Metabolomics and stable isotope labelling studies of virulent Mycobacterium tuberculosis reveal a de-centralised metabolic network able to utilise various amino acids as nitrogen sources to a better extent than ammonium.
In vivo imaging reveals that gradually increased amount of glucose mediates the heterogeneous functional development of individual β-cells by activating its major downstream calcineurin/NFAT signaling pathway.
The DMA-1/LRR-TM cell surface receptor signals through partially redundant pathways to cell-autonomously pattern dendrites, including by directly forming a complex with both the TIAM-1/GEF and ACT-4/Actin.
An in vivo drug screen of FDA-approved compounds in zebrafish identified host-directed therapies against mycobacterial infection, including the drug clemastine, which targets the P2RX7-inflammasome axis to enhance bacterial control.
Specific attachment of molecularly defined gold nanoparticles enables precise localization, critical for structural studies in vivo, of proteins of unknown structure within the cellular milieu by cryo-electron tomography.
Computer simulations reveal the potential and limitations of recently proposed CRISPR-based cell lineage recorders, and suggest how the recorders' design can be optimised to yield more accurate cell lineage trees.
Fly protein families Dprs and DIPs can create a multitude of complementary interfaces for homo- and heterophilic adhesion complexes, resulting in instructive roles for connectivity in the motor neuron circuitry.
The first comprehensive insight into speed, trajectory and morphology profiles of tangentially migrating dopaminergic neurons and the alterations in their migratory behavior in absence of Reelin signaling.
During behavior, many neurons do not have classic trial-averaged responses to behaviorally relevant stimuli, but can still have activity and population dynamics related to stimulus and behavioral choice on single trials.
Purkinje cells of the cerebellum, a conserved vertebrate brain region important for sensorimotor integration, receive sensory and motor information from distinct input streams and are functionally clustered into modules reflecting the larval zebrafish's behavioral repertoire.
The histone chaperone FACT and the deubiquitinating enzyme Ubp10 act in concert to remove ubiquitin from histone H2B in nucleosomes, and likely coordinate nucleosome assembly during DNA replication and transcription.
Humans intranasally administered the neuropeptide oxytocin waste less and earn more spoils during intergroup conflict because oxytocin enables group members to better coordinate strategic attacking of out-groups.
The requirements for preinitiation complex formation/stability and transcription by RNA polymerase II in yeast cells are different from those in vitro, thereby altering the current view of basal transcription.
A key transcription-factor for osteogenic differentiation, PLZF, acts as a transcriptional activator by binding to active developmental enhancers and facilitates mediator recruitment, but is not involved in enhancer looping.
In Drosophila oocytes, the exclusion of the scaffold protein PAR3 from the posterior cortex depends on PAR1 and endocytosis, while its anterior localisation requires microtubules and recycling endosomes.
Heterogeneity in perceptual sensitivity of human cone-mediated vision across wavelength originates in the cone photoreceptors, where S cones exhibit distinct functional properties in comparison to L and M cones.
Interaction of HIV capsids with the cellular protein cleavage-and-polyadenylation factor 6 at the inner side of nuclear pores promotes nuclear entry of the viral replication complex in primary human macrophages.
Rostromedial tegmental neurons encode motivational valence and opponent responses across a wide range of affective stimulus modalities, while also driving dopamine inhibition and conditioned place aversion to aversive stimuli.
This paper describes an effective pipeline for conversion of conventional monoclonal antibodies into recombinant form that results in an IgG subclass switch that greatly expands their utility for multiplex labeling.
Genomic deletions and gene conversions, caused by template switching associated with restarted DNA replication, are detected downstream of a collapsed replication fork and are suppressed by several conserved DNA helicases.
Primed Track is an image analysis tool that allows for computational correction of drifting specimen to enable accurate lineage tracing of mammalian pre-implantation development even for larger imaging time intervals.
Biophysical analyses indicate that Munc18-1, Munc13-1, synaptotagmin-1 and complexin-1 maintain assembled trans-SNARE complexes in the presence of NSF-alphaSNAP, suggesting that they form part of the primed state of synaptic vesicles.
A near-complete flux balance analysis model of a minimal cell demonstrates the high essentiality of its metabolic genes, agrees well with experimental essentiality data and suggests some further gene removals.
Genetic, developmental and pharmacological analysis in Caenorhabditis elegans demonstrate that ATAT-2 tubulin acetyltransferase activity regulates synapse maintenance by acting within the RPM-1 signaling network, but independent of the DLK-1 MAP3K.
Training-induced perceptual gain in the discrimination between odor enantiomers is nostril-specific and structure-based, indicating that early olfactory processing of the chemical features of unirhinal input remains plastic in human adults.
CaImAn is an open-software package that equips the neuroscience community with a set of turnkey, fast and scalable solutions to pre-processing problems arising in single cell calcium imaging data analysis.
TRIM28 was found to be a versatile dual-function latency contributor by bridging both suppressive epigenetic modifications and RNAP II transcriptional-pausing, and can be a novel target to develop latency-reversing agents.
A Drosophila fertility gene is identified that acts as a linker between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development and transposon silencing..
Structures of a TMEM16 phospholipid scramblase reveal that its Ca2+-dependent activation entails global conformational changes and how these rearrangements affect the membrane to enable transbilayer lipid transfer.
A correlation between the periplasmic embellishment of the flagellar motor and its stator system type is described, motors with dual H+-dependent stator systems have one periplasmic ring formed by MotY.
Gene knock-out of the omega-1 ribonuclease of Schistosoma mansoni eggs resulted in immunologically impaired phenotype, showcasing the novel application of CRISPR/Cas9 genome editing and utility for functional genomics in schistosomes.
Multiscale Graph Correlation, an interpretable hypothesis test with strong theoretical guarantees for discerning relationships in complex data, requires about half the sample size as other methods, whilst maintaining computational tractability.
UV-reflective dragonfly wax is shown to consist of very long-chain methyl ketones and aldehydes, and a synthetic dragonfly wax spontaneously forms light-scattering fine structures with strong UV reflection.
Genomic associations with lifespan principally reflect heart disease/smoking/dementia but not other cancers, and distinguish lifespan differences of five years between top/bottom deciles of a score derived from DNA alone.
TALE homeodomain transcription factors have been independently recruited to regulate gametophyte to sporophyte transitions in two complex multicellular eukaryotic supergroups, land plants in Archaeplastida and brown algae in Chromalveolata.
The myopathic transcription factor DUX4 induces discordant dysregulation of transcript and protein levels, demonstrating a key role for post-transcriptional gene regulation in facioscapulohumeral muscular dystrophy.
Prostate cancer cells maintain heterogeneous androgen receptor transcriptional activity through upregulation of AR-regulated coactivator GREB1, and cells with high activity rapidly develop resistance to antiandrogen therapy in a GREB1-dependent manner.
As the first fully genetically encoded method, PARIS allows cell-specific, long-term, repeated measurements of gap junctional coupling with high spatiotemporal resolution, facilitating its study in both health and disease.
Hantaan virus nucleocapsid cryo-EM structure determined at 3.3 Å resolution reveals how nucleoproteins assemble into a metastable helix containing a continuous RNA-binding groove compatible with genome encapsidation and compaction.
The molecular microenvironment of coronaviral replicase complexes provides functional and spatial links between conserved cellular processes and viral RNA synthesis, and highlights potential targets for the development of novel antivirals.
Integrin a11 is identified as an Osteolectin receptor, revealing a new mechanism for adult skeletal bone maintenance in which Osteolectin/a11b1 signaling promotes bone formation by activating the Wnt pathway.
Cryo-EM structures of the gating cycle of bestrophin reveal the molecular underpinnings of activation and inactivation gating in this calcium-activated chloride channel and reveal a surprisingly wide pore.
A complete connectome of the ON and OFF motion pathways of the Drosophila optic lobe is acquired using three-dimensional EM methods, and the similarities and differences of the two pathways are uncovered.
Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.
The importance of synchronous Purkinje cell complex spikes for controlling cerebellar output was investigated by simultaneously recording from cerebellar nuclear cells and arrays of Purkinje cells that synapse onto them.
Biochemical analyses of transcription complexes, including kinetic studies and probes of translocational and conformational states, establish the elemental mechanism of pausing, which underlies regulation of gene expression in all organisms.
When ancestral Xenopus returned to water ~170mya, they evolved a new method for producing courtship calls underwater without airflow, using vibrations that also preserve essential acoustic information on species identity.
Fixational eye movements transform the spatial scene into temporal modulations on the retina, which, together with the known sensitivities of retinal neurons, provide a comprehensive account of human spatial sensitivity.
The atomic structure of GtACR1 provides new insight into the chemical mechanism of natural light-gated anion membrane conductance, and enables its optimization for optogenetic photoinhibition of neuron firing.
Analysis of epigenetic recombinant inbred lines of Arabidopsis identified four hypomethylated DNA loci controlling quantitative disease resistance, which is associated with genome-wide priming of defence genes without affecting plant growth.
Investigations of binding of the scaffold protein PICK1 to transmembrane proteins in their native membrane environment demonstrate potent but slow dynamics and reveal distinct binding modes supporting different biological functions.
Microtubule streaming driven by molecular motors covers characteristic times that span several orders of magnitude from fast, single-microtubule sliding on molecular scales to slow, collective motion on cellular scales.