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Satisfies in TypeScript

This is a post about one of TypeScript’s less common features: the satisfies keyword. It’s occasionally incredibly useful, and knowing how to properly wield it is a valuable trick to have up your sleeve. Let’s take a look!

🧑‍💻 frontendmasters.com/blog/satis

frontendmasters.comSatisfies in TypeScript – Frontend Masters BlogThe `satisfies` keyword allows you to assert that a certain value

🥳BESSER version 3.0 released🎉

New major version of the #opensource #lowcode BESSER framework just released 👏👏👏

Main New Features and Improvements:

☑️ Model (and generate) your #conversational #agents with our new BESSER Agentic Framework graphical editor

☑️Enhanced #structural models with #metadata support - you can now add descriptions and URIs to classes

☑️Improved the Python Generator to support generation of methods to handle bidirectional consistency in associations

⚙️Full details: github.com/BESSER-PEARL/BESSER

"RNA-Puzzles Round V dives into blind predictions by 18 modeling groups for 23 #RNA structures. 🧬

From #aptamers to #riboswitches, it highlights progress and challenges in RNA #3D #modeling.

Proud to contribute to this incredible journey! A heartfelt thank you to the organizers, collaborators, and the amazing community advancing RNA #structural #biology.

Together, we’re pushing the boundaries of #RNA3D, #StructuralBiology, #Bioinformatics, and #ComputationalBiology.

doi.org/10.1038/s41592-024-025

Pyramidal cell types and 5-HT2A receptors are essential for #psilocybin's lasting drug action biorxiv.org/content/10.1101/20 on #structural #neural #plasticity #neuroscience

"We find that a single dose of psilocybin increased the density of dendritic spines in both the subcortical-projecting, pyramidal tract (PT) and intratelencephalic (IT) cell types."

bioRxiv · Pyramidal cell types and 5-HT2A receptors are essential for psilocybin's lasting drug actionPsilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses. At the cellular level, psychedelics induce structural neural plasticity, exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells. A key question is how these cellular modifications map onto cell type-specific circuits to produce psychedelics' behavioral actions. Here, we use in vivo optical imaging, chemogenetic perturbation, and cell type-specific electrophysiology to investigate the impact of psilocybin on the two main types of pyramidal cells in the mouse medial frontal cortex. We find that a single dose of psilocybin increased the density of dendritic spines in both the subcortical-projecting, pyramidal tract (PT) and intratelencephalic (IT) cell types. Behaviorally, silencing the PT neurons eliminates psilocybin's ability to ameliorate stress-related phenotypes, whereas silencing IT neurons has no detectable effect. In PT neurons only, psilocybin boosts synaptic calcium transients and elevates firing rates acutely after administration. Targeted knockout of 5-HT2A receptors abolishes psilocybin's effects on stress-related behavior and structural plasticity. Collectively these results identify a pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex as playing essential roles for psilocybin's long-term drug action. ### Competing Interest Statement A.C.K. has been a scientific advisor or consultant for Boehringer Ingelheim, Empyrean Neuroscience, Freedom Biosciences, and Psylo. A.C.K. has received research support from Intra-Cellular Therapies. The other authors report no financial relationships with commercial interests.

#Structural and #virologic #mechanism of the emergence of #resistance to #Mpro #inhibitors in #SARS-CoV-2, PNAS: pnas.org/doi/abs/10.1073/pnas.

We generated SARS-CoV-2 variants resistant to three SARS-CoV-2 main protease (Mpro) inhibitors (#nirmatrelvir, TKB245, and 5h), by propagating the ancestral SARS-CoV-2WK521WT in VeroE6TMPRSS2 cells with increasing concentrations of each inhibitor and examined their structural and virologic profiles.

Limitarianism: why we need to put a cap on the super-rich

Suppose you worked 50 hours a week between the ages of 20 and 65
– week in week out, year in year out
❓how much would your hourly wage need to be so that by the end you had amassed Musk’s wealth?

The answer is: $1,871,794 per hour.

💥Almost two million dollars per hour. Every working hour for 45 years.

Elon Musk might be seen as exceptional, but there were 2,668 other billionaires on that Forbeslist.

Together they held $12,700,000,000,000.

Do you, like me, see all those zeros dancing before your eyes?

That’s because we don’t know how to take in that number.

On average the value of their assets is $4.75bn.
If we ask the same question again
– what’s the average lifetime hourly wage?
– we get $40,598 per hour, the equivalent to what many Americans hope to earn in a year.

How much is too much?
When I started this research, 10 years ago, several of my colleagues
– professors in philosophy, economics and related disciplines
– were initially amused that I wanted to delve into this question.
Some argued that #poverty was what mattered, not #inequality.
A few felt that focusing on the rich was an indication of envy on my part.

But I wasn’t alone.
Across various disciplines, scholars were starting to see that something was happening at the upper levels of society,
and we ought to pay attention.
I started to think through the #ethics of extreme wealth concentration in a systematic way,
and after a decade I became convinced that
👉we must create a world in which no one is super-rich
– that there must be a cap on the amount of wealth any one person can have.
❇️I call this #limitarianism.

As a concept, limitarianism is simple.
But what does it mean in practice?

My book endeavours to answer that question, but it can best be understood as a regulative ideal
– an outcome to strive for but which, like the eradication of poverty, is unlikely to be definitively achieved.

In practical terms, limitarianism calls for three kinds of action.
♦️First there is #structural action. Our societies’ key social and economic institutions should give people genuinely equal opportunities, through ❇️affordable childcare, free high-quality education and a comprehensive anti-poverty strategy.
The more structural steps we take to reduce inequality, the less need there will be for the second strategy:

♦️fiscal action.
If taxation were our only tool for achieving a limitarian society,
💥the tax rate would need to be set at 100% for wealth and income beyond a certain point
(spoiler alert: it is not the only tool).
Still, there is a very strong case for imposing a cap on extreme wealth.

The third kind of action limitarianism calls for is
♦️ethical action: we all need to embrace a limitarian ethos.

One objection to this might be that limiting how much wealth a person can accrue would require us to give up private property or the market mechanism, and force us into USSR-style communism.

Such an objection is nonsense,
and it’s probably just another attempt to silence meaningful criticism of the status quo.

Markets are a very powerful tool for securing material welfare;
private property is a cornerstone of our security, autonomy and prosperity.

The real question, which we must seek to answer, is rather which constraints on the market and private property we need if we are to achieve limitarianism.

theguardian.com/books/2024/jan

The Guardian · Limitarianism: why we need to put a cap on the super-richBy Guardian staff reporter

#Structural #Mapping of #Polyclonal #IgG Responses to #HA After #Influenza Virus #Vaccination or #Infection, BioRxIV: biorxiv.org/content/10.1101/20

These data establish a baseline for assessing polyclonal #antibody responses in vaccination and infection, providing context for future vaccine #trials and emphasizing the importance of carefully designing vaccines to boost protective responses towards conserved epitopes.

bioRxiv · Structural Mapping of Polyclonal IgG Responses to HA After Influenza Virus Vaccination or InfectionCellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses against H1 predominantly targeted the central stem epitope in infected patients and vaccinated donors, whereas head epitopes were more prominently targeted on H3. Responses against H3 were less abundant, but a greater diversity of H3 epitopes were targeted relative to H1. While our analysis is limited by sample size, on average, vaccinated donors responded to a greater diversity of epitopes on both H1 and H3 than infected patients. These data establish a baseline for assessing polyclonal antibody responses in vaccination and infection, providing context for future vaccine trials and emphasizing the importance of carefully designing vaccines to boost protective responses towards conserved epitopes. ### Competing Interest Statement J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, a former member of the Scientific Advisory Boards of Gigagen (Grifols), of Meissa Vaccines, and BTG International, is founder of IDBiologics and receives royalties from UpToDate. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda Vaccines, and IDBiologics during the conduct of the study. CBC has served as a consultant to Sanofi Pasteur, Pfizer, Moderna, GSK, TDCowen, Debiopharm, and CommenseBio and receives royalties from UoToDate. All other authors declare they have no competing interests.