Kiwamu Kudo, Kamalini G Ranasinghe ... Srikantan S Nagarajan
Event-based sequencing models for Alzheimer’s disease progression revealed that abnormal neural synchrony occurs during the earliest preclinical stages of the disease, preceding brain atrophy and cognitive decline.
Arthur L Schneider, Rita Martins-Silva ... Nuno L Barbosa-Morais
voyAGEr is an online platform that facilitates the exploration of age-related gene expression dynamics in human tissues, allowing users to analyse tissue- and sex-specific changes alongside donor medical histories.
Participants' subjective beliefs about the treatment received in an intervention study can explain variability in mental health symptoms and cognition.
Osteocytes, sensing mechanical stimulation generated by exercise, inhibit the proliferation of non-small cell lung cancer cells and sustain their dormancy by releasing small extracellular vesicles containing tumor-suppressive micro-RNAs.
Anchoring of grid firing fields to task environments is consistent with roles specifically in path integration rather than spatial localisation in general.
The human body shapes how we perceive and interact with the environment, with body size serving as a boundary for defining potential actions, hereby enlightening research on foundation agents.
Mouse models reveal fundamental roles of SMAD1/5 in mediating both bone morphogenetic protein signaling pathways and the transcriptional response to progesterone during decidualization.
New ATP-competitive inhibitors show properties of conformation selection when complexed with the MAP kinase, ERK2, altering movements around the activation loop.
Intermittent fasting affects intestinal immunity through new interactions between macrophages and ILC3s, increasing ILC3 secretion of IL-22 and thus promoting white adipose tissue beigeing, and improving metabolism.
Measurement of the effect of all single-codon variants of the AAV2 rep gene on recombinant adeno-associated virus production identifies novel beneficial variants, which may facilitate improvement of gene therapy production.
A microfluidic device induces doxorubicin-resistant polyaneuploid cancer cells from triple negative breast cancer cells, revealing NUPR1/HDAC11 axis dysfunction drives chemoresistance, increasing tumor heterogeneity and impacting clinical outcomes.
The transmembrane protein Kit Ligand and the Kit receptor tyrosine kinase are required for synapse function between specific cell types in the mouse cerebellum.
Mendelian randomization and transcriptome-wide association studies delineate the causal relationships and genetic markers between circulating immune cells and periodontitis, pinpointing neutrophils as the predominant contributors.
Karolina Honzejkova, Dalibor Kosek ... Tomas Obsil
Thioredoxin functions as a negative allosteric effector of ASK1 by altering the interaction between the thioredoxin-binding and tetratricopeptide repeats domains, thereby reducing access to the kinase domain's activation segment.
Hippocampal sharp-wave ripples are not required for rats to successfully perform spatial tasks that rely on memorization of locations at short timescales.
Imaging analysis confirms ChIP-Seq data on the distinct genomic distribution of histone H1 variants in AT-rich, nuclear peripheral regions (H1.2, H1.3, H1.5, H1.0) or GC-rich, throughout the nucleus (H1.4, H1X).
Theoretical scenario for prebiotic polymers capable of nonenzymatic replication to acquire an early catalytic function, specifically cleavage activity.
Brain lactate and pH changes, identified as common features in diverse neuropsychiatric animal models, may represent transdiagnostic endophenotypes associated with cognitive impairment.
Luca Casiraghi, Francesco Mambretti ... Tommaso Bellini
A variant of SELEX introduced here to induce abiotic evolution in a molecular system enables to observe and study speciation, the nature of fitness, and the interplay between use of resources and interactions between individuals.
Repulsive guidance cues enhance a dual-functioning axonal trafficking facilitator, allowing navigating axons to ensure proper pathfinding by coordinating positive extension and negative steering during nervous system development.
Amir Hossein Kayvanjoo, Iva Splichalova ... Elvira Mass
Identification of distinct yolk sac-derived macrophage subpopulations in the fetal liver reveals their crucial role in shaping the hematopoietic niche, impacting erythropoiesis and granulopoiesis through direct interactions with long-term hematopoietic stem cells.
Smrithi Prem, Bharati Dev ... Emanuel DiCicco-Bloom
Alterations in mTOR signaling drive similar dysregulations in the critical mid-fetal neurodevelopmental processes of neurite outgrowth and cell migration in two distinct subsets of autism, idiopathic and 16p11.2 deletion.
A novel antibody recognizing receptor-binding region of MARV glycoprotein was developed and displays broad-spectrum neutralizing activity to filovirus species when NPC2 was fused to the N-terminus of the mAb.
Striatal neurons preferentially fire at specific phases of the gait cycle, and the strength of gait encoding is selectively increased in indirect pathway neurons following dopamine lesions.
In quiescent yeast, a stable bundle of parallel microtubules is assembled from the centrosome by an original multistep mechanism that follows a precise temporality and involves Aurora B and various kinesins.
The intrinsic disorder of the circadian clock protein Frequency organizes binding partners, facilitates liquid–liquid phase separation, modulates Frequency phosphorylation, and derives from sequence properties conserved with homologous clock components.
Biochemical and instrumental analysis showed that the membrane-induced exposure of myristoyl from the MA protein of Mason-Pfizer monkey virus triggers allosteric conformational changes resulting in MA oligomerization and unfolding of the cleavage site between MA and downstream domains of Gag.
Veronica Teresa Ober, George Boniface Githure ... Michael Boshart
A minimal subset of two to three residues in cyclic nucleotide binding (CNB) domains controls nucleoside vs. cyclic nucleotide specificity, repurposing PKA of certain pathogens for novel nucleoside signaling pathways or sensing.
Genetic analysis of Hippo pathway kinases in a close unicellular relative of animals suggests an ancestral role of this ancient pathway in regulating cytoskeletal dynamics and density of multicellular aggregates.
The number of sporozoites expelled by mosquitoes that are infected with lab-cultured or naturally circulating Plasmodium falciparum gametocytes is heterogeneous and associated with the sporozoite load in their salivary glands.
Wayne Mitchell, Ludger JE Goeminne ... Vadim N Gladyshev
Partial chemical reprogramming is able to reduce the biological age of cells by diverting them to a different metabolic state marked by a strong upregulation of mitochondrial oxidative phosphorylation.
Michael P Dalton, Mary Hongying Cheng ... Jonathan A Coleman
The structure of the vesicular monoamine transporter 2 bound to Huntington’s chorea drug tetrabenazine elucidates mechanisms of inhibition and neurotransmitter transport.
Brain-wide activation patterns reveal the distinct and shared neurophysiological impacts of ketamine and isoflurane, highlighting key nuclei involved in the modulation of general anesthesia.
Andrea Salazar Lázaro, Thorsten Trimbuch ... Christian Rosenmund
Structure–function studies on the synaptic vesicle release protein syntaxin-1 identified structural motifs on the surface of the SNARE complex controlling vesicle priming and spontaneous release unique for synaptic signaling.
Mina O Seedhom, Devin Dersh ... Jonathan W Yewdell
Quantitative protein and ribosome 'accounting' in T cells highlights a gap in our understanding of how activated T cells sufficiently replicate their proteome during rapid cell division driven by infection.
Dopamine and GABA neurons in the ventral tegmental area encode short-term memory in the T-maze task, which cannot be explained by reward-related processes, motivated behavior, or motor-related activities.
The SARS-CoV-2 Spike proteins demonstrate in vivo cellular tropism, ascertain targets within human mononuclear cells, and provide insights into their functional consequences, thereby enhancing comprehension of their impact on humans.
Martin Wohlwend, Pirkka-Pekka Laurila ... Johan Auwerx
CERS1 reduction in aging skeletal muscle contributes to impaired muscle function, myogenesis and increases inflammation and fibrosis, highlighting the significance of very long chain ceramides in age-related muscle homeostasis.
There are many fine-scale scene-selective areas within the visual system, beyond the occipital, temporal, and medial place areas, whose function may be key to performing complex tasks in dynamic environments.
Spatiotemporal mapping of a variety of proteins in and around the Golgi apparatus in budding yeast was performed using super-resolution live imaging microscopy and identified the ER-Golgi intermediate compartment that matures into the Golgi.
The finding that deletion of the genome folding motor leaves a significant fraction of a key structural feature of chromosome at the single cell and ensemble level has been explained.
Combined cutting-edge technologies discovered a pair of carboxylate transporters that appears evolutionarily different among novel transporters and that is essential for parasite physiology.
Genetic and pharmacological tools are used to dissect the mechanisms by which the presynaptic actin cytoskeleton facilitates membrane internalization at synapses and, thereby, neurotransmission.
Habitat loss rather than fragmentation per se can weaken the positive BEF relationship by reducing the percentage of grassland specialists in the community.
Single-particle imaging of RSC and ISW2 chromatin remodelers on DNA stretched between dual optical tweezers reveals distinctive 1D diffusion and opposing push–pull nucleosome translocation on engagement with sparse nucleosome arrays.
Ts65dn mice exhibit structural, functional, molecular, and genetic alterations that are modulated but unrecovered by prenatal chronic GTE-EGCG, highlighting the importance of holistic studies to understand complex disorders and treatments.
Zachary Paul Billman, Stephen Bela Kovacs ... Edward A Miao
Amphibians, reptiles, and birds engage pyroptosis using caspase-1 and GSDMA, filling an evolutionary gap in which caspase-1 cleaves GSDME in fish and GSDMD in mammals.
scRNA-seq revealed the fish kidney is a dual-functional entity with functionalities of both primary and secondary lymphoid organs and highlighted the multifaced biology of kidney in ancient vertebrates.
Cryo-EM structures uncover glycosylation in the ectodomains of full-length HER4 homodimer and HER2/HER4 heterodimer complexes, revealing how the binding of various growth factors alters dynamics at the dimerization interface.
Alain Pulfer, Diego Ulisse Pizzagalli ... Santiago Fernandez Gonzalez
ADeS, a novel deep learning approach for apoptosis detection, achieves 98% accuracy in vitro and in vivo while providing unprecedented insights into the spatial–temporal foundation of cell death.
Protein language deep learning models can quickly and accurately translate amino acid sequences into profile hidden Markov models or a structure alphabet, dramatically improving remote homology search sensitivity without compromising space or time efficiency.
Of the two divisions proposed long ago to describe the autonomic nervous system, thoraco-lumbar sympathetic and cranio-sacral parasympathetic, the latter finds no support from transcriptionally defined neuron types.
Genetic analyses and biochemical studies show that JMJD6 promotes MYC-mediated transformation and is required for neuroblastoma growth by complexing with pre-mRNA splicing factors.
WRNIP1 has been identified as a pivotal factor in preventing the pathological persistence of R-loop-induced transcription-replication conflicts and the accumulation of DNA damage, thereby ensuring genome integrity.
Open-top Bessel beam two-photon light sheet microscopy have the potential for rapid and accurate nondestructive pathology by visualizing 3D histological information.
Rachel L Doser, Kaz M Knight ... Frederic J Hoerndli
In response to neuronal activity in vivo, mitochondria in dendrites of excitatory neurons inhibit recruitment of ionotropic glutamate receptors through a reactive oxygen signaling mechanism.
Hamidreza Jafarinia, Erik van der Giessen, Patrick R Onck
Length-dependent interference of arginine-containing dipeptide repeat proteins with multiple components of the nucleocytoplasmic transport machinery is a potential mechanistic pathway of C9orf72 amyotrophic lateral sclerosis or frontotemporal dementia toxicity.
Luyang Xiong, Irina Zhevlakova ... Tatiana V Byzova
Cell and animal-based models revealed the new function of TLR2 andcarboxyethylpyrrole as an endogenous TLR2 ligand in the hair follicle cycle in homeostasis and hair follicle regeneration in injury.
The promising potential of plasma extracellular vesicle synaptic proteins as clinical biomarkers of disease progression in Parkinson's disease has been presented.
Nicolas Gutierrez-Castellanos, Dario Sarra ... Zachary F Mainen
Anatomical tracing, in combination with a genetic ablation approach, identifies a critical maturation period for neocortex to dorsal raphe afferents pivotal for the development of behavioral persistence over adolescence in mice.
Instead of repelling, Desmodium, a hallmark of pest suppressive sustainable intercropping, acts as a mechanical and developmental barrier to larvae, thereby truncating population development.
Mattia Privitera, Lukas M von Ziegler ... Johannes Bohacek
Targeted manipulation of the locus coeruleus noradrenaline circuitry combined with extensive transcriptomic analyses in the mouse hippocampus reveal a unique set of noradrenaline-dependent, stress-related genes and point to astrocytic engagement.
A series of experiments suggest that the fronto-parietal attentional network is involved in controlling eye-based attention, and FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.
Marie-Sophie H van der Goes, Jakob Voigts ... Mark T Harnett
Dual site recordings of mouse anterodorsal thalamic nucleus and retrosplenial cortex reveal near 0-ms lag between the head direction representations of the two regions after cue rotations and correlated drift in darkness.
Signatures of criticality that have been observed across diverse neural systems, such as power-law avalanche distributions and exponent relationships, can arise without fine-tuning in networks coupled to latent, dynamical variables.
An integrative approach allows investigations of the relationship between an initial plasticity and the subsequent adaptive evolution during rapid adaptive modification of complex systems in the wild.
A brown-to-white adipogenic transdifferentiation process in the periureter region of mouse renal adipose tissue gives rise to a population of cold-inducible adipocytes with a transcriptome distinct from subcutaneous beige adipocytes.
Individual listening behaviour and neural filtering ability follow independent developmental trajectories in a large, N = 105, cohort of ageing individuals.
Ivan Corbeski, Pablo Andrés Vargas-Rosales ... Amedeo Caflisch
A multidisciplinary study reveals the reaction mechanism and transition state of adenosine-N6 methyl transfer catalyzed by human METTL3-14, deepening our insight into RNA methyltransferases and paving the way for similar studies on related enzymes.
Molecular and biochemical methods provide the first evidence of toxicity of imidacloprid causing developmental retardation in honeybee larvae, highlighting the potential risks of prolonged exposure to insecticides during animal development.
TGN46 is a cargo receptor, with its luminal domain being necessary and sufficient to load soluble secretory proteins into transport carriers for export out of the trans-Golgi network.
Corefucosylation contributes to the maintenance of the articular cartilage phenotype and depletion of FUT8 inhibits recovery from cartilage damage and promotes cartilage degeneration.
Kent W Jorgenson, Jamie E Hibbert ... Troy A Hornberger
A novel imaging method for measuring myofibril size/number reveals that the radial growth of muscle fibers that occurs in response to increased mechanical loading is largely mediated by myofibrillogenesis.
The utilization of hydrogen/deuterium exchange mass spectrometry reveals dynamic insights and interactions driving liquid-liquid demixing of the chromosome passenger complex.
A new high-resolution approach to probing tooth chemistry shows real potential to uncover changing rainfall patterns and environmental conditions during human prehistory.
Domingos Leite de Castro, Miguel Aroso ... Paulo Aguiar
Adaptive delayed feedback control is presented as a new real-time, closed-loop control algorithm for neurostimulation which can disrupt oscillations and reduce network synchrony in neuronal populations.
Hannah L Payne, Jennifer L Raymond, Mark S Goldman
A comprehensive modeling approach reconciles experimental observations with classic plasticity mechanisms in the cerebellar cortex, demonstrating how learning-related changes in neural activity can appear to contradict the sign of the underlying plasticity when feedback is present.
Aleksandra Kovacevic, David RM Smith ... Lulla Opatowski
The mathematical modeling approach disentangles the impacts of the COVID-19 pandemic on antibiotic resistance in Streptococcus pneumoniae in the community setting and identifies the three most plausible driving mechanisms responsible for the observed trends in invasive isolates and pneumococcal carriage.
Ampakines demonstrate efficacy in enhancing bladder function in animal models of spinal cord injury, presenting promising prospects for innovative pharmacotherapy to alleviate post-injury bladder dysfunction.
A prospective study of intraoperative swab collections from 187 patients identified a putative fallopian tube microbiota and a clear shift in ovarian cancer patients compared to non-cancer patients.
Multi-electrode recordings and modeling work indicate that sequentially activated discrete modules of spiking neurons may appear as traveling waves in low spatial resolution measurements, suggesting caution when interpreting phase delay measurements as continuously propagating wavefronts.
Hugo Siegfried, Georges Farkouh ... Mélina L Heuzé
Depletion of VAPA in cancer cells induces defects in actin organization, adhesion dynamics and cell migration, together with a perturbation of phosphoinositide levels at the plasma membrane and a lack of anchoring of ER-PM contact sites to focal adhesions.
Epilepsy caused by focal Pten deletion is only prevented when both mTOR complexes are simultaneously inhibited, but not alone, suggesting they play independent roles in the development of epilepsy.
The dorsolateral prefrontal cortex represents different conflict types within an organized cognitive space of cognitive control, positioning more similar conflict types closer together.
Johannes N Greve, Anja Marquardt ... Dietmar J Manstein
Mutation E334Q in cytoskeletal γ-actin leads to impaired interaction of actin filaments with actin-binding proteins belonging to the myosin and ADF/cofilin families.
Benson Otarigho, Anna Frances Butts, Alejandro Aballay
Molecular and genetics approaches reveal a dual regulatory role of neuronal G-protein-coupled receptor NPR-15 in both immunity and avoidance behavior, independent of aerotaxis, mediated by amphid sensory neurons, ASJ.
Application of a polyvinyl alcohol-based culture system reveals extensive differentiation but simultaneous robust murine hematopoietic stem cell (HSC) expansion, which are characterized by phenotypic, functional, and molecular properties shared with freshly isolated bone marrow HSCs.
Live imaging, transcriptional profiling and mouse models demonstrated that the mesenchyme controls the growth pace but not the mode of branching of the mammary epithelium and unveiled a unique function for Igf1/Igfr1 in embryonic development mammary gland.
Genetics, socioeconomic conditions, and family and school environments influence cognitive intelligence in children, and this impact may lead to the individual variability of the current and future PLEs.
Negative Gravitropic Response of roots (NGRs), pivotal for root gravitropic bending, are indispensable for the gravity-induced translocation of D6 protein kinase, a key regulator of PIN3 auxin efflux carrier activity.
A cellular experiment and animal model reveals that nifuroxazide can inhibit the expression of PD-L1 through the proteasome pathway, rather than at the genetic level.
Jana Muroňová, Zine Eddine Kherraf ... Christophe Arnoult
CCDC146 is a structural component of the flagellum in sperm, located in the doublet microtubules of the axoneme, whose absence leads to multiple morphological anomalies of the flagellum.
Bone marrow-derived macrophages reveal that leucine promotes M2 polarization through mTORC1/LXRα/Arg1 signaling pathway, establishing a fundamental link between metabolism and immunity.
Visuo-auditory associative memories in the neocortex are formed through cholecystokinin-mediated heterosynaptic plasticity, primarily involving entorhinal cortex projections to the auditory cortex, highlighting intricate neural dynamics in multisensory memory processing.
Ioannis Bakoyiannis, Eva Gunnel Ducourneau ... Guillaume Ferreira
Obesogenic diet intake throughout adolescence impairs different types of memory through overactivation of specific hippocampal efferent pathways and targeting these overactive pathways has therapeutic potential.
Ando Christian Zehrer, Ana Martin-Villalba ... Helge Ewers
High-quality fluorescence live-cell and single molecule imaging via computer-controlled, user-assembled microscope that fits in incubator, can in large parts be 3D printed and employs open source software and electronics.
NetTCR 2.2 demonstrates advances in predicting MHC-peptide-TCR interactions through integration of pan- and peptide-specific training strategies, loss-scaling and sequence similarity scoring.
A new Bayesian algorithm for tracking subjects’ choice strategies on every trial reveals when subjects learn and what they tried while doing so, providing strong evidence that reward- and loss-driven exploration change independently.
Using cytosolic explants from Drosophila syncytial embryos combined with quantitative microscopy and perturbations, the mechanical forces separating Drosophila microtubule asters are revealed.
