January 2020

Cover articles

Research articles

    1. Cell Biology
    2. Neuroscience

    The orphan receptor GPR88 blunts the signaling of opioid receptors and multiple striatal GPCRs

    Thibaut Laboute et al.
    GPR88 inhibits G-protein signaling of nearby GPCRs, and dampens b-arrestin recruitment by all GPCRs tested, likely by sequestration in intracellular compartments.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    A tryparedoxin-coupled biosensor reveals a mitochondrial trypanothione metabolism in trypanosomes

    Samantha Ebersoll et al.
    African trypanosomes have a trypanothione-based mitochondrial thiol redox metabolism.
    1. Plant Biology

    A cis-carotene derived apocarotenoid regulates etioplast and chloroplast development

    Christopher I Cazzonelli et al.
    Carotenoids are not just required as core components for plastid biogenesis, they can be cleaved into an apocarotenoid signal that regulates etioplast and chloroplast development during extended periods of darkness.
    1. Neuroscience

    Auditory cortex shapes sound responses in the inferior colliculus

    Jennifer M Blackwell et al.
    Feedback from the mammalian auditory cortex to the midbrain decreases sound selectivity, altering how sounds are processed in the brain.
    1. Genetics and Genomics

    Variable prediction accuracy of polygenic scores within an ancestry group

    Hakhamanesh Mostafavi et al.
    The prediction accuracies of polygenic scores in humans vary depending on the characteristics of the samples, as well as based on the study design, within a single ancestry group.
    1. Neuroscience

    Shifting from fear to safety through deconditioning-update

    Bruno Popik et al.
    Deconditioning is a safe and efficient new approach to updating traumatic memories, in which fear memory is rewritten to a very low level in a long-lasting way.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Quantitative analysis of 1300-nm three-photon calcium imaging in the mouse brain

    Tianyu Wang et al.
    Quantitative experiments and analysis determine the limit of excitation power of 1300-nm three-photon microscopy, and the imaging depth where three-photon outperforms two-photon for calcium imaging in the mouse brain.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation

    Matthew C Johnson, Justin M Kollman
    Assembly of the human enzyme inosine monophosphate dehydrogenase 2 into filaments promotes substrate-dependent resistance to feedback inhibition by downstream products, promoting increased flux during proliferative states.
    1. Structural Biology and Molecular Biophysics

    Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction

    Lan Wang et al.
    Msp1 recruits substrates at the open seam of the spiral oligomer and extracts them with functionally adapted elements.
    1. Neuroscience

    Distinct roles for innexin gap junctions and hemichannels in mechanosensation

    Denise S Walker, William R Schafer
    The innexin protein UNC-7, a homologue of vertebrate pannexins, plays a specific, gap junction-independent role in C. elegans mechanosensation.
    1. Cell Biology
    2. Developmental Biology

    Notochord vacuoles absorb compressive bone growth during zebrafish spine formation

    Jennifer Bagwell et al.
    Live imaging and genetic analyses revealed that notochord vacuoles play a critical role in spine morphogenesis by absorbing vertebral bone growth, thus implicating notochord mechanics in congenital scoliosis.
    1. Neuroscience

    The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation

    Brandon Podyma et al.
    A novel neurotrophin signaling axis underpins a behavioral response to food scarcity.
    1. Cell Biology

    SIRT6 is a DNA double-strand break sensor

    Lior Onn et al.
    Hundreds of proteins are involved in the DNA damage response but only three sensors for DSB were known but now SIRT6 is identified as a fourth DSB sensor.
    1. Cell Biology
    2. Immunology and Inflammation

    Microtubule plus-end dynamics link wound repair to the innate immune response

    Clara Taffoni et al.
    Microtubules orchestrate wound repair and innate immune response in the Caenorhabditis elegans epidermis.
    1. Ecology
    2. Microbiology and Infectious Disease

    Bacterial interspecies interactions modulate pH-mediated antibiotic tolerance

    Andrés Aranda-Díaz et al.
    Shifts in pH that result from metabolic interactions between members of the Drosophila gut microbiota were sufficient to modulate Lactobacillus plantarum tolerance to the antibiotics rifampin and erythromycin.
    1. Ecology

    Genomic adaptations in information processing underpin trophic strategy in a whole-ecosystem nutrient enrichment experiment

    Jordan G Okie et al.
    Trait-based metagenomic analysis of an ecosystem fertilization experiment shows that genomic traits that affect the costs and rates of biochemical information-processing mediate community assembly.
    1. Physics of Living Systems

    High-speed motility originates from cooperatively pushing and pulling flagella bundles in bilophotrichous bacteria

    Klaas Bente et al.
    Bacteria reach swimming speeds of several hundred body lengths per second and change direction in less than 5 ms by using coordinated flagella bundle agitation.
    1. Cancer Biology
    2. Immunology and Inflammation

    Preclinical murine tumor models: a structural and functional perspective

    Marion V Guerin et al.
    Dissecting structural, cellular and molecular differences between transplanted and spontaneous mouse tumor models, highlighting their relevance for predicting the efficacy of anti-cancer treatments in patients.
    1. Cell Biology

    Actin assembly ruptures the nuclear envelope by prying the lamina away from nuclear pores and nuclear membranes in starfish oocytes

    Natalia Wesolowska et al.
    Combined light and electron microscopy reveals a new function for Arp2/3-mediated actin assembly in nuclear envelope rupture, which leads to a separation of nuclear membranes and pores from the lamina.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast

    Courtney R Johnson et al.
    A naturally-occurring small molecule acts as a chemical chaperone in vivo to alter the folding of a budding yeast septin and promote an oligomerization pathway that was lost during evolution.
    1. Genetics and Genomics
    2. Stem Cells and Regenerative Medicine

    Multiplex CRISPR/Cas screen in regenerating haploid limbs of chimeric Axolotls

    Lucas D Sanor et al.
    A novel CRISPR-based genetic screen of candidate regeneration genes in haploid axolotl limbs reveals two genes required for proper regeneration.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Modulation of the Erwinia ligand-gated ion channel (ELIC) and the 5-HT3 receptor via a common vestibule site

    Marijke Brams et al.
    Development of nanobodies against a model pentameric ligand-gated ion channel demonstrates they can be functionally active as negative or positive allosteric modulators and offers opportunities for future drug development.
    1. Human Biology and Medicine
    2. Immunology and Inflammation

    TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury

    Salik Hussain et al.
    The response to TLR4 ligands in mice and humans is modulated by TLR5, which participates in the TLR4 signaling complex.
    1. Developmental Biology

    A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity

    Franz S Gruber et al.
    A high-throughput phenotypic human sperm screening platform was developed which allows for major drug discovery programmes for male contraception.
    1. Neuroscience

    Learning improves decoding of odor identity with phase-referenced oscillations in the olfactory bulb

    Justin Losacco et al.
    Tetrode recordings show that the amplitude of gamma oscillations encodes for information on contextual odorant identity when observed at the peak phase of the theta oscillation in the olfactory bulb.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Zika seroprevalence declines and neutralizing antibodies wane in adults following outbreaks in French Polynesia and Fiji

    Alasdair D Henderson et al.
    A combination of eight serological surveys shows a decline in seroprevalence over a two-year period following the first reports of Zika transmission in Fiji and French Polynesia.
    1. Developmental Biology
    2. Genetics and Genomics

    GLI transcriptional repression regulates tissue-specific enhancer activity in response to Hedgehog signaling

    Rachel K Lex et al.
    GLI3 represses Hedgehog target gene expression by regulating histone modifications at a subset of tissue-specific GLI-bound enhancers.
    1. Neuroscience

    Integration of locomotion and auditory signals in the mouse inferior colliculus

    Yoonsun Yang et al.
    Robust and wide-spread locomotion-related neural signals, revealed in the mouse auditory midbrain, suggest that integrating movement-related information is an essential aspect of midbrain sound processing.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Deep learning models predict regulatory variants in pancreatic islets and refine type 2 diabetes association signals

    Agata Wesolowska-Andersen et al.
    Combination of deep learning models trained on tissue-specific genomic data and fine-mapping approaches supports efforts to identify causal variants and mechanisms at GWAS loci.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism

    J Robert Lane et al.
    The occupation of a sub-pocket near the Na+-binding site in D2R by the Na+-insensitive antagonists is the structural basis for their greater inverse agonism than that of the Na+-sensitive ligands.
    1. Computational and Systems Biology

    Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments

    Christopher A Jackson et al.
    Single cell expression data can be used to determine how regulatory transcription factors and target genes are connected, and is especially useful when studying transcription factors controlling heterogeneous cell states.
    1. Developmental Biology
    2. Genetics and Genomics

    celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish

    Chunmei Li et al.
    The use of forward genetic screens in zebrafish identifies a new model of vertebrate aging, defining the regulating of the onset of aging phenotypes through maintenance of progenitor cell populations.
    1. Cancer Biology
    2. Chromosomes and Gene Expression

    Loss of Kat2a enhances transcriptional noise and depletes acute myeloid leukemia stem-like cells

    Ana Filipa Domingues et al.
    Histone acetyl-transferase Kat2a preserves leukemia stem cells through frequent transcriptional firing of metabolic and regulatory gene promoters and maintenance of a largely invariant self-renewal program.
    1. Neuroscience

    LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses

    Alessandra Sclip, Thomas C Südhof
    LAR-RPTPs are not essential for synapse formation, but they are important determinants of synapse properties as they contribute to regulate postsynaptic NMDA receptor function.
    1. Cell Biology
    2. Computational and Systems Biology

    A regulatory microRNA network controls endothelial cell phenotypic switch during sprouting angiogenesis

    Stefania Rosano et al.
    Coordinated microRNAs activity induced by VEGF represses cell proliferation and favors cell migration at the onset of sprouting angiogenesis in endothelial cells.
    1. Neuroscience

    Sound exposure dynamically induces dopamine synthesis in cholinergic LOC efferents for feedback to auditory nerve fibers

    Jingjing Sherry Wu et al.
    Based on the animal’s recent history of sound exposure, cholinergic auditory brainstem neurons dynamically regulate dopamine synthesis for inhibitory feedback to the inner ear.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    The carboxyl-terminal sequence of bim enables bax activation and killing of unprimed cells

    Xiaoke Chi et al.
    The C-terminal membrane binding domain of Bim is shown to interact with and activate Bim enabling it to kill cells not dependent on anti-apoptotic proteins for survival.
    1. Human Biology and Medicine
    2. Neuroscience

    Human hippocampal CA3 damage disrupts both recent and remote episodic memories

    Thomas D Miller et al.
    Human hippocampal cornu ammonis 3 damage impairs both recent and remote autobiographical episodic memory, and disrupts functional integration in medial temporal lobe subsystem regions of the default network.
    1. Cell Biology
    2. Developmental Biology

    Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins

    Chih-Yung S Lee et al.
    The intrinsically-disordered protein MEG-3 recruits mRNAs to P granules by forming gel-like condensates with ribosome-depleted mRNAs.
    1. Neuroscience

    Damage to the right insula disrupts the perception of affective touch

    Louise P Kirsch et al.
    Lesion analyses in right hemisphere stroke patients reveal the crucial role of the right anterior and posterior insula in the perception of affective touch.
    1. Cell Biology
    2. Plant Biology

    Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants

    Madhumitha Narasimhan et al.
    The examination of the ultra-structure and in vivo dynamics of endocytosis in plants reveal plants unique actin-independent, clathrin-mediated endocytosis mechanisms to overcome their unique physiological properties.
    1. Computational and Systems Biology

    Hidden long-range memories of growth and cycle speed correlate cell cycles in lineage trees

    Erika E Kuchen et al.
    The combination of statistical inference and perturbation experiments reveals that trans-generational inheritance of cell size and cell-cycle speed, coupled through a minimum-size checkpoint, shapes paradoxical cell-cycle correlations in lineage trees.
    1. Neuroscience
    2. Physics of Living Systems

    Variability in locomotor dynamics reveals the critical role of feedback in task control

    Ismail Uyanik et al.
    Animals rely on sensory feedback rather than the precise tuning in the nervous system to achieve robust behavioral performances.
    1. Chromosomes and Gene Expression

    Stop codon context influences genome-wide stimulation of termination codon readthrough by aminoglycosides

    Jamie R Wangen, Rachel Green
    Ribosome profiling reveals genome-wide stimulation of stop codon readthrough by aminoglycosides that is influenced sequence context.
    1. Neuroscience

    C1 neurons are part of the circuitry that recruits active expiration in response to the activation of peripheral chemoreceptors

    Milene R Malheiros-Lima et al.
    An unbiased description reveals potential implications for understanding the developmental mechanisms that match respiratory supply and demand during hypoxia.
    1. Neuroscience

    Area 2 of primary somatosensory cortex encodes kinematics of the whole arm

    Raeed H Chowdhury et al.
    Area 2 of somatosensory cortex represents kinematic details of the entire arm during movement, but this mapping from limb state to neural activity differs for reaching and passive limb displacement.
    1. Neuroscience

    CXCL12-induced rescue of cortical dendritic spines and cognitive flexibility

    Lindsay K Festa et al.
    Unveiling a novel role of the chemokine CXCL12 in the mature brain that opens up new lines of investigation for the development of therapeutics against cognitive impairment.
    1. Cell Biology
    2. Developmental Biology

    Stepwise polarisation of developing bilayered epidermis is mediated by aPKC and E-cadherin in zebrafish

    Prateek Arora et al.
    Polarity cascade initiated by aPKC in the periderm is transduced by adherens junction component E-cadherin to the basal epidermis during the development of zebrafish bilayered epidermis.
    1. Human Biology and Medicine
    2. Neuroscience

    Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data

    Samuel A Neymotin et al.
    Human Neocortical Neurosolver is a new user-friendly software tool for researchers to develop and test hypotheses on cellular/circuit origins of human MEG/EEG signals using a biophysical model.
    1. Microbiology and Infectious Disease

    Single cell analysis reveals human cytomegalovirus drives latently infected cells towards an anergic-like monocyte state

    Miri Shnayder et al.
    Single-cell and bulk expression analyses reveal that HCMV latent infection drives cells towards a weaker immune-responsive state, which is important for its expression and reactivation.
    1. Biochemistry and Chemical Biology

    HOPS recognizes each SNARE, assembling ternary trans-complexes for rapid fusion upon engagement with the 4th SNARE

    Hongki Song et al.
    The tethering complex HOPS employs affinity for each of the 4 SNAREs to catalyze assembly of 3-SNARE intermediates, supporting an immediate burst of membrane fusion triggered by the 4th SNARE.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    A polyomavirus peptide binds to the capsid VP1 pore and has potent antiviral activity against BK and JC polyomaviruses

    Joshua R Kane et al.
    A peptide derived from BK and JC polyomavirus protein VP2/3 inhibits viral infection by targeting a binding site in the pore of polyomavirus VP1 pentamers, enabling future VP1-targeted therapeutic strategies.
    1. Ecology

    Substantial near-infrared radiation-driven photosynthesis of chlorophyll f-containing cyanobacteria in a natural habitat

    Michael Kühl et al.
    Cyanobacteria with chlorophyll f show substantial near-infrared radiation-driven photosynthesis and can play an important role for primary production in endolithic, intertidal habitats.
    1. Epidemiology and Global Health

    Development of a confinable gene drive system in the human disease vector Aedes aegypti

    Ming Li et al.
    Highly efficient and confinable split gene drives are a new tool for the control of the dengue mosquito vector.
    1. Neuroscience

    Emergence of social cluster by collective pairwise encounters in Drosophila

    Lifen Jiang et al.
    Cascades of transient pairwise interactions, stabilized by multisensory inputs, drive the formation of a well-organized social structure from a group of loosely distributed flies.
    1. Cell Biology
    2. Neuroscience

    Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory

    Junjun Zhao et al.
    Two homologous kinesin motors, KIF5A and KIF5B, have distinct functions in dendritic spine morphogenesis, and KIF5B plays a role in synaptic plasticity and memory.
    1. Cell Biology
    2. Developmental Biology

    Tgfβ signaling is critical for maintenance of the tendon cell fate

    Guak-Kim Tan et al.
    Conditional deletion of TGFβ signaling results in tenocyte dedifferentiation in vivo demonstrating a key role for TGFβ signaling in the maintenance of the tendon cell fate.
    1. Cancer Biology

    T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity

    Marta Canel et al.
    Cancer cell expression of the T-cell co-stimulatory molecule CD80, or treatment with agonistic antibodies targeting the T-cell co-stimulatory receptors OX-40 or 4-1BB, enhances the anti-tumor activity of FAK inhibition.
    1. Computational and Systems Biology
    2. Physics of Living Systems

    Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks

    Eugenia Lyashenko et al.
    Preferential endocytosis of activated receptors allows cells to memorize their past and perform relative sensing.
    1. Human Biology and Medicine
    2. Neuroscience

    Bottom-up and top-down neural signatures of disordered multi-talker speech perception in adults with normal hearing

    Aravindakshan Parthasarathy et al.
    Ear canal EEG and pupillometry reveal disordered temporal processing in adults with normal hearing who struggle to understand conversations in noisy backgrounds.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding

    Tatyana Bodrug et al.
    Biochemical, single molecule, cell and structural biology studies reveal an interaction between the kinesin-5 tail and motor domains regulating high-force production, which is critical for microtubule sliding motility.
    1. Microbiology and Infectious Disease

    Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase

    Tobias Geiger et al.
    Biochemical analyses and the crystal structure of TtsA reveal fundamental insight into the mechanisms by which this muramidase recognizes its peptidoglycan substrate to facilitate typhoid toxin secretion.
    1. Cell Biology
    2. Developmental Biology

    YAP1 and TAZ negatively control bone angiogenesis by limiting hypoxia-inducible factor signaling in endothelial cells

    Kishor K Sivaraj et al.
    The interplay between the transcriptional co-regulators YAP1/TAZ and the hypoxia-controlled transcription factor HIF1α differentially regulates endothelial cell behavior in the hypoxic environment of bone compared to other organs.
    1. Developmental Biology
    2. Neuroscience

    Altered corticolimbic connectivity reveals sex-specific adolescent outcomes in a rat model of early life adversity

    Jennifer A Honeycutt et al.
    Early life adversity led to hyper-innervation from the basolateral amygdala to the prefrontal cortex earlier in females than males and disrupted maturation of functional connectivity, which predicted anxiety-like outcomes.
    1. Developmental Biology

    tec-1 kinase negatively regulates regenerative neurogenesis in planarians

    Alexander Karge et al.
    RNAi screening in planarians finds that inhibition of the TEC-family protein tyrosine kinase tec-1 increases the regeneration of neurons through enhancement of cell survival.
    1. Genetics and Genomics

    Loss of centromere function drives karyotype evolution in closely related Malassezia species

    Sundar Ram Sankaranarayanan et al.
    The centromeres in Malassezia species, by breakage or inactivation, facilitate genome rearrangements that can result in varying karyotypes and contribute to the evolution of these species.
    1. Cancer Biology
    2. Physics of Living Systems

    Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior

    Debanjan Goswami et al.
    Compared to other isoforms of RAS, KRAS4b has unique membrane diffusion behavior related to its biology, and the two major domains of the protein both contribute to this diffusion behavior.
    1. Neuroscience

    Mechanisms underlying the response of mouse cortical networks to optogenetic manipulation

    Alexandre Mahrach et al.
    Combining experimental and theoretical approaches reveals the interplay between optogenetic manipulation and recurrent interactions in mouse cortex.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Transcriptional adaptation in Caenorhabditis elegans

    Vahan Serobyan et al.
    Genes implicated in mutant mRNA decay and small RNA maturation and transport into the nucleus are required for transcriptional adaptation in C. elegans.
    1. Structural Biology and Molecular Biophysics

    Structure of the human BBSome core complex

    Björn Udo Klink et al.
    The structure of the human BBSome explains how the subunits interact with each other and how disease-causing mutations hamper this interaction.
    1. Structural Biology and Molecular Biophysics

    The inner junction complex of the cilia is an interaction hub that involves tubulin post-translational modifications

    Ahmad Abdelzaher Zaki Khalifa et al.
    A structure of the ciliary inner junction at 3.6 Å resolution permits atomic modeling of six inner junction proteins and their interactions with acetylated lysine 40 loops of alpha tubulins.
    1. Cell Biology

    Kinesin Kif2C in regulation of DNA double strand break dynamics and repair

    Songli Zhu et al.
    Kinesin Kif2C is recruited to DNA damage sites, modulates the mobility and dynamics of DNA damage foci, and promotes DNA double strand break repair.
    1. Cell Biology
    2. Physics of Living Systems

    Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis

    Matthew Akamatsu et al.
    An experimentally constrained multiscale mathematical model predicts that branched actin networks self-organize at endocytic sites and bend to produce force, which was verified with cryo-electron tomography of intact cells.
    1. Microbiology and Infectious Disease

    Dynamic post-translational modification profiling of Mycobacterium tuberculosis-infected primary macrophages

    Jonathan M Budzik et al.
    Measurement of post-translational modifications in primary macrophages infected with Mtb revealed phosphorylation of TAX1BP1, an autophagy receptor that enables full maturation of the Mtb autophagosome.
    1. Microbiology and Infectious Disease

    Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features

    Yaara Finkel et al.
    Unbiased mapping of viral open reading frames (ORFs) and transcripts in HHV-6 genomes uncovers novel ORFs and lncRNAs that are conserved across betaherpesviruses.
    1. Human Biology and Medicine

    Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation

    Ankit Jambusaria et al.
    Vascular endothelial cells in the brain, heart and lung exhibit tissue-specific heterogeneity and plasticity, expressing genes that were traditionally thought to be only expressed by the surrounding parenchymal tissue cells.
    1. Neuroscience

    Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination

    Liang Zhou et al.
    Gab1 is a key downstream effector of PDGF signaling and essential to oligodendrocyte differentiation by linking PDGF signaling with GSK3β/β-catenin module.
    1. Neuroscience
    2. Developmental Biology

    Phrenic-specific transcriptional programs shape respiratory motor output

    Alicia N Vagnozzi et al.
    Molecular programs regulated by Hox5 transcription factors establish a set of inhibitory inputs onto phrenic motor neurons that control the pattern of respiratory motor output.
    1. Developmental Biology
    2. Immunology and Inflammation

    Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila

    Katrin Kierdorf et al.
    A cytokine partly derived from macrophages is required to promote normal muscle health and metabolism by inhibiting the activity of the insulin signalling pathway in the fruitfly Drosophila melanogaster.
    1. Evolutionary Biology

    Symptom evolution following the emergence of maize streak virus

    Adérito L Monjane et al.
    Phylogenetic analyses demonstrate an evolutionary trade-off between the amount of harm inflicted by a broad host-range virus and how effectively the virus positions itself within plants to enable onward transmission.
    1. Genetics and Genomics
    2. Neuroscience

    A genetic, genomic, and computational resource for exploring neural circuit function

    Fred P Davis et al.
    Transcriptomes of cells in the Drosophila visual system combined with anatomy and other information reveal new functional insight into the visual circuit.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    CNApp, a tool for the quantification of copy number alterations and integrative analysis revealing clinical implications

    Sebastià Franch-Expósito et al.
    CNApp is a novel and unique web-based software that enables the performance of comprehensive and integrative analysis of genomic copy number alterations to uncover new associations with patient-oriented relevance.
    1. Physics of Living Systems
    2. Structural Biology and Molecular Biophysics

    Myosin V executes steps of variable length via structurally constrained diffusion

    David Hathcock et al.
    A theoretical model comprehensively describes the stepping dynamics of the motor protein myosin V, unraveling the significance of a recently discovered structural constraint on the angle between its lever arms.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency

    Tara L Mastro et al.
    Deletion of one copy of the postsynaptic density protein synGAP in rodents causes an increase in the level of the AMPA receptor auxiliary protein TARP in PSDs only in females.
    1. Cell Biology

    Cardiac mitochondrial function depends on BUD23 mediated ribosome programming

    Matthew Baxter et al.
    BUD23 links ribosome function with mitochondrial protein expression and efficient oxidative phosphorylation by promoting selective mRNA translation and is therefore critical to mouse development and postnatal cardiac function.
    1. Structural Biology and Molecular Biophysics

    Structure and activation mechanism of the BBSome membrane protein trafficking complex

    Sandeep K Singh et al.
    Two cryo-EM structures of the mammalian BBSome show how the BBSome is recruited to membranes and activated by the GTPase ARL6 prior to binding transmembrane proteins.
    1. Physics of Living Systems

    Flower-like patterns in multi-species bacterial colonies

    Liyang Xiong et al.
    Mechanical interactions between bacterial species with different motility characteristics play an important role in spatial-temporal dynamics of multi-species bacterial colonies and can lead to formation of complex patterns.
    1. Evolutionary Biology

    Rank orders and signed interactions in evolutionary biology

    Kristina Crona
    Rectangular order perturbations generalize sign epistasis, capture global aspects of fitness landscapes, and clarify how rank order approaches relate.
    1. Cell Biology
    2. Neuroscience

    Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons

    Chantell S Evans, Erika LF Holzbaur
    In neuronal mitophagy, Parkin and OPTN induce efficient sequestration of damaged somal mitochondria into autophagosomes, but slow turnover via lysosomal acidification may be a point of vulnerability for the cell.
    1. Structural Biology and Molecular Biophysics

    Structural basis of substrate recognition by a polypeptide processing and secretion transporter

    Virapat Kieuvongngam et al.
    Cryo-EM structure of a peptidase-containing ABC transporter in complex with its protein substrate reveals a mechanism of coupling substrate cleavage to translocation.
    1. Cancer Biology

    MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity

    Renumathy Dhanasekaran et al.
    MYC and Twist1 drive metastasis by a novel non-cell-autonomous transcriptional mechanism of eliciting a cytokinome that mediates the crosstalk between cancer cells and macrophages, and its therapeutic blockade inhibits metastasis.
    1. Cell Biology

    Prickle isoforms determine handedness of helical morphogenesis

    Bomsoo Cho et al.
    The Pkpk and Pksple isoforms of the Prickle protein determine right- or left-handed bristle morphogenesis by coupling Frizzled/Vang signaling to the Fat/Dachsous PCP directional signal in opposite directions.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    TRF1 averts chromatin remodelling, recombination and replication dependent-break induced replication at mouse telomeres

    Rosa Maria Porreca et al.
    TRF1 suppresses replication fork stalling, which triggers break induced replication at telomeres associated with DNA damage response, alteration in the telomere chromatin environment, and re-localisation of telomeres to PML bodies.
    1. Cell Biology
    2. Developmental Biology

    The tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer

    Ling-Shih Chang et al.
    Two cancer related proteins, tyrosine phosphatase PTPRK and ubiquitin ligase ZNRF3, interact to downregulate Wnt receptors, thereby regulating Spemann organizer function during Xenopus development.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Nanopore direct RNA sequencing maps the complexity of Arabidopsis mRNA processing and m6A modification

    Matthew T Parker et al.
    Sequencing mRNA directly with nanopores can reveal the authentic combinations of multiple mRNA processing events in full-length mRNA molecules in addition to identifying base modifications.
    1. Cell Biology

    In vitro reconstitution of branching microtubule nucleation

    Ammarah Tariq et al.
    Purification of two conserved protein complexes, the γ-TuRC and Augmin, using a simple affinity technique, demonstrates that they are necessary and sufficient for the essential phenomenon of branching microtubule nucleation.
    1. Cell Biology
    2. Neuroscience

    TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons

    Emily Bowie, Sarah C Goetz
    Signaling at the primary cilium is important to sustain the morphology, connectivity, and survival of a key neural population within the brain.
    1. Human Biology and Medicine

    Intermittent hypoxia mediated by TSP1 dependent on STAT3 induces cardiac fibroblast activation and cardiac fibrosis

    Qiankun Bao et al.
    Targeting STAT3 provides a potential therapeutic strategy for obstructive sleep apnea-related fibrotic heart disease mediated by TSP1.
    1. Cancer Biology
    2. Immunology and Inflammation

    Inflammation-induced IgE promotes epithelial hyperplasia and tumour growth

    Mark David Hayes et al.
    Natural IgE supports epithelial cell growth and differentiation in healthy skin, but during chronic tissue inflammation, IgE drives tumour outgrowth of epithelial cells harbouring oncogenic mutations.
    1. Developmental Biology
    2. Immunology and Inflammation

    Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice

    Ken-ichi Hirano et al.
    Notch ligand, Dll4 needs the flexible loop structure in the MNNL domain of the extracellular region to efficiently trigger the Notch signaling.
    1. Computational and Systems Biology

    The bottom-up and top-down processing of faces in the human occipitotemporal cortex

    Xiaoxu Fan et al.
    Both bottom-up and top-down processing are involved in the occipital-temporal face network, with the top-down modulation more extensively engaged when available information is sparse in the face images.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Midkine is a dual regulator of wound epidermis development and inflammation during the initiation of limb regeneration

    Stephanie L Tsai et al.
    Elucidation of the molecular basis of early wound epidermis dependence during salamander limb regeneration reveals midkine as a key modulator of wound epidermis development and wound-healing resolution.
    1. Developmental Biology
    2. Neuroscience

    Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

    Tamsin J Samuels et al.
    Single molecule mRNA imaging uncovers post-transcriptional regulation of myc mRNA, via a cell-intrinsic mechanism allowing individualised control of neural stem cell proliferation during Drosophila brain development.
    1. Human Biology and Medicine
    2. Neuroscience

    Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain

    Alejandra Escudero-Lara et al.
    A mouse model of endometriosis reveals that moderate doses of Δ9-tetrahydrocannabinol produce clear regression of ectopic endometrial growths, pronounced alleviation of pelvic pain and unexpected memory improvements.
    1. Neuroscience

    State-dependent brainstem ensemble dynamics and their interactions with hippocampus across sleep states

    Tomomi Tsunematsu et al.
    Sub-second pontine waves functionally interact with hippocampal population activity in a state-dependent manner across sleep states, while brainstem ensemble dynamics exhibit slow, long-lasting state-predictive activity.
    1. Neuroscience

    NINscope, a versatile miniscope for multi-region circuit investigations

    Andres de Groot et al.
    A light-weight, compact and open-source miniaturized fluorescence microscope integrates dual region brain imaging, optogenetic stimulation and behavioral parsing using an accelerometer.
    1. Human Biology and Medicine

    Ankyrin-G mediates targeting of both Na+ and KATP channels to the rat cardiac intercalated disc

    Hua-Qian Yang et al.
    The functional interaction of Na+ and KATP channels at the intercalated disk of cardiomyocytes depends on Ankyrin G and is clinically relevant since KATP channel mutations affect Na+ channel expression.
    1. Cell Biology

    Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model

    Magdalena Kasendra et al.
    Combining Organs-on-Chips technology with adult intestinal organoids provides an improved model of human duodenum and a new platform for preclinical drug assessment.
    1. Developmental Biology

    Lola regulates Drosophila adult midgut homeostasis via non-canonical hippo signaling

    Xue Hao et al.
    The transcription factor Lola is defined as a non-canonical Hippo signaling component essential for Drosophila midgut homeostasis via its interaction with Warts and suppression on Dref and SkpA expression levels.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Biochemical reconstitution of branching microtubule nucleation

    Raymundo Alfaro-Aco et al.
    The protein TPX2 and the protein complex augmin together recruit the microtubule nucleator γ-TuRC to a pre-existing microtubule where they initiate branching microtubule nucleation.
    1. Evolutionary Biology

    The structure of species discrimination signals across a primate radiation

    Sandra Winters et al.
    Machine learning and experimental tests of receiver bias identify signal components critical to correct species classification in guenons, linking face pattern diversity to selection for species discrimination.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Cytomegalovirus protein m154 perturbs the adaptor protein-1 compartment mediating broad-spectrum immune evasion

    Ivana Strazic Geljic et al.
    Single mouse cytomegalovirus protein, m154, downmodulates surface expression of numerous targets important for NK and CD8 T cell activation by perturbing adaptor protein-1 sorting and redirecting targets to lysosomal degradation.
    1. Chromosomes and Gene Expression
    2. Structural Biology and Molecular Biophysics

    Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome

    Evan J Worden et al.
    The structure of the COMPASS methyltransferase bound to an H2B-ubiquitinated nucleosome provides insights into mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.
    1. Structural Biology and Molecular Biophysics

    Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane

    Yifan Ge et al.
    An in vitro reconstitution assay reveals stoichiometric levels of the short form of Opa1 work together with the long form of Opa1 to mediate efficient and fast membrane pore opening.
    1. Neuroscience

    Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine

    Antoine Cherix et al.
    1H-Magnetic resonance spectroscopy at 14T reveals a metabolic signature for anti-depressant-like effects of acetyl-L-carnitine in nucleus accumbens of susceptible mouse.
    1. Microbiology and Infectious Disease

    Coordination of humoral immune factors dictates compatibility between Schistosoma mansoni and Biomphalaria glabrata

    Hongyu Li et al.
    A coordinated humoral immune response that includes recognition, effector and cytotoxic factors engages the cell-mediated immune response to defend a snail against infection by schistosome parasites.
    1. Structural Biology and Molecular Biophysics

    A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery

    Zev A Ripstein et al.
    Understanding of bacterial protein degradation is illuminated by cryo-EM structures of the substrate-bound ClpXP complex from Neisseria meningitidis at 2.3 to 3.3 Å resolution.
    1. Cell Biology

    Cardiac ryanodine receptor distribution is dynamic and changed by auxiliary proteins and post-translational modification

    Parisa Asghari et al.
    Repositioning the type II ryanodine receptors on the sarcoplasmic reticulum membrane is a potential new mechanism regulating their function, and therefore the strength of cardiac contraction.
    1. Microbiology and Infectious Disease

    Distinct cytoskeletal proteins define zones of enhanced cell wall synthesis in Helicobacter pylori

    Jennifer A Taylor et al.
    The helical bacterium Helicobacter pylori patterns cell wall synthesis using two distinct cytoskeletal proteins, CcmA and MreB, to achieve its characteristic shape.
    1. Neuroscience

    Cell-type-specific control of basolateral amygdala neuronal circuits via entorhinal cortex-driven feedforward inhibition

    E Mae Guthman et al.
    Sst+ interneurons drive feedforward inhibition in the basolateral amygdala, and thus provide a framework for why interneuron subtypes may mediate different archetypal circuit motifs across different brain regions.
    1. Physics of Living Systems

    Origin and role of the cerebrospinal fluid bidirectional flow in the central canal

    Olivier Thouvenin et al.
    The combination of data and modelling shows the mechanisms underlying bidirectional flow of cerebrospinal fluid and its impact on long range transport in the CSF between brain and spinal cord.
    1. Neuroscience

    Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex

    Viktor Szegedi et al.
    Abundant self-inhibitory synapses in the layer 2/3 of human neocortex strongly regulate the function of basket cells.
    1. Developmental Biology
    2. Neuroscience

    Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space

    Travis A Babola et al.
    Supporting cells in the cochlea change their shape in response to purinergic receptor activation, which influences hair cell excitability by altering potassium redistribution in the extracellular space.
    1. Cell Biology

    YAP regulates cell size and growth dynamics via non-cell autonomous mediators

    Douaa Mugahid et al.
    Besides a cell autonomous role in regulating proliferation, YAP regulates the production of several extracellular molecules allowing for population-level coordination of cell growth and death.
    1. Genetics and Genomics
    2. Neuroscience

    A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture

    Mark F Sabbagh, Jeremy Nathans
    In vitro culture of brain endothelial cells leads to a rapid loss of the blood-brain barrier transcriptional and accessible chromatin landscapes that is resistant to the effects of beta-catenin stabilization.
    1. Developmental Biology
    2. Neuroscience

    Presynaptic developmental plasticity allows robust sparse wiring of the Drosophila mushroom body

    Najia A Elkahlah et al.
    Sensory innervation density in the insect associative learning center is set by postsynaptic cells and accomplished by flexible allocation of processes by presynaptic cells.
    1. Neuroscience

    Resolving multisensory and attentional influences across cortical depth in sensory cortices

    Remi Gau et al.
    The different laminar profiles observed across the cortical depth for multisensory and attentional influences indicate partly distinct neural circuitries of information-flow control.
    1. Cell Biology
    2. Neuroscience

    Cell-type-specific regulation of neuronal intrinsic excitability by macroautophagy

    Ori J Lieberman et al.
    In addition to its classic role in synaptic function and plasticity, macroautophagy regulates neuronal intrinsic excitability via degradation of acetylated Kir2 channels to control neurotransmission.
    1. Cancer Biology

    STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells

    Jong Wook Kim et al.
    ST recruitment of STRIPAK facilitates PP2A-mediated dephosphorylation of MAP4K4 and induces cell transformation highlighting that STRIPAK complex plays a key role in defining PP2A specificity and activity.
    1. Structural Biology and Molecular Biophysics

    Casposase structure and the mechanistic link between DNA transposition and spacer acquisition by CRISPR-Cas

    Alison B Hickman et al.
    The tetrameric structure of a casposase bound to DNA and its biochemical properties show how a transposase could have evolved to perform CRISPR-Cas spacer acquisition.
    1. Developmental Biology
    2. Neuroscience

    Comprehensive transcriptome analysis of cochlear spiral ganglion neurons at multiple ages

    Chao Li et al.
    RNA-Seq analysis and in vivo validation via genetic approach uncover that Scrt2 and Celf4 are expressed in inner ear auditory neurons throughout development.
    1. Immunology and Inflammation

    Defining murine monocyte differentiation into colonic and ileal macrophages

    Mor Gross-Vered et al.
    Detailed analysis of the sequence of monocyte differentiation into distinct gut tissue macrophages provides insights into monocyte biology and can serve as a platform for the design of cell therapies.
    1. Chromosomes and Gene Expression

    Two roles for the yeast transcription coactivator SAGA and a set of genes redundantly regulated by TFIID and SAGA

    Rafal Donczew et al.
    The transcription coactivators SAGA and TFIID have redundant function at a subset of yeast genes while SAGA also contributes to transcription of all genes through regulation of chromatin modifications.
    1. Chromosomes and Gene Expression

    The genetic basis of aneuploidy tolerance in wild yeast

    James Hose et al.
    A single gene allele underlies differences in aneuploidy tolerance in yeast.
    1. Developmental Biology

    Compartmentalized oskar degradation in the germ plasm safeguards germline development

    Catherine E Eichler et al.
    RNP granules confer temporal and spatial regulation of oskar mRNA degradation to minimize inheritance of oskar mRNAby germ cells and thereby protect germline development.
    1. Biochemistry and Chemical Biology

    The GTPase Nog1 co-ordinates the assembly, maturation and quality control of distant ribosomal functional centers

    Purnima Klingauf-Nerurkar et al.
    The GTPase Nog1 orchestrates stalk assembly, peptidyl transferase centre maturation and polypeptide exit tunnel quality control.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Attacks on genetic privacy via uploads to genealogical databases

    Michael D Edge, Graham Coop
    Direct-to-consumer genetic genealogy services that allow users to upload their own datasets are vulnerable to attacks on genetic privacy that exploit the structure of genetic variation.
    1. Human Biology and Medicine

    Decreasing human body temperature in the United States since the Industrial Revolution

    Myroslava Protsiv et al.
    Since the Industrial Revolution, normal body temperature in both men and women has decreased monotonically by 0.03°C per birth decade.
    1. Structural Biology and Molecular Biophysics

    Nucleotide inhibition of the pancreatic ATP-sensitive K+ channel explored with patch-clamp fluorometry

    Samuel G Usher et al.
    Simultaneous measurements of ligand binding and channel currents are used to understand gating of the ATP-sensitive K+ channel.
    1. Cell Biology
    2. Developmental Biology

    Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth

    Steve Dos-Santos Carvalho et al.
    The core PCP protein acts as a internal brake to neuronal outgrowth.
    1. Developmental Biology

    Roles of C/EBP class bZip proteins in the growth and cell competition of Rp (‘Minute’) mutants in Drosophila

    Jorge Blanco et al.
    Xrp1 contributes to cell competition as a heterodimer with the Drosophila C/EBP homolog Irbp18 and although rapidly evolving is itself conserved beyond Drosophila.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress

    Mable Lam et al.
    Death receptor 5 can directly sense misfolded proteins downstream of the endoplasmic reticulum to provide a quality control mechanism that executes apoptosis and prevents further production of misfolded proteins.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Class-A penicillin binding proteins do not contribute to cell shape but repair cell-wall defects

    Antoine Vigouroux et al.
    Class-A penicillin-binding proteins are dispensable for rod-like cell-shape but essential for mechanical integrity by sensing and repairing cell-wall defects locally, as investigated in the model system Escherichia coli.
    1. Neuroscience

    Cell-specific non-canonical amino acid labelling identifies changes in the de novo proteome during memory formation

    Harrison Tudor Evans et al.
    Quantitative de novo proteomics paired with in vivo cell-specific non-canonical amino acid labelling identified several spatial long-term memory-induced changes in protein synthesis in hippocampal neurons.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Perturbation of base excision repair sensitizes breast cancer cells to APOBEC3 deaminase-mediated mutations

    Birong Shen et al.
    Accumulation of mutations in some cancers is correlated with an aberration of DNA repair and access of a DNA deaminase to normal genomic DNA.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    In vivo single-cell lineage tracing in zebrafish using high-resolution infrared laser-mediated gene induction microscopy

    Sicong He et al.
    Infrared laser-mediated gene induction microscopy enables precise single-cell labeling in various tissues of zebrafish, and in vivo visualized single-cell lineage tracing reveals the lineage heterogeneity in hematopoietic endothelial cells.
    1. Developmental Biology
    2. Neuroscience

    A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

    Weidong Feng et al.
    A molecular mechanism that involves highly conserved transcription factors enables cholinergic motor neurons of the nematode Caenorhabditis elegans to become and remain functional.
    1. Cell Biology
    2. Developmental Biology

    Hair follicle stem cells regulate retinoid metabolism to maintain the self-renewal niche for melanocyte stem cells

    Zhiwei Lu et al.
    Metabolite mediates communication between stem cells and influences stem cell maintenance.
    1. Biochemistry and Chemical Biology

    Inhibition of synucleinopathic seeding by rationally designed inhibitors

    Smriti Sangwan et al.
    Inhibitors of seeded propagation of alpha-synuclein may be developed into diagnostics and therapeutics for Parkinson's disease.
    1. Computational and Systems Biology
    2. Neuroscience

    From behavior to circuit modeling of light-seeking navigation in zebrafish larvae

    Sophia Karpenko et al.
    Light-seeking strategies in Zebrafish larvae are dissected using a virtual-reality assay, and these data are used to establish minimal stochastic and neural-circuits models that quantitatively capture this behavior.
    1. Chromosomes and Gene Expression

    The CDK Pef1 and protein phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes

    Adrien Birot et al.
    Cohesin loader activity is regulated by phosphorylation of its cohesin substrate.

Magazine

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    Cell Competition: Counting the Minutes

    Stephano Mello, Dirk Bohmann