The combined use of NAD+ with ribitol or ribose potentiates the rescue of α-dystroglycan functional glycosylation in FKRP-mutant patient-specific iPSC-derived myotubes, representing potential novel treatments for FKRP muscular dystrophies.
Cellular immunological and biochemical analyses reveal how decoy IL-1RII is induced by human CD4+ T cells upon TCR-stimulation and regulates the Th17-Treg balance by modulating IL-1β responsiveness in IL-1RI+ cells.
Ligands with different efficacy profiles shift the free energy landscape of the beta2 adrenergic receptor activation and stabilize diverse active-like states via the switch of microswitches lining an allosteric pathway.
Findings of this population-based sibling-matched cohort study corroborate an association of loss of a co-twin at birth with risk of psychiatric disorders, supporting the hypothesis of twin-bond development in utero.
Excitability gradients in heart tissue, imposed by structured sub-threshold optogenetic stimulation, induce drift and termination of spiral waves, thus providing an explanation for successful optogenetic defibrillation in small animal hearts.
Single-cell RNA sequencing highlights the influence of host–pathogen interactions and stochasticity on transcriptional and phenotypic variance in lymphoblastoid cell lines derived from Epstein–Barr virus-infected primary B cells.
A single dose of a characterized motility-deficient mutant was sufficient to induce robust anti-protein antibodies' response and cross-protective immunity against death and colonization in two different animal models of leptospirosis.
Optogenetic experiments show that bridging microtubules buffer chromosome movements and promote their alignment through forces transferred to the associated kinetochore fibers, which rely on precise regulation of the overlap region.
Seven distinct cryo-electron microscopy structures delineate the elaborate mechanism for how E. coli Mfd, a transcription repair coupling factor, disassembles the RNA polymerase transcription elongation complex to initiate transcription-coupled repair.
Combining electron microscopy and solution scattering demonstrated that properdin oligomers adopt extended rigid and well-defined conformations that are integral to the biological function of this complement regulator.
Transcriptome and eCLIP analyses in mouse and human reveal splicing factor proline/glutamine rich (SFPQ) as a conserved and critical guardian of long-intron integrity, splicing, and circular RNA (circRNA) production.
In vivo experiments on transgenic mice, and cell culture studies, establish Schwann cell c-Jun as a central regulator of peripheral nerve repair, and repair failure, during aging and chronic denervation.
Acquisition of antibiotic resistance plasmids induces collateral sensitivity to clinically relevant antibiotics in Escherichia coli, paving the way for targeted 'anti-plasmid' therapies able to preferentially eliminate plasmid-carrying bacteria.
Placing the PACAP/PAC1 signaling within glutamate/GABA cell type and subregional contexts in mouse brain reveals its conspicuous role for sensorimotor circuit interaction through modulating neuronal plasticity.
Habitats of satellite-tracked blue sharks were shifted surfaceward by an oxygen minimum zone (OMZ) at depth thereby increasing their susceptibility to capture by longline fishing focused above the OMZ.
Knocking out Folliculin (FLCN) in human renal epithelial cells activates STAT1/2-mediated gene expression, independent of interferon, uncovering a tissue-specific process potentially relevant in the cancer syndrome Birt-Hogg-Dubé (BHD).
ICOSL-dependent T-cell co-stimulation contributes to the host defense against herpesvirus infections, and accordingly, these pathogens have developed immune evasion mechanisms to interrupt the ICOSL:ICOS signaling pathway.
Combining global and local force measurements of reconstituted muscle tissue using a new chamber system that is compatible with high-resolution microscopy shows mechanical homeostasis already within a week.
Modeling weighted transfer ratios enable statistical analysis of maternal–infant transfer at a more general level and can indicate whether any transfer is persistent, transient, or originates from alternate sources.
The molecular identity of bi-fated tendon-to-bone attachment cells, which display a mixture of transcriptomes of two neighboring cell types, enables the formation of the unique transitional tissue of the enthesis.
Light-harvesting complex stress-related is a protein from photosynthetic green algae that prevents damage from sunlight via two distinct conformational processes, which protect against different timescales of solar fluctuations.
Temperature-dependent fasciation mutants of Arabidopsis unexpectedly connect mitochondrial RNA processing to the control of cell proliferation during lateral root morphogenesis via electron transport chain activity and reactive oxygen species production.
Long-term immune outcomes vary with age, for both adults and children in HIV-infected populations, e.g. long-term scaled carrying capacity is lower in HIV-infected younger individuals compared to older individuals.
A mutual information algorithm points to macrophage activation syndrome as a specific pathogenic mechanism in COVID-19, correlated with disease severity, which could be used to monitor disease and therapeutics.
Analysis of knockout and knockdown melanoma cells and TCGA melanoma data shows that the microphthalmia-associated transcription factor (MITF) is a major repressor of extracellular matrix (ECM) and focal adhesion genes.
Immunological analysis of wild-type and Crlf2-/- mice reveals a role for the cytokine thymic stromal lymphopoietin on memory CD8+ T-cell responses to viral infection, findings with potential translational implications.
Drosophila clock neurons manifest remarkable heterogeneity, which might be generally true and help explain why Drosophila has a sophisticated behavioral repertoire despite a tiny brain of about 100,000 neurons.
Excitatory synapses that occur further away from the postsynaptic cell soma exhibit greater neurotransmitter release probability, which appears to improve signal transfer fidelity for high-frequency afferent firing.
HIV vaccine-induced binding and neutralizing antibody epitope specificities were mapped at high resolution directly from polyclonal sera, overcoming shortcomings in traditional serum mapping approaches and enabling highly detailed vaccine design.
High-resolution risk estimates of opisthorchiasis were produced in major endemic countries of Southeast Asia, providing valuable information for guiding disease control and serving as a baseline for future progress assessment.
A new imaging modality is described that can simultaneously record from several dishes without using robotics, which enables researchers to perform high-throughput, continuous measurements on biological samples.
A basidiomycete yeast closely related to fungal smuts is an antagonistic microbe in the Arabidopsis leaf phyllosphere that inhibits infection by Albugo laibachii via a GH25 hydrolase with lysozyme activity.
Out breeding depression in Caenorhabditis tropicalis is due to common maternal-offspring incompatibilities that interact with a highly heterogeneous genetic background and may provide a short-term advantage to inbreeding.
Single-cell transcriptomes of Drosophila olfactory projection neurons correspond to previously defined cell types, exhibit unique characteristics at different developmental stages, and reveal cell-type-specific gene expression programs in development and function.
HIV-specific antibodies that mediate antibody-dependent cellular cytotoxicity vary in their paths to achieve function but commonly rely on mutations in multiple regions, including framework regions, to reach full potency.
Investigation into methotrexate's effects in the vascular endothelium reveals it exerts anti-inflammatory effects through a unique adenosine-adenosine receptor A3-SMAD3/4-miR-181b signaling axis with implications for controlling vascular inflammation.
In this ideal example of pharmacogenomics, individuals with a common variant in a gene encoding for an inflammatory lipid mediator benefit selectively from standard-of-care anti-inflammatory treatment used for tuberculous meningitis.
Interaction of oncoprotein transcription factor MYC with chromatin-associated protein host cell factor–1 controls expression of genes important for ribosome biogenesis and mitochondrial vigor, loss of which promotes tumor regression.
A mouse-adapted strain of Crimean-Congo hemorrhagic fever virus that recapitulates human disease in wild-type mice significantly improves our ability to study Crimean-Congo hemorrhagic fever virus pathogenesis.
The mechanism underlying Shprintzen–Goldberg syndrome is solved and reveals that missense mutations in the transcriptional repressor SKI abolish ligand-induced SKI degradation, which results in attenuation of TGF-β transcriptional responses.
For many bacterial species, recombination dominates genome evolution and phylogenetic patterns that have so far been assumed to reflect clonal relationships, in fact reflect variation in recombination rates across lineages.
Proteases from diverse viruses, the first described pathogen-encoded activators of human NLRP1, cleave NLRP1 at a sequence that mimics the viral polyprotein, resulting in inflammasome activation and pro-inflammatory cytokine release.
Deep imaging, machine-learning-based segmentation, and tissue annotation resulted in a developmental series of 3D digital ovules with cellular resolution allowing next-level analysis of the ontogenesis of this complex organ.
Physiological differentiation during symbiosis leads to division of labor between smaller and larger cells in an uncultured bacterial tubeworm symbiont population and results in remarkable metabolic diversity and complexity.
A combination of animal models reveal how the molecular mechanisms of exosome secretion (RalA/B-dependent) are linked to their cargo content and their function in breast cancer pre-metastatic niche formation.
An optogenetic dual-color Ca2+-imaging approach shows how submucosal pacemaker-cells, interstitial cells of Cajal, modulate smooth-muscle responses and drive colonic motility via complex Ca2+ signaling.
Admixture-mediated adaptation to malaria in a human population demonstrates that detectible signatures in genomic patterns of ancestry can be leveraged to better characterize recent selection in populations with mixed ancestry.
The LINC complex has a core 6:6 structure in which KASH-binding induces head-to-head interactions between SUN trimers, suggesting force transduction between cytoskeletal and nuclear components through branched LINC complex networks.
A molecular atlas of the chick retina provides a comprehensive classification and characterization of 136 cell types, yielding novel insights into retinal structure, function, development, and evolution.
Skin epithelium can tolerate oncogene-expressing clones through a novel cellular mechanism of inter-clonal competition between renewing progenitors along the clone's edge and differentiating progenitors within the clone's core.