"Here, we show that neuronal signal-regulatory protein alpha (SIRPα) is a permissive cue for microglial #phagocytosis in the developing murine retina. Removal of neuronal, but not microglial, SIRPα reduced microglial phagocytosis, increased synpase numbers, and impaired circuit function. Conversely, prolonging neuronal SIRPα expression extended developmental microglial phagocytosis. These outcomes depended on the interaction of presynaptic SIRPα with postsynaptic CD47."
#Immunity #Immunology #Microglia #Neuroimmunology
https://www.cell.com/immunity/fulltext/S1074-7613(22)00559-3
"Acontece que este movimento é apenas mais um de um enorme esforço de apoio às empresas que o Estado português tem feito, sem evidência de que esteja a funcionar no sentido de promover ciência ou inovação e sem a esperada canalização de fundos para investigação académica."
Joana Sa on the recent (very disturbing) #SciencePolicy #ScienceFunding trends in Portugal
https://www.publico.pt/2022/11/17/opiniao/opiniao/ciencia-melhores-empresas-2027963
"A new study, based on 25 years of data from Australia, suggests that environmental changes have been driving these spillovers by radically altering the ecology of black flying foxes. Deforestation, coupled with climate-linked food shortages, has driven the bats into human-dominated habitats like farms, where food is readily available but may be of poorer quality, scientists reported in Nature on Wednesday."
"We show that memories of mitotic duration are integrated by a p53-based mitotic stopwatch pathway to exert tight control over proliferation. The stopwatch halts proliferation of the products of a single significantly extended mitosis or of successive modestly extended mitoses. Time in mitosis is monitored via mitotic kinase-regulated assembly of stopwatch complexes that are transmitted to daughter cells."
Recently wrote for #NatureMedicine this postmortem of the Oxford/AZ mucosal Covid vaccine trial. The intranasal spray version of ChAdOx1 failed to induce strong antibody responses.
But the column also includes a bit on the positive outcome of CanSino's trial using an inhaler (approved as a booster for 2x Coronavac).
"In mice, the loss of Sharpin leads to severe dermatitis due to excessive cell death in keratinocytes. Here we report the first patient with SHARPIN deficiency, manifesting fever, arthritis, colitis, chronic otitis media and hepatic glycogenosis but unexpectedly, not associated with dermatologic manifestations."
#Immunology #HumanGenetics #Immunedeficiency #LUBAC #Sharpin
https://www.medrxiv.org/content/10.1101/2022.11.09.22281431v1
"Despite revolutions, sieges, World War I shelling, and World War II bombings, Paris still possesses a remarkable architectural unity. The city’s center looks much as it did in the late 19th century. But while the scars are not immediately visible, they are there, and the worst of them are self-inflicted: the product of a single hideous week in May 1871. This was the week that the Paris Commune died."
#InnateImmunity #MucosalImmunology #Covid19 #SarsCoV2 #Preprint #Immunology
"We designed a study to characterize the expression of interferon alpha-2 (IFNA2) and interferon beta-1 (IFNB1), both type-1 interferons (IFN-1), interferongamma (IFNG), a type-2 interferon (IFN-2), ISGs, and NF-κB response genes in the upper respiratory tract (URT) of patients with mild (outpatient) versus severe (hospitalized) COVID-19. Further, we characterized the weekly dynamics of these responses in the upper and lower respiratory tracts (LRTs) and blood of severe patients to evaluate for compartmental differences."
https://www.medrxiv.org/content/10.1101/2022.11.08.22281846v1
#Telomeres #Telomerase #tumorigenesis #Preprint from Charles Kinzig, Titia de Lange et al
"Here, we aimed to determine whether telomerase can add telomeric DNA to DSBs in human cells and how this process is regulated. The data indicate that telomerase can create a functional neotelomere at a Cas9-induced DSB that bears the TS sequence at one 3′ end. The frequency of neotelomere formation is increased upon overexpression of telomerase, suggesting that the low level of telomerase in most human cells minimizes these deleterious events. In addition, neotelomere formation is inhibited by ATR signaling at resected DSBs. We discuss these findings in the context of genome instability during tumorigenesis, where neotelomere formation by telomerase might end BFB cycles as originally proposed by McClintock."
"It was late in 1972 — a year in which the science of genetic engineering really began to sizzle — that two California researchers announced the unusually tidy transfer of genetic information from one bacterium to another with help from a specialized enzyme. It was a scientifically heralded result, but behind the hoopla was just one small catch. The information transferred enabled a common human disease bacterium, E. coli, to resist not just one antibiotic, but two.
“Alarm bells should have rung,” writes @matthewcobb, in his deeply researched and often deeply troubling history of gene science."
https://www.nytimes.com/2022/11/14/books/review/as-gods-matthew-cobb.html
The latest episode of the #EMBOPodcast is out today.
I spoke with Roberto di Lauro who's had a fascinating career at the NCI during the golden age of molecular biology there, in Naples - both at Federico II & running one of biology's mythical places, the Stazione Zoologica Anton Dohrn, and even served some time in the diplomatic core.
This was a fun talk about science, #SciencePolicy, #HistoryOfScience, #MolecularBiology, science in Italy and much more.
https://www.embo.org/podcasts/we-should-know-more-this-is-our-main-job/
"The controlled expression of one cellular feature -- the cilium -- was likely critical during early animal evolution. Two key transcription factors, RFX and FoxJ1, coordinate ciliogenesis in animals but are absent from the genomes of most other ciliated eukaryotes, raising the question of how the transcriptional regulation of ciliogenesis has evolved."
"In the hippocampus, the activation of microglia was associated with inhibited neurogenesis, which could explain impaired memory formation in patients. The activation of microglia appeared to be mediated by persistently elevated levels of a molecule called C-C motif chemokine 11 (CCL11). CCL11 has been associated with aging and with inhibition of neurogenesis."
https://www.nejm.org/doi/full/10.1056/NEJMcibr2210069?query=featured_home
"The Swiss Surrealist sculptor and painter Alberto Giacometti is to have a new museum in a former train station in Paris after fears the world’s largest collection of his work could be moved abroad.
The Giacometti Foundation will take up residence in the former Gare des Invalides, better known in postwar years as the former headquarters of Air France. Its opening is scheduled for 2026."
Animal models for long Covid, review at #PlosPathogens
"We review SARS-CoV-2 infection and disease manifestations in mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs). Specifically, the virology, pathology, immune responses, and multiorgan involvement are summarized. These models are rationally examined for their use in understanding the complexities of the multiorgan involvement during Long COVID and the potential for their use in screening therapeutics such as anti-inflammatory drugs, which are currently used for treating other diseases. The aim of this review is to highlight Long COVID preclinical animal models that could be used for Long COVID research and to screen for pharmacological interventions."
#Covid19 #LongCovid #Covid #SarsCoV2
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010741
"La llamada Oficina C —por la letra inicial de ciencia y congreso— es una iniciativa de la Cámara Baja y la Fundación Española para la Ciencia y la Tecnología (FECYT). El nuevo equipo, formado por ocho personas asesoradas por algunos de los mejores investigadores de España, recoge la evidencia científica sobre temas candentes y la sintetiza para los diputados. "
"Influential groups established close bonds with the Creation Research Institute in the United States and creationism found its way into textbooks in the mid-1980s. Cult leader Harun Yahya came to the fore during the following decade, leading a well-funded campaign to spread ‘intelligent design’ concepts at home and abroad. The situation further hardened in the early 2000s when the AKP won its first elections."
"To assess the nanoscale relationship between neuronal adjacency and connectivity, we evaluate the expansive set of C. elegans connectomes. We find that synaptic connectivity can be accurately modeled as a path-length-dependent process of neuronal adjacency and brain strata, offering strong support for Peters' rule as an organizational principle of C. elegans brain wiring."
"In both the case of SARS-CoV-2 and EBOV, a rush to judgment obscured the facts and led researchers and policymakers to make errant claims that wasted time and resources. Discerning the origins of COVID-19 is an important mission. It must be a mission that’s approached with care—false leads not only unfairly place blame on ethical research and researchers but also fail to advance public health so that we’re better prepared for the next pandemic. The following careful telling of events early on in the pandemic elucidates the facts—and the distortions."
A role for the STING pathway in nervous system regeneration.
"Here, we found that protein tyrosine phosphatase non-receptor type 2 (Ptpn2) inhibition combined with low-dose IFNγ enhances CNS axon regeneration by amplifying IFNγ-STAT1 signaling, with the cGAS-STING pathway as the functional downstream signaling. In the PNS, the IFNγ-cGAS-STING axis is coordinated by both neuronal and non-neuronal cells to support spontaneous axon regeneration."
https://www.cell.com/neuron/fulltext/S0896-6273(22)00961-8#.Y25_9yuiGgQ.twitter
I've worked on all of science, from B cells to T cells.
https://fellowsherpa.com