Notes

Recuperation trajectories of kelp woodland animals tend to be fast but spatially varying over the network involving mild sea guarded regions.
The NIH BRAIN Initiative is aimed at revolutionizing our understanding of the human brain. Here, we present a discussion of support for team research in investigative neuroscience at different stages and on various scales.In this issue of Neuron, Jordan and Keller (2020) explore subthreshold computations underlying predictive coding using whole-cell recordings in mouse visual cortex. Their findings suggest that layer 2/3, but not layer 5/6, neurons compute prediction errors by subtracting predicted and actual visual flow inputs generated by locomotion.Prager et al. demonstrate an opposite regulation of activity in striosomes and matrix of the striatum. By a D1-receptor-linked L-VGCC-dependent mechanism, dopamine release can extend upstates in matrix D1-expressing direct pathway projection neurons (dSPNs) but shorten them in striosomal dSPNs.Protein synthesis must be finely tuned in the developing nervous system as the final essential step of gene expression. This study investigates the architecture of ribosomes from the neocortex during neurogenesis, revealing Ebp1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest during start codon initiation and N-terminal peptide elongation, regulating ribosome occupancy of these codons. Membrane-targeting domains emerging from the 60S tunnel, which recruit SRP/Sec61 to the shared binding site, displace Ebp1. Ebp1 is particularly abundant in the early-born neural stem cell (NSC) lineage and regulates neuronal morphology. BLU-945 Ebp1 especially impacts the synthesis of membrane-targeted cell adhesion molecules (CAMs), measured by pulsed stable isotope labeling by amino acids in cell culture (pSILAC)/bioorthogonal noncanonical amino acid tagging (BONCAT) mass spectrometry (MS). Therefore, Ebp1 is a central component of protein synthesis, and the ribosome TE is a focal point of gene expression control in the molecular specification of neuronal morphology during development.Retinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for >30 mature types and several developmental intermediates. We used this dataset to engineer transgenic driver lines, enabling specific experimental access to a subset of RGC types. Expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit specific functional tuning. Finally, chemogenetic ablation of eomesa+ RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.Our brains at rest spontaneously replay recently acquired information, but how this process is orchestrated to avoid interference with ongoing cognition is an open question. Here we investigated whether replay coincided with spontaneous patterns of whole-brain activity. We found, in two separate datasets, that replay sequences were packaged into transient bursts occurring selectively during activation of the default mode network (DMN) and parietal alpha networks. These networks are believed to support inwardly oriented attention and inhibit bottom-up sensory processing and were characterized by widespread synchronized oscillations coupled to increases in high frequency power, mechanisms thought to coordinate information flow between disparate cortical areas. Our data reveal a tight correspondence between two widely studied phenomena in neural physiology and suggest that the DMN may coordinate replay bursts in a manner that minimizes interference with ongoing cognition.Recent studies have demonstrated immunologic dysfunction in severely ill coronavirus disease 2019 (COVID-19) patients. We use single-cell RNA sequencing (scRNA-seq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) from healthy (n = 3) and COVID-19 patients with moderate disease (n = 5), acute respiratory distress syndrome (ARDS, n = 6), or recovering from ARDS (n = 6). Our data reveal transcriptomic profiles indicative of defective antigen presentation and interferon (IFN) responsiveness in monocytes from ARDS patients, which contrasts with higher responsiveness to IFN signaling in lymphocytes. Furthermore, genes involved in cytotoxic activity are suppressed in both natural killer (NK) and CD8 T lymphocytes, and B cell activation is deficient, which is consistent with delayed viral clearance in severely ill COVID-19 patients. Our study demonstrates that COVID-19 patients with ARDS have a state of immune imbalance in which dysregulation of both innate and adaptive immune responses may be contributing to a more severe disease course.The major effect of allosteric HIV integrase (IN) inhibitors (ALLINIs) is observed during virion maturation, where ALLINI treatment interrupts IN-RNA interactions via drug-induced IN aggregation, leading to the formation of aberrant virions. To understand the structural changes that accompany drug-induced aggregation, we determined the soft matter properties of ALLINI-induced IN aggregates. Using small-angle neutron scattering, SEM, and rheology, we have discovered that the higher-order aggregates induced by ALLINIs have the characteristics of weak three-dimensional gels with a fractal-like character. Their formation is inhibited by the host factor LEDGF/p75, as well as ex vivo resistance substitutions. Mutagenesis and biophysical analyses reveal that homomeric carboxy-terminal domain interactions are required to achieve the branched-polymer nature of the ALLINI-induced aggregates. These studies provide key insight into the mechanisms of ALLINI action and resistance in the context of the crowded virion environment where ALLINIs exert their effect.
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