The development of active binocular vision under normal and alternate rearing conditions
We present a computational model for the learning and self-calibration of active binocular vision based on the Active Efficient Coding framework, an extension of classic efficient coding ideas to active perception. Under normal rearing conditions with naturalistic input, the model develops disparity tuned neurons and precise vergence control, allowing it to correctly interpret random dot stereograms. Under altered rearing conditions modeled after neurophysiological experiments, the model qualitatively reproduces key experimental findings on changes in binocularity and disparity tuning. Furthermore, the model makes testable...
Source: eLife - August 17, 2021 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research
A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance
Source: eLife - August 17, 2021 Category: Biomedical Science Tags: Epidemiology and Global Health Genetics and Genomics Source Type: research
HIF1 α is required for NK cell metabolic adaptation during virus infection
Natural killer (NK) cells are essential for early protection against virus infection, and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia inducible factor-1 α (HIF-1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infectionin vivo. HIF-1 α -deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF-1α KO NK cells however, their numbers were significantly reduced. Loss of HIF-1 α did not affect NK cell proliferation duringin vivo infection andin vitro cyt...
Source: eLife - August 16, 2021 Category: Biomedical Science Tags: Immunology and Inflammation Source Type: research
Single-cell RNA analysis identifies pre-migratory neural crest cells expressing markers of differentiated derivatives
The neural crest is a migratory population of stem-like cells that contribute to multiple traits including the bones of the skull, peripheral nervous system, and pigment. How neural crest cells differentiate into diverse cell types is a fundamental question in the study of vertebrate biology. Here, we use single-cell RNA sequencing to characterize transcriptional changes associated with neural crest cell development in the zebrafish trunk during the early stages of migration. We show that neural crest cells are transcriptionally diverse and identify pre-migratory populations already expressing genes associated with differe...
Source: eLife - August 16, 2021 Category: Biomedical Science Tags: Developmental Biology Source Type: research
A CTP-dependent gating mechanism enables ParB spreading on DNA
Proper chromosome segregation is essential in all living organisms. The ParA-ParB-parS system is widely employed for chromosome segregation in bacteria. Previously, we showed thatCaulobacter crescentus ParB requires cytidine triphosphate to escape the nucleation siteparS and spread by sliding to the neighboring DNA (Jalal et al., 2020). Here, we provide the structural basis for this transition from nucleation to spreading by solving co-crystal structures of a C-terminal domain truncatedC. crescentus ParB withparS and with a CTP analog. Nucleating ParB is an open clamp, in whichparS is captured at the DNA-binding domain (th...
Source: eLife - August 16, 2021 Category: Biomedical Science Tags: Chromosomes and Gene Expression Source Type: research
Spinal lumbar dI2 interneurons contribute to stability of bipedal stepping
We report that lumbar dI2 spinal interneurons in chicks receive synaptic input from afferents and premotor neurons. These interneurons innervate contralateral premotor networks in the lumbar and brachial spinal cord, and their ascending projections innervate the cerebellum. These findings suggest that dI2 neurons function as interneurons in local lumbar circuits, are involved in lumbo-brachial coupling, and that part of them deliver peripheral and intraspinal feedback to the cerebellum. Silencing of dI2 neurons leads to destabilized stepping in P8 hatchlings, with occasional collapses, variable step profiles and a wide-bas...
Source: eLife - August 16, 2021 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research
Spatially patterned excitatory neuron subtypes and projections of the claustrum
The claustrum is a functionally and structurally complex brain region, whose very spatial extent remains debated. Histochemical-based approaches typically treat the claustrum as a relatively narrow anatomical region that primarily projects to the neocortex, whereas circuit-based approaches can suggest a broader claustrum region containing projections to the neocortex and other regions. Here, in the mouse, we took a bottom-up and cell-type-specific approach to complement and possibly unite these seemingly disparate conclusions. Using single-cell RNA-sequencing, we found that the claustrum comprises two excitatory neuron sub...
Source: eLife - August 16, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Sustained expression of < i > unc-4 < /i > homeobox gene and < i > unc-37/Groucho < /i > in postmitotic neurons specifies the spatial organization of the cholinergic synapses in < i > C. elegans < /i >
Neuronal cell fate determinants establish the identities of neurons by controlling gene expression to regulate neuronal morphology and synaptic connectivity. However, it is not understood if neuronal cell fate determinants have postmitotic functions in synapse pattern formation. Here we identify a novel role for UNC-4 homeobox protein and its corepressor UNC-37/Groucho, in tiled synaptic patterning of the cholinergic motor neurons inCaenorhabditis elegans. We show thatunc-4 is not required during neurogenesis but is required in the postmitotic neurons for proper synapse patterning. In contrast,unc-37 is required in both de...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research
Widespread variation in heat tolerance and symbiont load are associated with growth tradeoffs in the coral < i > Acropora hyacinthus < /i > in Palau
Climate change is dramatically changing ecosystem composition and productivity, leading scientists to consider the best approaches to map natural resistance and foster ecosystem resilience in the face of these changes. Here we present results from a large-scale experimental assessment of coral bleaching resistance, a critical trait for coral population persistence as oceans warm, in 221 colonies of the coralAcropora hyacinthus across 37 reefs in Palau. We find that bleaching resistant individuals inhabit most reefs but are found more often in warmer microhabitats. Our survey also found wide variation in symbiont concentrat...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Ecology Source Type: research
Scaled, high fidelity electrophysiological, morphological, and transcriptomic cell characterization
The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for the combined electrophysiological, morphological, and transcriptomic characterization of individual neurons. To generate Patch-seq datasets at scale, we identified and refined key factors that contribute to the efficient collection of high-quality data. We developed patch-clamp electrophysiology software with analysis functions specifically designed to automate acquisition with online quality control. We recognized the importance of extracting the nucleus for transcriptomic success and maximizing membrane integrity during nucleus ex...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Genetics and Genomics Neuroscience Source Type: research
Intracellular functions and motile properties of bi-directional kinesin-5 Cin8 are regulated by neck linker docking
In this study, we analyzed intracellular functions and motile properties of neck-linker (NL) variants of the bi-directionalS. cerevisiae kinesin-5 motor, Cin8. We also examined – by modeling – the configuration of H-bonds during NL docking. Decreasing the number of stabilizing H-bonds resulted in partially functional variants, as long as a conserved backbone H-bond at the N-latch position (proposed to stabilize the docked conformation of the NL) remained intact. Elimin ation of this conserved H-bond resulted in production of a non-functional Cin8 variant. Surprisingly, additional H-bond stabilization of the N-latch pos...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Cell Biology Source Type: research
Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels as compared with therapy based on protease inhibitors
BACKGROUND: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress HIV replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). (Source: eLife)
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Medicine Microbiology and Infectious Disease Source Type: research
Imaging cytoplasmic lipid droplets < i > in vivo < /i > with fluorescent perilipin 2 and perilipin 3 knock-in zebrafish
Cytoplasmic lipid droplets are highly dynamic storage organelles that are critical for cellular lipid homeostasis. While the molecular details of lipid droplet dynamics are a very active area of investigation, this work has been primarily performed in cultured cells. Taking advantage of the powerful transgenic andin vivoimaging opportunities available in zebrafish, we built a suite of tools to study lipid droplets in real-time from the subcellular to the whole organism level. Fluorescently tagging the lipid-droplet-associated proteins, perilipin 2 and perilipin 3, in the endogenous loci permits visualization of lipid dropl...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Cell Biology Developmental Biology Source Type: research
Patterns of within-host genetic diversity in SARS-CoV-2
Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed stron...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Epidemiology and Global Health Genetics and Genomics Source Type: research
Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation
The Rad53 DNA checkpoint protein kinase plays multiple roles in the budding yeast cell response to DNA replication stress. Key amongst these is its enigmatic role in safeguarding DNA replication forks. Using DNA replication reactions reconstituted with purified proteins, we show Rad53 phosphorylation of Sld3/7 or Dbf4-dependent kinase blocks replication initiation whilst phosphorylation of Mrc1 or Mcm10 slows elongation. Mrc1 phosphorylation is necessary and sufficient to slow replication forks in complete reactions; Mcm10 phosphorylation can also slow replication forks, but only in the absence of unphosphorylated Mrc1. Mr...
Source: eLife - August 13, 2021 Category: Biomedical Science Tags: Chromosomes and Gene Expression Source Type: research