bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional reprogramming culture conditions facilitate growth of lower-grade glioma models
Authors: Yuan Ming , White David , Resar Linda , Bar Eli , Groves Mari , Cohen Alan , Jackson Eric , Bynum Jennifer , Rubens Jeffrey , Mumm Jeff , Chen Liam , Jiang Liqun , Raabe Eric , Rodriguez Fausto J , Eberhart Charles G 
Published: November 2020

Abstract

Background
The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture with irradiated fibroblasts and the addition of a small molecule Rho kinase (ROCK) inhibitor. The aim of this study was to determine whether this approach would facilitate the culture of compact low-grade gliomas.

Methods
We attempted to culture 4 pilocytic astrocytomas, 2 gangliogliomas, 2 myxopapillary ependymomas, 2 anaplastic gliomas, 2 difficult-to-classify low-grade neuroepithelial tumors, a desmoplastic infantile ganglioglioma, and an anaplastic pleomorphic xanthoastrocytoma using a modified conditional reprogramming cell culture approach.

Results
Conditional reprogramming resulted in robust increases in growth for a majority of these tumors, with fibroblast conditioned media and ROCK inhibition both required. Switching cultures to standard serum containing media, or serum-free neurosphere conditions, with or without ROCK inhibition, resulted in decreased proliferation and induction of senescence markers. Rho kinase inhibition and conditioned media both promoted Akt and Erk1/2 activation. Several cultures, including one derived from a NF1-associated pilocytic astrocytoma (JHH-NF1-PA1) and one from a BRAF p.V600E mutant anaplastic pleomorphic xanthoastrocytoma (JHH-PXA1), exhibited growth sufficient for preclinical testing in vitro. In addition, JHH-NF1-PA1 cells survived and migrated in larval zebrafish orthotopic xenografts, while JHH-PXA1 formed orthotopic xenografts in mice histopathologically similar to the tumor from which it was derived.

Conclusions
These studies highlight the potential for the conditional reprogramming cell culture method to promote the growth of glial and glioneuronal tumors in vitro, in some cases enabling the establishment of long-term culture and in vivo models.
A high-capacity cathode for rechargeable K-metal battery based on reversible superoxide-peroxide conversion
Authors: Qiao Yu , Deng Han , Chang Zhi , Cao Xin , Yang Huijun , Zhou Haoshen 
Published: November 2020

Abstract
As a promising low-cost energy storage device, the development of a rechargeable potassium-ion battery (KIB) is severely hindered by the limited capacity of cathode candidates. Regarded as an attractive capacity-boosting strategy, triggering the O-related anionic redox activity has not been achieved within a sealed KIB system. Herein, in contrast to the typical gaseous open K-O2 battery (O2/KO2 redox), we originally realize the reversible superoxide/peroxide (KO2/K2O2) interconversion on a KO2-based cathode. Controlled within a sealed cell environment, the irreversible O2 evolution and electrolyte decomposition (induced by superoxide anion (O2−) formation) are effectively restrained. Rationally controlling the reversible depth-of-charge at 300 mAh/g (based on the mass of KO2), no obvious cell degradation can be observed during 900 cycles. Moreover, benefitting from electrolyte modification, the KO2-based cathode is coupled with a limited amount of K-metal anode (merely 2.5 times excess), harvesting a K-metal full-cell with high energy efficiency (∼90%) and long-term cycling stability (over 300 cycles).
A Role for Somatostatin-Positive Interneurons in Neuro-Oscillatory and Information Processing Deficits in Schizophrenia
Authors: Van Derveer Alice B , Bastos Georgia , Ferrell Antanovia D , Gallimore Connor G , Greene Michelle L , Holmes Jacob T , Kubricka Vivien , Ross Jordan M , Hamm Jordan P 
Published: November 2020

AbstractAlterations in neocortical GABAergic interneurons (INs) have been affiliated with neuropsychiatric diseases, including schizophrenia (SZ). Significant progress has been made linking the function of a specific subtype of GABAergic cells, parvalbumin (PV) positive INs, to altered gamma-band oscillations, which, in turn, underlie perceptual and feedforward information processing in cortical circuits. Here, we review a smaller but growing volume of literature focusing on a separate subtype of neocortical GABAergic INs, somatostatin (SST) positive INs. Despite sharing similar neurodevelopmental origins, SSTs exhibit distinct morphology and physiology from PVs. Like PVs, SSTs are altered in postmortem brain samples from multiple neocortical regions in SZ, although basic and translational research into consequences of SST dysfunction has been relatively sparse. We highlight a growing body of work in rodents, which now indicates that SSTs may also underlie specific aspects of cortical circuit function, namely low-frequency oscillations, disinhibition, and mediation of cortico-cortical feedback. SSTs may thereby support the coordination of local cortical information processing with more global spatial, temporal, and behavioral context, including predictive coding and working memory. These functions are notably deficient in some cases of SZ, as well as other neuropsychiatric disorders, emphasizing the importance of focusing on SSTs in future translational studies. Finally, we highlight the challenges that remain, including subtypes within the SST class.
G protein–coupled receptor GPR151 is involved in trigeminal neuropathic pain through the induction of Gβγ/extracellular signal-regulated kinase-mediated neuroinflammation in the trigeminal ganglion
Authors: Jiang Bao-Chun , Zhang Jing , Wu Bin , Jiang Ming , Cao Hanzhong , Wu Hao , Gao Yong-Jing 
Published: November 2020

Abstract
Trigeminal nerve injury–induced neuropathic pain is a debilitating chronic orofacial pain syndrome but lacks effective treatment. G protein–coupled receptors (GPCRs), especially orphan GPCRs (oGPCRs) are important therapeutic targets in pain medicine. Here, we screened upregulated oGPCRs in the trigeminal ganglion (TG) after partial infraorbital nerve transection (pIONT) and found that Gpr151 was the most significantly upregulated oGPCRs. Gpr151 mRNA was increased from pIONT day 3 and maintained for more than 21 days. Furthermore, GPR151 was expressed in the neurons of the TG after pIONT. Global mutation or knockdown of Gpr151 in the TG attenuated pIONT-induced mechanical allodynia. In addition, the excitability of TG neurons was increased after pIONT in wild-type (WT) mice, but not in Gpr151

−/−
mice. Notably, GPR151 bound to Gαi protein, but not Gαq, Gα12, or Gα13, and activated the extracellular signal-regulated kinase (ERK) through Gβγ. Extracellular signal-regulated kinase was also activated by pIONT in the TG of WT mice, but not in Gpr151

−/−
mice. Gene microarray showed that Gpr151 mutation reduced the expression of a large number of neuroinflammation-related genes that were upregulated in WT mice after pIONT, including chemokines CCL5, CCL7, CXCL9, and CXCL10. The mitogen-activated protein kinase inhibitor (PD98059) attenuated mechanical allodynia and reduced the upregulation of these chemokines after pIONT. Collectively, this study not only revealed the involvement of GPR151 in the maintenance of trigeminal neuropathic pain but also identified GPR151 as a Gαi-coupled receptor to induce ERK-dependent neuroinflammation. Thus, GPR151 may be a potential drug target for the treatment of trigeminal neuropathic pain.
Concussion Baseline Retesting Is Necessary When Initial Scores Are Low
Authors: Fraser Melissa A. , Kilchrist Leah M. , Kuo Michael 
Published: November 2020

Objective:
To determine whether (1) initial baseline scores are significantly better for those who have valid (initial valid) versus invalid scores (initial invalid) on their concussion baseline testing, (2) retesting results in significantly improved baseline scores, and (3) there is a significant difference in scores between those who have valid scores on their initial attempt and those who retook baseline tests (retest valid).

Design:
Prospective, repeated-measures.

Setting:
Two years of collegiate preparticipation concussion baseline testing.

Participants:
Five hundred forty-seven male and female Division I collegiate athletes (19.02 ± 1.31 years, female = 217).

Independent Variables:
Participants were divided into initial valid and initial invalid. The retest group was further divided into their initial (initial invalid) and final valid attempt (retest valid).

Main Outcome Measures:
Data were analyzed to determine the relationship between the 3 groups and overall initial and final scores on 28 individual items: total symptoms score, coordination, near-point convergence, CNS Vital Signs (CNSVS), Senaptec Sensory Station, and Neurocom Sensory Organization Test (SOT).

Results:
The initial valid group scored significantly better than the initial invalid group on 8 CNSVS items and 5 Senaptec items (P < 0.002). The retest valid scores were significantly better compared with the initial invalid scores on 17 items (P < 0.002).

Conclusions:
Retesting is recommended for individuals who score below acceptable ranges. This is important because athletes may experience a learning effect and are highly motivated during postinjury testing, so accurate baseline scores are imperative for athlete safety. Completion time for the coordination test may be a more informative option.
Exploring Risks of Human Challenge Trials for COVID-19
Authors: Manheim David , Więcek Witold , Schmit Virginia , Morrison Josh ,   1Day Sooner Research Team
Published: November 2020

Human Challenge Trials (HCTs) are a potential method to accelerate development of vaccines and therapeutics. However, HCTs for COVID-19 pose ethical and practical challenges, in part due to the unclear and developing risks. In this paper, we introduce an interactive model for exploring some risks of a SARS-COV-2 dosing study, a prerequisite for any COVID-19 challenge trials. The risk estimates we use are based on a Bayesian evidence synthesis model which can incorporate new data on infection fatality risks (IFRs) to patients, and infer rates of hospitalization. The model estimates individual risk, which we then extrapolate to overall mortality and hospitalization risk in a dosing study. We provide a web tool to explore risk under different study designs.Based on the Bayesian model, IFR for someone between 20 and 30 years of age is 15.1 in 100,000, with a 95% uncertainty interval from 11.8 to 19.2, while risk of hospitalization is 130 per 100,000 (100 to 160). However, risk will be reduced in an HCT via screening for comorbidities, selecting lower-risk population, and providing treatment. Accounting for this with stronger assumptions, we project the fatality risk to be as low as 2.5 per 100,000 (1.6 to 3.9) and the hospitalization risk to be 22.0 per 100,000 (14.0 to 33.7). We therefore find a 50-person dosing trial has a 99.74% (99.8% to 99.9%) chance of no fatalities, and a 98.9% (98.3% to 99.3%) probability of no cases requiring hospitalization.
Observing plasticity of the auditory system: Volumetric decreases along with increased functional connectivity in aspiring professional musicians
Authors: Wenger Elisabeth , Papadaki Eleftheria , Werner André , Kühn Simone , Lindenberger Ulman 
Published: November 2020

AbstractPlaying music relies on several sensory systems and the motor system, and poses strong demands on control processes, hence, offering an excellent model to study how experience can mold brain structure and function. While most studies on neural correlates of music expertise rely on cross-sectional comparisons, here we compared within-person changes over time in aspiring professionals intensely preparing for an entrance exam at a University of the Arts to skilled amateur musicians not preparing for a music exam. In the group of aspiring professionals, we observed gray-matter volume decrements in left planum polare, posterior insula, and left inferior frontal orbital gyrus over a period of about six months that were absent among the amateur musicians. At the same time, the left planum polare, the largest cluster of structural change, showed increasing functional connectivity with left and right auditory cortex, left precentral gyrus, left supplementary motor cortex, left and right postcentral gyrus, and left cingulate cortex, all regions previously identified to relate to music expertise. In line with the expansion–renormalization pattern of brain plasticity (Wenger, Brozzoli, et al. 2017), the aspiring professionals might have been in the selection and refinement period of plastic change.
Medial frontal cortex activity predicts information sampling in economic choice
Authors: Kaanders Paula , Nili Hamed , O’Reilly Jill X. , Hunt Laurence T. 
Published: November 2020

AbstractDecision-making not only requires agents to decide what to choose, but also how much information to sample before committing to a choice. Previously established frameworks for economic choice argue for a deliberative process of evidence accumulation across time. These tacitly acknowledge a role of information sampling, in that decisions are only made once sufficient evidence is acquired, yet few experiments have explicitly placed information sampling under the participant’s control. Here, we use functional MRI to investigate the neural basis of information sampling in economic choice, by allowing participants to actively sample information in a multi-step decision task. We show that medial frontal cortex (MFC) activity is predictive of further information sampling prior to choice. Choice difficulty (inverse value difference) was also encoded in MFC, but this effect was explained away by the inclusion of information sampling as a co-regressor in the general linear model. A distributed network of regions across prefrontal cortex encoded key features of the sampled information at the time it was presented. We propose that MFC is an important controller of the extent to which information is gathered before committing to an economic choice. This role may explain why MFC activity has been associated with evidence accumulation in previous studies, in which information sampling was an implicit rather than explicit feature of the decision.
Weak Vestibular Response in Persistent Developmental Stuttering: Implications for Own Voice Identification
Authors: Gattie Max , Lieven Elena , Kluk Karolina 
Published: November 2020

AbstractSpeech-motor and psycholinguistic models employ feedback control from an auditory stream corresponding to own voice. Such models underspecify how own voice is identified. It is proposed that own voice is identified through coincidence detection between the neural firing rates arising from deflection of cochlear and vestibular mechanoreceptors by the sound and vibration generated during vocalisation. The coincidence detection is proposed to differ in people who stutter. In an update to the approach-avoidance conflict model of Sheehan (1953, 1975) instances of stuttering are proposed to coincide with uncertainty over an ongoing speech act. Discussion covers speech-induced suppression, auditory scene analysis, and theories of mental content.
ProCbA: Protein Function Prediction based on Clique Analysis
Authors: Khanteymoori A. , Ghajehlo M. B. , Behrouzinia S. , Olyaee M. H. 
Published: November 2020

AbstractProtein function prediction based on protein-protein interactions (PPI) is one of the most important challenges of the Post-Genomic era. Due to the fact that determining protein function by experimental techniques can be costly, function prediction has become an important challenge for computational biology and bioinformatics. Some researchers utilize graph- (or network-) based methods using PPI networks for un-annotated proteins. The aim of this study is to increase the accuracy of the protein function prediction using two proposed methods.To predict protein functions, we propose a Protein Function Prediction based on Clique Analysis (ProCbA) and Protein Function Prediction on Neighborhood Counting using functional aggregation (ProNC-FA). Both ProCbA and ProNC-FA can predict the functions of unknown proteins. In addition, in ProNC-FA which is not including new algorithm; we try to address the essence of incomplete and noisy data of PPI era in order to achieving a network with complete functional aggregation. The experimental results on MIPS data and the 17 different explained datasets validate the encouraging performance and the strength of both ProCbA and ProNC-FA on function prediction. Experimental result analysis as can be seen in Section IV, the both ProCbA and ProNC-FA are generally able to outperform all the other methods.
AttentiveDist: Protein Inter-Residue Distance Prediction Using Deep Learning with Attention on Quadruple Multiple Sequence Alignments
Authors: Jain Aashish , Terashi Genki , Kagaya Yuki , Maddhuri Venkata Subramaniya Sai Raghavendra , Christoffer Charles , Kihara Daisuke 
Published: November 2020

ABSTRACTProtein 3D structure prediction has advanced significantly in recent years due to improving contact prediction accuracy. This improvement has been largely due to deep learning approaches that predict inter-residue contacts and, more recently, distances using multiple sequence alignments (MSAs). In this work we present AttentiveDist, a novel approach that uses different MSAs generated with different E-values in a single model to increase the co-evolutionary information provided to the model. To determine the importance of each MSA’s feature at the inter-residue level, we added an attention layer to the deep neural network. The model is trained in a multi-task fashion to also predict backbone and orientation angles further improving the inter-residue distance prediction. We show that AttentiveDist outperforms the top methods for contact prediction in the CASP13 structure prediction competition. To aid in structure modeling we also developed two new deep learning-based sidechain center distance and peptide-bond nitrogen-oxygen distance prediction models. Together these led to a 12% increase in TM-score from the best server method in CASP13 for structure prediction.
ChIP-R: Assembling reproducible sets of ChIP-seq and ATAC-seq peaks from multiple replicates
Authors: Newell Rhys , Pienaar Richard , Balderson Brad , Piper Michael , Essebier Alexandra , Bodén Mikael 
Published: November 2020

AbstractChromatin immunoprecipitation followed by sequencing (ChIP-seq) is the primary protocol for detecting genome-wide DNA-protein interactions, and therefore a key tool for understanding transcriptional regulation. A number of factors, including low specificity of antibody and cellular heterogeneity of sample, may cause “peak” callers to output noise and experimental artefacts. Statistically combining multiple experimental replicates from the same condition could significantly enhance our ability to distinguish actual transcription factor binding events, even when peak caller accuracy and consistency of detection are compromised.We adapted the rank-product test to statistically evaluate the reproducibility from any number of ChIP-seq experimental replicates. We demonstrate over a number of benchmarks that our adaptation “ChIP-R” (pronounced ‘chipper’) performs as well as or better than comparable approaches on recovering transcription factor binding sites in ChIP-seq peak data. We also show ChIP-R extends to evaluate ATAC-seq peaks, finding reproducible peak sets even at low sequencing depth. ChIP-R decomposes peaks across replicates into “fragments” which either form part of a peak in a replicate, or not. We show that by re-analysing existing data sets, ChIP-R reconstructs reproducible peaks from fragments with enhanced biological enrichment relative to current strategies.
Bradyrhizobium diazoefficiensUSDA110 nodulation ofAeschynomene afrasperais associated with atypical terminal bacteroid differentiation and suboptimal symbiotic efficiency
Authors: Nicoud Quentin , Lamouche Florian , Chaumeret Anaïs , Balliau Thierry , Bars Romain Le , Bourge Mickaël , Pierre Fabienne , Guérard Florence , Sallet Erika , Tuffigo Solenn , Pierre Olivier , Dessaux Yves , Gilard Françoise , Gakière Bertrand , Nagy Istvan , Kereszt Attila , Zivy Michel , Mergaert Peter , Gourion Benjamin , Alunni Benoit 
Published: November 2020

AbstractLegume plants can form root organs called nodules where they house intracellular symbiotic rhizobium bacteria. Within nodule cells, rhizobia differentiate into bacteroids, which fix nitrogen for the benefit of the plant. Depending on the combination of host plants and rhizobial strains, the output of rhizobium-legume interactions is varying from non-fixing associations to symbioses that are highly beneficial for the plant.Bradyrhizobium diazoefficiensUSDA110 was isolated as a soybean symbiont but it can also establish a functional symbiotic interaction withAeschynomene afraspera. In contrast to soybean,A. afrasperatriggers terminal bacteroid differentiation, a process involving bacterial cell elongation, polyploidy and membrane permeability leading to loss of bacterial viability while plants increase their symbiotic benefit. A combination of plant metabolomics, bacterial proteomics and transcriptomics along with cytological analyses was used to study the physiology of USDA110 bacteroids in these two host plants. We show that USDA110 establish a poorly efficient symbiosis withA. afraspera, despite the full activation of the bacterial symbiotic program. We found molecular signatures of high level of stress inA. afrasperabacteroids whereas those of terminal bacteroid differentiation were only partially activated. Finally, we show that inA. afraspera, USDA110 bacteroids undergo an atypical terminal differentiation hallmarked by the disconnection of the canonical features of this process. This study pinpoints how a rhizobium strain can adapt its physiology to a new host and cope with terminal differentiation when it did not co-evolve with such a host.ImportanceLegume-rhizobium symbiosis is a major ecological process in the nitrogen cycle, responsible for the main input of fixed nitrogen in the biosphere. The efficiency of this symbiosis relies on the coevolution of the partners. Some legume plants, but not all, optimize their return-on-investment in the symbiosis by imposing on their microsymbionts a terminal differentiation program that increases their symbiotic efficiency but imposes a high level of stress and drastically reduce their viability. We combined multi-omics with physiological analyses to show that the non-natural symbiotic couple formed byBradyrhizobium diazoefficiensUSDA110 andAeschynomene afrasperais functional but displays a low symbiotic efficiency associated to a disconnection of terminal bacteroid differentiation features.