#immune receptor

[medicomunicare]

Prostanoids enemies forever: we'll keep on fighting (IL-)2 exhaustion 'TIL cancer cells will die

Tumors actively prevent the formation of immune responses by so-called cytotoxic T cells, which are essential in combating cancer. In cancer, tumors often impair the body’s immune response. For example, they can prevent immune cells from perceiving cancer cells as a threat or render them inactive. Immunotherapies aim to overcome these mechanisms and stimulate the immune system, in particular the…

[colinwilson11]

The cGAS-STING Pathway: A Key Immune Surveillance Mechanism

The innate immune system provides the first line of defense against invading pathogens like viruses and bacteria. One of its key mechanisms for detecting microbial infections is the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. This cellular surveillance pathway plays a critical role in detecting foreign DNA from invading microbes and mounting appropriate immune responses.

How It Works

When microbial DNA enters the cytosol of host cells, it is recognized by the cGAS enzyme. cGAS has the unique ability to bind to DNA and produce the second messenger cyclic GAMP (cGAMP) from ATP and GTP. cGAMP then acts as a ligand to bind and activate the endoplasmic reticulum-associated adaptor protein called STING.

Activation of STING leads to its association with tumor necrosis factor receptor-associated factor 3 and 6 (TRAF3/6). This triggers a downstream signaling cascade involving the protein kinases TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3).

Phosphorylation of IRF3 by TBK1 causes IRF3 dimerization and translocation into the host cell nucleus. There, IRF3 induces the expression of Type I interferons (IFN-α and IFN-β) and other proinflammatory cytokines that signal the presence of invading pathogens to other cells and recruit additional immune defenses.

Role In Antiviral Defense

The cGAS-STING Pathway plays a critical role in the host defense against various DNA viruses like herpes simplex virus 1, cytomegalovirus, Epstein-Barr virus, vaccinia virus and HIV. Upon viral DNA entry in the cytosol, cGAS binds and activates STING to induce Type I IFN production. This initiates an antiviral state in infected cells and neighboring uninfected cells to limit viral replication and spread. Mice lacking cGAS or STING exhibit impaired IFN responses and increased susceptibility to infection by these DNA viruses.

Protecting Against Cancer

Aside from fighting infections, the cGAS-STING Pathway also acts as a tumor suppressor mechanism by detecting aberrant genomic DNA in cancer cells. Many cancer cells have disruptions like broken DNA strands that could lead to cell death if sensed by the immune system. However, cancer cells often develop ways to evade this cGAS-STING surveillance.

Studies have shown that loss of or reduced expression and activity of cGAS or STING promotes tumorigenesis in various cancer types like colon cancer and prostate cancer. At the same time, therapeutically activating the cGAS-STING Pathway seems to stimulate antitumor immunity and enhance the effectiveness of cancer immunotherapies in mouse models. This highlights the pathway's potential for developing new immunotherapeutic strategies against cancer.

Role In Autoimmune Disease

While the cGAS-STING Pathway protects against infections and tumors, its overactivation can also lead to inflammatory and autoimmune conditions. Defects that cause constitutive STING signaling have been linked to autoinflammatory diseases. Genetic mutations that make STING hyperactive and uncontrollable result in a group of rare hereditary inflammatory syndromes known as STING-associated vasculopathies with onset in infancy (SAVI). Patients with SAVI exhibit symptoms resembling systemic lupus erythematosus due to excess Type I IFN production.

Meanwhile, environmental and endogenous cytosolic DNA from dying cells have been shown to aberrantly trigger the cGAS-STING Pathway and IFN responses during conditions like systemic lupus erythematosus or Aicardi-Goutières syndrome. Figuring out ways to modulate cGAS-STING activation or signaling may yield new therapeutic approaches for these diseases.

Pharmaceutical Applications

Given its crucial contribution to antiviral immunity and cancer immunosurveillance, the cGAS-STING Pathway represents an attractive target for pharmaceutical intervention. Small molecule drugs that activate cGAS or STING are being developed as potential antiviral and anticancer agents. STING agonists administered alone or in combination with checkpoint inhibition immunotherapy show promise in treating solid tumors in clinical trials.

Moreover, cGAS or STING inhibitors may offer new ways to treat autoinflammatory conditions caused by overactive cGAS-STING signaling. Researchers continue working to refine drugs that can selectively modulate different points along the pathway for optimal therapeutic benefit while avoiding side effects. As understanding of this defense mechanism deepens, more opportunities may arise to harness it against an array of diseases with immunological underpinnings.

The cGAS-STING Pathway serves as a critical surveillance system helping our innate immune defenses detect cytosolic DNA. Its ability to sense microbial as well as aberrant self-DNA makes it an important regulator of antiviral immunity, tumor suppression, and inflammatory balance. Ongoing investigations into modulating cGAS-STING activation hold promise for developing new immunotherapies targeting infections, cancer, and autoimmune disorders.

Get more insights on this topic:   https://www.ukwebwire.com/role-of-cgas-sting-pathway-in-detecting-cytosolic-dna/

Author Bio:

Alice Mutum is a seasoned senior content editor at Coherent  Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital ing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of  insights. (LinkedIn: www.linkedin.com/in/alice-mutum-3b247b137 )

*Note: 1. Source: Coherent  Insights, Public sources, Desk research 2. We have leveraged AI tools to mine information and compile it

[faultfalha]

The Solanum americanum genome has been used to discover immune receptors that detect potato late blight pathogen effectors. The discovery could lead to the development of new, more effective ways to fight the late blight pathogen.

[reasonsforhope]

"People living with diabetes might have a new hope. Scientists have tested a new drug therapy in diabetic mice, and found that it boosted insulin-producing cells by 700% over three months, effectively reversing their disease.

Beta cells in the pancreas have the important job of producing insulin in response to blood sugar levels, but a hallmark of diabetes is that these cells are either destroyed or can’t produce enough insulin. The most common treatment is regular injections of insulin to manage blood sugar levels.

But a recent avenue of research has involved restoring the function of these beta cells. In some cases that’s started with stem cells being coaxed into new beta cells, which are then transplanted into patients with diabetes. Researchers behind this kind of work have described it as a “functional diabetes cure.”

Now, scientists at Mount Sinai and City of Hope have demonstrated a new breakthrough. Previous studies have mostly involved growing new beta cells in a lab dish, then transplanting them into mice or a small device in humans. But this new study has been able to grow the insulin-producing cells right there in the body, in a matter of months.

The therapy involved a combination of two drugs: one is harmine, a natural molecule found in certain plants, which works to inhibit an enzyme called DYRK1A found in beta cells. The second is a GLP1 receptor agonist. The latter is a class of diabetes drug that includes Ozempic, which is gaining attention lately for its side effect of weight loss.

The researchers tested the therapy in mouse models of type 1 and 2 diabetes. First they implanted a small amount of human beta cells into the mice, then treated them with harmine and GLP1 receptor agonists. Sure enough, the beta cells increased in number by 700% within three months of the treatment. The signs of the disease quickly reversed, and stayed that way even a month after stopping the treatment.

“This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo,” said Dr. Adolfo Garcia-Ocaña, corresponding author of the study. “This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes.”

The results are intriguing, but of course being an animal study means there’s still much more work to be done before it could find clinical use. So far, harmine alone has recently undergone a phase 1 clinical trial in humans to test its safety and tolerability, while other DYRK1A inhibitors are planned for trials in humans next year.

Perhaps most importantly, the team will soon experiment with combining beta-cell-regenerating drugs with others that modulate the immune system. Ideally this should help overcome a major hurdle: the immune system will continue attacking new beta cells as they’re produced.

The research was published in the journal Science Translational Medicine."

-via New Atlas, July 14, 2024

[thebibliosphere]

Hello, I apologize if this is something you've already talked about or you've answered this question before or don't want to speak more on it but I saw that ask you responded to the other day that your 'mast cells burnt down your gi track' and I wanted to ask what the name of that condition is called? Several years ago I randomly lost 45 pounds and couldn't explain it. And while I already had gi issues before, after it happened I started developing new ones that got worse with time to the point that now I am physically unable to work. There are a lot of other factors with my situation that could be to blame but I've gotten an absurd amount of various tests with no answers to show for it. And now I'm wondering if maybe whatever happened to you has happened to me.

Oh, bestie, you're all good; all I do is bitch on this app about having mast cell dysfunction.

There are a handful of different mast cell disorders, but my condition is known as Mast Cell Activation Syndrome, or MCAS for short. If you want to know what a mast cell is and how it operates in the immune system, I'd recommend checking out The Mast Cell Disease Society:

They're currently redoing their content, but there's still a wealth of information on there.

You can also search my blog for #MCAS and find a handful of posts where I break it down in detail, along with the current flaws in testing for mast cell patients.

The reason I lost a lot of weight was because my mast cells made my GI tract so inflamed that I couldn't digest anything I was eating. It was going in through my mouth, causing excruciating pain and giving me no nutritional value whatsoever.

Histamine type 2 blockers, such as famotidine/pepcid used to treat acid reflux, can help with GI inflammation from mast cell dysfunction (the GI tract is lined with histamine receptors), but I needed extra support, which I finally got late last year when my GI doctor realized after a biopsy that I was being undermedicated and needed more help managing my MCAS.

If you want to ask more specific questions, I'm happy to try to answer them, but I'd suggest reading through the above link first to see if any of it resonates with you.

[liketolaugh-writes]

Yo so. I’ve never exactly vibed with the headcanon that Danny gets high on fear gas. As far as I know, Scarecrow’s toxin isn’t actually human fear chemicals, it’s a hallucinogen that induces a fear response. (Did I explain that well? Not the point.)

Anyway, as far as I’m concerned, Danny in ghost form doesn’t have the right chemical receptors to respond to Anything in that form, though you could probably get something out of his human form. In other words: his human form has a reduced vulnerability to fear gas, while his ghost form is immune.

The crush of fear that comes from a Scarecrow gas attack, though?

See, Danny wasn’t expecting that. Fear is generally kind of a snack for him, if he bothers to think of it as anything but a guide toward his obsession. But the first Scarecrow attack that he’s there for - the mass hysteria, the intensity and the crowd and the density - it’s more fear than a ghost invasion, more fear than an office fire, more raw fear than the end of the world.

He doesn’t exactly get high off it. He doesn’t exactly get drunk. But his head spins as the mass hysteria zings through him, and he can’t focus at first, and for a moment he forgets that he’s there to help. He can’t find the fear and horror in himself at the sight in front of him, not until later.

(He gets used to the feeling, with time and practice, but he always remembers that first time.)

[covid-safer-hotties]

also preserved on our archive

By Erica Sloan

These days, it’s tempting to compare COVID-19 with the common cold or flu. It can similarly leave you with a nasty cough, fever, sore throat—the full works of respiratory symptoms. And it’s also become a part of the societal fabric, perhaps something you’ve resigned yourself to catching at least a few times in your life (even if you haven’t already). But let’s not forget: SARS-CoV-2 (the virus responsible for COVID) is still relatively new, and researchers are actively investigating the toll of reinfection on the body. While there are still a lot of unknowns, one thing seems to be increasingly true: Getting COVID again and again is a good deal riskier than repeat hits of its seasonal counterparts.

It turns out, SARS-CoV-2 is more nefarious than these other contagious bugs, and our immune response to it, often larger and longer-lasting. COVID has a better ability to camouflage itself in the body, “and it has the keys to the kingdom in the sense that it can unlock any cell and get in,” says Esther Melamed, PhD, an assistant professor in the department of neurology at Dell Medical School, University of Texas Austin, and the research director of the Post-COVID-19 program at UT Health Austin. That’s because SARS-CoV-2 binds to ACE2 receptors, which exist in cells all over your body, from your heart to your gut to your brain. (By contrast, cold and flu viruses replicate mostly in your respiratory tract.)

It only follows that a bigger threat can trigger an outsize immune response. In some people, the body’s reaction to COVID can turn into a “cytokine storm,” Dr. Melamed tells SELF, which is characterized by an excessive release of inflammatory proteins that can wreak havoc on multiple organ systems—not a common scenario for your garden-variety cold or flu. But even a “mild” case of COVID can throw your immune system into a tizzy as it works to quickly shore up your defenses. And each reinfection is a fresh opportunity for the virus to win the battle.

While you develop some immunity after a COVID infection, it doesn’t just grow with each additional hit. You might be thinking, “Aren’t I more protected against COVID and less likely to have a serious case after having been infected?” Part of that is true, to an extent. In the first couple years after COVID burst onto the scene, reinfections were generally (though not always) milder than a person’s initial bout of the virus. “The way we understand classic immunology is that your body will say to a virus [it’s seen before], ‘Oh, I know how to deal with you, and I’m now going to deal with you in a better way the second time around,’” says Ziyad Al-Aly, PhD, a clinical epidemiologist at Washington University in St. Louis School of Medicine and the chief of research and development at the Veterans Affairs St. Louis Health Care System.

But any encounter with COVID can also cause your immune system to “go awry or develop some form of dysfunction,” Dr. Al-Aly tells SELF. Specifically, “immune imprinting” can happen, where, upon a second (or third or fourth) exposure to the virus, your immune cells launch the same response as they did for the initial infection, in turn blocking or limiting the development of new antibodies necessary to fight off the current variant that’s stirring up trouble. So, “when you get hit an [additional] time, your immune system may not behave classically,” Dr. Al-Aly says, and could struggle with mounting a good defense.

Pair that dip in immune efficiency with the fact that your antibody levels also wane with time post-infection, and it’s easy to see how another hit can rock your body in a new way. Indeed, the more time that passes after any given COVID infection, the less of a “competitive advantage” you’ll have against any future one, Richard Moffitt, PhD, an associate professor at Emory University, in Atlanta, tells SELF. His research found that, while people who got sick initially during the delta phase were less likely to get reinfected during the first omicron wave (as compared to folks who were infected in a prior period), that benefit leveled off with following omicron variants.

There’s also the fact that no matter how your immune system has responded to a prior strain (or strains!) of the virus, it could react differently to a new mutation. “We tend to think of COVID as one homogeneous thing, but it’s really not,” Dr. Al-Aly says. So even if your body successfully thwarted one of these intruders in the past, there’s no guarantee it’ll do the same for another, now or in the future, he says.

Getting COVID again and again is especially risky if it previously made you very ill. Dr. Moffitt’s study above also found that the “severity of your first infection is very predictive of the severity of a reinfection,” he says. Meaning, you’re more likely to have a severe case of COVID—for instance, requiring hospitalization or intensive care, such as ventilation—when reinfected if you had a rough go of it the first time around.

It’s possible that some folks are more prone to an off-kilter immune response to the virus, which could then happen consistently with reinfections. The antibodies created in people who’ve had severe cases “may not function as well as those in folks who’ve had mild infections or were able to fight the virus off,” Dr. Melamed says. Though researchers don’t fully understand why, some people’s immune systems are also more likely to overreact to COVID (remember the cytokine storm?), which can cause serious symptoms—like fluid in the lungs and shortness of breath—whenever they’re infected.

Being over the age of 65, having a chronic illness or other medical condition, and lacking access to health care have all been shown to spike your risk of serious outcomes with a COVID infection, whether it’s your first or fifth fight with the virus.

But you’re not home free if you’ve only had, say, a brief fever or cough with COVID in the past; Dr. Moffitt points out that a small subset of people in his research who had minor reactions with their initial infection went on to be hospitalized with a repeat hit. The probability of that might be lower, but it’s still a possibility, he says.

Even if you’ve only had “mild” cases, each reinfection strains your body, upping your chances of developing long COVID. A 2022 study led by Dr. Al-Aly found that COVID reinfections also increase your risk of complications across the board, regardless of whether you recovered just fine in the past or got vaccinated. In particular, it showed that reinfection raises the likelihood that you’ll need hospitalization; have heart or lung problems; or experience, among other possible issues, GI, neurological, mental health, or musculoskeletal symptoms. “We use the term ‘cumulative effects,’” Dr. Al-Aly says, “so, multiple hits accrue and then leave the body more vulnerable to all the potential long-term health effects of COVID.”

That doesn’t mean your experience of a second (or third or fourth) infection will necessarily be worse, in and of itself, than what you felt during a prior case. But with each new hit, a fresh batch of the virus seeps into your system, where, even if you have a mild case, it has another chance to trigger any of the longer-term complications above. While the likelihood of getting long COVID (a constellation of symptoms lingering for three months or longer post-infection) is likely greatest after initial infection, “The bottom line is, people are still getting diagnosed with long COVID after reinfection,” Dr. Moffitt says.

Researchers don’t totally know why one person might deal with lasting health effects over another, but it seems that, in some folks, the immune system misfires, generating not only antibodies to attack the virus but also autoantibodies that go after the body’s own healthy cells, Dr. Al-Aly says. This may be one reason why COVID has been linked to the onset of autoimmune conditions like psoriasis and rheumatoid arthritis.

A different hypothesis suggests that pieces of the virus could linger in the body, even after a person has seemingly “recovered” (reminder that SARS-CoV-2 is scarily good at weaseling its way into all sorts of cells). “Maybe the first time, your immune system was able to fully clear it, but the second time, it found a way to hang around,” Dr. Al-Aly posits. And a third theory involves your gut microbiome, the community of microbes in your GI tract, including beneficial bacteria. It’s conceivable that “when we get sick with COVID, these bacteria do, too, and perhaps they recover [on initial infection], but not on the second or third hit,” he says, throwing off your balance of good-to-bad gut bugs (which can impact your health in all sorts of ways).

Another unnerving possibility: The shock to your system triggered by COVID may “wake up” a latent (a.k.a. dormant) virus or two lurking in your body, Dr. Melamed says. We all carry anywhere from eight to 12 of these undetected bugs at a time—things like Epstein-Barr, varicella-zoster (which causes chickenpox and shingles), and herpes simplex. And research suggests their reactivation could be a contributing factor in long COVID. Separately, the systemic inflammation often created by COVID may spark the onset of high blood pressure and increased clotting (which can up your risk of stroke and pulmonary embolism), as well as type 2 diabetes, Dr. Melamed says.

There’s no guarantee that any given COVID infection snowballs into something debilitating, but each hit is like another round of Russian roulette, Dr. Al-Aly says. From a sheer numbers standpoint, the more times you play a game with the possibility of a negative outcome, the greater your chances are of that bad result occurring. And because every COVID case has at least some potential to leave you very ill or dealing with a host of persistent symptoms, why take the risk any more times than you need to?

Bottom line: You should do your best to avoid COVID reinfection and bolster your defenses against the virus. At this stage of the pandemic’s progression, it’s not realistic to suggest you can avoid any exposure to the virus, given that societal protections against its spread have been rolled back. But what you should do is take some common-sense precautions, which can help you avoid any contagious respiratory virus. (A cold or the flu may not pose as many potential health risks as COVID, but being sick is still not fun!)

It’s a good idea to wear a mask when you’re in a crowded environment (especially indoors), choose well-ventilated or outdoor spaces for group hangouts, and test for COVID if you have cold or flu-like symptoms, Dr. Al-Aly says. If you do get infected, talk to your doctor about whether your personal risk of a severe case is enough to qualify for a Paxlovid prescription (which you need to take within the first five days of symptoms for it to be effective).

The other important thing you should do is get the updated COVID vaccine (the 2024-2025 formula was recently approved and released). Unlike getting reinfected, the vaccine triggers “a very targeted immune response…because it’s [made with] a specific tiny part of the virus,” Dr. Melamed says. Meaning, you get the immune benefit of a little exposure without the potential of your whole system going haywire. Getting the current shot also ensures you restore any protection that has waned since you received a prior jab and that you have an effective shield against the dominant circulating strains. Plus, research shows that being vaccinated doesn’t just lower your chances of catching the virus; it also reduces your risk of having a severe case or winding up with long COVID if you do get it.

So, too, can the deceivingly simple act of keeping up with healthy habits—like exercising regularly, eating nutritious foods, and clocking quality sleep. Maintaining this kind of lifestyle can help you stave off other health issues that could increase your risk of harm from COVID, Harlan Krumholz, PhD, a cardiologist at Yale University and founder of the Yale Center for Outcomes Research and Evaluation (CORE), tells SELF. “Given that we will be repetitively exposed to the virus, the best investments we can make are in our baseline health,” he says.

Doing any (or all!) of the above is a big act of compassion for yourself, the people you love, and your greater community. “For the average person, it’s like, ‘Oh, COVID is gone,’ but they’re just not seeing the impact,” Dr. Al-Aly says, noting the invisibility of long COVID symptoms like disorienting brain fog and crushing fatigue. The truth is, in plenty of people, just one more infection could be the difference between living their best life and facing a devastating chronic condition.

[charlesoberonn]

Wait, are all humans allergic to capsaicin?

No. Allergies are caused by the immune system being wrongly activated. The pain sensation and digestive irritation caused by capsaicin are caused by the activation of pain and heat receptors in our tissues.

[medicomunicare]

Chimering interferon on a myeloma receptor: meet modakafusp and its "single-agent" abilities

Chimering interferon on a myeloma receptor: meet modakafusp and its “single-agent” abilities

According to the American Cancer Society, about 12,640 deaths from multiple myeloma are expected to occur in the U.S. in 2022. The cancer is uncommon, affecting less than 1% of the population, especially elder people over the 75 of age. Myeloma is currently not curable, and despite advances in treatment, all patients see their cancers relapse after initial treatment and other early lines of…

[prncssie]

TWO ⎯⎯ ★ s. ryomen m. list

content warning minors and trump supporters do not interact. neither are welcome here. in this specific chapter, it gets suggestive towards the end but there is no on page smut. you can expect consensual groping in a public setting and "dick" is written once. also, the bouncer is described as creepy and acts as such but his appearance is short

WHEN I GROW UP

you thought when you strolled through the glass doors of an acting agency, — a grand building lined with glass walls, allowing the sunlight to filter into the lobby — you’d be greeted with warm smiles and maybe even a mint. this is not what you were expecting. it smells clean, citrusy, like fresh squeezed lemons and pine. the hardwood flooring, tan and matte, are smooth beneath your new balances. it’s nearly glittering a pathway guiding you to the front desk. your resume, shielded behind the manilla folder, is tucked tightly to your chest. you’ve even worn your best off-duty outfit, aiming for something simple to show off your spark. a black tube top and black jeans, perfect for forcing focus to your face full of sweet features, dollike and docile enough to render a certain impression on camera, you hope.

“hi,” you speak soft at first, a smile gracing your mouth when the receptionist lifts her head. “yeah, um, my name is ⭐︎ and i heard you had an open call today.” you can’t help the way your shoulders inch up towards your ear, a subconscious way of making yourself smaller, biting away at the ball of white hot nervousness rolling in the base of your tummy. “i was hoping to get in on that.”

it’s a shame her blonde bun is pulled so tight, straining what little polite receptors she has in her system because all the receptionist does is size you up with so much of a twitch of her glossed lips. she doesn’t smile when she slaps the clipboard atop the reflective material of the black desk. “sign here,” for a millisecond, if you'd even count it that, her lips pull tight upwards before she’s returning to whatever she was doing before, nails clacking against the keyboard. “head down that hall to the left. they’ll give you a number. wait for it to be called.”

as soon as you’re finished scribbling the black gen pen down on the white sheet, boxes full of signatures, pages stacked on over the other, she takes it back with a flat palm, dragging it over the open space. “break a leg.” and then it’s as if you were never there. you fade into the background. perhaps in her eyes, you’ve dissipated into light particles. “thanks so much,” is all you can say, lifting your eyebrows with an unamused grin, “brenda.” you catch her name off the nameplate as you leave.

this has to be normal, right? it’s not like hospitality comes with the service, if you can even call it that. people are snobby, thinking their proximity to the stars gives them some sort of privilege or immunity. sure, you wouldn’t normally take such disrespect or disregard for you as a person but maybe you could consider it as a good thing. a blessing in disguise, a side effect of success. this is the closest you’ve been to being in something bigger than yourself, an open call for anything other than a commercial for whole milk or sponsorship from some website.

you have to believe it. otherwise . . .

down the hall and the left, right? you couldn’t miss it if you tried. the bodies milling about give enough clue as to what was going on, numbers taped and pinned to shirts, pants, skirts. the jitters that you swallowed, or tried to, threaten to break free, itching just below the surface of your skin. your mouth is dry but far too wet at the same time. are you drooling? but when your hand lifts to your lips, disguised as checking for lipgloss rolling too far out of place, you don’t feel anything out of the ordinary. still, with each step  closer to the check-in table, your brain cannot stop formulating new possibilities of embarrassment. you could trip, you could forget your lines, you could throw up. none of it’s helping, especially when they’re looking at you with such expecting gazes. getting the number is the easy part, though. all you have to do is write your name down and pick it up. alike many of the others, you opt to tape it, pressing the sticky adhesive into the denim of your pants.

you find yourself in your own desolate space in the hallway, stuck between warm bodies rehearsing their lines and casting sparing glances at the competition around them. you’re unsure where to look. there’s nothing particularly beneficial about staring down the other wannabe actors around you but the idea of focusing so hard on the tiling doesn’t seem too idealistic, either. you’ve always been told it’s best to stand tall anyway, pushing an aura of confidence, even if it’s fake.

and so you do for as long as you stand there. you push your shoulders back and force all that tension between your shoulder blades, straightening your posture for as long as the situation demands. evidently, until your casting is over and you get to return home.

it’s a slow process, slower than you think it would be. you were sure when you left work a few hours ago that you’d have enough time to rinse the smell of fryer grease and burgers off your skin — you’ve since replaced it with silky strawberry lotion and powdery vanilla perfume — and arrive with more than enough time to spare. of course, you did hope it wouldn’t take too long, maybe an hour or two to finish the whole thing. however, when you pull your phone out of your little black prada shoulder bag, you learn that more than three hours have passed.

that’s a ridiculous amount of time to stand, waiting as others go into that room and leave with smiles on their faces or tears in their eyes. sometimes, they don’t have an expression at all. they simply open that heavy door and wander down the hallway, leaving an air of mystery as to what could have happened. you like to fantasize, making up stories about each person and what they could have possibly done to fail. it’s your only entertainment, one that sends you into a trance-like state as you watch and eye each passerby.

it works for a while, dulling your boredom while you wait for your turn. you would have missed the sudden whispery uproar if it weren’t for the girl beside you. her hair brushes against your arm when she turns her head to whisper to the person next to you. instinctively, you cover the tickled area with your palm and look over, bringing your attention closer to the chatter. it’s bit unexpected how suddenly it rises. in just a few minutes, the dull crowd, tired of standing and waiting, begins to buzz with excitement. around you, people whisper, eyes gawking and following figures moving through the hall.

at first glance, it doesn’t take you long to identify just who is attracting all this uproar. even if people weren’t damn near pointing at the hulking figure disregarding his attention, you’d recognize him regardless. it’s hard to miss the dyed pink hair, black roots peaking just below the tufts. his undercut is just as crisp as the pictures, fresh from recent maintenance. there’s a smirk tugging at his lips, arrogant and knowing, like all the attention he’s receiving simply strokes his ego, filling up his head with pride. he walks in a saunter, fingers wrapped around his phone and tilting his head in the onlookers direction. you can get glimpses of his iconic black gel polish, catching the glimmer of the overhead lighting.

sukuna ryomen, one of the greatest stars in the industry at this very moment. the it boy, the icon, the muse of most directors. you could be seeing too far into things when he passes you, but for a second, when your eyes make contact, there’s a particular . . . tension. perhaps you’re imagining it, a warped notion in your head that blended reality with fantasy, but his eyebrows furrow, just slightly. they twitch, jumping upwards before letting you become one with the rest of his admirers.

“ – role in another movie,” it’s a whisper coming from beside you, a comment made in his wake, after he had already made his appearance and left a notable impact. “that’s what i heard, at least. i think it’s a thriller. some psychological shit.”

a thriller? the sukuna ryomen in a thriller? it’s been a while since there’s been a movie you’be been genuinely excited to see but the prospect of such a big name with an equally big aura taking on a role like that? you’re already itching with anticipation at the thought. you wish you could be there, watch him rehearse his lines, see how he prepares for the role. there’s endless lessons you an take out of his book but you’ll never have the chance. not as long as you’re just someone auditioning and he’s at the top of the ranks.

⎯⎯⎯⎯⎯ ★

“no, cherry. i’m not getting the role.” you’re shoving airpods into your ears as you dejectedly make your way out the building. you pull your bag even farther on your shoulder, ignoring the harsh squeals your shoes make when you don’t entirely lift them off the ground. it’s what they deserve anyway, this whole company, after throwing you to the side like that. it contrasts with the clicks of heels and draws judging glares towards you but you ignore them. they’re nothing and they mean nothing after setting up such a massive event, one that you spent weeks preparing for, just for it to be pointless. “turns out, they already had someone in mind. it’s such —,” you pause, just long enough to step outside the glass doors, “such bullshit.”

“aw, honey,” her sweet southern drawl does little to comfort you as warm as it is. if anything, the empathy dripping from it riles you up further. she means well, truly. cherry is as disappointed as you are. in the short span of working together, she’s become something of a confidant, the only person who knows your goals of reaching the stars. it’s not a secret you hold close to your heart for any particular reason. it’s just . . . well, it’s just this. no one wants people to know about their setbacks. you wouldn’t find any joy in sharing your worst failures.

cherry is different, though. she’s kind about it. she has a big heart, keeping in negative comments she might have to herself. besides, cherry has a dream, too, to walk in fashion week. it was a drunken confession, sitting on the floor of your studio apartment after consuming enough white wine to send you both into fits of giggles. you considered it a housewarming.

“how do you know that? did they tell you?” she has to raise her voice over the beeping fryer alarm and the rustling around her. of course in normal cherry fashion, she picks up the phone during work hours when business is slow and she has time to waste.

“they don’t have to tell me for me to know.” you want to press your hands into your eyes, perhaps lay down beneath your sheets and hide away from the world until the fury building inside withers away. “i went in there and did my audition. they were all like ‘oh, ⭐︎, you did so good. you look so cute on camera, you’re so talented’,” you raise your voice a couple octaves to mock the casting directors, rolling your brown eyes in tandem with your words. “that’s not what they actually said but whatever. the point is, some girl walks in and they’re all over her.”

you click your tongue in a fluid motion, scrolling through the app library in search of whichever rideshare app you’ve downloaded since moving out here. with what little income you make, there’s no way you’ll be able to afford a car for the next couple of months, or even years in this economy. a ten minute ride back to your home is nothing compared to the cost of car payments and gas. “i’ve never seen her before, which is the crazy part. i don’t remember what they said her name was. edamame, uraume, whatever the fuck.”

“wait, no. i’ve heard of that name before. i’m pretty sure she was in that show with that guy.” for a moment, you hear her pause, presumably directing her attention to someone else. “yeah, honey. i’ll be right with you, m’kay? listen, ⭐︎, i gotta go, but i’ll see you tonight. we’re still on for tonight, right? i’ll take you out to this place i know. you’ll love it. i hear lotsa famous people go there. maybe you’ll meet someone who can get you a fancy role.”

your eyes settle on the dark colored sedan underlined with an identifying combination of letters and numbers. it’s only a couple dollars and you have the money to spare. you didn’t feel particularly inclined to walk those couple blocks, anyway. you find her words sort of . . . comforting, now. as optimistic as such a small possibility seems, the idea of simply running into someone worthwhile all while dancing the night away excites you. as unlikely as such an easy shortcut to success is, you still consider the small chance to be a chance at all.

“yeah, okay,” you respond with a distant sounding voice as you navigate through the nine dollar payment. it takes a few seconds for the screen to reload, proposing you begin to make your way to the pickup location. “i’ll see you later.”

⎯⎯⎯⎯⎯ ★

the club cherry took you to, it’s everything and nothing you expected it to be at the same time. you scrolled through pictures of the three story building on google reviews while cherry showered, filling up the small confines of her bathroom with steam and the scent of dove cucumber body wash; she insisted on you getting ready at her place after seeing the lackluster apparel hanging in your closet. you didn’t think they were that bad and yet, she parroted on and on that the bouncer would not let you in the clothes you planned on wearing. and she was right, he wouldn’t. here he stood, scrutinizing and slightly predatory gaze across each clubgoer. he took his time with the women, eyebrow quirking when someone particularly piqued his interest. gross, but expected.

it’s just as lively as you thought it would be, people milling around the entrance with id in hand. occasionally, the cars driving by would slow down and glance at the pedestrians, some gathered in groups and drunkenly skipping down the pavement. the lights are flashy, the people are giggly. it's exactly as a club scene should be. the only thing that’s missing is . . . well, the music.

you make note of it as you stand in line, arms wrapped around your body and shifting your weight from leg to leg. there’s no music, at least none you can hear. back in your little town closer to the rural edges of the countryside, you spent quite enough time at the club. you treated it as your own personal spotlight, finding great fun in putting on different personas to enchant men for the night. it could be considered where your love for acting really started, or maybe not. maybe you just sound crazy.

“okay, when we get up there,” cherry leans into you, ducking her head to get her words more clearly heard in your ear. she’s already a couple inches taller than you and with the heels on her black boots pushing her up, those inches became more than just a couple, “don’t say anythin’. well, you can speak but i’ll handle most of it. mike is real fickle. he likes to flirt with the girls and if you don’t make him happy, you don’t get in.” 

“you brought me to a place where the girls are forced to be creeped on by the bouncer for admission?”

cherry clicks her tongue at your words. she follows the flow of the line and takes a step forward, momentarily looking over her shoulder to meet your eyes. “sometimes he doesn’t make us pay.”

⎯⎯⎯⎯⎯ ★

you’re drunk. you don’t have to ask someone to know. there’s no need for a breathalyzer, no need to hang of cherry’s shoulder and smile that pink-lipped, sugar-coated, loopy smile. the confirmation is in the way you walk. it’s in your tingling hands and your tingling lips. it’s in your airy laughter and your slurred words as you teeter across the dance floor. it’s in the way you sit now, perched on the edge of a chair and drunkenly kissing . . . someone. a girl, a guy, you don’t know. it wouldn’t make any difference really.

they’re probably just as drunk as you are, hands gripping and pulling at  your dress, or rather the dress you borrowed. in the back of your mind, you’re scowling and making note to check for snags later, considering how ungracious they’re being. so much so that you’ve been tasked with the responsibility of tugging your dress up every so often as the constant threat of your boobs slipping out. 

you’re not enjoying this, not as much as you want to be. you’re meant to loosen up, get out there, “make connections, whatever that means to you”, as cherry said in her honeyed dialect. that’s what you hoped to do, connect your mouth to another’s in a way that enthralled you in a more lustrous way, with tensions that weigh heavy in a bubble that surrounds you and makes you hungry for more.

you kind of sit there while they begin to mouth along your jawline with more tongue than you prefer. the distaste hits you strong enough you to put your hands on their shoulders after minutes of kissing starving lips. with a firm grasp, you push just slightly, politely even. you still give them that drunken smile even with the sudden detachment and rise to your feet. the base of your shoes knock against the metal leg of the chair and you stumble a few steps on your way up. “i will be right back.” you doubt your voice carries over the bass-boosted music. the beat alone vibrates the floor and rattles your brain in your skull. you both know this isn’t true, or at least you know and that’s enough for you. your toothy smile is concealed as your face falls to rest and you turn, purposefully taking a winding route through the crowd.

you lost cherry a while ago. in retrospect, she’s a bit of a terrible friend for vanishing like that so suddenly with the assumption that you’d be fine. the fault really lied in the decision that you should both drink tonight, as if two wasted girls were ever a good idea. however, it’s too late to be playing the blame game. you’re already taking wobbly strides under the strobe lights while a mixture of house and electronic plays in the background. there’s no real destination you’re heading towards. you follow the movement of the crowd, swaying and leaning. left, right, left, right.

in the moment, staying just where you are is appealing. it calls to you like a siren’s song, begging and pleading with you to stay. have another drink, kiss someone else, live under the colored lights. before you know it, you’re dancing to the music. it’s not what you’d typically listen to but when you’ve had this many shots in those cute little glasses, anything will do. your eyes are still closed as you dance, pulling moves from your mental catalog of video vixens and pop icons. it’s a mess, a flurry of arms and legs. your hair becomes an accessory, an extension of yourself, an object of seduction when you brush it out your face. your hips find the beat with ease and you find enjoyment in being alone, despite knowing you probably should be apprehensive.

it doesn’t take long before there’s a hand settled on your hip, hovering at first, waiting for permission to make contact with your skin. you spot it somehow in your drunken haze and take a hold of it without hesitation. you stamp the hand against your hip, ruffling the dress you adorn beneath their light hold. you only have a short moment to glance over your shoulder and assess the stranger you have welcomed into your one person party. he’s a pleasing sight, although slightly obscured by the blinding overhead lighting, constantly moving and flashing shades of blue, purple, and red. you catch tufts of black and pink lips upturned into a smirk.

it’s good enough for you so you turn and bend at the waist, dipping your head and letting your soft curls toss over your crown. you push the clothed and plush fat of your ass against the stiff fabric of this stranger’s jeans. you both move in an enthralling whirl. you just, met, or rather just become aware of each other’s presence, but somehow you mesh together in a balanced blend of bodies and flirtatious glances.

his hand is firm on your chest. he can feel the warmth of your bare skin where the dress leaves you exposed. he’s pleased to discover he can also feel the swell of your breasts and where they begin to deviate from your otherwise leveled skin. he has to bend at the waist to get to you, but once he does, you’re back to standing, chest to back and a grin on your face. his breath is hot on your ear and his voice is deep. it warms your drunken insides like a warm cider, thoroughly spiced. “are you here with someone?”

your feet tangle with themselves as you turn to face him. you’re careful, slow, calculating each step and maintaining your balance with a strong grip of his forearms. you squeeze and hum at the strong muscle relaxed beneath. “maybe, probably. if she’s still here.” you’re moving again, languidly resting your arm over his shoulder. “what’s your name?” you have to place a hand over the top of your head to cover your eyes from the glaring color changing lights. he looks familiar, extremely familiar. however, you’re drunk and it’s dark. you aren’t so concerned with placing a distinct name to a face and more concerned with what you’ll be calling this person you presume you’re going home with tonight.

sure, it wasn’t what you originally believed yourself to be doing. the thought hadn’t even crossed your mind, nor would you do this on any other occasion but it’s your first night out in a new town. you’ve had the letdown of a century and your boss is absolute shit, never showing up to do anything but complain and order you around. with a pretty boy right at your fingertips, why should you deny yourself? just for one night, at least.

it takes him a second. you assume he doesn’t quite hear you over the music bumping in the background because he blinks, dark eyebrows drawing together just slightly, and that smirk is returning right back on his pink lips. “kuyo,” his hands downwards, smoothening under the crease of your butt.

“unusual name but whatever you say.” your eyes track him low-lidded and just barely disguising the hearts beginning to form in your eyes. he moves close enough for you to smell the alcohol on his breath. it reeks of something strong, something like henessey cocktailed with a flurry of drinks downed without a second thought.

kuyo can only chuckle, one that goes unheard in your ears. he ignores your little comment, experimentally grazing his fingers along your body, both clothed and unclothed while gauging your reaction. and when he finds none, just your sweet smile, he continues pulling and squeezing and groping with little regard for those around you. you’re in a club. people should expect to see a little frisking. “i don’t like beating around the bush and i’m sure you’re a smart girl so you know what i’m gonna say. do you want to go back with me or not? we’d have to go to yours though. roommates.”

you almost laugh. there’s already a giggle building in your throat at his sheer audacity. kuyo didn’t even ask. he didn’t suggest, didn’t pose a question. he simply invited himself over, granted, that’s if you let him. usually, you’d pull back. you’d scoff in kuyo’s face, shake your head and disappear, never to be seen again. but his hands, they’re so strong. and his shoulders are so broad, and his chest is so firm, and his smile is so— “this better be the best night of my life, pretty boy.”

he gives one final squeeze to your midsection, savoring that feeling of plush skin molding around his fingers. the next time kuyo feels it, he knows it’ll be without these silly restrictions such as clothes and peering eyes. not that he’d mind, but he does doubt you want to be split on his dick in the middle of a club. “oh trust, it will be.”

©️ prncessie | do not repost on to other platforms, plagiarize, modify, translate, or use for any ai platforms. my work is my own and it comes from my brain so you’ll have to use yours too

taglist — comment to be added

@excedr

[colinwilson11]

The cGAS-STING Pathway plays a crucial role in host defense against cytoplasmic DNA from invading pathogens. When double-stranded DNA is present in the cytoplasm, which is not normal, it activates the enzyme cyclic GMP-AMP synthase or cGAS. cGAS acts as a DNA sensor that detects cytosolic DNA and produces the second messenger cyclic GMP-AMP (cGAMP) from GTP and ATP.

[literaryvein-reblogs]

Hello! First of all, thank you for the wonderful content! It's a real joy, and an enrichment, food for both the brain and the heart! I was wondering if through your treasures, you could find some writing notes/words/concepts/vocabulary relating to genetic engineering? Like...creating a virus, and a vaccine for it, modifying the virus so it has certain specific effects.... Thank you in advance!

Writing Notes: Virus & Vaccine

References How Viruses Work; Replication Cycle; Mutation, Variants, Strains, Genetically Engineering Viruses; Writing Tips; Creating your Fictional Virus & Vaccine

Virus - an infectious microbe consisting of a segment of nucleic acid (either DNA or RNA) surrounded by a protein coat.

It is a tiny lifeform that is a collection of genes inside a protective shell. Viruses can invade body cells where they multiply, causing illnesses.

It cannot replicate alone; instead, it must infect cells and use components of the host cell to make copies of itself. Often, a virus ends up killing the host cell in the process, causing damage to the host organism.

Well-known examples of viruses causing human disease include AIDS, COVID-19, measles and smallpox. Examples of viruses:

Viruses are even smaller than bacteria and can invade living cells—including bacteria. They may interfere with the host genes, and when they move from host to host, they may take host genes with them.

Bacteriophages (also known as phages)—viruses that infect and kill bacteria.

Size differential between virus and bacterium

Viruses are measured in nanometers (nm).

They lack the cellular structure of bacteria, being just particles of protein and genetic material.

How Viruses Work

Viruses use an organism’s cells to survive and reproduce.

They travel from one organism to another.

Viruses can make themselves into a particle called a virion.

This allows the virus to survive temporarily outside of a host organism. When it enters the host, it attaches to a cell. A virus then takes over the cell’s reproductive mechanisms for its own use and creates more virions.

The virions destroy the cell as they burst out of it to infect more cells.

Viral shedding - when an infected person releases the virus into the environment by coughing, speaking, touching a surface, or shedding skin.

Viruses also can be shed through blood, feces, or bodily fluids.

Virus Replication Cycle

While the replication cycle of viruses can vary from virus to virus, there is a general pattern that can be described, consisting of 5 steps:

Attachment – the virion attaches to the correct host cell.

Penetration or Viral Entry – the virus or viral nucleic acid gains entrance into the cell.

Synthesis – the viral proteins and nucleic acid copies are manufactured by the cells’ machinery.

Assembly – viruses are produced from the viral components.

Release – newly formed virions are released from the cell.

Mutations, Variants, and Strains

Not all mutations cause variants and strains. Below are definitions that explain how mutations, variants, and strains differ.

Mutation - errors in the replication of the virus’s genetic code; can be beneficial to the virus, deleterious to the virus, or neutral

Variants - viruses with these mutations are called variants; the Delta and Omicron variants are examples of coronavirus mutations that cause different symptoms from the original infection

Strains - variants that have different physical properties are called strains; these strains may have different behaviors or mechanisms for infection or reproduction

Genetically Engineering Viruses

Using reverse genetics, the sequence of a viral genome can be identified, including that of its different strains and variants.

This enables scientists to identify sequences of the virus that enable it to bind to a receptor, as well as those regions that cause it to be so virulent.

Vaccine - a special preparation of substances that stimulate an immune response, used for inoculation

Vaccines & Fighting Viruses with Viruses

Common pathogenic viruses can be genetically modified to make them less pathogenic, such that their virulent properties are diminished but can still be recognized by the immune system to produce a robust immune response against. They are described as live attenuated.

This is the basis of many successful vaccines and is a better alternative than traditional vaccine development which typically includes heat-mediated disabling of viruses that tend to be poorer in terms of immunogenicity.

Viruses can also be genetically modified to ‘fight viruses’ by boosting immune cells to make more effective antibodies, especially where vaccines fail. Where vaccines fail, it is often due to the impaired antibody production by B-cells, even though antibodies can be raised against such viruses – including HIV, EBV, RSV & cold-viruses.

Related Articles: Modified virus used to kill cancer cells ⚜ Genetic Engineering ⚜ Engineering Bacterial Viruses ⚜ Benefits of Viruses

A Few Writing Tips

As more writers look to incorporate infectious diseases into their work, there are quite a few things writers should keep in mind:

Don’t anthropomorphize. Really easy to do, but scientifically wrong. Viruses don’t want to kill you; bacteria don’t want to infect you; parasites don’t want to make your blood curdle. None of these things are big enough to be sentient to want to do anything. They just do it (or don’t do it).

Personal protective equipment. This includes wearing gloves, lab coats, safety glasses, and tying your hair back if it’s long. It is the same as Edna Mode’s “no capes.” Flowing hair looks cool all the way to the explosive ball of flames that engulfs someone’s head.

Viruses are small. You can’t see viruses down a normal microscope—they need a special microscope called an electron microscope. These are highly specialized and take a long time to make the preparations to be able to see the virus. Normally viruses are detected by inference—measuring part of them using an assay that can amplify tiny amounts of material, for example PCR.

Viruses don’t really cause zombie apocalypses. 

Vaccines work. But they take time. The best vaccine in the world will still only prevent infections two weeks after it is given. Drugs are quicker, but still take some time. But the good news is an infection is not going to kill you (or turn you into a zombie) quickly, so they both have time to work.

Scientists use viruses as a vector to introduce healthy genes into a patient’s cells:

Your Fictional Virus & Vaccine

When creating your own fictional virus, research further on the topic and consider choosing a specific one as your basis/inspiration.

Here's one resource. For some of them, you'll need a subscription to access, but those that are available give you a good overview of the virus, as well as treatment options.

You can do the same for creating your fictional vaccine:

Here's one resource. And here's one on vaccine developments.

Sources: 1 2 3 4 5 6 7 8 9 10 11 12 13 ⚜ Writing Notes & References

Lastly, here's an interesting article on how science fiction can be a valuable tool to communicate widely around pandemic, whilst also acting as a creative space in which to anticipate how we may handle similar future events.

Thanks so much for your kind words, you're so lovely! Hope this helps with your writing. Would love to read your work if it does :)

[mindblowingscience]

Scientists have figured out a way to detonate the 'doors' that lead to the heart of cancerous tumors, blowing them wide open for drug treatments. The strategy works by triggering a 'timer bomb' on the cells that line a tumor's associated blood vessels. These vessels control access to the tumor tissue, and until they are opened, engineered immune cells can't easily gain entry to the cancer to fight it off. The timer bomb on these cells is actually a 'death' receptor, called Fas (or CD95). When activated by the right antibody, it triggers the programmed death of that cell. Scientists at the University of California, Davis (UCD) and Indiana University argue that until recently, Fas has been "undervalued in cancer immunotherapy". To date, not one Fas antibody has made it to clinical trials.

Continue Reading.

[humancelltournament]

Human Cell Tournament Round 1

Propaganda!

A killer T cell is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response and is often produced by cancer cells, viruses, bacteria or intracellular signals. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell.

In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.