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As expected, Starmer's born-again Hard Brexiter stance (no EU, no single market, no customs union) is falling apart even before Labour's elected. It's like he's promising to cure a disease without using any medicine. Making Brexit work by homeopathy.

Within a year or two, he & Reeves will have to backtrack in the face of economic reality or look like fools when their do-nothing approach fails to cure any of the crippling problems caused by their own Hard Brexit policy.

theguardian.com/uk-news/articl

'The book is also something of a diptych. The resonances between the two greatest public-health crises of Fauci’s tenure at niaid are impossible to ignore. Both cases involve asymptomatic infection, a scramble for tests and treatments, public-information campaigns, and the search for a vaccine—miraculously fast for covid-19, still unfulfilled for H.I.V. '
newyorker.com/magazine/2024/06

It took five years to write, but here's the full story behind Lambda School, Silicon Valley's disastrous foray into for-profit education.

I explain how they burned through $120 million in funding, why Income Share Agreements failed, the crimes committed along the way, and how one developer turned journalist put an end to the fraud.

sandofsky.com/lambda-school/

'Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response. In multiple mouse models, we show that liver metastases siphon activated CD8+ T cells from systemic circulation. Within the liver, activated antigen-specific Fas+CD8+ T cells undergo apoptosis following their interaction with FasL+CD11b+F4/80+ monocyte-derived macrophages.'

nature.com/articles/s41591-020

Tasty, but often lacking in nutritional value:
"First, there is Causal Salad: You put everything into a regression equation, toss with some creative story-telling, and hope the reviewers eat it. In general, this is not a valid approach, for well-known reasons. But it can get you published. Causal salad can discover causes too. But you have to get lucky. The Salad isn’t only regression. Really any procedure that hopes to take a list of variables (features) and return causal inference is Causal Salad. No amount of data reliably turns salad into sense."
elevanth.org/blog/2021/06/15/r

@adhdeanasl

Parents: Kids are more depressed these days, i wonder why?

Kids: You destroyed the economy for us, the earth is literally dying, we are going to work until we die and on top of that the Nazis are back.

Parents: It's those pesky Necco Wafers

'We find that diapause evolved by a recent remodeling of regulatory elements at very ancient gene duplicates (paralogs) present in all vertebrates. CRISPR-Cas9-based perturbations identify the transcription factors REST/NRSF and FOXOs as critical for the diapause gene expression program, including genes involved in lipid metabolism.'

cell.com/cell/fulltext/S0092-8

'De pouquíssimos intelectuais públicos se pode dizer que estão em condições de comemorar em vida os 85 anos do seu primeiro artigo político. Mas é o caso de Chomsky: foi em 1939, tinha ele dez anos, que publicou um primeiro artigo político no jornal da sua escola, em Filadélfia, sobre a Guerra Civil de Espanha.'
@ruitavares
expresso.pt/opiniao/2024-06-20

Why is #immunotherapy so difficult in patients with #liver #metastases. In this systematic analyses, Weiping Zou and colleagues try to unravel the #immunology at work in their manuscript.
nature.com/articles/s41591-020

"Among the 247,854 COVID-19-related papers published in PubMed, 12,152 were initially released as preprints and were eventually published in 1,380 journals. This number is more than five times the 246 journals to which submissions can be made directly from bioRxiv through the B2J program. Journals with higher impact factors and Normalized Eigenfactor scores tend to publish a larger number of preprint-derived articles"
biorxiv.org/content/10.1101/20

The Impact of Preprints on COVID-19 Research Dissemination: A Quantitative Analysis of Journal Publications

Preprints have played an unprecedented role in disseminating COVID-19-related science results to the public. The study aims to elucidate the role of preprints during the COVID-19 public health emergency (2020-2023) through a quantitative analysis of journal papers. Among the 247,854 COVID-19-related papers published in PubMed, 12,152 were initially released as preprints and were eventually published in 1,380 journals. This number is more than five times the 246 journals to which submissions can be made directly from bioRxiv through the B2J program. Journals with higher impact factors and Normalized Eigenfactor scores tend to publish a larger number of preprint-derived articles. The proportion of preprints among PubMed papers was 0.049, but this varies significantly by journal. In the top 30 journals, most exceed this proportion, indicating that these journals are preferred by authors for submitting their work. These findings highlight the growing acceptance and impact of preprints in the scientific community, particularly in high-impact journals. ### Competing Interest Statement The authors have declared no competing interest.

www.biorxiv.org

Conformational modulation of a mobile loop controls catalysis in the (βα)8-barrel enzyme of histidine biosynthesis HisF biorxiv.org/content/10.1101/20

Conformational modulation of a mobile loop controls catalysis in the (βα)8-barrel enzyme of histidine biosynthesis HisF

The overall significance of loop motions for enzymatic activity is generally accepted. However, it has largely remained unclear whether and how such motions can control different steps of catalysis. We have studied this problem on the example of the mobile active site β1α1-loop (loop1) of the (βα)8-barrel enzyme HisF, which is the cyclase subunit of imidazole glycerol phosphate synthase. Loop1 variants containing single mutations of conserved amino acids showed drastically reduced rates for the turnover of the substrates N'-[(5'-phosphoribulosyl) formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PrFAR) and ammonia to the products imidazole glycerol phosphate (ImGP) and 5-aminoimidazole-4-carboxamide-ribotide (AICAR). A comprehensive mechanistic analysis including stopped-flow kinetics, X-ray crystallography, NMR spectroscopy, and molecular dynamics simulations detected three conformations of loop1 (open, detached, closed) whose populations differed between wild-type HisF and functionally affected loop1 variants. Transient stopped-flow kinetic experiments demonstrated that wt-HisF binds PrFAR by an induced-fit mechanism whereas catalytically impaired loop1 variants bind PrFAR by a simple two-state mechanism. Our findings suggest that PrFAR-induced formation of the closed conformation of loop1 brings active site residues in a productive orientation for chemical turnover, which we show to be the rate-limiting step of HisF catalysis. After the cyclase reaction, the closed loop conformation is destabilized, which favors the formation of detached and open conformations and hence facilitates the release of the products ImGP and AICAR. Our data demonstrate how different conformations of active site loops contribute to different catalytic steps, a finding that is presumably of broad relevance for the reaction mechanisms of (βα)8-barrel enzymes and beyond. ### Competing Interest Statement The authors have declared no competing interest.

www.biorxiv.org
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