Mainlined Science

Hi, all!

Excited to see this community grow. Still figuring out Lemmy, so thanks for bearing with us. I want posts to have some form of identifier for ease in finding things so lets start every post with a tag before the title. Here are a few tag rules for now.

TAGS

• [QUESTION] - for posts directly asking input from the community.
• [PAPER] - for posts about specific papers
• [REVIEW] - for posts reviewing scientific literature, make sure to cite all papers discussed
• [DISCUSSION] - for a more general post around any given topic or multiple topics

FORMAT

!

If none of the tags seem to fit, a descriptive title will suffice.

Thanks!

TLDR: wanna read a paper without the dumb publication house paywalls? Check out Sci-Hub. Don't know how to properly read scientific literature? Boom

This is mostly a PSA for the uninitiated, but you might find this useful. If nothing else I hope this is an enjoyable read to accompany you on the bus, at home, on the toilet, etc.

One of the biggest hurdles in science is access to quality literature. Unfortunately, there are many roadblocks in place that prevent people from immediate entry to this material. Some journals frequently release free copies of their publications, but for the most part you need to be connected either through the academic field or by directly paying publishing companies. Paying is bullshit. This money does not go to the authors, and honestly, many of them will gladly give you copies of their published material if you ask. But if reaching out to random authors proves troublesome, you can always utilize Sci-Hub.

You'll notice that the link redirects to the wiki about Sci-Hub and the founder, Alexandra Elbakyan. The site domain changes often (which is why I didn't bother with a link) but with a little sleuthing you can find the most active and current iteration. This lovely site unlocks pay-walled scientific literature and provides you with a full text document that you can read in browser or save for later. One caveat is that it will be less reliable for current or new publications, they paused uploading new documents due to legal issues and it's unclear if they'll ever resume.

Alright, next topic! ReaDINg ComPReHenSIon

Still here? Oh, goodie! This isn't as boring as it sounds, but it also sorta is. Reading science papers is A LOT of work, like, a lot. But not for the reasons you might think. Yes, the material can be dense and seem completely undecipherable, but the biggest issues are sifting through the BULLSHIT. As you delve through the literature as a whole it's pretty clear that some papers are of a much higher quality than others. Why? Well, many reasons. Funding for the research, limitations in the researchers abilities to record quality data, and on and on. When I say BULLSHIT I don't mean that people are deliberately trying to put out false information, but poor data is a thing and it's out there. But I digress. Lets walk before we run.

Here is a lovely paper about how to read papers. You'll notice that it's pay-walled (womp womp) but lucky for you there's a way to get around that! I know, I'm making you work for it. If you don't want to test out Sci-Hub I did leave a direct link in the TLDR for ya. Anyway, this paper has a very simple and approachable method on how to digest lots of information. It does get a bit more intense near the end with most of the information targeted for individuals participating in research so don't despair on that front.

I'll hop off my box for now. If you made it this far, thanks for reading! Looking forward to really getting into that good good niche research with y'all someday soon.

Ok, so I had a patient. The actual history isn't terribly important because this sort of thing happens relatively frequently, but to give you a quick one-liner: he was an older male with rheumatoid arthritis admitted for Staph bacteremia. In cases of blood infections, we order tests called "clearance cultures" to track and confirm that the organism we're fighting disappears with treatment. In this case, 1 out of 4 of these samples tested positive for a potential Bacillus species—the genus to which anthrax belongs. That being said, completely inert species of Bacillus are common contaminants in this setting, and the fact that only 1 out of 4 samples tested positive definitely makes you think this is such a case of contamination.

However, we treat it as if it were anthrax until we're completely certain it isn't. It's Schrödinger's anthrax! After all, you don’t want to be the lab that missed anthrax.

Bacillus anthracis Identification Colonies of B. anthracis appear non-hemolytic, consist of gram-variable rods with spore forms, and are non-motile. In other words, when grown on sheep's blood agar, they do not break down hemoglobin (a feature many microorganisms possess), appear elongated and purple or pink under a microscope after staining (gram-variable), produce spores (a survival mechanism), and lack motility (i.e., they don’t move via structures like flagella). We use these properties to rule out B. anthracis. While mass spectrometry is the gold standard for organism identification in modern microbiology, when it comes to potential anthrax, we revert to basic microbiological methods for safety reasons (which we can discuss more in the comments if you're interested).

Bacillus anthracis: What Sets It Apart? Bacillus anthracis, the causative agent of anthrax, is a zoonotic disease, meaning it can be transmitted to humans through the handling or consumption of contaminated animal products. Due to its potential use as a bioweapon, B. anthracis is classified as a Tier I Category A agent by the CDC. Even though infection is rare in the United States, the micro lab remains vigilant in identifying this organism due to its serious implications.

Plasmids and Virulence Factors What makes B. anthracis particularly dangerous are its virulence plasmids, pXO1 and pXO2, which carry the genes responsible for toxin production and capsule formation, respectively. These plasmids play a crucial role in the organism’s ability to cause disease, enabling it to evade the immune system and produce lethal toxins.

But what exactly is a plasmid?

What is a Plasmid? A plasmid is a small, circular piece of DNA that exists independently of the bacterial chromosome. Unlike the bacterial genome, which contains essential genes for the organism’s survival, plasmids often carry genes that provide advantages under certain conditions—such as antibiotic resistance or, in the case of B. anthracis, virulence factors.

Plasmids are particularly interesting biologically and evolutionarily because they can be transferred between bacteria via a process called horizontal gene transfer. This means bacteria can acquire new traits, such as antibiotic resistance or enhanced pathogenicity, from other bacteria without evolving them slowly over generations. In essence, plasmids allow bacteria to adapt quickly to new challenges, making them highly versatile and resilient organisms. From an evolutionary standpoint, plasmids accelerate genetic diversity and adaptability, giving certain bacteria a survival edge in hostile environments.

Think of it this way: plasmids let bacteria "plug and play" abilities. Imagine if I could transfer my height, immune system, or ability to play the ocarina just by touching you... now you're getting it. Because of these abilities plasmids are, in many ways, the cornerstone of modern biomedical tech. We will definitely be talking about them again.

What is Bacillus cereus biovar anthracis and why use it to intro plasmids? Now, why bring up plasmids in this way? Because I can. Stories are nice. Anyway, plasmids are key to understanding another entity: Bacillus cereus biovar anthracis. This variant of B. cereus (the contaminant in our story) has acquired plasmids nearly identical to those found in B. anthracis, meaning it can cause anthrax-like diseases, particularly in animals. While B. cereus is more commonly known for causing food poisoning or being a random contaminant, its biovar anthracis variant is a real concern due to its ability to acquire these plasmids, making it capable of causing serious infections similar to anthrax. Mother nature is getting scarier!

In 2016, this variant was added to the CDC’s select agent list, emphasizing the significance of monitoring its presence, especially in cases involving animals. Though not as common in humans, its existence underscores the evolutionary importance of plasmids in spreading virulence factors across bacterial species.

Conclusion To wrap it up: Plasmids are fascinating, highly relevant to the changing landscape of infectious diseases, and, as will be discussed later, they might even change what it means to be human.

Full disclosure, this is outside my area of expertise (whatever that means…).

I want to talk about the thymus and its importance in aging. I recently came across a fascinating paper that builds on a model of human lymphopoiesis across development and aging, and I wanted to share it with you all: (https://pubmed.ncbi.nlm.nih.gov/38908962).

The thymus plays a key role in the immune system, especially in the production and maturation of T-cells, which are crucial for immune responses. One of the things that really piqued my interest is how the paper discusses developmental transitions in the thymus and how these changes potentially affect the immune system throughout life. It’s especially interesting how thymic involution with age may impact immune health, and how this could tie into the overall aging process.

To me, it's wild that the thymus pretty much "dies" before we’re even out of our teens... Seriously, look at Figure 5. This idea has kept me up at night for about a decade now. Anyway, I’m in a transition phase of my career and am fortunate enough to have the latitude to start thinking deeply about the thymus. So let’s chat—we can struggle through my learning phase together!

While I’m still learning the specifics, this got me thinking about the potential implications for therapies aimed at rejuvenating or maintaining thymic function in older individuals. Could these interventions help us preserve immune function as we age? You ever hear of this guy Greg Fahy? Interesting person. He has a fascinating publication history in the area of cryopreservation (another field I want to dive into, and we should totally discuss), but he’s also attempting to rejuvenate the thymus. Here’s one of his papers: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826138.

Honestly, I’m not sure where I stand on this yet. I find the hypothesis really interesting, but I’m in no way an immunologist. I’d love to hear your thoughts! If you’ve worked in this space or know of any relevant research, feel free to share. And if you haven’t but have a hot take, I’d love to hear that too! No barrier to entry—feel free to open this up.

What areas in aging or immunology are you curious about? What do you think will get us to 130+ years on this planet!?

Let’s continue our dive into gene therapy with one of my favorite papers. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876218/

In this study, researchers delivered three longevity-associated genes (FGF21, αKlotho, and sTGFβR2) to mice using a gene therapy cocktail. These genes target metabolism, heart function, and kidney health—three areas that typically decline with age. Here’s why this is a big deal:

Obesity & Diabetes? Reversed. Mice fed a high-fat diet lost weight and saw their diabetes symptoms disappear, just by tweaking how their cells handled energy.

Heart Failure? Improved. The therapy improved heart function by 58%, meaning it could help tackle the leading cause of death worldwide.

Kidney Disease? Protected. Mice treated with this gene therapy avoided the typical kidney damage seen with age-related conditions.

What’s most exciting is that a single gene therapy cocktail—combining just two of the three genes—was able to treat all of these diseases simultaneously. Imagine being able to tackle multiple age-related health issues with just one treatment!

This approach could be a game-changer in how we think about aging and disease. Instead of targeting one condition at a time, we might be able to treat aging itself by addressing the root causes of multiple diseases.

What do you think—are we on the verge of a breakthrough in how we fight age-related diseases?

See this similar paper here targeting TERT and follistatin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171804/

Do these papers pass our threshold of believability? Are we concerned that one of these papers had a few post publication amendments? I may circle back to poke holes in them (if I can find any) at a later time. Feel free to beat me to it!

What is Fasting and why do so many people seem to be into it?

There are many flavors of fasting, but they can be categorized into two main categories: intermittent fasting (IF) and time restricted eating (TRE). IF is defined as eating once every 24hrs and TRE is characterized by a shortened eating window, usually seen as 8hrs eating and 16hrs fasting.

IF also know as one-meal-a-day (OMAD) and TRE have been farily popular over the last few years. They gained a lot of traction, almost a decade ago, with the hope that fasting mimicking diets could help with age related declines. The overall consensus now is that this type of fasting only imparts lifespan health benefits if you also restrict total calories. However, the hype was strong and most of these dietary methods are still championed today as a way to promote health. But can they actually provide any health benefit? Well, it depends. In the scope of nutrition and health, there's no better alternative than a well balanced diet. That being said, I think these interventions can be excellent tools for targeted goals i.e. weight loss/maintenance.

Alright, this is gonna be real subjective, and your results may vary. Of course the metrics I'm most interested in might not apply to your desires or needs. For me, I prioritize dietary changes that can help me loose weight, primarily fat, quickly while maintaining as much lean mass as possible. Over the last 7 years I've dabbled with various dietary interventions, and here are my anecdotal results.

IF/OMAD

For me, IF has been the most effective tool for rapid weight loss, second only to prolonged fasting. As a rock climber it has been beneficial for me to apply a short stint of IF, 1-2 weeks, periodically when I'm trying to shed excess fat. Usually I resort to this type of eating after a multi month course of unchecked eating, especially when coming back from vacation. After some trial and error I learned that this can increase my chances for climbing injuries, and climbing after a few days of IF left me with really annoying achey fingers, primarily in my proximal and distal interphalangeal joints. Other activities were fine, such as hiking or mild resistance training. My takeaway is that IF is a very powerful tool for rapid weight loss, however, the potential for climbing related injuries makes it a short term success, but a long term failure.

TRE

Eating within time restricted windows is something my body has gravitated towards naturally. Growing up I was surrounded by people who were adamant about the importance of breakfast and I forced myself to eat in the mornings. This helped spark my hunger and after forcing down a small breakfast I would become ravenous 2 hours later. I now let my body choose and in the absence of food I really don't feel hungry until noon. So by default I mostly eat within an 8 hour window. This type of eating works well for me, but I wouldn't say it does anything special. However, this way of eating can help with weight maintenance. If you fall into the pattern of forcing down food every morning because you think you should, and your weight tends to fluctuate easily, this might be a beneficial diet.

Ketogenic Diets

Yes, this one is a wildcard. While this diet might not be recognized as a fasting intervention it does mimic fasts, since it puts your body into a state of ketosis, which is what fasting also does. Also, this is the one dietary intervention that has been consistently effective in helping me lose fat while maintaining, even gaining, muscle mass. I've had a lot of trial and error with this one too, and I've now come to prefer a more carb and protein friendly version that allows me to keep climbing at peak performance. Typically a keto diet is very low carb, modest protein and liberal fat. I prefer higher protein, aiming for 150g on a daily basis, and am not worried about gluconeogenesis, where dietary protein is converted to glucose. On a daily basis my carb intake is between 50g and 100g, depending on my activity levels. I eat a large amount of vegetables, including higher carb sources such as red bell pepper, squash and zucchini. With small amounts of fruit, usually blueberries or dried plums. My fat intake is tied into my protein intake as I prioritize beef over other forms of protein, but will cook vegetables in avocado oil. For me, this hybrid ketogenic diet has worked well. I'm still able to lose weight at a rate comparable to IF (not quite as potent), but am able to maintain athletic performance and keep climbing without injuries. However, this way of eating does come with risks, namely high cholesterol. I've attempted various modes of ketosis, and have played around with other sources of protein and fat, but so far it hasn't made a difference. After prolonged use (>1 month) my LDL rises dramatically. If I were using this diet long term I would utilize pharmaceuticals to get these levels under control, but in the interim I apply this diet briefly and very infrequently. I tend to slip into ketosis somewhat easily, but I'm not sure if this is something my body is naturally predisposed to or if my keto cycles have promoted this adaptation. My current protocol is to apply this diet for about 3 weeks at a time and I'll cycle this about 3-4 times a year depending on needs. Pros: fat loss, strength gains, higher perceived energy levels. Cons: high cholesterol, can't eat pie.

So, those are my thoughts. But what do you think? Is there a dietary intervention that has been life-changing for you? Do you have any concerns with diets? Do tell!

Hello Mainlined Science! We’re always looking for new topics and ideas to dive into, so we’d like to start getting some engagement! Got a question, a research area you’re curious about, or just something science-related that you’ve been pondering? Let’s talk about it! Even if it's outside our fields, no wrong answers!

Whether it’s a specific field you want to explore or a “random thought of the day,” feel free to start up the chat, we will reply. We’re here to start discussions, share knowledge, and learn together. Drop your ideas below—there are also no wrong questions!

I’m also thinking about occasionally hosting some hypothesis-generating sessions, starting small research projects, and maybe even setting up a little DIY lab. If there’s interest of course.. Maybe we could get into some 3D printing or simple bio experiments too! Let's see where this can go. Let's get the hive mind goin!

OK, Time for Something Random: Lyme disease and its strange connection to lizards.

Lyme disease is a big deal. Especially, or at least historically, here on the east coast US. Did you know that some animals can actually cure infected tick carriers!? I didn't either.

In parts of California, western fence lizards play a surprising role in controlling Lyme disease. When ticks feed on these lizards, a protein in their blood kills the bacteria (Borrelia burgdorferi) that causes Lyme disease. Some factor in the lizards blood is ingested and kills the bacteria present in the gut of the tick.

To conclude, nature is wild. Much of our innovation in biology/medicine, including CRISPR (see earlier related posts) and the majority of our antibiotics, aren't so much inventions but are more accurately 'discoveries.'

Relevant papers I happened upon: https://pubmed.ncbi.nlm.nih.gov/9488334/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413869/

Let’s talk CRISPR-Cas9 and why it’s one of the most significant breakthroughs in modern biology.

At its core, CRISPR-Cas9 is a tool for precise genome editing. Before CRISPR, genetic modification was a slow, expensive, and often imprecise process. CRISPR changed the game by allowing scientists to cut DNA at specific sites, guided by an RNA molecule that can be customized to target nearly any gene. Once the DNA is cut, it can be repaired in a way that adds, deletes, or alters the genetic sequence. This kind of precision has opened up endless possibilities.

Why is this such a big deal?

Speed and Efficiency: CRISPR allows scientists to make changes to the DNA of organisms in weeks, not years. You want to knock out a gene? You can do that. Want to introduce a new one? Done. The speed and flexibility are revolutionary compared to older methods.

Precision: CRISPR can zero in on specific genes with high accuracy, reducing the risk of off-target effects (though this is still an area of research). Precision matters when you’re editing the building blocks of life.

Wide Applications: It’s not just a tool for basic research—CRISPR is shaping medicine, agriculture, and even biotechnology. Scientists are working on curing genetic disorders, creating disease-resistant crops, and engineering cells to fight cancer. The potential here is massive.

How is CRISPR shaping biology today?

Gene Therapy: One of the most exciting applications is in treating genetic diseases like sickle cell anemia, muscular dystrophy, and certain forms of blindness. By directly editing the faulty genes responsible for these conditions, CRISPR could offer permanent cures rather than just treating symptoms.

Cancer Research: CRISPR is being used to edit immune cells, making them better at recognizing and attacking cancer. We’re moving closer to personalized medicine where your immune system can be genetically fine-tuned to fight off specific diseases.

Agriculture: In crops and livestock, CRISPR is being used to enhance yields, create resistance to pests and disease, and improve nutritional content. This could help address food security as populations grow and climates change.

Basic Research: Perhaps one of its most profound impacts is that CRISPR makes it easier to explore how genes work. We’re learning more about gene functions at a faster pace than ever before, and this knowledge feeds into all other areas of biology.

Of course, with great power comes great responsibility. There are ethical considerations around using CRISPR, especially when it comes to editing human embryos or making changes that can be passed down to future generations. The technology is advancing quickly, but society will need to decide how to handle the moral implications.

In summary, CRISPR-Cas9 is a huge deal because it makes genome editing faster, cheaper, and more accurate than ever before. It’s shaping everything from how we fight diseases to how we grow food, and it’s rapidly transforming the future of biology. We’re just starting to scratch the surface of its potential.

Suggested reading:

The paper that started all https://pubmed.ncbi.nlm.nih.gov/22745249/

A look at a future where everyone has access to the power of CRISPR https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297044/

This is a preprint, which means that the article has not been peer-reviewed yet. This is all part of the normal process, researchers will often present their findings before their work is published.

Here the deets!

The AgelessRx-sponsored Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) trial was a 48-week randomized, double-blind, placebo-controlled trial investigating the safety and potential efficacy of different intermittent rapamycin doses for mitigating signs of aging.

More info!

https://clinicaltrials.gov/study/NCT04488601

https://agelessrx.com/results-of-the-pearl-trial/