Aleksandra Agapova, Agnese Serafini ... Luiz Pedro Sório de Carvalho
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.
A statistical model rescues multi-mapping reads with high accuracy and demonstrates their impact in all facets of the analysis of genome-wide high throughput conformation capture datasets.
In epithelial cells, anillin organizes the medial-apical actomyosin cortex into a contractile load-bearing structure and increases tissue-level stiffness.
Visualization methods display the dynamics of the currents in conductance-based model neurons, and show how their contribution changes in response to perturbation.
The exceptionally large size of the human brain is the result of accelerating evolution towards larger brains in hominins, but is not the product of neocortical expansion.
In addition to increasing glycolysis, some proliferating cells exhibiting the Warburg effect also increase oxidative phosphorylation through mitochondrial fusion.
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.
Leo TH Tang, Carlos A Diaz-Balzac ... Hannes E Bülow
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.
Angela M Ramos-Lobo, Pryscila DS Teixeira ... Jose Donato Jr
A mouse model that grew without functional leptin receptors until adulthood reveals that early defects in leptin signaling lead to permanent metabolic and developmental problems.
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 GARP complex is important for the endocytic recycling of amino phospholipid flippases and cell wall proteins, and thus membrane and lipid organization in yeast.
Evanthia Zacharioudaki, Julia Falo Sanjuan, Sarah Bray
Depleting Mi-2 in the progeny of neural stem cells prevents normal enhancer decommissioning so that they become sensitive to Notch activity and re-acquire stem cell properties.
Spatial factors generate neuroblast-specific open chromatin, thereby biasing the subsequent binding of transcription factors to produce neuroblast-specific neurons.
Ankita Ravi Vaswani, Beatrice Weykopf ... Sandra Blaess
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.
Maia Azubel, Stephen D Carter ... Roger D Kornberg
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.
Single-molecule FRET experiments reveal that G40P, a DnaB-like helicase, unwinds double-stranded DNA in single base pair steps and its processivity is enhanced by host primase DnaG.
Michele N Insanally, Ioana Carcea ... Robert C Froemke
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.
Irepan Salvador-Martínez, Marco Grillo ... Maximilian J Telford
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.
Melesse Nune, Michael T Morgan ... Cynthia Wolberger
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.
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.
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.
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.
Brian C Del Rosario, Andrea J Kriz ... Jeannie T Lee
The chromosome architectural protein, CTCF, is phosphorylated at Ser224 in a cell-cycle-dependent manner and abrogation of phosphorylation leads to a cell growth defect.
Shuchi Agrawal Singh, Mads Lerdrup ... Klaus Hansen
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.
David Alejandro Bejarano, Ke Peng ... Hans-Georg Kräusslich
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.
By distributing regulation to both the GTPase and downstream kinases, the Mitotic Exit Network creates a single signal from spatial and temporal inputs.
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.
Mature myelin sheaths are scaffolded by the anillin-dependent assembly of septin filaments, thereby facilitating rapid nerve conduction in the healthy CNS.
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.
Nicolas P Andrews, Justin X Boeckman ... James S Trimmer
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.
Asher Preska Steinberg, Sujit S Datta ... Rustem F Ismagilov
Polymers from dietary fiber can control the aggregation of particulates in the murine small intestine in a manner qualitatively consistent with depletion interactions.
TGFβ signaling to retinal microglia is central to the regulation of neuroinflammatory responses relevant to age-related macular degeneration (AMD), a leading cause of blindness in the developed world.
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.
Maaike Welling, Manuel Alexander Mohr ... Periklis Pantazis
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.
Jessica Ausborn, Natalia A Shevtsova ... Ilya A Rybak
A new computational model of brainstem control of locomotor speed and gait was developed to reproduce and explain recent experimental data and propose predictions for subsequent experimental testing.
Marian Breuer, Tyler M Earnest ... Zaida Luthey-Schulten
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.
Neurite geometry enables expansive and highly-branched neuronal structures to operate like single electrical compartments and simple linear integrators.
Alan MV West, Scott C Rosenberg ... Kevin D Corbett
Meiotic chromosome axis 'core' proteins from fungi, plants, and mammals form a conserved filament architecture, and use a common mechanism to recruit HORMAD proteins for meiotic recombination control.
Eric A Prinslow, Karolina P Stepien ... Josep Rizo
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 method of generating comprehensive maps of cochlear cells was created and enabled researchers to study characteristics of cellular damage in aged and noise-exposed inner ear.
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.
Andrea Giovannucci, Johannes Friedrich ... Eftychios A Pnevmatikakis
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.
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.
James E Voss, Alicia Gonzalez-Martin ... Dennis R Burton
Antibody paratopes can be added to the human repertoire by CRISPR-Cas9 editing of B lymphocytes using a strategy that allows for hypermutation and class switching of resulting B cell receptors.
Mohammed Kaplan, Debnath Ghosal ... Grant J Jensen
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.
The protein Pat1 functions in the assembly of processing bodies, cellular membraneless organelles, by promoting the liquid–liquid phase separation of the DEAD-box ATPase Dhh1 and RNA.
Maria E Falzone, Jan Rheinberger ... Alessio Accardi
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.
In the peripheral nervous system, the large GTPase dynamin 2 is required for Schwann cell survival, developmental radial sorting of axons, myelination, and myelin maintenance.
Jessica McFadyen, Jason B Mattingley, Marta I Garrido
A subcortical white matter connection from the pulvinar to the amygdala predicts how well we recognise fearful faces and the strength of feed-forward neural connectivity.
A map of the genetic variants affecting chromatin accessibility in 1000 individuals from 10 diverse populations reveals how cis-regulatory variants impact transcription and disease.
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..
Sujatha Jagannathan, Yuko Ogata ... Robert K Bradley
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.
Wannaporn Ittiprasert, Victoria H Mann ... Paul J Brindley
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.
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.
Feng Zhang, Kenton Jon Swartz, Andres Jara-Oseguera
TRPV channels share general mechanisms of activation while exhibiting subtype-specific features along the activation pathway that can determine their apparent sensitivity to stimuli.
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.
Amelia J Thompson, Eva K Pillai ... Kristian Franze
During embryonic development, tissue stiffness, which provides an important signal to motile cells, changes locally within tens of minutes in a well-controlled manner.
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.
Joshua T Vogelstein, Eric W Bridgeford ... Cencheng Shen
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.
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.
Silvia C Bobeica, Shi-Hui Dong ... Wilfred A van der Donk
Structural and biochemical characterization of the protease domain of an ABC transporter demonstrates the basis for recognition of substrate leader peptides.
SHH signaling acts through FOXF1/2 transcription factors and antagonizes BMP signaling to specify oral fate and pattern the oral-aboral axis of the mandibular arch to ensure proper formation of jaws.
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.
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.
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.
Nagarajan Nandagopal, Leah A Santat, Michael B Elowitz
Activation of Notch receptors by ligands in the same cell (cis-activation) is a prevalent and functional mode of signaling in the Notch pathway, and co-exists with trans-activation and cis-inhibition.
Alexandria N Miller, George Vaisey, Stephen B Long
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.
Wang Zheng, Elena O Gracheva, Sviatoslav N Bagriantsev
A functionally conserved inactivation gate in the inner helix of Piezo channels controls the majority of the inactivation process via a hydrophobic mechanism.
The innervation of the mammary gland is controlled by opposing effects of neurotrophic and repulsive factors and, once trophic signaling is inhibited the repulsive factors, may promote axonal pruning.
Kazunori Shinomiya, Gary Huang ... Ian A Meinertzhagen
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.
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.
Yao Liang Wong, Lauren LeBon ... Carmela Sidrauski
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.
Body color change of locusts reveals a new 'palette effect' mechanism by which the red βCBP–β-carotene pigment complex acts as a switch to coordinate between black and green coloration.
The findings have a major impact in understanding the different reward systems involved in two types of addictive behavior, and these advances have implications for prevention and treatment.
Ursula Kwong-Brown, Martha L Tobias ... Darcy B Kelley
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.
Arid3a, a component of H3K9 me3 demethylases, regulates regeneration of the proximal nephric tubule through the evolutionarily conserved regeneration signal-response enhancer.
A combination of genetics, experimental evolution and mathematical modelling defines information necessary to predict the outcome of short-term adaptive evolution.
Mehdi Goudarzi, Kathryn Berg ... Alexander F Schier
Defining the biological functions of long non-coding RNAs, individually or as a class, and teasing apart the role of underlying genomic sequences remains the biggest challenge for this field.
Pathogens, particularly viruses, target the same genes over deep evolutionary time, resulting in shared signatures of positive selection and transcriptional responses at the same genes.
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.
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.
A combination of experimental and theoretical analysis identifies body size-dependent energy storage as the physiological cause of 3/4-power law scaling of the metabolic rate in planarians.
Brittany K Miller, Ryan Hughes ... Miriam Braunstein
SatS of Mycobacterium tuberculosis is a new protein export chaperone with a role in exporting proteins by the specialized SecA2 pathway and a role in intracellular growth in macrophages.
Simon Erlendsson, Thor Seneca Thorsen ... Kenneth Lindegaard Madsen
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.
Ilaria Sani, Brent C McPherson ... Winrich A Freiwald
Primate attention is not limited to a dorsal fronto-parietal network, but includes a ventral temporal node and its dorso-ventral interactions with other attentional areas.
Oliver J Wilkinson, Alejandro Martín-González ... Mark Simon Dillingham
Structural and biochemical analysis of human CtIP provides new insights into DNA break recognition, binding and bridging during homologous recombination.
A new optical tweezers assay sheds light on the mechanism of cooperation and force generation by the subunits of RecBCD, critical for the repair of double strand breaks in bacteria.
Arvind Ravichandran, Özer Duman ... Gerhard Gompper
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.
Laura Pereira, Florian Aeschimann ... Oliver Hobert
The timing of sexual differentiation in the brain of the nematode Caenorhabditis elegans is controlled by a phylogenetically conserved pathway of gene regulatory factors.
