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Disruption of seasonal influenza circulation and evolution during the 2009 H1N1 and COVID-19 pandemics in Southeastern Asia
Perceiving inter-leg speed differences while walking on a split-belt treadmill
AbstractWalking is one of the most common forms of self-motion in humans. Most humans can walk effortlessly over flat uniform terrain, but also a variety of more challenging surfaces, as they adjust their gait to the demands of the terrain. In this, they rely in part on the perception of their own gait and of when it needs to be adjusted. Here, we investigated how well N = 48 participants detected speed differences between two belts of a split-belt treadmill. As participants walked at a constant speed, we either accelerated or decelerated one of the belts at quasi-random intervals and asked participants to judge their relative speeds in a two-alternative forced-choice task. Using an adaptive psychophysical procedure, we obtained precise perception-threshold estimates for inter-leg speed differences after accelerating or decelerating one belt. We found that most participants could detect even very small speed differences, with mean threshold estimates of just over 7% for both perturbation types. These were relatively stable within, but highly variable across participants. Increased-speed and decreased-speed thresholds were highly correlated, indicating that despite different biomechanics, the detection mechanisms might be similar. This sheds light on how perceiving their own motion helps humans manage interlimb coordination in perturbed walking.
MPicker: visualizing and picking membrane proteins for cryo-electron tomography
Abstract Advancements in cryo-electron tomography (cryoET) allow the structure of macromolecules to be determined in situ, which is crucial for studying membrane protein structures and their interactions in the cellular environment. However, membranes are often highly curved and have a strong contrast in cryoET tomograms, which masks the signals from membrane proteins. These factors pose difficulties in observing and revealing the structures of membrane proteins in situ. Here, we report a membrane-flattening method and the corresponding software, MPicker, designed for the visualization, localization, and orientation determination of membrane proteins in cryoET tomograms. This method improves the visualization of proteins on and around membranes by generating a flattened tomogram that eliminates membrane curvature and reduces the spatial complexity of membrane protein analysis. In MPicker, we integrated approaches for automated particle picking and coarse alignment of membrane proteins for sub-tomogram averaging. MPicker was tested on tomograms of various cells to evaluate the method for visualizing, picking, and analyzing membrane proteins.
Predicting high-quality ecologically suitable areas of Astragalus mongholicus Bunge based on secondary metabolites content using Biomod2 model
A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD
Abstract An abnormal expansion of a GGGGCC (G 4 C 2 ) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the G 4 C 2 repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits. This high-fidelity system possessed improved transcriptome-wide specificity compared to its native form and mediated targeting in motor neuron-like cells derived from a patient with ALS. These results lay the foundation for the implementation of RNA-targeting CRISPR technologies for C9ORF72-linked ALS/FTD.
Characteristics of gut microbiota profiles in Asian elephants (Elephas maximus) with gastrointestinal disorders
CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses
Boosting skin cancer diagnosis accuracy with ensemble approach
Defining ortholog-specific UHRF1 inhibition by STELLA for cancer therapy
Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization
Dynamic transitions of initiator binding coordinate the replication of the two chromosomes in Vibrio cholerae
Abstract The replication of the two chromosomes in the pathogenic bacterium Vibrio cholerae is coordinated by the binding of initiator protein RctB to a checkpoint sequence, crtS . Replication of crtS on the primary chromosome (Chr1) triggers replication of the secondary chromosome (Chr2), but the details are poorly understood. Here, we analyze RctB binding patterns in the V. cholerae genome across various cell cycle stages. We find that RctB primarily binds to sites inhibiting replication initiation at the Chr2 origin ( ori2 ). This inhibitory effect is counteracted when crtS is replicated on Chr1, causing a shift in RctB binding to sites that activate replication at ori2 . Structural analyzes indicate the formation of diverse oligomeric states of RctB, coupled to the allosteric effect of DNA, which determine ori2 accessibility. We propose a synchronization model where, upon replication, crtS locally destabilizes the RctB inhibition complex, releasing the Chr2 replication origin.
Partner conflict during their index pregnancy and its correlates among a cohort of six weeks postpartum women in Ethiopia
Biochemical and structural characterization of Rab3GAP reveals insights into Rab18 nucleotide exchange activity
Experimental data on aerosols exhaled into the environment from different wind musical instruments
MoS2-confined Rh-Zn atomic pair boosts photo-driven methane carbonylation to acetic acid
The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAB receptors under ischemic conditions by inhibiting fast receptor recycling
AbstractGABAB receptors mediate prolonged inhibition in the brain and are important for keeping neuronal excitation and inhibition in a healthy balance. However, under excitotoxic/ischemic conditions, GABAB receptors are downregulated by dysregulated endocytic trafficking and can no longer counteract the severely enhanced excitation, eventually triggering neuronal death. Recently, we developed interfering peptides targeting protein-protein interactions involved in downregulating the receptors. Treatment with these peptides restored GABAB receptor expression after an ischemic insult and thereby inhibited neuronal overexcitation and progressive neuronal death. In this study, we searched for GABAB receptor interactions that specifically occur under ischemic conditions. We found that the E3 ubiquitin ligase MARCH1 is specifically upregulated under ischemic/excitotoxic conditions. Upregulated MARCH1 interacts with GABAB receptors and triggered downregulation of plasma membrane GABAB receptors by inhibiting fast recycling of the receptors. We developed an interfering peptide that inhibits the MARCH1/GABAB receptor interaction. Treatment of cultured neurons subjected to ischemic stress with this peptide restored receptor expression and as a consequence stopped progressive neuronal death. Thus, inhibiting the interaction of GABAB receptors with MARCH1 to restore cell surface receptor expression might be a promising strategy to prevent progressive neuronal death induced by ischemic conditions.