A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study

International audienc

PlexinA4-Semaphorin3A mediated crosstalk between main cortical interneuron classes is required for superficial interneurons lamination

SummaryIn the mammalian cerebral cortex, the developmental events governing the allocation of different classes of inhibitory interneurons (INs) into distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 (PLXNA4) is upregulated in serotonin receptor 3a-expressing (HTR3A+) cortical INs (hINs) as they invade the cortical plate and that it regulates their laminar allocation to superficial cortical layers. We find that the PLXNA4 ligand Semaphorin3A (SEMA3A) acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that SEMA3A specifically controls their laminar positioning through PLXNA4. We identify that deep layer INs constitute a major source of SEMA3A in the developing cortex and demonstrate that cell-type specific genetic deletion of SEMA3A in these INs specifically affects the laminar allocation of hINs. These data demonstrate that in the neocortex, deep layer INs control the laminar allocation of hINs into superficial layers.</jats:p

PlexinA4-Semaphorin3A-mediated crosstalk between main cortical interneuron classes is required for superficial interneuron lamination

In the mammalian cerebral cortex, the developmental events governing allocation of different classes of inhibitory interneurons (INs) to distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 (PLXNA4) is upregulated in serotonin receptor 3a-expressing (HTR3A+) cortical INs (hINs) as they invade the cortical plate, and that it regulates their laminar allocation to superficial cortical layers. We find that the PLXNA4 ligand Semaphorin3A (SEMA3A) acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that SEMA3A specifically controls their laminar positioning through PLXNA4. We identify deep-layer INs as a major source of SEMA3A in the developing cortex and demonstrate that targeted genetic deletion of Sema3a in these INs specifically affects laminar allocation of hINs. These data show that, in the neocortex, deep-layer INs control laminar allocation of hINs into superficial layers

Study of Blood Biomarkers in Athletes with Lower Gastrointestinal Symptoms After an Ultra-Trail Race

Background/Objectives: To investigate the value of intestinal fatty acid-binding protein (I-FABP), D-Lactate, interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), electrolytes and creatinine in athletes with lower gastrointestinal symptoms in a cohort of ultra-trailers. Methods: This is a prospective study set in the ultra-trail of Puy Mary Aurillac, a 105 km race. Athletes included were given two questionnaires to collect demographic data and clinical signs related to the race. Blood samples were also collected before and 1 h after the race. Biomarker results were interpreted according to the occurrence of exercise-induced lower gastrointestinal symptoms, and whether the race was completed or forfeited. Results: Of the 76 runners included, 35 (45.5%) presented lower gastrointestinal symptoms. Runners that presented these symptoms had significantly higher IL-10 concentrations (8.7 pg/mL (interquartile range (IQR): 4.2&ndash;1.6)) when compared to runners without symptoms (4.8 pg/mL (IQR: 2.4&ndash;9)) (p = 0.01). The pre/post-race amplitude of IL-1Ra variation was greater in the group of runners with lower gastrointestinal symptoms (median: +231% (IQR: 169&ndash;551)) compared to runners without symptoms (median: +172% (IQR: 91&ndash;393)) (p = 0.04). Finally, the 13 (16.9%) runners who forfeited the race displayed lower AST (p &lt; 0.001), LDH (p = 0.002) and IL-6 (p = 0.002) concentrations, compared to runners who finished the race. These lower concentrations were independent from running time. Conclusions: IL-10 and IL-1Ra could be associated with the occurrence of lower gastrointestinal symptoms

MiR-137 and miR-122, two outer subventricular zone-enriched non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation

AbstractCortical expansion in the primate brain relies on the presence and the spatial enlargement of multiple germinal zones during development and on a prolonged developmental period. In contrast to other mammals, which have two cortical germinal zones, the ventricular zone (VZ) and subventricular zone (SVZ), gyrencephalic species display an additional germinal zone, the outer subventricular zone (OSVZ), which role is to increase the number and types of neurons generated during corticogenesis. How the OSVZ emerged during evolution is poorly understood but recent studies suggest a role for non-coding RNAs, which allow tight regulations of transcriptional programs in time and space during development (Dehay et al. 2015; Arcila et al., 2014). Here, usingin vivofunctional genetics, single-cell RNA sequencing, live imaging and electrophysiology to assess progenitor and neuronal properties in mice, we identify two ferret and human OSVZ-enriched microRNAs (miR), miR-137 and miR-122, which regulate key cellular features associated with cortical expansion. MiR-137 promotes basal progenitor self-replication and superficial layer neuron fate, while miR-122 slows down neuronal differentiation pace. Together, these findings support a cell-type specific role for miR-mediated transcriptional regulation in cortical expansion.</jats:p

Transcriptomic and anatomic parcellation of 5-HT3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing

Cortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify three main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons largely confined to the cortical white matter. These MEIS2-expressing interneurons appear to originate from a restricted region located at the embryonic pallial-subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled