MiSiC, a general deep learning-based method for the high-throughput cell segmentation of complex bacterial communities
Studies of bacterial communities, biofilms and microbiomes, are multiplying due to their impact on health and ecology. Live imaging of microbial communities requires new tools for the robust identification of bacterial cells in dense and often inter-species populations, sometimes over very large scales. Here, we developed MiSiC, a general deep-learning-based 2D segmentation method that automatically segments single bacteria in complex images of interacting bacterial communities with very little parameter adjustment, independent of the microscopy settings and imaging modality. Using a bacterial predator-prey interaction mod...
Source: eLife - September 9, 2021 Category: Biomedical Science Tags: Computational and Systems Biology Microbiology and Infectious Disease Source Type: research
Structural basis for diguanylate cyclase activation by its binding partner in < i > Pseudomonas aeruginosa < /i >
Cyclic-di-guanosine monophosphate (c-di-GMP) is an important effector associated with acute-chronic infection transition inPseudomonas aeruginosa. Previously, we reported a signaling network SiaABCD which regulates biofilm formation by modulating c-di-GMP level. However, the mechanism for SiaD activation by SiaC remains elusive. Here we determine the crystal structure of SiaC-SiaD-GpCpp complex and revealed a unique mirror symmetric conformation: two SiaD form a dimer with long stalk domains, while four SiaC bind to the conserved motifs on the stalks of SiaD and stabilize the conformation for further enzymatic catalysis. F...
Source: eLife - September 9, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Structural Biology and Molecular Biophysics Source Type: research
The interplay of RNA:DNA hybrid structure and G-quadruplexes determines the outcome of R-loop-replisome collisions
R-loops are a major source of genome instability associated with transcription-induced replication stress. However, how R-loops inherently impact replication fork progression is not understood. Here, we characterize R-loop-replisome collisions using a fully reconstituted eukaryotic DNA replication system. We find that RNA:DNA hybrids and G-quadruplexes at both co-directional and head-on R-loops can impact fork progression by inducing fork stalling, uncoupling of leading strand synthesis from replisome progression, and nascent strand gaps. RNase H1 and Pif1 suppress replication defects by resolving RNA:DNA hybrids and G-qua...
Source: eLife - September 8, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Chromosomes and Gene Expression Source Type: research
Telomere length is associated with growth in children in rural Bangladesh
Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth. (Source: eLife)
Source: eLife - September 8, 2021 Category: Biomedical Science Tags: Epidemiology and Global Health Source Type: research
Activity-dependent modulation of synapse-regulating genes in astrocytes
Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expr...
Source: eLife - September 8, 2021 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research
Sex specific pubertal and metabolic regulation of Kiss1 neurons via Nhlh2
Hypothalamic Kiss1 neurons control gonadotropin-releasing hormone (GnRH) release through the secretion of kisspeptin. Kiss1 neurons serve as a nodal center that conveys essential regulatory cues for the attainment and maintenance of reproductive function. Despite this critical role, the mechanisms that control kisspeptin synthesis and release remain largely unknown. Using Drop-Seq data from the arcuate nucleus of adult mice andin situ hybridization, we identified Nescient Helix-Loop-Helix 2 (Nhlh2), a transcription factor (TF) of the basic helix-loop-helix family, to be enriched in Kiss1 neurons. JASPAR analysis revealed s...
Source: eLife - September 8, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Multi-color fluorescence fluctuation spectroscopy in living cells via spectral detection
Signaling pathways in biological systems rely on specific interactions between multiple biomolecules. Fluorescence fluctuation spectroscopy provides a powerful toolbox to quantify such interactions directly in living cells. Cross-correlation analysis of spectrally separated fluctuations provides information about inter-molecular interactions but is usually limited to two fluorophore species. Here, we present scanning fluorescence spectral correlation spectroscopy (SFSCS), a versatile approach that can be implemented on commercial confocal microscopes, allowing the investigation of interactions between multiple protein spec...
Source: eLife - September 8, 2021 Category: Biomedical Science Tags: Physics of Living Systems Structural Biology and Molecular Biophysics Source Type: research
Vision, challenges and opportunities for a Plant Cell Atlas
With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environ...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Cell Biology Source Type: research
Distributed functions of prefrontal and parietal cortices during sequential categorical decisions
Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, whic...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation
Inducible regulatory T (iTreg) cells play a central role in immune suppression. As iTreg cells are differentiated from activated T (Th0) cells, cell metabolism undergoes dramatic changes, including a shift from fatty acid synthesis (FAS) to fatty acid oxidation (FAO). Although the reprogramming in fatty acid metabolism is critical, the mechanism regulating this process during iTreg differentiation is still unclear. Here we have revealed that the enzymatic activity of ATP-citrate lyase (ACLY) declined significantly during iTreg differentiation upon transforming growth factor β1 (TGFβ1) stimulation. This reduction was due ...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Immunology and Inflammation Source Type: research
β-hydroxybutyrate accumulates in the rat heart during low-flow ischaemia with implications for functional recovery
In conclusion, net ketone generation occurs in the heart under conditions of low-flow ischaemia. The process is driven by flux through both HMGCS2 and SCOT, and impacts on cardiac functional recovery from ischaemia/reperfusion. (Source: eLife)
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cell Biology Source Type: research
Activity-dependent regulation of mitochondrial motility in developing cortical dendrites
Developing neurons form synapses at a high rate. Synaptic transmission is very energy-demanding and likely requires ATP production by mitochondria nearby. Mitochondria might be targeted to active synapses in young dendrites, but whether such motility regulation mechanisms exist is unclear. We investigated the relationship between mitochondrial motility and neuronal activity in the primary visual cortex of young mice in vivo and in slice cultures. During the first 2 postnatal weeks, mitochondrial motility decreases while the frequency of neuronal activity increases. Global calcium transients do not affect mitochondrial moti...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Gut bacterial aggregates as living gels
The spatial organization of gut microbiota influences both microbial abundances and host-microbe interactions, but the underlying rules relating bacterial dynamics to large-scale structure remain unclear. To this end we studied experimentally and theoretically the formation of three-dimensional bacterial clusters, a key parameter controlling susceptibility to intestinal transport and access to the epithelium. Inspired by models of structure formation in soft materials, we sought to understand how the distribution of gut bacterial cluster sizes emerges from bacterial-scale kinetics. Analyzing imaging-derived data on cluster...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Physics of Living Systems Source Type: research
Separable neural signatures of confidence during perceptual decisions
Perceptual confidence is an evaluation of the validity of perceptual decisions. While there is behavioural evidence that confidence evaluation differs from perceptual decision-making, disentangling these two processes remains a challenge at the neural level. Here, we examined the electrical brain activity of human participants in a protracted perceptual decision-making task where observers tend to commit to perceptual decisions early whilst continuing to monitor sensory evidence for evaluating confidence. Premature decision commitments were revealed by patterns of spectral power overlying motor cortex, followed by an atten...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
A universal pocket in Fatty acyl-AMP ligases ensures redirection of fatty acid pool away from Coenzyme A-based activation
Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4'-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and acceptholo-ACP unlike other members of the ANL superfamily remains elusive. We show FAALs have plugged the promiscuous canonical CoA-binding pockets ...
Source: eLife - September 7, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Source Type: research
