Cryo-EM, Molecular Dynamics, and in vitro binding assays are combined to elucidate a new occluded conformation associated with zinc binding and energy coupling with the proton motive force.
Maruthi Kumar Pabba, Christian Ritter ... M Cristina Cardoso
Live cell tracking of labeled DNA reveals that replisome loading rather than DNA synthesis decreases the chromatin motion during S-phase in human cells.
Controlling for the effects of mechanical stimulation during sleep deprivation reveals substantial multi-cycle sleep rebound in Drosophila and reveals serotonin as a potential sleep substance in the fly brain.
Nydia Tejeda-Munoz, Yagmur Azbazdar ... Edward M De Robertis
The archetypal tumor promoter PMA, which promotes cancer without mutating the DNA, increases Wnt signaling by activating macropinocytosis and membrane trafficking in Xenopus embryos and tumor cells.
Acetate concentration, which is significantly increased in association with energy stresses such as those that occur with diabetes or starvation, is emerging as a novel 'ketone body' with potential as a parameter for evaluating the progression of energy stress.
A complex colour polymorphism which links colour with behavioural and life-history traits is associated with a single gene duplication in male wood tiger moths.
Jennifer T Pentz, Kathryn MacGillivray ... William C Ratcliff
Clonal development, but not aggregation, promotes the transition of Darwinian individuality from cells to groups, emphasizing the fundamental role of initial multicellular life cycles in the evolution of multicellularity.
Glucocorticoids are assumed to reflect 'stress,' but they increase proportionally to the increase in metabolic rate induced by stressors, leading us to propose that glucocorticoids reflect metabolic rate, not stress.
Deep reinforcement model and experimental evaluations identified a small-molecule CRM1 inhibitor that can selectively ablate extranodal NK/T cell lymphoma cells.
Diego Candia-Rivera, Federico Raimondo ... Jacobo D Sitt
Brain-heart interactions under the processing of auditory irregularities could help to distinguish whether a patient is in a vegetative state or in a minimally conscious state.
Vanessa Dumeaux, Samira Massahi ... Michael T Hallett
Candida albicans cells respond in two distinct ways to fluconazole exposure where cells enter the Ribo-dominant state characterized by an upregulation of ribosomal-related proteins and processes, or cells enter the Stress-dominant state characterized by the upregulation of stress responses.
Isoform-specific variations in doublecortin-like kinases offer a new framework for understanding kinome-wide modulation of protein stability and catalytic activity.
A common genetic variant in Black patients increases the risk of renal disease, which increases the risk of sepsis, but there is no direct association between the variant and sepsis.
Maria Ruesseler, Lilian Aline Weber ... Laurence Tudor Hunt
Human behaviour in a continuous decision making task adapts to the overall statistics of the sensory environment, and these adaptations are also reflected in changes in neural responses to incoming sensory evidence.
Lars N Royall, Diana Machado ... Annina Denoth-Lippuner
Genetic birthdating in forebrain organoids shows asymmetric inheritance of centrosomes in human neural progenitor cells, required for proper human neurogenesis.
The bicontinuous nanospheres platform enables dual encapsulation and in vivo activation of lipid and protein antigen-specific T cells, resulting in enduring lipid depots for sustained immune responses.
Tom G Richardson, Genevieve M Leyden, George Davey Smith
Leveraging time-varying and tissue-dependent genetic instruments into Mendelian randomization studies may help develop insight over more conventional applications.
Jessica Jacobs-Li, Weiyi Tang ... Marianne E Bronner
Single-cell transcriptome analysis of sacral compared with vagal neural crest-derived cells in the developing chick enteric nervous system reveals both similarities and differences between these two cell populations.
CK21 emerges as a compelling candidate for pancreatic cancer treatment, and its capacity to target the NF-κB pathway, induce mitochondrial-mediated apoptosis, and do so with minimal toxicity is a significant stride in the quest for improved therapies.
A novel in vivo strategy for reversible, multiplexed control of circulating hormone expression levels, achieved by combining genome-editing and intramuscular electroporation of fluorescently tagged hormones in the naturally short-lived turquoise killifish.
Genetic analyses reveal the importance of dynamic protein processing at the apical cell membrane in response to forces damaging cell membranes during tube expansion in tubular organs.
A toxin-antidote element, identified for its role as a selfish genetic element that spreads through a population by killing certain offspring, also plays a beneficial role to the host.
Xiang Wang, Vitaliy V Bondar ... Anastasia G Henry
Rab12 was identified as a key modulator of LRRK2-dependent Rab phosphorylation that mediates the recruitment of LRRK2 to lysosomes in response to damage.
Herschel S Dhekne, Francesca Tonelli ... Suzanne R Pfeffer
Activating mutations in the leucine-rich repeat kinase 2 cause Parkinson’s disease, and an unbiased genome-wide screen revealed an unexpected, specific role for Rab12 in activating this kinase directly for Rab GTPase phosphorylation.
The analysis of T cell movement in multiple tissues (lymph node, villi, and lung under two different inflammatory conditions) sheds new light on how T cells navigate different tissue environments to improve immunity and search processes.
In vitro and in vivo data show that C-natriuretic peptide is significant for increasing mitochondrial bioenergetics by cAMP-PKA pathway and improving cytoplasmic and nuclear maturation of maternally aged oocyte.
Christopher T Boughter, Martin Meier-Schellersheim
A comprehensive computational study of germline-encoded T cell receptor CDR loops and MHC alpha-helices finds limited evidence for evolutionary conserved interactions, and instead suggests broad biophysical compatibility guides the interactions between the two proteins.
Elmehdi Bahafid, Imke Bradtmöller ... Rüdiger GW Simon
Mutant and gene expression analyses shows that phytohormones and mobile transcription factors interact to coordinate organ formation with stem cell maintenance in the plant shoot meristem.
The Foxa2 lineage-based organ generative strategy allows us to establish a unique paradigm for the simultaneous generation of functional whole lungs and thymus, which can be applied to future transplantation therapy.
Manfred G Kitzbichler, Daniel Martins ... Neil A Harrison
Revealing two distinct brain systems linked to obesity, this research illuminates the intricate relationship between obesity, brain microstructure and genetics with potential implications for treatment and prevention.
Habituation to mechanical vibration of crawling Drosophila larvae exhibits distinct time constants that characterize desensitization, re-sensitization, and further adaptation to repeated stimulus patterns.
Disruption of the intracellular vimentin network upon cellular stress results in enhanced cell surface vimentin on human osteoarthritic chondrocytes and might represent a novel membrane-associated marker of stress-induced premature senescence.
Yingnan Zhang, Kelly Zhang ... Natalia A Trayanova
A novel computational approach integrates personal genetics into personalized whole heart digital twins to predict ventricular arrhythmia circuits for patients with arrhythmogenic right ventricular cardiomyopathy.
Enterovirus D68, a pathogen associated with a rare child paralysis disease, depends on the cellular protein SIRT-1 for release of virus, indicating that SIRT-1 may be an important therapeutic target.
Marco Leibinger, Charlotte Zeitler ... Dietmar Fischer
Systemic treatment with di-methyl-amino-parthenolide facilitates CNS axon regeneration and functional recovery by reducing the induction of microtubule detyrosination by established regenerative therapies.
A new type of mRNAs-loaded CD133+ vesicles, named intercellsome, mediate cell-cell communications to compensate intracellular proliferative signal deficit, representing a previously unrecognized mechanism of cell proliferation under stress.
Stefano Mammola, Martino Adamo ... Ricardo A Correia
Different species-level characteristics and sociocultural factors influence scientific and societal interest in biodiversity, with important implications for species-level conservation and dissemination.
A novel trans-humeral prosthesis control method based on artificial intelligence, and the proof of its effectiveness in virtual reality as well as on a robotic platform.
Germline extrachromosomal circular DNAs are mainly formed by microhomology-mediated ligation of nucleosome-protected fragments and barely contribute to de novo genomic deletions at meiotic recombination hotspots.
Gayathri Nagaraj, Shaveta Vinayak ... Dimpy P Shah
Sociodemographic (age, race/ethnicity) and clinical (Eastern Cooperative Oncology Group performance status, pre-existing comorbidities, and active and progressing cancer) risk factors were associated with worse COVID-19 outcomes in patients with breast cancer.
Juvenile and adult metabolism are constrained from evolving independently from each other even in a species that lacks developmental continuity between juvenile and adult organs.
Guillaume Viejo, Daniel Levenstein ... Adrien Peyrache
Pynapple advances data analysis in systems neuroscience with a versatile, open-source framework that uses common objects to handle diverse data streams, ensuring reliable and reproducible analysis while maintaining long-term backward compatibility.
σ28-Dependent sRNAs fine-tune flagella synthesis, with one sRNA connecting synthesis with metabolism and two sRNAs with opposing effects connecting synthesis with ribosomal protein production through unique binding within coding sequences.
Tim Aguirre, Gillian L Dornan ... Dorothea Fiedler
A subtle mutation in the ATP-binding site of inositol hexakisphosphate kinases increases their conformational flexibility and thereby makes them susceptible to isozyme-selective, allosteric inhibition.
Dysmyelination of GABAergic hippocampal interneurons causes mislocalization of axonal ionic channels and disturbs their intrinsic physiological properties, suggesting that it may contribute to cognitive deficits observed in multiple sclerosis patients.
Neural network modeling shows that hierarchical application of the simple computational principle of predicting future sensory input from its past can capture features of visual motion processing from the retina to the visual cortex.
The hippocampus demonstrates flexible coding during memory encoding, prioritizing either distance or time information based on the specific requirements of the experiment.
The COVID Tissue Atlas Consortium, Alejandro A Granados ... Bruce Wang
A conserved transcriptional signature in macrophages and endothelial cells occurs in multiple organs in response to COVID-19 and suggests potential molecular interactions between the two cell types.
Frontal cortical circuit alterations and cognitive deficits identified in mouse genetic models are reversed by chemogenetic or optogenetic stimulation of the mesocortical dopamine circuit in an adolescent period.
Proteomic analysis of brain organoids from creatine transporter deficiency (CTD) patients enhance the understanding of CTD offering potential therapeutic targets and a robust foundation for continued research in the field.
Liang-Yu Pang, Steven DeLuca ... Allan C Spradling
Chromatin changes downstream from Drosophila germline stem cells and fertilized zygotes alter how transposable element activity and gene expression are controlled to facilitate differentiation.
Louiza S Velentzis, Megan A Smith ... Karen Canfell
Results from this modelled analysis indicate that short-term delays in HPV vaccination of adolescents are unlikely to have substantial long-term effects on HPV-related cancers, provided catch-up of missed vaccine doses can be implemented.
Modeling the evolution of PRDM9 in light of recent results implicating the importance of PRDM9 binding symmetry suggests the advantage of new PRMD9 alleles is in limiting the number of binding sites used effectively rather than increasing net binding.
Inducing the formation of mitochondrial respiratory chain supercomplexes in Drosophila melanogaster, where they are normally absent, does not have any noticeable impact in the function of the respiratory chain.
Marija Markicevic, Oliver Sturman ... Nicole Wenderoth
The structural characteristics of a circuit and its hierarchical dimensions are shown to influence regional time-series dynamics after targeted cellular-level manipulations.
Mathematical modeling shows how RAF inhibitors can actually activate RAF kinases by stabilizing RAF proteins in the conformation capable of dimerization.
Patrik Simmler, Eleonora I Ioannidi ... Gerald Schwank
SF3B1-K700E, a gene mutaiton found recurrently mutated in pancreatic cancer, increases malignancy in an autochthonous mouse model of pancreatic cancer and induces resistance against TGF-β-induced apoptosis in vitro by missplicing of MAP3K7.
Van Thien Chi Nguyen, Trong Hieu Nguyen ... Le Son Tran
SPOT-MAS (screening for the presence of tumor by methylation and size) is an affordable and effective multi-cancer early detection test analyzing multiple features of circulating tumor DNA.
Julie C Necarsulmer, Jeremy M Simon ... Todd J Cohen
Impairing TDP-43 RNA-binding capacity through a single acetylation-mimic mutation alters TDP-43 function and recapitulates biochemical, molecular, and behavioral features of sporadic TDP-43 proteinopathies, thus providing opportunities for new research into pathogenic mechanisms and therapeutic interventions.
Jayashree Jena, Luis Miguel García-Peña ... Renata O Pereira
Deletion of optic atrophy 1 in brown adipose tissue induces secretion of growth differentiation factor 15 as a batokine to attenuate diet-induced obesity and improve glucose clearance, hepatic steatosis, and thermoregulation in mice by increasing energy expenditure.
Improvement in levels of anxious-depression corresponds with increased confidence in performance among individuals receiving mental health treatment within a large longitudinal dataset.
The coupling between neural oscillatory activity, haemodynamics, and metabolism is localised to the temporo-parietal region in response to social stimuli, providing evidence of the importance of investigating the energetic basis of brain functional specialisation.
Interactions between cortical and subcortical circuits in the mammalian brain flexibly control the flow of information streams that drive decisions by shifting the balance of power both within and between action representations.
First 3D-structure and first observation of organized protofilaments of MreB from a Gram-positive bacterium, suggesting a model where ATP drives the formation of dynamic pairs of MreB protofilaments on a lipid surface.
Wind and ocean wave conditions experienced by albatrosses were estimated using an animal-borne recorder and revealed that take-off was easier under higher wave conditions.
Genetic variation in a biogenic amines receptor underlies a means of gain control for nonassociative learning and hence an important form of attention that is the basis for tradeoffs in foraging in a social collective.
We are writing to respond to the comment by Anderson et al., 2023 on our article about limb movements in male little torrent frogs (Zhao et al., 2022).
Inhibitory innervation in the dorsolateral geniculate nucleus is crucial for adult thalamic and cortical ocular dominance plasticity, highlighting potential thalamic involvement in conditions like amblyopia and learning disabilities.
Revisiting limitations in time-resolved X-ray free-electron laser structures of the bacterial photosynthetic reaction center uncovers their irrelevance to proposed structural changes in electron transfer dynamics.
Abhishek Jamwal, Cristina F Constantin ... Matthew K Higgins
The most effective growth-neutralising antibodies which target the PfRH5 protein from a malaria parasite function by preventing the parasite from binding to basigin-containing membrane protein complexes on human erythrocytes.
Khalyd J Clay, Yongzhi Yang ... Michael Petrascheck
Carefully controlling the level of protein synthesis reduction and mode of translation inhibitor action reveal different and sometimes opposing phenotypic effects following proteostasis stress, wherein protection via initiation inhibition specifically depends on heat shock factor 1.
Cori K Cahoon, Colette M Richter ... Diana E Libuda
Developing eggs and sperm differentially regulate specific steps of meiotic DNA repair by altering the composition and dynamics of proteins within synaptonemal complex.
A spiking neural network model explains how hippocampal theta sequences in two-dimensional arenas can arise from a combination of sensory-motor inputs, short-term synaptic plasticity, and intrinsic connectivity.
Alan V Rincon, Bridget M Waller ... Jérôme Micheletta
Detailed quantification of macaque facial behavior reveals a positive link between social and communicative complexity, and helps us to better understand the evolution of animal communication.
TNFAIP2 was found to interact with IQGAP1 and Integrin β4, which activates RAC1 through TNFAIP2 and IQGAP1 and confers DNA damage-related drug resistance in triple-negative breast cancer.
Christopher H Emfinger, Lauren E Clark ... Alan D Attie
Analysis of islet calcium oscillation responses will provide the field with a resource with which to determine the strain of interest for their specific islet biology questions.
María Rodríguez-López, Nicola Bordin ... Jürg Bähler
Large-scale screens and computational approaches reveal phenotypes for 3492 genes and gene-ontology predictions for 783 genes, including hitherto unstudied genes, which provides a potent platform to further dissect protein function.
Xenopus laevis arose from hybridization of two different frog species millions of years ago, leading to adaptation of the genetic networks controlling early embryonic development and stem cell induction to balance expression between the genes inherited from each ancestor.
Mohamad Ibrahim Cheikh, Joel Tchoufag ... Konstantin Doubrovinski
Direct mechanical microcantilever-based measurements establish key material parameters describing mechanical response of the early Drosophila embryonic epithelium.
Márton A Simon, Iordan Iordanov ... László Csanády
Functional studies on CFTR anion channels harboring combinations of catalytic site mutations in the active ATPase site reveal the true stability of the prehydrolytic open-pore state as well as nucleotide-binding domain interface features that are unique to human CFTR.
