Catálogo de publicaciones - revistas

<jats:p> In this work, we find that CD8 <jats:sup>+</jats:sup> T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49 <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8 <jats:sup>+</jats:sup> T cells efficiently eliminated pathogenic gliadin-specific CD4 <jats:sup>+</jats:sup> T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells, but not CD4 <jats:sup>+</jats:sup> regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49 <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8 <jats:sup>+</jats:sup> T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases. </jats:p>

<jats:p> Alvarez-Buylla and colleagues provide an alternative interpretation of some of the data included in our manuscript and question whether well-validated markers of adult hippocampal neurogenesis (AHN) are related to this phenomenon in our study. In Terreros-Roncal <jats:italic>et al</jats:italic> ., reconstruction of the main stages of human AHN revealed its enhanced vulnerability to neurodegeneration. Here, we clarify ambiguities raised by these authors. </jats:p>

<jats:p> Terreros-Roncal <jats:italic>et al</jats:italic> . investigated the impacts of human neurodegeneration on immunostainings assumed to be associated with neurogenesis. However, the study provides no evidence that putative proliferating cells are linked to neurogenesis, that multipolar nestin <jats:sup>+</jats:sup> astrocytes are progenitors, or that mature-looking doublecortin <jats:sup>+</jats:sup> neurons are adult-born. Their histology-marker expression differs from what is observed in species where adult hippocampal neurogenesis is well documented. </jats:p>

<jats:p>Gut bacteria influence brain functions and metabolism. We investigated whether this influence can be mediated by direct sensing of bacterial cell wall components by brain neurons. In mice, we found that bacterial peptidoglycan plays a major role in mediating gut-brain communication via the Nod2 receptor. Peptidoglycan-derived muropeptides reach the brain and alter the activity of a subset of brain neurons that express Nod2. Activation of Nod2 in hypothalamic inhibitory neurons is essential for proper appetite and body temperature control, primarily in females. This study identifies a microbe-sensing mechanism that regulates feeding behavior and host metabolism.</jats:p>

<jats:p>Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) remain without effective therapies. The mechanistic target of rapamycin complex 1 (mTORC1) pathway is a potential therapeutic target, but conflicting interpretations have been proposed for how mTORC1 controls lipid homeostasis. We show that selective inhibition of mTORC1 signaling in mice, through deletion of the RagC/D guanosine triphosphatase–activating protein folliculin (FLCN), promotes activation of transcription factor E3 (TFE3) in the liver without affecting other mTORC1 targets and protects against NAFLD and NASH. Disease protection is mediated by TFE3, which both induces lipid consumption and suppresses anabolic lipogenesis. TFE3 inhibits lipogenesis by suppressing proteolytic processing and activation of sterol regulatory element–binding protein-1c (SREBP-1c) and by interacting with SREBP-1c on chromatin. Our data reconcile previously conflicting studies and identify selective inhibition of mTORC1 as a potential approach to treat NASH and NAFLD.</jats:p>

<jats:p>A new federal agency—approved last month by the United States Congress—is already off to a rocky start. The Advanced Research Projects Agency for Health (ARPA-H), proposed by President Biden in 2021, aims to tackle the most intractable biomedical problems by funding innovative, high-risk, high-reward research and swiftly turning discoveries into treatments and cures. But Congress gave the agency a much smaller budget than sought by the administration—$ 1 billion over 3 years, a fraction of the $6.5 billion requested. And as happens whenever there is new money and a new federal agency, a political scrum has erupted over who should control ARPA-H. It is now expected to answer to both the National Institutes of Health (NIH) and the Department of Health and Human Services (HHS). If it is to deliver on its mission, ARPA-H needs to be an autonomous entity that approaches biomedical research in a way never done before by the federal government. The stakes are high: If ARPA-H fails to produce new clinical advances relatively quickly, it will erode trust in US science. It’s time for clear thinking and action about what it will take to make ARPA-H successful.</jats:p>

<jats:p>Pandemic propels international efforts to understand incidence of rare side effects</jats:p>

<jats:p>Campaign probes for earliest signs of oxygen-producing life</jats:p>

<jats:p>Efficiency jump in key component raises hopes for storing renewable energy as heat</jats:p>