A genetic variant within a newly identified enhancer regulates the expression of a key pharmacogene and alters the balance between resistance and sensitivity to a widely used chemotherapeutic.
Longitudinal calcium imaging in awake mice after stroke suggests impairments in neuronal activity, functional connectivity, and neural assembly architecture is transient and limited to cortex immediately adjacent to the stroke.
Older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.
Case Vincent Miller, Jen A Bright ... Michael Pittman
Enantiornithine birds reached similar dietary diversity to modern birds in a similar amount of time many millions of years earlier, but how exactly they did that requires further research.
Because nociceptors can achieve similar excitability using different sodium channel subtypes, it is difficult to know which channels are being used yet this information is critical for predicting if subtype-selective drugs will reduce pain.
Timothy J Walker, Eduardo Reyes-Alvarez ... Lois M Mulligan
TMEM127 depletion alters membrane dynamics, promoting cell surface accumulation and constitutive activity of growth factor receptors, and ultimately providing a novel paradigm for oncogenesis through aberrant receptor localization and signaling.
Xiao-Ru Chen, Karuna Dixit ... Tatyana I Igumenova
Integrated biophysical, structural, and in-cell approaches demonstrate a non-canonical and non-isomerizable binding motif-dependent mode of protein kinase C regulation by the peptidyl-prolyl isomerase Pin1 in mammalian cells.
New toolkits have been developed to enable cell-type-specific manipulation of CCT genes with remarkable efficiency while also uncovering the role of CNMa signal in regulating morning anticipation.
Magdalena Podkowik, Andrew I Perault ... Bo Shopsin
A new framework for examining tolerance in the context of quorum-sensing that may ultimately help predict and manage bacterial tolerance and, therefore, improve clinical outcome during infection.
Matthew F Wipperman, Allen Z Lin ... Olivier Harari
Biosensor data collected by digital insoles is comparable to lab-based clinical assessments and can be used to identify subject-specific gait patterns.
A new and efficient continuous flash suppression (CFS) method is presented that provides breakthrough and suppression thresholds to quantify depth of target suppression.
ElegansBot, a two-dimensional rigid body chain model, simulates various locomotion of C. elegans, including omega and delta turns, using Newtonian equations of motion.
Gregory Caleb Howard, Jing Wang ... William P Tansey
Analysis of the action of WDR5 inhibitors in leukemia cells reveals decreased ribosome inventory, impaired protein synthesis, induction of nucleolar stress, and activation of p53 via alternative splicing of MDM4.
An individual-based model framework of sub-exponentially growing replicator systems suggests that parabolic dynamics could have been able to maintain genetic diversity and circumvent the error threshold problem during early evolution.
AlphaFold-Multimer was used to investigate extracellular protein interactions involved in mammalian egg-sperm recognition, suggesting a putative pentameric complex that includes TMEM81, a sperm protein not previously involved in gamete recognition.
Christian Galicia, Giambattista Guaitoli ... Wim Versées
Conformation-specific nanobodies enable to capture and solve the first GTP-bound active structure of a bacterial homolog of the Parkinson-associated LRRK2 protein, providing insights into the activation mechanism of these proteins.
Analysis of mice lacking the precursor for irisin, FNDC5, provides evidence for a sex-specific role of irisin in calcium release from bone due to osteocytic osteolysis.
The distinct transcriptomic features of extraocular muscle satellite cells, partially mimicked by NaBu treatment, endow enhanced self-renewal and axon attraction, contribute to neuromuscular junction preservation during ALS progression.
Experimental Piper gardens across five neotropical sites reveal complex contingencies in the influence of species and population-level biodiversity on the flow of resources to insect herbivores and ecosystem resilience to changes in water availability.
Mariana I Tsap, Andriy S Yatsenko ... Halyna R Shcherbata
Drosophila model reveals that NTE/SWS-associated neurodegeneration is a lysosomal storage disorder accompanied by a leaky brain permeability barrier, abnormal fatty acid metabolism, and inflammation.
Simona Bolamperti, Hiroaki Saito ... Hanna Taipaleenmäki
A novel mechanism underlying the regulation of osteoblast morphology, adherence, and migration that has implications in bone remodeling, regeneration, and response to the pharmacological effects of PTH treatment.
Sleep-encoded vocabulary influences awake decision-making 36 hr later, particularly when targeting the vocabulary to slow-wave troughs, which suggests that unconscious episodic memory formation during deep sleep is possible.
Sangeetha Kandoi, Cassandra Martinez ... Deepak A Lamba
Stem cell-derived retinal organoids are a useful tool to understand the pathobiology of devastating retinal degenerations and can aid to identify and validate therapeutics to promote rescue.
Seemingly disparate working memory biases, including short-term serial and contraction biases, may arise from a common mechanism via the interaction of multiple networks, each operating over a distinct timescale.
Alyssa D Huff, Marlusa Karlen-Amarante ... Jan-Marino Ramirez
Glutamatergic–cholinergic neurons in the postinspiratory complex are critical for swallow motor patterning and the coordination of swallow and breathing, which is disrupted by chronic intermittent hypoxia, a condition seen in many disorders associated with dysphagia and aspiration pneumonia.
Foxp3 and Ikaros, two transcription factors genetically linked to autoimmune disease in humans, cooperate to establish the epigenomic and transcriptomic landscape of regulatory T cells.
Structural promiscuity in PURA protein, induced by patient mutations, impacts nucleic acid binding, unwinding, and subcellular localization, indicating why so many patients display the full disease spectrum of PURA syndrome.
Alexander D Cook, Mark Carrington, Matthew K Higgins
A structure derived from cryogenic electron microscopy shows how ISG65, an African trypanosome receptor that aids virulence, binds C3b and suggests mechanisms through which ISG65 might aid complement resistance.
Subtelomeric sequences in the yeast S. cerevisiae are dispensable for either cell proliferation or homologous recombination-mediated telomere maintenance in telomerase-null cells, suggesting that these sequences represent remnants of genome evolution.
Intense starvation with high internal energy levels results in remarkably stable food-related memories that persist beyond actual food intake and are associated with overeating.
Differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance hemodialysis subjects are comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in hemodialysis subjects.
The mechanical stability of a nucleosome is enhanced upon the introduction of a single base pair mismatch that makes DNA more bendable, with implications on mismatch repair in vivo.
An unbiased approach unveils a non-canonical substrate of the known transporters, highlighting the mechanism behind the use of D-serine as a kidney biomarker.
The split mNeonGreen system enables fast and efficient endogenous tagging in human iPSCs and facilitates the study of proteins in human stem cells and differentiated cells by live imaging.
A combination of patch clamp electrophysiology and FRET determine critical interactions between HCN4 channels and the ER resident protein LRMP and suggest a possible mechanism for reduced cAMP sensitivity.
Sensory hair cells in the inner ear use inhibitory G proteins with different regulators at different stages of development to break symmetry, adopt a proper orientation, and grow stereocilia.
Venkateshwari Varadharajan, Iyappan Ramachandiran ... J Mark Brown
MBOAT7 loss of function in hepatocytes contributes to ethanol-induced liver injury, offering crucial insights into the dysregulated lipid metabolism and impaired autophagy associated with advanced liver disease.
Warming and altered precipitation reduce the growth rates of alpine soil bacteria by 40-90%, and the growth of ~70% taxa is influenced by antagonistic interactions between factors.
Integrated analyses of acute myeloid leukemia genetics and epigenetics demonstrate that epigenetic evolution occurs in a convergent manner in the absence of DNA mutations at relapse post-chemotherapy.
Using sequence-determined functional genomic features instead of original genotypes can partially overcome challenges in genetic association studies, such as rare variant exclusion and population structure.
Detailed molecular characterization of a constitutively active bacterial NADPH oxidase (NOX) provides clues to the activation mechanism required to trigger electron transfer and reactive oxygen species (ROS) production in tightly regulated eukaryotic NOX.
Evolution-guided structure-function analyses reveal that CD4 transmembrane and intracellular juxtamembrane motifs play a more profound role in initiating pMHCII-specific TCR-CD3 signaling than previously characterized CD4-Lck interactions.
The N-terminal domain of Staphylococcus aureus GpsB, a scaffolding protein, forms an atypical asymmetric dimer and binds to the C-termini of FtsZ and PBP4, influencing the localization and regulation of both the Z-ring and cell wall synthesis.
The new vaccine candidate for tuberculosis displays superior protection against disease when compared the currently available vaccine, and can potentially provide new options for global childhood vaccination programs.
Katharina Eichler, Stefanie Hampel ... Andrew M Seeds
A synaptic resolution somatotopic map of nearly all mechanosensory neurons on the Drosophila head that individually elicit aimed grooming of specific head locations and collectively elicit a head grooming sequence.
A forebrain nucleus contributes specifically to the variability of syllable sequencing in songs of Bengalese finches, a songbird with complex syntactic song structure.
Edgar M Pera, Josefine Nilsson-De Moura ... Ivana Milas
An extracellular proteolytic pathway involving the serine protease HtrA1, its inhibitor SerpinE2, and the transmembrane proteoglycan Syndecan-4 control collective migration of neural crest cells in the developing embryo.
Jean-David Larouche, Céline M Laumont ... Claude Perreault
Multiomic analyses provide new insights into the involvement of transposable elements in T-cell development in the thymus and central tolerance induction.
Having compared cross-species cortical folding patterns between humans and macaques, it is shown that 'Gyral Peaks' can stably exist across different species.
Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
The sensitivity of Arabidopsis meiotic centromeres to heat stress suggests that centromere function is one of the key determinants of plant reproduction under rising temperatures.
Entrainment of global synchronization of vasomotion induced by repeated presentation of oscillating visual stimuli may facilitate efficient energy delivery to meet the demand for coordinated neuronal activity and circuit reorganization.
Hypobaric hypoxia exposure initiates splenic ferroptosis, reducing red pulp macrophages and exacerbating high-altitude polycythemia by impairing erythrophagocytosis and increasing red blood cell retention.
There is substantial individual variation in behavioral and neural responses to acute ketamine administration in healthy controls, which emphasises the need for personalized approaches when harnessing ketamine as a treatment for depression.
Integration of language model and geometric deep learning enables accurate and efficient genome-scale annotation of comprehensive protein-ligand binding sites.
Nguyen Thi Khanh Nhu, Minh-Duy Phan ... Mark A Schembri
E. coli that cause neonatal meningitis largely derive from two global clonal lineages that can additionally form intestinal reservoirs to seed recrudescent invasive infection even when appropriate antibiotics are used.
Broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2 as the virus and the landscape of immunity continue to evolve.
Brain region-specific profiling of O-GlcNAcylation interactome in Drosophila mushroom body suggests that hypo-O-GlcNAcylation impacts cognitive function by regulating translational activity.
HIV escapes human immune pressure through a single mutation in V2 domain of envelope protein leading to emergence of mutant-specific broadly reactive antibodies, a phenomenon recapitulated in combinatorial vaccine design.
Genetic and biochemical approaches reveal that mammalian cells possess a novel DDI2 and transcription-independent pathway for the rapid recovery of proteasome activity after clinically relevant pulse treatment with proteasome inhibitors.
The endosomal apparatus of African trypanosomes consists a continuous membrane system with functional subdomains rather than distinct compartments for early, late, and recycling endosomes.
2-Oxoglutarate and Fe(II)-dependent dioxygenases from clade C23 are the major source of guanidine in plants and release guanidine from arginine or homoarginine by C5 or C6 hydroxylation, respectively.
Pharmacological activation of farnesoid X (FXR) receptor by hammerhead-type agonists induces a novel enhancer RNA, termed Fincor, contributing to the amelioration of nonalcoholic steatohepatitis in mice.
Robert Horvath, Nikolaos Minadakis ... Anne C Roulin
Disentangling the different selective forces shaping the evolutionary dynamics of transposable elements (TEs) in the wild grass Brachypodium distachyon.
Toyoshi Yanagihara, Kentaro Hata ... Isamu Okamoto
Increased CD16+ T cell populations in bronchoalveolar lavage fluid highlight a potential biomarker and immune response mechanism in Pneumocystis jirovecii pneumonia.
A single-nucleus transcriptomic atlas reveals the molecular signatures and trajectory dynamics of the neurogenic lineage in the human hippocampus during neonatal development, adulthood, aging, and after injury.
Kristine B Walhovd, Stine K Krogsrud ... Didac Vidal-Pineiro
Greater early developmental growth, as indexed by birth weight, relates to greater cortical volume and area in a stable way through the human lifespan.
Genetic and biochemical analysis reveals that the anti-inflammatory effect of statins is due to decreasing cholesterol in macrophages and upregulating Jmjd3 to achieve the anti-inflammatory action.
Cryo-EM studies of doublet microtubules from wild-type and acetylation mutants suggest that acetylation of K40 affects the lateral rotational angle between protofilaments, leading to changes in the structure and stability.
Marcos Moreno-Aguilera, Alba M Neher ... Carme Gallego
KIS, a kinase upregulated in the developmental brain, phosphorylates the PTBP2 splicing complex and modulates alternative exon usage for proper synaptic spine emergence and maturation.
Thomas Grandits, Christoph M Augustin ... Alexander Jung
Neural networks can emulate normal and abnormal human ventricular action potentials accurately and potentially much faster than regular simulations paving the way for more efficient quantitative systems pharmacology studies.
Giulia Leanza, Francesca Cannata ... Nicola Napoli
In individuals with type 2 diabetes, downregulation of bone canonical Wnt signaling is linked to higher levels of advanced glycation end-products within the bone, contributing to lower bone strength.
Cristina Cacho-Navas, Carmen López-Pujante ... Jaime Millán
ICAM-1 engagement controls hepatic cell polarity, but this receptor can also signal without prior leukocyte interaction, thanks to its confinement into apical, microvilli-enriched, bile-canalicular domains and its actin connector EBP50.
Evidence of a relationship between substrate curvature, water evaporation and the building behavior of termites capable of mediating collective nest-building with no need for a building pheromone.
Columnar architectures, developed in early Cambrian phosphatic-shelled brachiopods, are highly biologically controlled and organic-matrix mediated, which sheds new light on the evolution and adaptation of biomineralization during the Cambrian explosion.
The bacterial AAA+ chaperone ClpL recognizes aggregated proteins via multiple contacts of its unique N-terminal domain and refolds them with high efficiency providing superior heat resistance.
Jacob H Wilmot, Cassiano RAF Diniz ... Brian Joseph Wiltgen
Locus coeruleus responses to salient environmental stimuli drive increases in hippocampal dopamine that are important for long-term memory formation during trace fear conditioning.
Genetically determined type 2 diabetes (T2D) may not increase the risk of fracture, but managing T2D-related risk factors is crucial to prevent fracture in patients with T2D.
Julian JA Hoving, Elizabeth Harford-Wright ... Alison C Lloyd
N-cadherin and Slit2/3/Robo interactions provide the outward force to drive collective Schwann cell migration during nerve regeneration, identifying a dual role for N-cadherin in both adhesion and repulsion processes during Schwann cell collective migration.
Optical imaging from macaque monkeys performing a detection task reveals the contribution of neural populations in V1 to the phenomenon of camouflage, where detectability decreases with target-background similarity.
A comprehensive review focusing on the role of osteoclasts as active regulators of bone homeostasis by influencing osteoblast function explores the currently known mechanisms and coupling factors involved in osteoclast–osteoblast communication and their potential as treatments for bone diseases.
Rafael Naime Ruggiero, Danilo Benette Marques ... Joao Pereira Leite
The enduring impacts of early-life seizures on cognition and behavior are not attributed to neuronal loss but to disrupted hippocampus-prefrontal cortex network dynamics, heightened neuroinflammation, and altered dopaminergic transmission.
Johannes Paladini, Annalena Maier ... Stephan Grzesiek
High-resolution NMR data and precise kinase activity assays on Abelson kinase bearing mutations in its αI-helix identify the αI-helix parts involved in disassembly of Abelson’s regulatory core and kinase activation.
The BTB zinc finger gene Bm-mamo regulates melanin pigmentation in silkworm caterpillars from multiple aspects, including melanin synthesis, pigment granules maturation, and cuticle construction.
Behzad Yaghmaeian Salmani, Laura Lahti ... Thomas Perlmann
Single nuclei RNA sequencing unmasks 16 variants of midbrain dopamine neurons within a continuum of their gene expression landscape and resolves their differential vulnerability.
Structural insights into the orthosteric inhibition and subtype specificity of P2X receptors by classical P2X antagonists facilitate the rational design of novel competitive antagonists for P2X receptors.
Bingjiang Lyu, William D Marslen-Wilson ... Lorraine K Tyler
Structural representations of sentences generated by deep language models correlate with human listeners' behaviours and neural activity, providing a quantifiable framework to uncover the neural dynamics underpinning incremental speech comprehension.
DePARylation is essential for cell survival and thus poly(ADP-ribose) glycohydrolase (PARG) expression correlates with cytotoxicity induced by PARG inhibition, which will benefit the development of PARG inhibitors for cancer treatment.
Individuals with higher blood levels of omega-3 and omega-6 fatty acids, especially omega-3, are less likely to die, either from any cause, cancer or cardiovascular disease.
A novel hydrogel-based platform uses a limited number of cells for tissue generation and offers unique advantages for high-throughput cardiac tissue culture.
The existence of a slow-moving zone around the transcription site may unify conflicting models of co-transcriptional versus post-transcriptional mRNA splicing.
A new in vitro approach allows measurement of the efficiency of the early steps of translation initiation on every messenger RNA in yeast simultaneously.
Vilazodone could bind to the 5-Hydroxtrayptamine receptor 1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production.
Eman Hijaze, Tsvia Gildor ... Smadar Ben-Tabou de-Leon
ROCK and the actomyosin network are essential for multiple aspects of sea urchin skeletogenesis, suggesting an independent deployment of these factors in biomineralization across Eukaryotes.
Fruit flies have special neurons in their pharynx with ionotropic receptors to prevent consuming too much salt, which was confirmed using a variety of behavioral and physiological assays.
Isotope tracing, mathematical modeling, and single-cell ATP analysis reveal changes in blood cell metabolism under various conditions, showing stressed hematopoietic stem cells support hematopoiesis through glycolytic ATP production via PFKFB3.
Multifaceted properties of the water-soluble derivative of antibiotic heliomycin enable it to offer greater antitumor value than its parent compound by inhibiting the tNOX-NAD+-SIRT1 axis to induce apoptosis.
Microfluidic methods are used to quantitatively probe single yeast cells' response to either simultaneous or sequential stresses, revealing the dynamic interplay between two antagonistic inputs, osmotic stress and glucose starvation.
James W Truman, Lynn M Riddiford ... Michelle Herko
This sesquiterpene hormone likely acted as a morphogenesis-to-differentiation switch in archaic embryos before it evolved its postembryonic function as the status quo regulator of insect metamorphosis.
Jonathan Zirin, Barbara Jusiak ... Norbert Perrimon
A CRISPR knock-in approach enables the efficient generation of tissue-specific LexA and QF driver lines which can simultaneously control gene expression in multiple tissues.
Fibroblast growth factor (FGF) ligands exhibit different preferences for signaling cascades triggered through FGFR1, a receptor which is critical for skeletal development, and these differences likely contribute to the amazing complexity of developmental processes.
The ~20,000 origins of replication in human cell lines that are reproducibly identified by multiple techniques in multiple cell lines are distant from known origin recognition complex and MCM2-7-binding sites.
Binocular combination of monocular neuronal responses involves response suppression for neurons more preferring one eye and response enhancement for neurons more preferring both eyes in macaque V1.
Jacques Pesnot Lerousseau, Christopher Summerfield
Spatial mapping serves as a cognitive scaffold for acquiring abstract conceptual invariances across sensory domains, shedding light on the mechanisms of human learning.
Masaya Harada, Laia Serratosa Capdevila ... Tommaso Patriarchi
Optogenetic manipulation and photometry recordings in the lateral hypothalamus show how interactions between dopamine and orexin systems underlie reward expectation revealing dopaminergic modulation of orexinergic activity via D2 receptors.
A majority of transcribed transposons during aging are derived from transcriptional defects, most notably intron retention and transcriptional readthrough.
Acute myeloid leukemia-specific predictive logic models reveal new therapeutic targets involved in cancer resistance mechanisms paving the way for personalized precision medicine.
Kyounghee Min, Batuhan Yenilmez ... Michael P Czech
Stellate cell lactate transporter MCT1 significantly contributes to liver fibrosis through increased collagen 1 protein expression in vitro and in vivo.
Integrating multiple protein language models using protein geometric graphs can dramatically improve the model performance for predicting the contacting residue pairs between interacting proteins.
Giovanni Anobile, Irene Petrizzo ... Guido Marco Cicchini
Evidence for a selective sensorimotor brain mechanism responsible for translating sensory numerical information into the number of actions in a sequence.
The kinetoplastid parasite Trypanosoma brucei employs a unique mechanism to target the conserved Aurora B kinase to kinetochores and the central spindle.
Laure Mignerot, Clotilde Gimond ... Christian Braendle
Caenorhabditis elegans egg-laying behaviour shows pronounced variation in natural populations, making it a promising model to investigate the microevolution of a simple neural circuit.
