bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary association of receptor-wide amino acids with G protein coupling selectivity in aminergic GPCRs
Authors: Selçuk Berkay , Erol Ismail , Durdağı Serdar , Adebali Ogun 
Published: September 2021

AbstractG protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins (Gs, Gi, Gq, G12/13), selectively. However, G protein selective activation mechanisms and residual determinants in GPCRs have remained obscure. Herein, we performed an extensive phylogenetic analysis and identified specifically conserved residues for the receptors having similar coupling profiles in each aminergic receptor. By integrating our methodology of differential evolutionary conservation of G protein-specific amino acids with structural analyses, we identified selective activation networks for Gs, Gi1, Go, and Gq. To validate that these networks could determine coupling selectivity we further analyzed Gs specific activation network and associated it with the larger TM6 tilt which is a signature of Gs-coupled receptors. Through molecular dynamics simulations, we showed that previously uncharacterized Glycine at position 7×41 plays an important role in both receptor activation and Gs coupling selectivity by inducing a larger TM6 movement. Finally, we gathered our results into a comprehensive model of G protein selectivity called “sequential switches of activation” describing three main molecular switches controlling GPCR activation: ligand binding, G protein selective activation mechanisms and G protein contact.
Correlated variability in primate superior colliculus depends on functional class
Authors: Katz Leor N. , Yu Gongchen , Herman James P. , Krauzlis Richard J. 
Published: September 2021

SummaryCorrelated variability (spike count correlations, rSC) in a population of neurons can constrain how information is read out, depending on behavioral task and neuronal tuning. Here we tested whether rSC also depends on neuronal functional class. We recorded from populations of neurons in macaque superior colliculus (SC), a structure that contains well-defined functional classes. We found that during a guided saccade task, different classes of neurons exhibited differing degrees of rSC. “Delay class” neurons displayed the highest rSC, especially during the delay epoch of saccade tasks that relied on working memory. This was only present among Delay class neurons within the same hemisphere. The dependence of rSC on functional class indicates that subpopulations of SC neurons occupy distinct circuit niches with distinct inputs. Such subpopulations should be accounted for differentially when attempting to model or infer population coding principles in the SC, or elsewhere in the primate brain.
Circuit contributions to sensory-driven glutamatergic drive of olfactory bulb mitral and tufted cells during odorant inhalation
Authors: Moran Andrew K. , Eiting Thomas P. , Wachowiak Matt 
Published: September 2021

AbstractIn the mammalian olfactory bulb (OB), mitral/tufted (MT) cells respond to odorant inhalation with diverse temporal patterns that are thought to encode odor information. Much of this diversity is already apparent at the level of glutamatergic input to MT cells, which receive direct, monosynaptic excitatory input from olfactory sensory neurons (OSNs) as well as multisynaptic excitatory drive via glutamatergic interneurons. Both pathways are also subject to modulation by inhibitory circuits in the glomerular layer of the OB. To understand the role of direct OSN input versus postsynaptic OB circuit mechanisms in shaping diverse dynamics of glutamatergic drive to MT cells, we imaged glutamate signaling onto MT cell dendrites in anesthetized mice while blocking multisynaptic excitatory drive with ionotropic glutamate receptor antagonists and blocking presynaptic modulation of glutamate release from OSNs with GABAB receptor antagonists. GABAB receptor blockade increased the magnitude of inhalation-linked glutamate transients onto MT cell apical dendrites without altering their inhalation-linked dynamics, confirming that presynaptic inhibition impacts the gain of OSN inputs to the OB. Surprisingly, blockade of multisynaptic excitation only modestly impacted glutamatergic input to MT cells, causing a slight reduction in the amplitude of inhalation-linked glutamate transients in response to low odorant concentrations and no change in the dynamics of each transient. Postsynaptic blockade also modestly impacted glutamate dynamics over a slower timescale, mainly by reducing adaptation of the glutamate response across multiple inhalations of odorant. These results suggest that direct glutamatergic input from OSNs provides the bulk of excitatory drive to MT cells, and that diversity in the dynamics of this input may be a primary determinant of the temporal diversity in MT cell responses that underlies odor representations at this stage.
Accurate Name Entity Recognition for Biomedical Literatures: A Combined High-quality Manual Annotation and Deep-learning Natural Language Processing Study
Authors: Huang Dao-Ling , Zeng Quanlei , Xiong Yun , Liu Shuixia , Pang Chaoqun , Xia Menglei , Fang Ting , Ma Yanli , Qiang Cuicui , Zhang Yi , Zhang Yu , Li Hong , Yuan Yuying 
Published: September 2021

ABSTRACTA combined high-quality manual annotation and deep-learning natural language processing study is reported to make accurate name entity recognition (NER) for biomedical literatures. A home-made version of entity annotation guidelines on biomedical literatures was constructed. Our manual annotations have an overall over 92% consistency for all the four entity types — gene, variant, disease and species —with the same publicly available annotated corpora from other experts previously. A total of 400 full biomedical articles from PubMed are annotated based on our home-made entity annotation guidelines. Both a BERT-based large model and a DistilBERT-based simplified model were constructed, trained and optimized for offline and online inference, respectively. The F1-scores of NER of gene, variant, disease and species for the BERT-based model are 97.28%, 93.52%, 92.54% and 95.76%, respectively, while those for the DistilBERT-based model are 95.14%, 86.26%, 91.37% and 89.92%, respectively. The F1 scores of the DistilBERT-based NER model retains 97.8%, 92.2%, 98.7% and 93.9% of those of BERT-based NER for gene, variant, disease and species, respectively. Moreover, the performance for both our BERT-based NER model and DistilBERT-based NER model outperforms that of the state-of-art model—BioBERT, indicating the significance to train an NER model on biomedical-domain literatures jointly with high-quality annotated datasets.
A B73 x Palomero Toluqueño mapping population reveals local adaptation in Mexican highland maize
Authors: Perez-Limón Sergio , Li Meng , Carolina Cintora-Martinez G. , Rocio Aguilar-Rangel M , Nancy Salazar-Vidal M. , González-Segovia Eric , Blöcher-Juárez Karla , Guerrero-Zavala Alejandro , Barrales-Gamez Benjamin , Carcaño-Macias Jessica , Costich Denise E. , Nieto-Sotelo Jorge , de la Vega Octavio Martinez , Simpson June , Hufford Matthew B. , Ross-Ibarra Jeffrey , Flint-Garcia Sherry , Diaz-Garcia Luis , Rellán-Álvarez Rubén , Sawers Ruairidh J. H. 
Published: September 2021

ABSTRACTGenerations of farmer selection have produced a unique collection of traditional maize varieties adapted to the environmental challenges of the central Mexican highlands. In addition to agronomic and cultural value, Mexican highland maize represents a good system for the study of local adaptation and acquisition of adaptive phenotypes under cultivation. In this study, we characterized a recombinant inbred line population derived from the cross of the B73 reference line and the Mexican highland maize variety Palomero Toluqueño. Evaluation over multiple years in lowland and highland field sites in Mexico identified genomic regions linked to yield components and putatively adaptive morphological traits. A region on chromosome 7 associated with ear weight showed antagonistic allelic effects in lowland and highland fields, suggesting a trade-off consistent with local adaptation. We identified several alleles of highland origin associated with characteristic highland traits, including reduced tassel branching, increased stem pigmentation and the presence of stem macrohairs. The oligogenic architecture of characteristic morphological traits supports their role in adaptation, suggesting they have arisen from consistent directional selection acting at distinct points across the genome. We discuss these results in the context of the origin of phenotypic novelty during selection, commenting on the role ofde novomutation and the acquisition of adaptive variation by gene flow from endemic wild relatives.
Alzheimer’s disease alters astrocytic functions related to neuronal support and transcellular internalization of mitochondria
Authors: Lampinen Riikka , Belaya Irina , Saveleva Liudmila , Liddell Jeffrey R , Rait Dzhessi , Huuskonen Mikko T , Giniatullina Raisa , Sorvari Annika , Soppela Liisi , Mikhailov Nikita , Boccuni Isabella , Giniatullin Rashid , Cruz-Haces Marcela , Konovalova Julia , Koskuvi Marja , Rauramaa Tuomas , Domanskyi Andrii , Hämäläinen Riikka H , Goldsteins Gundars , Koistinaho Jari , Malm Tarja , Chew Sweelin , Rilla Kirsi , White Anthony R , Marsh-Armstrong Nicholas , Kanninen Katja M 
Published: September 2021

AbstractUnder physiological conditionsin vivoastrocytes internalize and degrade neuronal mitochondria in a process called transmitophagy. Mitophagy is widely reported to be impaired in neurodegeneration but it is unknown whether and how transmitophagy is altered in Alzheimer’s disease (AD). Here we report that the internalization and degradation of neuronal mitochondria are significantly increased in astrocytes isolated from aged AD mouse brains. We also demonstrate for the first time a similar phenomenon between human neurons and AD astrocytes, and in murine hippocampiin vivo. The results suggest the involvement of S100a4 in impaired mitochondrial transfer between neurons and aged AD astrocytes. Significant increases in the mitophagy regulator Ambra1 were observed in the aged AD astrocytes. These findings demonstrate altered neuron-supporting functions of aged AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.
Global chromosome topology and the two-component systems in concerted manner regulate transcription in Streptomyces
Authors: Gongerowska-Jac Martyna , Szafran Marcin J. , Mikołajczyk Jakub , Szymczak Justyna , Bartyńska Magda , Gierlikowska Anna , Biały Sylwia , Elliot Marie A. , Jakimowicz Dagmara 
Published: September 2021

ABSTRACTBacterial gene expression is controlled at multiple levels, with chromosome supercoiling being one of the most global regulators. Global DNA supercoiling is maintained by the orchestrated action of topoisomerases. In Streptomyces, mycelial soil bacteria with a complex life cycle, topoisomerase I depletion led to elevated chromosome supercoiling, changed expression of significant fraction of genes, delayed growth and blocked sporulation. To identify supercoiling-induced sporulation regulators, we searched for S. coelicolor transposon mutants that were able to restore sporulation despite high chromosome supercoiling. We established that transposon insertion in genes encoding a novel two-component system named SatKR reversed the sporulation blockage resulting from topoisomerase I depletion. Transposition in satKR abolished the transcriptional induction of the genes within the so-called supercoiling-hypersensitive cluster (SHC). Moreover, we found that activated SatR also induced the same set of SHC genes under normal supercoiling conditions. We determined that the expression of genes in this region impacted S. coelicolor growth and sporulation. Interestingly, among the associated products is another two-component system (SitKR), indicating the potential for cascading regulatory effects driven by the SatKR and SitKR two-component systems. Thus, we demonstrated the concerted activity of chromosome supercoiling and a hierarchical two-component signalling system that impacts gene activity governing Streptomyces growth and sporulation.IMPORTANCEStreptomyces, soil bacteria with complex life cycle, are the producers of a broad range of biologically active compounds (e.g. antibiotics). Streptomyces respond to various environmental signals using complex transcriptional regulation mechanism. Understanding regulation of their gene expression is crucial for Streptomyces application as industrial organisms. Here, based on extensive transcriptomics analyses, we describe the concerted regulation of genes crucial for growth and development by global DNA supercoiling and novel two-component system. Our data indicate that regulated genes encode growth and sporulation regulator. Thus, we demonstrate that Streptomyces link the global regulatory strategies to adjusts life cycle to unfavourable conditions.
Collective dynamics support group drumming, reduce variability, and stabilize tempo drift
Authors: Dotov Dobromir , Delasanta Lana , Cameron Daniel J , Large Edward , Trainor Laurel J 
Published: September 2021

AbstractHumans are social animals who engage in a variety of collective activities requiring coordinated action. Among these, music is a defining and ancient aspect of human sociality. Human social interaction has largely been addressed in dyadic paradigms and it is yet to be determined whether the ensuing conclusions generalize to larger groups. Studied more extensively in nonhuman animal behaviour, the presence of multiple agents engaged in the same task space creates different constraints and possibilities than in simpler dyadic interactions. We addressed whether collective dynamics play a role in human circle drumming. The task was to synchronize in a group with an initial reference pattern and then maintain synchronization after it was muted. We varied the number of drummers, from solo to dyad, quartet, and octet. The observed lower variability, lack of speeding up, smoother individual dynamics, and leader-less inter-personal coordination indicated that stability increased as group size increased, a sort of temporal wisdom of crowds. We propose a hybrid continuous-discrete Kuramoto model for emergent group synchronization with pulse-based coupling that exhibits a mean field positive feedback loop. This research suggests that collective phenomena are among the factors that play a role in social cognition.
Movement shapes the structure of fish communities along a cross-shore section in the California Current
Authors: Guiet Jérôme , Bianchi Daniele , Maury Olivier , Barrier Nicolas , Kessouri Fayçal 
Published: September 2021

AbstractPelagic fish communities are shaped by bottom-up and top-down processes, transport by currents, and active swimming. However, the interaction of these processes remains poorly understood. Here, we use a regional implementation of the APex ECOSystem Model (APECOSM), a mechanistic model of the pelagic food web, to investigate these processes in the California Current, a highly productive upwelling system characterized by vigorous mesoscale circulation. The model is coupled with an eddy-resolving representation of ocean currents and lower trophic levels, and is tuned to reproduce observed fish biomass from fisheries independent trawls. Several emergent properties of the model compare realistically with observations. First, the epipelagic community accounts for one order of magnitude less biomass than the vertically migratory community, and is composed by smaller species. Second, the abundance of small fish decreases from the coast to the open ocean, while the abundance of large fish remains relatively uniform. This in turn leads to flattening of biomass size-spectra away from the coast for both communities. Third, the model reproduces a cross-shore succession of small to large sizes moving offshore, consistent with observations of species occurrence. These cross-shore variations emerge in the model from a combination of: (1) passive offshore advection by the mean current, (2) active swimming towards coastal productive regions to counterbalance this transport, and (3) mesoscale heterogeneity that reduces the ability of organisms to return to coastal waters. Our results highlight the importance of passive and active movement in structuring the pelagic food web, and suggest that a correct representation of these processes is needed for realistic simulations with marine ecosystem models.
Increased temporal discounting and reduced model-based control in problem gambling are not substantially modulated by exposure to virtual gambling environments
Authors: Bruder Luca R. , Wagner Ben , Mathar David , Peters Jan 
Published: September 2021

AbstractHigh-performance virtual reality (VR) technology has opened new possibilities for the examination of the reactivity towards addiction-related cues (cue-reactivity) in addiction. In this preregistered study (https://osf.io/4mrta), we investigated the subjective, physiological, and behavioral effects of gambling-related VR environment exposure in participants reporting frequent or pathological gambling (n=31) as well as non-gambling controls (n=29). On two separate days, participants explored two rich and navigable VR-environments (neutral: café vs. gambling-related: casino/sports-betting facility), while electrodermal activity and heart rate were continuously measured using remote sensors. Within VR, participants performed a temporal discounting task and a sequential decision-making task designed to assess model-based and model-free contributions to behavior. Replicating previous findings, we found strong evidence for increased temporal discounting and reduced model-based control in participants reporting frequent or pathological gambling. Although VR gambling environment exposure increased subjective craving, there was if anything inconclusive evidence for further behavioral or physiological effects. Instead, VR exposure substantially increased physiological arousal (electrodermal activity), across groups and conditions. VR is a promising tool for the investigation of context effects in addiction, but some caution is warranted since effects of real gambling environments might not generally replicate in VR. Future studies should delineate how factors such as cognitive load and ecological validity could be balanced to create a more naturalistic VR experience.
Soluble ECM promotes organotypic formation in lung alveolar model
Authors: Valdoz Jonard C. , Franks Nicholas A. , Cribbs Collin G. , Jacobs Dallin J. , Dodson Ethan L. , Knight Connor J. , Poulson P. Daniel , Garfield Seth R. , Johnson Benjamin C. , Hemeyer Brandon M. , Sudo Miranda T. , Saunooke Jordan A. , Kartchner Braden C. , Saxton Aubrianna , Vallecillo-Zuniga Mary L. , Santos Matheus , Chamberlain Brandon , Christensen Kenneth A. , Nordin Greg P. , Narayanan A. Sampath , Raghu Ganesh , Van Ry Pam M. 
Published: September 2021

AbstractMicropatterned suspension culture creates consistently sized and shaped cell aggregates but has not produced organotypic structures from stable cells, thus restricting its use in accurate disease modeling. Here, we show that organotypic structure is achieved in hybrid suspension culture via supplementation of soluble extracellular matrix (ECM). We created a viable lung organoid from epithelial, endothelial, and fibroblast human stable cell lines in suspension culture. We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of lumen-like structures with airspace showing feasible gas exchange units, formation of branching, perfusable vasculature, and long-term 70-day maintenance of lumen structure. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We also demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.
Cardiotoxic effects of methamphetamine associated with electrophysiological and epigenetic aberrations in zebrafish
Authors: Zhang Jimmy , Nguyen Anh H. , Schmiess-Heine Lauren , Le Tai , Xia Xing , Lau Michael P.H. , Lee Juhyun , Cao Hung 
Published: September 2021

AbstractLong-term methamphetamine (Meth) abuse damages functional and molecular changes in the brain that causes chronic and relapsing disease. In this study, we sought to investigate a relationship between cardiotoxicity and arrhythmia with associated Meth abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with Meth as well as to assess the applicability of zebrafish as an appropriate model for cardiac-related drug screening studies. Over a two-week duration, zebrafish were first treated with various concentrations of Meth, ranging from 0 to 50 μM. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement for electrophysiological analysis. Results show that a higher incidence of increased heart rate over the duration of the experiment, corroborating with results from previous human case studies involving Meth users. However, abnormalities commonly cited in those same case studies, such as prolongation of QTc, were not significantly presented in obtained ECG recordings. We have also conducted genetic, epigenetic, and histochemical analysis in an attempt to understand the cardiotoxic effects of Meth on zebrafish cardiac function. These results suggested myocardial damage and decrease in gene expression associated with normal physiological function. Finally, this paper provides insights into potential reasons for the apparent discrepancies in our data with prior research as well as an outlook of zebrafish cardiotoxic drug screening studies.
Combi-Seq: Multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets
Authors: Mathur L , Szalai B , Utharala R , Ballinger M , Landry JJM , Ryckelynck M , Benes V , Saez-Rodriguez J , Merten CA 
Published: September 2021

AbstractAnti-cancer therapies often exhibit only short-term effects. Tumors typically develop drug resistance causing relapses that might be tackled with drug combinations. Identification of the right combination is challenging and would benefit from high-content, high-throughput combinatorial screens directly on patient biopsies. However, such screens require a large amount of material, normally not available from patients. To address these challenges, we developed a scalable microfluidic workflow to screen hundreds of drug combinations in picoliter-size droplets using transcriptome changes as a readout for drug effects. We devised a deterministic combinatorial DNA barcoding approach to encode treatment conditions, enabling the gene expression-based readout of drug effects in a highly multiplexed fashion. We applied our method to screen the effect of 420 drug combinations on the transcriptome of K562 cells using only ∼250 single cell droplets per condition, to successfully predict synergistic and antagonistic drug pairs, as well as their pathway activities.