Duller-Finite

That describes a related but previous Nature paper from the same group, whereas this is referring to a more recent Science paper.

Yeah seems like related to homeopathic medicine (aromatherapy or essential oils or tinctures)

the study said that the 5 patients with VITT that they looked at had the IGLV3-21 * 02 polymorphism, but it's a fallacy to say that means that you can't get clotting without it

that study used TALENs; this one used CRISPR base editors

It's a shame that Perceptive Automata shut down.

Glp and G9a are ubiquitous as they are import epigenetic regulators (histone methyltransferases). Sounds difficult to work on, and hard to supplement if they play an important role in many cell types

TRP channels were first cloned over 20 years ago, and are indeed medically relevant for nociception and pain. The piezos are equally relevant; knockouts are embryonically lethal, and the function of mechanosenstation in somatosenation and in general continue to be elucidated. For instance, it was only a few years that they were identified as being required for the baroreceptor reflex.

As an example, Douglas Bates, the author of R's lme4 excellent package for generalized linear mixed-effects models, has switched to julia to develop MixedModels.jl. The julia version is already excellent, and has many improvements over lme4.

David Baker's group (author of the RoseTTAFold paper out today in science) has multiple exciting examples of de novo design of proteins.

For example, see [1] or [2], and [2] was spun off into a company (Neoleukin Therapeutics).

[1] https://science.sciencemag.org/content/371/6531/eabc8182 [2] https://www.nature.com/articles/s41586-018-0830-7

This paper is the first structure of any odorant receptor-ligand interaction. There's currently no equivalent structure for mammalian odorant receptors to validate the docking theory, but it's likely correct.

Not really. GPCRs amplify signals at each step via their second messenger cascade. These channels form homotetramers whose structure differs greatly from the canonical seven transmembrane domain structure of GPCRs. So this study is important since there were no studies indicating how odorants bind and activate odorant receptors. However, it is unlikely that the mechanisms in insects odorant receptors will directly apply to those of mammalian odorant receptors. In contrast, mammalian odor receptors will work much more like those of other class A GPCRs like the β-adrenergic receptor, of which there are numerous structures interacting with ligands and in various configurations, and which was the basis of the work that won the nobel prize in 2012.

This is truly a landmark study. This is the first structure of any odorant receptor. It is, however, one from an insect, so the structure is not homologous to mammalian olfactory receptors, which are a large family of G-protein-coupled receptors.

The Code Breaker by Walter Isaacson is a recent biography of Jennifer Doudna, who won the Nobel Prize for her pioneering work on CRISPR, that you might enjoy

I don't follow. What's stunning about it? Doesn't it just mean that there is little evolutionary pressure or selection on the olfactory receptor genes? Not sure what the discovery is, or its significance.

RNA uses uracil/uridine rather than thymine, but uridine is actually quite immunogenic. That's what has prevented people from using mRNA as a therapy until recently, when the founders of BioNTech figured out that they could use pseudouridine (abbreviated as Ψ) instead. See [1] for more information.

[1]https://www.wired.co.uk/article/mrna-coronavirus-vaccine-pfi...

lipofectamine is used for in vitro transfection, not in vivo gene delivery. The vaccines use lipid nanoparticles rather than liposomes

A similar article was published in Wired about a month ago: https://www.wired.co.uk/article/mrna-coronavirus-vaccine-pfi...

I have no idea why you think that there were no studies in April. A quick search shows that's wrong. There were initial reports in March, followed by many peer-reviewed studies that started coming out in April, which were then followed by studies with more objective measures (rather than retrospective self-reports) and larger sample sizes.

[1] https://academic.oup.com/cid/article/71/15/889/5811989

[2] https://link.springer.com/article/10.1007/s00405-020-05965-1

[3] https://onlinelibrary.wiley.com/doi/full/10.1002/alr.22592

[4] https://jamanetwork.com/journals/jama/fullarticle/2765183

[5] https://www.nature.com/articles/s41591-020-0916-2

Yes, there were a lot of reports back in March about the loss of smell as a frequent and specific symptom for COVID-19. I'm not sure why this article acts like it's a new thing. And, yes, patients recovering from the loss of smell (hyposmia or anosmia) can often have smell distortions and disturbances (known as parosmias and phantosmias).

There were many papers that came out over 4 months ago with more people and other approaches, all with similar conclusion [1-3]. Not sure why this paper is getting a lot of press.

[1] https://www.nature.com/articles/s41591-020-0916-2 [2] https://elifesciences.org/articles/58227 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386529.1/

This is an interesting and well-done paper. It is, however, difficult to evaluate these mouse studies because, unlike human ACE2, mouse ACE2 doesn't facilitate SARS-CoV-2 cell entry. Therefore, they had to first deliver hACE2 either with an intranasal adenovirus injection, or use transgenic mice expressing hACE2 in a pattern that does not recapitulate its expression in humans.

It does seem like they do an especially good job at blocking infections in the respiratory system, but that's both the system that they primed for infection and where they provided the ChAd vaccine, so I don't know how fair of a comparison the intramuscular injection experiments are.

While you're right they edited the embryos the sentence you quoted is describing a drug (680C91) that they bath-applied to inhibit the TDO enzyme (as a positive control), rather than the CRISPR strategy they used, in which they injected the Cas9 and sgRNA into the embryo.

The article reports on the in vitro results and says they're going to be doing further validation in vivo. As I mentioned before, the same has been true for basically every other antibody being developed (monoclonals and ones isolated from patients), which were also initially published in Nature/Science/etc with only in vitro and structural data.

There are multiple aspects that are novel here: their size, the trimer (rather than a cocktail), and their stability/delivery. All of these seem worthy of reporting. They say they're about to start clinical trials to see if they could be efficacious; they don't say that they will.

Normally I agree that press releases way oversell the research, but I don't think that was the case here. Their camelid nanobody approach seems to be a fairly novel idea with some nice benefits over traditional antibodies, and most of the linked article actually does a nice job of walking you through the figures in the preprint.

Sure there's not any clinical data, but they actively admit that and I'm sure that's something they're working on. Furthermore, there have been multiple Nature papers published on SARS-CoV-2 neutralizing antibodies and antibody cocktails that use the same experiments (e.g. Vero cells) without testing in animal models or in humans. One step at a time!

That's why I'm in favor of this change in nomenclature.

Excel isn't the program of choice for most scientists and computational biologists, who typically use R, python, or command line tools. However, we often get data from other scientists or reanalyze data from other groups that can have these errors. It's so frequent of a problem that there are scientific papers about it [1].

[1] https://genomebiology.biomedcentral.com/articles/10.1186/s13...

As a follow-up for those that have said genetic studies have been fruitful, here's excerpts from the most recent genetic study [1]. This study looked at a link in the μ-opioid receptor gene, which was the only gene that barely reached genome-wide significance in their meta-analysis of 8529 individuals with opioid use disorder (OUD). In contrast, smoking, alcohol use, and education status showed clear effects on OUD.

"Understanding the genetic architecture of OUD might provide clinically useful clues about its biology. However, to our knowledge, only a few risk variants have been identified by GWAS so far, and none has had clear external replication. Several factors contribute to this situation: (1) OUD is a complex psychiatric disease with relatively low heritability, and there is no single variant with a large effect size that can be detected in small cohorts"

[1] https://jamanetwork.com/journals/jamapsychiatry/article-abst...

SCN9A variants have certainly been linked to changes in pain sensitivity (in both directions), but where have they been linked to changes in risk for opiate addiction? Even for the variant identified in this paper, the fact that it was linked to increased pain doesn't necessarily mean that it would put one at an increased risk for opiate addiction; in fact, you could easily imagine the opposite.

Furthermore, in spite of the strong genetic evidence, especially for the cases for congenital pain insensitivity, it has also been hard for the industry to develop Nav1.7 inhibitors, but that could mostly be due to targeting specificity.

Why are people so keen to look for genetic explanations, rather than socioeconomic ones?

Yes, this was noted in the article, which certainly does not proclaim that the CS50 model is the one that all universities and courses should be adopting.

"Malan’s contract at Harvard allows him to focus almost exclusively on CS50; even the research he publishes centers mainly on the class...Malan’s method of remote teaching is not easily replicable; CS50’s pyrotechnics would not be possible without an unusually deep well of resources and his own fanatical commitment"