May 2019

Cover articles

    1. Evolutionary Biology

    A theropod from the Late Jurassic

    Oliver WM Rauhut, Helmut Tischlinger, Christian Foth
    1. Cancer Biology

    Growth factor activation

    Sawan Kumar Jha, Khushbu Rauniyar ... Michael Jeltsch
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Physical niches guide stem cells in fish

    Julian Stolper, Elizabeth Mayela Ambrosio ... Lazaro Centanin

Highlights controls:

Research articles

    1. Chromosomes and Gene Expression

    The PCNA unloader Elg1 promotes recombination at collapsed replication forks in fission yeast

    Sanjeeta Tamang, Anastasiya Kishkevich ... Matthew C Whitby
    Unloading the polymerase sliding clamp PCNA from DNA by Elg1 promotes recombination at the RTS1 replication fork barrier by limiting Fbh1 and Srs2 activity.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Ceapins block the unfolded protein response sensor ATF6α by inducing a neomorphic inter-organelle tether

    Sandra Elizabeth Torres, Ciara M Gallagher ... Peter Walter
    Ceapins specifically inhibit the unfolded protein sensor ATF6α by directly tethering the cytosolic domain of ATF6α to ABCD3 in cells and in vitro.
    1. Evolutionary Biology

    The genomes of polyextremophilic cyanidiales contain 1% horizontally transferred genes with diverse adaptive functions

    Alessandro W Rossoni, Dana C Price ... Andreas PM Weber
    Horizontal gene transfer (HGT) analysis in polyextremophile red algae (Cyanidiales) provides explanations for the nonexistence of cumulative effects and eukaryotic pangenomes, and highlights differences between HGT and native genes.
    1. Developmental Biology

    Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF

    Manju Sharma, Anuj Srivastava ... Robert E Braun
    Promyelocytic leukemia zinc finger (PLZF) regulates the proliferative rate of eomesodermin (EOMES) spermatogonial stem cells.
    1. Cancer Biology
    2. Cell Biology

    DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs

    Samantha VH Bayer, Whitney R Grither ... Gregory D Longmore
    The action of the collagen receptor DDR2 in CAFs regulates Rap1-Talin1 mediated Integrin mechanotransduction in breast tumors to impact tumor stiffness and metastases.
    1. Cancer Biology

    NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma

    Ganapati V Hegde, Cecile de la Cruz ... Erica L Jackson
    TP63 regulates NRG1 in squamous cell cancers, and targeting of NRG1 induces cancer cell differentiation thereby NRG1 is a potential therapeutic target in squamous cell cancers.
    1. Developmental Biology

    In vivo study of gene expression with an enhanced dual-color fluorescent transcriptional timer

    Li He, Richard Binari ... Norbert Perrimon
    A simple and effective method facilitates the study of in vivo transcriptional dynamics using transcriptional enhancers and destabilized fluorescent protein, which is suitable for both live imaging and fixed studies.
    1. Cancer Biology
    2. Cell Biology

    Club cells form lung adenocarcinomas and maintain the alveoli of adult mice

    Magda Spella, Ioannis Lilis ... Georgios T Stathopoulos
    Airway cells are required for the maintenance of the adult mouse lung and for carcinogen-induced lung adenocarcinoma development, and are thus marked therapeutic targets.
    1. Developmental Biology
    2. Genetics and Genomics

    Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

    Lauren M Saunders, Abhishek K Mishra ... David M Parichy
    Single-cell transcriptomics combined with genetic analyses identify post-embryonic neural crest subpopulations and thyroid hormone dependencies in zebrafish adult pigment pattern development.
    1. Cancer Biology
    2. Cell Biology

    Transcriptional control of subtype switching ensures adaptation and growth of pancreatic cancer

    Christina R Adams, Htet Htwe Htwe ... Rushika M Perera
    The GLI2 transcription factor is a master regulator of the aggressive basal-like subtype of pancreatic cancer and enables adaptation to oncogenic KRAS ablation.
    1. Microbiology and Infectious Disease

    Density-dependent resistance protects Legionella pneumophila from its own antimicrobial metabolite, HGA

    Tera C Levin, Brian P Goldspiel, Harmit S Malik
    Legionella pneumophila can be inhibited by its own antimicrobial, HGA (homogentisic acid), but its density-dependent resistance to HGA restricts the potential for self-harm.
    1. Cancer Biology
    2. Cell Biology

    Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation

    Karoliina Stefanius, Kelly Servage ... Kim Orth
    Exosomes secreted from pancreatic cancer cells can function as a classic initiator in the multi-step cellular transformation process.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint

    Nicolas Bigot, Matthew Day ... Laurence H Pearl
    Two phosphorylation sites on 53BP1 are found to mediate interaction with TOPBP1-RAD9 and shown to be essential for assembling the G1 DNA damage checkpoint response apparatus.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Transcriptome maps of general eukaryotic RNA degradation factors

    Salma Sohrabi-Jahromi, Katharina B Hofmann ... Patrick Cramer
    Mapping of 30 general RNA degradation factors onto the yeast transcriptome provides the global distribution of factors for RNA turnover and surveillance in a eukaryotic cell.
    1. Chromosomes and Gene Expression
    2. Plant Biology

    Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation

    Shengbo He, Martin Vickers ... Xiaoqi Feng
    Transposon activation during male gametogenesis is caused by interactions between DNA demethylation and linker histone H1, developmental depletion of which promotes pollen fertility.
    1. Structural Biology and Molecular Biophysics

    An order-to-disorder structural switch activates the FoxM1 transcription factor

    Aimee H Marceau, Caileen M Brison ... Seth M Rubin
    Structural and biochemical analysis reveals that two intrinsically disordered domains of the transcription factor FoxM1 co-fold to form an autoinhibited conformation, which is disrupted by a specific activating phosphorylation event.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs

    Bert van de Kooij, Pau Creixell ... Michael B Yaffe
    The human NimA-related kinases (Neks) recognize divergent substrate motifs, and include Nek10 as a dual-specificity serine/tyrosine kinase, and Nek6, Nek7 and Nek9 as amplifiers of the Plk1 phospho-motif.
    1. Neuroscience

    Local online learning in recurrent networks with random feedback

    James M Murray
    A biologically plausible learning rule enables recurrent neural networks to model the way in which neural circuits use supervised learning to perform time-dependent computations.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

    Benjamin Albert, Isabelle C Kos-Braun ... David Shore
    Ribosome assembly is monitored to promote proteostatis through a system whereby unassembled ribosomal proteins lead to activation of heat shock factor 1 and inactivation of the RP gene activator Ifh1.
    1. Chromosomes and Gene Expression

    Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity

    Jeffrey M Alexander, Juan Guan ... Orion D Weiner
    Sox2 transcription is not correlated with spatial proximity of its essential regulatory enhancer in embryonic stem cells, suggesting gene transcription is not limited to periods of direct enhancer-promoter contact.
    1. Stem Cells and Regenerative Medicine

    Cell non-autonomous functions of S100a4 drive fibrotic tendon healing

    Jessica E Ackerman, Anne EC Nichols ... Alayna E Loiselle
    Inhibition of S100a4 represents a novel anti-fibrotic target to improve tendon healing.
    1. Microbiology and Infectious Disease

    HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors

    Pratibha C Koneru, Ashwanth C Francis ... Mamuka Kvaratskhelia
    Pyridine-based allosteric inhibitors selectively target HIV-1 integrase tetramers and exhibit enhanced antiviral activity against a dolutegravir resistant mutant virus indicating potential clinical benefits for combining these two classes of inhibitors.
    1. Epidemiology and Global Health

    Estimating the burden of α-thalassaemia in Thailand using a comprehensive prevalence database for Southeast Asia

    Carinna Hockham, Supachai Ekwattanakit ... Frédéric B Piel
    The incorporation of as yet underused local epidemiological data on α-thalassaemia in Southeast Asia within a geostatistical model suggests that the burden of severe α-thalassaemia forms may have been underestimated.
    1. Neuroscience

    Early-generated interneurons regulate neuronal circuit formation during early postnatal development

    Chang-Zheng Wang, Jian Ma ... Yong-Chun Yu
    Early-generated interneurons are more mature in intrinsic properties and neuronal connectivity during early postnatal stage, and are critical for proper spontaneous network synchronization and the wiring of immature cortical circuits.
    1. Neuroscience

    Preserved extrastriate visual network in a monkey with substantial, naturally occurring damage to primary visual cortex

    Holly Bridge, Andrew H Bell ... Kristine Krug
    Even when the primary visual cortical area is absent bilaterally from early life, the rest of a primate visual brain can develop and function normally to support day-to-day visual behaviour.
    1. Epidemiology and Global Health

    Opportunities for improved surveillance and control of dengue from age-specific case data

    Isabel Rodriguez-Barraquer, Henrik Salje, Derek A Cummings
    Age-specific incidence data, combined with mechanistic models of immunity, provides a unique opportunity to characterize disease transmission of dengue and other immunizing diseases at high temporal and spatial resolution.
    1. Neuroscience

    Complementary congruent and opposite neurons achieve concurrent multisensory integration and segregation

    Wen-Hao Zhang, He Wang ... Si Wu
    Opposite neurons in multisensory areas compute the cue disparity information essential for information segregation.
    1. Neuroscience

    Context-dependent signaling of coincident auditory and visual events in primary visual cortex

    Thomas Deneux, Evan R Harrell ... Brice Bathellier
    Abrupt sounds boost coincident visual cortex responses which could help localization of sudden audio-visual events.
    1. Cell Biology

    PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole cartwheel to the microtubule wall

    Tyler Chistopher Moyer, Andrew Jon Holland
    Cell biological, biochemical, and genetic analyses reveal that PLK4 controls two different phospho-dependent binding interactions that act together to promote procentriole assembly.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR

    Nancy L Meyer, Guiqing Hu ... Michael Stewart Chapman
    Cryo-electron microscopy reveals interactions at the interface between adeno-associated virus and its cellular receptor at 2.4Å resolution.
    1. Structural Biology and Molecular Biophysics

    Mechanism of completion of peptidyltransferase centre assembly in eukaryotes

    Vasileios Kargas, Pablo Castro-Hartmann ... Alan John Warren
    Cryo-EM reveals how the central functional site of the ribosome is assembled and provides a framework to interpret the consequences of mutations linked to leukaemia-associated ribosomopathies.
    1. Neuroscience

    Functional and anatomical specificity in a higher olfactory centre

    Shahar Frechter, Alexander Shakeel Bates ... Gregory Jefferis
    The Drosophila lateral horn, a higher olfactory brain area, contains >165 genetically defined cell types with stereotyped odour responses across animals and improved odor categorisation compared with their inputs.
    1. Neuroscience

    Neurogenetic dissection of the Drosophila lateral horn reveals major outputs, diverse behavioural functions, and interactions with the mushroom body

    Michael-John Dolan, Shahar Frechter ... Gregory SXE Jefferis
    The generation and systematic characterisation of driver lines labelling a large number of neurons in the Drosophila innate olfactory processing centre bridges electron microscopy neuronal reconstructions, circuits and behaviour.
    1. Biochemistry and Chemical Biology
    2. Immunology and Inflammation

    Synergy between serum amyloid A and secretory phospholipase A2

    Shobini Jayaraman, Marcus Fändrich, Olga Gursky
    SAA removes toxic products of lipolysis of the cell membrane by sPLA2, indicating that SAA and sPLA2 act synergistically to clear debris from injured sites, as required for tissue healing.
    1. Cancer Biology
    2. Cell Biology

    GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor

    Jenna L Jewell, Vivian Fu ... Kun-Liang Guan
    Protein kinase A (PKA) phosphorylates Raptor and inhibits mammalian target of rapamycin complex 1 (mTORC1) activity.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore

    Josef Fischböck-Halwachs, Sylvia Singh ... Franz Herzog
    The chromosomal passenger complex interacts with the inner kinetochore COMA complex through the Ctf19 C-terminus in vitro which is shown to be important for mediating accurate chromosome segregation.
    1. Genetics and Genomics
    2. Neuroscience

    The ion channel ppk301 controls freshwater egg-laying in the mosquito Aedes aegypti

    Benjamin J Matthews, Meg A Younger, Leslie B Vosshall
    The ion channel ppk301 is required for the evaluation of water purity during egg-laying, which promotes offspring survival in the arboviral vector mosquito Aedes aegypti.
    1. Neuroscience

    Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

    Mary L Phillips, Holly Anne Robinson, Lucas Pozzo-Miller
    Input from the ventral hippocampus to the medial prefrontal cortex regulates social memory in wild type mice and atypically-strengthened input causes social memory dysfunction in Rett syndrome mice.
    1. Neuroscience

    Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval in rats

    Briac Halbout, Andrew T Marshall ... Sean B Ostlund
    Inhibiting ventral tegmental dopamine neurons, or their inputs to nucleus accumbens, disrupts cue-motivated reward seeking in a manner that depends on the microstructure of behavior.
    1. Cell Biology
    2. Plant Biology

    Live cell imaging of meiosis in Arabidopsis thaliana

    Maria A Prusicki, Emma M Keizer ... Arp Schnittger
    Live cell imaging and the in vivo dissection into distinct stages, called landmarks, represents a new methodology for analyzing meiosis in Arabidopsis and likely in other species as well.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    Cysteine dioxygenase 1 is a metabolic liability for non-small cell lung cancer

    Yun Pyo Kang, Laura Torrente ... Gina M DeNicola
    By increasing intracellular cysteine levels, NRF2 engages a tumor suppressive metabolic pathway mediated by cysteine dioxygenase 1.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly

    Snježana Mikuličić, Jérôme Finke ... Luise Florin
    ADAM17 is a key player in the non-canonical endocytosis pathway that is used by oncogenic papillomaviruses as it allows virus/receptor platform assembly by activation of the ERK1/2 signaling pathway.
    1. Stem Cells and Regenerative Medicine

    Chemical modulation of transcriptionally enriched signaling pathways to optimize the conversion of fibroblasts into neurons

    Joseph Herdy, Simon Schafer ... Fred H Gage
    An unbiased RNAseq based strategy to identify targetable pathways and a streamlined lentiviral system provide a state of the art advance on direct fibroblast to neuron conversion.
    1. Developmental Biology
    2. Neuroscience

    FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

    Ryan J Kast, Alexandra L Lanjewar ... Pat Levitt
    Foxp2 is dispensable for several features of cortical development that were previously considered to depend on its function.
    1. Cell Biology

    Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis

    Alenka Guček, Nikhil R Gandasi ... Sebastian Barg
    Live cell imaging shows that the cAMP-sensor Epac2, a target of major antidiabetic drugs, is central to fusion pore control during insulin granule exocytosis.
    1. Neuroscience

    Accelerated redevelopment of vocal skills is preceded by lasting reorganization of the song motor circuitry

    Michiel Vellema, Mariana Diales Rocha ... Manfred Gahr
    The ability to quickly re-acquire a previously lost motor skill is associated with lasting synaptic changes in the brain circuit that controls that motor skill.
    1. Cancer Biology

    KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D

    Sawan Kumar Jha, Khushbu Rauniyar ... Michael Jeltsch
    Both VEGF-C and VEGF-D can be activated by KLK3/PSA and Cathepsin D, producing two novel VEGF-C forms and the known VEGFR-2-specific form of VEGF-D.
    1. Neuroscience

    Synapse-specific opioid modulation of thalamo-cortico-striatal circuits

    William T Birdsong, Bart C Jongbloets ... Tianyi Mao
    By differentially modulating the two major excitatory inputs to the striatum, mu- and delta-opioid receptors regulate the balance between thalamic and cortical inputs to the striatum.
    1. Neuroscience

    PI3K-Yap activity drives cortical gyrification and hydrocephalus in mice

    Achira Roy, Rory M Murphy ... Kathleen J Millen
    Embryonic PI3K-Yap activity regulates apical adhesion and proliferation of neural progenitors lining the lateral ventricular surface, to maintain the smooth, non-folded mouse brain and to prevent developmental hydrocephalus.
    1. Cell Biology

    Misfolded GPI-anchored proteins are escorted through the secretory pathway by ER-derived factors

    Eszter Zavodszky, Ramanujan S Hegde
    ER-resident chaperones and cargo receptors make excursions to the cell surface and endocytic compartments when they accompany misfolded clients to lysosomes for degradation.
    1. Chromosomes and Gene Expression

    Asymmetry between the two acidic patches dictates the direction of nucleosome sliding by the ISWI chromatin remodeler

    Robert F Levendosky, Gregory D Bowman
    Unlike Chd1, ISWI remodelers preferentially shift asymmetric nucleosomes toward the side possessing a wild type acidic patch, regardless of DNA lengths flanking the nucleosome.
    1. Microbiology and Infectious Disease

    The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development

    Devendra Kumar Gupta, Laurent Dembele ... Thierry Tidiane Diagana
    LISP2 expression marks the beginning of awakening of dormant hypnozoite to developing malaria liver stages, which are susceptible to a novel prophylactic drug, Plasmodium PI4K inhibitor.
    1. Developmental Biology

    Reciprocal action of Casein Kinase Iε on core planar polarity proteins regulates clustering and asymmetric localisation

    Helen Strutt, Jessica Gamage, David Strutt
    Casein kinase Iε phosphorylation has opposite effects on the stability of the core planar polarity proteins Strabismus and Dishevelled, leading to their sorting to opposite cell ends.
    1. Structural Biology and Molecular Biophysics

    Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes

    Lejla Zubcevic, Allen L Hsu ... Seok-Yong Lee
    Ligand-induced two-fold symmetric arrangement in TRPV2 is observed in the native-like nanodisc-reconstituted condition using cryo-electron microscopy.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Predominance of cis-regulatory changes in parallel expression divergence of sticklebacks

    Jukka-Pekka Verta, Felicity C Jones
    Cis-regulation such as enhancers and promoters plays a major role in parallel gene expression divergence and has features that make it a well-poised substrate for adaptive evolution.
    1. Neuroscience

    Elevated synaptic vesicle release probability in synaptophysin/gyrin family quadruple knockouts

    Mathan K Raja, Julia Preobraschenski ... John F Wesseling
    Synaptophysins and gyrins dampen synaptic strength selectively at low frequencies, hinting that synaptic transmission may play a frequency filtering role in biological computation that is more general than currently envisioned.
    1. Neuroscience

    Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse

    Jie Zhang, Liang Li ... Yang Hu
    An effective and reversible mouse glaucoma model that replicates the secondary glaucoma in human patients caused by silicone oil after retina surgeries presents significant neurodegeneration, and is suitable for neuroprotectants selection.
    1. Immunology and Inflammation

    IFNγ induces epigenetic programming of human T-bethi B cells and promotes TLR7/8 and IL-21 induced differentiation

    Esther Zumaquero, Sara L Stone ... Frances E Lund
    IFNγ increases the responsiveness of human B cells to IL-2, TLR7/8 and IL-21 signals and therefore enhances antibody production in inflammatory settings associated with autoimmune or chronic disease.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Stem cell topography splits growth and homeostatic functions in the fish gill

    Julian Stolper, Elizabeth Mayela Ambrosio ... Lazaro Centanin
    The fish gill, an ever-growing organ with fast turnover rate, displays dedicated stem-cell populations for growth and homeostasis that are interchangeable upon external challenges.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    HSV-1 single-cell analysis reveals the activation of anti-viral and developmental programs in distinct sub-populations

    Nir Drayman, Parthiv Patel ... Savaş Tay
    Single-cell analyses of cells infected by Herpes Simplex Virus 1 revealed extreme heterogeneity among infected cells, including the robust activation of developmental gene programs in highly infected cells.
    1. Chromosomes and Gene Expression

    A multiplexed DNA FISH strategy for assessing genome architecture in Caenorhabditis elegans

    Brandon D Fields, Son C Nguyen ... Scott Kennedy
    The design and validation of an oligo-based DNA FISH library that targets the entire Caenorhabditis elegans genome at chromosome, three megabase, and 500 kb scales.
    1. Physics of Living Systems

    Spatial control of irreversible protein aggregation

    Christoph Weber, Thomas Michaels, L Mahadevan
    A theoretical basis for the spatial regulation of protein aggregation shows how aggregates can partition preferentially into intracellular liquid compartments.
    1. Immunology and Inflammation

    Identification of potential biomarkers of vaccine inflammation in mice

    Paul F McKay, Deniz Cizmeci ... Robin J Shattock
    Molecular biosignatures that identify an inflammatory and potentially adverse reaction to vaccination have been defined in mice, a critical gatekeeper for progression of novel vaccine candidates into humans.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Independent amylase gene copy number bursts correlate with dietary preferences in mammals

    Petar Pajic, Pavlos Pavlidis ... Omer Gokcumen
    Comprehensive analyses of amylase duplications and salivary activity across mammals underscore the importance of recurrent copy number variation as a flexible and rapid evolutionary mechanism.
    1. Computational and Systems Biology
    2. Physics of Living Systems

    Imaging single-cell blood flow in the smallest to largest vessels in the living retina

    Aby Joseph, Andres Guevara-Torres, Jesse Schallek
    By using a specialized camera that corrects for eye blur, millions of single-blood-cells are imaged, and their speed measured, as they travel through the largest-to-smallest vessels of the retina.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Neck linker docking is critical for Kinesin-1 force generation in cells but at a cost to motor speed and processivity

    Breane G Budaitis, Shashank Jariwala ... Kristen J Verhey
    Force generation by kinesin motor proteins requires formation of both a 2-stranded cover-neck bundle and an asparagine-based latch for transport of membrane-bound cargoes in cells.
    1. Microbiology and Infectious Disease
    2. Physics of Living Systems

    Influenza A virus surface proteins are organized to help penetrate host mucus

    Michael D Vahey, Daniel A Fletcher
    By distributing receptor-binding and receptor-destroying proteins asymmetrically on their surface, filamentous influenza A virus particles create a Brownian ratchet that facilitates their passage through mucus.
    1. Immunology and Inflammation

    IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis

    Qian Wang, Christin M Lepus ... William H Robinson
    Osteoarthritis pathogenesis is driven by IgE-mediated mast cell activation.
    1. Evolutionary Biology

    A multidisciplinary approach to a unique palaeolithic human ichnological record from Italy (Bàsura Cave)

    Marco Romano, Paolo Citton ... Marco Avanzini
    Traces of crawling locomotion, including children younger than 3 years old, are documented for the first time in the global human ichnological record.
    1. Chromosomes and Gene Expression

    Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins

    Haiyang Zhang, Meghan V Petrie ... Oscar M Aparicio
    Establishment of replication-timing involves Fkh1-dependent recruitment and execution of DDK function in G1 phase resulting in dynamic relocalization of origins within the nucleus in anticipation of CDK-dependent origin activation.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction

    Mohsen Afshar Bakooshli, Ethan S Lippmann ... Penney M Gilbert
    Human skeletal muscle progenitors and motor neurons self-organize in three-dimensional co-culture to form functional neuromuscular junctions that developmentally mature from the embryonic to the adult state.
    1. Evolutionary Biology

    A non-archaeopterygid avialan theropod from the Late Jurassic of southern Germany

    Oliver WM Rauhut, Helmut Tischlinger, Christian Foth
    A new taxon from the Late Jurassic of southern Germany represents the second volant bird known from that time period and documents the improvement of flapping flight in bird evolution.
    1. Neuroscience

    Increased anxiety and decreased sociability induced by paternal deprivation involve the PVN-PrL OTergic pathway

    Zhixiong He, Larry Young ... Fadao Tai
    The PVN-mPFC OT circuit is an important target for the treatment of disorders related to early adverse experiences.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    A combination of transcription factors mediates inducible interchromosomal contacts

    Seungsoo Kim, Maitreya J Dunham, Jay Shendure
    A pooled mutational scanning approach for 3D chromosome conformation reveals how multiple transcription factors can jointly specify condition-specific genome conformations.
    1. Plant Biology

    Plant–necrotroph co-transcriptome networks illuminate a metabolic battlefield

    Wei Zhang, Jason A Corwin ... Daniel J Kliebenstein
    Simultaneously measuring the transcriptomes of both a host plant and fungal pathogen, co-transcriptomics, identified diverse, dynamic and independent communication mechanisms conveying information between the two organisms via discrete gene modules.
    1. Neuroscience

    Short-term plasticity at cerebellar granule cell to molecular layer interneuron synapses expands information processing

    Kevin Dorgans, Valérie Demais ... Frédéric Doussau
    Molecular, structural and functional diversity of cerebellar granule cell inputs on single molecular layer interneurons extends information processing in feed-forward inhibition microcircuits.
    1. Computational and Systems Biology
    2. Neuroscience

    Fast and flexible sequence induction in spiking neural networks via rapid excitability changes

    Rich Pang, Adrienne L Fairhall
    Biologically plausible changes in the excitabilities of single neurons may suffice to selectively modulate sequential network dynamics, without modifying of recurrent connectivity.
    1. Biochemistry and Chemical Biology

    The dynamic conformational landscape of the protein methyltransferase SETD8

    Shi Chen, Rafal P Wiewiora ... Minkui Luo
    Integrated experimental-computational approaches were implemented to reveal the dynamic conformational landscape of a biologically relevant protein methyltransferase SETD8 for functional annotation.
    1. Neuroscience

    Sensory perception drives food avoidance through excitatory basal forebrain circuits

    Jay M Patel, Jessica Swanson ... Benjamin R Arenkiel
    Glutamatergic projection neurons downstream of cholinergic cells in the basal forebrain potently affect feeding behavior by modulating downstream reward and aversion circuits.
    1. Neuroscience

    Critical role for Piccolo in synaptic vesicle retrieval

    Frauke Ackermann, Kay Oliver Schink ... Craig Curtis Garner
    The active zone protein Piccolo regulates efficient recycling of SVs via Pra1 and Rab5 and is therefore critical for integrity and reliability of synaptic function.
    1. Microbiology and Infectious Disease

    Differences across cyclophilin A orthologs contribute to the host range restriction of hepatitis C virus

    Jenna M Gaska, Metodi Balev ... Alexander Ploss
    Incompatibilities between the viral replication machinery and orthologs of the essential host factor cyclophilin A (CypA) contribute to the narrow host range of hepatitis C virus.
    1. Neuroscience

    Self-organized reactivation maintains and reinforces memories despite synaptic turnover

    Michael Jan Fauth, Mark CW van Rossum
    Despite ongoing rewiring and continuous turnover of synapses, a computational model shows that memories can maintain and even strengthen their connectivity by self-reactivating during periods without sensory input.
    1. Neuroscience

    Computational mechanisms of curiosity and goal-directed exploration

    Philipp Schwartenbeck, Johannes Passecker ... Karl J Friston
    Distinct computational levels of uncertainty compel agents to gain information about hidden states in the world (‘active inference’) or optimise their ‘world model’ as such (‘active learning’).
    1. Genetics and Genomics

    Gene-centric functional dissection of human genetic variation uncovers regulators of hematopoiesis

    Satish K Nandakumar, Sean K McFarland ... Vijay G Sankaran
    A gene-centric functional screen uncovers biological mechanisms underlying genome-wide association study signals for human red blood cell traits.
    1. Structural Biology and Molecular Biophysics

    Regulatory switch at the cytoplasmic interface controls TRPV channel gating

    Lejla Zubcevic, William F Borschel ... Seok-Yong Lee
    C-terminal domain of thermoTRPV channels regulates channel gating at the cytoplasmic interface through a switch-like process.
    1. Neuroscience

    Circulating transforming growth factor-β1 facilitates remyelination in the adult central nervous system

    Machika Hamaguchi, Rieko Muramatsu ... Toshihide Yamashita
    Although central nervous system (CNS) regeneration has been considered to be controlled by CNS microenvironment, CNS injury causes leading to leakage of circulating factors into CNS, which promotes CNS regeneration.
    1. Developmental Biology
    2. Genetics and Genomics

    Dlg1 activates beta-catenin signaling to regulate retinal angiogenesis and the blood-retina and blood-brain barriers

    Chris Cho, Yanshu Wang ... Jeremy Nathans
    Discs large homologue 1 (Dlg1) activates beta-catenin (i.e., canonical Wnt) signaling in CNS endothelial cells to regulate retinal angiogenesis and the development and maintenance of the blood-brain and blood-retina barriers.
    1. Neuroscience

    The relationship between spatial configuration and functional connectivity of brain regions revisited

    Janine Diane Bijsterbosch, Christian F Beckmann ... Samuel J Harrison
    The estimation of functional connectivity network matrices from resting state fMRI is driven by a combination of spatial and temporal factors in the presence of spatially overlapping network structure.
    1. Cell Biology
    2. Developmental Biology

    Asymmetric recruitment and actin-dependent cortical flows drive the neuroblast polarity cycle

    Chet Huan Oon, Kenneth E Prehoda
    Neural stem cells dynamically polarize through the stepwise activity of polarized cortical targeting and cortical flows that coalescence discontinuous cortical patches into an organized cap structure.
    1. Cell Biology

    Generation of endogenous pH-sensitive EGF receptor and its application in high-throughput screening for proteins involved in clathrin-mediated endocytosis

    Mads Breum Larsen, Mireia Perez Verdaguer ... Alexander Sorkin
    CRISPR/Cas9 gene-editing was used to generate a novel endogenous pH-sensitive EGF receptor chimera with the unique utility to study receptor endocytosis in a single-cell and high-throughput experimental formats.
    1. Cell Biology
    2. Physics of Living Systems

    Spatiotemporal organization of branched microtubule networks

    Akanksha Thawani, Howard A Stone ... Sabine Petry
    A sequential reaction pathway involving TPX2, augmin and γ-TuRC governs the assembly and architecture of branched microtubule networks.
    1. Biochemistry and Chemical Biology
    2. Evolutionary Biology

    'Palaeoshellomics’ reveals the use of freshwater mother-of-pearl in prehistory

    Jorune Sakalauskaite, Søren H Andersen ... Beatrice Demarchi
    Ancient proteomes from tiny shell ornaments were successfully characterised for the first time, showing the unexpected use of mother-of-pearl from local riverine molluscs in both coastal and inland prehistoric sites.
    1. Neuroscience

    Dissociable laminar profiles of concurrent bottom-up and top-down modulation in the human visual cortex

    Samuel JD Lawrence, David G Norris, Floris P de Lange
    Neural activity in the visual system is increased in different layers of the neocortex for bottom-up and top-down modulations.
    1. Cell Biology

    Mammalian cell growth dynamics in mitosis

    Teemu P Miettinen, Joon Ho Kang ... Scott R Manalis
    High-resolution single-cell mass accumulation and protein synthesis rate measurements are used to quantify the extent, dynamics and consequences of animal cell growth in mitosis and cytokinesis.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    An acquired scaffolding function of the DNAJ-PKAc fusion contributes to oncogenic signaling in fibrolamellar carcinoma

    Rigney E Turnham, F Donelson Smith ... John D Scott
    Fibrolamellar carcinoma results from a genetic lesion that produces the DNAJ-PKAc fusion kinase, which is recruited into macromolecular complexes and is sensitive to combinations of signal transduction inhibitor drugs.
    1. Developmental Biology

    Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography

    Yifu Ding, Daniel J Vanselow ... Keith C Cheng
    X-ray histotomography produces the first 3-dimensional images with the combined submicron resolution, centimeter fields-of-view, soft-tissue contrast, and potential throughput to enable quantitative, histopathological and centimeter-scale phenotyping for whole-organism phenomics.
    1. Biochemistry and Chemical Biology

    A terpene synthase-cytochrome P450 cluster in Dictyostelium discoideum produces a novel trisnorsesquiterpene

    Xinlu Chen, Katrin Luck ... Feng Chen
    The social amoeba Dictyostelium discoideum employs a terpene synthase-cytochrome P450 metabolic gene cluster to produce a novel trisnorsesquiterpene discodiene.
    1. Neuroscience

    Non-selective inhibition of inappropriate motor-tendencies during response-conflict by a fronto-subthalamic mechanism

    Jan R Wessel, Darcy A Waller, Jeremy DW Greenlee
    Action-selection under response-conflict is buttressed by an inhibitory control signal from the basal ganglia that non-selectively suppresses motor excitability.
    1. Neuroscience

    CNS myelination and remyelination depend on fatty acid synthesis by oligodendrocytes

    Penelope Dimas, Laura Montani ... Ueli Suter
    Endogenous synthesis of fatty acids by oligodendrocytes is essential for development and repair in the central nervous system.
    1. Neuroscience

    Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

    Jordan N Norwood, Qingguang Zhang ... Patrick J Drew
    Chemical ablation of olfactory sensory neurons blocks cerebrospinal fluid outflow into the nasal epithelium, leading to alterations of cerebrospinal fluid dynamics.
    1. Structural Biology and Molecular Biophysics

    Structural basis of phosphatidylcholine recognition by the C2–domain of cytosolic phospholipase A2α

    Yoshinori Hirano, Yong-Guang Gao ... Rhoderick E Brown
    The C2-domain of cytoplasmic phospholipase A2α is structurally designed to target PC-rich membrane regions to increase the enzymatic efficiency of the catalytic domain, which prefers PCs with polyunsaturated acyl chains.
    1. Cell Biology

    Stable Pom1 clusters form a glucose-modulated concentration gradient that regulates mitotic entry

    Corey A H Allard, Hannah E Opalko, James B Moseley
    Dynamic signaling protein clusters sample and map the cell surface to ensure that cells divide at the proper size.
    1. Cell Biology

    Multi-phosphorylation reaction and clustering tune Pom1 gradient mid-cell levels according to cell size

    Veneta Gerganova, Charlotte Floderer ... Sophie G Martin
    Advanced microscopy techniques reveal that clusters of Pom1 kinase at the membrane represent the functional unit that shape the concentration gradients and modulate Pom1 mid-cell levels according to cell size.
    1. Cancer Biology
    2. Cell Biology

    PAX8 regulon in human ovarian cancer links lineage dependency with epigenetic vulnerability to HDAC inhibitors

    Kaixuan Shi, Xia Yin ... Guanglei Zhuang
    A functional ovarian-specific PAX8-centric regulon is susceptible to FDA-approved HDAC inhibitors, providing the rationale to target human cancers driven by lineage-survival oncogenes with epigenetic therapeutics perturbing the enhancer topology.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Response to comment on 'The distribution of antibiotic use and its association with antibiotic resistance'

    Scott W Olesen, Marc Lipsitch, Yonatan H Grad
    We are writing to reply to the comment by Pouwels et al., 2019 about our recent study (Olesen et al., 2018) on antibiotic use and antibiotic resistance.
    1. Developmental Biology

    The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila

    Katrin Domsch, Julie Carnesecchi ... Ingrid Lohmann
    The Hox transcription factor Ultrabithorax (Ubx) represses alternative gene programs during lineage development by lineage-specific Polycomb protein complex retention at Ubx-targeted chromatin sites.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans

    Chaolie Huang, Sara Wagner-Valladolid ... Della C David
    Age-dependent protein aggregation closely resembles protein aggregation associated with neurodegenerative diseases and other amyloidoses, and initiates early functional decline in different tissues.
    1. Developmental Biology

    GIPC proteins negatively modulate Plexind1 signaling during vascular development

    Jorge Carretero-Ortega, Zinal Chhangawala ... Jesús Torres-Vázquez
    Zebrafish mutants and human endothelial cell experiments reveal that GIPC family endocytic adaptors bind to the Semaphorin receptor PLEXIND1, a critical regulator of vascular development, to negatively modulate its signaling.
    1. Neuroscience

    Cerebellar Purkinje cells control eye movements with a rapid rate code that is invariant to spike irregularity

    Hannah L Payne, Ranran L French ... Jennifer L Raymond
    Patterned optogenetic stimulation and analysis of neural activity provide convergent evidence that cerebellar Purkinje cells drive eye movements with a rapid rate code, without an additional contribution of spike irregularity.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Comment on 'The distribution of antibiotic use and its association with antibiotic resistance'

    Koen B Pouwels, Christopher C Butler, Julie V Robotham
    We are writing to comment on the recent study by Olesen et al., 2018 on antibiotic use and antibiotic resistance.
    1. Epidemiology and Global Health

    Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions

    Oliver John Watson, Robert Verity ... Hannah C Slater
    The timing of surveillance for pfhrp2/3-deletions within a transmission season impacts estimates of the proportion of false-negative RDTs due to deletions, which may cause premature decisions to change RDT.
    1. Neuroscience

    A valve-like mechanism controls desensitization of functional mammalian isoforms of acid-sensing ion channels

    Yangyu Wu, Zhuyuan Chen, Cecilia M Canessa
    Three residues work together as a valve-like mechanism to control desensitization from pre-open and open states in the ion channels ASIC1a, ASIC2a, and ASIC3.
    1. Ecology

    Ant colonies maintain social homeostasis in the face of decreased density

    Andreas P Modlmeier, Ewan Colman ... David P Hughes
    Organizational resilience allows ant colonies to retain high interaction rates in the face of decreased density by altering their spatial and social dynamics.
    1. Ecology

    5α-cyprinol sulfate, a bile salt from fish, induces diel vertical migration in Daphnia

    Meike Anika Hahn, Christoph Effertz ... Eric von Elert
    A fish-derived bile salt was shown to act as interspecific infochemical, inducing the widespread predator avoidance behavior diel vertical migration at picomolar concentrations in freshwater zooplankton of the genus Daphnia.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity

    Tamara M Sirey, Kenny Roberts ... Chris P Ponting
    Mitochondrial energy metabolism is post-transcriptionally regulated through an interplay between long and short non-coding RNAs.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules

    Emily Anne Scarborough, Trisha N Davis, Charles L Asbury
    Flexibility of Ndc80 provides an inherent mode of regulation for the conserved kinetochore complex, unique from well-studied phospho-regulation.
    1. Cell Biology

    Megakaryocyte emperipolesis mediates membrane transfer from intracytoplasmic neutrophils to platelets

    Pierre Cunin, Rim Bouslama ... Peter A Nigrovic
    In a novel cell-in-cell interaction termed emperipolesis, neutrophils routinely transit through the cytoplasm of bone marrow megakaryocytes to pass surface membrane to newly-generated hybrid platelets.
    1. Neuroscience

    Unimodal statistical learning produces multimodal object-like representations

    Gábor Lengyel, Goda Žalalytė ... Daniel M Wolpert
    Mere exposure to scenes with statistical contingencies in the visual or haptic modality alone allows participants to decompose scenes into object-like multimodal representations.
    1. Cell Biology
    2. Neuroscience

    Structural plasticity of actin-spectrin membrane skeleton and functional role of actin and spectrin in axon degeneration

    Guiping Wang, David J Simon ... Xiaowei Zhuang
    Neurotrophin deprivation leads to rapid caspase-independent disassembly of the actin-spectrin-based membrane skeleton and spectrin-dependent retrograde signaling in axon degeneration.