Exploration of the phenotype space corresponding to the sequence space of viable SARS-CoV-2 nucleocapsid protein species reveals significant diversity of biophysical characteristics, nonlocal mutation effects, and functional constraints.
A gene expression data-informed model reveals that a small fraction of interferon-producing cells can effectively constrain early virus spread in epithelial tissue, elucidating connections between critical dynamics and infection heterogeneity.
Etienne Combrisson, Ruggero Basanisi ... Andrea Brovelli
Reward and punishment learning is represented in partly overlapping regions of the brain while relying on specific intra- and inter-regional interactions.
Dopaminergic and serotonergic neurons in the dorsal raphe nucleus have distinct electrical and morphological properties, which are differentially altered following dopamine and noradrenaline depletion.
Carlos Gonzalez-Islas, Zahraa Sabra ... Peter Wenner
Chronic perturbations of spiking activity trigger compensatory changes in GABAergic synaptic strength, but not compensatory changes in AMPAergic synaptic strength.
Sean V Connelly, Nicholas F Brazeau ... Jeffrey A Bailey
Parasite migration between mainland Tanzania and Zanzibar and ongoing transmission clusters within Zanzibar highlight the need for continued preventive measures to reduce malaria transmission in the archipelago.
Neuron-specific sequencing of aged wild-type, daf-2, and daf-16;daf-2 mutants revealed transcriptomic changes with age, and in longevity mutants, putative neuroprotective genes are upregulated, which are required for prolonged cognitive functions.
Gretchen Diffendall, Aurelie Claes ... Artur Scherf
RNA polymerase III plays a crucial role in controlling virulence in response to environmental changes and provides a new molecular perspective into the development of asymptomatic malaria.
Patrick E Brown, Sze Hang Fu ... Ab-C Study Collaborators
Population-level hybrid immunity depends substantially on vaccination coverage, including among those previously infected, and dried blood spot collection serves as a practicable biological surveillance platform for these immune responses.
Dimensionality reduction approaches on functional MRI data reveal that human reward-based motor learning emerges from dynamic changes in functional brain network interactions among sensorimotor, attention, and default mode networks.
Samuel Pattillo Smith, Gregory Darnell ... Lorin Crawford
Computational analysis reveals that additive summary statistics from genome-wide association studies can provide evidence of non-additive heritability in complex traits.
The vaginal immunoproteome in pregnancy is more predictive of spontaneous preterm birth (sPTB) than maternal characteristics alone, with sPTB cases showing heightened pro-inflammatory profiles accompanied by reduced levels of antimicrobial proteins/peptides.
Implicit defensive reactions to a learned threat-predictive cue and novel stimuli may be significantly downregulated through a repetitive transcranial magnetic stimulation procedure over the medial anterior prefrontal cortex in humans.
Efference copy dysfunctions in heightened autistic traits impair the use of eye movement information for spatial representation and object localization.
Laurie Peverini, Sophie Shi ... Pierre-Jean Corringer
Conformational motions elicited by antagonists, partial agonists, and agonists in serotonin-gated ion channels 5-HT3AR progressively spread from the extracellular to the transmembrane domain.
This time-shortened work flow improves sensitivity and specificity for the identification of bacteria in bone infections independently of bacterial culturability.
Stephanie A Wankowicz, Ashraya Ravikumar ... James S Fraser
Creating structural models with multiple conformations of proteins improves the fit of the model to experimental data X-ray crystallography and improve the model geometry.
The parasitoid Trichopria drosophilae has evolved both molecular adaptions (venom proteins and teratocytes) and ecological strategies (tolerance of intraspecific and avoidance of interspecific competition) to successfully parasitize Drosophila suzukii.
Sanjay Kumar Sukumar, Vimala Antonydhason ... Ruth H Palmer
The newly characterized activity regulating neuropeptide encoding gene Spar is a transcriptional target of the Jeb/Alk receptor tyrosine kinase signaling pathway in the Drosophila nervous system.
The protein hyaluronan-mediated motility receptor interacts with microtubules to enhance their stability and recruits TPX2 to promote microtubule emanation in neurons.
Nguyen Lam Vuong, Nguyen Than Ha Quyen ... Ronald Geskus
Higher plasma viremia levels in early dengue and a slower subsequent decline are associated with worse clinical outcomes and provide valuable outcome measures for future therapeutic intervention trials.
The termination of medulla neuroblasts is specified by the depletion of the neuroepithelium and mediated by apoptosis, differentiation, and gliogenic switch.
The 'low water' agar assay provides a reliable and practical high-throughput method for studying plant molecular signaling responses to drought stress.
ROH-DICE is an efficient method for detecting ROH clusters in biobank data, enabling the study of population history of large cohorts, and providing a new genome-wide association analysis approach for finding disease-causing loci with multi-marker recessive effects.
Elissavet Chartampila, Karim S Elayouby ... Helen E Scharfman
Supplementing the diet in early life with choline improved memory, neuronal morphology, and neuronal activity in mice with a genetic form of Alzheimer's disease, whereas low choline had mixed effects.
Individual performance in rhythm perception and production is maximized within a range of domain-specific rates and is adversely affected by temporal context, and this effect is amplified with age.
Integrating an innovative community science platform with statistical modelling advances biodiversity monitoring and improves species habitat estimation across diverse taxa, supporting more effective conservation strategies.
In addition to the exon-F-binding domain and the globular tail domain-binding motif, the actin-binding domain of melanophilin interacts with myosin-5a tail region and mediates the association of myosin-5a with melanosomes.
Multimodal brain connectome analysis reveals patterns of structure–function coupling and links their developmental changes to cognitive function and transcriptomic architecture.
Irini Papazian, Maria Kourouvani ... Lesley Probert
Severely immunodeficient B2m-NOG mice transplanted with human peripheral blood mononuclear cells from multiple sclerosis patients partially reproduce disease immunopathology and represent novel experimental models for studying human immune responses to the central nervous system in a rapid and personalized manner.
Analysis of human cytomegalovirus-encoded glycoprotein US10 targeting human leucocyte antigen class I molecules reveals a multimodal strategy, resulting in a geno- and allotypic-dependent effects.
Computational and theoretical biomechanical analysis reveals how actomyosin filaments and axial muscles conjugate their activity to realize a fourfold elongation during C. elegans embryogenesis, 4 hr just before hatching.
Genetic and molecular analysis shows that Deltex modulates the Wingless gradient and counters Wingless signaling by promoting Armadillo/β-catenin degradation through a conserved regulatory mechanism.
The conserved AMP-activated protein kinase inhibits mitochondrial import of misfolded proteins and helps preserve mitochondrial and cellular fitness under proteotoxic stress.
Depleting senescent osteoclasts using the senolytic drug Navitoclax (ABT263) can reduce sensory innervation in the endplate and attenuate low back pain, thus representing a potent therapy for treating spinal pain.
Harshvardhan Gazula, Henry FJ Tregidgo ... Juan E Iglesias
New open-source software enables, for the first time, extraction of quantitative information from brain dissection photographs that are routinely taken at brain banks for archiving purposes but otherwise not exploited.
An inoculation experiment shows phyllosphere microbiome plays an important role in invader Ageratina adenophora population establishment by killing seedlings at very early growth stage.
Javier I Ottaviani, Virag Sagi-Kiss ... Gunter GC Kuhnle
The reliance on food composition databases for the assessment of dietary intake is unreliable and results in a large bias when investigating the associations between diet and disease risk.
Extrachromosomal DNA containing tumors up-regulate DNA damage and repair, cell cycle control, and mitotic processes, but down-regulate global immune regulation pathways, suggesting new avenues for therapeutic intervention.
Vilde Olsson Lalun, Maike Breiden ... Melinka A Butenko
A molecular investigation on the role of the peptide ligand inflorescence deficient in abscission (IDA) in regulating immunity and development during cell separation in Arabidopsis thaliana.
Marie Breeur, George Stepaniants ... Vivian Viallon
A computational method based on optimal transport enables state-of-the-art alignment between untargeted metabolomic studies and is evaluated on cord blood and cancer datasets.
The pseudokinase Tribbles1 is expressed in human monocytes after mycobacterial challenge and can be manipulated to be host protective against mycobacterial infection, due to control of innate immune cell function, in a zebrafish tuberculosis model.
Mathew Thayer, Michael B Heskett ... Phillip A Yates
Molecular genetic analyses of ASARs reveals regulation of large-scale mammalian chromosome structure and function that includes long non-coding RNAs and nuclear RNA binding proteins as essential regulators of chromosome dynamics.
A combination of cryo-electron microscopy, structure prediction, and evolutionary analyses reveal several functional states of the dynamic protein translocation machinery at the mammalian endoplasmic reticulum.
Katarzyna Drożdżyk, Martina Peter, Raimund Dutzler
Structural studies revealing the organization of assemblies consisting of CALHM2 and CALHM4 subunits provide insight into the mechanism of heteromerization of large pore channels.
Enigmatic long-lived plasma cells display an enhanced clustering in bone marrow niches and require CXCR4 for retention, survival, and maintenance of antibody titers.
Roberto Efraín Díaz, Andrew K Ecker ... James S Fraser
Biochemical and structural investigations of the pH adaptability of mouse Acidic Mammalian Chitinase offer insights for designing enhanced enzyme variants that can function in both lung and gut.
Genetic engineering of murine myeloid cells reveals the challenges in ectopic expression of chemiric receptors and provides a novel framework to endow them with tumor-specific cytotoxic ability.
Epithelial to mesenchymal transition (EMT) is a continuous process, in which the transition or intermediate states can be molecularly and spatially defined, shedding new light on development and disease EMT.
Haley R Noonan, Alexandra M Thornock ... Leonard I Zon
An in vivo reporter of TGFb signaling in zebrafish reveals that melanoma cells undergoing chronic TGFb signaling up-regulate extracellular matrix genes, down-regulate IFN, and are preferentially phagocytosed by macrophages compared to non-TGFb responsive melanoma cells.
Jonathan AC Menzies, André Maia Chagas ... Claudio R Alonso
A novel behavioural pipeline enables the quantitative analysis of the onset of movement in Drosophila embryos revealing that a microRNA modulates this process through regulatory effects in the sensory system.
Comparative transcriptome analyses of human placenta reveal regulatory divergence between native highlanders and lowland immigrants living at high altitude, and a sex-biased pattern of genetic adaptation.
When used to capture fluid cognition, Brain Age likely fails to add substantially more information over and above chronological age and could miss up to around one-third of the variation.
Nicolas Loyer, Elizabeth KJ Hogg ... Jens Januschke
PAR-3/Baz function is regulated by CDK1 in asymmetrically dividing cells in the central and peripheral nervous system of Drosophila revealing direct regulation of cell polarity by the cell cycle machinery in the context of cell fate specification.
Uninterrupted CAG repeat length determines onset age in Huntington's disease, and therefore, base editing strategies to generate CAA interruption offer new therapeutic opportunities as they diminish the disease-causing mutation.
Scaffolding protein RAPSYN can exert its NEDD8 E3 ligase activity to neddylate and stabilize oncogenic BCR-ABL by competing proteasomal degradation in Ph+ leukemia.
Viral evolution can lead to mutations that render specific glycosylation sites dispensable for folding and for supporting the protein's function, allowing changes in the shield, and in the immunogenic profile.
Phosphate and calcium from resorbing bone can find their way to the coronary circulation and contribute to atherosclerotic calcification of the blood vessels.
Maximilian Kurjahn, Antaran Deka ... Stefan Karpitschka
The self-buckling behavior of filamentous cyanobacteria allowed a quantification of their propulsion forces, indicating that adhesion plays an important role in gliding motility.
Amyloid-beta aggregates and lipopolysaccharide differ in their kinetics of Myddosome formation and size of Myddosome formed, providing an explanation for the less efficient triggering of TLR4 observed with aggregates.
Thomas Morgan Li, Victoria Zyulina ... Theresa T Lu
Interferon contributes to photosensitivity at least in part by causing Langerhans cell ADAM17 dysfunction, raising the possibility that anifrolumab ameliorates lupus skin disease in part by restoring Langerhans cell function.
A circuit within the nucleus accumbens that exists during a specific developmental window through early adolescence male rats may serve as a substrate that underlies heightened reward seeking in this population.
A novel bilinear modeling approach reveals genetic code of neuronal connectivity, offering insights for targeted genetic interventions in neural circuits.
Direct inhibition of pyridoxal phosphatase activity by 7,8-dihydroxyflavone indicates a pharmacological entry point into brain disorders associated with vitamin B6 deficiency.
LRRK plays an essential, cell-intrinsic role in the protection of dopaminergic neurons during aging, and new genetic findings suggest that LRRK2 mutations may impair its function, leading to dopaminergic neurodegeneration in PD.
Thomas RM Germe, Natassja G Bush ... Anthony Maxwell
DNA gyrase, a regulator of bacterial genomes topology, is shown to undergo rearrangements while functioning on DNA in vitro, with important potential consequences for gyrase-targeted antibiotics activity and bacterial evolution.
The peptidoglycan hydrolase activity of Enterococcus faecium secreted antigen A is crucial for cell wall remodeling during bacterial cell separation and generates muropeptides that stimulate host immunity to enhance immune checkpoint inhibitor anti-cancer therapy.
A detailed physiological characterization of inputs to the motor thalamus adds nuance to the notion that information from the cerebellum and basal ganglia are segregated and provides a mechanism by which the basal ganglia can gate communication between cortical areas.
Analysis of mouse zygotic genome activation (ZGA) reveals that a mis-annotated multicopy homeobox gene Obox4 functions redundantly with Dux to promote ZGA.
Single-cell RNA sequencing analysis of diabetic mouse cavernous tissue revealed that LBH is a novel pericyte marker and may interact with Crystallin Alpha B and Vimentin to promote neurovascular regeneration.
Weiting Zhang, Karl Petri ... Jing-Ruey Joanna Yeh
Strategic pegRNA designs and other approaches mitigating 5' and 3' interactions within pegRNAs can often lead to substantial improvements in prime editing efficiency.
Yi-Ting Chang, Eric A Finkel ... Daniel H O'Connor
Preparatory states within the motor cortex play a critical role in selecting an appropriate action in response to sensory input, dependent on the context.
Bulk and single-cell RNA-seq data demonstrated that muscle stem cells express low levels of canonical endothelial cell markers, including VEGFA receptors, and VEGFA-FLT1 pathway has a drastic effect on muscle stem cell survival through AKT1 in vitro and in vivo.
Ivan Castello-Serrano, Frederick A Heberle ... Ilya Levental
Direct measurements of trafficking kinetics between organelles of the secretory pathway suggest that lipid-driven membrane domains laterally sort proteins during membrane traffic.
Conditional abolishment of a G protein subunit in a subset of ectopic tuft cells engenders severer injury, slower recovery, and increased fatality following the infection of the influenza viruses.
A combined theoretical and experimental study revealed the mechanistic and structural basis of mutational effects on allostery and provided insights into the intrinsic connection of intra- and inter-domain properties.
It is shown that the absence of the centrosome protein ninein provokes premature ossification during mouse development, due to a defect in the fusion of precursor cells into syncytial osteoclasts.
Escherichia coli exhibits sensitive chemotaxis to potassium, mediated by differential responses of Tar and Tsr chemoreceptors to intracellular pH changes induced by potassium concentration gradients.
Giuseppina Porciello, Alessandro Monti ... Salvatore Maria Aglioti
Direct measures of inner gastrointestinal signals via ingestible capsules highlight the role of stomach pH in shaping human feelings of disgust, fear and happiness.
The autophagosomal membrane becomes negatively charged during maturation due to the accumulation of PI4P, leading to the recruitment of syntaxin 17, which is required for autophagosome-lysosome fusion.
Rafael F Guerrero, Tandin Dorji ... C Brandon Ogbunugafor
Inspired by notions of 'druggability' from medicinal chemistry, two new metrics, drug applicability and variant vulnerability, utilize evolutionary perspectives and methods to improve attempts to treat infectious diseases.
Advanced statistical and computational methods are reviewed and compared for integrating microbiome, host genomics, and metabolomics data, together with future research directions.
Individual olfactory-driven behaviors, odor preferences, and olfactory sensitivity have rapidly evolved in blind Mexican cavefish, as a quantitative genetic trait.
Yannick Schäfer, Katja Palitzsch ... Jaanus Suurväli
As a result of frequent gene duplication and haplotypic variation, a family of immune genes in the model vertebrate zebrafish has thousands of gene copies that are population- or individual-specific.
The first neurodevelopmental study using a novel, wearable brain imaging system based on optically pumped magnetometers, shows age-related changes in neural oscillatory task responses and cortical functional connectivity.
Abraham Escobedo, Salli-Ann Holloway ... Aaron J Norris
Activation of a population of glutamatergic neurons in supramammillary nucleus enhances active coping behaviors in response to threats, offering new insights for therapeutic strategies against anxiety and mood disorders.
Physiologically, vesicle replenishment at the fast calyx synapse requires both fast-endocytosis and scaffold machinery to support rapid neurotransmission, whereas at the slow hippocampal CA1 synapse only endocytosis is necessary.
Caroline Krag, Maria Saur Svane ... Tinne Laurberg
Treatment of colorectal cancer with colonic resection compared with rectal resection results in sligthly increased T2D risk, whereas chemotherapy treatment does not impact risk of developing T2D.
Fanny-Mei Cloarec-Ung, Jamie Beaulieu ... David JHF Knapp
Precision genome editing in human hematopoietic stem and progenitor cells can achieve near-perfect efficiency with tunable zygosity, thus enabling isogenic disease modeling for monogenic blood disorders and improving therapeutic applications.
A computational model of skeletal muscle regeneration reveals complex interplay of cytokines, angiogenesis, and cell behaviors, predicting that synergistic cytokine perturbations enhance skeletal muscle regeneration beyond individual cytokine interventions.
Styxl2, a sarcomeric muscle-specific pseudophosphatase in vertebrates, functions in sarcomere assembly by promoting protein degradation of non-muscle myosin IIs.
Deborah H Brotherton, Sarbjit Nijjar ... Alexander David Cameron
The mutation of Lys125 in connexin26 to glutamate, a carbamylation mimetic, pushes the equilibrium of the gap junction channel seen in cryo-EM towards a more closed conformation.
DUX4 expression is a common feature of metastatic tumors, where it is significantly associated with immune cell exclusion, decreased objective response to immune checkpoint blockade, and reduced patient survival.
