bluuebunny/crossref_metadata_2025_split huggingface dataset:
Batf-mediated Epigenetic Control of Effector CD8+ T Cell Differentiation
Authors: Tsao Hsiao-Wei , Kaminski James , Kurachi Makoto , Barnitz R. Anthony , DiIorio Michael A. , LaFleur Martin W. , Ise Wataru , Kurosaki Tomohiko , Wherry E. John , Haining W. Nicholas , Yosef Nir 
Published: January 2021

SUMMARYThe response of cytotoxic T cells to their cognate antigen involves rapid and broad changes in gene expression that are coupled with extensive chromatin remodeling. Here, we study the mechanisms by which the basic leucine zipper ATF-like transcription factor Batf helps regulate this process. Through genome-scale profiling, we observe critical roles for Batf in inducing transcriptional changes in stimulated naive cells, while affecting the chromatin at several levels, namely binding of key transcription factors, accessibility, and long range contacts. We identify a critical network of transcription factors that cooperate with Batf, including its binding partner Irf4, as well as Runx3 and T-bet, and demonstrate its synergistic activity in initiating aspects of the effector T cells’ transcriptional and epigenetic program in ectopically-induced fibroblasts. Our results provide a comprehensive resource for studying the epigenomic and transcriptomic landscape of effector differentiation of cytotoxic T cells.
Intricate regulation of ribosome biogenesis genes in response to mTORC1 signaling
Authors: Kumar Sanjay , Mashkoor Muneera , Balamurugan Priya , Grove Anne 
Published: January 2021

SummaryGenes encoding ribosomal proteins are repressed in response to inhibition of mTORC1. InSaccharomyces cerevisiae, this involves dissociation of the activator Ifh1p in a process that depends on Utp22p, a protein that also functions in pre-rRNA processing. Ifh1p has a paralog, Crf1p, which can mediate mTORC1 inhibition by acting as a repressor. Ifh1p and Crf1p derive from a common ancestor, which may have acted as both an activator and a repressor. We report here thatUTP22andRRP7, which encodes another pre-rRNA processing factor, are controlled by mTORC1; both gene promoters are bound by Ifh1p, which dissociates on mTORC1 inhibition. Notably, Crf1p acts as an activator as evidenced by reduced expression in acrf1Δstrain. By contrast, Crf1p is required to repress expression ofHMO1, which encodes a cofactor involved in communicating mTORC1 activity to target genes. Our data therefore indicate that Crf1p exhibits the dual repressor/activator functions of the Ifh1p-Crf1p ancestor.
HIV-1-induced apathy: Mitigation by the gut metabolite, S-Equol
Authors: McLaurin Kristen A. , Bertrand Sarah J. , Illenberger Jessica M. , Harrod Steven B. , Mactutus Charles F. , Booze Rosemarie M. 
Published: January 2021

ABSTRACTThe persistence of motivational alterations, including apathy, in older HIV-1 seropositive individuals, despite treatment with combination antiretroviral therapy, necessitates the development of innovative adjunctive therapeutics. S-Equol (SE), a selective estrogen receptor β agonist, has been implicated as a neuroprotective and/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for apathy, however, has yet to be systematically evaluated. Thus, beginning at approximately seven to nine months of age, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2 mg) or vehicle and assessed in a series of tasks to evaluate goal-directed behavior. First, at the genotypic level, apathetic behavior in older HIV-1 Tg rats treated with vehicle was characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose and enhanced drug seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated alterations in goal-directed behaviors and reduced drug seeking behavior in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited prominent decreases in dendritic branching and a shift towards longer dendritic spines with decreased head diameter; synaptic dysfunction that was partially restored by SE treatment. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.
Folding and Persistence Time of Intramolecular G-Quadruplexes Transiently Embedded in a DNA duplex
Authors: Thao Tran Phong Lan , Rieu Martin , Hodeib Samar , Joubert Alexandra , Ouellet Jimmy , Alberti Patrizia , Bugaut Anthony , Allemand Jean-François , Boulé Jean-Baptiste , Croquette Vincent 
Published: January 2021

ABSTRACTG-quadruplex (G4) DNA structures have emerged as important regulatory elements during DNA replication, transcription or repair. While manyin-vitrostudies have focused on the kinetics of G4 formation within DNA single-strands, G4 are foundin-vivoin double-stranded DNA regions, where their formation is challenged by pairing between the two complementary strands. Since the energy of hybridization of Watson-Crick structures dominates the energy of G4 folding, this competition should play a critical role on the persistence of G4in vivo. To address this issue, we designed a single molecule assay allowing measuring G4 folding and persistence while the structure is periodically challenged by the complementary strand. We quantified both the folding rate and the persistence time of biologically relevant G4 structures and showed that the dynamics of G4 formation depends strongly on the genomic location. G4 are found much more stable in promoter regions and replication origins than in telomeric regions. In addition, we characterized how G4 dynamics was affected by G4 ligands and showed that both folding rate and persistence increased. Our assay opens new perspectives for the measurement of G4 dynamics, which is critical to understand their role in genetic regulation.
Oscillatory brain activity links experience to expectancy during associative learning
Authors: Riels Kierstin , Campagnoli Rafaela , Thigpen Nina , Keil Andreas 
Published: January 2021

AbstractAssociating a novel situation with a specific outcome involves a cascade of cognitive processes, including selecting relevant stimuli, forming predictions regarding expected outcomes, and updating memorized predictions based on experience. The present manuscript uses computational modeling and machine learning to test the hypothesis that alpha-band (8-12 Hz) neural oscillations are involved in the updating of expectations based on experience. Participants learned that a visual cue predicted an aversive loud noise with a probability of 50 percent. The Rescorla-Wagner model of associative learning explained trial-wise changes in self-reported noise expectancy as well as alpha power changes. Both experience in the past trial and self-reported expectancy for the subsequent trial were accurately decoded based on the topographical distribution of alpha power. Decodable information during initial association formation and contingency report recurred when viewing the conditioned cue. Findings support the idea that alpha oscillations have multiple, simultaneous, and unique roles in association formation.
Serial passage of the human probioticE. coliNissle 1917 in an insect host leads to changed bacterial phenotypes
Authors: Schröder Nicolas C. H. , Korša Ana , Wami Haleluya , Dobrindt Ulrich , Kurtz Joachim 
Published: January 2021

SummaryProbiotics are living microorganisms that are increasingly and successfully used for the therapy of various diseases. The most common use of probiotics is the therapeutic and preventive application for gastrointestinal disorders. The probioticEscherichia colistrain Nissle 1917 (EcN) has been proven to effectively prevent and alleviate intestinal diseases, including various types of inflammatory bowel disease. Despite the widespread medical application ofEcN, the underlying mechanisms of its protective effect remain elusive. The present work aimed to establish an insect model system to enable further research on the modes of action ofEcN and the dynamics of adaptation to a novel host organism. Using a long-term serial passage approach, we orally introducedEcN to the host, the red flour beetleTribolium castaneum. After multiple cycles of intestinal colonization in beetle larvae, several attributes of the passaged replicate lines were assessed. We observed phenotypic changes in growth and motility but no genetic changes in the lines after passaging through the host and its flour environment. One of theEcN lines exposed to the host displayed peculiar morphological and physiological characteristics showing that serial passage ofEcN can generate differential phenotypes.
Determinants of genetic diversity and species richness of North American amphibians
Authors: Schmidt Chloé , Munshi-South Jason , Dray Stéphane , Garroway Colin J 
Published: January 2021

AbstractEcological limits on the population sizes and number of species a region is capable of supporting are thought to simultaneously produce spatial patterns in genetic diversity and species richness. However, we do not know the extent to which resource-based environmental limits jointly determine these patterns of biodiversity in ectotherms because of their low energy requirements compared to endotherms. Here, we adapt a framework for the ways ecological limits may shape genetic diversity and species richness previously tested in mammals for amphibians to determine whether similar processes produce continental patterns of biodiversity across both taxa. Repurposing open, raw microsatellite data from 19 species sampled at 554 sites in North America we found that spatial patterns of genetic diversity run opposite to patterns of species richness and genetic differentiation. However, while measures of resource availability and niche heterogeneity predict 89% of the variation in species richness, these landscape metrics are poor predictors of genetic diversity. Although heterogeneity appears to be an important driver of genetic and species biodiversity patterns in both amphibians and mammals, our results suggest that variation in genetic diversity both within and across species makes it difficult to infer general processes producing spatial patterns of amphibian genetic diversity.
Low STING expression in a transplantable KrasG12D/P53kolung cancer model contributes to SiglecF+neutrophil and CD103+Treg accumulation in tumors
Authors: Gros Laurent , Ursino Chiara , Constanzo Julie , Zangger Nadine , Meylan Etienne , Bonnefoy Nathalie , Faget Julien 
Published: January 2021

AbstractLung cancer is the leading cause of mortality by cancer worldwide. Non-small cell lung cancer is the most common type of lung cancer and mutations in theKRASgene are frequently found in this pathology. While immune checkpoint inhibitors are providing new hope for lung cancer care, only a subset of patients show durable benefit from these new therapies designed to drive an efficient anti-tumor immune response. Hence, it is crucial to better understand the mechanisms through which the tumor immune microenvironment is established in lung tumors. Using bioinformatics, we observed that high expression of the STimulator of INterferon Gene (STING) associates with a longer overall survival specifically in KRAS mutant cancer patients. In lung cancer cell lines, STING expression is linked to interferon response and epithelial-to-mesenchymal transition. Because STING activation in immune cells of the tumor microenvironment using specific agonists is an emerging strategy to trigger an anti-tumor immune response, we took advantage of two transplantable models ofKrasdriven lung cancer, expressing high or low levels of STING, to investigate the function of STING directly in cancer cellsin vivo. We observed that high-STING expression and constitutive STING signaling were critical for transplanted tumor formation rather than playing a major role in tumor immunogenicity. Besides, low-STING expression in cancer cells is associated with an immunosuppressive tumor microenvironment characterized by the accumulation of tumor promoting SiglecF+neutrophils and CD103+regulatory T cells. In that model, knocking out STING increased the early response to anti-PD1 treatment. We conclude that low-STING expression in cancer cells might confer them an independence from pro-inflammatory signals and a greater immunosuppressive capability and aggressiveness.
A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease
Authors: Leinenga Gerhard , Koh Wee Kiat , Götz Jürgen 
Published: January 2021

AbstractBackgroundAducanumab is an anti-amyloid-β (Aβ) antibody that achieved reduced amyloid pathology in Alzheimer’s disease (AD) trials, but it is controversial whether it also improved cognition. It has been claimed that this would require a sufficiently high cumulative dose of the antibody in the brain. Therapeutic ultrasound, in contrast, has only begun to be investigated in human AD clinical trials. We have previously shown that scanning ultrasound in combination with intravenously injected microbubbles (SUS), that temporarily and safely opens the blood-brain barrier (BBB), removes amyloid and restores cognition in APP23 mice. It has not been directly tested how the effects of SUS compare to immunotherapy or whether a combination therapy is more effective.MethodsIn a study comprising four treatment arms, we tested the efficacy of an Aducanumab analogue, Adu, in comparison to SUS, as well as a combination therapy in APP23 mice, using sham as a control (aged 13-22 months). The active place avoidance (APA) test was used to test spatial memory, and histology and ELISA were used to measure amyloid. Brain antibody levels were also determined.ResultsWe found that both Adu and SUS reduced the total plaque area in the hippocampus to a similar degree, with no additive effect in the combination treatment (SUS+Adu). Whereas there was only a trend towards a reduction for both Adu and SUS in the cortex, the combination trial yielded a statistically significant reduction compared to sham. Only the SUS and SUS+Adu groups included animals that had their plaque load reduced to below 1% from above 10%. There was a robust improvement in spatial memory for SUS+Adu only. In this group, when measured three days post-treatment, Adu levels were still 5-fold increased in the combination therapy compared to delivery of Adu on its own.Together, these findings suggest that SUS should be seriously considered as a treatment option for AD. Alternatively, a combination trial using Aducanumab together with ultrasound to increase brain levels of Aducanumab may be warranted, as the two approaches may engage different (albeit shared) clearance mechanisms.
Stress-induced alterations of mesocortical and mesolimbic dopaminergic pathways
Authors: Quessy F , Bittar T , Blanchette LJ , Lévesque M , Labonté B 
Published: January 2021

AbstractOur ability to develop the cognitive strategies required to deal with daily-life stress is regulated by region-specific neuronal networks. Experimental evidences suggest that prolonged stress in mice induces depressive-like behaviors via morphological, functional and molecular changes affecting the mesolimbic and mesocortical dopaminergic pathways. Yet, the molecular interactions underlying these changes are still poorly understood and whether they affect males and females similarly is unknown. Here, we used chronic social defeat stress (CSDS) to induce depressive-like behaviors in male and female mice. Density of the mesolimbic and cortical projections was assessed via immuno-histochemistry combined with Sholl analysis along with the staining of the activity-dependent markers pERK and c-Fos in the ventral tegmental area (VTA), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We showed that social stress decreases the density of dopaminergic axonal projections to the mPFC but not to the NAc in susceptible and resilient mice. This was accompanied by sex-specific alterations of pERK and c-Fos expression in the VTA of susceptible but not resilient mice. Our results indicate that social defeat stress impacts the mesolimbic and mesocortical pathways by altering the molecular interactions regulating somatic and axonal plasticity differently in males and females.
Edible insects, what about the perceptions of Belgian youngsters?
Authors: Detilleux Loïc , Wittock Gabrielle , Dogot Thomas , Francis Frédéric , Caparros Megido Rudy 
Published: January 2021

PurposeEdible insects are considered as a novel food in western countries, with their introduction to cuisine having to overcome major barriers, such as disgust. The studies related to acceptance of entomophagy have exponentially grown since 2015. However, such studies generally focus on people older than 18 years old. The purpose of this study is to assess the perceptions of youngsters towards edible insects.Design/methodology/approachA survey associated with an optional tasting session was conducted to record opinion of 151 youngsters in Belgium (9–17-year-olds).FindingsMany respondents are acquainted with entomophagy and had already eaten insect-based food. Most youngsters associated insects as snacks and salty foods, and they agreed to consume processed insects (falafel) during the tasting session. Tasters had to evaluate the falafel, and higher ratings were recorded in male respondents, as highlighted in studies including adults. More negative evaluations would be expected among older respondents if unprocessed insects were served, as they were more willing to consume processed insects than entire insects. Finally, attitudes towards entomophagy evolved positively after the tasting session. Such events are consequently recommended to promote entomophagy across western youngsters.Originality/valueFew studies explored the attitude of western youngsters towards entomophagy. This paper aims to fill this gap by focusing on this young component of the Belgian population.
Is feedforward the way forward? A case of managers in a manufacturing firm
Authors: Dixit Ramnath , Sinha Vinita 
Published: January 2021

Purpose
The purpose of this case study is to highlight the role of feedforward as a potential tool for managers in encouraging coworkers and subordinates to excel at their workplace performance.

Design/methodology/approach
Insights were captured through real-time observations made during three feedforward sessions conducted at regular intervals during the course of a six-month training intervention. Semi-structured interviews were also conducted with participants to gather individual perspectives.

Findings
The findings of the study showed positive results in feedforward as a mechanism to strengthen employee performance at the workplace. Participants also reported deeper involvement in the feedforward process as compared to the conventional feedback method.

Practical implications
The study has wider practical implications in the corporate world, as it provides managers with a practical tool to mentor subordinates and coworkers toward on-the-job performance. Feedforward is easy to apply and forward-looking in its approach.

Social implications
Feedforward has applications in corporate environments as well as families, associations, and academic institutions. It offers immense value by fostering a climate of social support and mutual co-operation.

Originality/value
The feedforward exercise mentioned in the study is relevant on account of its applicability in various organizations across industries. It provides managers with an opportunity to receive and share insightful suggestions with coworkers in an open and transparent environment.
Simulations of micropolar nanofluid-equipped natural convective-driven flow in a cavity
Authors: Naeem Ullah  , Nadeem Sohail , McCash Luthais , Saleem Anber , Issakhov Alibek 
Published: January 2021

Purpose
This paper aims to focus on the natural convective flow analysis of micropolar nanofluid fluid in a rectangular vertical container. A heated source is placed in the lower wall to generate the internal flow. In further assumptions, the left/right wall are kept cool, while the upper and lower remaining portions are insulated. Free convection prevails in the regime because of thermal difference in-between the lower warmer and upper colder region.

Design/methodology/approach
The physical setup owns mathematical framework in-terms of non-linear partial differential equations. For the solution purpose of the differential system, finite volume method is adopted. The interesting features of the flow along with thermal transportation involve both translational and rotational movement of fluid particles.

Findings
Performing the simulations towards flow controlling variables the outputs are put together in contour maps and line graphs. It is indicated that the variations in flow profile mass concentration and temperature field augments at higher Rayleigh parameter because of stronger buoyancy effects. Higher viscosity coefficient implies decrease in flow and thermal transportation. Further, the average heat transfer rate also grows by increasing both the Rayleigh parameter and heated source length.

Originality/value
To the best of the authors’ knowledge, no such study has been addressed yet. Further, the results are validated by comparing with previously published work.
Design and implementation of construction cost prediction model based on SVM and LSSVM in industries 4.0
Authors: Fan Miao , Sharma Ashutosh 
Published: January 2021

PurposeIn order to improve the accuracy of project cost prediction, considering the limitations of existing models, the construction cost prediction model based on SVM (Standard Support Vector Machine) and LSSVM (Least Squares Support Vector Machine) is put forward.Design/methodology/approachIn the competitive growth and industries 4.0, the prediction in the cost plays a key role.FindingsAt the same time, the original data is dimensionality reduced. The processed data are imported into the SVM and LSSVM models for training and prediction respectively, and the prediction results are compared and analyzed and a more reasonable prediction model is selected.Originality/valueThe prediction result is further optimized by parameter optimization. The relative error of the prediction model is within 7%, and the prediction accuracy is high and the result is stable.
Assessment of the current state of sustainability in a manufacturing firm
Authors: Pande Bhavya , Adil Gajendra Kumar 
Published: January 2021

PurposeSustainable manufacturing is gaining prominence in light of the rising environmental and social concerns worldwide. One major task to enhance manufacturing sustainability is assessment of the current state of sustainability of a manufacturing firm. This paper reviews the existing sustainability assessment approaches applicable for manufacturing firms and observes that most of these approaches are not easy to apply for reasons such as high amount of skill, data and time requirement. Towards bridging this gap, this study proposes a sustainability assessment approach.Design/methodology/approachThe assessment approach proposed in the paper uses a predefined list of potential sustainable manufacturing practices (SMPs) covering the primary and support activity domains of a manufacturing firm's value chain. It proposes a method to assess the extent of implementation of SMPs and identify associated drivers and barriers for each SMP area/category along the value chain of a firm as well as at overall firm level. A case study from textile industry is presented to demonstrate the utility of this approach.FindingsThe sustainability assessment approach adopted in this study uses less time and skills as well as ensures comprehensive coverage of SMPs. It provided valuable information to the management of the case company on how sustainable their practices are and why?Originality/valueThe study highlights the importance of sustainability assessment at SMP area/category level as well as explores practice area/category specific drivers and barriers. It provides a useful approach for a quick assessment of the current state of sustainability in manufacturing firms.