Phosphorylated tau was related to a loss of structural stability in medial temporal lobe connectivity, and this loss of stability moderated the relationship between phosphorylated tau accumulation and memory decline.
This review considers the evolutionary processes and physiological mechanisms that maintain or end pregnancy in mammals to formulate general, testable theoretical models that provide insights into the biology of parturition.
Genomic analyses provide new insights into natural history and pathogenesis of cytomegalovirus infection and suggest new testable hypotheses that could be important for the design and implementation of new vaccines.
Deep and comprehensive proteomic resource of human intervertebral disc at high spatial resolution with a methodological flow reveals new insights in disc homeostasis and degeneration.
Developmental defects of the cochlea caused by dysregulation of sonic hedgehog signaling are the potential etiology for hearing loss in a group of ciliopathies with defective ciliogenesis.
Timothy A Currier, Andrew MM Matheson, Katherine I Nagel
Electrophysiology identifies a population of fan-shaped body neurons that encode airflow in two directions relative to the fly midline and whose silencing disrupts proper orientation to airflow.
The immune effector Drosomycin buffers stress signaling in hypertrophic salivary glands to inhibit their disintegration, detection by the cellular immune response, and promotes further overgrowth.
A novel role of endosomal machineries retromer and ESCRT in membrane delivery of Drosophila septate junction components is required for maintenance of junction integrity and epithelial barrier function.
Emx2 is not required for sibling HCs to acquire their designated locations within the neuromast, inferring that Emx2 mediates opposite HC orientation by changing location of hair bundle establishment.
A new nomenclature convention for mammalian cell types utilizing shared taxonomies and quantitative cell features is applied to high-quality, open data from the mouse and human brain.
Behnom Farboud, Catherine S Novak ... Barbara J Meyer
RNA binding protein FOX-1 functions as a dose-dependent X-signal element to communicate X-chromosome number and determine nematode sex by controlling alternative non-productive pre-mRNA splicing of the master sex-determination switch gene.
Ensemble fluidity, observed as synaptic turnover and temporal drift in neuronal patterns, supports memory-updating and flexibility while maintaining memory stability.
Computational models and software connect metagenomics to metabolic network reconstruction, assess metabolic complementarity between species, and identify critical species associated to functions of interest.
Inhibitory neurons in the hypothalamus and amygdala push and pull on the midbrain vocal gating circuit to trigger and suppress ultrasonic vocalization (USV) production in the mouse.
A series of selective events, each improving fitness relative to an immediate predecessor, can result in organisms that are less fit compared to a distant ancestor.
Long under-appreciated, fibroblast biology is a key aspect of understanding how the immune system responds to tumors and may hold the key to improving immunotherapy in this tricky space.
Diverse muscle spindle firing, critical for a range of sensorimotor behaviors, is compactly explained by first principles of force development in specialized muscle fibers within the sensors.
Representation of goals in the forms previously reported in the PFC is not required for performance of a novel spatial working memory task where goal information must be used flexibly.
Theoretical study shows how enzymes can achieve substrate proofreading by taking advantage of existing molecular gradients in the cell while not being endowed with structural features typically required for proofreading.
Systematic CRISPR-based editing of tRNA genes revealed that different human cells that span a range of growth rates and different modes of proliferation states require diverse tRNA sets.
Alexandre B Leitão, Ramesh Arunkumar ... Francis M Jiggins
Single-cell transcriptomics of immune cells demonstrates that populations evolve inducible defences when infection rates are low and constitutive defences when infection is common.
Elastic forces generated by the giant protein titin define both passive and active tension of skeletal muscle fibers and protect the sarcomeric myosin filaments from severe disruption during contraction.
Trans-synaptic protein interactions are required for synapse specification and function, and the combination between neuroligin3 and αneurexin1 controls inhibitory synaptic function in a splice isoform- and interneuron-specific manner.
Lauretta El Hayek, Islam Oguz Tuncay ... Maria H Chahrour
Successful autism spectrum disorder gene discovery using forward genetics identifies KDM5A, which encodes a histone H3 lysine 4 demethylase, as a disease gene.
Rebecca C Adikes, Abraham Q Kohrman ... David Q Matus
During organismal development, CDK activity at mitotic exit is predictive of future cell behavior, indicating whether a cell will divide again or enter a quiescent state.
Sean R Cuddy, Austin R Schinlever ... Anna R Cliffe
Herpes simplex virus reactivates from a latent infection when neurons become hyperexcitable in response to an inflammatory cytokine known to be released during fever and stress.
Structural and biochemical data suggest a mechanism for the Synaptojanin1-catalysed reaction and the role of mutations in the onset of associated neurological diseases.
Optogenetic and electrical low-frequency stimulation in the sclerotic hippocampus prevents the emergence of spontaneous focal and evoked generalized seizures in a mouse epilepsy model.
An integrated cryoEM and X-ray crystallography study resolves the structural basis for antibody-mediated targeting of the hantavirus fusion glycoprotein and provides insight into the conformational landscape of the hantavirion surface.
Integration of automatic behavioral tracking with brain molecular profiling reveals the role of gene regulatory network plasticity in the regulation of behavioral phenotypes.
Contrary to the high absolute number of white-eyes in other parts of the world, the Indonesian archipelago is the center of phylogenetic diversity of this great speciator.
Class 1 histone deacetylase (HDAC) inhibitor MS-275 enhances the efficacy of glucagon-like peptide 1 receptor (GLP-1R) therapy for glycemic control and reduction of obesity.
Hierarchical modeling of internalizing symptoms and task performance reveals that difficulty adapting probabilistic learning to second-order uncertainty is common to anxiety and depression and holds across rewarding and punishing outcomes.
Sonia Accossato, Felix Kessler, Venkatasalam Shanmugabalaji
SUMOylation contributes to the fine-tuning of the proteostatic equilibrium of essential chloroplast protein import receptor TOC159 at early plant development.
Diffusion-MRI-based cerebral cortical microstructure encoding regionally differential dendritic arborization and synaptic formation at birth robustly predicts future 2-year-old cognitive and language outcomes with regionally heterogeneous contribution that exhibits functional selectivity.
Hugo Ducuing, Thibault Gardette ... Valerie Castellani
A combination of in vivo models and imaging techniques reveals the distribution of guidance cues and their mechanisms of action during commissural axon navigation of intermediate target.
Simultaneous voltage and calcium two-photon imaging of Purkinje neuron dendrites in awake mice reveals multiple interplaying mechanisms underlying sensory-evoked dendritic coincidence detection of parallel fiber and climbing fiber input.
Iku Tsutsui-Kimura, Hideyuki Matsumoto ... Mitsuko Watabe-Uchida
Dopamine signals in the ventral, dorsomedial, and dorsolateral striatum are modulated by various variables, such as stimulus-associated value, choice, confidence, but these modulations can be inclusively explained by TD errors.
In the processing of spoken narratives, bottom-up acoustic cues and top-down linguistic knowledge separately contribute to neural construction of linguistic units.
Loss of hepatic Cdk1 leads to oxidative stress, increased fatty acids in blood, and hyperinsulinemia, which resulted in insulin resistance and hepatic steatosis, similar as in diabetes.
Introgression makes hemiplasy more likely, and the probability of hemiplasy incorporating incomplete lineage sorting (ILS) and introgression can be estimated using the presented simulation software.
Peter Jan Hooikaas, Hugo GJ Damstra ... Anna Akhmanova
Kinesin-4 KIF21B promotes rapid reorientation of the microtubule network during formation of immunological synapse in T cells by acting as a pausing and catastrophe-inducing factor that keeps microtubules short.
David E Cook, H Martin Kramer ... Bart P H J Thomma
Assessment of DNA methylation, histone modifications, and DNA accessibility revealed that physical DNA characteristics are associated with adaptive genome evolution in the broad host range plant pathogenic fungus Verticillium dahliae.
Daniel A Lee, Grigorios Oikonomou ... David A Prober
Experiments using zebrafish identify a novel sleep-promoting neuronal circuit in which hypothalamic NPVF neurons promote sleep via the hindbrain serotonergic raphe nuclei, which promote sleep in both zebrafish and mice.
Rapid, label-free, volumetric, and automated assessment of the immunological synapse dynamics is demonstrated by combining optical diffraction tomography and deep-learning-based segmentation, providing a new option for immunological research.
Michaela Gregorova, Daniel Morse ... Ruth C Massey
Post-acute or long-COVID is associated with bystander T-cell activation and a recurring antimicrobial resistant, bacterial ventilator-associated pneumonia.
Selective activation of FZD7 signaling with an engineered WNT mimetic promotes early developmental programs, including endodermal lineage specification, in human pluripotent stem cells.
Pierre-Louis Bazin, Anneke Alkemade ... Birte U Forstmann
An open-source software tool enables the anatomical parcellation of an unprecedented number of subcortical structures in magnetic resonance images of the human brain, automatically and in individual subjects.
Yanjun Li, Katherine EM Tregillus ... Stephen A Engel
The visual system can learn to rapidly adjust itself through experience, switching modes to stabilize vision perception and optimize perceptual processes.
José Antonio Escudero, Aleksandra Nivina ... Didier Mazel
The coexistence of ancestral and innovative functions is possible and fosters evolutionary innovation in events involving the acquisition of whole protein domains.
The INM protein LAP1B, an activator of Torsin ATPases, is a chromatin-binding factor that erroneously persists on mitotic chromatin if Torsin functionality is compromised, inducing chromosome segregation defects and binucleation.
Lucas R Glover, Kerry M McFadden ... Andrew Holmes
A neural circuit between the prefrontal cortex and bed nucleus of the stria terminalis is shown to limit fear to cues that only partially associate with threat.
Jennifer D Deem, Chelsea L Faber ... Gregory J Morton
A combination of neuroscience approaches and indirect calorimetry demonstrate a physiological role for AgRP neurons in cold-induced hyperphagia and strongly suggest temperature is an important regulator of AgRP neuron activity.
For perceptual inference, human observers do not estimate sensory uncertainty instantaneously from the current sensory signals alone, but by combining past and current sensory inputs consistent with a Bayesian learner.
A widespread family of chaperones functions to stabilize membrane protein effectors by mimicking transmembrane helical environments and promotes effector export by the bacterial type VI secretion system.
Benjamin M Adams, Nathan P Canniff ... Daniel N Hebert
Natural substrates of the central endoplasmic reticulum quality control glycoprotein sensors UDP-glucose:glycoproteinglucosyltransferase (UGGT)1 and UGGT2 were identified using a glycoproteomics approach and the role for their modification was explored.
Huiliang Zhang, Nathan N Alder ... Peter S Rabinovitch
The primary respiratory defect seen in aged cardiomyocytes is an elevated proton leak mediated by ANT1, and this is prevented by treatment with SS-31 (elamipretide).
Teeth and dermal odontodes diverge from the same set of founder odontodes, demonstrating they are modified subsets of the same system, and both oral and dermal epithelial have patterning capacity.
Time-resolved and site-directed in vivo photo-crosslinking analysis of VemP allows identification of both cis- and trans-elements required for its regulated arrest-cancelation.
Zachary M March, Katelyn Sweeney ... James Shorter
Exploring natural Hsp104 variation reveals unexpected tuning of a passive activity that inhibits aggregation of specific substrates to selectively counter TDP-43 or alpha-synuclein proteotoxicity connected to neurodegenerative disease.
Andrey A Parkhitko, Divya Ramesh ... Norbert Perrimon
The tyrosine degradation pathway reprogramming connects mitochondrial dysfunction, aging, and production of tyrosine-derived neuromediators that can be targeted with an FDA-approved drug, Tigecycline.
Aleksei Innokentev, Kentaro Furukawa ... Tomotake Kanki
Ppg1-dependent assembly of the mitochondrial Far complex and association/dissociation between the Far complex and Atg32 are crucial determinants for mitophagy regulation in yeast.
Atsuko Kinoshita, Alice Vayssières ... George Coupland
The shoot meristem becomes domed in shape during floral transition and this is controlled by flowering pathways and the phytohormone gibberellin causing increases in cell size and number.
Jack Alfred Bryant, Faye C Morris ... Ian R Henderson
Analysis of the E. coli protein DolP reveals the first dual BON-domain structure and identifies phospholipid binding as a new mechanism for protein localisation to the outer membrane division site.
Dana M Talsness, Katie G Owings ... Clement Y Chow
An ion transporter is hyperglycosylated and 50% less functional in NGLY1-deficient cells, potentially explaining several symptoms of NGLY1 deficiency such as lack of sweat and tears.
Daniel Martins, Anthony S Gabay ... Yannis Paloyelis
Single measurements of baseline salivary and plasmatic oxytocin are not sufficiently reliable to provide valid trait markers of the physiology of the oxytocin system in humans.
Jakob Malsy, Andrea C Alvarado ... Alexander G Marneros
Characterization of the effects of complement- and inflammasome-mediated inflammation on choroidal neovascularization in a mouse model of neovascular age-related macular degeneration suggests synergistic benefits from targeting both forms of inflammation.
Jeong Hyang Park, Chang Geon Chung ... Sung Bae Lee
Genetic and optogenetic analyses in Drosophila neurons reveal calcium as one of the key regulators of nucleocytoplasmic localization of TDP-43 via Calpain-A and Importin α3.
The gustatory receptor PxylGr34 is tuned to the steroid plant hormone brassinolide and mediates the deterrent effects of brassinolide on feeding and ovipositing behaviors in Plutella xylostella.
Scott McWilliams, Barbara Pierce ... Ulf Bauchinger
Migratory birds with fuel stores composed of more omega-6 fats saved energy during long-duration flights, but this short-term energy saving came at the long-term cost of higher oxidative damage.
Adhesion force measurements reveal that proper N-glycosylation of flagellar membrane proteins is crucial for adhering C. reinhardtii cells onto surfaces.
Kathleen M Cunningham, Kirstin Maulding ... Thomas E Lloyd
Impaired nuclear import of the transcription factor TFEB/MITF is a major cause of autophagy and lysosome dysfunction in amyotrophic lateral sclerosis caused by mutations in the C9orf72 gene.
Matthew D Keefe, Haille E Soderholm ... Joshua L Bonkowsky
Neurological pathology and chronic activation of the induced stress response are caused by expression of a truncated EIF2B5 in vanishing white matter disease.
Holger Dannenberg, Hallie Lazaro ... Michael E Hasselmo
Spatial accuracy of grid cell firing correlates with the slope of the local field potential theta frequency vs. running speed relationship and integrates velocity signals over past time.
Augusto Berrocal, Nicholas C Lammers ... Michael B Eisen
Live quantitative monitoring of transcriptional bursting reveals that enhancers responding to different regulators use the same kinetic strategy to produce a complex composite pattern of developmental expression.
Hillary A Miller, Elizabeth S Dean ... Scott F Leiser
Modulation of the aging process through cell signaling represents a recent and exciting area of study with the potential for development of therapeutics to extend human health.
The interplay between the Flower Ca2+ channel and PI(4,5)P2 spatiotemporally couples synaptic vesicle exocytosis to activity-dependent bulk endocytosis and synaptic vesicle reformation from bulk endosomes.
Victoria G Castiglioni, Helena R Pires ... Mike Boxem
PAR-6 and PKC-3/aPKC are essential for postembryonic development of C. elegans and control the organization of non-centrosomal microtubule bundles in the epidermis, likely through recruitment of NOCA-1/Ninein.
Silvia Vergarajauregui, Robert Becker ... Felix B Engel
AKAP6 is a site-specific adaptor required and sufficient to anchor centrosomal proteins and golgi to the nuclear envelope and establishes a non-centrosomal microtubule organization center (ncMTOC).
Christina M Kelliher, Randy Lambreghts ... Jay C Dunlap
Casein kinase I, a pivotal kinase in the circadian clock encoded by ck-1a, is positively regulated by a novel RNA-binding protein that protects ck-1a transcripts from nonsense-mediated decay.
Stacyann Bailey, Grazyna E Sroga ... Deepak Vashishth
Global extracellular bone matrix phosphorylation level is optimized for appropriate mechanical function and is affected by the presence and heterogeneity in phosphorylation of osteopontin.
Models of chromosome compaction by condensins demonstrate that two-sided loop extrusion and long residence times are required for high compaction, suggesting a tight coupling between these two properties in vivo.
The likelihood to perform tool use during foraging is linked to personality traits in ants, suggesting an original interplay between consistent inter-individual variability and division of labor in social species.
Sofya A Kasatskaya, Kristin Ladell ... Dmitriy M Chudakov
Functional subsets of helper CD4+ T cells carry TCR repertoires with distinct features that are reproducible across donors and are partially acquired at the level of thymic selection.
María Crespo, Barbara Gonzalez-Teran ... Guadalupe Sabio
Circadian neutrophil infiltration in the liver modulates liver clock-gene expression and daily hepatic metabolism through the secretion of elastase and activation of JNK-FGF21-Bmal1 axis in the hepatocyte.
17α-Estradiol, a life-span extending compound, signals through estrogen receptor α (ERα) in the liver and hypothalamus to elicit health benefits in a sex-specific manner.
Florelle Domart, Peter Cloetens ... Richard Ortega
The development of high-resolution correlative imaging of metals and proteins reveals the interaction of copper and zinc with the synaptic architecture of neurons.
Alejandro Tabas, Glad Mihai ... Katharina von Kriegstein
Representations in the subcortical sensory pathway do not only adapt to stimulus properties but also rely on the observer’s subjective model of the world.
Clemens Heissenberger, Jarod A Rollins ... Markus Schosserer
In nematode worms, NSUN-1 methylates ribosomal RNA and influences phenotypes related to aging, stress resistance, germ line development, and cuticle integrity by regulating translation of specific mRNAs.
Sean M Carney, Andrew T Moreno ... Joseph J Loparo
The disordered C-terminal tail allows XRCC4-like factor (XLF) to find and bind the XRCC4-Lig4 complex, enabling DNA end synapsis and subsequent ligation during non-homologous end joining.
Yulia Bereshpolova, Xiaojuan Hei ... Harvey A Swadlow
In the visual system, three rules guide the thalamocortical connectivity of cortical fast-spike interneurons and are key to understand the potent and broadly tuned feed-forward inhibition that they generate.
Natalya N Pavlova, Bryan King ... Craig B Thompson
Amino acid limitation triggers preferential uncharging of glutamine-specific tRNAs and depletes polyglutamine tract-containing proteins from mammalian cells, revealing a potential role for polyglutamine tracts as sensors of glutamine sufficiency.
Christine R Collins, Fiona Hackett ... Michael J Blackman
Genetic analysis identifies an enzyme of the malaria parasite that is required to seal its host red blood cell membrane upon invasion, a key requirement of this important intracellular pathogen.
Soner Yildiz, João P Pereira Bonifacio Lopes ... Mirco Schmolke
A respiratory tissue-associated commensal Lactobacillus strain confers colonization resistance to Streptococcus pneumoniae, when applied therapeutically in a post influenza virus super-infection model.
Astrocyte microdomain calcium transients are mediated by TrpML, stimulated by ROS and tyramine, and mediate astrocyte–tracheal interactions in CNS gas exchange.
Hypersensitivity of cohesin-deficient cells to Wnt signaling is concomitant with beta catenin stabilization and offers promise that Wnt agonists could be therapeutically effective in cohesin mutant cancers.
Christoph N Schlaffner, Konstantin Kahnert ... Hanno Steen
FLEXIQuant-LF provides the framework to enable large-scale identification of differentially modified peptides and quantification of their modification extent in label-free mass spectrometry data without prior knowledge of the modification type.
Omar Al Rifai, Catherine Julien ... Mathieu Ferron
In mice, but not in humans, the bone-derived hormone osteocalcin is O-glycosylated, a post-translational modification controlling its half-life in vivo.
James F Pelletier, Christine M Field ... Timothy J Mitchison
Live imaging of multiple cytoplasmic networks in frog egg extracts calls for new models for how egg cytoplasm is physically organized during cleavage divisions.
When two signals increase transcription of the same gene, their combined effect tends to reflect either the sum of the individual increases or the product of the individual fold-changes.
Opeyemi O Alabi, M Felicia Davatolhagh ... Marc Vincent Fuccillo
Disruption of the disease-associated synaptic adhesion molecule Neurexin1a in cortical excitatory neurons perturbs decision making and disrupts value-associated neural activity in downstream striatal circuits.
Long-term imaging of dentate granule cells reveals that the presence of synaptopodin within large spines, rather than their size, conveys long-term stability to large spines.
The collective dynamics of cell signaling relays are at once dramatically sensitive to the system dimensionality and insensitive to many biological details.
Hundreds of loci underlying ecological adaptation to different environmental conditions show striking differences in allele frequencies between ecotypes of Atlantic herring.
A phosphorylation circuitry balancing among kinase, transcription factor, transcription repressor, and phosphatase in response against host immunity during M. oryzae–rice interaction.
A disinhibitory motif in the retina mediates noise resilience of motion detection using an inverted algorithm of disinhibition due to the interplay between network activity and synaptic plasticity.
Phosphorylation-mediated inactivation of pro-apoptotic BCL-2 family protein BAD confers the apoptosis resistance on synovial sublining macrophages, thereby contributing to the development of rheumatoid arthritis.
Jakob Voigts, Christopher A Deister, Christopher I Moore
Changing which layer 6 neurons are active during sensory tasks disrupts the detection and encoding of changes, but still allows integration of sensory information in the absence of changes.
Grant Kinsler, Kerry Geiler-Samerotte, Dmitri A Petrov
A set of adaptive mutations affect only a small number of phenotypes that matter in the evolution condition, and yet contain substantial latent functional diversity revealed in distant environments.
A novel single-molecule sequencing method reveals previously unappreciated heterogeneity in nucleosome positioning on individual chromatin fibers across the human genome.
Konstantin Riege, Helene Kretzmer ... Martin Fischer
A resource of p63-regulated genes, genomic loci bound by p63, p63 DNA recognition motifs, and potential co-factors is generated through a meta-analysis of high-throughput datasets.
Kirsteen M Tullett, Peck Szee Tan ... Mireille H Lahoud
Dendritic cell recognition and processing of antigens from dead cells, utilising the Clec9A-damage recognition receptor, is controlled by a novel RNF41-ubiquitin-mediated regulatory pathway.
In the injured sciatic nerve, blood-derived monocytes and macrophages eat dying leukocytes, thereby contributing to nerve debridement and inflammation resolution, and this correlates with neuronal regeneration.
From as early as primary visual cortex and across posterior cortical areas, neural responses to visual pulses during an evidence-accumulation task exhibit a multitude of task-related amplitude modulations/gain changes.
p53 folding is critically dependent on zinc, and a synthetic metallochaperone rescues tumorigenic mutations that reduce p53's zinc affinity as well as thermodynamic stability.
Valentina Vellani, Lianne P de Vries ... Tali Sharot
L-DOPA administration increases information-seeking about potential losses without impacting information-seeking about potential gains, and as a result, it reduces the effect of valence on information-seeking.
Percy Griffin, Patrick W Sheehan ... Erik S Musiek
The BMAL1-REV-ERB axis controls expression of complement C4b expression and microglial synaptic phagoctyosis, providing a link between cellular circadian clock function and synaptic regulation.
Crosslinking the AAA+ protease interface does not abolish protein degradation by ClpAP, establishing that rotation of the AAA+ unfoldase with respect to its partner peptidase is not essential for activity.
Valerie J Morley, Clare L Kinnear ... Andrew F Read
Cholestyramine, an FDA-approved bile acid sequestrant, can be repurposed to inactivate the antibiotic daptomycin in the gut, which prevents the emergence of transmissible antibiotic resistance in gastrointestinal Enterococcus faecium populations.
Mice exposed to complex early adversity show similar diffusion MRI changes to those reported in humans and sex-specific changes in connectivity that differentially affect contextual deficits in males and females.
Isabelle Schmutz, Arjen R Mensenkamp ... Titia de Lange
Mutations in TIN2, a component of shelterin that keeps telomere length in check, lead to cancer-predisposition by disabling the telomere tumor suppressor pathway.
Inhibition from the cerebellar nuclei to the inferior olive is exclusively asynchronous and GABAergic, whereas the vestibular nuclei provide rapid synchronous inhibition mediated by mixed GABA and glycinergic synapses.
Peter C Dumoulin, Joshua Vollrath ... Barbara Burleigh
Trypanosoma cruzi intracellular amastigotes exhibit rapid resistance to azoles, independent of genetic selection, which is dependent on metabolic state and mechanistically distinct from latency.
Daniel Shriner, Amy R Bentley ... Charles N Rotimi
Despite health disparities among groups, the lifetime risk of hypertension approaches 100% for African Americans, European Americans, and Mexican Americans.
