Controlling motor neurons of every muscle for fly proboscis reaching
We describe the anatomy of all the primary motor neurons in the fly proboscis and characterize their contributions to its diverse reaching movements. Pairing this behavior with the wealth ofDrosophila ’s genetic tools offers the possibility to study motor control at single-neuron resolution, and soon throughout entire circuits. As an entry to these circuits, we provide detailed anatomy of proboscis motor neurons, muscles, and joints. We create a collection of fly strains to individually manipulate every proboscis muscle through control of its motor neurons, the first such collection for an appendage. We generate a mo...
Source: eLife - June 25, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Numerical magnitude, rather than individual bias, explains spatial numerical association in newborn chicks
We associate small numbers with the left and large numbers with the right side of space. Recent evidence from human newborns and non-human animals has challenged the primary role assigned to culture, in determining this spatial numerical association (SNA). Nevertheless, the effect of individual spatial biases has not been considered in previous research. Here, we tested the effect of numerical magnitude in SNA and we controlled for itablendividual biases. We trained 3-day-old chicks (Gallus gallus) on a given numerical magnitude (5). Then chicks could choose between two identical, left or right, stimuli both representing e...
Source: eLife - June 25, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Specific labeling of synaptic schwann cells reveals unique cellular and molecular features
Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100 β+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the...
Source: eLife - June 25, 2020 Category: Biomedical Science Tags: Cell Biology Neuroscience Source Type: research

Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and < i > APOE < /i > in < i > Nrf2-Nfkb < /i > interactions
The neurotoxicity of air pollution is undefined for sex andAPOE alleles. These major risk factors of Alzheimer ’s disease (AD) were examined in mice given chronic exposure to nPM, a nano-sized subfraction of urban air pollution. In the cerebral cortex, female mice had two-fold more genes responding to nPM than males. Transcriptomic responses to nPM had sex-APOE interactions in AD-relevant pathways. OnlyAPOE3 mice responded to nPM in genes related to Abeta deposition and clearance (Vav2,Vav3,S1009a). Other responding genes included axonal guidance, inflammation (AMPK, NFKB, APK/JNK signaling), and antioxidant signalin...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Computational and Systems Biology Neuroscience Source Type: research

Slow oscillation-spindle coupling predicts enhanced memory formation from childhood to adolescence
Precise temporal coordination of slow oscillations (SO) and sleep spindles is a fundamental mechanism of sleep-dependent memory consolidation. SO and spindle morphology changes considerably throughout development. Critically, it remains unknown how the precise temporal coordination of these two sleep oscillations develops during brain maturation and whether their synchronization indexes the development of memory networks. Here, we use a longitudinal study design spanning from childhood to adolescence, where participants underwent polysomnography and performed a declarative word-pair learning task. Performance on the memory...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research

Echinoderms provide missing link in the evolution of PrRP/sNPF-type neuropeptide signalling
Neuropeptide signalling systems comprising peptide ligands and cognate receptors are evolutionarily ancient regulators of physiology and behaviour. However, there are challenges associated with determination of orthology between neuropeptides in different taxa. Orthologs of vertebrate neuropeptide-Y (NPY) known as neuropeptide-F (NPF) have been identified in protostome invertebrates, whilst prolactin-releasing peptide (PrRP) and short neuropeptide-F (sNPF) have been identified as paralogs of NPY/NPF in vertebrates and protostomes, respectively. Here we investigated the occurrence of NPY/NPF/PrRP/sNPF-related signalling sys...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Evolutionary Biology Neuroscience Source Type: research

SynGAP isoforms differentially regulate synaptic plasticity and dendritic development
SynGAP is a synaptic Ras GTPase-activating protein (GAP) with four C-terminal splice variants: α1, α2, β, and γ. Although studies have implicatedSYNGAP1 in several cognitive disorders, it is not clear which SynGAP isoforms contribute to disease. Here, we demonstrate that SynGAP isoforms exhibit unique spatiotemporal expression patterns and play distinct roles in neuronal and synaptic development in mouse neurons. SynGAP- α1, which undergoes liquid-liquid phase separation with PSD-95, is highly enriched in synapses and is required for LTP. In contrast, SynGAP-β, which does not bind PSD-95 P...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

AR phosphorylation and CHK2 kinase activity regulates IR stabilized AR-CHK2 interaction and prostate cancer survival
We have previously demonstrated that checkpoint kinase 2 (CHK2) is a critical negative regulator of androgen receptor (AR) transcriptional activity, prostate cancer (PCa) cell growth, and androgen sensitivity. We have now uncovered that the AR directly interacts with CHK2 and ionizing radiation (IR) increases this interaction. This IR-induced increase in AR –CHK2 interactions requires AR phosphorylation and CHK2 kinase activity. PCa associated CHK2 mutants with impaired kinase activity reduced IR-induced AR–CHK2 interactions. The destabilization of AR–CHK2 interactions induced by CHK2 variants impairs CHK...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cancer Biology Source Type: research

Control of adaptive action selection by secondary motor cortex during flexible visual categorization
Adaptive action selection during stimulus categorization is an important feature of flexible behavior. To examine neural mechanism underlying this process, we trained mice to categorize the spatial frequencies of visual stimuli according to a boundary that changed between blocks of trials in a session. Using a model with a dynamic decision criterion, we found that sensory history was important for adaptive action selection after the switch of boundary. Bilateral inactivation of the secondary motor cortex (M2) impaired adaptive action selection by reducing the behavioral influence of sensory history. Electrophysiological re...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress
During herpesvirus infection, egress of nascent viral capsids from the nucleus is mediated by the viral nuclear egress complex (NEC). NEC deforms the inner nuclear membrane (INM) around the capsid by forming a hexagonal array. However, how the NEC coat interacts with the capsid and how curved coats are generated to enable budding is yet unclear. Here, by structure-guided truncations, confocal microscopy, and cryoelectron tomography, we show that binding of the capsid protein UL25 promotes the formation of NEC pentagons rather than hexagons. We hypothesize that during nuclear budding, binding of UL25 situated at the pentago...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

Mitigating memory effects during undulatory locomotion on hysteretic materials
This study reveals how memory effects stymied the locomotion of a diversity of snakes in our previous studies (Marvi et al., 2014) and indicates avenues to improve all-terrain robots. (Source: eLife)
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Physics of Living Systems Source Type: research

Differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain
To date, microglia subsets in the healthy CNS have not been identified. Utilizing autofluorescence (AF) as a discriminating parameter, we identified two novel microglia subsets in both mice and non-human primates, termed autofluorescence-positive (AF+) and negative (AF-). While their proportion remained constant throughout most adult life, the AF signal linearly and specifically increased in AF+ microglia with age and correlated with a commensurate increase in size and complexity of lysosomal storage bodies, as detected by transmission electron microscopy and LAMP1 levels. Post-depletion repopulation kinetics revealed AF- ...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Immunology and Inflammation Neuroscience Source Type: research

Microglia < i > TREM2 < sup > R47H < /sup > < /i > Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF- α levels
To study the mechanisms by which the p.R47H variant of the microglia gene and Alzheimer's disease (AD) risk factor TREM2 increases dementia risk, we created Trem2R47H KI rats.Trem2R47H rats were engineered to produce human A β to define human-Aβ-dependent and -independent pathogenic mechanisms triggered by this variant. Interestingly, pre- and peri-adolescentTrem2R47H rats present increased brain concentrations of TNF- α, augmented glutamatergic transmission, suppression of Long-term-Potentiation (LTP), an electrophysiological surrogate of learning and memory, but normal Ab levels. Acute reduction of TNF-&a...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Nanobody-directed targeting of optogenetic tools to study signaling in the primary cilium
Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. The primary cilium constitutes a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling has been challenging due to the lack of tools investigate ciliary signaling. Here, we describe a nanobody-based targeting approach for optogenetic tools in mammalian cells andin vivo in zebrafish to specifically analyze ciliary signaling and function. Thereby, we overcome the loss of protein function observed after fu...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Cell Biology Source Type: research

Dynamic behavior of the locus coeruleus during arousal-related memory processing in a multi-modal 7T fMRI paradigm
A body of animal and human evidence points to the norepinephrine (NE) locus coeruleus (LC) system in modulating memory for arousing experiences, but whether the LC would recast its role along memory stages remains unknown. Sedation precluded examination of LC dynamics during memory processing in animals. Here, we addressed the contribution of the LC during arousal-associated memory processing through a unique combination of dedicated ultra-high-field LC-imaging methods, a well-established emotional memory task, online physiological and saliva alpha-amylase measurements in young adults. Arousal-related LC activation followe...
Source: eLife - June 24, 2020 Category: Biomedical Science Tags: Human Biology and Medicine Neuroscience Source Type: research

Antibodies to SARS-CoV-2 and their potential for therapeutic passive immunization
We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID-19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients, monoclonal antibodies against the viral S-protein, and soluble forms of the receptor for the virus, angiotensin converting enzyme 2. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition
The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally depositedDrosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of ...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Chromosomes and Gene Expression Developmental Biology Source Type: research

Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism
In conclusion, the structure of RNF213 uncovers a distinct type of an E3 enzyme, highlighting the growing mechanistic diversity in ubiquitination cascades. Our results also provide the molecular framework for investigating the emerging role of RNF213 in lipid metabolism, hypoxia, and angiogenesis. (Source: eLife)
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Structural Biology and Molecular Biophysics Source Type: research

A community-maintained standard library of population genetic models
The explosion in population genomic data demands ever more complex modes of analysis, and increasingly these analyses depend on sophisticated simulations. Re-cent advances in population genetic simulation have made it possible to simulate large and complex models, but specifying such models for a particular simulation engine remains a difficult and error-prone task. Computational genetics researchers currently re-implement simulation models independently, leading to inconsistency and duplication of effort. This situation presents a major barrier to empirical researchers seeking to use simulations for power analyses of upco...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Computational and Systems Biology Evolutionary Biology Source Type: research

Unsupervised machine learning reveals risk stratifying glioblastoma tumor cells
A goal of cancer research is to reveal cell subsets linked to continuous clinical outcomes to generate new therapeutic and biomarker hypotheses. We introduce a machine learning algorithm, Risk Assessment Population IDentification (RAPID), that is unsupervised and automated, identifies phenotypically distinct cell populations, and determines whether these populations stratify patient survival. With a pilot mass cytometry dataset of 2 million cells from 28 glioblastomas, RAPID identified tumor cells whose abundance independently and continuously stratified patient survival. Statistical validation within the workflow included...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Computational and Systems Biology Human Biology and Medicine Source Type: research

A new genetic strategy for targeting microglia in development and disease
As the resident macrophages of the brain and spinal cord, microglia are crucial for the phagocytosis of infectious agents, apoptotic cells and synapses. During brain injury or infection, bone-marrow derived macrophages invade neural tissue, making it difficult to distinguish between invading macrophages and resident microglia. In addition to circulation-derived monocytes, other non-microglial central nervous system (CNS) macrophage subtypes include border-associated meningeal, perivascular and choroid plexus macrophages. Using immunofluorescent labeling, flow cytometry and Cre-dependent ribosomal immunoprecipitations, we d...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Immunology and Inflammation Neuroscience Source Type: research

Lack of evidence for associative learning in pea plants
Gagliano et al. (Learning by association in plants, 2016) reported associative learning in pea plants. Associative learning has long been considered a behavior performed only by animals, making this claim particularly newsworthy and interesting. In the experiment, plants were trained in Y-shaped mazes for 3 days with fans and lights attached at the top of the maze. Training consisted of wind consistently preceding light from either the same or the opposite arm of the maze. When plant growth forced a decision between the two arms of the maze, fans alone were able to influence growth direction, whereas the growth direction o...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Plant Biology Source Type: research

Skd3 (human < i > CLPB < /i > ) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations
Cells have evolved specialized protein disaggregases to reverse toxic protein aggregation and restore protein functionality. In nonmetazoan eukaryotes, the AAA+ disaggregase Hsp78 resolubilizes and reactivates proteins in mitochondria. Curiously, metazoa lack Hsp78. Hence, whether metazoan mitochondria reactivate aggregated proteins is unknown. Here, we establish that a mitochondrial AAA+ protein, Skd3 (humanCLPB), couples ATP hydrolysis to protein disaggregation and reactivation. The Skd3 ankyrin-repeat domain combines with conserved AAA+ elements to enable stand-alone disaggregase activity. A mitochondrial inner-membrane...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Source Type: research

Tuning of feedforward control enables stable muscle force-length dynamics after loss of autogenic proprioceptive feedback
Animals must integrate feedforward, feedback and intrinsic mechanical control mechanisms to maintain stable locomotion. Recent studies of guinea fowl (Numida meleagris) revealed that the distal leg muscles rapidly modulate force and work output to minimize perturbations in uneven terrain. Here we probe the role of reflexes in the rapid perturbation responses of muscle by studying the effects of proprioceptive loss. We induced bilateral loss of autogenic proprioception in the lateral gastrocnemius muscle (LG) using self-reinnervation. We comparedin vivo muscle dynamics and ankle kinematics in birds with reinnervated and int...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Neuroscience Physics of Living Systems Source Type: research

Sequentially induced motor neurons from human fibroblasts facilitate locomotor recovery in a rodent spinal cord injury model
Generation of autologous human motor neurons holds great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows generation of target cells from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic that are not scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducingPOU5F1(OCT4) andLHX3. Our strategy enables scalable production of pure iMNs because of the t...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Stem Cells and Regenerative Medicine Source Type: research

Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth
Glucose utilization increases in tumors, a metabolic process that is observed clinically by18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development.18F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which i...
Source: eLife - June 23, 2020 Category: Biomedical Science Tags: Cancer Biology Source Type: research

A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission
Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show thatPlasmodium berghei CDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. During a replicative cycle, CRK5 stabl...
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

The Wg and Dpp morphogens regulate gene expression by modulating the frequency of transcriptional bursts
Morphogen signaling contributes to the patterned spatiotemporal expression of genes during development. One mode of regulation of signaling-responsive genes is at the level of transcription. Single-cell quantitative studies of transcription have revealed that transcription occurs intermittently, in bursts. Although the effects of many gene regulatory mechanisms on transcriptional bursting have been studied, it remains unclear how morphogen gradients affect this dynamic property of downstream genes. Here we have adapted single molecule fluorescence in situ hybridization (smFISH) for use in theDrosophila wing imaginal disc i...
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Developmental Biology Source Type: research

Evidence for transmission of COVID-19 prior to symptom onset
We collated contact tracing data from COVID-19 clusters in Singapore and Tianjin, China and estimated the extent of pre-symptomatic transmission by estimating incubation periods and serial intervals. The mean incubation periods accounting for intermediate cases were 4.91 days (95%CI 4.35, 5.69) and 7.54 (95%CI 6.76, 8.56) days for Singapore and Tianjin, respectively. The mean serial interval was 4.17 (95%CI 2.44, 5.89) and 4.31 (95%CI 2.91, 5.72) days (Singapore, Tianjin). The serial intervals are shorter than incubation periods, suggesting that pre-symptomatic transmission may occur in a large proportion of transmission e...
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Epidemiology and Global Health Source Type: research

Brain states govern the spatio-temporal dynamics of resting state functional connectivity
This study provides further evidence that changes in functional connectivity are dependent on the brain ’s current state, directly linked to the generation of slow waves. (Source: eLife)
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe < i > Pet1 < /i > neurons
We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show thatP2ry1-Pet1 DR neurons – the most molecularly distinct subtype – possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomi c identification ofPet1 neuron subtypes. (Source: eLife)
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Genetics and Genomics Neuroscience Source Type: research

Intentional text
It is important to read what the authors have written and to pay attention to every word when you write. (Source: eLife)
Source: eLife - June 22, 2020 Category: Biomedical Science Source Type: research

Local frustration determines loop opening during the catalytic cycle of an oxidoreductase
Local structural frustration, the existence of mutually exclusive competing interactions, may explain why some proteins are dynamic while others are rigid. Frustration is thought to underpin biomolecular recognition and the flexibility of protein binding sites. Here we show how a small chemical modification, the oxidation of two cysteine thiols to a disulfide bond, during the catalytic cycle of the N-terminal domain of the key bacterial oxidoreductase DsbD (nDsbD), introduces frustration ultimately influencing protein function. In oxidized nDsbD, local frustration disrupts the packing of the protective cap-loop region agai...
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Computational and Systems Biology Structural Biology and Molecular Biophysics Source Type: research

The caudate nucleus contributes causally to decisions that balance reward and uncertain visual information
Our decisions often balance what we observe and what we desire. A prime candidate for implementing this complex balancing act is the basal ganglia pathway, but its roles have not yet been examined experimentally in detail. Here, we show that a major input station of the basal ganglia, the caudate nucleus, plays a causal role in integrating uncertain visual evidence and reward context to guide adaptive decision-making. In monkeys making saccadic decisions based on motion cues and asymmetric reward-choice associations, single caudate neurons encoded both sources of information. Electrical microstimulation at caudate sites du...
Source: eLife - June 22, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

A trans-eQTL network regulates osteoclast multinucleation and bone mass
We report opposing effects of MMnet genes on bone mass in mice and osteoclast multinucleation/resorption in humans with strong correlation between the two. These results identify MMnet as a functionally conserved network that regulates osteoclast multinucleation and bone mass. (Source: eLife)
Source: eLife - June 19, 2020 Category: Biomedical Science Tags: Cell Biology Genetics and Genomics Source Type: research

Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha
Adipocytes arise from distinct progenitor populations during development and adult, but little is known about how developmental progenitors differ from adult progenitors. Here, we investigate the role of platelet-derived growth factor receptor alpha (PDGFR α) in the divergent regulation of the two different adipose progenitor cells (APCs). Usingin vivo adipose lineage tracking and deletion mouse models, we found that developmental PDGFR α+ cells are adipogenic and differentiated into mature adipocytes, and the deletion ofPdgfra in developmental adipose lineage disrupted white adipose tissue (WAT) formation. Int...
Source: eLife - June 19, 2020 Category: Biomedical Science Tags: Cell Biology Developmental Biology Source Type: research

Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19
Previously we showed that 31/1,032 (3%) asymptomatic healthcare workers (HCW) from a large teaching hospital in Cambridge UK tested positive for SARS-CoV-2 in April 2020. 26/169 (15%) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive (Rivett et al., 2020). Here we show that the proportion of both asymptomatic and symptomatic HCWs testing positive rapidly declined to near-zero between 25th April and 24th May 2020, corresponding with a decline in patient admissions with COVID-19 during the ongoing UK 'lockdown'. These data demonstrate how infection prevention and control measures including staff ...
Source: eLife - June 19, 2020 Category: Biomedical Science Tags: Epidemiology and Global Health Human Biology and Medicine Source Type: research

Correction: A unicellular relative of animals generates a layer of polarized cells by actomyosin-dependent cellularization
(Source: eLife)
Source: eLife - June 19, 2020 Category: Biomedical Science Tags: Cell Biology Evolutionary Biology Source Type: research

Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation
This study will aid not only in our understanding of how cellular networks form but highlight vulnerable cellular circuit motifs that might be generalized across disease states. (Source: eLife)
Source: eLife - June 19, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

A quantitative inventory of yeast P body proteins reveals principles of composition and specificity
P bodies are archetypal biomolecular condensates that concentrate proteins and RNA without a surrounding membrane. While dozens of P body proteins are known, the concentrations of components in the compartment have not been measured. We used live cell imaging to generate a quantitative inventory of the major proteins in yeast P bodies. Only 7 proteins are highly concentrated in P bodies (5.1-15 uM); the 24 others examined are appreciably lower (most ≤ 2.6 uM). P body concentration correlates inversely with cytoplasmic exchange rate. Sequence elements driving Dcp2 concentration into P bodies are distributed across the pr...
Source: eLife - June 19, 2020 Category: Biomedical Science Tags: Cell Biology Source Type: research

Positive density dependence acting on mortality can help maintain species-rich communities
Conspecific negative density dependence is ubiquitous and has long been recognized as an important factor favoring the coexistence of competing species at local scale. By contrast, a positive density-dependent growth rate is thought to favor species exclusion by inhibiting the growth of less competitive species. Yet, such conspecific positive density dependence often reduces extrinsic mortality (e.g. reduced predation), which favors species exclusion in the first place. Here, using a combination of analytical derivations and numerical simulations, I show that this form of positive density dependence can favor the existence...
Source: eLife - June 18, 2020 Category: Biomedical Science Tags: Ecology Source Type: research

MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans
The molecular roles of HOX transcriptional activity in human prostate epithelial cells remain unclear, impeding the implementation of new treatment strategies for cancer prevention and therapy. MEIS proteins are transcription factors that bind and direct HOX protein activity. MEIS proteins are putative tumor suppressors that are frequently silenced in aggressive forms of prostate cancer. Here we show that MEIS1 expression is sufficient to decrease proliferation and metastasis of prostate cancer cells in vitro and in vivo murine xenograft models. HOXB13 deletion demonstrates that the tumor-suppressive activity of MEIS1 is d...
Source: eLife - June 18, 2020 Category: Biomedical Science Tags: Cancer Biology Human Biology and Medicine Source Type: research

The analysis of living systems can generate both knowledge and illusions
Life relies on phenomena that range from changes in molecules that occur within nanoseconds to changes in populations that occur over millions of years. Researchers have developed a vast range of experimental techniques to analyze living systems, but a given technique usually only works over a limited range of length or time scales. Therefore, gaining a full understanding of a living system usually requires the integration of information obtained at multiple different scales by two or more techniques. This approach has undoubtedly led to a much better understanding of living systems but, equally, the staggering complexity ...
Source: eLife - June 18, 2020 Category: Biomedical Science Tags: Cell Biology Developmental Biology Source Type: research

Correction: Polyunsaturated fatty acid analogues differentially affect cardiac Na < sub > V < /sub > , Ca < sub > V < /sub > , and K < sub > V < /sub > channels through unique mechanisms
(Source: eLife)
Source: eLife - June 18, 2020 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research

LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome
Primary cilia are sensory organelles crucial for cell signaling during development and organ homeostasis. Cilia arise from centrosomes and their formation and function is governed by numerous factors. Through our studies on Townes-Brocks Syndrome (TBS), a rare disease linked to abnormal cilia formation in human fibroblasts, we uncovered the leucine-zipper protein LUZP1 as an interactor of truncated SALL1, a dominantly-acting protein causing the disease. Using TurboID proximity labeling and pulldowns, we show that LUZP1 associates with factors linked to centrosome and actin filaments. Here, we show that LUZP1 is a cilia reg...
Source: eLife - June 18, 2020 Category: Biomedical Science Tags: Cell Biology Developmental Biology Source Type: research

Ciliate mitoribosome illuminates evolutionary steps of mitochondrial translation
To reveal steps in the evolution of translation, we identified ciliates as a model with high coding capacity of the mitochondrial genome and characterized its mitoribosomes by cryo-EM. It revealed a 94-protein and 4-rRNA assembly with an additional protein mass of ~700 kDa on the small subunit, while the large subunit lacks 5S rRNA. The structure shows that the small subunit head is constrained, tRNA binding sites are formed by mitochondria-specific protein elements, conserved protein bS1 is excluded, and bacterial RNA polymerase binding site is blocked. We provide evidence for intrinsic protein targeting system through vi...
Source: eLife - June 18, 2020 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research

Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes
Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor sto...
Source: eLife - June 17, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

Ca < sup > 2+ < /sup > entry through Na < sub > V < /sub > channels generates submillisecond axonal Ca < sup > 2+ < /sup > signaling
Calcium ions (Ca2+) are essential for many cellular signaling mechanisms and enter the cytosol mostly through voltage-gated calcium channels. Here, using high-speed Ca2+ imaging up to 20 kHz in the rat layer 5 pyramidal neuron axon we found that activity-dependent intracellular calcium concentration ([Ca2+]i) in the axonal initial segment was only partially dependent on voltage-gated calcium channels. Instead, [Ca2+]i changes were sensitive to the specific voltage-gated sodium (NaV) channel blocker tetrodotoxin. Consistent with the conjecture that Ca2+ enters through the NaV channel pore, the optically resolvedICa in the a...
Source: eLife - June 17, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

The roles of online and offline replay in planning
Animals and humans replay neural patterns encoding trajectories through their environment, both whilst they solve decision-making tasks and during rest. Both on-task and off-task replay are believed to contribute to flexible decision making, though how their relative contributions differ remains unclear. We investigated this question by using magnetoencephalography (MEG) to study human subjects while they performed a decision-making task that was designed to reveal the decision algorithms employed. We characterised subjects in terms of how flexibly each adjusted their choices to changes in temporal, spatial and reward stru...
Source: eLife - June 17, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface
The type one interferon induced restriction factor Myxovirus resistance B (MxB) restricts HIV-1 nuclear entry evidenced by inhibition of 2-LTR but not linear forms of viral DNA. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. This has suggested that nuclear import mechanism may determine MxB sensitivity. Here we h...
Source: eLife - June 17, 2020 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research