The axial organization and dynamics of the HOPS complex at membrane surface are resolved by graphene-induced energy transfer with subnanometer resolution.
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.
Karl N Miller, Nirmalya Dasgupta ... Maria Grazia Vizioli
Cytoplasmic chromatin fragment formation pathways in senescent cells are a potential therapeutic target for modulation of inflammation in aging, which contributes to age-associated diseases.
Tracing the evolution of an old master sex determination gene reveals a diversity of sex determination transitions, including a complete Y chromosome loss, among an old teleost order (Esociformes).
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.
Jaakko I Lehtimäki, Eeva Kaisa Rajakylä ... Pekka Lappalainen
Live-cell microscopy studies revealed that stress fibers can be generated de novo from the actin cortex without the involvement of stress fiber precursors.
Stem cell transplantation reduces intraocular pressure and preserves retinal ganglion cell function in a mouse glaucoma model, which could lead to a novel therapy for glaucoma to preserve vision.
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.
Amit Frishberg, Inge van den Munckhof ... Irit Gat-Viks
A novel type of metabolic syndrome, derived from computational modeling of phenotypic diversity in normal physiological settings, increases the risk of certain complex diseases.
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.
Multi-dimensional global proteomics describes the SUMO-modified proteome during meiosis and reveals novel roles in regulating the key events of meiotic chromosome metabolism.
Foxc1 proteins prepare the genomes of neural crest-derived cells to facilitate their later development into the cartilages that support the embryonic face.
Sayedeh Hussaini, Vishalini Venkatesan ... Stefan Luther
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.
Bercem Dutagaci, Grzegorz Nawrocki ... Michael Feig
Charge complementarity between RNA and proteins may be a universal principle for phase separation in biology without requiring disorder or specific multivalent interactions.
Elizabeth A Landis, Angela M Oliverio ... Benjamin E Wolfe
In the most comprehensive survey of sourdough starter biodiversity, this work identifies processes that control the diversity and function of sourdough microbiomes at a continental scale.
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.
A flexible and accurate methodology to fit reduced compartmental models to dendritic morphologies shows that models with very few compartments can capture many dendritic computations.
Jacob L Johansen, Lauren E Nadler ... Jodie Rummer
The ability of animals to adjust to thermal stress is critical for survival under global warming, yet the adjustment process and scope have (until now) remained obscure in marine fishes.
Fernando R Balestra, Andrés Domínguez-Calvo ... Pierre Gönczy
TRIM37 prevents the formation of centriolar protein assemblies through an atypical de novo assembly pathway that would otherwise threaten genome integrity.
A supervised methodology for mutational signatures outperforms the current standard unsupervised approach revealing new tissue-dependent mutational signatures among which some for obesity.
Although Rad51 is the central protein involved in recombinational DNA repair, multiple auxiliary factors potentiate its activity by binding to a single, evolutionarily conserved motif.
Michael Borg, Ranjith K Papareddy ... Frédéric Berger
Epigenetic reprogramming of the distinct repressive marks H3K27me3 or H3K9me2 guides the transition between the haploid and diploid life forms that encompass the life cycle of land plants.
A ClC chloride channel protein allows neurons to interpret both temporal resolution and intensity of sensory input, which thereby contributes to an experience-dependent navigation behavior.
Distinct selective landscapes in mosquito and human cells shape dengue virus genetic diversity and highlight mechanisms of host adaptation in arboviruses.
Asymmetric forward and backward swimming speeds reveal that the rotational bias, and not reversal frequencies, is an appropriate measure of chemotaxis signaling in Helicobacter pylori..
Identification of heterogenous cranial neural crest (CNC)-derived cell populations and their roles in guiding craniofacial muscle development through cell-cell interactions.
The molecular regulatory mechanisms that control the interaction between mesenchymal stem cells and transit amplifying cells to maintain tissue homeostasis.
Dennis V Pedersen, Martin Nors Pedersen ... Gregers R Andersen
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.
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.
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.
The discovery of non-canonical telomeric dsDNA-binding proteins in Caenorhabditis elegans reveal their contribution in the maintenance of telomere length and germline immortality.
Lotte Victoria Winther Stagsted, Eoghan Thomas O'Leary ... Thomas Birkballe Hansen
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.
Laura J Wagstaff, Jose A Gomez-Sanchez ... Kristjan R Jessen
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.
Lavanya H Palavalli Parsons, Sridevi Challa ... W Lee Kraus
PARP-7 is a mono(ADP-ribosyl) transferase that directs an extensive ADP-ribosylated proteome to control microtubule stability, and regulate ovarian cancer cell growth and motility.
Kelsie M Rodriguez, Sara C Buch-Larsen ... Michael S Cohen
A combined chemical genetics, proximity labeling, and ADP-ribose site mapping approach shows that PARP-7 mono-ADP-ribosylates immune-relevant proteins on cysteine amino acids.
Andrew W DeVilbiss, Zhiyu Zhao ... Sean J Morrison
A method was developed for the metabolomic analysis of small numbers of flow cytometrically isolated cells from rare cell populations such as hematopoietic stem cells and circulating cancer cells.
Cristina Herencias, Jerónimo Rodríguez-Beltrán ... Álvaro San Millán
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.
Active DNA demethylation at some defence gene promoters is causal for DNA binding of WRKY transcription factors as well as for transcriptional activation of these genes during plant immune response.
The courtship master gene fruitless tunes functional flexibility of courtship circuitry during development instead of switching on its function as conventionally viewed.
Lara Urban, Andre Holzer ... Maximilian R Stammnitz
From now on, nanopore metagenomics can be used to monitor aquatic environments with high spatiotemporal resolution, by use of a benchmarked, standardised and cost-effective workflow.
The structures of plant CIII2, CIV, and SC III2+IV challenge long-standing assumptions, generate new mechanistic hypotheses and allow for the generation of more selective agricultural inhibitors.
The arcuate nucleus kisspeptin neurons express multiple transmitters but use only the neuropeptide kisspeptin to drive the episodic secretion of gonadotropin-releasing hormone.
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.
Phylogenetic and computational methods reveal that at least two seasonal coronaviruses are evolving adaptively in the region of the viral spike protein exposed to the human humoral immune system.
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.
Milo S Johnson, Shreyas Gopalakrishnan ... Michael M Desai
Experimentally evolved yeast populations increase in fitness predictably but do not divide into coexisting lineages or dramatically increase their mutation rates after 10,000 generations.
Megan M Colonnetta, Lauren R Lym ... Girish Deshpande
A molecular duel between germline and somatic determinants ensures proper establishment of transcriptional quiescence in the primordial germ cells of early Drosophila embryos.
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.
Reza K Hammond, Matthew C Pahl ... Struan FA Grant
By integrating GWAS data sets with ATAC-seq and promoter-focused Capture C data, one can uncover further loci beyond those that reach genome-wide significance (p<5x10-8).
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.
A dual-channel image registration pipeline combined with deep-learning inference achieves accurate-and-flexible registration/segmentation/mapping of mouse brain.
Mathematical modelling suggests that the evolution of communication between bacterial viruses requires repeated outbreak events, and the model then predicts typical communication strategies.
Iris E Glykofridis, Jaco C Knol ... Rob MF Wolthuis
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).
Julianne M Troiano, Federico Perozeni ... Gabriela S Schlau-Cohen
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.
Jason W Millington, George P Brownrigg ... Elizabeth J Rideout
The ability to adjust body size in response to diet is greater in Drosophila females than males because of a sex difference in the nutrient-dependent regulation of the insulin pathway.
Danielle Janosevic, Jered Myslinski ... Pierre C Dagher
Single-cell RNA-sequencing identifies the precise cellular and molecular events that occur along the sepsis timeline in the kidney, pointing to potential biomarkers and therapeutic targets.
Martin Steen Mortensen, Morten Arendt Rasmussen ... Søren Johannes Sørensen
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.
Innate antiviral factors do not always perfectly distinguish between self and foreign, and potential adverse effects of antiviral defense mechanisms for the host have been discussed.
Marcos H de Moraes, FoSheng Hsu ... Joseph D Mougous
Interbacterial interactions can promote mutagenesis, and possibly adaptation, when intoxicated cells survive exposure to type VI secretion-delivered DNA deaminase toxins.
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.
Eva Liliane Ujeneza, Wilfred Ndifon ... IeDEA-Southern Africa collaboration
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.
Kelsey E Huntington, Anna D Louie ... Wafik S El-Deiry
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.
M Fernanda López-Gutiérrez, Zeus Gracia-Tabuenca ... Sarael Alcauter
Brain functional connectivity shows a neurobiological predisposition to social bonding, and network-wide changes occur as a result of cohabitation in the prairie vole.
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.
Alexander J Sercel, Alexander N Patananan ... Michael A Teitell
Applied pressure enables efficient isolated mitochondrial transfer and stable mitochondrial DNA (mtDNA) transplantation into a range of mtDNA-depleted cell types to restore respiration.
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.
Dingbang Ma, Dariusz Przybylski ... Michael Rosbash
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.
Risa Ebina-Shibuya, Erin E West ... Warren J Leonard
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.
Oxytocin, but not the structurally similar vasopressin, modulates both the chemosensory decoding of femininity in straight men and that of masculinity in gay men in an inverted-U-shaped manner.
Chronic exposure to a potent chemical contact sensitizer drives a self-limiting expansion of a polyclonal population of T cells recognizing a small number of dominant antigens.
Andrea Cipriano, Martina Macino ... Monica Ballarino
The epigenetic regulation of adult muscle stem cell fate by lnc-Rewind relies on the RNA-mediated recruitment of G9a methyltransferase on the Wnt7b genomic locus.
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.
Rejuvenation of corneal epithelium in homeostasis is determined by the interplay between corneal cells replicative lifespan and the spatial correlation between cell replication and cell removal.
Leaf-cutting ants use their fecal fluid to vector enzymes produced by their fungal symbiont to degrade plant biomass with a combination of degradation enzymes and Fenton chemistry.
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.
Florian Mattenberger, Victor Latorre ... Ron Geller
Comprehensive analyses of how mutations in a picornavirus capsid affect viral fitness provide novel insights into viral biology, evolution, and host interactions.
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.
Laura E Doepker, Sonja Danon ... Julie M Overbaugh
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.
Sashank Pisupati, Lital Chartarifsky-Lynn ... Anne K Churchland
During perceptual decision-making, some errors on easy decisions (lapses) are not simply mistakes, but instead reflect strategic decisions to explore actions associated with uncertain rewards.
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.
Nicole Rosskothen-Kuhl, Alexa N Buck ... Jan WH Schnupp
Early deaf human CI users are often insensitive to sub-millisecond interaural time differences (ITDs); however, with synchronized CIs, early deafened rats learned to lateralize small ITDs near 50 µs.
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.
Ancient protein domains remain shaped by amino acid availability during early life, while young animal proteins are shaped by a need for high intrinsic structural disorder.
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.
David W Hawman, Kimberly Meade-White ... Heinz Feldmann
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.
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.
Laura Whitworth, Jacob Coxon ... Lalita Ramakrishnan
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.
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.
Brian V Tsu, Christopher Beierschmitt ... Matthew D Daugherty
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.
Adishesh K Narahari, Alex JB Kreutzberger ... Douglas A Bayliss
Purified Pannexin 1 channels activated by caspase cleavage in proteoliposomes reconstitute a permeation pathway for intercellular signaling molecules important in inflammation and cell clearance.
Xiaochuan Zhao, Umar F Shahul Hameed ... Jianing Li
Combining in silico and experimental approaches to identify and understand the residue changes in the H-NS protein that allowed bacteria to adapt environment-sensing to different habitats.
Aynur Kaya-Çopur, Fabio Marchiano ... Frank Schnorrer
Muscle fiber growth during development is controlled by the Hippo pathway that links the assembly state of the contractile sarcomeres with the transcriptional state of the sarcomeric genes.
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.
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.
UPF1 mutations were reportedly present at high frequencies in a cohort of pancreatic adenosquamous carcinoma patients, but these lesions are unlikely to be functional drivers of this cancer subtype.
Tjorven Hinzke, Manuel Kleiner ... Stephanie Markert
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.
Julio D Perez, Susanne tom Dieck ... Erin M Schuman
Single somata and dendrites of individual rat neurons were laser-captured and sequenced to discover and compare the subcellular transcriptomes, identifying over 4000 mRNAs in GABAergic dendrites.
John P Russell, Xinhong Lim ... Cynthia L Andoniadou
Stem cells of the pituitary gland contribute to organ growth cell non-autonomously by promoting proliferation of committed progenitors through WNT ligand secretion.
Salah A Baker, Wesley A Leigh ... Kenton M Sanders
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.
Spontaneous elongation of epithelial colonies is related to the orientation of the mean nematic cell elongation field, as shown and tested with experiments and theory.
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.
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.
Whereas SARS-CoV-2 utilizes cathepsins to enter most cell lines, human airway organoids revealed that entry into relevant cells is dependent on serine proteases, which can be targeted for treatment.
Marc A Schureck, Joseph E Darling ... Sanjay A Desai
A high-resolution structure reveals how the RhopH complex traffics within Plasmodium-infected human erythrocytes to serve divergent, essential functions.
Humans supplement complex, resource-demanding strategies with simple heuristics for solving the exploration-exploitation dilemma, and noradrenaline functioning controls their utilisation.
Samuel J Gershman, Petra EM Balbi ... Jeremy Gunawardena
Single cells are believed to be incapable of complex forms of learning, but reconsideration of historical studies and more recent developments suggest that this orthodoxy must now be reconsidered.
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.
Genetic lineage tracing approach combined with live imaging visualized the functional stem cell activity of Doublecortin-like kinase 1+ cells within pancreatic cancer in vivo.
Single cell transcriptomic analysis provides a reference map for human oral muscosa in health and disease and a framework for the development of new therapeutic strategies.
