognitive function. It's clear that those who engage in intellectually challenging endeavors on a regular basis reap the benefits of a clear mind. There is, however a need for each individual to balance sufficient variety with a proper degree of challenge. Without variety and challenge, tasks become too mundane and too easy, eventually growing stale and losing their capacity to adequately stimulate the brain. We must also realize that mental activity goes beyond 'cognitive' tasks. Mental activities also include practices like meditative focus, relaxation and stress reduction techniques, as well as social interaction. These active and dynamic processes challenge the mind as well. Mixing cognitive challenges with emotional regulation provides a more complete mental workout that will help you to use it to improve it.