bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactivation of hedonic but not sensory representations in human emotional learning
Authors: Ehlers M. R. , Kryklywy J. H. , Beukers A. O. , Moore S. R. , Forys B. J. , Anderson A.K. , Todd R. M. 
Published: November 2021

AbstractLearning which stimuli in our environment co-occur with painful or pleasurable events is critical for survival. Previous research has established the basic neural and behavioural mechanisms of aversive and appetitive conditioning; however, it is unclear what precisely is learned. Here we examined what aspects of the unconditioned stimulus (US) – sensory and hedonic – are transferred to the conditioned stimulus (CS). To decode the content of brain activation patterns elicited during appetitive (soft touch) and aversive (painful touch) conditioning of faces, a novel variation of representational similarity analysis (RSA) based on theoretically driven representational patterns of interest (POIs) was applied to fMRI data. Once face associations were learned through conditioning, globally the CS reactivated US representational patterns showing conditioning-dependent reactivation. More specifically, in higher order brain regions, the CS only reactivated hedonic but not sensory aspects of the US – suggesting that affective conditioning primarily carries forward the valence of the experience rather than its sensory origins.
Bitter taste perception in BaYaka hunter-gatherers
Authors: Keestra Sarai , Miabangana Edmond Sylvestre , Chaudhary Nikhil , Derkx Inez , Sikka Gaurav , Salali Gul Deniz 
Published: November 2021

AbstractAversion towards bitter tastes evolved across vertebrate species to enable the recognition of harmful plant toxins. Most studies to date have investigated the variation in bitter taste sensitivity between human populations. However, there is a lack of research investigating phenotypic plasticity and the variation in bitter taste perception within the same population. Here we examined bitter taste perception among the Mbendjele BaYaka hunter-gatherers from Congo, a group of forest hunter-gatherers who exhibit a variation in their levels of market integration. We conducted an experiment using phenylthiocarbamide (PTC) and thiourea infused paper strips and compared the prevalence of bitter tasting phenotypes between the BaYaka who grew up in town and forest camps. We found that 45.1% of BaYaka experience PTC as bitter, and 42.5% experience thiourea as bitter. There were no sex and age differences in bitter taste perception. Despite a shared genetic background, we found that BaYaka who grew up in town were more sensitive to bitter taste than those living in the forest, suggesting a developmental component in taste perception. We suggest that a decreased use of traditional plant medicine in town-born BaYaka may underlie this variation in bitter taste perception.
Survey on Open Science Practices in Functional Neuroimaging
Authors: Paret Christian , Unverhau Nike , Feingold Franklin , Poldrack Russell A. , Stirner Madita , Schmahl Christian , Sicorello Maurizio 
Published: November 2021

AbstractReplicability and reproducibility of scientific findings is paramount for sustainable progress in neuroscience. Preregistration of the hypotheses and methods of an empirical study before analysis, the sharing of primary research data, and compliance with data standards such as the Brain Imaging Data Structure (BIDS), are considered effective practices to secure progress and to substantiate quality of research. We investigated the current level of adoption of open science practices in neuroimaging and the difficulties that prevent researchers from using them.Email invitations to participate in the survey were sent to addresses received through a PubMed search of human functional magnetic resonance imaging studies between 2010 and 2020. 283 persons completed the questionnaire.Although half of the participants were experienced with preregistration, the willingness to preregister studies in the future was modest. The majority of participants had experience with the sharing of primary neuroimaging data. Most of the participants were interested in implementing a standardized data structure such as BIDS in their labs. Based on demographic variables, we compared participants on seven subscales, which had been generated through factor analysis. It was found that experienced researchers at lower career level had higher fear of being transparent, researchers with residence in the EU had a higher need for data governance, and researchers at medical faculties as compared to other university faculties reported a higher need for data governance and a more unsupportive environment.The results suggest growing adoption of open science practices but also highlight a number of important impediments.
Genome-wide analyses reveal a strong association between LEPR gene variants and body fat reserves in ewes
Authors: Macé Tiphaine , González-García Eliel , Foulquié Didier , Carrière Fabien , Pradel Julien , Durand Christian , Douls Sebastien , Parisot Sara , Hazard Dominique 
Published: November 2021

AbstractAmong the adaptive capacities of animals, the management of energetic body reserves (BR) through the BR mobilization and accretion processes (BR dynamics, BRD) has become an increasingly valuable attribute for livestock sustainability, allowing animals to cope with more variable environments. BRD has previously been reported to be heritable in ruminants. In the present study, we conducted genome-wide studies (GWAS) in sheep to determine genetic variants associated with BRD. BR levels and BR changes over time were obtained through body condition score measurements at eight physiological stages throughout each productive cycle in Romane ewes (n=1034) and were used as phenotypes for GWAS. After quality controls and imputation, 48,513 single nucleotide polymorphisms (SNP) were included in the GWAS. Among the QTLs identified, a major QTL associated with BR levels during pregnancy and lactation was identified on chromosome 1. In this region, several significant SNPs mapped to the leptin receptor gene (LEPR), among which one SNP mapped to the coding sequence. The point mutation induces the p.P1019S substitution in the cytoplasmic domain, close to tyrosine phosphorylation sites. The frequency of the SNP associated with increased BR levels was 32%, and the LEPR genotype explained up to 5% of the variance of the trait. These results provide strong evidence for involvement of LEPR in the regulation of BRD in sheep and highlight it as a major candidate for improving adaptive capacities.
Case Study of High-Throughput Drug Screening and Remote Data Collection for SARS-CoV-2 Main Protease by Using Serial Femtosecond X-ray Crystallography
Authors: Guven Omur , Gul Mehmet , Ayan Esra , Johnson J. Austin , Cakilkaya Baris , Usta Gozde , Ertem Fatma Betul , Tokay Nurettin , Yuksel Busra , Gocenler Oktay , Buyukdag Cengizhan , Botha Sabine , Ketawala Gihan , Su Zhen , Hayes Brandon , Poitevin Frederic , Batyuk Alexander , Yoon Chun Hong , Kupitz Christopher , Durdagi Serdar , Sierra Raymond G. , DeMirci Hasan 
Published: November 2021

AbstractSince early 2020, COVID-19 has grown to affect the lives of billions globally. A worldwide investigation has been ongoing for characterizing the virus and also for finding an effective drug and developing vaccines. As time has been of the essence, a crucial part of this research has been drug repurposing; therefore, confirmation of in-silico drug screening studies has been carried out for this purpose. Here we demonstrated the possibility of screening a variety of drugs efficiently by leveraging a high data collection rate of 120 images/second with the new low-noise, high dynamic range ePix10k2M Pixel Array Detector installed at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS). The X-ray Free-Electron Laser (XFEL) is used for remote high-throughput data collection for drug repurposing of the main protease (Mpro) of SARS-CoV-2 at ambient temperature with mitigated X-ray radiation damage. We obtained multiple structures soaked with 9 drug candidate molecules in two crystal forms. Although our drug binding attempts failed, we successfully established a high-throughput Serial Femtosecond X-ray crystallographic (SFX) data collection protocol.
Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality
Authors: Fears Alyssa C , Beddingfield Brandon J , Chirichella Nicole R , Slisarenko Nadia , Killeen Stephanie Z , Redmann Rachel K , Goff Kelly , Spencer Skye , Picou Breanna , Golden Nadia , Bush Duane J , Branco Luis M , Boisen Matthew L , Gao Hongmei , Montefiori David C , Blair Robert V , Doyle-Meyers Lara A , Russel-Lodrigue Kasi , Maness Nicholas J , Roy Chad J 
Published: November 2021

AbstractThe novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques (Macaca mulatta, RMs) and African green monkeys (Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.
A stochastic mathematical model of 4D tumour spheroids with real-time fluorescent cell cycle labelling
Authors: Klowss Jonah J. , Browning Alexander P. , Murphy Ryan J. , Carr Elliot J. , Plank Michael J. , Gunasingh Gency , Haass Nikolas K. , Simpson Matthew J. 
Published: November 2021

AbstractIn vitro tumour spheroid experiments have been used to study avascular tumour growth and drug design for the last 50 years. Unlike simpler two-dimensional cell cultures, tumour spheroids exhibit heterogeneity within the growing population of cells that is thought to be related to spatial and temporal differences in nutrient availability. The recent development of real-time fluorescent cell cycle imaging allows us to identify the position and cell cycle status of individual cells within the growing population, giving rise to the notion of a four-dimensional (4D) tumour spheroid. In this work we develop the first stochastic individual-based model (IBM) of a 4D tumour spheroid and show that IBM simulation data qualitatively and quantitatively compare very well with experimental data from a suite of 4D tumour spheroid experiments performed with a primary human melanoma cell line. The IBM provides quantitative information about nutrient availability within the spheroid, which is important because it is very difficult to measure these data in standard tumour spheroid experiments. Software required to implement the IBM is available on GitHub, https://github.com/ProfMJSimpson/4DFUCCI.
Development of machine learning model for predicting hospitalization in the prehospital setting
Authors: Morisawa Kenichiro , Goto Tadahiro , Fujitani Shigeki 
Published: November 2021

ABSTRACTBackgroundStudies have developed models for predicting patient outcomes for successful risk stratification in the prehospital setting. However, these models generally require many predictors to achieve high prediction ability, resulting in a bar for implementing models in the real clinical setting.ObjectiveWe aimed to develop a simple and implementable machine learning model using automatically-collected data (age, sex, vital signs) to predict patient outcomes during transportation in comparison with National Early Warning Score (NEWS).MethodsThis is a retrospective cohort study using data from the ED of three tertiary care hospitals in Japan from April 2017 to March 2020. We included adult patients (aged ≥18 years) who were transported to the ED of participating hospitals. We excluded patients with trauma/injury, cardiac arrest, transferred from other hospitals, patients with missing vital signs data, or having data of obvious outliers. The predictors were patient age, sex, mental status evaluated with Japan Coma Scale, systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and oxygen saturation. The primary outcome was hospitalization. We developed a model using XGBoost.ResultsDuring the study period, 3528 visits transported by emergency medical services were eligible. The median NEWS was 4.0, and 2081 patients were hospitalized. The discrimination ability of the newly developed model was 0.70 (95%CI 0.67-0.73), which was better than those of NEWS 0.64 (95%CI 0.61-0.68). The newly developed model’s performance measures (e.g., sensitivity, specificity) were comparable with NEWS.ConclusionsOur newly developed machine learning model using routinely available data has moderate prediction ability and was better than NEWS.
The HUSH complex controls brain architecture and protocadherin fidelity
Authors: Hagelkruys Astrid , Horrer Marion , Taubenschmid-Stowers Jasmin , Kavirayani Anoop , Novatchkova Maria , Orthofer Michael , Pai Tsung-Pin , Cikes Domagoj , Zhuk Sergei , Balmaña Meritxell , Esk Christopher , Koglgruber Rubina , Cronin Shane J.F. , Elling Ulrich , Knoblich Jürgen A. , Penninger Josef M. 
Published: November 2021

AbstractFine-tuning of neural connectivity is important for cerebral functions and brain evolution. Protocadherins provide barcodes for neuronal identity as well as synapse formation and expansion of protocadherin cluster genes has been linked to advanced cognitive functions. The tightly controlled stochastic and combinatorial expression of the different protocadherin isoforms in individual neurons provides the molecular basis for neuronal diversity, neuronal network complexity and function of the vertebrate brain. How protocadherins are epigenetically controlled has not yet been fully elucidated. Here we show that the HUSH (human silencing hub) complex containing H3K9me3 binding protein M-phase phosphoprotein 8 (MPP8) and Microrchidia CW-type zinc finger protein 2 (MORC2), critically controls the fidelity of protocadherin expression. MPP8 and MORC2A are highly expressed in the murine brain and exclusively found in neurons. Genetic inactivation of Mphosph8 (coding for MPP8) or Morc2a in the nervous system of mice leads to increased brain size, altered brain architecture, and behavioral changes. Mechanistically, MPP8 and MORC2A precisely and selectively suppress the repetitive-like protocadherin gene cluster on mouse chromosome 18 in a H3K9me3-dependent manner, thereby affecting synapse formation. Moreover, we demonstrate that individual MPHOSPH8- or MORC2-deficient neurons in human cerebral organoids express increased numbers of clustered protocadherin isoforms. Our data identify the HUSH complex, previously linked to silencing of repetitive transposable elements, as a key epigenetic regulator of protocadherin expression in the nervous system and thereby brain development and neuronal individuality in mice and humans.
Using child-friendly movie stimuli to study the development of face, place, and object regions from age 3 to 12 years
Authors: Kamps Frederik S. , Richardson Hilary , Ratan Murty N. Apurva , Kanwisher Nancy , Saxe Rebecca 
Published: November 2021

AbstractScanning young children while watching short, engaging, commercially-produced movies has emerged as a promising approach for increasing data retention and quality. Movie stimuli also evoke a richer variety of cognitive processes than traditional experiments – allowing the study of multiple aspects of brain development simultaneously. However, because these stimuli are uncontrolled, it is unclear how effectively distinct profiles of brain activity can be distinguished from the resulting data. Here we develop an approach for identifying multiple distinct subject-specific Regions of Interest (ssROIs) using fMRI data collected during movie-viewing. We focused on the test case of higher-level visual regions selective for faces, scenes, and objects. Adults (N=13) were scanned while viewing a 5.5 minute child-friendly movie, as well as a traditional experiment with isolated faces, scenes, and objects. We found that just 2.7 minutes of movie data could identify subject-specific face, scene, and object regions. While successful, the movie approach was still less effective than a traditional localizer. Having validated our approach in adults, we then used the same methods on movie data collected from 3–12-year-old children (N=122). Movie response timecourses in 3-year-old children’s face, scene, and object regions were already significantly and specifically predicted by timecourses from the corresponding regions in adults. We also found evidence of continued developmental change, particularly in the face-selective posterior superior temporal sulcus. Taken together, our results reveal both early maturity and functional change in face, scene, and object regions, and more broadly highlight the promise of short, child-friendly movies for developmental cognitive neuroscience.
Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood
Authors: Khan Kanza M. , Bierlein-De La Rosa Gabrielle , Biggerstaff Natalie , Pushpavathi Selvakumar Govindhasamy , Mason Suzanne , Dailey Michael E. , Marcinkiewcz Catherine A. 
Published: November 2021

ABSTRACTAdolescent alcohol use can permanently alter brain function and lead to poor health outcomes in adulthood. Emerging evidence suggests that alcohol use predispose to pain disorders or exacerbate existing pain conditions, but the neural mechanisms are currently unknown. Here we report that mice exposed to adolescent intermittent access to ethanol (AIE) exhibit increased pain sensitivity and depressive-like behaviors that persist after alcohol cessation and are accompanied by elevated CD68 expression in microglia and reduced numbers of serotonin (5-HT)-expressing neurons in the dorsal raphe nucleus (DRN). 5-HT expression was also reduced in the thalamus, anterior cingulate cortex (ACC) and amygdala as well as the lumbar dorsal horn of the spinal cord. We then found that chronic minocycline administration after AIE alleviated hyperalgesia and social deficits, while chemogenetic activation of microglia in the DRN of Cx3cr1-cre-GFP mice reproduced the effects of AIE on pain and social interaction. Taken together, these results indicate that microglial activation in the DRN may be a primary driver of pain and negative affect after AIE.
Ectosome effect on endothelial monolayers in hyperglycemic and normoglycemic conditions
Authors: Drożdż Anna , Kołodziej Tomasz , Wróbel Sonia , Misztal Krzysztof , Targosz-Korecka Marta , Drab Marek , Jach Robert , Przybyło Małgorzata , Rajfur Zenon , Stępień Ewa Ł 
Published: November 2021

AbstractExtracellular vesicles, namely those larger ones - Ectosomes (Ect), are thought to be important cell-to-cell communication medium. Ect are considered as a potential therapeutic for type-1 and type-2 diabetes mellitus. Ect can be internalized by endothelial cells and, owing to their cargo, they modulate targeted cell behavior. Under hyperglycemic conditions (HGC), endothelial cells changed their properties and became stiffer and less mobile which causes endothelial dysfunction and abnormalities in micro- and macrovascular systems. The aim of this study was to find whether Ect restore mobility and motility of macrovascular endothelial cells under HGC. Uptake of Ect, cell morphology, cytoskeleton organization and membrane stiffness (by atomic force microscopy) were analyzed after the exposure to isolated Ect. To find which cellular pathways were deregulated by HGC and whether Ect could potentially restore gene expression profile, transcriptome analysis was done. We observed that endothelial cells internalized more Ect under normoglycemic conditions (NGC) then HGC. Hyperglycemic cells (HG) were bigger and showed the stiffer surface with denser actin cytoskeleton in comparison to normoglycemic cells. Number of metabolic pathways was influenced under HGC, especially those related to intracellular transport, metabolism and cellular component organization and Ect did not restore HGC impaired cell signaling. Ectosomes cannot reverse this harmful effect of hyperglycemia in endothelial cells, which can have clinical implication in use Ect as therapeutic target in diabetes treatment.
A subcellular cookie cutter for spatial genomics in human tissue
Authors: Bury Alexander G. , Pyle Angela , Marcuccio Fabio , Turnbull Doug M. , Vincent Amy E. , Hudson Gavin , Actis Paolo 
Published: November 2021

AbstractIntracellular heterogeneity contributes significantly to cellular physiology and, in a number of debilitating diseases, cellular pathophysiology. This is greatly influenced by distinct organelle populations and to understand the aetiology of disease it is important to have tools able to isolate and differentially analyse organelles from precise location within tissues. Here we report the development of a subcellular biopsy technology that facilitates the isolation of organelles, such as mitochondria, from human tissue. We compared the subcellular biopsy technology to laser capture microdissection (LCM) that is the state of art technique for the isolation of cells from their surrounding tissues. We demonstrate an operational limit of (>20μm) for LCM and then, for the first time in human tissue, show that subcellular biopsy can be used to isolate mitochondria beyond this limit.
Diversity of Lepidoptera in urban parks at Pasir Gudang, Johor, Malaysia
Authors: Syed Nisranshah Sharifah Fatin Naqliah , Zakaria Nurulhuda 
Published: November 2021

ABSTRACTUrban parks are a valuable habitat for Lepidoptera, which are often neglected despite their potential role as pollinators and important food source for small animals. Lepidoptera in urban parks in Pasir Gudang are still under-studied. Yet, there is no publication on Lepidoptera in these urban parks. The objectives of this study were to determine and to compare the diversity of Lepidoptera in three urban parks (Laman Rekreasi Sungai Buluh, Tasik Dahlia and Taman Bandar) at Pasir Gudang, Johor. Visual Encounter Survey (VES) method was used to capture the Lepidoptera from February 2021 until April 2021. Four sampling sessions were conducted for each study site. A total of nine species from 117 individuals comprised of family Pieridae (43%), Nymphalidae (29%) and Lycaenidae (28%) were recorded from this study. The most abundant species were Zizula hylax and Elymnias hypermnestra, while Leptosia nina was the least abundant. The results from this study showed that the diversity of Lepidoptera have established in these three urban parks. Diversity of Lepidoptera in Tasik Dahlia was significantly lower compared to the other two study sites. The findings from this study could be useful as a baseline data for future research and conservation management of the order Lepidoptera around the urban parks and indirectly can support the sustainable development of the urban parks.