The meiotic recombination landscape in vertebrates was re-engineered via the co-evolution of a dual histone H3K4/H3K36 methylation 'writer' PRDM9 and its 'reader' ZCWPW1 that facilitates efficient double strand break repair.
Quantitative analysis of behavior coupled with computational modeling reveal the set of circuit-level principles that underlie cerebellar-dependent motor learning in smooth pursuit eye movements of monkeys across timescales.
SKAP2 is critical for hematopoietic cell protection against Klebsiella infection in mouse lungs, for full phosphorylation of Src Family Kinases, Syk, and Pyk2, and for Klebsiella-induced reactive oxygen species production.
The forces that multicellular tumor aggregates exert on their environment lead to non-linear, scale-invariant tissue deformations far away from the tumor, which can be exploited to quantify its collective contractility.
Newly formed tetraploid cells rapidly lose extra centrosomes acquired upon tetraploidization via asymmetric centrosome clustering during cell division and selective advantage of tetraploid daughter cells that inherit a single centrosome.
Maternal spindle transfer is a feasible approach to enhance embryonic developmental of compromised oocytes, which can represent a new strategy for patients with forms of infertility refractory to current treatments.
Drosophila synaptotagmin 7 functions to restrict SV availability and release, but does not act as the Ca2+ sensor mediating the asynchronous release and facilitation remaining in synaptotagmin 1 mutants.
Combined simulations and electrophysiological experiments show that the CLC channels and exchangers form physically distinct and evolutionarily conserved pathways through which Cl- and H+ ions move when crossing biological membranes.
Disease-associated mutants of the TRPM3 ion channel are overactive, and they are inhibited by the antiepileptic medication primidone, offering a potential therapeutic intervention to treat this channelopathy.
Tucked within a well-known story of diverging gene function is a single enhancer encoding two inseparable specificities that regulates two adjacent genes, each with different spatiotemporal expression patterns.
Regenerating neural progenitors of the Xenopus tropicalis tail prioritize differentiation to motor neuron types earlier than proliferation, a decision partly regulated by the transcription factors Pbx3 and Meis1.
Unexpected structural diversity of nematode small molecules, as revealed by high-resolution phylogenetic analysis, suggests recurrent biochemical innovation, a pattern that is probably typical across animals.
Glycolysis is locally enhanced and redirected in zebrafish to generate lactate, which functions as a signaling molecule to fully activate Fgf target genes required for proper sensory and neural development.
A combination of NMR, fluorescence, and molecular dynamics simulations reveals the recognition mechanism for the intrinsically disordered regulator of protein kinase A, highlighting the enzyme's nuclear export process.
Genetic and molecular analyses identify and characterize an evolutionary battle over lysis timing wherein a bacteriophage delays lysis through lysis inhibition while a defensive phage satellite accelerates lysis.
A major consequence of ductal-to-squamous lineage transition in pancreatic cancer cells is to augment inflammation, which may explain the exceptionally poor clinical outcomes of squamous-subtype tumors.
Orthogonal to traditional paradigms that manipulate neuroligin expression level, optogenetic stimulation of tyrosine phosphorylation highlights a role of the intracellular domain of endogenous neuroligin-1 in excitatory synaptic differentiation and potentiation.
A simple, computationally efficient method provides spatiotemporally precise optogenetic perturbations in freely walking Drosophila, revealing the asymmetries and region-specificity of behavioral programs evoked by activating mechanosensory and chemosensory neurons.
The juxtacrine signaling molecule EphA7, when expressed on terminally-differentiated myocytes, non-cell-autonomously induces adjacent myoblasts to also commit to terminal differentiation leading to rapid coordinated differentiation across the entire population.
Male-type aggressive and courtship behaviors of the fruit flies are differentially specified by two sex-determining genes, providing a substrate for the evolution to sculpt these two behaviors independently.
Pathological vessel leakage in mouse retinopathy models depends on VE-cadherin Y685 phosphorylation status, which in turn is regulated by a signaling cascade originating with VEGFR2 Y949 phosphorylation.
Networks simulations and in vivo imaging suggest a stable backbone of stimulus representation formed by neurons with low population coupling, alongside a flexible substrate of neurons with high population coupling.
Llama-derived single-domain antibodies, formatted as bispecific antibodies with human Fc domains, reduce and prevent bunyavirus-induced morbidity and mortality in mice upon prophylactic and therapeutic administration.
Single-turnover studies reveal quantitative insights into the inner mechanics and unfold hidden facets in the conformational coupling of ATP binding, hydrolysis, and substrate translocation by ABC transporters.
Novel mechanisms for cellular centering and symmetry breaking involving persistent contractile actomyosin flows and their hydrodynamic interactions with the fluid cytosol are presented and studied using a minimal, reconstituted system.
A library of the paired peptide/HLA multimers and artificial APCs allows for construction of a large database of class I-restricted peptides and cognate tumor-reactive TCR genes at an unprecedented scale.
Combining psychophysics and functional MRI reveals a qualitative asymmetry in neural engagement when reflecting on whether a stimulus is seen (detection) compared to reflecting on what a stimulus is (discrimination).
Crystallography together with electron-resonance spectroscopy, molecular-dynamics simulations, and transport measurements reveal the molecular details of protein conformational change, and how this change contributes to function in a CLC-type chloride/proton exchanger.
Centromere deletion in Cryptococcus deuterogattii results in neocentromeres, which span actively expressed genes and at elevated temperatures cen10∆ mutants are unstable leading to chromosome fusion and silencing of the neocentromere.
In vertebrates, large regulatory landscapes sometimes behave as coherent regulatory units, which may explain the lack of effect sometimes observed when single enhancer sequences are deleted in isolation.
A combination of genetic fate-mapping and parabiotic experiments reveals the chronological expansion of yolk-sac-derived renal tissue-resident macrophages with age by cellular proliferation and recruitment from circulating progenitors.
Cell lineage tracing and biochemical analysis of cell fate during murine stem cell differentiation demonstrates a specific cooperativity between perturbations in histone methylation and eroded telomeres that destabilize cell differentiation.
Step-wise processing of plant peptide hormone precursors by subtilisin-like proteinases in consecutive compartments of the secretory pathway is required for formation and secretion of the bioactive peptides.
Open source software enables neuroscientists to integrate single neuron or synaptic-resolution datasets from different imaging modalities to analyse morphology and connectivity at the scale of whole brains and connectomes.
The chloride channel Ano1/Tmem16a plays an essential and non-redundant role in the developing airway by inhibiting mucus cell hyperplasia and promoting proper immune function of the airway mucosal barrier.
Confidence-dependent reinforcement learning is active and produces trial-to-trial choice updating even in well-learned perceptual decisions without explicit reward biases, across species and sensory modalities.
The structure of the potassium-chloride cotransporter KCC4 provides insight into the basis of ion specificity, transport stoichiometry, and activity regulation for a broadly physiologically and clinically important transporter family.
Vps29 promotes retromer localization in the adult Drosophila brain, engaging Rab7 and TBC1D5, and its loss triggers age-dependent neuronal impairments in endolysosomal trafficking and synaptic transmission.
Single-molecule immunoprecipitation method reveals that the high catalytic rate and multi-tasking capability make a concerted contribution to the strong signaling potency of the HER2-HER3 heterodimers.
A new analysis algorithm (DISC) enables accurate analysis of data from high-throughput single-molecule paradigms and reveals a non-cooperative binding mechanism of cyclic nucleotide-binding domains from HCN ion channels.
A gain-of-function in a new chemical defense resulted in no trade-offs and and independent evolution between novel and ancestral defenses, suggesting low redundancy among different defensive chemicals.
Aconitate decarboxylase 1-derived itaconate reduces mitochondrial respiration via inhibition of succinate dehydrogenase but does not regulate inflammatory response or NRF2 expression in response to particulate matter.
Artificial selection on wing color and CRISPR/Cas9 knockout of the optix gene both alter scale lamina thickness in Junonia coenia, which shifts structural color wavelength and mimics macroevolutionary butterfly diversity.
The condensin I subunit Cap-G is expressed in post-mitotic neurons and its removal, especially from less mature neurons, results in gene expression changes, reduced survival and behavioural defects in Drosophila.
In the ancestor of mammals, a multifunctional innate immune protein evolved when a mutation enhanced the protein’s pro-inflammatory activity and proteolytic regulation without disrupting the protein’s antimicrobial activity.
People who have attempted suicide exhibit blunted sensory processing during breathing and pain perturbations, as well as lower heartbeat perception accuracy and reduced mid/posterior insula activity during interoceptive attention.
Skin-associated bacteria underlie the production of a potent defensive neurotoxin in newts, impacting host physiology, molecular evolution, and predator-prey interactions in a coevolutionary arms race.
Seemingly contradictory findings of single-molecule and in vivo experiments on a major mechanism of chromosome organization are reconciled by computationally investigating mechanisms of loop extrusion that are consistent with both.
Collective responses of animals are generally controlled by complex biological mechanisms and in Caenorhabditis eleganscollective dynamics are purely controlled by physical parameters such as oxygen penetration and bacterial diffusion.
A combination of in vitro and in vivo experiments demonstrate a cell-autonomous role of the KIT ligand/KIT signaling pathway in protecting retinal photoreceptor cells from environmentally or genetically caused degeneration.
Application of laser-capture microdissection to planarian intestinal tissue provides a new tool for analysis of tissue-specific gene expression in flatworms, and a new resource to advance investigations of gastrointestinal regeneration.
HLA class I-disease associations have been studied for decades; a new approach for investigating the underlying mechanism can overcome past problems with interpretation and help to understand the etiology of human diseases.
Multiphoton live-imaging illuminates the dynamic underpinnings of how different types of progenitor cells migrate and interact to robustly build the mammalian Dentate Gyrus neural circuitry and new outer neurogenic niche.
Vascular degeneration of the choroid and RPE disorganization were associated with pharmacological macrophage ablation, indicating that insufficiency of macrophage function may be a mechanism underlying age- and AMD-associated pathology.
In mouse brain slices, native delta glutamate receptors carry ionic current and underlie the α1-adrenergic receptor-mediated depolarization of dorsal raphe neurons that drives action potential firing in vivo.
Single cell RNA sequencing leads to identification and separation of transcriptionally and functionally heterogeneous, natural human satellite cells, including a subpopulation marked by CAV1 harboring quiescence phenotypes and engraftment potential.