bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial-temporal dynamics of a microbial cooperative behavior robust to cheating
Authors: Monaco Hilary , Sereno Tiago , Liu Kevin , Reagor Caleb , Deforet Maxime , Xavier Joao B. 
Published: January 2020

AbstractIndividuals living in dense populations control their behaviors by sensing, integrating and responding to many cues. How can these processes enable the evolution and stability of cooperative behaviors that could easily be exploited by cheaters? Here we shed light on how bacteria regulate cooperation by studying swarming inPseudomonas aeruginosa, a behavior requiring cooperative secretions of rhamnolipid surfactants to facilitate collective movement over surfaces. By combining fluorescent imaging and computational analyses we show, counterintuitively, that rhamnolipid expression peaks at swarming edges. We then show that the integration of competing diffusive cues—quorum sensing signals and growth-limiting nutrients—enablesP. aeruginosato communicate across centimeters and adopt expression patterns unseen in well-mixed liquid culture. Integration of multiple cues enables robustness against cheating even when we experimentally perturb the quorum sensing system. Taken together, these results illuminate how the integration of cues in spatially structured communities can stabilize cooperation.
A Spiking Neural Network Model for Category Learning
Authors: Iyer Laxmi R. , Basu Arindam 
Published: January 2020

AbstractThe creation of useful categories from data is an important cognitive ability, and from the extensive research on categorization, it is now known that the brain has distinct systems for category learning. In this paper, we present the first spiking neural network (SNN) model of human category learning. Here categories are combinations of features - such categories are observed in the prefrontal cortex (PFC). The system follows an architecture commonly used to model the cortex - features are arranged in a topological 2D grid with short range excitatory connectivity and long range inhibitory connectivity - however, here, this architecture is used differently from other models to model higher level cognition. Earlier we presented an artificial neural network (ANN) model of category learning; however, here, a simpler model was adequate, as desired functionality emerges from the SNN dynamics. We identified the objectives that had to be fulfilled for the model to achieve the desired functionality, and performed a design space exploration (DSE) to identify the parameter range in which each of the objectives was fulfilled, and the parameter range for which the system exhibits good performance. Finally, we compared triphasic STDP (a variant of spike time dependant plasticity (STDP)) with standard STDP and observed that triphasic STDP exhibited quicker convergence.
USP15 deubiquitinase safeguards hematopoiesis and genome integrity in hematopoietic stem cells and leukemia cells
Authors: van den Berk Paul , Lancini Cesare , Company Carlos , Serresi Michela , Hulsman Danielle , Pritchard Colin , Song Ji-Ying , Schmitt Matthias Jürgen , Tanger Ellen , Huijbers Ivo J. , Jacobs Heinz , van Lohuizen Maarten , Gargiulo Gaetano , Citterio Elisabetta 
Published: January 2020

SummaryAltering ubiquitination by disruption of individual deubiquitinating enzymes (DUBs) has proven to affect hematopoietic stem cell (HSC) maintenance. However, comprehensive knowledge of DUB function during hematopoiesisin vivois lacking. To accomplish this goal, we systematically inactivated DUBs in mouse hematopoietic progenitors usingin vivosmall hairpin RNAs (shRNAs) screens. We found that multiple DUBs may be individually required for hematopoiesis and that the ubiquitin-specific protease 15 (USP15) is particularly important for the maintenance of murine hematopoietic stem and progenitor cellsin vitroandin vivo.Consistently,Usp15knockout mice exhibited a reduced HSC pool. The defect was intrinsic to HSCs, as demonstrated by competitive repopulation assays. Importantly, USP15 is highly expressed in normal human hematopoietic cells and leukemias, and USP15 depletion in murine early progenitors and myeloid leukemia cells impairedin vitroexpansion and increased genotoxic stress. Our study underscores the importance of DUBs in preserving normal hematopoiesis and uncovers USP15 as a critical DUB in safeguarding genome integrity in HSC and in leukemia cells.
Distinct neural variables underlie subjective reports of attention
Authors: Whitmarsh Stephen , Gitton Christophe , Jousmäki Veikko , Sackur Jérôme , Tallon-Baudry Catherine 
Published: January 2020

AbstractAttention is subjectively experienced as a unified cognitive effort. This unitary experience of attention contrasts with the diversity of neural and peripheral correlates of attention. While the effects of attention on stimulus-evoked responses, alpha oscillations and pupil diameter, are well-known the relationship between these indices and thesubjectiveexperience of attention, has not yet been assessed. Participants performed a sustained (10 s to 30 s) attention task in which rare (10%) targets were detected within continuous tactile stimulation (16 Hz). Trials were followed by attention ratings on an 8-point Likert scale. Steady-state evoked fields (SSEFs) in response to tactile stimulation, as measured by magnetoencephalography, provided an objective measure of sensory processing. Beamformer source analysis of somatosensory alpha power was used as a measure of cortical excitability, while pupillometry provided a peripheral index of arousal. Attention ratings correlated negatively with contralateral somatosensory alpha power, and positively with pupil diameter. The effect of pupil diameter on attention ratings extended into the following trial, reflecting a sustained aspect of attention related to vigilance. The effect of alpha power did not carry over to the next trial, and furthermore mediated the effect of pupil diameter on attention ratings. Variation in SSEF power reflected stimulus processing under the influence of alpha oscillations, but were not readily expressed through subjective ratings of attention. Together, our results show that both alpha power and pupil diameter are reflected in the subjective experience of attention, albeit on different time spans, while continuous stimulus processing might not be metacognitively accessible.1Significance StatementAttention is subjectively experienced as a unified cognitive effort, in contrast with a diversity of neural and peripheral measures shown to correlate with attention. We present the first comprehensive study on the complex inter-relationship between the most common bio-physiological indices of attention, and their association with the subjective experience of attention. We show that the subjective experience of attention correlates negatively with cortical alpha oscillations, and positively with pupil diameter. The latter reflected a sustained aspect of attention, spanning several tens of seconds, related to vigilance. Alpha power, representing cortical control, fluctuated faster and mediated the effect of pupil diameter on attention. Tactile steady-state power reflected stimulus processing, also under the influence of alpha oscillations, but did not contribute much to subjective ratings of attention.
Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrosis
Authors: Fu Yang , Hu Huan , Li Meng , Xia Huasong , Liu Yue , Sun Xiaopei , Hu Yang , Song Fulin , Cheng Xiaoshu , Li Ping , Wu Yanqing 
Published: January 2020

ABSTRACTPrevious studies have demonstrated that targeting inflammation is a promising strategy for treating lipopolysaccharide (LPS)-induced sepsis and related heart injury. Interleukin-35 (IL-35), which consists of two subunits, Epstein–Barr virus-induced gene 3 (EBI3) and p35, is an immunosuppressive cytokine of the IL-12 family and exhibits strong anti-inflammatory activity. However, the role of IL-35 in LPS-induced heart injury remains obscure. In this study, we explored the role of IL-35 in heart injury induced by LPS and its potential mechanisms. Mice were treated with a plasmid encoding IL-35 (pIL-35) and then injected intraperitoneally (ip) with LPS (10 mg/kg). Cardiac function was assessed by echocardiography 12 h later. LPS apparently decreased the expression of EBI3 and p35 and caused cardiac dysfunction and pathological changes, which were significantly improved by pIL-35 pretreatment. Moreover, pIL-35 pretreatment significantly decreased the levels of cardiac proinflammatory cytokines including TNF-α, IL-6, and IL-1β, and the NLRP3 inflammasome. Furthermore, increased BCL-2 levels and decreased BAX levels inhibited apoptosis, and LPS-induced upregulation of the expression of pro-fibrotic genes (MMP2 and MMP9) was inhibited. Further investigation indicated that pIL-35 pretreatment suppressed the activation of the cardiac NF-κBp65 and TGF-β1/Smad2/3 signaling pathways in LPS-treated mice. Similar cardioprotective effects of IL-35 pretreatment were observed in mouse myocardial fibroblasts challenged with LPS in vitro. In summary, IL-35 pretreatment can attenuate cardiac inflammation, apoptosis, and fibrosis induced by LPS, implicating IL-35 as a promising therapeutic target in sepsis-related cardiac injury.
Natural selection maintains species despite widespread hybridization in the desert shrubEncelia
Authors: DiVittorio Christopher D , Singhal Sonal , Roddy Adam B , Zapata Felipe , Ackerly David D , Baldwin Bruce G , Brodersen Craig R , Burquez Alberto , Fine Paul VA , Padilla Flores Mayra , Solis Elizabeth , Morales-Villavicencio Jaime , Morales-Arce David , Kyhos Don W 
Published: January 2020

ABSTRACTNatural selection is an important driver of genetic and phenotypic differentiation between species. A powerful way to test the role of natural selection in the formation and maintenance of species is to study species complexes in which potential gene flow is high but realized gene flow is low. For a recent radiation of New World desert shrubs (Encelia: Asteraceae), we use fine-scale geographic sampling and population genomics to determine patterns of gene flow across two hybrid zones formed between two independent pairs of species with parapatric distributions. After finding evidence for extremely strong selection at both hybrid zones, we use a combination of field experiments, high-resolution imaging, and physiological measurements to determine the ecological basis for selection at one of the hybrid zones. Our results identify multiple ecological mechanisms of selection (drought, salinity, herbivory, and burial) that together are sufficient to maintain species boundaries despite high rates of hybridization. Given that multiple pairs of species hybridize at ecologically divergent parapatric boundaries in the adaptive radiation ofEncelia, such mechanisms may maintain species boundaries throughout this group.SIGNIFICANCE STATEMENTIn Baja California, the deserts meet the coastal dunes in a narrow transition visible even from satellite images. We study two species pairs of desert shrubs (Encelia) that occur across this transition. Although these species can interbreed, they remain distinct. Using a combination of genetics, field experiments, 3D-imaging, and physiological measurements, we show that natural selection counteracts the homogenizing effects of gene exchange. The different habitats of these species create multiple mechanisms of selection - drought, salinity, herbivory, and burial, which together maintain these species in their native habitats and their hybrids in intermediate habitats. This study illustrates how environmental factors influence traits and fitness and how this in turn maintain species, highlighting the importance of natural selection in speciation.
A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia
Authors: Grimes William N , Aytürk Didem Göz , Hoon Mrinalini , Yoshimatsu Takeshi , Gamlin Clare , Carrera Daniel , Ahlquist Richard M , Sabnis Adit , Diamond Jeffrey S , Wong Rachel O. , Cepko Connie , Rieke Fred 
Published: January 2020

AbstractAmacrine cells are interneurons comprising the most diverse cell type in the mammalian retina. They help encode visual features such as edges or directed motion by mediating excitatory and inhibitory interactions between input (i.e. bipolar) and output (i.e. ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, neurovascular control and metabolic regulation. Here, we report that a previously poorly characterized, but relatively abundant, inhibitory amacrine cell type in the mouse retina is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed extensive associations with Müller glia, whose processes often completely ensheathe the neurites of this amacrine cell type. Microinjections of small tracer molecules into the somas of these amacrine cells led to selective labelling of nearby Müller glia, leading us to suggest the name “Müller glia-coupled amacrine cell” or MAC. Our electrophysiological data also indicate that MACs release glycine at conventional chemical synapses with amacrine, bipolar and retinal ganglion cells (RGCs), and viral transsynaptic tracing showed connections to several known RGC types. Visually-evoked responses revealed a strong preference for light increments; these “ON” responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling to other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function.Significance StatementGap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system, and play a myriad of roles including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells are rare and poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia.
Molecular evolution of luciferase diversified bioluminescent signals in sea fireflies
Authors: Hensley Nicholai M. , Ellis Emily A. , Leung Nicole Y. , Coupart John , Mikhailovsky Alexander , Taketa Daryl A. , Tessler Michael , Gruber David F. , De Tomaso Anthony W. , Mitani Yasuo , Rivers Trevor J. , Gerrish Gretchen A. , Torres Elizabeth , Oakley Todd H. 
Published: January 2020

AbstractUnderstanding the genetic causes of evolutionary diversification is challenging because differences across species are complex, often involving many genes. However, cases where single or few genetic loci affect a feature that varies dramatically across a radiation of species would provide tractable opportunities to understand the genetics of diversification. Here, we show the diversification of bioluminescent signals in cypridinid ostracods (“sea fireflies”) to be strongly influenced by a single gene, cypridinid-luciferase. We find different evolutionary processes, including selection, drift, and constraint, each acted on c-luciferase at different times during evolutionary history and impacted different phenotypes, diversifying behavioral signals across species. In particular, some amino acid sites in c-luciferase evolved under episodic diversifying selection, and are associated significantly with phenotypic changes in both enzyme kinetics and color, which impact signals directly. We also find that multiple other amino acid positions in c-luciferase evolved neutrally or under purifying selection and may have impacted the variation of color of bioluminescent signals across genera. This work provides a rare glimpse into the genetic basis of diversification across many species, showing how multiple evolutionary processes may act at different times during a radiation of species to diversify phenotypes. These results indicate not only selection but also drift and constraint may be important evolutionary drivers of species diversification.Significance statementA hallmark of life is its astounding diversity. While we are beginning to understand the drivers of biodiversity, uncovering the genetic basis remains challenging. As such, how different molecular evolutionary processes act to diversify phenotypes is a major question in biology. Here we show a single gene to be important in a riotous diversity of fantastical behaviors - the bioluminescent signals of sea fireflies - allowing us to demonstrate multiple evolutionary forces including selection, drift, and constraint contributed to diversification. Our work highlights that not only selection but also neutral processes and constraint have each worked at different times to shape phenotypic diversity.
VINYL: Variant prIoritizatioN bY survivaL analysis
Authors: Chiara Matteo , Mandreoli Pietro , Tangaro Marco Antonio , D’Erchia Anna Maria , Sorrentino Sandro , Forleo Cinzia , Horner David S. , Zambelli Federico , Pesole Graziano 
Published: January 2020

AbstractMotivationClinical applications of genome re-sequencing technologies typically generate large amounts of data that need to be carefully annotated and interpreted to identify genetic variants associated with pathological conditions. In this context, accurate and reproducible methods for the functional annotation and prioritization of genetic variants are of fundamental importance, especially when large volumes of data - like those produced by modern sequencing technologies - are involved.ResultsIn this paper, we present VINYL, a highly accurate and fully automated system for the functional annotation and prioritization of genetic variants in large scale clinical studies. Extensive analyses of both real and simulated datasets suggest that VINYL show higher accuracy and sensitivity when compared to equivalent state of the art methods, allowing the rapid and systematic identification of potentially pathogenic variants in different experimental settings.
LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes
Authors: Bonet-Ponce Luis , Beilina Alexandra , Williamson Chad D. , Lindberg Eric , Kluss Jillian H. , Saez-Atienzar Sara , Landeck Natalie , Kumaran Ravindran , Mamais Adamantios , Bleck Christopher K. E. , Li Yan , Cookson Mark R. 
Published: January 2020

ABSTRACTMutations in the leucine rich repeat kinase 2 (LRRK2) gene are a cause of familial and sporadic Parkinson’s disease (PD). Nonetheless, the biological functions of LRRK2 remain incompletely understood. Here, we observed that LRRK2 is recruited to lysosomes that have a ruptured membrane. Using unbiased proteomics, we observed that LRRK2 is able to recruit the motor adaptor protein JIP4 to permeabilized lysosomes in a kinase-dependent manner through the phosphorylation of RAB35 and RAB10. Super-resolution live cell imaging microscopy and FIB-SEM revealed that once at the lysosomal membrane, JIP4 promotes the formation of LAMP1-negative lysosomal tubules that release membranous content from ruptured lysosomes. Released vesicular structures are able to interact with other lysosomes. Thus, we described a new process that uses lysosomal tubulation to release vesicular structures from permeabilized lysosomes. LRRK2 orchestrates this process that we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2) that, given the central role of the lysosome in PD, is likely to be disease relevant.
Comprehensive bioinformatic analysis of newly sequencedTurdoides affinismitogenome reveals the persistence of translational efficiency and dominance of NADH dehydrogenase complex-I in electron transport system over Leiothrichidae family
Authors: Sarkar Indrani , Dey Prateek , Sharma Sanjeev Kumar , Ray Swapna Devi , Singh Ram Pratap 
Published: January 2020

AbstractMitochondrial genome provides useful information about species with respect to its evolution and phylogenetics. We have taken the advantage of high throughput next-generation sequencing technique to sequence the complete mitogenome of Yellow-billed babbler (Turdoides affinis), a species endemic to Peninsular India and Sri Lanka. Both, reference-based andde-novoassemblies of mitogenome were performed and observed thatde-novoassembled mitogenome was most appropriate. The complete mitogenome of yellow-billed babbler (assembledde-novo) was 17,671 bp in length with 53.2% AT composition. Thirteen protein-coding genes along with 2 rRNAs and 22 tRNAs were detected along with duplicated control regions. The arrangement pattern of these genes was found conserved among Leiothrichidae family mitogenomes. Downstream bioinformatics analysis revealed the effect of translational efficiency and purifying selection pressure over all the thirteen protein-coding genes in yellow-billed babbler mitogenome. Moreover, genetic distance and variation analysis indicated the dominance of NADH dehydrogenase complex-I in the electron transport system ofT. affinis. Evolutionary analysis revealed the conserved nature of all the protein-coding genes across Leiothrichidae family mitogenomes. Our limited phylogenetics results suggest thatT. affinisis closer toGarrulax.