Marius Landau, Sherif Elsabbagh ... Joachim E Schultz
The dodecahelical membrane anchors of mammalian adenylyl cyclase isoforms are receptors for unsaturated free fatty acids and, as a tonic signal, enhance or attenuate GPCR/Gsα-stimulated cyclic AMP formation.
Metabolomics analysis identified potential neuroactive metabolites, issued from food and microbial fermentation, that are linked to symptoms of depression, anxiety and alcohol craving.
CPT1A downregulation enhances radioresistance in colorectal cancer (CRC) via FOXM1-mediated antioxidant response, making it a potential biomarker for radiosensitivity and a novel target for improving CRC radiotherapy.
While monitoring neuronal activity in freely moving Drosophila is challenging, HI-FISH enables brain-wide mapping of active neurons and reveals behavior-specific neural activity.
Jake VanBelzen, Bennet Sakelaris ... Jason H Brickner
An alternative method for mapping RNA polymerase II occupancy over the genome provides new insights into the kinetics and molecular mechanism of transcription.
A deep learning-based system objectively and reliably scores the Rey–Osterrieth complex figure test, enhancing the assessment of visual memory deficits from hand-drawn images in clinical settings.
Andrew E Worthy, Joanna T Anderson ... Francisco J Alvarez
Major differences among the main spinal V1 inhibitory interneuron subgroups were revealed based on neurogenesis, circuit placement, and motoneuron targeting, and Foxp2-V1 interneurons were identified tightly coupled to limb control.
Knockout of Terc impedes effective immune defense against bacterial lung infections in mice, exacerbating disease course and revealing the critical function of Terc in pulmonary immunity.
Pituitary organoids help identify NFKB2 as a new actor during pituitary development, and mutations of this gene as the cause for pituitary deficit observed in patients with DAVID syndrome.
Masahiro Takigawa, Marta Huelin Gorriz ... Daniel Bendor
A novel tool enables cross-checking the quality of replay events and evaluating the effectiveness of a given replay detection method in the absence of a ground truth.
Friedrich Schuessler, Francesca Mastrogiuseppe ... Omri Barak
An analysis of the relation between neural activity and behavioral output uncovers two dynamical regimes, shows how to model them, and demonstrates how to find them in experimental data.
Sudhanvan Iyer, Kathryn Maxson Jones ... Mary A Majumder
The BRAIN Initiative data-sharing ecosystem, consisting of seven data archives, faces interoperability and data stewardship challenges but nevertheless offers adaptability to the needs of particular research communities and raw material for network evolution.
Astrocytic ER calcium release and gap junction communication exhibit circadian modulation driven by HERPUD1, highlighting the importance of astrocytic circadian rhythms in brain function.
Computational modeling suggests that the BLA is capable of producing the recorded LFP rhythms via interactions of interneuron subtypes, and that those rhythms may be necessary for associative learning.
John H Day, Catherine M Della Santina ... Laurie A Boyer
A simple and accessible method for high-throughput super-resolution fluorescence microscopy that is compatible with commonly used staining practices, 96-well cell culture plates, and confocal microscopes.
A new peptidoglycan hydrolase mined from Acinetobacter baumannii proteome by lysin-derived antimicrobial peptide-primed screening strategy undergoes a unique switch between dimer and monomer after heat treatment and protects mice from A. baumannii infection.
µGUIDE is a Bayesian framework that leverages simulation-based inference to efficiently estimate posterior distributions of any forward model parameters, allowing for uncertainty quantification and degeneracy detection.
Mir802 serves as a pivotal mediator facilitating communication between adipose tissue and macrophages through the activation of NF-KB signaling pathways.
High mutational load tumors mitigate effects from protein-damaging mutations by up-regulating complexes that buffer against misfolding stress, revealing therapeutic vulnerabilities and suggesting disrupted proteostasis is a hallmark of somatic evolution.
Liliana R Teixeira, Radha Akella ... Elizabeth J Goldsmith
WNKs sense osmotic pressure by binding specific water molecules to the inactive dimeric configuration of WNK1 and WNK3, integrating signals with chloride inhibition as demonstrated by mutagenesis and structure.
Syeda Nayab Fatima Abidi, Sara Chan ... Christian W Siebel
Inhibition of Notch signaling through the Jag2 ligand, blocks homeostatic sebocyte differentiation, and pushes the cells to a progenitor fate, in a reversible manner.
Gradual downregulation of each of the subunits of the evolutionary-conserved exocyst holocomplex shows that the complex is required for biogenesis, maturation, and exocytosis of secretory granules in Drosophila salivary glands.
The amphipathic helix at the C-terminus of Complexin II prevents premature secretion, whereas its N-terminal domain regulates mechanisms which are governed by the forward rate of Ca2+ binding to Synaptotagmin I.
Stimulation of the ipsilateral motor cortex after spinal cord injury activates bilateral motor synergy and restores hindlimb movement, advancing neuroprosthetic strategies for motor recovery.
Juan Carlos Boffi, Brice Bathellier ... Robert Prevedel
Bespoke volumetric calcium imaging, validated with neuropixels recordings, evidence a population code for sound azimuth at the dorsal cortex of the inferior colliculus, with a contribution of noise correlations.
T-regulatory type 1 cells inherit a broad repertoire of epigenetic marks from T-follicular helper T-cells, offering new insights into the developmental biology of this subset.
The interaction between the sperm hook and the female reproductive tract, including various sperm dynamics related to their movement through the reproductive tract, has been directly observed for the first time using deep tissue live imaging.
Fatima Tleiss, Martina Montanari ... C Leopold Kurz
Bacterial location quantifications highlights how Drosophila melanogaster larvae discriminate bacteria to isolate and later eliminate pathogens in the anterior midgut through coordinated mechanisms involving reactive oxygen species (ROS) and antimicrobial peptides (AMPs).
Corentin Bernou, Marc-André Mouthon ... François Dominique Boussin
Characterization of an abundant clonogenic and multipotent population of immature neuroblasts, at the transition between transient-amplifying progenitor (TAP) neuroblasts and migratory neuroblasts, reversibly engaged in neuronal differentiation.
The automated workflow significantly enhances the precision and scalability of cell cycle analysis, enabling high-throughput studies in both non-adherent and adherent cells for advanced cancer research and drug development.
The USP-50/USP8 protease removes the Rab5 GEF Rabex5 from endosomes while facilitating recruitment of the Rab7 GEF SAND-1/Mon1, promoting endosome maturation.
During zebrafish embryogenesis, dact1 and dact2 are necessary for axis lengthening and craniofacial morphogenesis, and the protease capn8 is misexpressed in dact1/2 mutants.
Stephanie Guillet, Tomi Lazarov ... Frédéric Geissmann
Loss-of-function variants of human ACK1 and BRK kinase underlie systemic lupus erythematosus in young patients from multiplex families and disrupt the anti-inflammatory response of macrophages to apoptotic cells.
Katie Morris, Edita Bulovaite ... Mathew H Horrocks
PSD95 supercomplexes maintain long-term stability through gradual subunit replacement, with the slowest turnover in cortical synapses associated with memory storage.
Differences in the ribosomal densities of the two daughters produced by a mother Escherichia coli could explain the asymmetry of aging and growth rate in previously reported such daughter pairs.
A member of the Inhibitor of DNA-binding (Id) gene family, best known as negative regulators of tissue-specific master regulatory bHLH transcription factors, also suppresses non-apoptotic caspase activities.
Samyogita Hardikar, Bronte Mckeown ... Jonathan Smallwood
Interactions between attention systems and the default mode network are linked to individual differences in trait and state-level experience and cognition.
A combined approach of genome sequencing and fluctuation assays shows that antibiotic pressure does not induce adaptive mutations in Mycobacterium smegmatis, supporting drug resistance as a consequence of phenotypic tolerance.
Clément Mazeaud, Stefan Pfister ... Laurent Chatel-Chaix
Through interactions with viral RNA and NS5, Zika virus changes the composition of the IGF2BP2-containing ribonucleoprotein complex for the benefit of the viral RNA amplification step of its life cycle.
Nrn1, a novel extracellular evolutionarily conserved molecule, impacts cellular electric and metabolic state and contributes to cell fate and immune response outcome.
John P Grogan, Matthias Raemaekers ... Sanjay G Manohar
Muscarinic antagonism is causally involved in motivation and incentivisation in healthy human participants, partially mediated via preparatory neural signatures, with implications for cholinergic treatment of Parkinson's disease.
An analysis of vestibular projection neurons lacking their motor neuron partners resolves outstanding controversies for whether and how motor neurons shape vestibulo-ocular reflex circuit assembly.
The results of central nervous regulation in mice provide a new neural circuit and receptor regulatory mechanisms for the recovery of consciousness after midazolam administration.
Although activity in mouse V1 increases substantially during volitional running, such modulations in the foveal/central representation of primate V1 appear much smaller and suppressive.
Bacillus velezensis has broad-spectrum antibacterial activity and can reduce the colonization of Salmonella Typhimurium in the intestinal tract of mice.
Takashi Watanabe, Hikaru Hata ... Hidehiro Fukuyama
A Golden Gate-based dual-expression vector enables rapid screening, which facilitates efficient isolation of high-affinity cross-reactive antibodies for therapeutic or diagnostic use and provides a crucial advance for pandemic preparedness.
Tommaso Amico, Samuel Toluwanimi Dada ... Amos Maritan
The scaling invariance of the droplet size distribution as a universal aspect of protein phase separation is reported, providing a quantitative approach to determinate the critical concentration for this process.
Human intracranial electroencephalography recordings across 177 participants and four diverse episodic memory experiments demonstrate how the anterior insula node of the salience network orchestrates dynamics of large-scale brain networks.
Commonly used covalent PPARγ inhibitors weaken, but do not block, binding of other ligands via an allosteric mechanism where ligands clash with a covalent ligand-induced transcriptionally repressive structural conformation.
Mighten C Yip, Mercedes M Gonzalez ... Craig R Forest
Patch-walking is a novel automated patch clamp approach for finding synaptic connections in brain tissue, yielding 80–92% more probed connections than traditional approaches.
Changes in cortical neural ensembles and heightened coupling between the hippocampus and cortex enable the eventual behavioral integration of memories with overlapping sequential information.
Selectively eliminating resident astrocytes in lumbar enlargement attenuated neuropathic pain associated with type I interferons (IFNs) signal activation in microglia.
Gaetan De Waele, Gerben Menschaert, Willem Waegeman
It is possible to accurately recommend antimicrobial drugs from mass spectra using neural networks and large datasets, paving the way for more efficient clinical diagnostics.
Machine learning models effectively predict the risk of post-stroke epilepsy using extensive clinical data, offering new insights for improving patient management in clinical neurology.
A novel pair of isobaric crosslinking reagents is described, which allow relative quantification of crosslinker-modified peptides during mass spectrometry analysis for comparative structural studies of proteins and protein complexes.
The binding site and potential mechanism of human SCARF1 for lipoprotein recognition are identified by combining the crystal structural determination of the N-terminal fragments and biochemical and cellular assays.
Alejandro J Brenes, Eva Griesser ... Angus I Lamond
Human induced pluripotent stem cells and embryonic stem cells express a similar set of proteins, but the levels of cytoplasmic and mitochondrial proteins vary, with concomitant effects on phenotypes including transport and mitochondrial function.
Asymmetric activation of the dysgranular mid-insula during interoceptive processing contributes to disrupted bodily awareness in individuals with anxiety, depression, and eating disorders.
Natalia Mendes, Ariane Zanesco ... Licio A Velloso
A subset of myeloid cells expressing CXCR3 is recruited to the hypothalamus and protects against the metabolic abnormalities generated in diet-induced obesity.
Jae Hun Shin, Jooyoung Park ... Alfred LM Bothwell
DKK2 is crucial for the development of lysozyme-expressing cancer cells with Paneth cell characteristics necessary for liver metastasized colon cancer growth.
Martina Jabloñski, Guillermina M Luque ... Mariano G Buffone
The double helix actin network surrounding the mitochondrial sheath of the sperm midpiece undergoes structural changes prior to the motility cessation during sperm-egg fusion.
Ignacy Czajewski, Bijayalaxmi Swain ... Daan MF van Aalten
Modelling O-GlcNAc transferase intellectual disability reveals the roles of this post-translational modification in regulating normal axonal terminal morphology and maintaining appropriate sleep homeostasis, pharmacological and genetic rescues of O-GlcNAcylation highlight the complexities of addressing this disorder.
All-atom molecular dynamics simulations revealed both direct and indirect salt effects and led to an amino-acid composition-based predictor for four classes of salt dependence of IDP phase separation.
Adding suppressors of spontaneous differentiation enables precise control of human induced pluripotent stem cell (hiPSC) status in suspension culture conditions and leads to scalable and automated cell therapy using hiPSCs.
Rachel Sharninghausen, Jiwon Hwang ... Ryan D Baldridge
A generalizable approach to identify sequence features driving degradation from the endoplasmic reticulum (ER) provides useful tools for enabling ER-localized protein degradation.
Michael James Chambers, Sophia B Scobell, Meru J Sadhu
The innate immune protein PKR, which is inhibited by viral proteins that mimic its natural substrate, has access to a wide spectrum of inhibitor-evading mutations that maintain natural substrate binding.
Abolishing opposing hair cell orientation in mouse otolith and zebrafish neuromast organs preserves segregation of afferent innervation but affects zebrafish mechanotransduction and mouse vestibular reflexes.
In congenital stationary night blindness type 2, Cav3 channels may maintain cone synaptic output and visual function provided that the nonconducting role of Cav1.4 in cone synaptogenesis remains intact.
Programmed cell death during plant development (dPCD) is crucial for Arabidopsis thaliana root defense, limiting microbial invasion and maintaining a balanced relationship with beneficial microbes.
The conformation of an isoleucine gate located along the TM6 segment on the intracellular side below the selectivity filter is a critical component leading to a non-conductive state in the C-type inactivation process of K+ channels.
Marie-Eve Picard, Miriam Kunz ... Pierre Rainville
Facial expression provides a complementary channel to communicate pain experiences and reflects the activation of brain mechanisms partly distinct from those associated with subjective self-reports of pain.
Jiayun Xu, Mauricio Girardi-Schappo ... Leonard Maler
Mice can use self-motion cues to learn a cognitive map thereby permitting them to take shortcut trajectories in an open maze without requiring prior experience of such routes.
The protein stability of WDR5, the core component of TrxG complex, is controlled by the ubiquitin ligase RNF220, which involves in the maintenance of Hox patterns in mouse hindbrain.
Potential commensalism between saprophytic and pathogenic Leptospira within a vertebrate host protects against severe leptospirosis and improves kidney homeostasis which helps Leptospira interrogans complete its enzootic cycle.
The local PI(4,5)P2 nanodomain promotes the dimerization and activation of EGFR in the plasma membrane, whereas activated EGFR dissolves the nanodomain structure of PI(4,5)P2 through PLCγ.
FABP4 plays a central role in driving the formation lipid-laden macrophages induced by unsaturated fats and enhances macrophage-tumor interactions, thereby promoting breast cancer migration and metastasis.
Transplanted human iPSC-derived microglial cells with immune responses and phagocytic abilities integrate and occupy native microglial cell space and functionally respond to retinal injuries.
The dynamic over-wintering range of migratory birds, resulting from the newly described 'foxtrot migration' pattern, reveals potential errors in single mid-winter population assessments and highlights implications for their conservation status.
Giulia Ferraretti, Paolo Abondio ... Marco Sazzini
A combination of composite-likelihood and gene network-based methods to investigate the impact of Denisovan introgression on the evolution of complex (i.e., polygenic) adaptive traits in high-altitude populations of Tibetan/Sherpa ancestry.
Single-cell RNA sequencing of biopsy samples from advanced-stage lung cancer reveals tumor and immune cell features associated with response to immune checkpoint therapy.
Florent Colomb, Abhishek Jamwal ... Henry J McSorley
The HpARI family members can either suppress or amplify responses to IL-33, and also differ in their half-life in vivo due to binding to the extracellular matrix constituent, heparan sulphate.
Integrated ecological and genetic methods show that Bursicon signaling pathway and miR-6012 regulate the transition from summer-form to winter-form in Cacopsylla chinensis through affecting cuticle pigment and cuticle thickness.
Nishal Pradeepbhai Shah, AJ Phillips ... EJ Chichilnisky
A novel method of electrical stimulation to precisely control neural activity for sensory restoration exhibits improvements in visual stimulus reconstruction, enables efficient hardware design, and extends to naturalistic conditions.
The water channel AQP4 contributes to a tonic water outflow from brain astrocytes, thereby modulating their volume dynamics and the ambient water homeostasis.
SLC35G1 is the first highly chloride-sensitive transporter localized on the basolateral membrane of intestinal epithelial cells, responsible for citrate absorption.
A plant autophagy pathway transports chloroplast stroma and envelope components into the vacuole through the division and encapsulation of the site of chloroplasts that is associated with developing autophagosome.
Two alternative models of PKA activation were tested in neurons, and the results support the classical model in which the catalytic subunit dissociated from the regulatory subunit upon activation.
Formation of a giant unilocular vacuole through a macropinocytosis-like process in cells with disrupted actin cytoskeleton promotes resistance to anoikis.
Experimental results suggest a previously unknown regulatory mechanism for GLP-1 production in L cells, which could offer new insights into diabetes treatments.
Theoretical and experimental evidence that Hh signaling dynamics balances robust positioning and sharpness of different target genes in the Drosophila wing disc.
Sebastian Deichsel, Lisa Frankenreiter ... Anja C Nagel
Pkc53E kinase-mediated downregulation of CSL/Su(H) activity is a direct molecular response to parasitoid wasp infestation in Drosophila, allowing the differentiation of encapsulation-active lamellocytes, thereby ensuring an appropriate immune defense.
GluK1-1 splice variant alters the gating properties of kainate receptors, providing crucial insights into receptor modulation by auxiliary proteins and advancing the understanding of synaptic transmission.
In the CA1 region of the hippocampus, VTA inputs signal reward proximity while LC inputs respond to novelty, illustrating distinct catecholaminergic roles in hippocampal processing during navigation and learning.
Rebecca Warfvinge, Linda Geironson Ulfsson ... Göran Karlsson
Single-cell analysis of CML patients bone marrow at diagnosis reveals coexistence of CD26-CD35+ healthy stem cells and CD26+CD35- CML stem cells, and how the ratio between these impacts TKI response.
Causal investigation of engram ensembles shows that natural forgetting is an active and reversible process driven by perceptual feedback, supporting the perspective of forgetting an adaptive function of the brain.
Chromatin immunoprecipitation sequencing and RNA sequencing have elucidated the complex transcript regulation pathways orchestrated by SntB, pivotal for Aspergillus flavus's development, mycotoxin production, and virulence.
Sebastian Quiroz Monnens, Casper Peters ... Bernhard Englitz
The recurrent temporal restricted Boltzmann machine applied to whole-brain neuronal recordings from larval zebrafish brains provides substantial advantages in discovering the neuronal assembly structure and their connectivity.
A global reduction in tRNA differentially affects brain regions and tissues in a mouse model of Polr3-related disease leading to activation of integrated stress and innate immune responses and neurodegeneration.
Quantitative models for responses of rod and cone photoreceptors are developed that allow direct tests of the impact of the photoreceptors on responses of downstream visual neurons.
Targeted memory reactivation improved memory performance of easy-to-learn words, but had no effect of difficult-to-learn words, which suggests a critical role of word learning difficulty in sleep associated memory reactivation.
Sex differences in the age-related decline of blood-brain barrier function vary across brain regions, with a more pronounced decrease observed in males beginning in the early 60s.
Anna Herrmannová, Jan Jelínek ... Leoš Shivaya Valášek
eIF3, despite being a general translation initiation factor, functions in mRNA-specific regulation, having a profound impact on the synthesis and activation of the MAPK pathway components and ribosomal proteins.
Proteins in the Transmembrane Channel-Scramblase (TCS) superfamily share an evolutionarily conserved ability to permeate ions and phospholipids, challenging distinctions between ion channels and lipid scramblases.
Galectin-9 directly binds to arabinogalactan (AG), leading to the identification of AG-specific monoclonal antibodies that effectively inhibit Mycobacterium tuberculosis growth, providing insights for novel tuberculosis therapies.
By harnessing antibody fragments conjugated to small gold nanoparticles together with high pressure freezing, FIB/SEM milling and cryo-electron tomography, AMPA receptors were identified from mouse brain tissue.
SIRT4 regulates cellular communication network factor 2 expression through U2 small nuclear RNA auxiliary factor 2-mediated pre-mRNA splicing, presenting a potential therapeutic target for kidney fibrosis.
Allison T Goldstein, Terrence R Stanford, Emilio Salinas
Psychophysical measurements using time pressure indicate that when attention is willfully deployed, a congruent scaccade is automatically planned, but the coupling is weak and can be rapidly broken.
Robust NMR approach allowed simultaneous detection of substrate cleavage site and real-time kinetics of hydrolysis for Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM, and revealed D-alanyl-glycine activity for LytM.
A novel 2D-to-3D human brain organoid protocol reveals the pivotal role of FGF8 signaling in driving regional patterning and cellular diversity, while also modulating genes crucial for both normal and pathological neural development.
For mRNA decapping by enhancing DCP2's mRNA-binding affinity and regulating distinct biological processes through DCP1a and DCP1b, human DCP1 is essential.
New methods for investigating connectivity between genetically defined neuronal populations are introduced and used to investigate the organisation of excitatory-inhibitory interactions in the superficial entorhinal cortex.
Ageing is broadly accepted as a by-product of evolution, as thus, models allowing to conceive ageing as an adaptive force of evolution could show significant importance at a time of biogerontology mostly aiming at curing ageing.
Kate Huffer, Matthew CS Denley ... Kenton J Swartz
The cooling agent pocket in TRPM8 is conserved in a subset of other TRPM channels and the cooling agent icilin can regulate opening of TRPM4 channels in response to calcium and voltage.
Giordano de Guglielmo, Lieselot Carrette ... Olivier George
Genetically diverse rats reveal a single underlying construct linking key addiction-like behaviors, challenging compulsivity as an independent measure, and offering a new perspective on vulnerability and resilience to addiction.
The mirror-symmetric structure of the Caenorhabditis elegans gonad is established through the Wnt-independent function of a Frizzled protein and three Wnt proteins with distinct roles.
