Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution
Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constra...
Source: eLife - September 2, 2020 Category: Biomedical Science Tags: Evolutionary Biology Microbiology and Infectious Disease Source Type: research

What do adversarial images tell us about human vision?
Deep convolutional neural networks (DCNNs) are frequently described as the best current models of human and primate vision. An obvious challenge to this claim is the existence ofadversarial images that fool DCNNs but are uninterpretable to humans. However, recent research has suggested that there may be similarities in how humans and DCNNs interpret these seemingly nonsense images. We reanalysed data from a high-profile paper and conducted five experiments controlling for different ways in which these images can be generated and selected. We show human-DCNN agreement is much weaker and more variable than previously reporte...
Source: eLife - September 2, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

< i > CD163 < /i > and < i > pAPN < /i > double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance
Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO ...
Source: eLife - September 2, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24h revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96h in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, i.e. Th17 and Th1Th17 subsets. Of note, HIV exposure created a...
Source: eLife - September 2, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

Ultra-high field imaging reveals increased whole brain connectivity underpins cognitive strategies that attenuate pain
We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at 7 tesla. Participants were asked to rate their pain after each trial. We related the trial-by-trial variability of the attenuation performance to the trial-by-trial functional connectivity strength change of brain data. Across all conditions, we found that a higher performance of pain attenuatio...
Source: eLife - September 2, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Activation of astrocytes in hippocampus decreases fear memory through adenosine A < sub > 1 < /sub > receptors
Astrocytes respond to and regulate neuronal activity, yet their role in mammalian behavior remains incompletely understood. Especially unclear is whether, and if so how, astrocyte activity regulates contextual fear memory, the dysregulation of which leads to pathological fear-related disorders. We generatedGFAP-ChR2-EYFP rats to allow the specific activation of astrocytes in vivo by optogenetics. We found that after memory acquisition within a temporal window, astrocyte activation disrupted memory consolidation and persistently decreased contextual but not cued fear memory accompanied by reduced fear-related anxiety behavi...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Does culture shape hunting behavior in bonobos?
New evidence that neighboring communities of bonobos hunt different prey species, despite extensive overlaps in where they live and hunt, is difficult to explain without invoking cultural factors. (Source: eLife)
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Evolutionary Biology Source Type: research

Behavioural diversity of bonobo prey preference as a potential cultural trait
The importance of cultural processes to behavioural diversity in our closest living relatives is central to revealing the evolutionary origins of human culture. However, the bonobo is often overlooked as a candidate model. Further, a prominent critique to many examples of proposed animal cultures is premature exclusion of environmental confounds known to shape behavioural phenotypes. We addressed these gaps by investigating variation in prey preference between neighbouring bonobo groups that associate and overlap space use. We find group preference for duiker or anomalure hunting otherwise unexplained by variation in spati...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Evolutionary Biology Source Type: research

KATANIN-dependent mechanical properties of the stigmatic cell wall mediate the pollen tube path in Arabidopsis
Successful fertilization in angiosperms depends on the proper trajectory of pollen tubes through the pistil tissues to reach the ovules. Pollen tubes first grow within the cell wall of the papilla cells, applying pressure to the cell. Mechanical forces are known to play a major role in plant cell shape by controlling the orientation of cortical microtubules (CMTs), which in turn mediate deposition of cellulose microfibrils (CMFs). Here, by combining imaging, genetic and chemical approaches, we show that isotropic reorientation of CMTs and CMFs in aged Col-0 andkatanin1-5 (ktn1-5) papilla cells is accompanied by a tendency ...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Plant Biology Source Type: research

Axonal mechanisms mediating γ-aminobutyric acid receptor type A (GABA-A) inhibition of striatal dopamine release
Axons of dopaminergic neurons innervate the striatum where they contribute to movement and reinforcement learning. Past work has shown that striatal GABA tonically inhibits dopamine release, but whether GABA-A receptors directly modulate transmission or act indirectly through circuit elements is unresolved. Here, we use whole-cell and perforated-patch recordings to test for GABA-A receptors on the main dopaminergic neuron axons and branching processes within the striatum of adult mice. Application of GABA depolarized axons, but also decreased the amplitude of axonal spikes, limited propagation and reduced striatal dopamine...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19
The PRC2 (Polycomb repressive complex 2) complex is a multi-component histone H3K27 methyltransferase, best known for silencingHox genes during embryonic development. The Polycomb-like proteins PHF1, MTF2 and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem (ES) cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3in vitro. However, some other studies suggest that PHF1 and PHF19 co-localize with the H3K27me3 mark, but not H3K36me3 in cells. Here, we provide further evidence that PHF1 co-localizes with H3t in testis, and its Tudor domain prefere...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research

Recurrent processes support a cascade of hierarchical decisions
Perception depends on a complex interplay between feedforward and recurrent processing. Yet, while the former has been extensively characterized, the computational organization of the latter remains largely unknown. Here, we use magneto-encephalography to localize, track and decode the feedforward and recurrent processes of reading, as elicited by letters and digits whose level of ambiguity was parametrically manipulated. We first confirm that a feedforward response propagates through the ventral and dorsal pathways within the first 200 ms. The subsequent activity is distributed across temporal, parietal and prefrontal cor...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala
The basolateral amygdala complex (BLA), extensively connected with both local amygdalar nuclei as well as long-range circuits, is involved in a diverse array of functional roles. Understanding the mechanisms of such functional diversity will be greatly informed by understanding the cell-type-specific landscape of the BLA. Here, beginning with single-cell RNA sequencing, we identified both discrete and graded continuous gene-expression differences within the mouse BLA. Viain situhybridization, we next mapped this discrete transcriptomic heterogeneity onto a sharp spatial border between the basal and lateral amygdala nuclei,...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Growing straight through walls
The pollen tube in a flowering plant grows in a direction that is influenced by the mechanical properties of the stigma papillae and the organization of structures called cortical microtubules inside these cells. (Source: eLife)
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Plant Biology Source Type: research

Structural basis for the reaction cycle of DASS dicarboxylate transporters
We report multiple cryo-EM and X-ray structures in four different states, inclu ding three hitherto unseen states, along with molecular dynamics simulations, of both a cotransporter and an exchanger. Comparison of these outward- and inward-facing structures reveal how the transport domain translates and rotates within the framework of the scaffold domain through the transport c ycle. Additionally, we propose that DASS transporters ensure substrate coupling by a charge-compensation mechanism, and by structural changes upon substrate release. (Source: eLife)
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research

Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact
Vitamin K epoxide reductase (VKOR) drives the vitamin K cycle, activating vitamin K-dependent blood clotting factors. VKOR is also the target of the widely used anticoagulant drug, warfarin. Despite VKOR ’s pivotal role in coagulation, its structure and active site remain poorly understood. In addition, VKOR variants can cause vitamin K-dependent clotting factor deficiency or alter warfarin response. Here, we used multiplexed, sequencing-based assays to measure the effects of 2,695 VKOR missense v ariants on abundance and 697 variants on activity in cultured human cells. The large-scale functional data, along with an...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Genetics and Genomics Source Type: research

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit
APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Cell Biology Source Type: research

Intra-species differences in population size shape life history and genome evolution
The evolutionary forces shaping life history divergence within species are largely unknown. Turquoise killifish display differences in lifespan among wild populations, representing an ideal natural experiment in evolution and diversification of life history. By combining genome sequencing and population genetics, we investigate the evolutionary forces shaping lifespan among wild turquoise killifish populations. We generate an improved reference genome assembly and identify genes under positive and purifying selection, as well as those evolving neutrally. Short-lived populations from the outer margin of the species range ha...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research

Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons
Parabrachial CGRP neurons receive diverse threat-related signals and contribute to multiple phases of adaptive threat responses in mice, with their inactivation attenuating both unconditioned behavioral responses to somatic pain and fear-memory formation. Because CGRPPBN neurons respond broadly to multi-modal threats, it remains unknown how these distinct adaptive processes are individually engaged. We show that while three partially separable subsets of CGRPPBN neurons broadly collateralize to their respective downstream partners, individual projections accomplish distinct functions: hypothalamic and extended amygdalar pr...
Source: eLife - August 28, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Neural signatures of α2-Adrenergic agonist-induced unconsciousness and awakening by antagonist
How the brain dynamics change during anesthetic-induced altered states of consciousness is not completely understood. The α2-adrenergic agonists are unique. They generate unconsciousness selectively through α2-adrenergic receptors and related circuits. We studied intracortical neuronal dynamics during transitions of loss of consciousness (LOC) with the α2-adrenergic agonist dexmedetomidine and return of consciousnes s (ROC) in a functionally interconnecting somatosensory and ventral premotor network in non-human primates. LOC, ROC and full task performance recovery were all associated with distinct neural...
Source: eLife - August 28, 2020 Category: Biomedical Science Tags: Medicine Neuroscience Source Type: research

A broad mutational target explains a fast rate of phenotypic evolution
The rapid evolution of a trait in a group of organisms can be explained by the sustained action of natural selection or by a high mutational variance, i.e. the propensity to change under spontaneous mutation. The causes for a high mutational variance are still elusive. In some cases, fast evolution depends on the high mutation rate of one or few loci with short tandem repeats. Here, we report on the fastest evolving cell fate among vulva precursor cells inCaenorhabditis nematodes, that of P3.p. We identify and validate causal mutations underlying P3.p's high mutational variance. We find that these positions do not present ...
Source: eLife - August 27, 2020 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research

Enteric glia as a source of neural progenitors in adult zebrafish
The presence and identity of neural progenitors in the enteric nervous system (ENS) of vertebrates is a matter of intense debate. Here we demonstrate that the non-neuronal ENS cell compartment of teleosts shares molecular and morphological characteristics with mammalian enteric glia but cannot be identified by the expression of canonical glia markers. However, unlike their mammalian counterparts, which are generally quiescent and do not undergo neuronal differentiation during homeostasis, we show that a relatively high proportion of zebrafish enteric glia proliferate under physiological conditions giving rise to progeny th...
Source: eLife - August 27, 2020 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research

A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lu...
Source: eLife - August 27, 2020 Category: Biomedical Science Tags: Cell Biology Plant Biology Source Type: research

Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase
Asymmetric astral microtubule organization drives the polarized orientation of theS. cerevisiaemitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featured in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sit...
Source: eLife - August 27, 2020 Category: Biomedical Science Tags: Cell Biology Source Type: research

An essential role for MEF2C in the cortical response to loss of sleep in mice
Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is req...
Source: eLife - August 27, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Cortical ROR β is required for layer 4 transcriptional identity and barrel integrity
Retinoic Acid-Related Orphan Receptor Beta (ROR β) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is large ly unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age in wildtype mice. Loss of RORβ delays excitatory input and disrupts gene expre...
Source: eLife - August 27, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

A missense in HSF2BP causing Primary Ovarian Insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with 3 cases of POI, we identified the candidate missense variant S167L inHSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss of function (knock-out) mouse model.Hsf2bpS167L/S167L females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Cell Biology Source Type: research

m6A RNA methylation impacts fate choices during skin morphogenesis
N6-methyladenosine is the most prominent RNA modification in mammals. Here we study mouse skin embryogenesis to tackle m6A ’s functions and physiological importance. We first landscape the m6A modifications on skin epithelial progenitor mRNAs. Contrasting within vivoribosomal profiling, we unearth a correlation between m6A-modification in coding sequences and enhanced translation, particularly of key morphogenetic signaling pathways. Tapping physiological relevance, we show that m6A loss profoundly alters these cues and perturbs cellular fate choices and tissue architecture in all skin lineages. By single-cell transc...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Developmental Biology Source Type: research

The nucleosome DNA entry-exit site is important for transcription termination and prevention of pervasive transcription
Compared to other stages in the RNA polymerase II transcription cycle, the role of chromatin in transcription termination is poorly understood. We performed a genetic screen inSaccharomyces cerevisiae to identify histone mutants that exhibit transcriptional readthrough of terminators. Amino acid substitutions identified by the screen map to the nucleosome DNA entry-exit site. The strongest H3 mutants revealed widespread genomic changes, including increased sense-strand transcription upstream and downstream of genes, increased antisense transcription overlapping gene bodies, and reduced nucleosome occupancy particularly at ...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Chromosomes and Gene Expression Source Type: research

Clusters of polymorphic transmembrane genes control resistance to schistosomes in snail vectors
Schistosomiasis is a debilitating parasitic disease infecting hundreds of millions of people. Schistosomes use aquatic snails as intermediate hosts. A promising avenue for disease control involves leveraging innate host mechanisms to reduce snail vectorial capacity. In a genome-wide association study ofBiomphalariaglabrata snails, we identify genomic region PTC2 which exhibits the largest known correlation with susceptibility to parasite infection (>15-fold effect). Using new genome assemblies with substantially higher contiguity than theBiomphalaria reference genome, we show that PTC2 haplotypes are exceptionally diver...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Epidemiology and Global Health Genetics and Genomics Source Type: research

Puromycin reactivity does not accurately localize translation at the subcellular level
Puromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes. Puromycin has been used in molecular biology research for decades as a translation inhibitor. The development of puromycin antibodies and derivatized puromycin analogs has enabled the quantification of active translation in bulk and single-cell assays. More recently,in vivo puromycylation assays have become popular tools for localizing translating ribosomes in cells. These assays often use elongation inhibitors to purportedly inhibit the release of puromycin-labeled nascent peptides ...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cell Biology Source Type: research

Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling
Arginine methyltransferase PRMT7 is associated with human breast cancer metastasis. Endosomal FAK signalling is critical for cancer cell migration. Here we identified the pivotal roles of PRMT7 in promoting endosomal FAK signalling activation during breast cancer metastasis. PRMT7 exerted its functions through binding to scaffold protein SHANK2 and catalyzing di-methylation of SHANK2 at R240. SHANK2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade, promoting in co-accumulation of dynamin2, talin, FAK, cortactin with SHANK2 on endosomes. In addition, SHANK2 R240 methylation activated endosomal F...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Cancer Biology Cell Biology Source Type: research

Cryo-EM analysis of PIP < sub > 2 < /sub > regulation in mammalian GIRK channels
G protein-gated inward rectifier potassium (GIRK) channels are regulated by G proteins and PIP2. Here using cryo-EM single particle analysis we describe the equilibrium ensemble of structures of neuronal GIRK2 as a function of the C8-PIP2 concentration. We find that PIP2 shifts the equilibrium between two distinguishable structures of neuronal GIRK (GIRK2), extended and docked, towards the docked form. In the docked form the cytoplasmic domain, to which Gβγ binds, becomes accessible to the cytoplasmic membrane surface where Gβγ resides. Furthermore, PIP2 binding reshapes the Gβγ binding sur...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research

Theoretical musings
There is more to theory in biology than replicating the results of experiments – the best theory papers help experimentalists to identify which of their results might be general and to plan a path through the maze of all possible future experiments. (Source: eLife)
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response
It is being increasingly appreciated that the immunomodulatory functions of PARP inhibitors (PARPi) underlie their clinical activities in variousBRCA-mutated tumors. PARPi possess both PARP1 inhibition and PARP1 trapping activities. The relative contribution of these two mechanisms toward PARPi-induced innate immune signaling, however, is poorly understood. We find that the presence of the PARP1 protein with uncompromised DNA-binding activities is required for PARPi-induced innate immune response. The activation of cGAS-STING signaling induced by various PARPi closely depends on their PARP1 trapping activities. Finally, we...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Cancer Biology Cell Biology Source Type: research

Elongation inhibitors do not prevent the release of puromycylated nascent polypeptide chains from ribosomes
Puromycin is an amino-acyl transfer RNA analog widely employed in studies of protein synthesis. Since puromycin is covalently incorporated into nascent polypeptide chains, anti-puromycin immunofluorescence enables visualization of nascent protein synthesis. A common assumption in studies of local messenger RNA translation is that the anti-puromycin staining of puromycylated nascent polypeptides in fixed cells accurately reports on their original site of translation, particularly when ribosomes are stalled with elongation inhibitors prior to puromycin treatment. However, when we attempted to implement a proximity ligation a...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cell Biology Source Type: research

Anatomy of nerve fiber bundles at micrometer-resolution in the vervet monkey visual system
Although the primate visual system has been extensively studied, detailed spatial organization of white matter fiber tracts carrying visual information between areas has not been fully established. This is mainly due to the large gap between tracer studies and diffusion-weighted MRI studies, which focus on specific axonal connections and macroscale organization of fiber tracts, respectively. Here we used 3D polarization light imaging (3D-PLI), which enables direct visualization of fiber tracts at micrometer resolution, to identify and visualize fiber tracts of the visual system, such as stratum sagittale, inferior longitud...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

The transcriptional elongation rate regulates alternative polyadenylation in yeast
Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3' mRNA isoforms for most genes. This altered poly(A) pattern is extremely similar to that observed in cells containing Pol II derivatives with slow elongation rates. Conversely, cells containing derivatives with fast elongation rates show a subtle downstream shift in poly(A) sites. Polyadenylation patterns of many genes are sensitive to both fast and slow elongation rates, and a global shift of poly(A) utilization is strongly linked to increased purin...
Source: eLife - August 26, 2020 Category: Biomedical Science Tags: Chromosomes and Gene Expression Source Type: research

Ageing compromises mouse thymus function and remodels epithelial cell differentiation
Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This is first observed in the thymus, the primary lymphoid organ that generates and selects T cells. However, the molecular and cellular mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing, we find that progenitor cells are the principal targets of ageing, wh...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Immunology and Inflammation Source Type: research

Transformation of a temporal speech cue to a spatial neural code in human auditory cortex
In speech, listeners extract continuously-varying spectrotemporal cues from the acoustic signal to perceive discrete phonetic categories. Spectral cues are spatially encoded in the amplitude of responses in phonetically-tuned neural populations in auditory cortex. It remains unknown whether similar neurophysiological mechanisms encode temporal cues like voice-onset time (VOT), which distinguishes sounds like /b/-/p/. We used direct brain recordings in humans to investigate the neural encoding of temporal speech cues with a VOT continuum from /ba/ to /pa/. We found that distinct neural populations respond preferentially to ...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Sensory experience during early sensitive periods shapes cross-modal temporal biases
Typical human perception features stable biases such as perceiving visual events as later than synchronous auditory events. The origin of such perceptual biases is unknown. To investigate the role of early sensory experience, we tested whether a congenital, transient loss of pattern vision, caused by bilateral dense cataracts, has sustained effects on audio-visual and tactile-visual temporal biases and resolution. Participants judged the temporal order of successively presented, spatially separated events within and across modalities. Individuals with reversed congenital cataracts showed a bias towards perceiving visual st...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Polyploidy in the adult < i > Drosophila < /i > brain
Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal ’s lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become po lyploid in the adultDrosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region. Inducing...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Developmental Biology Source Type: research

Nongenetic inheritance and multigenerational plasticity in the nematode < i > C. elegans < /i >
A rapidly growing body of literature in several organisms suggests that environmentally-induced adaptive changes in phenotype can be transmitted across multiple generations. Although within-generation plasticity has been well documented, multigenerational plasticity represents a significant departure from conventional evolutionary thought. Studies ofC. elegans have been particularly influential because this species exhibits extensive phenotypic plasticity, it is often essentially isogenic, and it has well-documented molecular and cellular mechanisms through which nongenetic inheritance occurs. However, while experimentalis...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research

A novel acidification mechanism for greatly enhanced oxygen supply to the fish retina
Previously, we showed that the evolution of high acuity vision in fishes was directly associated with their unique pH-sensitive hemoglobins that allow O2 to be delivered to the retina at PO2s more than ten-fold that of arterial blood (Damsgaard et al., 2019). Here, we show strong evidence that vacuolar-type H+-ATPase and plasma-accessible carbonic anhydrase in the vascular structure supplying the retina act together to acidify the red blood cell leading to O2 secretion. In vivo data indicate that this pathway primarily affects the oxygenation of the inner retina involved in signal processing and transduction, and that the ...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Evolutionary Biology Neuroscience Source Type: research

A transient role of the ciliary gene < i > Inpp5e < /i > in controlling direct versus indirect neurogenesis in cortical development
During the development of the cerebral cortex, neurons are generated directly from radial glial cells or indirectly via basal progenitors. The balance between these division modes determines the number and types of neurons formed in the cortex thereby affecting cortical functioning. Here, we investigate the role of primary cilia in controlling the decision between forming neurons directly or indirectly. We show that a mutation in the ciliary geneInpp5e leads to a transient increase in direct neurogenesis and subsequently to an overproduction of layer V neurons in newborn mice. Loss ofInpp5e also affects ciliary structure c...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Developmental Biology Source Type: research

A molecular dual carriageway
In order to enter a cell, an ammonium ion must first dissociate to form an ammonia molecule and a hydrogen ion (a proton), which then pass through the cell membrane separately and recombine inside. (Source: eLife)
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Source Type: research

Poultry farmer response to disease outbreaks in smallholder farming systems in southern Vietnam
Avian influenza outbreaks have been occurring on smallholder poultry farms in Asia for two decades. Farmer responses to these outbreaks can slow down or accelerate virus transmission. We used a longitudinal survey of 53 small-scale chicken farms in southern Vietnam to investigate the impact of outbreaks with disease-induced mortality on harvest rate, vaccination, and disinfection behaviors. We found that in small broiler flocks ( ≤16 birds/flock) the estimated probability of harvest was 56% higher when an outbreak occurred, and 214% higher if an outbreak with sudden deaths occurred in the same month. Vaccination and dis...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Epidemiology and Global Health Microbiology and Infectious Disease Source Type: research

Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer
Breast cancer stem cells (BCSCs) contribute to intra-tumoral heterogeneity and therapeutic resistance. However, the binary concept of universal BCSCs co-existing with bulk tumor cells is over-simplified. Through single-cell RNA-sequencing, we found that Neu, PyMT and BRCA1-null mammary tumors each corresponded to a spectrum of minimally overlapping cell differentiation states without a universal BCSC population. Instead, our analyses revealed that these tumors contained distinct lineage-specific tumor propagating cells (TPCs) and this is reflective of the self-sustaining capabilities of lineage-specific stem/progenitor cel...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Cancer Biology Genetics and Genomics Source Type: research

Atomic structure of a mitochondrial complex I intermediate from vascular plants
Respiration, an essential metabolic process, provides cells with chemical energy. In eukaryotes, respiration occurs via the mitochondrial electron transport chain (mETC) composed of several large membrane-protein complexes. Complex I (CI) is the main entry point for electrons into the mETC. For plants, limited availability of mitochondrial material has curbed detailed biochemical and structural studies of their mETC. Here, we present the cryoEM structure of the known CI assembly intermediate CI* fromVigna radiata at 3.9 Å resolution. CI* contains CI’s NADH-binding and CoQ-binding modules, the proximal-pumping m...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Structural Biology and Molecular Biophysics Source Type: research

Social interactions drive efficient foraging and income equality in groups of fish
The social interactions underlying group foraging and their benefits have been mostly studied using mechanistic models replicating qualitative features of group behavior, and focused on a single resource or a few clustered ones. Here, we tracked groups of freely foraging adult zebrafish with spatially dispersed food items and found that fish perform stereotypical maneuvers when consuming food, which attract neighboring fish. We then present a mathematical model, based oninferred functional interactions between fish, which accurately describes individual and group foraging of real fish. We show that these interactions allow...
Source: eLife - August 25, 2020 Category: Biomedical Science Tags: Computational and Systems Biology Physics of Living Systems Source Type: research