#double-stranded RNA

[krishgen]

Looking for a reliable way to detect double-stranded RNA (dsRNA) in your samples? Krishgen Biosystems has got you covered with our KRIBIOLISA dsRNA ELISA Kit! Designed for simplicity and accuracy, this kit is perfect for researchers in academia, biotechnology, and pharmaceuticals. Whether you're studying viral infections, RNA interference, or gene expression, our ELISA kit provides precise results with straightforward protocols. No need to be an expert - our kit is user-friendly for all levels of experience. Order now to advance your research with confidence!

[mleprae]

What are your opinions on the OTHER human originating obligate intercellular parasite, herpes simplex virus?

HSV-1 had a good munch on my brain about a decade ago so I wouldn't say we're on friendly terms, but I still think it's pretty neat

Sorry to hear 😭 if it's any consolation, I had TB when I was 15 and it drove me to love TB and leprosy, I still wake up with stridor sometimes.. 6 years later...

I don't have a lot of strong opinions on viruses other than retroviruses and oncoviruses (HIV fascinates me) but the herpes family is familiar territory for me... they are DNA viruses if I'm not misremembering, which is kind of interesting.. I always wonder what's the advantage over RNA? The impression I have is that RNA viruses are way more efficient at their jobs

There's herpes zoster too, which has become increasingly louder in my radar, some acquaintances who work in the medical field told me there's an growing demand to lab jobs to study it while I noticed some very sparse campaigns conscientizing about it, I have a very bad feeling that it's going to get big here, perhaps I should polish my virus knowledge... 🤔 Shingles has some similar symptoms to leprosy but its pathogenesis and pathophysiology is different, which might just be a bonus for me

[medicomunicare]

Autoimmunity crosses alteRNAtive threads: meet SLIRP and its mitochondrial businesses

SLIRP: an anomalous factotum on nuclear signaling SLIRP (SRA stem-loop interacting RNA binding protein) was firstly identified in 2006 and found to bind to a functional substructure of SRA called STR7. Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NURs). SLIRP is expressed in normal and tumor tissues, contains an RNA…

[hellsite-proteins]

Are there ways to actually "program" cells to produce these proteins? Like if you fed ribosomes the right RNA sequence, would it synthesize a bullshit protein molecule that does nothing useful, or would it start falling apart immediately in reality? My knowledge on DNA splicing is old and I know near nothing about proteins so I'm just curious if it'd ever be possible to get a real world representation of anything on your blog (setting aside the cost and effort it would take to do that)

yes there is! and you actually got pretty close, but you have to go a bit further back and use DNA (there are ways of delivering RNA to cells, but I haven't done that personally, and for something like protein purification that would not be the method of choice, so I won't be going into that. there are two main ways of inserting coding DNA into cells: using a transient expression plasmid and gene editing. note: all of these will be very brief overviews, so if you want more detail about any part of this, then please ask!

first i'll go over the simpler method which is using plasmids. i've been doing a lot of molecular cloning lately specifically to put proteins into expression vectors so i can purify them and do some work with the pure protein, which is what i assume you would want to do here. (sidetone: once you have some purified protein, there are a number of different things you can do to find out its sequence or structure, but that is a whole other post). plasmids are circular bits of DNA outside of the genome that are not necessary for survival, but carry useful information. most of the ones used in labs will also have an antibiotic resistance gene or some other marker so we can select for only the cells with the plasmid by growing them in media with the right drug. using specific enzymes, we can cut these plasmids and then insert a new fragment of DNA coding for whatever we want, before sealing them back up. Then, a small amount of the plasmid can be transformed into cells (bacteria and yeast are commonly used), which will multiply and make more of your plasmid, as well as whatever it encodes if the conditions are right!

Genome editing is a broad topic, so i'm just going to give you a quick overview of CRISPR-Cas9, which I have a bit of experience with. this isn't something i would do if i just wanted to make a lot of a given protein, but it is useful to look at how much of a protein is made under the native expression system within a cell, or to edit the sequence of a protein being made (and much more...). Cas9 makes a cut in both strands of genomic DNA, but the really neat thing about this is that you can easily tell it specifically where to cut. to do this, you will build a plasmid with the gene for the Cas9 protein, as well as the guide RNA matching the sequence where you want the cut to be. there are other design considerations, but i'll save that for now. once the DNA has been cut, the cell starts to panic and try and stick it back together, but not before some random bases get added and/or deleted from either of the broken ends. this is useful if you want to knock out a gene, because you can go in and mess up its promoter or something similar so that it never gets made. if that is too messy and random, or if you want to knock something in instead of knocking it out, you can also take advantage of the cell's repair mechanisms. if a double stranded break happens, the cell would prefer to fix it properly, and so it will try and remake the DNA using the other matching chromosome as a template. but, if you add in another plasmid instead that contains sequences matching either side of the break with something you want to add in sandwiched in between them, you can make the DNA repair itself with your new sequence!

finally, all of this assumes that the protein would be successfully translated, and would not be so toxic to cells that anything expressing it dies. we would need to add a methionine (start) to the beginning of nearly all of these sequences, and ideally codon optimize them for the specific organism. ordering the custom DNA sequences also wouldn't be cheap, but is also not impossible. an inducible expression system would also help reduce the risk of toxicity and let us make a lot at once if we so desired. we would probably also want to add a tag to make these easier to purify if we wanted to use the protein itself.

again i am not great at being brief and i have no idea how much the average person knows about any of this, so please ask more if anything i've said needs clarification!

letter sequence in this ask matching protein-coding amino acids:

AretherewaystactallyprgramcellstprdcetheseprteinsLikeifyfedrismestherightRNAseqencewlditsynthesieallshitprteinmleclethatdesnthingseflrwlditstartfallingapartimmediatelyinrealityMyknwledgenDNAsplicingisldandIknwnearnthingatprteinssImstcrisifitdeverepssiletgetarealwrldrepresentatinfanythingnyrlgsettingasidethecstandeffrtitwldtaketdthat

protein guy analysis:

you know that feeling when you're writing a test and aren't really sure what the answer is, but you try and put down everything you know in the hopes of getting some part marks? i feel like that's what this protein looks like. there is an assortment of secondary structures all spread out between loops and even a beta sheet, as if AlphaFold was trying its best to make something out of this. still, it doesn't look the way we would expect from an ordered protein, and i do not trust it.

predicted protein structure:

[kang-yina]

Why would you as a rna strand evolve into double stranded dna and make us have to put up with this shit that is being this specific type of eukaryote that lives in a capitalist society

[darkmaga-returns]

Who is Geoff Pain?

Dr. Geoff Pain is a passionate and relentless Australian scientist who has been ringing alarm bells since the beginning of the COVID-19 injection rollout. Unlike paid experts toeing the government line, Pain isn’t afraid to speak out. His investigations dig deep into the murky world of vaccine contaminants—elements that were never supposed to be injected into anyone’s body. He's been publishing his research and findings on Substack, and many of us who care about truth have stood beside him. I even made a video—Deadly Betrayal—to support his work.

Now, with new evidence in hand, the time has come to say the quiet part out loud.

The Dirty Secret Hidden in the Vials

Most Australians still don’t know this: the COVID-19 mRNA injections (Pfizer and Moderna) have been found to contain genetic contaminants that were never supposed to be there—contaminants that could trigger harmful, even deadly, immune reactions. These include:

Double-stranded RNA (dsRNA) – known to provoke severe inflammation and autoimmune diseases

Bacterial DNA – a foreign genetic pollutant from the manufacturing process using E. coli bacteria

These substances are not theoretical risks. They have been measured—even acknowledged—by the manufacturers and regulatory bodies. But the public was never told.

And the Australian Therapeutic Goods Administration (TGA)? They knew. And they did next to nothing.

[ai-botz]

You:

explain crispr mRNA

Ai:

CRISPR RNA (crRNA) is a sophisticated, programmable molecular tool that leverages the prokaryotic adaptive immune system's mechanism of defense against invasive genetic elements. This RNA-based component serves as a guide to direct the Cas9 nuclease enzyme toward specific genomic loci for targeted editing.

The crRNA structure consists of three distinct regions: the scaffold, the repeat sequence, and the protospacer. The scaffold provides structural support and facilitates binding with the Cas9 protein, while the repeat segment is derived from the CRISPR array in the bacterial genome and promotes crRNA-Cas9 complex formation.

The protospacer region, which constitutes the majority of the crRNA sequence, harbors the desired target specificity information. It possesses a complementarity to a predefined genomic sequence (the target site), thereby enabling the crRNA-guided Cas9 endonuclease to recognize and cleave the target DNA at the precise location.

crRNA synthesis typically involves in vitro transcription from a DNA template or ribosomal RNA processing in vivo. The resulting mature crRNAs are then processed into their functional forms through 5' and 3' trimming, which removes non-essential regions and generates a single-stranded structure that can base-pair with the target site.

Upon binding to Cas9, the crRNA acts as an adaptor, positioning the nuclease at its cognate genomic location. Upon encountering the target sequence, the Cas9-crRNA complex excises the DNA, creating a double-strand break (DSB). The DSB can then be repaired by the cell's endogenous pathways, which may result in precise gene editing via homology-directed repair (HDR) or introduce insertions/deletions (indels) through non-homologous end joining (NHEJ), effectively creating a mutation at the targeted site.

The programmable nature of crRNAs allows researchers to tailor them for specific applications, including gene knockouts, point mutations, and even precise base editing. Moreover, advances in RNA engineering have enabled the development of complex crRNA designs capable of targeting multiple genomic loci simultaneously or recognizing non-canonical target sites.

In summary, CRISPR RNA is a highly specialized, versatile molecular tool that empowers scientists to precisely manipulate genomes through its intricate interactions with Cas proteins and cellular repair machinery. Its unique properties have revolutionized the field of genome engineering, offering unprecedented control over genetic information.

You:

explain how a virus can be used as an mRNA encapsulate to deliver crisper RNA

Ai:

Viruses, particularly those in the families Lentiviridae (e.g., HIV-1), Adenoviridae (e.g., adenovirus serotype 5), and AAVidiae (adeno-associated viruses), can be engineered to function as mRNA encapsulation vectors for CRISPR RNA delivery.

The process typically involves:

Cloning the desired crRNA sequence into an expression plasmid, which is then transfected into virus-producing cells. The viral vector is assembled with its capsid protein and genomic RNA, replacing the original viral genetic material. The modified virus acquires the CRISPR RNA as a passenger payload, encapsulated within its lipid envelope or protein capsid. Upon infection of target host cells, the virus delivers its crRNA cargo into the cytoplasm via endocytosis and lysosomal escape. After entering the nucleus through nuclear pore complexes, the released crRNA can then interact with Cas proteins to initiate genome editing at the desired loci.

The choice of viral vector largely depends on factors such as host specificity, transduction efficiency, and immunogenicity concerns. Lentiviral vectors, for example, are capable of infecting non-dividing cells but may elicit stronger immune responses compared to AAV or adenoviral alternatives. AAVs, being less immunogenic, have become popular choices for gene therapy applications.

Incorporating CRISPR RNA into viral delivery systems offers several advantages over direct crRNA administration. It enables targeted and efficient transduction of cells, enhances the stability of crRNA in circulation, reduces off-target effects due to improved tissue specificity, and can facilitate simultaneous editing or multiplexed gene modifications.

However, challenges persist, including concerns over potential off-target effects from viral-mediated delivery itself, immune responses against the viral vector, and the need for further optimization of viral design and packaging strategies to ensure precise genome editing with minimal collateral damage. Continued research is necessary to refine this approach and maximize its therapeutic potential in various applications, ranging from treating genetic diseases to agricultural biotechnology.

————————————————————————

Virus AI describes as being the likely candidate for spreading crisper RNA

“A digital cryo-electron micrograph of the Adenovirus serotype 5 (Ad-5)/HVR5-33RGD vector. Adenoviruses are non-enveloped, double-stranded DNA viruses that cause cold-like infections of the upper respiratory tract.”

[science-lover33]

Genetic engineering: CRISPR and beyond

In genetic engineering, we find ourselves amidst a scientific revolution with the advent of revolutionary technologies like CRISPR-Cas9. However, our journey into the intricate landscape of genetic manipulation is far from complete. This post delves into the nuanced world of genetic engineering, exploring cutting-edge technologies and their remarkable potential in shaping the future of medicine and biotechnology.

CRISPR-Cas9: Precision at the Molecular Level

CRISPR-Cas9, a revolutionary genome editing tool, stands for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9. It utilizes a guide RNA (gRNA) to target specific DNA sequences, and the Cas9 protein acts as molecular scissors to cut the DNA at precisely defined locations. This break in the DNA prompts the cell's natural repair machinery to make changes, either through non-homologous end joining (NHEJ) or homology-directed repair (HDR). CRISPR-Cas9's precision allows for gene knockout, modification, or insertion with remarkable accuracy.

Beyond CRISPR: Emerging Technologies

While CRISPR-Cas9 has dominated the field of genetic engineering, numerous promising technologies have emerged on the horizon. These include CRISPR-Cas variants like CRISPR-Cas12 and CRISPR-Cas13, which offer unique advantages such as smaller size, increased specificity, and targeting of RNA. Additionally, base editing techniques, such as adenine base editors (ABEs) and cytosine base editors (CBEs), enable the direct conversion of one DNA base into another without causing double-strand breaks, expanding the range of genetic modifications possible.

Applications in Medicine

The implications of these advancements are profound, particularly in medicine. Genetic engineering can potentially treat various genetic disorders, from cystic fibrosis to sickle cell anemia, by correcting disease-causing mutations at their source. Precision medicine, tailored to an individual's genetic makeup, is becoming increasingly feasible, allowing for personalized therapies with minimal side effects.

Ethical Considerations and Regulation

As we venture further into the genetic frontier, we must acknowledge the ethical considerations surrounding genetic engineering. The ability to modify the human germline, with implications for future generations, raises ethical dilemmas that necessitate rigorous oversight and regulation. The international community is developing guidelines to ensure responsible use of these powerful tools.

Future Directions and Challenges

While genetic engineering offers immense promise, it is not without its challenges. Off-target effects, unintended consequences, and the potential for creating designer babies are among the issues that demand careful consideration. Researchers and ethicists must work in tandem to navigate this uncharted territory.

References

Doudna, J. A., & Charpentier, E. (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096.

Anzalone, A. V., Randolph, P. B., Davis, J. R., Sousa, A. A., Koblan, L. W., Levy, J. M., … & Liu, D. R. (2019). Search-and-replace genome editing without double-strand breaks or donor DNA. Nature, 576(7785), 149-157.

Kime, E. (2021). CRISPR and the ethics of gene editing. Nature Reviews Genetics, 22(1), 3-4.

This post only scratches the surface of the profound transformations occurring in genetic engineering. The relentless pursuit of knowledge and ethical exploration will shape the future of this field as we continue to unlock the intricate secrets of our genetic code.

[magnetictapedatastorage]

Topological issues in DNA arise due to the intertwined nature of its double-helical structure, which, for example, can lead to overwinding of the DNA duplex during DNA replication and transcription. If left unchanged, this torsion would eventually stop the DNA or RNA polymerases involved in these processes from continuing along the DNA helix. A second topological challenge results from the linking or tangling of DNA during replication. Left unresolved, links between replicated DNA will impede cell division. The DNA topoisomerases prevent and correct these types of topological problems. They do this by binding to DNA and cutting the sugar-phosphate backbone of either one (type I topoisomerases) or both (type II topoisomerases) of the DNA strands. This transient break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed. Since the overall chemical composition and connectivity of the DNA do not change, the DNA substrate and product are chemical isomers, differing only in their topology.

[covid-safer-hotties]

Molnupiravir May Offer Modest 6-Month Benefits for High-Risk COVID Patients - Published Sept 11, 2024

by Katherine Kahn

People with acute COVID-19 who took the antiviral drug molnupiravir (Lagevrio) reported modest improvements in symptoms, less time off from work or study, and less healthcare utilization at 6 months post-infection, a follow-up analysis of the prospective, open-label PANORAMIC trial suggested.

Among patients who received molnupiravir 800 mg twice per day plus usual care for 5 days after diagnosis with COVID-19, 8.5% reported persistent symptoms at 6 months compared with 11% who received usual care only (adjusted risk difference -2.5%), reported Christopher Butler, MBChB, MD, of the University of Oxford in England, and colleagues in Lancet Infectious Diseasesopens in a new tab or window.

At 3 months after treatment, use of healthcare or social services was also lower in the molnupiravir group at 14.1% versus 15.5% in the usual care group (adjusted risk difference -1.4%). There was a trend in the same direction at 6 months, but the adjusted risk difference was only -0.5%.

There were no differences in hospitalizations or deaths between the two groups at 3 and 6 months follow-up.

"This study was a secondary long-term analysis, and although we did not correct for multiplicity, the number of statistically superior outcomes make chance a very unlikely explanation of the results," the researchers wrote. "The trial design was pragmatic and open-label; therefore, participants were not masked and recovery and well-being outcomes were ascertained by self-reporting."

The study showed that the numbers needed to treat were high, noted co-author Victoria Harris, PhD, also of University of Oxford, in a press releaseopens in a new tab or window. "For instance, only one person would have less severe symptoms from a total of 53 people who took molnupiravir, and only one person would have used fewer NHS [National Health Service] services from a total of 71 people who took molnupiravir," she said.

Among participants who received molnupiravir, 17.9% reported having any time off from work or study at 3 months versus 22.4% in the usual care group, for an adjusted risk difference of -5.3%. At 6 months, 4.4% in the molnupiravir group reported having time off from work or study versus 5.4% in the usual treatment group (adjusted risk difference -1.1%), and about 91 patients would need to be treated to benefit one patient.

Molnupiravir is an expensive drug, Harris pointed out. In the U.S., a 5-day course costs about $1,000 opens in a new tab or windowwithout insurance coverage.

"Given the small additional number of participants who benefited from taking molnupiravir, compared to those who did not take the drug, long-term health benefits will need to be weighed up against costs and any unwanted effects," she emphasized.

The trial did not address the efficacy of molnupiravir in preventing long COVID, but Ziyad Al-Aly, MD, of the VA St. Louis Health Care System in Missouri, said in an accompanying editorialopens in a new tab or window that antivirals may one day play a role in long COVID treatment and prevention.

"The use of antivirals to reduce the risk of long COVID is grounded in the hypothesis that viral persistence and possible ongoing replication of SARS-CoV-2 are major mechanistic pathways responsible for long COVID," he commented. "Evidence for this hypothesis is growing." Studies have identified persistence of viral RNA or protein fragmentsopens in a new tab or window and the presence of T-cell activationopens in a new tab or window and double-stranded viral RNA months to years after infection with SARS-CoV-2, Al-Aly noted.

"The promising results from the PANORAMIC trial are consistent with results from well conducted observational analyses as they both converge on finding a modest effect of molnupiravir in reducing the risk of long COVID in high-risk individuals," Al-Aly wrote.

"Concerns, however, have been raised about the mutagenicity of molnupiravir," he pointed out. "Furthermore, effectiveness of molnupiravir or [other SARS-CoV-2 antivirals] in reducing risk of long COVID in low-risk populations, including younger individuals with no comorbid medical conditions, has not been evaluated," he cautioned.

The CDC recommendsopens in a new tab or window molnupiravir as an alternative to nirmatrelvir-ritonavir (Paxlovid) for the treatment of acute mild-to-moderate COVID-19 in non-pregnant adults at risk for severe disease, to be started within 5 days of symptom onset.

The PANORAMIC trial took place from December 2021 to April 2022 and included 25,783 participants who were randomly assigned to molnupiravir twice a day for 5 days plus usual care (n=12,821) or usual care alone (n=12,962) generally within 5 days of a COVID-19 infection.

To enroll, patients had to be either 50 years and older or 18 and older with at least one comorbidity. Mean age of participants was 56.6 years, 58.6% were female, and 93% had received at least three vaccine doses. Comorbidities included lung disease in 24%, hypertension in 22%, obesity in 15%, diabetes in 12%, a weakened immune system in 9%, and heart disease in 8%.

In the initial analysisopens in a new tab or window of the trial, molnupiravir failed to reduce the risk for hospitalization or death at 28 days from COVID-19 in high-risk, vaccinated outpatients, but did shorten recovery times from a median of 15 days to 9 days (HR 1.36).

Long-term follow-up data for the current analysis were available for about 89% of all participants -- about 92% in the treatment group and 87% in the usual care group.

Researchers contacted participants at 3 and 6 months and asked them to complete online or telephone questionnaires. Patients were asked to rate how well they felt, whether they had taken time off from work or study, or if they had been hospitalized. Patients also rated symptoms on a 4-point scale. Symptoms included fever, cough, shortness of breath, fatigue, muscle aches, nausea, vomiting, diarrhea, loss of taste or smell, headache, dizziness, abdominal pain, or feeling unwell.

The authors acknowledged that the open-label study design may have influenced patient self-reports of recovery and well-being. They also emphasized that the study was not an efficacy trial.

Study Link: www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00431-6/fulltext (PAYWALLED)

[owlservice]

Hepatitis B virus (HBV) specifically infects hepatocytes and causes severe liver diseases. The HBV life cycle is unique in that the genomic DNA (relaxed-circular partially double-stranded DNA: rcDNA) is converted to a molecular template DNA (covalently closed circular DNA: cccDNA) to amplify a viral RNA intermediate, which is then reverse-transcribed back to viral DNA.

Why would you do this?

[krishgen]

Krishgen Biosystems shares the top five medical applications of double stranded RNA (dsRNA) and how dsRNA is leveraged to address some of the most pressing medical challenges today. From its critical role in gene therapy and vaccine development to its potential in combating viral diseases, each application is presented with clear, engaging visuals and essential facts.

[science-sculpt]

Exploring RNA Interference

Imagine a molecular switch within your cells, one that can selectively turn off the production of specific proteins. This isn't science fiction; it's the power of RNA interference (RNAi), a groundbreaking biological process that has revolutionized our understanding of gene expression and holds immense potential for medicine and beyond.

The discovery of RNAi, like many scientific breakthroughs, was serendipitous. In the 1990s, Andrew Fire and Craig Mello were studying gene expression in the humble roundworm, Caenorhabditis elegans (a tiny worm). While injecting worms with DNA to study a specific gene, they observed an unexpected silencing effect - not just in the injected cells, but throughout the organism. This puzzling phenomenon, initially named "co-suppression," was later recognized as a universal mechanism: RNAi.

Their groundbreaking work, awarded the Nobel Prize in 2006, sparked a scientific revolution. Researchers delved deeper, unveiling the intricate choreography of RNAi. Double-stranded RNA molecules, the key players, bind to a protein complex called RISC (RNA-induced silencing complex). RISC, equipped with an "Argonaut" enzyme, acts as a molecular matchmaker, pairing the incoming RNA with its target messenger RNA (mRNA) - the blueprint for protein production. This recognition triggers the cleavage of the target mRNA, effectively silencing the corresponding gene.

So, how exactly does RNAi silence genes? Imagine a bustling factory where DNA blueprints are used to build protein machines. RNAi acts like a tiny conductor, wielding double-stranded RNA molecules as batons. These batons bind to specific messenger RNA (mRNA) molecules, the blueprints for proteins. Now comes the clever part: with the mRNA "marked," special molecular machines chop it up, effectively preventing protein production. This targeted silencing allows scientists to turn down the volume of specific genes, observing the resulting effects and understanding their roles in health and disease.

The intricate dance of RNAi involves several key players:dsRNA: The conductor, a long molecule with two complementary strands. Dicer: The technician, an enzyme that chops dsRNA into small interfering RNAs (siRNAs), about 20-25 nucleotides long. RNA-induced silencing complex (RISC): The ensemble, containing Argonaute proteins and the siRNA. Target mRNA: The specific "instrument" to be silenced, carrying the genetic instructions for protein synthesis.

The siRNA within RISC identifies and binds to the complementary sequence on the target mRNA. This binding triggers either:Direct cleavage: Argonaute acts like a molecular scissors, severing the mRNA, preventing protein production. Translation inhibition: RISC recruits other proteins that block ribosomes from translating the mRNA into a protein.

From Labs to Life: The Diverse Applications of RNAi

The ability to silence genes with high specificity unlocks various applications across different fields:

Unlocking Gene Function: Researchers use RNAi to study gene function in various organisms, from model systems like fruit flies to complex human cells. Silencing specific genes reveals their roles in development, disease, and other biological processes.

Therapeutic Potential: RNAi holds immense promise for treating various diseases. siRNA-based drugs are being developed to target genes involved in cancer, viral infections, neurodegenerative diseases, and more. Several clinical trials are underway, showcasing the potential for personalized medicine.

Crop Improvement: In agriculture, RNAi offers sustainable solutions for pest control and crop development. Silencing genes in insects can create pest-resistant crops, while altering plant genes can improve yield, nutritional value, and stress tolerance.

Beyond the Obvious: RNAi applications extend beyond these core areas. It's being explored for gene therapy, stem cell research, and functional genomics, pushing the boundaries of scientific exploration.

Despite its exciting potential, RNAi raises ethical concerns. Off-target effects, unintended silencing of non-target genes, and potential environmental risks need careful consideration. Open and responsible research, coupled with public discourse, is crucial to ensure we harness this powerful tool for good.

RNAi, a testament to biological elegance, has revolutionized our understanding of gene regulation and holds immense potential for transforming various fields. As advancements continue, the future of RNAi seems bright, promising to silence not just genes, but also diseases, food insecurity, and limitations in scientific exploration. The symphony of life, once thought unchangeable, now echoes with the possibility of fine-tuning its notes, thanks to the power of RNA interference.

[annealgd4]

Week 1: Introduction to "Anneal"

What is "Anneal"?

The word anneal is rich with meaning across various contexts, from its technical applications in material science to its metaphorical significance in resilience and transformation. Here's what I found out so far:

Dictionary Definitions

Material Science: To heat (metal or glass) and allow it to cool slowly, removing internal stresses and making the material easier to work with. Example: "Copper tubes must be annealed after bending, or they will be brittle."

Biology: The process of recombining DNA in double-stranded form

Figurative Meaning: To strengthen or toughen through hardship. Example: "She was annealed by the tragedies of her childhood."

Origins and Etymology

Old English: onǣlan (on + ǣlan), meaning "to set on fire."

Derived from āl (fire, burning), reflecting its early association with heat and transformation.

The term evolved in Middle English to include altering material by fire.

Applications Across Disciplines

Material Science:

Annealing is a heat treatment process that increases ductility and reduces hardness, making materials more workable. The process involves several thermal cycles:

Subcritical Annealing: Heating below the critical temperature.

Full Annealing: Heating above the upper critical temperature.

Common materials: Copper, silver, brass.

Annealing is used to improve machinability, and electrical properties, and reduce internal stresses.

Biology:

Annealing refers to binding complementary DNA or RNA strands. It is a process fundamental to genetic research and laboratory testing. It can involve heating and cooling cycles to separate and recombine strands, often with primers.

Metaphorical Use:

To anneal people or ideas is to reshape, strengthen, or unite them, as if through a transformative heating and cooling process.

Synonyms and Antonyms

Synonyms: Strengthen, temper, fortify, reinforce, adjust, acclimate

Antonyms: Weaken, soften, sensitize, incapacitate.

Quote of the Week

"Art is a language which anneals individuals to each other through experiences that are uniquely human, that demand connection at the level of making meaning."

- Ann Lauterbach, The Night Sky: Writing on the Poetics of Experience

Looking Ahead

This week, I've focused on understanding some of the historical, semantic, and technical roots of anneal. Moving forward, ill explore how this concept can inspire 2D, 3D, and 4D visualizations, focusing on its themes of transformation and resilience.

Stay tuned for updates on my research journey and creative process!

[hellsite-proteins]

I LOVE THIS BLOG… would you be able to explain the stuff you’re doing to someone who knows nothing about proteins? all I can remember is something to do with dna ..?

of course! ill do my best to give an entry level crash course here, but if any of this is unclear please leave a comment or send an ask so i can better explain.

DISCLAIMER: all of this has been simplified, and because biology is messy, there are exceptions to pretty much everything i've said. the point is not to give a perfect explanation, but rather a general understanding

the central dogma of molecular biology is pretty much our version of "the mitochondria is the powerhouse of the cell", and since you've alluded to it already, i'll start there. it states that genetic information goes from DNA to RNA to proteins. inside of almost any cell is DNA, which codes for all of the genetic information allowing the cell to function. for our purposes right now, just think of DNA as an instruction manual. when a protein is going to be made, the part of the DNA sequence encoding it is copied over to make a RNA sequence.

RNA is structurally similar to DNA, but while DNA is usually found as a double helix (with two complementary strands), RNA is more often single stranded. it is less stable than DNA, so it does not work as well for long term information storage, but is smaller and can cary out numerous crucial functions.

prokaryotes are things like bacteria, and are distinct from eukaryotes (which includes us) because they lack a nucleus. this means that their DNA is loose inside their cell, rather than sectioned away. in prokaryotes, transcription (which copies information from DNA -> RNA) and translation (which is the process of going from RNA -> proteins) can happen at the same time, while in eukaryotes these processes are separated, as DNA is too large to leave the nucleus. messenger RNA (mRNA) is the specific type of RNA used to code for proteins in all cells. inside a eukaryotic cell, mRNA must be processed to increase its stability and allow it to exit the nucleus.

now, getting to the part about proteins! proteins are made through a process called translation, which translates the information stored using a sequence of nucleic acids on RNA to a string of amino acids known as a protein. each set of three nucleic acids, which on mRNA can be A, U, C or G, makes up the codon for one amino acid. the code is referred to as 'degenerate', since there is a lot of redundancy built in and so some information is lost along the way. there are more possible codons than there are amino acids, and so there is a lot of overlap with several codons coding for the same amino acid.

translation is accomplished using organelles known as ribosomes. these bind to the relevant RNA sequence and help join together the amino acids that are encoded by their sequence, forming peptide bonds. this is done using another specialized type of RNA called a transfer RNA (tRNA), which sticks temporarily to the three-letter codon on the mRNA and carries the corresponding amino acid to the ribosome so that it can be joined with the others in the sequence. all proteins start with the same codon (AUG), and subsequent amino acids are added one at a time. RNA and proteins both have directionality, which means that the two different ends of these molecules are not the same, and the direction you read the sequence in matters.

as a protein is assembled, the N terminal end is put together first, and so this part exits the ribosome while the rest is still being built. at this point, it comes in contact with the liquid inside the cell, and starts to bend itself into different shapes in order to make the most thermodynamically stable structure. this happens spontaneously, and is an effort to minimize the free energy of the protein and the surrounding water molecules. basically, everything wants to be in a state that requires as little energy as possible, and will fold itself to get there. think of this as a similar process to getting home after a long day, and trying to make yourself comfortable as fast as possible. protein folding is the equivalent to you taking off your jeans and lying down on your couch.

the thing is, proteins are complicated, and they need to fold quickly, because the inside of a cell is crowded and chaotic. the way they fold is influenced by several different factors, including how fast translation takes place and whether anything else is nearby to help them fold correctly. proteins do countless different highly specific things in any given cell, and their ability to function is based entirely around their structure. just like how you probably have numerous different tools in your home made of plastic, but each one is a different shape and therefore does something unique. if someone came along and melted your plastic cups until they were completely deformed, they wouldn't be of much use.

the primary structure of a protein is its amino acid sequence, and the secondary structure is made by interactions between nearby backbone atoms, but the tertiary structure is the main thing you'll see looking at any real protein structure. it is the combination of interactions between all the atoms within one amino acid chain. if this gets damaged (which can happen with things like heat and strong chemicals), the protein is said to be denatured. some proteins also have a quaternary structure, which is formed as different folded chains of amino acids each making up one subunit assemble together to make a bigger, more complicated protein.

whether they folded wrong from the start (like your plastic cup getting made with a hole in the bottom at the factory) or they started off fine but then got broken (like your plastic cup melting after you leave it on the hot stove), misfolded proteins are the wrong shape and therefore cannot perform their function correctly. these can do a lot of damage in an organism, and are generally a waste of resources to keep around, so they get destroyed and their parts are recycled.

hope this helps!

letter sequence in this ask matching protein-coding amino acids:

ILVETHISLGwldyealeteplainthestffyredingtsmenewhknwsnthingatprteinsallIcanrememerissmethingtdwithdna

protein guy analysis:

this protein is strange, terrible and filled with holes! just like many of the other structures, the myriad of loops want nothing to do with each other, and everything is all over the place. this whole structure is disordered and likely wiggling around trying to find something else to stick to and mess with. just a toxic trainwreck that should never have existed.

predicted protein structure:

[smalleststories]

hi! would you like to tell us about your research?

thank you anon, this means a lot to me.

The lab I'm working in this summer studies a type of virus called reovirus. It's an RNA virus like HIV or Covid, but unlike those viruses reovirus doesn't cause disease in humans. This brings us to the first and second uses of reovirus in virology: it's a good first virus for undergrads like me because it isn't dangerous, and it's a way to study the basics of more dangerous viruses without putting people at risk. Reovirus is a common model for rotavirus, which also has a double-stranded RNA genome but does cause disease in humans (it's a common cause of diarrhea in kids).

The third reason we study reovirus is because of how it interacts with our immune system. Much of what we think of as being sick is actually our immune system trying to kill off a pathogen- inflammation, runny noses, and other fun reasons to skip work are all signs of the immune system functioning as intended. Reovirus triggers immune responses that don't cause physical symptoms, however.

Which leads us to cancer.

Fundamentally, cancer is a failure of the immune system. Cells and the organisms they are a part of have a lot of failsafes to stop cancer from happening, and tumors need to avoid getting caught in them. This typically looks like accumulating mutations to cause unrestricted growth and then suppressing the immune system to allow that growth to continue (more on this). This has led to the idea that we could treat cancer by reactivating the immune system when cancer shuts it off. There are a wide range of therapies in this vein that are currently being developed, with intentional infection with reovirus being one that's currently in human clinical trials. The idea, metaphorically, is to have reovirus move into a tumor and have a housewarming party so wild that the cops get called, even though this is a neighborhood that the cops usually turn a blind eye to.

What makes reovirus particularly promising is that it prefers to infect cancer cells over healthy cells! To quote the American Cancer Society on why this is important:

Cancer cells tend to form new cells more quickly than normal cells and this makes them a better target for chemotherapy drugs. However, chemo drugs can’t tell the difference between healthy cells and cancer cells. This means normal cells are damaged along with the cancer cells, and this causes side effects. Each time chemo is given, it means trying to find a balance between killing the cancer cells (in order to cure or control the disease) and sparing the normal cells (to lessen side effects).

This means that one of the main issues of treatments like chemo, that they target quick-dividing cells rather than tumor cells only, could possibly be a nonissue with reovirus treatment.

What my labmates and I are looking at this summer (besides getting the lab back up and running, but that's a whole different story) is how reovirus specifically pulls in a part of the immune system called the interferon response, which is basically an SOS signal that causes cells to turn a bunch of genes on or off. We're also looking at whether cells with different metabolism profiles react to infection differently, and whether this can be used to specifically target certain cancers. My lab is just getting started right now (see: above parenthetical), but the work that's already been done is so exciting and I love talking about it!

Here's a chapter on reovirus from an ancient textbook, and here's a review of work on interferons, if you want to know more!