bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Stray Appetites’: A Socio-Ecological Analysis of Free-Ranging Dogs Living Alongside Human Communities in Bangalore, India
Authors: Bhalla Shireen Jagriti , Kemmers Roy , Vasques Ana , Vanak Abi Tamim 
Published: July 2020

AbstractAcross the developing world, humans and free-ranging domestic dogs share common spaces. The relationship between these dogs and humans can range from one of dependence, to apathy, to conflict. Given the high number of humans attacked by dogs every year in India, and the lack of an effective population control strategy, we seek to provide insights into the conflict and propose alternative population management options based on reducing the carrying capacity of the environment. We used a mixed methods approach to understand both ecological and sociological underpinnings of free-ranging dog-human relationships in Bangalore, India. We conducted a photographic capture-recapture survey of free-ranging dogs to estimate population size and linked it to the availability of potential food sources. We also conducted a qualitative survey to assess attitudes of residents towards the dog population. We found that dog population varied from 192 to 1888 per square kilometre across a gradient of housing densities. The density of houses, bakeries and garbage piles were significant predictors of dog population size. Crucially, as low as 10 to 18.3% of houses supported the large population of dogs, highlighting the need for residents to act responsibly towards the dogs. Further, we found that garbage, although significant, is a secondary food source to household-maintained dogs. Since on the whole, respondents expressed the desire for a reduction in dog population, we suggest decreasing the carrying capacity of the environment by targeting these three food sources.
Reframing Psychiatry for Precision Medicine
Authors: Torres Elizabeth B 
Published: July 2020

AbstractThe art of observing and describing behaviors has driven diagnosis and informed basic science in Psychiatry. In recent times, studies of mental illness are focused on understanding the brain’s neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In Precision Medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes genes’ expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate genes’ expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing the genes’ expressions on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological ones. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g. Autism, Schizophrenia, Depression) through DSM-observation criteria, have strong convergence with well-known neurological ones (e.g. Ataxias, Parkinson), but less overlap with non-neurological ones. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain-body connection and the contributions of the peripheral nervous systems to mental health.
A deep learning framework for high-throughput mechanism-driven phenotype compound screening
Authors: Pham Thai-Hoang , Qiu Yue , Zeng Jucheng , Xie Lei , Zhang Ping 
Published: July 2020

ABSTRACTTarget-based high-throughput compound screening dominates conventional one-drug-one-gene drug discovery process. However, the readout from the chemical modulation of a single protein is poorly correlated with phenotypic response of organism, leading to high failure rate in drug development. Chemical-induced gene expression profile provides an attractive solution to phenotype-based screening. However, the use of such data is currently limited by their sparseness, unreliability, and relatively low throughput. Several methods have been proposed to impute missing values for gene expression datasets. However, few existing methods can performde novochemical compound screening. In this study, we propose a mechanism-driven neural network-based method named DeepCE (Deep Chemical Expression) which utilizes graph convolutional neural network to learn chemical representation and multi-head attention mechanism to model chemical substructure-gene and gene-gene feature associations. In addition, we propose a novel data augmentation method which extracts useful information from unreliable experiments in L1000 dataset. The experimental results show that DeepCE achieves the superior performances not only inde novochemical setting but also in traditional imputation setting compared to state-of-the-art baselines for the prediction of chemical-induced gene expression. We further verify the effectiveness of gene expression profiles generated from DeepCE by comparing them with gene expression profiles in L1000 dataset for downstream classification tasks including drug-target and disease predictions. To demonstrate the value of DeepCE, we apply it to patient-specific drug repurposing of COVID-19 for the first time, and generate novel lead compounds consistent with clinical evidences. Thus, DeepCE provides a potentially powerful framework for robust predictive modeling by utilizing noisy omics data as well as screening novel chemicals for the modulation of systemic response to disease.
Structural models of mitochondrial uncoupling proteins obtained in DPC micelles are not physiologically relevant for their uncoupling activity
Authors: Piel Mathilde S. , Masscheleyn Sandrine , Bouillaud Frédéric , Moncoq Karine , Miroux Bruno 
Published: July 2020

AbstractUncoupling protein 1 (UCP1) is found in the inner mitochondrial membrane of brown adipocyte. In the presence of long-chain fatty acids (LCFA), UCP1 increases the proton conductance, which, in turn, increases fatty acid oxidation and energy release as heat. Several atomic models of UCP1 and UCP2 have been obtained by NMR in dodecylphosphocholine (DPC), a detergent known to inactivate UCP1. Based on NMR titration experiment on UCP1 with LCFA, it has been proposed that K56 and K269 are crucial for LCFA binding and UCP1 activation. Given the numerous controversies on the use of DPC for structure-function analyses of membrane proteins, we revisited those UCP1 mutants in a more physiological context by expressing them in the mitochondria ofS. cerevisiae. Mitochondrial respiration, assayed on permeabilized spheroplasts, enables the determination of UCP1 activation and inhibition. The K56S, K269S and K56S/K269S mutants did not display any default in activation, which shows that the NMR experiments in DPC detergent are not relevant to understand UCP1 function.
Leaf and flower consumption modulate the drinking behavior in a folivorous-frugivorous arboreal mammal
Authors: Chaves Óscar M. , Fortes Vanessa B. , Hass Gabriela P. , Azevedo Renata B. , Stoner Kathryn E. , Bicca-Marques Júlio César 
Published: July 2020

AbstractWater is vital for the survival of any species because of its key role in most physiological processes. However, little is known about the non-food-related water sources exploited by arboreal mammals, the seasonality of their drinking behavior and its potential drivers (including diet composition, temperature, and rainfall). We investigated this subject in 14 wild groups of brown howler monkeys (Alouatta guariba clamitans) inhabiting small, medium, and large Atlantic Forest fragments in southern Brazil. We found a wide variation in the mean rate of drinking among groups (range=0-16 records/day). Streams (44% of 1,258 records) and treeholes (26%) were the major types of water sources, followed by bromeliads in the canopy (16%), pools (11%), and rivers (3%). The type of source influenced whether howlers used a hand to access the water or not. Drinking tended to be evenly distributed throughout the year, except for a slightly lower number of records in the spring than in the other seasons, but it was unevenly distributed during the day. It increased in the afternoon in all groups, particularly during temperature peaks around 15:00 and 17:00. We found via generalized linear mixed modelling that the daily frequency of drinking was mainly influenced by flower (negatively) and leaf (positively) consumption, whereas fruit consumption, fragment size, rainfall, and mean ambient temperature played negligible roles. The influence of leaf consumption is compatible with the ‘metabolite detoxification hypothesis,’ which states that the processing of this fibrous food requires the ingestion of larger volumes of water to help in the detoxification/excretion of its metabolites. In sum, we found that irrespective of habitat size and climatic conditions, brown howlers seem to seek a positive water balance by complementing preformed and metabolic water with drinking water, even when it is associated with a high predation risk in terrestrial sources.
A human disease model of SARS-CoV-2-induced lung injury and immune responses with a microengineered organ chip
Authors: Zhang Min , Wang Peng , Luo Ronghua , Wang Yaqing , Li Zhongyu , Guo Yaqiong , Yao Yulin , Li Minghua , Tao Tingting , Chen Wenwen , Han Jianbao , Liu Haitao , Cui Kangli , zhang Xu , Zheng Yongtang , Qin Jianhua 
Published: July 2020

AbstractCoronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that seriously endangers human health. There is an urgent need to build physiological relevant human models for deep understanding the complex organ-level disease processes and facilitating effective therapeutics for COVID-19. Here, we first report the use of microengineered alveolus chip to create a human disease model of lung injury and immune responses induced by native SARS-CoV-2 at organ-level. This biomimetic system is able to reconstitute the key features of human alveolar-capillary barrier by co-culture of alveolar epithelial and microvascular endothelial cells under microfluidic flow. The epithelial cells on chip showed higher susceptibility to SARS-CoV-2 infection than endothelial cells identified by viral spike protein expression. Transcriptional analysis showed distinct responses of two cell types to SARS-CoV-2 infection, including activated type I interferon (IFN-I) signaling pathway in epithelium and activated JAK-STAT signaling pathway in endothelium. Notably, in the presence of circulating immune cells, a series of alveolar pathological changes were observed, including the detachment of endothelial cells, recruitment of immune cells, and increased production of inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α). These new findings revealed a crucial role of immune cells in mediating lung injury and exacerbated inflammation. Treatment with antiviral compound remdesivir could suppress viral copy and alleviate the disruption of alveolar barrier integrity induced by viral infection. This bioengineered human organ chip system can closely mirror human-relevant lung pathogenesis and immune responses to SARS-CoV-2 infection, not possible by otherin vitromodels, which provides a promising and alternative platform for COVID-19 research and preclinical trials.
Neurometabolite Mapping Highlights Elevated Myo-inositol Profiles within the Developing Brain in Down Syndrome
Authors: Patkee Prachi A. , Baburamani Ana A. , Long Katherine R. , Dimitrova Ralica , Ciarrusta Judit , Allsop Joanna , Hughes Emer , Kangas Johanna , McAlonan Grainne , Rutherford Mary A. 
Published: July 2020

AbstractThe neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer’s disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (Myo-ins). The NA+/Myo-ins co-transporter, is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain Myo-ins has previously been associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain Myo-ins is increased earlier in development.The aim of this study was to assess Myo-ins and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine(Cr)] in the developing brain in DS and aged-matched controls. To achieve this we used mass spectrometry in early (10-20 weeks post conception)ex vivofetal brain tissue samples from DS (n=14) and control (n=30) cases; andin vivomagnetic resonance spectroscopy (MRS) in neonates with DS (n=18) and aged matched controls (n= 25) scanned just after birth (36-45 weeks postmenstrual age.We observed elevated Myo-ins in theex vivofetal cortical brain tissue in DS compared with controls. Relative to reference metabolites Cho and Cr, we also detected elevated ratios of Myo-ins and NAAin vivoin the basal ganglia and thalami, in neonates with DS, when compared to age-matched typically developing controls. Thus, a higher level of brain Myo-ins was evident as early as 10 weeks post conception and was measurablein vivofrom 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.
Axon guidance at the midline – a live imaging perspective
Authors: Dumoulin Alexandre , Zuñiga Nikole R. , Stoeckli Esther T. 
Published: July 2020

ABSTRACTDuring neural circuit formation, axons navigate several choice points to reach their final target. At each one of these intermediate targets, growth cones need to switch responsiveness from attraction to repulsion in order to move on. Molecular mechanisms that allow for the precise timing of surface expression of a new set of receptors that support the switch in responsiveness are difficult to studyin vivo. Mostly, mechanisms are inferred from the observation of snapshots of many different growth cones analyzed in different preparations of tissue harvested at distinct time points. However, to really understand the behavior of growth cones at choice points, a single growth cone should be followed arriving at and leaving the intermediate target.Here, we describe a spinal cord preparation that allows for live imaging of individual axons during navigation in their intact environment. The possibility to observe single growth cones navigating their intermediate target allows for measuring growth speed, changes in morphology, or aberrant behavior. Moreover, observation of the intermediate target – the floor plate – revealed its active participation and interaction with commissural axons during midline crossing.Summary statementLive tracking of single growth cones is more informative about axonal behavior during navigation than inference of behavior from the analyses of snapshots of different growth cones.
Three-dimensional beating dynamics ofChlamydomonasflagella
Authors: Mojiri Soheil , Isbaner Sebastian , Mühle Steffen , Jang Hongje , Bae Albert Johann , Gregor Ingo , Gholami Azam , Enderlein Jörg 
Published: July 2020

AbstractAxonemes are the basic structure of motile cilia and flagella, and the investigation of how they function and move requires rapid three-dimensional imaging. We built a multi-plane phase-contrast microscope for imaging the three-dimensional motion of unlabeled flagella of the model organismChlamydomonas reinhardtiiwith sub-μm spatial and 4 ms temporal resolution. This allows us to observe not only bending but also the three-dimensional torsional dynamics of these small structures. We observe that flagella swim counter-clockwise close to a surface, with negatively-valued torsion at their basal and positively-valued torsion at their distal tips. To explain the torsional dynamics and signature, we suggest the existence of an intrinsic negative twist at the basal end that is untwisted by active positive-twist-inducing dynein motor proteins. Moreover, dyneins walking towards the basal induce an opposite twist at the distal tip. Bending of the whole axoneme structure then translates this twist into an observable torsion. This interconnection between chiral structure, twist, curvature, and torsion is fundamental for understanding flagellar mechanics.
Light-powered reactivation of flagella and contraction of microtubules network: towards building an artificial cell
Authors: Ahmad Raheel , Kleineberg Christin , Nasirimarekani Vahid , Su Yu-Jung , Pozveh Samira Goli , Bae Albert , Sundmacher Kai , Bodenschatz Eberhard , Guido Isabella , Vidakovic-Koch Tanja , Gholami Azam 
Published: July 2020

AbstractArtificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications including medical treatments but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella that provide ATP for dynein molecular motors upon illumination. The flagellar propulsion is coupled to the beating frequency and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles inin vitromotility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.Graphical TOC Entry
Fluorescence Correlation and Cross-Correlation Spectroscopy Unveil Cytoplasmic mRNP Composition and Dynamics
Authors: Mateu-Regué Àngels , Christiansen Jan , Hellriegel Christian , Nielsen Finn Cilius 
Published: July 2020

ABSTRACTUnderstanding the mRNA life cycle requires analysis of the dynamic macromolecular composition and stoichiometry of mRNPs. Fluorescence correlation and cross-correlation spectroscopy (FCS and FCCS) are appealing technologies to study mRNP complexes because they readily provide information about the molecular composition, stoichiometry, heterogeneity and dynamics of the particles. We developed FCS protocols for analysis of live cells and cellular lysates, and demonstrate the feasibility of analysing common cytoplasmic mRNPs composed of core factor YBX1, IMPs (or IGF2BPs) and their interactions with other RNA binding proteins such as PABPC1, ELAVL2 (HuB), STAU1 and FMRP. FCCS corroborated previously reported RNA dependent interactions between the factors and provided an estimate of the relative overlap between the factors in the mRNPs. In this way FCS and FCCS provide a new and useful approach for the quantitative and dynamic analysis of mRNP macromolecular complexes that may complement current biochemical approaches.
Sex-specific speed-accuracy tradeoffs shape neural processing of acoustic signals in a grasshopper
Authors: Clemens Jan , Ronacher Bernhard , Reichert Michael S. 
Published: July 2020

AbstractSpeed-accuracy tradeoffs – being fast at the risk of being wrong – are fundamental to many decisions and natural selection is expected to resolve these tradeoffs according to the costs and benefits of behavior. We here test the prediction that females and males should integrate information from courtship signals differently because they experience different payoffs along the speed-accuracy continuum. We fitted a neural model of decision making (a drift-diffusion model of integration to threshold) to behavioral data from the grasshopperChorthippus biguttulusto determine the parameters of temporal integration of acoustic directional information used by male grasshoppers to locate receptive females. The model revealed that males had a low threshold for initiating a turning response, yet a large integration time constant enabled them to continue to gather information when cues were weak. This contrasts with parameters estimated for females of the same species when evaluating potential mates, in which response thresholds were much higher and behavior was strongly influenced by unattractive stimuli. Our results reveal differences in neural integration consistent with the sex-specific costs of mate search: Males often face competition and need to be fast, while females often pay high error costs and need to be deliberate.
Ether lipid and sphingolipid expression patterns are G-protein coupled estrogen receptor 1-dependently altered in breast cancer cells
Authors: Hahnefeld Lisa , Gruber Lisa , Schömel Nina , Fischer Caroline , Mattjus Peter , Gurke Robert , Beretta Martina , Ferreirós Nerea , Geisslinger Gerd , Wegner Marthe-Susanna 
Published: July 2020

AbstractIdentifying co-expression of lipid species is challenging, but indispensable to identify novel therapeutic targets for breast cancer treatment. Lipid metabolism is often dysregulated in cancer cells, and changes in lipid metabolism affect cellular processes such as proliferation, autophagy, and tumor development. In addition to mRNA analysis of sphingolipid metabolizing enzymes, we performed liquid chromatography time-of-flight mass spectrometry analysis in three breast cancer cell lines. These breast cancer cell lines differ in estrogen receptor and G-protein coupled estrogen receptor 1 status. Our data show that sphingolipids and non-sphingolipids are strongly increased in SKBr3 cells. SKBr3 cells are estrogen receptor negative and G-protein coupled estrogen receptor 1 positive. Treatment with G15, a G-protein coupled estrogen receptor 1 antagonist, abolishes the effect of increased sphingolipid and non-sphingolipid levels in SKBr3 cells. In particular, ether lipids are expressed at much higher levels in cancer compared to normal cells and are strongly increased in SKBr3 cells. Our analysis reveals that this is accompanied by increased sphingolipid levels such as ceramide, sphingadiene-ceramide and sphingomyelin. This shows the importance of focusing on more than one lipid class when investigating molecular mechanisms in breast cancer cells. Our analysis allows unbiased screening for different lipid classes leading to identification of co-expression patterns of lipids in the context of breast cancer. Co-expression of different lipid classes could influence tumorigenic potential of breast cancer cells. Identification of co-regulated lipid species is important to achieve improved breast cancer treatment outcome.HighlightsLC-HRMS analysis allows identification of co-expression between lipid classesPutative co-expression of sphingolipid and non-sphingolipid classesEther lipids are strongly upregulated in SKBr3 cells (ER negative, GPER1 positive)