bluuebunny/crossref_metadata_2025 huggingface dataset:
Adopting a Trauma-Informed Approach to Social-Emotional Learning
Authors: Elias Maurice J. , Powlo Erica R. , Lorenzo Ava , Eichert Brian
Published: November 2020

The Collaborative for Academic, Social, and Emotional Learning (CASEL) has identified 5 sets of social-emotional learning (SEL) skills (the CASEL 5): self-awareness; self-management; social awareness and empathy; relationship skills; and responsible, ethical decision-making. SEL is critical for students to be able to manage their own internal stressors, navigate their social environment successfully, and then access a comprehensive curriculum. It provides students with critical life skills such as problem-solving and perspective-taking that will span well beyond their schooling years, helping them to become productive members of society. In this chapter, the authors describe how to assess a school system’s infrastructure for SEL and discuss how to implement SEL at both Tier 1 and Tier 2 levels in an urban disadvantaged school district where many students have been impacted by trauma. A case study is presented.
Promoting School Safety, School Climate, and Student Mental Health
Authors: Griffiths Amy Jane , Diamond Elena , Maupin Zachary , Alsip James , Keller Michael J. , Moffa Kathryn , Furlong Michael J.
Published: November 2020

The reduction of school violence requires a coordinated effort that enhances school climate and improves the sense of safety on campus. This chapter addresses the related topics of school violence, school safety, and school climate; provides an overview of the interactions among these constructs; and illustrates how they are directly linked to student mental and emotional well-being. A multidisciplinary approach is described that addresses these constructs, which are grounded in a school safety model that provides a foundation to promote students’ mental health. The process for moving toward action includes selecting an appropriate model for organizing intervention efforts, building a multidisciplinary team, developing a plan for assessment, and creating a systematic process for intervention implementation. Finally, a case study is provided to illustrate how a school district can interpret and implement these key components in the real world.
Supporting the Well-Being of Highly Mobile Students
Authors: Sulkowski Michael L.
Published: November 2020

This chapter discusses efforts that educational and mental health professionals can take to help highly mobile students. These students often are impacted by homelessness, foster care, or the juvenile justice system. Although the needs of each respective student population differ, all highly mobile students experience residential instability, which is associated with an elevated risk for experiencing disruptions in academic and psychosocial functioning. However, consistent with a dual-factor model of mental health, many highly mobile students display considerable resilience and do not succumb to the pernicious effects of residential instability. Thus, under a multitiered system of support framework, this chapter also covers specific ways that school-based practitioners can attenuate risks while bolstering resilience to support well-being. Additionally, extant laws related to educational access and service delivery for highly mobile students are reviewed such as the McKinney–Vento Homeless Assistance Improvements Act and the Plyler v. Doe Supreme Court decision.
Module 2—Psychoeducation (Sessions 4–6)
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This chapter is designed to help clinicians deliver psychoeducation about schizophrenia to families in a culturally informed manner. The chapter guides clinicians to systematically examine clients’ cultural conceptualizations of the illness and modify interventions (or the framing of interventions) in a manner that is palatable and relevant to clients. Clinicians are instructed to review core symptoms of the illness, common relapse triggers, and factors that protect against relapse using detailed handouts to guide each session. Clients learn the correct professional terminology for their symptoms, which equips them to communicate more clearly with their psychiatrists and other mental health practitioners. Examples of relevant homework assignments to increase knowledge about schizophrenia and how to manage it are provided. The chapter concludes with a case example of psychoeducation with a family of Mexican origin.
Hardiness Predicts Post-Traumatic Growth and Well-Being in Severely Wounded Servicemen and Their Spouses
Authors: Bartone Paul T , Bowles Stephen V
Published: November 2020

Introduction

Thousands of military personnel have suffered severe wounds and traumatic amputations in recent overseas conflicts. They face multiple surgeries and long, painful rehabilitation. Despite the tremendous stress for these servicemen and families, many appear to cope quite well and even thrive despite their devastating wounds. Hardiness is a world view or mindset marked by high levels of commitment and engagement in the world, a strong sense of control, and the tendency to see change as a challenge and opportunity to learn and improve. Previous research has shown that military personnel high in hardiness are at lower risk for post-traumatic stress disorder, depression, and other psychiatric symptoms following combat exposure. This study evaluated the impact of personality hardiness on post-traumatic growth (PTG) and psychological well-being in severely wounded service members and their spouses.

Materials and Methods

Male volunteers were surveyed while in hospital for severe battle wounds including loss of limbs. All were married, and all spouses also agreed to participate. Participants (N = 44) completed measures of hardiness, PTG, well-being, and neuroticism, and answered a question regarding potential benefits of their experience.

Results

Hierarchical multiple regression showed that hardiness significantly predicted both PTG and well-being, while controlling for age, education, family income, and neuroticism. Both service members and spouses indicated they experienced benefits in the following areas: strengthened family ties and connections; greater appreciation for and perspective on life; new career and educational opportunities; stronger, more resilient as a person; and formed new relationships, friends, and connections.

Conclusion

These results suggest that seriously wounded military members and their spouses who are high in hardiness are more likely to experience PTG and psychological well-being following extremely stressful experiences. Hardiness entails positive reframing of negative experiences as opportunities and challenges to overcome, and taking action to solve problems. Training programs to increase hardiness attitudes and related coping skills may thus be beneficial in facilitating healthy adaptation for severely injured patients.
Validation of the 3D reconstructed human skin micronucleus (RSMN) assay: an animal-free alternative for following-up positive results from standardin vitrogenotoxicity assays
Authors: Pfuhler Stefan , Downs Thomas R , Hewitt Nicola J , Hoffmann Sebastian , Mun Greg C , Ouedraogo Gladys , Roy Shambhu , Curren Rodger D , Aardema Marilyn J
Published: November 2020

In vitro test batteries have become the standard approach to determine the genotoxic potential of substances of interest across industry sectors. While useful for hazard identification, standard in vitro genotoxicity assays in 2D cell cultures have limited capability to predict in vivo outcomes and may trigger unnecessary follow-up animal studies or the loss of promising substances where animal tests are prohibited or not desired. To address this problem, a team of regulatory, academia and industry scientists was established to develop and validate 3D in vitro human skin-based genotoxicity assays for use in testing substances with primarily topical exposure. Validation of the reconstructed human skin micronucleus (RSMN) assay in MatTek Epi-200™ skin models involved testing 43 coded chemicals selected by independent experts, in four US/European laboratories. The results were analysed by an independent statistician according to predefined criteria. The RSMN assay showed a reproducibly low background micronucleus frequency and exhibited sufficient capacity to metabolise pro-mutagens. The overall RSMN accuracy when compared to in vivo genotoxicity outcomes was 80%, with a sensitivity of 75% and a specificity of 84%, and the between- and within-laboratory reproducibility was 77 and 84%, respectively. A protocol involving a 72-h exposure showed increased sensitivity in detecting true positive chemicals compared to a 48-h exposure. An analysis of a test strategy using the RSMN assay as a follow-up test for substances positive in standard in vitro clastogenicity/aneugenicity assays and a reconstructed skin Comet assay for substances with positive results in standard gene mutation assays results in a sensitivity of 89%. Based on these results, the RSMN assay is considered sufficiently validated to establish it as a ‘tier 2’ assay for dermally exposed compounds and was recently accepted into the OECD’s test guideline development program.
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

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

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

Alterations 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

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.
The scale and dynamics of COVID-19 epidemics across Europe
Authors: Dye Christopher , Cheng Russell C. H. , Dagpunar John S. , Williams Brian G.
Published: November 2020

The number of COVID-19 deaths reported from European countries has varied more than 100-fold. In terms of coronavirus transmission, the relatively low death rates in some countries could be due to low intrinsic (e.g. low population density) or imposed contact rates (e.g. non-pharmaceutical interventions) among individuals, or because fewer people were exposed or susceptible to infection (e.g. smaller populations). Here, we develop a flexible empirical model (skew-logistic) to distinguish among these possibilities. We find that countries reporting fewer deaths did not generally have intrinsically lower rates of transmission and epidemic growth, and flatter epidemic curves. Rather, countries with fewer deaths locked down earlier, had shorter epidemics that peaked sooner and smaller populations. Consequently, as lockdowns were eased, we expected, and duly observed, a resurgence of COVID-19 across Europe.
Analysis of node2vec random walks on networks
Authors: Meng Lingqi , Masuda Naoki
Published: November 2020

Random walks have been proven to be useful for constructing various algorithms to gain information on networks. Algorithm node2vec employs biased random walks to realize embeddings of nodes into low-dimensional spaces, which can then be used for tasks such as multi-label classification and link prediction. The performance of the node2vec algorithm in these applications is considered to depend on properties of random walks that the algorithm uses. In the present study, we theoretically and numerically analyse random walks used by the node2vec. Those random walks are second-order Markov chains. We exploit the mapping of its transition rule to a transition probability matrix among directed edges to analyse the stationary probability, relaxation times in terms of the spectral gap of the transition probability matrix, and coalescence time. In particular, we show that node2vec random walk accelerates diffusion when walkers are designed to avoid both backtracking and visiting a neighbour of the previously visited node but do not avoid them completely.
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

Playing 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

Decision-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

Speech-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

Protein 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

Protein 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

Chromatin 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

Legume 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.

Importance

Legume-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.
Response of methanogen community to elevation of cathode potentials in the presence of magnetite
Authors: Gao Kailin , Wang Xin , Huang Junjie , Xia Xingxuan , Lu Yahai
Published: November 2020

Electromethanogenesis refers to the process where methanogens utilize electrons derived from cathodes for the reduction of CO2to CH4. Setting of low cathode potentials is essential for this process. In this study, we test if magnetite, an iron oxide mineral widespread in environment, can facilitate the adaption of methanogen community to the elevation of cathode potentials in electrochemical reactors. Two-chamber electrochemical reactors were constructed with inoculants obtained from a paddy field soil. We elevated cathode potentials stepwise from the initial −0.6 V vs standard hydrogen electrode (SHE) to −0.5 V and then to −0.4 V over the 120 days acclimation. Only weak current consumption and CH4production were observed in the reactors without magnetite. But biocathodes were firmly developed and significant current consumption and CH4production were recorded in the magnetite reactors. The robustness of electro-activity in the magnetite reactors was not affected with the elevation of cathode potentials from −0.6 V to −0.4 V. But, the current consumption and CH4production were virtually halted in the reactors without magnetite when cathode potential was elevated to −0.4 V. Methanogens related toMethanospirillumwere enriched on cathode surface of the magnetite reactors at −0.4 V, whileMethanosarcinarelatively dominated in the reactors without magnetite.Methanobacteriumalso increased in the magnetite reactors but stayed off electrodes in the culture medium at −0.4 V. Apparently, magnetite greatly facilitates the development of biocathodes, and it appears that with the aid of magnetiteMethanospirillumspp. can adapt to high cathode potentials performing the efficient electromethanogenesis.

IMPORTANCE

Converting CO2to CH4through bioelectrochemistry is a promising approach for development of green energy biotechnology. This process however requires setting the low cathode potentials, which takes cost. In this study, we test if magnetite, a conductive iron mineral, can facilitate the adaption of methanogens to the elevation of cathode potentials. In the two-chamber reactors constructed using inoculants obtained from a paddy field soil, biocathodes were firmly developed in the presence of magnetite, whereas only weak electro-activity was observed in the reactors without magnetite. The elevation of cathode potentials did not affect the robustness of electro-activity in the magnetite reactors over the 120 days acclimation.Methanospirillumwas identified as the key methanogens associated with cathode surface during the operation at relatively high potentials. The findings reported in this study shed a new light on the adaption of methanogen community to the elevated cathode potentials in the presence of magnetite.
Environment-driven reprogramming of gamete DNA methylation occurs during maturation and is transmitted intergenerationally in salmon
Authors: Wellband Kyle , Roth David , Linnansaari Tommi , Curry R. Allen , Bernatchez Louis
Published: November 2020

An epigenetic basis for transgenerational plasticity is widely theorized, but convincing empirical support is limited by taxa-specific differences in the presence and role of epigenetic mechanisms. In teleost fishes, DNA methylation generally does not undergo extensive reprogramming and has been linked with environmentally-induced intergenerational effects, but solely in the context of early life environmental differences. Using whole genome bisulfite sequencing, we demonstrate that differential methylation of sperm occurs in response to captivity during the maturation of Atlantic Salmon (Salmo salar), a species of major economic and conservation significance. We show that adult captive exposure further induces differential methylation in an F1 generation that is associated with fitness-related phenotypic differences. Genes targeted with differential methylation were consistent with genes differential methylated in other salmonid fishes experiencing early-life hatchery rearing, as well as genes under selection in domesticated species. Our results support a mechanism of transgenerational plasticity mediated by intergenerational inheritance of DNA methylation acquired late in life for salmon. To our knowledge, this is the first-time environmental variation experienced later in life has been directly demonstrated to influence gamete DNA methylation in fish.
Conservation of glutathione S-transferase mRNA and protein sequences similar to human and horse Alpha class GST A3-3 across dog, goat, and opossum species
Authors: Hubert Shawna M. , Samollow Paul B. , Lindström Helena , Mannervik Bengt , Ing Nancy H.
Published: November 2020

Recently, the glutathione S-transferase A3-3 (GST A3-3) homodimeric enzyme was identified as the most efficient enzyme that catalyzes isomerization of the precursors of testosterone, estradiol, and progesterone in the gonads of humans and horses. However, the presence of GST A3-3 orthologs with equally high ketosteroid isomerase activity has not been verified in other mammalian species, even though pig and cattle homologs have been cloned and studied. IdentifyingGSTA3genes is a challenge because of multipleGSTAgene duplications (12 in the human genome), so few genomes have a correspondingGSTA3gene annotated. To improve our understanding ofGSTA3gene products and their functions across diverse mammalian species, we cloned homologs of the horse and humanGSTA3mRNAs from the testes of a dog, goat, and gray short-tailed opossum, with those current genomes lackingGSTA3gene annotations. The resultant novelGSTA3mRNA and inferred protein sequences had a high level of conservation with humanGSTA3mRNA and protein sequences (≥ 70% and ≥ 64% identities, respectively). Sequence conservation was also apparent for the 13 residues of the “H-site” in the 222 amino acid GSTA3 protein that is known to interact with the steroid substrates. Modeling predicted that the dog GSTA3-3 is a more active ketosteroid isomerase than the goat or opossum enzymes. Our results help us understand the active sites of mammalian GST A3-3 enzymes, and their inhibitors may be useful for reducing steroidogenesis for medical purposes, such as fertility control or treatment of steroid-dependent diseases.
Comprehensive benchmarking of single cell RNA sequencing technologies for characterizing cellular perturbation
Authors: Karen Verboom , Assefa Alemu T , Yigit Nurten , Anckaert Jasper , Vandamme Niels , Rombaut Dries , Saeys Yvan , Thas Olivier , Speleman Frank , Durinck Kaat , Vandesompele Jo
Published: November 2020

Technological advances in transcriptome sequencing of single cells continues to provide an unprecedented view on tissue composition and cellular heterogeneity. While several studies have compared different single cell RNA-seq methods with respect to data quality and their ability to distinguish cell subpopulations, none of these studies investigated the heterogeneity of the cellular transcriptional response upon a chemical perturbation. In this study, we evaluated the transcriptional response of NGP neuroblastoma cells upon nutlin-3 treatment using the C1, ddSeq and Chromium single cell systems. These devices and library preparation methods are representative for the wide variety of platforms, ranging from microfluid chips to droplet-based systems and from full transcript sequencing to 3-prime end sequencing. In parallel, we used bulk RNA-seq for molecular characterization of the transcriptional response. Two complementary metrics to evaluate performance were applied: the first is the number and identity of differentially expressed genes as defined in consensus by two statistical models, and the second is the enrichment analysis of biological signals. Where relevant, to make the data more comparable, we downsampled sequencing library size, selected cell subpopulations based on specific RNA abundance features, or created pseudobulk samples. While the C1 detects the highest number of genes per cell and better resembles bulk RNA-seq, the Chromium identifies most differentially expressed genes, albeit still substantially fewer than bulk RNA-seq. Gene set enrichment analyses reveals that detection of a limited set of the most abundant genes in single cell RNA-seq experiments is sufficient for molecular phenotyping. Finally, single cell RNA-seq reveals a heterogeneous response of NGP neuroblastoma cells upon nutlin-3 treatment, revealing putative late-responder or resistant cells, both undetected in bulk RNA-seq experiments.
Reversed upper glycolysis and rapid activation of oxidative pentose phosphate pathway supports the oxidative burst in neutrophils
Authors: Britt Emily C. , Fan Jing
Published: November 2020

Neutrophils are abundant white blood cells at the frontline of innate immunity. Upon stimulation, neutrophils rapidly activate effector functions such as the oxidative burst and neutrophil extracellular traps (NETs) to eliminate pathogens. However, little is known about how neutrophil metabolism powers these functions. Our metabolomic analysis on primary human neutrophils revealed that neutrophil metabolism is rapidly rewired upon pro-inflammatory activation, with particularly profound changes observed in glycolysis and the pentose phosphate pathway (PPP). We found that the stimulation-induced changes in PPP were specifically coupled with the oxidative burst. The oxidative burst requires a large amount of NADPH to fuel superoxide production via NADPH Oxidase (NOX). Isotopic tracing studies revealed that in order to maximize the NADPH yield from glucose metabolism, neutrophils quickly adopt near complete pentose cycle during the oxidative burst. In this metabolic mode, all glucose is shunted into the oxidative PPP, and the resulting pentose-phosphate is recycled back to glucose-6-phosphate, which then re-enters the oxidative PPP. To enable this recycling, net flux through the upper glycolytic enzyme glucose-6-phosphate isomerase (GPI) is completely reversed. This allows oxidative PPP flux in neutrophils to reach greater than two-fold of the glucose uptake rate, far exceeding other known mammalian cells and tissues. Intriguingly, the adoption of this striking metabolic mode is completely dependent on an increased demand for NADPH associated with the oxidative burst, as inhibition of NOX resets stimulated neutrophils to use glycolysis-dominant glucose metabolism, with oxidative PPP flux accounting for less than 10% of glucose metabolism. Together, these data demonstrated that neutrophils have remarkable metabolic flexibility that is essential to enable the rapid activation of their effector functions.

Graphic Abstract
3D segmentation of perivascular spaces on T1-weighted 3 Tesla MR images with a convolutional autoencoder and a U-shaped neural network
Authors: Boutinaud Philippe , Tsuchida Ami , Laurent Alexandre , Adonias Filipa , Hanifehlou Zahra , Nozais Victor , Verrecchia Violaine , Lampe Leonie , Zhang Junyi , Zhu Yi-Cheng , Tzourio Christophe , Mazoyer Bernard , Joliot Marc
Published: November 2020

We implemented a deep learning (DL) algorithm for the 3-dimensional segmentation of perivascular spaces (PVSs) in deep white matter (DWM) and basal ganglia (BG). This algorithm is based on an autoencoder and a U-shaped network (U-net), and was trained and tested using T1-weighted magnetic resonance imaging (MRI) data from a large database of 1,832 healthy young adults. An important feature of this approach is the ability to learn from relatively sparse data, which gives the present algorithm a major advantage over other DL algorithms. Here, we trained the algorithm with 40 T1-weighted MRI datasets in which all “visible” PVSs were manually annotated by an experienced operator. After learning, performance was assessed using another set of 10 MRI scans from the same database in which PVSs were also traced by the same operator and were checked by consensus with another experienced operator. The Sorensen-Dice coefficients for PVS voxel detection in DWM (resp. BG) were 0.51 (resp. 0.66), and 0.64 (resp. 0.71) for PVS cluster detection (volume threshold of 0.5 within a range of 0 to 1). Dice values above 0.90 could be reached for detecting PVSs larger than 10 mm3and 0.95 for PVSs larger than 15 mm3. We then applied the trained algorithm to the rest of the database (1,782 individuals). The individual PVS load provided by the algorithm showed a high agreement with a semi-quantitative visual rating done by an independent expert rater, both for DWM and for BG. Finally, we applied the trained algorithm to an age-matched sample from another MRI database acquired using a different scanner. We obtained a very similar distribution of PVS load, demonstrating the interoperability of this algorithm.