bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-Tetrahydropalmatine, a Novel Dopamine Antagonist, Fails to Improve Psychiatric Symptoms as Adjunctive Treatment for Schizophrenia
Authors: Ponomareva Olga Y , Redman Brianne , Sayer MacKenzie A , Wehring Heidi J , Vyas Gopal , Richardson Charles M , Gold James M , Gorelick David A , Cihakova Daniela , Talor Monica V , Hoag Stephen W , Buchanan Robert W , Wang Jingtao , Chen Shuo , Liu Fang , Wang Jia Bei , Kelly Deanna L 
Published: May 2020

Abstract
Schizophrenia is a complex mental illness characterized by positive and negative symptoms. Antipsychotic medications are the main treatment for this condition; however, many patients have only a partial response. All currently available antipsychotics involve modulation of the dopamine system, although the underlying pathophysiology of this illness remains poorly understood. Increasing evidence suggests that inflammation plays a significant role in the development of schizophrenia. Thus, a medication that modulates both dopamine signaling and inflammation may be a promising treatment for schizophrenia. L-tetrahydropalmatine (l-THP) has modest affinity for dopamine receptors, acting as an antagonist at D1, D2, and D3 receptors. L-THP also has anti-inflammatory effects, decreasing levels of tumor necrosis factor-α and interleukin 6. We performed a 4-week, randomized, double-blind, placebo-controlled trial of oral l-THP (30 mg twice daily) as an adjunctive treatment in 63 adults with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) on stable antipsychotic medication. The primary psychiatric outcome measures were the presence of positive and negative symptoms. Plasma concentrations of 11 cytokines and C-reactive protein (CRP) were also measured. L-THP had no significant effect on any psychiatric measure but was well tolerated and associated with a significant decrease in extrapyramidal symptoms. L-THP significantly increased plasma concentrations, compared with placebo, of two inflammatory markers: soluble intracellular adhesion molecule 1 and CRP. These findings do not support the efficacy of L-THP as an add-on treatment for schizophrenia but suggest that L-THP may have previously unrecognized proinflammatory effects in people with this disease.
Effect of feed supplementation of Dacryodes edulis parts’ powder as prebiotic on the growth traits, ceca microbiota and blood parameters of local chickens
Authors: Tangomo Armel Ngnintedem , Keambou Christian Tiambo , Gicheha Mathew Gitau , Kagira John Maina 
Published: May 2020

AbstractThis study aimed at testing the efficacy and safety of Dacryodes edulis plant parts in diets fed to chicken. The plant has potential for use as a natural prebiotic to substitute the conventionally used antibiotic growth promoters in poultry production. Phytochemical analyses of the plant leaves, stem, and bark combination (stembark) and seed powders from the D. edulis were carried out. The powder from the three D. edulis plant parts were used as supplement in formulating six experimental diets tested in this study. The diets were TL0Ed (0.5% leaves powder), TL1Ed (1.0% leaves powder), TB0Ed (0.5% stembark powder), TB1Ed (1.0% stembark powder), TS0Ed (0.5% seeds powder), and TS1Ed (1.0% seeds powder). Besides, a positive (T+ positive control; 0.5-g oxytetracycline as recommended by the manufacturer) and a negative (T- negative control; having no commercial antibiotic and no plant supplement) diets were prepared for comparison purposes. The diets were fed to a total of 288 dual-purpose chicken for a period of 14 weeks. The chicken growth and body composition characteristics, blood chemistry, and microbiota count were collected and used as indicators of the plant parts efficacy and safety. The analysis of the D. edulis plant parts significantly differed (P ≤ 0.05) in their phytochemical contents. The initial body weight and feed conversion efficiency ratios were not significantly different (P ≥ 0.05) between and among treatment groups. However, significant differences (P ≤ 0.05) were detected in the feed intake and body weight gain at eighth week. Live weight at eighth week was significantly different (P ≤ 0.05) with its values ranging between 503.32 and 614.93 g for treatments TL1Ed and TNeg-, respectively. The dietary treatment of D. edulis leaves, stembark, and seed powder at the two inclusion levels significantly (P ≤ 0.05) decreased the colonies forming unit of Escherichia coli and Salmonella sp. as compared with negative control treatment in the eighth week phase. The level of glucose, total cholesterol, triglycerides, aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and the packed cell volume did not differ significantly (P ≥ 0.05) between and among dietary D. edulis treatments. The findings from this research provide crucial information on the efficacy and safety of D. edulis plant parts. This is an important step in testing the potential of the plant in use as a prebiotic in chicken feeds production.
Replacement of non-conforming goods ‘free of charge’: is there a need to differentiate between B2B and B2C sales contracts?
Authors: Atamer Yeşim M 
Published: May 2020

Abstract
The buyer’s right to request replacement of any non-conforming goods is today a standard remedy in many jurisdictions. This development was also influenced by the widespread effect of the United Nations Convention on Contracts for the International Sale of Goods (CISG) and the Council Directive (EC) 1999/44 on consumer sales, which both grant the buyer a right to replacement. However, some questions related to the requirement that replacement has to be ‘free of charge’ continue to be disputed under both legal systems, as well as under the newly introduced Council Directive (EC) 2019/771 on consumer sales. This article intends to discuss how the term ‘free of charge’ is being interpreted in business-to-business as well as in business-to-consumer sales contracts and whether there is any need to differentiate between the two types of sales contracts.
People Behavior Changes in China during COVID-19 Pandemic
Authors: Wu Yongzhong , Huang Mianmian , Xie Guie , Chen Xiangying 
Published: May 2020

AbstractWhile most countries implemented measures to reduce people activities and gathering to contain the coronavirus, the outcome may vary significantly depending on how and to what extent people behaviors have been changed. We conducted a survey of 1,048 people in five major cities in China to track and quantify the behavior changes in different periods since the outbreak. It is found that there was nearly 80% reduction of out-of-home activities (working, eating, shopping, taking public transportation, and travelling) during the peak period. Such activities are gradually increasing after the easing of containment measures but still significantly below pre-outbreak level. The significant behavior changes have contributed to the rapid control of virus transmission in China. While countries are reopening the economies before the virus disappears, the system and capacity of testing and contact tracing should be carefully designed with the tracking of people behavior changes in the future.
Global Root Traits (GRooT) Database
Authors: Guerrero-Ramirez Nathaly , Mommer Liesje , Freschet Grégoire T. , Iversen Colleen M. , McCormack M. Luke , Kattge Jens , Poorter Hendrik , van der Plas Fons , Bergmann Joana , Kuyper Thom W. , York Larry M. , Bruelheide Helge , Laughlin Daniel C. , Meier Ina C. , Roumet Catherine , Semchenko Marina , Sweeney Christopher J. , van Ruijven Jasper , Valverde-Barrantes Oscar J. , Aubin Isabelle , Catford Jane A. , Manning Peter , Martin Adam , Milla Rubén , Minden Vanessa , Pausas Juli G. , Smith Stuart W. , Soudzilovskaia Nadejda A. , Ammer Christian , Butterfield Bradley , Craine Joseph , Cornelissen Johannes H.C. , de Vries Franciska T. , Isaac Marney E. , Kramer Koen , König Christian , Lamb Eric G. , Onipchenko Vladimir G. , Peñuelas Josep , Reich Peter B. , Rillig Matthias C. , Sack Lawren , Shipley Bill , Tedersoo Leho , Valladares Fernando , van Bodegom Peter , Weigelt Patrick , Wright Justin P. , Weigelt Alexandra 
Published: May 2020

AbstractMotivationTrait data are fundamental to quantitatively describe plant form and function. Although root traits capture key dimensions related to plant responses to changing environmental conditions and effects on ecosystem processes, they have rarely been included in large-scale comparative studies and global models. For instance, root traits remain absent from nearly all studies that define the global spectrum of plant form and function. Thus, to overcome conceptual and methodological roadblocks preventing a widespread integration of root trait data into large-scale analyses we created the Global Root Trait (GRooT) Database. GRooT provides ready-to-use data by combining the expertise of root ecologists with data mobilization and curation. Specifically, we (i) determined a set of core root traits relevant to the description of plant form and function based on an assessment by experts, (ii) maximized species coverage through data standardization within and among traits, and (iii) implemented data quality checks.Main types of variables containedGRooT contains 114,222 trait records on 38 continuous root traits.Spatial location and grainGlobal coverage with data from arid, continental, polar, temperate, and tropical biomes. Data on root traits derived from experimental studies and field studies.Time period and grainData recorded between 1911 and 2019Major taxa and level of measurementGRooT includes root trait data for which taxonomic information is available. Trait records vary in their taxonomic resolution, with sub-species or varieties being the highest and genera the lowest taxonomic resolution available. It contains information for 184 sub-species or varieties, 6,214 species, 1,967 genera and 254 families. Due to variation in data sources, trait records in the database include both individual observations and mean values.Software formatGRooT includes two csv file. A GitHub repository contains the csv files and a script in R to query the database.
Inversion of pheromone preference optimizes foraging inC. elegans
Authors: Dal Bello M. , Pérez-Escudero A. , Schroeder F. C. , Gore J. 
Published: May 2020

SummaryForaging animals have to locate food sources that are usually patchily distributed and subject to competition. Deciding when to leave a food patch is challenging and requires the animal to integrate information about food availability with cues signaling the presence of other individuals (e.g. pheromones). To study how social information transmitted via pheromones can aid foraging decisions, we investigated the behavioral responses of the model nematodeCaenorhabditis elegansto food depletion and pheromone accumulation in food patches. We experimentally show that animals consuming a food patch leave it at different times and that the leaving time affects the animal preference for its pheromones. In particular, worms leaving early are attracted to their pheromones, while worms leaving later are repelled by them. We further demonstrate that the inversion from attraction to repulsion depends on associative learning and, by implementing a simple model, we highlight that it is an adaptive solution to optimize food intake during foraging.
Graph Properties of the AdultDrosophilaCentral Brain
Authors: Scheffer Louis K. 
Published: May 2020

AbstractThe recentDrosophilacentral brain connectome offers the possibility of analyzing the graph properties of the fly brain. Crucially, this connectome is dense, meaning all nodes and links are represented, within the limits of experimental error. We consider the connectome as a directed graph with weighted edges. This enables us to look at a number of graph properties, compare them to human designed logic systems, and speculate on how this may affect function. We look at input and output distributions, randomness of wiring, differences between compartments, path lengths, proximity of strong connections, known computational structures, electrical response as a function of compartment structure, and evidence for efficient packing.
ER-directed TREX1 limits cGAS recognition of micronuclei
Authors: Mohr Lisa , Toufektchan Eléonore , Chu Kevan , Maciejowski John 
Published: May 2020

ABSTRACTChromosomal instability in cancer results in the formation of nuclear aberrations termed micronuclei. Spontaneous loss of micronuclear envelope integrity exposes DNA to the cytoplasm, leading to chromosome fragmentation and innate immune activation. Despite connections to cancer genome evolution and anti-tumor immunity, the mechanisms underlying damage and immune sensing of micronuclear DNA are poorly understood. Here, we use a novel method for the purification of micronuclei and live-cell imaging to show that the ER-associated nuclease TREX1 inhibits cGAS sensing of micronuclei by stably associating with and degrading micronuclear DNA upon micronuclear envelope rupture. We identify aTREX1mutation, previously associated with autoimmune disease, that untethers TREX1 from the ER, disrupts TREX1 localization to micronuclei, alleviates micronuclear DNA damage, and enhances cGAS recognition of micronuclei. Together, these results establish ER-directed resection of micronuclear DNA by TREX1 as a critical regulator of cytosolic DNA sensing in chromosomally unstable cells and provide a mechanistic basis for the importance of TREX1 ER-tethering in preventing autoimmunity.
Inflammation is a stronger predictor of psychological trauma exposure than behavior in repeated social defeat
Authors: Elkhatib Safwan K. , Moshfegh Cassandra M. , Watson Gabrielle F. , Case Adam J. 
Published: May 2020

AbstractPost-traumatic stress disorder (PTSD) is a psychiatric illness that results in an increased risk for a variety of inflammatory diseases. The exact etiology of this increased risk in unknown, and thus, several animal models have been developed to investigate the neuroimmune interactions of PTSD. Repeated social defeat stress (RSDS) is an established preclinical model of psychological trauma that recapitulates certain behavioral and inflammatory aspects of human PTSD. Furthermore, RSDS has been utilized to subgroup animals into susceptible and resilient populations based on one specific behavioral phenotype (i.e., social interaction). Herein, we conducted an extensive investigation of circulating inflammatory proteins after RSDS, and found significant elevations in various cytokines and chemokines after exposure to psychological trauma. When categorizing animals into either susceptible or resilient populations based on social interaction, we found no inflammatory or other behavioral differences between these subgroups. Furthermore, assessment of associations between all detectable inflammatory proteins and behavioral outputs found no significant correlation between social interaction parameters and inflammation. In contrast, we identified a panel of 5 circulating inflammatory proteins that showed significant associations with elevated zero maze parameters. Strikingly, these 5 circulating inflammatory proteins displayed a stronger predictive ability of psychological trauma exposure compared to any behavioral outcome. These findings provide new insights into inflammatory markers associated with RSDS, and their ability to predict psychological trauma exposure more robustly than commonly utilized behavioral paradigms.HighlightsRepeated social defeat stress (RSDS) reproducibly produces peripheral inflammationPeripheral inflammation is not coupled to social interaction testing parametersSusceptible and resilient categorization does not reflect peripheral inflammationAnxiety-like behavioral parameters are linked to peripheral inflammation in RSDSPeripheral inflammation is more predictive of trauma than behavior in RSDS
Montane species track rising temperatures better in the tropics than in the temperate zone
Authors: Freeman Benjamin G. , Song Yiluan , Feeley Kenneth J , Zhu Kai 
Published: May 2020

AbstractMany species are responding to global warming by shifting their distributions upslope to higher elevations, but the observed rates of shifts vary considerably among studies. Here we test the hypothesis that this variation is in part explained by latitude, with tropical species being generally more responsive to warming temperatures than are temperate species. We find support for this hypothesis in each of two independent empirical datasets—shifts in species’ elevational ranges, and changes in composition of forest inventory tree plots. Tropical species are tracking rising temperatures 2.1–2.4 times (range shift dataset) and 10 times (tree plot dataset) better than their temperate counterparts. Models predict that for a 100 m upslope shift in temperature isotherm, species at the equator have shifted their elevational ranges 93–96 m upslope, while species at 45° latitude have shifted only 37–42 m upslope. For tree plots, models predict that a 1°C increase in temperature leads to an increase in community temperature index (CTI), a metric of the average temperature optima of tree species within a plot, of 0.56 °C at the equator but no change in CTI at 45° latitude (–0.033). This latitudinal gradient in temperature tracking suggests that tropical montane biotas may be on an “escalator to extinction” as global temperatures continue to rise.
The transcription factor Pou3f1 provides a new map to the glutamatergic neurons of the cerebellar nuclei
Authors: Han Wu Joshua Po , Yeung Joanna , Wu Sih-Rong , Zoghbi Huda , Goldowitz Dan 
Published: May 2020

AbstractPou3f1 is a transcription factor involved in early neural differentiation. Cap Analysis Gene Expression (5’-CAGE) analysis reveals thatPou3f1transcript is highly enriched in the developing cerebellum. Between embryonic (E) days E10.5 and E12.5, Pou3f1 expression is present prominently along the subpial stream (SS), suggesting that Pou3f1+cells are glutamatergic cerebellar nuclear (CN) neurons. This finding was confirmed by immunofluorescent (IF) co-labeling of Pou3f1 and Atoh1, the master regulator of cells from the rhombic lip (RL) that are destined for neurons of the glutamatergic lineage, as well as inAtoh1-null tissues, in which Pou3f1 expression is absent. Interestingly, the expression of Pax6, another key molecule for CN neuron survival, does not co-localize with that of Pou3f1. In thePax6-null Small Eye (Sey) mutant, which is characterized by a loss of many glutamatergic CN neurons, Pou3f1+CN neurons are still present. Furthermore, Pou3f1-labeled cells do not co-express Tbr1, a well-established marker of glutamatergic CN neurons. These results highlight that Pou3f1+cells are a distinct and previously unrecognized subtype of glutamatergic CN neurons that do not have the “canonical” sequence of Atoh1→Pax6→Tbr1 expressions. Instead, they express Atoh1, Pou3f1, and other markers of CN neurons, Brn2 and Irx3. These findings illustrate that glutamatergic CN neurons that arise from the RL are composed of molecularly heterogeneous subpopulations that are determined by at least two distinct transcriptional programs.Significance StatementThe present work has identified Pou3f1 as a marker for a previously unidentified subtype of glutamatergic cerebellar nuclear neurons, the principal output neurons of the cerebellum. The classical model of glutamatergic CN neurons development follows the sequential expression of transcription factors Atoh1→Pax6→Tbr1. However, we found that the development of Pou3f1+neurons requires Atoh1 but not Pax6. Moreover, Pou3f1+neurons do not express Tbr1, but instead express two other transcription factors, Brn2 and Irx3. Anatomically, Pou3f1+CN neurons populate the interposed and dentate nuclei, while the Tbr1+CN neurons populate the fastigial nucleus. These findings reveal the heterogeneity of CN neuron populations and the diversity of molecular programming that lead to different CN neuron subtypes.
Genome-wide landscape of RNA-binding protein dysregulation reveals a major impact on psychiatric disorder risk
Authors: Park Christopher Y. , Zhou Jian , Wong Aaron K. , Chen Kathleen M. , Theesfeld Chandra L. , Darnell Robert B. , Troyanskaya Olga G. 
Published: May 2020

AbstractDespite the strong genetic basis of psychiatric disorders, the molecular origins of these diseases are still largely unmapped. RNA-binding proteins (RBPs) are responsible for most post-transcriptional regulation, from splicing to translational to localization. RBPs thus act as key gatekeepers of cellular homeostasis, especially in the brain. Here, we leverage a deep learning approach to interrogate variant effects genome-wide, and discover that the dysregulation of RBP target sites is a principal contributor to psychiatric disorder risk. We show that specific modes of RBP regulation are genetically linked to the heritability of psychiatric disorders, and demonstrate that diverse RBP regulatory functions are reflected in distinct genome-wide negative selection signatures. Notably, RBP dysregulation has a stronger impact on psychiatric disorders than common coding region variants and explains heritability not currently captured by large-scale molecular QTL studies (expression QTLs and splicing QTLs). We share genome-wide profiles of RBP target site dysregulation, which we used to identify DDHD2 as a candidate schizophrenia risk gene, in a public web server. This resource provides a novel analytical framework to connect the full range of RNA regulation to complex disease.
Electronic blood vessel
Authors: Cheng Shiyu , Hang Chen , Ding Li , Jia Liujun , Tang Lixue , Mou Lei , Qi Jie , Dong Ruihua , Zheng Wenfu , Zhang Yan , Jiang Xingyu 
Published: May 2020

SummaryAdvances in bioelectronics have great potential to address unsolvable biomedical problems in the cardiovascular system. By using poly(L-lactide-co-ε-caprolactone) (PLC) that encapsulates the liquid metal to make flexible and bio-degradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelization process through electrical stimulation and can enable controlled gene delivery into specific part of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency three months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of vascular tissue-machine interface.