bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-human primates satisfy utility maximization in compliance with the continuity axiom of Expected Utility Theory
Authors: Ferrari-Toniolo Simone , Bujold Philipe M. , Grabenhorst Fabian , Báez-Mendoza Raymundo , Schultz Wolfram 
Published: February 2020

ABSTRACTExpected Utility Theory (EUT), the first axiomatic theory of risky choice, describes choices as a utility maximization process: decision makers assign a subjective value (utility) to each choice option and choose the one with the highest utility. The continuity axiom, central to EUT and its modifications, is a necessary and sufficient condition for the definition of numerical utilities. The axiom requires decision makers to be indifferent between a gamble and a specific probabilistic combination of a more preferred and a less preferred gamble. While previous studies demonstrated that monkeys choose according to combinations of objective reward magnitude and probability, a concept-driven experimental approach for assessing the axiomatically defined conditions for maximizing subjective utility by animals is missing. We experimentally tested the continuity axiom for a broad class of gamble types in four male rhesus macaque monkeys, showing that their choice behavior complied with the existence of a numerical utility measure as defined by the economic theory. We used the numerical quantity specified in the continuity axiom to characterize subjective preferences in a magnitude-probability space. This mapping highlighted a trade-off relation between reward magnitudes and probabilities, compatible with the existence of a utility function underlying subjective value computation. These results support the existence of a numerical utility function able to describe choices, allowing for the investigation of the neuronal substrates responsible for coding such rigorously defined quantity.SIGNIFICANCE STATEMENTA common assumption of several economic choice theories is that decisions result from the comparison of subjectively assigned values (utilities). This study demonstrated the compliance of monkey behavior with the continuity axiom of Expected Utility Theory, implying a subjective magnitude-probability trade-off relation which supports the existence of numerical subjective utility directly linked to the theoretical economic framework. We determined a numerical utility measure able to describe choices, which can serve as a correlate for the neuronal activity in the quest for brain structures and mechanisms guiding decisions.
An unbiased drug screen for seizure suppressors in Dup15q syndrome reveals 5HT1Aand dopamine pathway activation as potential therapies
Authors: Roy Bidisha , Han Jungsoo , Hope Kevin A. , Peters Tracy L. , Palmer Glen , Reiter Lawrence T. 
Published: February 2020

AbstractDuplication 15q syndrome (Dup15q) is a rare neurogenetic disorder characterized by autistic features and difficult to control (pharmacoresistant) epileptic seizures. Most individuals with isodicentric (idic15) have been on multiple medications to control their seizures and some are still seizing after years of treatment. We recently developed a model of Dup15q in Drosophila by elevating levels of fly Dube3a in glial cells, not neurons. Unlike other Dup15q models, these flies develop seizures that worsen as flies age. Here we used this new model to screen for previously approved compounds from the Prestwick Chemical Library which are able to suppress seizures in flies over-expressing Dube3a in glia using the pan glial driverrepo-GAL4. We identified 17 out of 1280 compounds in the library that could suppress a bang sensitive (seizure) phenotype. Eight of these compounds were able to suppress seizures significantly in both males and females by at least 50%. Half of these strong seizure suppressors regulated either serotoninergic or dopaminergic signaling and subsequent experiments confirmed that seizure suppression occurs through stimulation of serotonin receptor 5-HT1Abut can be further suppressed with the addition of L-Dopa (Levodopa). We provide further support for a seizure model where Dube3a regulation of the Na+/K+ exchanger ATPα in glia can also be modulated by serotonin/dopamine signaling. Finally, based on these pharmacological and genetic studies, we present an argument for the use of 5-HT1Aagonists in the treatment of Dup15q epilepsy.
SEEKING CANDIDATE MOLECULES AS PROGNOSTIC HEALING MARKERS IN CHRONIC VENOUS ULCERS
Authors: Cavassan Nayara Rodrigues Vieira , Mariani Noemia Aparecida Partelli , Camargo Caio Cavassan , Wolf Ivan Rodrigo , Barraviera Benedito , Ferreira Rui Seabra , Valente Guilherme Targino , Silva Erick José Ramos , Miot Hélio Amante , Abbade Luciana Patrícia Fernandes , dos Santos Lucilene Delazari 
Published: February 2020

ABSTRACTSeeking and identifying biomarker molecules in inflammatory exudate of chronic venous ulcers (CVUs) can aid health professionals in the healing prognosis. The therapeutic failure or cure is related to the quantitative expression of determinate proteins. This work aimed to identify the proteins expressed in inflammatory exudates from CVUs and correlate them with reduction or increase in the wound size. For 90 days, 28 participants that received standard treatment for 37 CVUs were monitored. The inflammatory exudates were collected before treatment initiation (T=0) and analyzed via the Label-free Shotgun. After 90 days the wound area was reduced in 25 (67.6%) of them. Mass spectrometry analysis of all the inflammatory exudates showed four proteins differentially expressed and related to favorable or unfavorable evolution of the healing process. Complement C3 and ceruloplasmin were identified in all the lesions analyzed and were expressed differentially in lesions that presented diminished area in the studied period. Apoliprotein A1 and neutrophil defensin-1 presented differential expression in ulcers that either did not diminish or augmented their wound area through 90 days. These results suggest that Complement C3, Ceruloplasmin, Apoliprotein A1 and Neutrophil-defensin-1 proteins are potential candidate molecules for prognostic healing markers in chronic venous ulcers.
Response to Tavares et al., “Covariation analysis with improved parameters reveals conservation in lncRNA structures”
Authors: Rivas Elena , Eddy Sean R. 
Published: February 2020

AbstractTavares’ conclusions depend on an assumption that the statistic they use (RAFS) is an appropriate measure of RNA base pair covariation, but RAFS was not designed to measure covariation alone. RAFS detects positive signals in common patterns of primary sequence conservation in absence of any covariation. To illustrate the severity of the problem, we show that Tavares’ analysis reports “significantly covarying base pairs” in 100% identical sequence alignments with no variation or covariation. We use Tavares’ sequence alignment of HOTAIR domain 1 as an example to show that the base pairs they identify as significantly covarying actually arise from primary sequence conservation patterns. Their analysis still reports similar numbers of “significant covarying” base pairs in a negative control in which we permute residues in independent alignment columns to destroy covariation. There remains no significant covariation support for evolutionarily conserved RNA structure in the HOTAIR lncRNA or other lncRNA structures and alignments we have analyzed.
Generative modeling of brain maps with spatial autocorrelation
Authors: Burt Joshua B. , Helmer Markus , Shinn Maxwell , Anticevic Alan , Murray John D. 
Published: February 2020

AbstractStudies of large-scale brain organization have revealed interesting relationships between spatial gradients in brain maps across multiple modalities. Evaluating the significance of these findings requires establishing statistical expectations under a null hypothesis of interest. Through generative modeling of synthetic data that instantiate a specific null hypothesis, quantitative benchmarks can be derived for arbitrarily complex statistical measures. Here, we present a generative null model, provided as an open-access software platform, that generates surrogate maps with spatial autocorrelation (SA) matched to SA of a target brain map. SA is a prominent and ubiquitous property of brain maps that violates assumptions of independence in conventional statistical tests. Our method can simulate surrogate brain maps, constrained by empirical data, that preserve the SA of cortical, subcortical, parcellated, and dense brain maps. We characterize how SA impactsp-values in pairwise brain map comparisons. Furthermore, we demonstrate how SA-preserving surrogate maps can be used in gene ontology enrichment analyses to test hypotheses of interest related to brain map topography. Our findings demonstrate the utility of SA-preserving surrogate maps for hypothesis testing in complex statistical analyses, and underscore the need to disambiguate meaningful relationships from chance associations in studies of large-scale brain organization.
Structure and immune recognition of the porcine epidemic diarrhea virus spike protein
Authors: Kirchdoerfer Robert N. , Bhandari Mahesh , Martini Olnita , Sewall Leigh M. , Bangaru Sandhya , Yoon Kyoung-Jin , Ward Andrew B. 
Published: February 2020

AbstractPorcine epidemic diarrhea virus is an alphacoronavirus responsible for significant morbidity and mortality in pigs. A key determinant of viral tropism and entry, the PEDV spike protein is a key target for the host antibody response and a good candidate for a protein-based vaccine immunogen. We used electron microscopy to evaluate the PEDV spike structure, as well as pig polyclonal antibody responses to viral infection. The structure of the PEDV spike reveals a configuration similar to that of HuCoV-NL63. Several PEDV protein-protein interfaces are mediated by non-protein components including a glycan at Asn264 and two bound palmitoleic acid molecules. The polyclonal antibody response to PEDV infection shows a dominance of epitopes in the S1 region. This structural and immune characterization provides new insights into coronavirus spike stability determinants and explores the immune landscape of viral spike proteins.
μ-Lat: A Mouse Model to Evaluate Human Immunodeficiency Virus Eradication Strategies
Authors: Sperber Hannah S. , Togarrati Padma Priya , Raymond Kyle A. , Bouzidi Mohamed S. , Gilfanova Renata , Gutierrez Alan G. , Muench Marcus O. , Pillai Satish K. 
Published: February 2020

AbstractA critical barrier to the development of a human immunodeficiency virus (HIV) cure is the lack of a scalable animal model that enables robust evaluation of eradication approaches prior to testing in humans. We established a humanized mouse model of latent HIV infection by transplanting “J-Lat” cells, Jurkat cells harboring a latent HIV provirus encoding an enhanced green fluorescent protein (GFP) reporter, into irradiated adult NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. J-Lat cells exhibited successful engraftment in several tissues including spleen, bone barrow, peripheral blood, and lung, in line with the diverse natural tissue tropism of HIV. Administration of tumor necrosis factor (TNF)-α, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues, reflecting viral reactivation. These data suggest that our murine latency (“μ-Lat”) model enables efficient determination of how effectively viral eradication agents, including latency reversal agents, penetrate and function in diverse anatomical sites harboring HIVin vivo.
Evidence of climate change impacts on the iconicWelwitschia mirabilisin the Namib Desert
Authors: Bombi Pierluigi , Salvi Daniele , Shuuya Titus , Vignoli Leonardo , Wassenaar Theo 
Published: February 2020

AbstractClimate change represents an important threat to global biodiversity and African ecosystems are particularly vulnerable. Recent studies predicted substantial variations of climatic suitability forWelwitschia mirabilisunder future conditions. Latitudinal/altitudinal range shifts are well-known responses to climate change but not coherent patterns were documented. This study aims to verify whether welwitschia populations are responding to climate change and if the assumption of a latitudinal/altitudinal shift is applicable. We collected field data on welwitschia distribution, health condition, reproductive status, and plant size in northern Namibia. We used ecological niche models to predict the expected geographic shift of climatic suitability under future scenarios. For each variable, we compared the observed pattern with the expected responses. Finally, we tested the presence of simple geographical gradients in the observed patterns. The realized thermal niche of welwitschia will be almost completely unavailable in the next 30 years in northern Namibia. Expected reductions of climatic suitability in the stand sites are strongly associated with indicators of negative population conditions. The same population conditions does not fit any simple latitudinal or altitudinal gradient. The observed pattern of population conditions mirrors the expected pattern of climate change effect but no simple geographical gradient was relieved. Overall, we observed negative population conditions in areas with stronger reductions of suitability. This makes welwitschia a suitable sentinel for climate change effect in the Namib Desert ecosystems. Our approach to detect population responses to climate change could be extensively adopted for selecting sentinel species in other regions and ecosystems.
Revisiting the expression signature ofpks15/1unveils regulatory patterns controlling phenolphtiocerol and phenolglycolipid production in pathogenic mycobacteria
Authors: Ramos Beatriz , Gordon Stephen V. , Cunha Mónica V. 
Published: February 2020

AbstractOne of the most relevant and exclusive characteristics of mycobacteria is its cell wall, composed by mycolic acids. Amid these are two related families of glycosylated lipids, diphthioceranates and phthiocerol dimycocerosate (PDIM) and its variant phenolic glycolipids (PGL). PGL have been associated with cell wall impermeability, phagocytosis, defence against nitrosative and oxidative stress and, supposedly, biofilm formation. In bacteria from theMycobacterium tuberculosiscomplex, the biosynthetic pathway of the phenolphthiocerol moiety of PGL depends upon the expression of several genes encoding type I polyketide synthases (PKS), namelyppsA-Eandpks15/1constituting the PDIM + PGL locus, highly conserved in PDIM/PGL-producing strains. Consensus has not been achieved regarding the genetic organization ofpks15/1locus and little effort has been put on the disclosure of its transcriptional signature. Here we explore publicly available datasets of transcriptome data (RNA-seq) from more than 100 experiments in 40 growth conditions to outline the transcriptional structure and signature ofpks15/1and use a differential expression approach to infer the regulatory patterns involving these and related genes. We show thatpks1is highly correlated withfadD22, Rv2949c, lppX, fadD29and, also,pks6andpks12, with the first three putatively integrating a polycistronic structure. We evidence dynamic heterogeneity of transcription within the genes involved in phenolphtiocerol and phenolglycolipid production, most exhibiting up-regulation upon acidic pH and antibiotic exposure and down-regulation under hypoxia, dormancy, and low/high iron concentration. We finally propose a model based on transcriptome data in which σDpositively regulatespks1, pks15andfadD22, while σBand σEfactors exert negative regulation at an upper level.
Assessing relationships between chromatin interactions and regulatory genomic activities using the self-organizing map
Authors: Kunz Timothy , Rieber Lila , Mahony Shaun 
Published: February 2020

ABSTRACTFew existing methods enable the visualization of relationships between regulatory genomic activities and genome organization as captured by Hi-C experimental data. Genome-wide Hi-C datasets are often displayed using “heatmap” matrices, but it is difficult to intuit from these heatmaps which biochemical activities are compartmentalized together. High-dimensional Hi-C data vectors can alternatively be projected onto three-dimensional space using dimensionality reduction techniques. The resulting three-dimensional structures can serve as scaffolds for projecting other forms of genomic information, thereby enabling the exploration of relationships between genome organization and various genome annotations. However, while three-dimensional models are contextually appropriate for chromatin interaction data, some analyses and visualizations may be more intuitively and conveniently performed in two-dimensional space.We present a novel approach to the visualization and analysis of chromatin organization based on the Self-Organizing Map (SOM). The SOM algorithm provides a two-dimensional manifold which adapts to represent the high dimensional chromatin interaction space. The resulting data structure can then be used to assess the relationships between regulatory genomic activities and chromatin interactions. For example, given a set of genomic coordinates corresponding to a given biochemical activity, the degree to which this activity is segregated or compartmentalized in chromatin interaction space can be intuitively visualized on the 2D SOM grid and quantified using Lorenz curve analysis. We demonstrate our approach for exploratory analysis of genome compartmentalization in a high-resolution Hi-C dataset from the human GM12878 cell line. Our SOM-based approach provides an intuitive visualization of the large-scale structure of Hi-C data and serves as a platform for integrative analyses of the relationships between various genomic activities and genome organization.
Integrating genetics with newborn metabolomics in infantile hypertrophic pyloric stenosis
Authors: Fadista João , Skotte Line , Courraud Julie , Geller Frank , Gørtz Sanne , Wohlfahrt Jan , Melbye Mads , Cohen Arieh S. , Feenstra Bjarke 
Published: February 2020

ABSTRACTBackgroundInfantile hypertrophic pyloric stenosis (IHPS) is caused by hypertrophy of the pyloric sphincter smooth muscle. Building on a previously reported association between IHPS and lipid metabolism, we aimed to (1) investigate associations between IHPS and a wide array of lipid-centric targeted metabolites in newborns, and (2) address causality of the associations by integrating genetic data.MethodsDried blood spots were taken from 267 pairs of IHPS cases and controls matched by sex and day of birth. A mixed effects linear regression model was used to evaluate associations between Biocrates p400 Kit selected 148 metabolites and IHPS in a matched case-control design.ResultsSeven metabolites showed significantly lower levels in IHPS cases. Levels of the top associated metabolite, phosphatidylcholine PC(38:4), were significantly correlated with levels of the remaining six metabolites (P<2.30 ⨯ 10−12). Associations were driven by case-control pairs with older age at sampling. IHPS cases had more diagnoses for neonatal difficulty in feeding at breast (P = 6.15 ⨯ 10−3). Genetic variants explaining a large proportion of variance in the levels of PC(38:4) did not associate with IHPS.ConclusionsWe detected lower levels of certain metabolites in IHPS, possibly reflecting different feeding patterns in the first days of life.Key points–Our previous GWAS of IHPS identified genetic associations between lipid metabolism and IHPS.–Building on that finding, this study investigated associations between a wide array of lipid-centric metabolites in newborns and IHPS.–Newborns who later developed IHPS had lower levels of certain metabolites. The associations were driven by individuals born at a later age at sampling, suggesting different feeding patterns after birth.
Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia
Authors: Hui Hui , Zhang Yingqian , Yang Xin , Wang Xi , He Bingxi , Li Li , Li Hongjun , Tian Jie , Chen Yundai 
Published: February 2020

AbstractObjectiveTo investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia.MethodsIn this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019.ResultsOf the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients.ConclusionOur results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.
Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia
Authors: Gong Jing , Dong Hui , Xia Qingsong , Huang Zhaoyi , Wang Dingkun , Zhao Yan , Liu Wenhua , Tu Shenghao , Zhang Mingmin , Wang Qi , Lu Fuer 
Published: February 2020

AbstractAimThe new coronavirus (COVID-19) pneumonia outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early.MethodsIn this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve.ResultsSignificantly, disease severity was associated with age (R=-0.564, P<0.001), interleukin-2 receptor (IL2R) (R=-0.534, P<0.001), interleukin-6 (IL-6) (R=-0.535, P<0.001), interleukin-8 (IL-8) (R=-0.308, P<0.001), interleukin-10 (IL-10) (R=-0.422, P<0.001), tumor necrosis factor α (TNFα) (R=-0.322, P<0.001), C-reactive protein (CRP) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=0.299, P=0.01).ConclusionWith following parameters such as age >67.5 years, IL2R >793.5U/mL, CRP >30.7ng/mL, ferroprotein >2252μg/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNFα and IL-8 might be promising therapeutic targets.