Pain or gain?
The 3D structures of a membrane protein called TMEM120A suggest that it may act as an enzyme in fat metabolism rather than as an ion channel that senses mechanical pain. (Source: eLife)
Source: eLife - September 29, 2021 Category: Biomedical Science Tags: Neuroscience Structural Biology and Molecular Biophysics Source Type: research
Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy
Removal of damaged organelles via the process of selective autophagy constitutes a major form of cellular quality control. Damaged organelles are recognized by a dedicated surveillance machinery, leading to the assembly of an autophagosome around the damaged organelle, prior to fusion with the degradative lysosomal compartment. Lysosomes themselves are also prone to damage and are degraded through the process of lysophagy. While early steps involve recognition of ruptured lysosomal membranes by glycan-binding Galectins and ubiquitylation of transmembrane lysosomal proteins, many steps in the process, and their inter-relati...
Source: eLife - September 29, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cell Biology Source Type: research
History of winning and hierarchy landscape influence stress susceptibility in mice
Social hierarchy formation is strongly evolutionarily conserved. Across species, rank within social hierarchy has large effects on health and behavior. To investigate the relationship between social rank and stress susceptibility, we exposed ranked male and female mice to social and non-social stressors and manipulated social hierarchy position. We found that rank predicts same sex social stress outcomes: dominance in males and females confers resilience while subordination confers susceptibility. Pre-existing rank does not predict non-social stress outcomes in females and weakly does so in males, but rank emerging under s...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Dietary nitrate supplementation prevents radiotherapy-induced xerostomia
Management of salivary gland hypofunction caused by irradiation (IR) therapy for head and neck cancer remains lack of effective treatments. Salivary glands, especially the parotid gland, actively uptake dietary nitrate and secrete it into saliva. Here, we investigated the effect of dietary nitrate on the prevention and treatment of IR-induced parotid gland hypofunction in miniature pigs, and elucidated the underlying mechanism in human parotid gland cells (hPGCs). We found that nitrate administration prevented IR-induced parotid gland damage in a dose-dependent manner, by maintaining the function of irradiated parotid glan...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Cell Biology Source Type: research
Mutation analysis links angioimmunoblastic T-cell lymphoma to clonal hematopoiesis and smoking
(Source: eLife)
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Cancer Biology Medicine Source Type: research
Tiled-ClickSeq for targeted sequencing of complete coronavirus genomes with simultaneous capture of RNA recombination and minority variants
High-throughput genomics of SARS-CoV-2 is essential to characterize virus evolution and to identify adaptations that affect pathogenicity or transmission. While single-nucleotide variations (SNVs) are commonly considered as driving virus adaption, RNA recombination events that delete or insert nucleic acid sequences are also critical. Whole genome targeting sequencing of SARS-CoV-2 is typically achieved using pairs of primers to generate cDNA amplicons suitable for next-generation sequencing (NGS). However, paired-primer approaches impose constraints on where primers can be designed, how many amplicons are synthesized and ...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Genetics and Genomics Microbiology and Infectious Disease Source Type: research
Mechanically transduced immunosorbent assay to measure protein-protein interactions
Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry. Yet, conventional methods rely upon the law of mass action and cannot measure many PPIs due to a scarcity of reagents and limitations in the measurable affinity ranges. Here, we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that correlates to binding potential. The mechanically transduced immunosorbent (METRIS) assay utilizes rolling magnetic probes to measure PPI interaction affinities. METRIS measures the translational displacement of protein-coated particles on a protein-fu...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Physics of Living Systems Source Type: research
Age-dependent changes in protein incorporation into collagen-rich tissues of mice by in vivo pulsed SILAC labelling
We report dynamic turnover of the matrisome, the proteins of the extracellular matrix, in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed changes in epigenetic modulators across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGF β in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several pathways were implicated in age-related disease. Fewer changes were observed f...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Cell Biology Source Type: research
An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis
Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anti-cancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential. (Source: eLife)
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Medicine Microbiology and Infectious Disease Source Type: research
Deep evolutionary origin of gamete-directed zygote activation by KNOX/BELL transcription factors in green plants
KNOX and BELL transcription factors regulate distinct steps of diploid development in plants. In the green algaChlamydomonas reinhardtii, KNOX and BELL proteins are inherited by gametes of the opposite mating types and heterodimerize in zygotes to activate diploid development. By contrast, in land plants such asPhyscomitrium patens andArabidopsis thaliana, KNOX and BELL proteins function in meristem maintenance and organogenesis during the later stages of diploid development. However, whether the contrasting functions of KNOX and BELL were acquired independently in algae and land plants is currently unknown. Here, we show ...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Developmental Biology Evolutionary Biology Source Type: research
PGFinder, a novel analysis pipeline for the consistent, reproducible, and high-resolution structural analysis of bacterial peptidoglycans
Many software solutions are available for proteomics and glycomics studies, but none are ideal for the structural analysis of peptidoglycan (PG), the essential and major component of bacterial cell envelopes. It icomprises glycan chains and peptide stems, both containing unusual amino acids and sugars. This has forced the field to rely on manual analysis approaches, which are time-consuming, labour-intensive, and prone to error. The lack of automated tools has hampered the ability to perform high-throughput analyses and prevented the adoption of a standard methodology. Here, we describe a novel tool called PGFinder for the...
Source: eLife - September 28, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research
A state space modeling approach to real-time phase estimation
Brain rhythms have been proposed to facilitate brain function, with an especially important role attributed to the phase of low frequency rhythms. Understanding the role of phase in neural function requires interventions that perturb neural activity at a target phase, necessitating estimation of phase in real-time. Current methods for real-time phase estimation rely on bandpass filtering, which assumes narrowband signals and couples the signal and noise in the phase estimate, adding noise to the phase and impairing detections of relationships between phase and behavior. To address this, we propose a state space phase estim...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Phase response analyses support a relaxation oscillator model of locomotor rhythm generation in < i > Caenorhabditis elegans < /i >
Neural circuits coordinate with muscles and sensory feedback to generate motor behaviors appropriate to an animal ’s environment. InC. elegans,the mechanisms by which the motor circuit generates undulations and modulates them based on the environment are largely unclear. We quantitatively analyzedC. eleganslocomotion during free movement and during transient optogenetic muscle inhibition. Undulatory movements were highly asymmetrical with respect to the duration of bending and unbending during each cycle. Phase response curves induced by brief optogenetic inhibition of head muscles showed gradual increases and rapid decr...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Computational and Systems Biology Neuroscience Source Type: research
Single-molecule imaging reveals the concerted release of myosin from regulated thin filaments
Regulated thin filaments (RTFs) tightly control striated muscle contraction through calcium binding to troponin, which enables tropomyosin to expose myosin-binding sites on actin. Myosin binding holds tropomyosin in an open position, exposing more myosin-binding sites on actin, leading to cooperative activation. At lower calcium levels, troponin and tropomyosin turn off the thin filament; however, this is antagonised by the high local concentration of myosin, questioning how the thin filament relaxes. To provide molecular details of deactivation, we used single-molecule imaging of green fluorescent protein (GFP)-tagged myo...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Structural Biology and Molecular Biophysics Source Type: research
Conformational changes in twitchin kinase in vivo revealed by FRET imaging of freely moving < i > C. elegans < /i >
The force-induced unfolding and refolding of proteins is speculated to be a key mechanism in the sensing and transduction of mechanical signals in the living cell. Yet, little evidence has been gathered for its existencein vivo. Prominently, stretch-induced unfolding is postulated to be the activation mechanism of the twitchin/titin family of autoinhibited sarcomeric kinases linked to the mechanical stress response of muscle. To test the occurrence of mechanical kinase activation in living working muscle, we generated transgenicC. elegans expressing twitchin containing FRET moieties flanking the kinase domain and developed...
Source: eLife - September 27, 2021 Category: Biomedical Science Tags: Physics of Living Systems Structural Biology and Molecular Biophysics Source Type: research
