'Fearful-place' coding in the amygdala-hippocampal network
Animals seeking survival needs must be able to assess different locations of threats in their habitat. However, the neural integration of spatial and risk information essential for guiding goal-directed behavior remains poorly understood. Thus, we investigated simultaneous activities of fear-responsive basal amygdala (BA) and place-responsive dorsal hippocampus (dHPC) neurons as rats left the safe nest to search for food in an exposed space and encountered a simulated 'predator'. In this realistic situation, BA cells increased their firing rates and dHPC place cells decreased their spatial stability near the threat. Import...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Characterizing human mobility patterns in rural settings of sub-Saharan Africa
Human mobility is a core component of human behavior and its quantification is critical for understanding its impact on infectious disease transmission, traffic forecasting, access to resources and care, intervention strategies, and migratory flows. When mobility data are limited, spatial interaction models have been widely used to estimate human travel, but have not been extensively validated in low- and middle-income settings. Geographic, sociodemographic, and infrastructure differences may impact the ability for models to capture these patterns, particularly in rural settings. Here, we analyzed mobility patterns inferre...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Computational and Systems Biology Epidemiology and Global Health Source Type: research
Ectocytosis prevents accumulation of ciliary cargo in < i > C. elegans < /i > sensory neurons
Cilia are sensory organelles protruding from cell surfaces. Release of Extracellular Vesicles (EVs) from cilia was previously observed in mammals, Chlamydomonas, and in maleC. elegans. Using the EV marker TSP-6 (an ortholog of mammalian CD9) and other ciliary receptors, we show that EVs are formed from ciliated sensory neurons inC. elegans hermaphrodites. Release of EVs is observed from two ciliary locations: the cilia tip and/or Periciliary Membrane Compartment (PCMC). Outward budding of EVs from the cilia tip leads to their release into the environment. EVs budding from the PCMC are concomitantly phagocytosed by the asso...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Cell Biology Source Type: research
Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
In this report we investigated presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanisms of protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial, which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy. Total RNA-seq in a clinical...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research
PARROT is a flexible recurrent neural network framework for analysis of large protein datasets
The rise of high-throughput experiments has transformed how scientists approach biological questions. The ubiquity of large-scale assays that can test thousands of samples in a day has necessitated the development of new computational approaches to interpret this data. Among these tools, machine learning approaches are increasingly being utilized due to their ability to infer complex nonlinear patterns from high-dimensional data. Despite their effectiveness, machine learning (and in particular deep learning) approaches are not always accessible or easy to implement for those with limited computational expertise. Here we pr...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Computational and Systems Biology Source Type: research
SUV39 SET domains mediate crosstalk of heterochromatic histone marks
The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeastSchizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach s...
Source: eLife - September 15, 2021 Category: Biomedical Science Tags: Chromosomes and Gene Expression Source Type: research
A projectome of the bumblebee central complex
Insects have evolved diverse and remarkable strategies for navigating in various ecologies all over the world. Regardless of species, insects share the presence of a group of morphologically conserved neuropils known collectively as the central complex (CX). The CX is a navigational center, involved in sensory integration and coordinated motor activity. Despite the fact that our understanding of navigational behavior comes predominantly from ants and bees, most of what we know about the underlying neural circuitry of such behavior comes from work in fruit flies. Here we aim to close this gap, by providing the first compreh...
Source: eLife - September 15, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
A PX-BAR protein Mvp1/SNX8 and a dynamin-like GTPase Vps1 drive endosomal recycling
Membrane protein recycling systems are essential for maintenance of the endosome-lysosome system. In yeast, retromer and Snx4 coat complexes are recruited to the endosomal surface where they recognize cargos. They sort cargo and deform the membrane into recycling tubules that bud from the endosome and target to the Golgi. Here, we reveal that the SNX-BAR protein, Mvp1, mediates an endosomal recycling pathway which is mechanistically distinct from the retromer and Snx4 pathways. Mvp1 deforms the endosomal membrane and sorts cargos containing a specific sorting motif into a membrane tubule. Subsequently, Mvp1 recruits the dy...
Source: eLife - September 15, 2021 Category: Biomedical Science Tags: Cell Biology Source Type: research
A novel form of bivalent chromatin associates with rapid induction of camalexin biosynthesis genes in response to a pathogen signal in Arabidopsis
Temporal dynamics of gene expression underpin responses to internal and environmental stimuli. In eukaryotes, regulation of gene induction includes changing chromatin states at target genes and recruiting the transcriptional machinery that includes transcription factors. As one of the most potent defense compounds inArabidopsis thaliana, camalexin can be rapidly induced by bacterial and fungal infections. Though several transcription factors controlling camalexin biosynthesis genes have been characterized, how the rapid activation of genes in this pathway upon a pathogen signal is enabled remains unknown. By combining publ...
Source: eLife - September 15, 2021 Category: Biomedical Science Tags: Plant Biology Source Type: research
A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
The ability to regulate DNA replication initiation in response to changing nutrient conditions is an important feature of most cell types. In bacteria, DNA replication is triggered by the initiator protein DnaA, which has long been suggested to respond to nutritional changes; nevertheless, the underlying mechanisms remain poorly understood. Here, we report a novel mechanism that adjusts DnaA synthesis in response to nutrient availability inCaulobacter crescentus. By performing a detailed biochemical and genetic analysis of thednaA mRNA, we identified a sequence downstream of thednaA start codon that inhibits DnaA translati...
Source: eLife - September 15, 2021 Category: Biomedical Science Tags: Chromosomes and Gene Expression Microbiology and Infectious Disease Source Type: research
A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within < i > Saccharomyces cerevisiae < /i >
Although studies ofSaccharomyces cerevisiae have provided many insights into mutagenesis and DNA repair, most of this work has focused on a few laboratory strains. Much less is known about the phenotypic effects of natural variation withinS. cerevisiae's DNA repair pathways. Here, we use natural polymorphisms to detect historical mutation spectrum differences among several wild and domesticatedS. cerevisiae strains. To determine whether these differences are likely caused by genetic mutation rate modifiers, we use a modified fluctuation assay with aCAN1 reporter to measurede novomutation rates and spectra in 16 of the anal...
Source: eLife - September 15, 2021 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research
Regulation of human mTOR complexes by DEPTOR
The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein that binds and regulates both complexes of mammalian target of rapamycin (mTOR), a central regulator of cell growth. Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. The PDZ domain binds tightly with mildly activating effect, but then acts as ...
Source: eLife - September 14, 2021 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research
Continuous attractors for dynamic memories
Episodic memory has a dynamic nature: when we recall past episodes, we retrieve not only their content, but also their temporal structure. The phenomenon of replay, in the hippocampus of mammals, offers a remarkable example of this temporal dynamics. However, most quantitative models of memory treat memories as static configurations, neglecting the temporal unfolding of the retrieval process. Here, we introduce a continuous attractor network model with a memory-dependent asymmetric component in the synaptic connectivity, which spontaneously breaks the equilibrium of the memory configurations and produces dynamic retrieval....
Source: eLife - September 14, 2021 Category: Biomedical Science Tags: Computational and Systems Biology Neuroscience Source Type: research
Cryo-EM reveals new species-specific proteins and symmetry elements in the Legionella pneumophila Dot/Icm T4SS
Legionella pneumophila is an opportunistic pathogen that causes the potentially fatal pneumonia known as Legionnaires' Disease. The pathology associated with infection depends on bacterial delivery of effector proteins into the host via the membrane spanning Dot/Icm type IV secretion system (T4SS). We have determined sub-3.0 Å resolution maps of the Dot/Icm T4SS core complex by single particle cryo-EM. The high-resolution structural analysis has allowed us to identify proteins encoded outside the Dot/Icm genetic locus that contribute to the core T4SS structure. We can also now define two distinct areas of symmetry mism at...
Source: eLife - September 14, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research
Distinct population code for movement kinematics and changes of ongoing movements in human subthalamic nucleus
We report an inhomogeneous population neural code in STN, with one sub-population encoding movement kinematics and direction and another encoding unexpected action switches. We suggest an elaborate neural code in STN that contributes to planning actions and changing the plans. (Source: eLife)
Source: eLife - September 14, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
