Quantifying the relationship between SARS-CoV-2 viral load and infectiousness
The relationship between SARS-CoV-2 viral load and infectiousness is poorly known. Using data from a cohort of cases and high-risk contacts, we reconstructed viral load at the time of contact and inferred the probability of infection. The effect of viral load was larger in household contacts than in non-household contacts, with a transmission probability as large as 48% when the viral load was greater than 1010 copies per mL. The transmission probability peaked at symptom onset, with a mean probability of transmission of 29%, with large individual variations. The model also projects the effects of variants on disease trans...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

A parameter-free statistical test for neuronal responsiveness
Neurophysiological studies depend on a reliable quantification of whether and when a neuron responds to stimulation. Simple methods to determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based methods require fitting and hyperparameter tuning. These parameter choices can change the results, which invites bad statistical practice and reduces the replicability. New recording techniques that yield increasingly large numbers of cells would benefit from a test for cell-inclusion that requires no manual curation. Here, we present the parameter-free ZETA-test, which outper...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research

Characterization and prediction of clinical pathways of vulnerability to psychosis through graph signal processing
Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Network analysis techniques have emerged as alternative approaches that could help shed light on the complex dynamics of early psychopathology. The present study attempts to address the two main limitations that have in our opinion hindered the application of network approaches in the ...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Medicine Source Type: research

TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis
TRPM7 contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in CNS neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dyn...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Cell Biology Neuroscience Source Type: research

Convergent and divergent brain structural and functional abnormalities associated with developmental dyslexia
Brain abnormalities in the reading network have been repeatedly reported in individuals with developmental dyslexia (DD); however, it is still not totally understood where the structural and functional abnormalities are consistent/inconsistent across languages. In the current multimodal meta-analysis, we found convergent structural and functional alterations in the left superior temporal gyrus across languages, suggesting a neural signature of DD. We found greater reduction in grey matter volume and brain activation in the left inferior frontal gyrus in morpho-syllabic languages (e.g. Chinese) than in alphabetic languages,...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research

Human embryo polarization requires PLC signaling to mediate trophectoderm specification
Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step p...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Cell Biology Developmental Biology Source Type: research

Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
Keratinocytes, the predominant cell type of the epidermis, migrate to reinstate the epithelial barrier during wound healing. Mechanical cues are known to regulate keratinocyte re-epithelialization and wound healing however, the underlying molecular transducers and biophysical mechanisms remain elusive. Here, we show through molecular, cellular and organismal studies that the mechanically-activated ion channel PIEZO1 regulates keratinocyte migration and wound healing. Epidermal-specificPiezo1 knockout mice exhibited faster wound closure while gain-of-function mice displayed slower wound closure compared to littermate contro...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Cell Biology Structural Biology and Molecular Biophysics Source Type: research

ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
CNS neurons have no sensory function, protected by the skull. For this reason, brain neuromodulation by ultrasound were either done at a high intensity or through auditory nerves. We demonstrate in this study CNS neurons react to ultrasound stimulation at an intensity (5 mW/cm2) far lower than typical therapeutic ultrasound (>30 mW/cm2). Using micropipette ultrasound in calcium imaging, we show ASIC1a channels play a role in the reactions of CNS neurons to ultrasound, pointing to the molecular basis for direct ultrasound neuromodulation at low intensity. Furthermore, we also show evidence of neurogenesis with the same u...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research

Linking spatial self-organization to community assembly and biodiversity
Temporal shifts to drier climates impose environmental stresses on plant communities that may result in community reassembly and threatened ecosystem services, but also may trigger self-organization in spatial patterns of biota and resources, which act to relax these stresses. The complex relationships between these counteracting processes - community reassembly and spatial self-organization - have hardly been studied. Using a spatio-temporal model of dryland plant communities and a trait-based approach, we study the response of such communities to increasing water-deficit stress. We first show that spatial patterning acts...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Ecology Source Type: research

Hippocampal replay of experience at real-world speeds
Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain ‘replay’ of spatial trajectories at ∼20x the movement speed of the animal. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload
Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band.MYPN gene mutations are causative for dilated (DCM), hypertrophic and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a n...
Source: eLife - September 24, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Source Type: research

A promising platform for predicting toxicity
Organ-on-chip approaches could help researchers to better predict the toxicity of cancer immunotherapy drugs. (Source: eLife)
Source: eLife - September 24, 2021 Category: Biomedical Science Tags: Cancer Biology Medicine Source Type: research

Creating SPACE to evolve academic assessment
Universities and research institutions have to assess individuals when making decisions about hiring, promotion and tenure, but there are concerns that such assessments are overly reliant on metrics and proxy measures of research quality that overlook important factors such as academic rigor, data sharing and mentoring. These concerns have led to calls for universities and institutions to reform the methods they use to assess research and researchers. Here we present a new tool called SPACE that has been designed to help universities and institutions implement such reforms. The tool focuses on five core capabilities and ca...
Source: eLife - September 23, 2021 Category: Biomedical Science Source Type: research

Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size
The gut is the primary interface between an animal and food, but how it adapts to qualitative dietary variation is poorly defined. We find that theDrosophilamidgut plastically resizes following changes in dietary composition. A panel of nutrients collectively promote gut growth, which sugar opposes. Diet influences absolute and relative levels of enterocyte loss and stem cell proliferation, which together determine cell numbers. Diet also influences enterocyte size. A high sugar diet inhibits translation and uncouples ISC proliferation from expression of niche-derived signals but, surprisingly, rescuing these effects genet...
Source: eLife - September 23, 2021 Category: Biomedical Science Tags: Developmental Biology Stem Cells and Regenerative Medicine Source Type: research

Correction: Resource plasticity-driven carbon-nitrogen budgeting enables specialization and division of labor in a clonal community
(Source: eLife)
Source: eLife - September 23, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Physics of Living Systems Source Type: research