bluuebunny/crossref_metadata_2025_split huggingface dataset:
Test-retest reliability of force plate-derived measures of reactive stepping
Authors: Saumur Tyler M. , Mathur Sunita , Nestico Jacqueline , Perry Stephen D. , Mochizuki George , Mansfield Avril 
Published: May 2020

AbstractBackgroundCharacterizing reactive stepping is important to describe the response’s effectiveness. Measures of reactive stepping related to step initiation, execution, and termination phases have been frequently reported to characterize reactive balance control. However, the test-retest reliability of these measures are unknown.Research questionsWhat is the between- and within-session test-retest reliability of various force plate-derived measures of reactive stepping?MethodsNineteen young, healthy adults responded to 6 small (~8-10% of body weight) and 6 large perturbations (~13-15% of body weight) using an anterior lean-and-release system. Tests were conducted on two visits separated by at least two days. Participants were instructed to recover balance in as few steps as possible. Step onset, foot-off, swing, and restabilization times were extracted from force plates. Relative test-retest reliability was determined through intraclass correlation coefficients (ICCs) and 95% confidence intervals (CIs). Absolute test-retest reliability was assessed using the standard error of the measurement (SEM).ResultsFoot-off and swing times had the highest between- and within-session test-retest reliabilities regardless of perturbation size (between-session ICC=0.898–0.942; within-session ICC=0.455–0.753). Conversely, step onset and restabilization time had lower ICCs and wider CIs (between-session ICC=0.495–0.825; within-session ICC=−0.040–0.174). Between-session test-retest reliability was higher (ICC=0.495-0.942) for all measures than within-session test-retest reliability (ICC=−0.040–0.753). SEMs were low (3–10% of mean) for all measures, except time to restabilization (SEM=15-20% of mean), indicating good absolute reliability.SignificanceThese findings suggest multiple baseline sessions are needed for measuring restabilization and step onset times. The SEMs provide an index for measuring meaningful change due to an intervention.
Eating to dare - Nutrition impacts human risky decision and related brain function
Authors: Liu Lu , Artigas Sergio Oroz , Ulrich Anja , Tardu Jeremy , Mohr Peter N. C. , Wilms Britta , Koletzko Berthold , Schmid Sebastian M. , Park Soyoung Q. 
Published: May 2020

AbstractMacronutrient composition modulates plasma amino acids that are precursors of neurotransmitters and can impact brain function and decisions. Neurotransmitter serotonin has been shown to regulate not only food intake, but also economic decisions. We investigated whether an acute nutrition-manipulation inducing plasma tryptophan fluctuation affects brain function, thereby affecting risky decisions. Breakfasts differing in carbohydrate/protein ratios were offered to test changes in risky decision making while metabolic and neural dynamics were tracked. We identified that a high-carbohydrate/protein meal increased plasma tryptophan which mapped to individual risk propensity changes. Moreover, the meal-driven fluctuation in tryptophan and risk propensity changes were modulated by individual difference in body fat mass. Using fMRI, we further identified activation in the parietal lobule during risk-processing, of which activities 1) were correlated with the risk propensity changes in decision making, 2) were sensitive to the tryptophan fluctuation, and 3) were modulated by individual’s body fat mass. Furthermore, the activity in the parietal lobule positively mediated the tryptophan-fluctuation to risk-propensity-changes relationship. Our results provide evidence for a personalized nutrition-driven modulation on human risky decisions and its metabolic and neural mechanisms.
Antibiotics in microbial communities: an ecological frame of resistance
Authors: Letten Andrew D. , Hall Alex , Levine Jonathan 
Published: May 2020

AbstractThere is growing awareness that our ability to tackle antibiotic resistance is limited by a lack of mechanistic understanding of the communities in which resistant microbes are embedded. The widespread coexistence of resistant and sensitive bacteria in microbial systems presents an especially frustrating paradox. Recent advances in ecological coexistence theory offer a powerful framework to probe the mechanisms regulating intra- and inter-specific coexistence, but the significance of this body of theory to the problem of antimicrobial resistance has been largely overlooked. In this Perspectives article, we draw on emerging ecological theory to illustrate how changes in both competitive ability and niche overlap are critical for understanding costs of resistance and the persistence of pathogens in microbial systems. We then show how trade-offs in resource acquisition strategies can have counter-intuitive consequences for the coexistence of resistant and susceptible genotypes in variable environments. These insights highlight numerous opportunities for innovative experimental and theoretical research into antibiotic resistance in the microbiome.
Metabolomic signatures of coral bleaching history
Authors: Roach Ty N.F. , Dilworth Jenna , Christian Martin H. , Jones A. Daniel , Quinn Robert , Drury Crawford 
Published: May 2020

AbstractCoral bleaching, a process where corals expel their photosynthetic symbionts, has a profound impact on the health and function of coral reefs. As global ocean temperatures continue to rise, bleaching poses the greatest threat to coral reef ecosystems. Here, untargeted metabolomics was used to analyze the biochemicals in pairs of adjacent corals from a patch reef in Kāne‘ohe Bay, Hawai‘i, where one colony in the pair bleached (in 2015) and recovered while the other did not bleach. There was a strong metabolomic signature of prior bleaching history four years after recovery found in both the host and its algal symbionts. Machine learning analysis determined that the strongest metabolite drivers of the difference in bleaching phenotype were a group of betaine lipids. Those with saturated fatty acids were significantly enriched in thermally tolerant corals and those with longer, unsaturated and diacyl forms were enriched in historically bleached corals. Host immune response molecules, Lyso-PAF and PAF, were also altered by bleaching history and were strongly correlated with symbiont community and algal-derived metabolites suggesting a role of coral immune modulation in symbiont choice and bleaching response. To validate these findings, we tested a separatein situset of corals and were able to predict the bleaching phenotype with 100% accuracy. Furthermore, corals subjected to an experimental temperature stress had strong phenotype-specific responses in all components of the holobiont, which served to further increase the differences between historical bleaching phenotypes. Thus, we show that natural bleaching susceptibility is simultaneously manifested in the biochemistry of the coral animal and the algal symbiont and that this bleaching history results in different physiological responses to temperature stress. This work provides insight into the biochemical mechanisms involved in coral bleaching and presents a valuable new tool for resilience-based reef restoration.
CEN-tools: An integrative platform to identify the ‘contexts’ of essential genes
Authors: Sharma Sumana , Dincer Cansu , Weidemüller Paula , Wright Gavin J , Petsalaki Evangelia 
Published: May 2020

I.ABSTRACTAn emerging theme from large-scale genetic screens that identify genes essential for fitness of a cell, is that essentiality of a given gene is highly context-specific and depends on a number of genetic and environmental factors. Identification of such contexts could be the key to defining the function of the gene and also to develop novel therapeutic interventions. Here we present CEN-tools (Context-specificEssentialityNetwork-tools), a website and an accompanying python package, in which users can interrogate the essentiality of a gene from large-scale genome-scale CRISPR screens in a number of biological contexts including tissue of origin, mutation profiles, expression levels, and drug response levels. We show that CEN-tools is suitable for both the systematic identification of genetic dependencies as well as for targeted queries into the dependencies of specific user-selected genes. The associations between genes and a given context within CEN-tools are represented as dependency networks (CENs) and we demonstrate the utility of these networks in elucidating novel gene functions. In addition, we integrate the dependency networks with existing protein-protein interaction networks to reveal context-dependent essential cellular pathways in cancer cells. Together, we demonstrate the applicability of CEN-tools in aiding the current efforts to define the human cellular dependency map.
Sensorimotor hallucinations in Parkinson’s disease
Authors: Bernasconi Fosco , Blondiaux Eva , Potheegadoo Jevita , Stripeikyte Giedre , Pagonabarraga Javier , Bejr-Kasem Helena , Bassolino Michela , Akselrod Michel , Martinez-Horta Saul , Sampedro Fred , Hara Masayuki , Horvath Judit , Franza Matteo , Konik Stéphanie , Bereau Matthieu , Ghika Joseph-André , Burkhard Pierre R. , Van De Ville Dimitri , Faivre Nathan , Rognini Giulio , Krack Paul , Kulisevsky Jaime , Blanke Olaf 
Published: May 2020

SummaryHallucinations in Parkinson’s disease (PD) are one of the most disturbing non-motor symptoms, affect half of the patients, and constitute a major risk factor for adverse clinical outcomes such as psychosis and dementia. Here we report a robotics-based approach, enabling the induction of a specific clinically-relevant hallucination (presence hallucination, PH) under controlled experimental conditions and the characterization of a PD subgroup with enhanced sensorimotor sensitivity for such robot-induced PH. Using MR-compatible robotics in healthy participants and lesion network mapping analysis in neurological non-PD patients, we identify a fronto-temporal network that was associated with PH. This common PH-network was selectively disrupted in a new and independent sample of PD patients and predicted the presence of symptomatic PH. These robotics-neuroimaging findings determine the behavioral and neural mechanisms of PH and reveal pathological cortical sensorimotor processes of PH in PD, identifying a more severe form of PD associated with psychosis and cognitive decline.
HCR-FlowFISH: A flexible CRISPR screening method to identify cis-regulatory elements and their target genes
Authors: Reilly SK , Gosai SJ , Gutierrez A , Ulirsch JC , Kanai M , Berenzy D , Kales S , Butler GB , Gladden-Young A , Finucane HK , Sabeti PC , Tewhey R 
Published: May 2020

AbstractCRISPR screens for cis-regulatory elements (CREs) have shown unprecedented power to endogenously characterize the non-coding genome. To characterize CREs we developed HCR-FlowFISH (Hybridization Chain Reaction Fluorescent In-Situ Hybridization coupled with Flow Cytometry), which directly quantifies native transcripts within their endogenous loci following CRISPR perturbations of regulatory elements, eliminating the need for restrictive phenotypic assays such as growth or transcript-tagging. HCR-FlowFISH accurately quantifies gene expression across a wide range of transcript levels and cell types. We also developed CASA (CRISPR Activity Screen Analysis), a hierarchical Bayesian model to identify and quantify CRE activity. Using >270,000 perturbations, we identified CREs forGATA1, HDAC6, ERP29, LMO2, MEF2C, CD164, NMU, FEN1and theFADSgene cluster. Our methods detect subtle gene expression changes and identify CREs regulating multiple genes, sometimes at different magnitudes and directions. We demonstrate the power of HCR-FlowFISH to parse genome-wide association signals by nominating causal variants and target genes.
Recognition memory via repetition suppression in mouse hippocampal dorsal CA2 pyramidal neurons expressing the vasopressin 1b receptor
Authors: Cymerblit-Sabba Adi , Stackmann Michelle , Avram Sarah K. Williams , Granovetter Michael C. , Cliz Nicholas I. , Pereira Francisco , Smith Adam S. , Song June , Lee Heon-Jin , Young W. Scott 
Published: May 2020

AbstractRecognition memory, often compromised in psychiatric disorders, is a major component of declarative memory, which permits the realization that an event, object or social subject has been previously encountered. The CA2 region of the dorsal hippocampus (dCA2) is involved in social memory and responds to novel objects, in time and space. However, it remains unclear how these neurons encode either social or inanimate object recognition. Here, we show that in dCA2, encoding of social recognition memory entails suppression of pyramidal neurons’ activity leading to a sparse representation of the familiar conspecific. We discuss the neural coding scheme by which dCA2 pyramidal neurons contribute to social memory.
Transcriptome signature ofE. coliunder a prolonged starvation environment
Authors: Takano Sotaro , Takahashi Hiromi , Yama Yoshie , Miyazaki Ryo , Tsuru Saburo 
Published: May 2020

ABSTRACTBackground“Non-growing” is a dominant life form of microorganisms in nature, where available nutrients and resources are extremely limited. However, the knowledge of the manner in which microorganisms resist nutrient deficiency is still rudimentary compared to those of the growing cells. In laboratory culture,Escherichia colican survive for several years under starvation, denoted as long-term stationary phase (LSP), where a small fraction of the cells survive by recycling resources released from the starved nonviable cells and constitute a model system for understanding survival mechanisms under long-term starvation. Although the physiology by which viable cells in LSP adapt to long-term starvation is of great interest, their genome-wide response has not yet been fully understood.ResultsTo understand the physiological state of viable cells in the LSP environment, we analyzed the transcriptional profiles of cells exposed to the supernatant of LSP culture. We found that high expression of transporter genes and low expression of biosynthesis genes are the primary responses of the cells in the LSP supernatant compared to growing cells, which display similar responses to cells entering the stationary phase from the exponential growth phase. We also revealed some specific transcriptional responses in the LSP supernatant, such as higher expression of stress-response genes and lower expression of translation-related genes, compared to other non-growing conditions. This suggests that cells in LSP are highly efficient in terms of cellular survival and maintenance functions under starvation conditions. We also found population-density-dependent gene expression profiles in LSP, which are also informative to understand the survival mechanism of bacterial population.ConclusionOur current comprehensive analysis of the transcriptome ofE. colicells provides an overview of the genome-wide response to the long-term starvation environment. We detected both common and distinctive responses in the primary transcriptional changes between the short- and long-term stationary phase cultures, which could provide clues to understand the possible molecular mechanisms underlying survivability in the starved environment.
A computer vision approach for studying fossorial and cryptic crabs
Authors: Herrera César , Sheaves Janine , Baker Ronald , Sheaves Marcus 
Published: May 2020

SummaryDespite the increasing need to catalogue and describe biodiversity and the ecosystem processes it underpins, these tasks remain inherently challenging. This is particularly true for species that are difficult to observe in their natural environment, such as fossorial and cryptic crabs that inhabit intertidal sediments. Traditional sampling techniques for intertidal crabs are often invasive, labour intensive and/or inconsistent. These factors can limit the amount and type of data that can be collected which in turn hinders our ability to obtain reliable ecological estimates and compare findings between studies. Computer vision and machine learning algorithms present an opportunity to innovate and improve sampling approaches. Moreover, cheaper and tougher recording devices and the diversity of open source software further boost the possibilities of achieving rigorous image-based sampling, which can broaden the range of questions that can be addressed from the data collected. Despite its significant potential, the software and algorithms associated with image-based sampling may be daunting to researchers without expertise in computer vision. Therefore, there is a need to develop protocols and data processing workflows to showcase the value of embracing new technologies. This paper presents a non-invasive computer vision and learning protocol for sampling fossorial and cryptic crabs in their natural environment. The image-based protocol is underpinned by fit-for-purpose and off-the-shelf software. We demonstrate this approach using fiddler crab and sediment recordings to study and quantify crab abundance, motion patterns, behaviour, intraspecific interactions, and estimate bioturbation rates. We discuss current limitations in this protocol and identify opportunities for improvement and additional data stream options that can be obtained from this approach. We conclude that this protocol can overcome some of the limitations associated with traditional techniques for sampling intertidal crabs, and could be applied to other taxa or ecosystems that present similar challenges. We believe this sampling and analytical framework represents an important step forward in understanding the ecology of species and their functional role within ecosystems.
Cellular water analysis in T cells reveals a switch from metabolic water gain to water influx
Authors: Saragovi A , Zilberman T , Yasur G , Turjeman K , Abramovich I , Kuchersky M , Gottlieb E , Barenholz Y , Berger M 
Published: May 2020

AbstractCell growth is driven by the acquisition and synthesis of dry biomass and water mass. This study examines the increase of water in T cells biomass during cell growth. We found that T cell growth is initiated by a phase of slow increase of cellular water, followed by a second phase of rapid increase in water content. To study the origin of the water gain, we developed a novel method, Cold Aqua Trap – Isotope Ratio Mass Spectrometry (CAT-IRMS), which allows analysis of intracellular water isotope composition. Applying CAT-IRMS, we discovered that glycolysis-coupled metabolic water accounts on average for 11 femtoliter (fL) out of the 20 fL of water gained per cell during the slow phase. At the end of the rapid phase, before initiation of cell division, a water influx occurs, increasing the water level by three-fold. Thus, activated T cells switch from acquiring metabolic water to incorporating water from the extracellular medium. Our work provides a method to analyze cell water content and an insight into the way cells regulate their water mass.
Intra-dimer cooperativity between the active site cysteines during the oxidation of peroxiredoxin 2
Authors: Peskin Alexander V , Meotti Flávia C , de Souza Luiz F , Anderson Robert F , Winterbourn Christine C , Salvador Armindo 
Published: May 2020

ABSTRACTPeroxiredoxin 2 (Prdx2) and other typical 2-Cys Prdxs function as homodimers in which hydrogen peroxide oxidizes each active site cysteine to a sulfenic acid which then condenses with the resolving cysteine on the alternate chain. Previous kinetic studies have considered both sites as equally reactive. Here we have studied Prdx2 using a combination of non-reducing SDS-PAGE to separate reduced monomers and dimers with one and two disulfide bonds, and stopped flow analysis of tryptophan fluorescence, to investigate whether there is cooperativity between the sites. We have observed positive cooperativity when H2O2is added as a bolus and oxidation of the second site occurs while the first site is present as a sulfenic acid. Modelling of this reaction showed that the second site reacts 2.2 ± 0.1 times faster. In contrast, when H2O2was generated slowly and the first active site condensed to a disulfide before the second site reacted, no cooperativity was evident. Conversion of the sulfenic acid to the disulfide showed negative cooperativity, with modelling of the exponential rise in tryptophan fluorescence yielding a rate constant of 0.75 ± 0.08 s-1when the alternate active site was present as a sulfenic acid and 2.29 ± 0.08-fold lower when it was a disulfide. No difference in the rate of hyperoxidation at the two sites was detected. Our findings imply that oxidation of one active site affects the conformation of the second site and influences which intermediate forms of the protein are favored under different cellular conditions.
Alternative splicing and gene expression play contrasting roles in the parallel phenotypic evolution of a salmonid fish
Authors: Jacobs Arne , Elmer Kathryn R. 
Published: May 2020

AbstractUnderstanding the contribution of different molecular processes to the evolution and development of divergent phenotypes is crucial for identifying the molecular routes of rapid adaptation. Here, we used RNA-seq data to compare patterns of alternative splicing and differential gene expression in a case of parallel adaptive evolution, the replicated postglacial divergence of the salmonid fish Arctic charr (Salvelinus alpinus) into benthic and pelagic ecotypes across multiple independent lakes.We found that genes that were differentially spliced and differentially expressed between the benthic and pelagic ecotypes were mostly independent (<6% overlap) and were involved in different processes. Differentially spliced genes were primarily enriched for muscle development and functioning, while differentially expressed genes were mostly involved in energy metabolism, immunity and growth. Together, these likely explain different axes of divergence between ecotypes in swimming performance and activity. Furthermore, we found that alternative splicing and gene expression are mostly controlled by independent cis-regulatory quantitative trait loci (<3.4% overlap). Cis-regulatory regions were associated with the parallel divergence in splicing (16.5% of intron clusters) and expression (6.7 - 10.1% of differentially expressed genes), indicating shared regulatory variation across ecotype pairs. Contrary to theoretical expectation, we found that differentially spliced genes tended to be highly central in regulatory networks (‘hub genes’) and were annotated to significantly more gene ontology terms compared to non-differentially spliced genes, consistent with a higher level of connectivity and pleiotropy.Together, our results suggest that the concerted regulation of alternative splicing and differential gene expression through different regulatory regions leads to the divergence of complementary phenotypes important for local adaptation. This study provides novel insights into the importance of contrasting but putatively complementary molecular processes for rapid and parallel adaptive evolution.