Using single nucleus transcriptomics, the authors showed that there are many different molecularly distinct cell types in the human cortex, and, surprisingly, that these types are largely conserved with mouse despite about 75 million years of evolution. At the same time, thousands of genes are expressed in different cells in human compared to mouse. Many of these genes are important for the function of neurons, including how they connect to other neurons and how they respond to drugs that are used to treat neuropsychiatric disorders.
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The authors have previously found that activation of "necroptosis" is accompanied by the production of a bunch of cytokines and chemokines. What's been a mystery is how a dying cell can pull this off. This paper finds is that necroptotic cells are actually able to continue translating protein even after their cell membranes have burst. They do this by keeping the endoplasmic reticulum intact; these necroptotic cell "corpses" are thereby able to keep translating messenger RNA for several hours after they are apparently "dead".
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Polycomb-based gene silencing is a central chromatin-based mechanism for shutting off genes during cell fate decisions in development. The authors looked at the functions of regulatory elements controlling a developmental gene for wings in Drosophila, and how Polycomb controls its expression. They found that Polycomb works to activate this gene, which had been suspected but not confirmed from other studies.
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This publication made a key discovery about the structural and functional characteristics of T cells that cross-recognize HLA-DQ8 and HLA-DQ8 transdimer in complex with epitopes derived from important islet antigens. It also uncovered a molecular and functional paradigm whereby disease risk may be altered primarily by increased T cell promiscuity driven by disease-predisposing HLAIIs. The reported mechanism is distinct from selective presentation of autoimmune peptides or altered T cell repertoires by HLAIIs as the primary drivers of autoimmune pathology.
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The authors studied different new mouse models that have mitochondrial dysfunction only in specific groups of neurons. Using a combination of molecular, genetic, and physiological approaches, they have identified that glutamatergic and GABAergic neurons are the ones involved in the progression of the disease. In particular, glutamatergic neurons in the brainstem are responsible for the motor and respiratory alterations, while GABAergic neurons in the basal ganglia lead to severe epilepsy.
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How did the first cells on Earth arise? In a minimal cell, a membrane separates proteins and RNA from the surrounding aqueous environment. Cell-like membranes spontaneously assemble from simple prebiotic surfactants called fatty acids. However, fatty acid membranes are unstable in solutions containing salts that were likely present in environments of the early Earth. We find that amino acids, the…
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West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death.…
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RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. The authors used a systems biology approach to define the contributions of each RLR in the innate immune response to WNV.
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If even a single chromosome is unattached or incorrectly attached, an enzyme, Mps1, initiates checkpoint signaling by binding to and modifying kinetochores, the large protein complexes that connect chromosomes to microtubules. The authors identified conditions that promote Mps1 release from native kinetochore particles isolated from yeast. Their findings suggest how the checkpoint “wait” signals might be turned off when kinetochores bind microtubules.
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The authors merged an old technology, anti-idiotypes, showing that it could be paired with newer approaches to develop vaccine candidates focused on inducing specific types of protective antibodies. They also found evidence that suggested that one of the reasons why broadly neutralizing antibodies similar to b12 are not induced by infection or vaccination is that this lineage is cross-reactive with self-antigens and subjected to tolerance mechanisms employed to prevent autoimmunity.
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