bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of endogenous retroviruses during brain development causes neuroinflammation
Authors: Jönsson Marie E , Garza Raquel , Sharma Yogita , Petri Rebecca , Södersten Erik , Johansson Jenny G , Johansson Pia A , Atacho Diahann AM , Pircs Karolina , Madsen Sofia , Yudovich David , Ramakrishnan Ramprasad , Holmberg Johan , Larsson Jonas , Jern Patric , Jakobsson Johan 
Published: July 2020

AbstractEndogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for neuroinflammation, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons.In vivodeletion ofTrim28in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERV expression in excitatory neurons in the adult brain. Neuronal ERV expression was linked to inflammation, including activated microglia, and aggregates of ERV-derived proteins. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causalin vivoevidence demonstrating that transcriptional activation of ERV in neurons results in neuroinflammation.
Gene-based mapping of trehalose biosynthetic pathway genes reveals association with source- and sink-related yield traits in a spring wheat panel
Authors: Lyra Danilo H. , Griffiths Cara A. , Watson Amy , Joynson Ryan , Molero Gemma , Igna Alina-Andrada , Hassani-Pak Keywan , Reynolds Matthew P. , Hall Anthony , Paul Matthew J. 
Published: July 2020

SummaryTrehalose 6-phosphate (T6P) signalling regulates carbon use and allocation and is a target to improve crop yields. However, the specific contributions of trehalose phosphate synthase (TPS) and trehalose phosphate phosphatase (TPP) genes to source- and sink-related traits remain largely unknown. We used exome-capture sequencing on TPS and TPP genes to estimate and partition the genetic variation of yield-related traits in a spring wheat (Triticum aestivum) breeding panel with diverse genetic heritage. Twelve phenotypes were directly correlated to TPS and TPP genes including final biomass (source) and spikes and grain numbers and grain filling traits (sink) showing indications of both positive and negative gene selection. Additionally, individual genes explained a substantial proportion of heritability (e.g. 3, 12, and 18% of the variance in gene homeologues most closely related to ArabidopsisTPS1for final biomass), indicating a considerable contribution of this regulatory pathway to the phenotypic variation. Most importantly, two significant missense point mutations in the exon 6 of theTPS1gene on chromosome 1D substantially increased plant height and peduncle length which was inversely related to grains per m2. Gene-based prediction resulted in significant gains of predictive ability (6% improvement) for grain weight when gene effects were combined with the whole genome markers, potentially helping breeding programs in designing strategic crosses. ThreeTPS1homeologues were particularly significant in trait variation. Our study has generated a wealth of information on the role of natural variation of TPS and TPP genes related to yield potential.
Mapping the Role of AcrAB-TolC Efflux Pumps in the Evolution of Antibiotic Resistance Reveals Near-MIC Treatments Facilitate Resistance Acquisition
Authors: Langevin Ariel M. , El Meouche Imane , Dunlop Mary J. 
Published: July 2020

ABSTRACTAntibiotic resistance has become a major public health concern as bacteria evolve to evade drugs, leading to recurring infections and a decrease in antibiotic efficacy. Systematic efforts have revealed mechanisms involved in resistance; yet, in many cases, how these specific mechanisms accelerate or slow the evolution of resistance remains unclear. Here, we conducted a systematic study of the impact of the AcrAB-TolC efflux pump on the evolution of antibiotic resistance. We mapped how population growth rate and resistance change over time as a function of both the antibiotic concentration and the parent strain’s genetic background. We compared the wild type strain to a strain overexpressing AcrAB-TolC pumps and a strain lacking functional pumps. In all cases, resistance emerged when cultures were treated with chloramphenicol concentrations near the MIC of their respective parent strain. The genetic background of the parent strain also influenced resistance acquisition. The wild type strain evolved resistance within 24 h through mutations in theacrABoperon and its associated regulators. Meanwhile, the strain overexpressing AcrAB-TolC evolved resistance more slowly than the wild type strain; this strain achieved resistance in part through point mutations inacrBand theacrABpromoter. Surprisingly, the strain without functional AcrAB-TolC efflux pumps still gained resistance, which it achieved through upregulation of redundant efflux pumps. Overall, our results suggest that treatment conditions just above the MIC pose the largest risk for the evolution of resistance and that AcrAB-TolC efflux pumps impact the pathway by which chloramphenicol resistance is achieved.IMPORTANCECombatting the rise of antibiotic resistance is a significant challenge. Efflux pumps are an important contributor to drug resistance; they exist across many cell types and can export numerous classes of antibiotics. Cells can regulate pump expression to maintain low intracellular drug concentrations. Here, we explored how resistance emerged depending on the antibiotic concentration, as well as the presence of efflux pumps and their regulators. We found that treatments near antibiotic concentrations that inhibit the parent strain’s growth were most likely to promote resistance. While wild type, pump overexpression, and pump knock out strains were all able to evolve resistance, they differed in the absolute level of resistance evolved, the speed at which they achieved resistance, and the genetic pathways involved. These results indicate that specific treatment regimens may be especially problematic for the evolution of resistance and that the strain background can influence how resistance is achieved.
Knockout of the serotonin transporter in the rat mildly modulates decisional anhedonia
Authors: Guo Chao Ciu-Gwok , Verheij Michel MM , Homberg Judith R 
Published: July 2020

AbstractSerotonin transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. While data exist on the effect of serotonin transporter gene knockout (5-HTT-/-) in rodents on consummatory and anticipatory anhedonia, with mixed outcomes, the effect on decisional anhedonia has not been investigated thus far. Here, we tested whether 5-HTT-/-contributes to decisional anhedonia. To this end, we established a novel touchscreen-based “go/go” task of visual decision-making. During the learning of stimulus discrimination, 5-HTT+/+rats performed more optimal decision-making compared to 5-HTT-/-rats at the beginning, but this difference did not persist throughout the learning period. During stimulus generalization, the generalization curves were similar between both genotypes and did not alter as the learning progress. Interestingly, the response time in 5-HTT+/+rats increased as the session increased in general, while 5-HTT-/-rats tended to decrease. The response time difference might indicate that 5-HTT-/-rats altered willingness to exert cognitive effort to the categorization of generalization stimuli. These results suggest that the effect of 5-HTT ablation on decisional anhedonia is mild and interacts with learning, explaining the discrepant findings on the link between 5-HTT gene and depression.
Innovation of heterochromatin functions drives rapid evolution of essential ZAD-ZNF genes inDrosophila
Authors: Kasinathan Bhavatharini , Colmenares Serafin U. , McConnell Hannah , Young Janet M. , Karpen Gary H. , Malik Harmit S. 
Published: July 2020

AbstractContrary to prevailing dogma, evolutionarily young and dynamic genes can encode essential functions. Here, we investigate genetic innovation inZAD-ZNFgenes, which encode the most abundant class of insect transcription factors. We find that evolutionarily dynamicZAD-ZNFgenes are more likely to encode essential functions inDrosophila melanogasterthan ancient, conservedZAD-ZNFgenes. To understand the basis of this unexpected correlation, we focus on theNicknack ZAD-ZNFgene.Nicknackis an evolutionarily young, poorly retained inDrosophilaspecies, and evolves under strong positive selection, yet we find that it is necessary for larval development inD. melanogaster.We show thatNicknackencodes a heterochromatin-localizing protein like its closely related paralogOddjob, also an evolutionarily dynamic, essentialZAD-ZNFgene. We find that the divergentD. simulansNicknack protein can still localize toD. melanogasterheterochromatin and rescue viability of female but not maleNicknack-nullD. melanogaster. Our findings suggest that innovation for rapidly changing heterochromatin functions might provide a general explanation for the essential functions of many evolutionarily dynamicZAD-ZNFgenes in insects.
Endogenous piRNA-guided slicing triggers responder and trailer piRNA production from viral RNA inAedes aegyptimosquitoes
Authors: Joosten Joep , Overheul Gijs J. , Van Rij Ronald P. , Miesen Pascal 
Published: July 2020

ABSTRACTIn the germline of animals, PIWI interacting (pi)RNAs protect the genome against the detrimental effects of transposon mobilization. InDrosophila,piRNA-mediated cleavage of transposon RNA triggers the production of responder piRNAs via ping-pong amplification. Responder piRNA 3’ end formation is coupled to the production of downstream trailer piRNAs mediated by the nuclease Zucchini, expanding the repertoire of transposon piRNA sequences. InAedes aegyptimosquitoes, piRNAs are generated from viral RNA, yet, it is unknown how viral piRNA 3’ ends are formed and whether viral RNA cleavage gives rise to trailer piRNA production. Here we report that inAe. aegypti, virus- and transposon-derived piRNAs have sharp 3’ ends, and are biased for downstream uridine residues, features reminiscent of Zucchini cleavage of precursor piRNAs inDrosophila. We designed a reporter system to study viral piRNA 3’ end formation and found that targeting viral RNA by abundant endogenous piRNAs triggers the production of responder and trailer piRNAs. Using this reporter, we identified theAe. aegyptiorthologs of Zucchini and Nibbler, two nucleases involved in piRNA 3’ end formation. Our results furthermore suggest that autonomous piRNA production from viral RNA can be triggered and expanded by an initial cleavage event guided by genome-encoded piRNAs.
Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer
Authors: Wilson-Robles H , Miller T , Jarvis J , Terrell J , Dewsbury N , Kelly T , Herzog M , Bygott T , Hardat N , Michel G 
Published: July 2020

AbstractIntroductionNucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer.Materials and MethodsBlood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results.ResultsNucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma.ConclusionsWhen samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.
Predictive Analysis for COVID-19 Spread in India by Adaptive Compartmental Model
Authors: Singh S. S. , Mohapatra D. K. 
Published: July 2020

AbstractThe role of mathematical modelling in predicting spread of an epidemic is of vital importance. The purpose of present study is to develop and apply a computational tool for predicting evolution of different epidemiological variables for COVID-19 in India. We propose a dynamic SIRD (Susceptible-Infected-Recovered-Dead) and SEIRD (Susceptible-Exposed-Infected-Recovered-Dead) model for this purpose. In the dynamic model, time dependent infection rate is assumed for estimating evolution of different variables of the model. Parameter estimation of the model is the first step of the analysis which is performed by least square optimization of priori data. In the second step of the analysis, simulation is carried out by using evaluated parameters for prediction of the outbreak. The computational model has been validated against real data for COVID-19 outbreak in Italy. Time to reach peak, peak infected cases and total reported cases were compared with actual data and found to be in very good agreement. Next the model is applied for the case of India and various Indian states to predict different epidemiological parameters. Priori data was taken from the beginning of nation-wide lockdown on 24 March to 6 July. It was found that peak of the outbreak may reach in the month of August-September with maximum 4-5 lakhs active cases at peak. Total number of reported cases all over India would be in between three to five millions. State wise, Maharashtra, Tamilnadu and Delhi would be worst affected.
Consumer perception towards familiar and innovative foods: the case of a Brazilian product
Authors: Goulart Gislayne da Silva , Viana Mayra Monteiro , Lucchese-Cheung Thelma 
Published: July 2020

PurposeThe purpose of this paper is to assess consumers' perception of a typical Brazilian food in its familiar and innovative versions through a survey combined with textual analysis.Design/methodology/approachThe study collected consumers’ data (N = 476) via survey and conducted two textual analysis – similitude and descending hierarchical classification (DHC) – using the Iramuteq software. In order to evaluate the consumers’ perception, traditional cheese breads (familiar) and cheese breads with carrots (innovative) were used. The consumers are from Central-West Brazil and had diverse socioeconomic status.FindingsSimilitude analysis showed that the familiar product presented mostly neutral or positive characteristics. The DHC analysis provided three relevant classes for the traditional cheese bread (familiar) product, considering the consumers’ perceptions and socioeconomic status. For the innovative product, the similitude analysis showed negative associations with the food (food neophobia), but there are also positive characteristics to be explored (food neophilia). Neophobia was attributed to hedonic aspects, e.g. doubts about the taste approval. Neophilia was related to normative aspects, e.g. the product's health benefits.Research limitations/implicationsThe results are exploratory and, therefore, cannot be generalized, but can arise insights to different food products. It was observed that the chosen method can be useful to access the consumer's perception and could be replicated in other cultures and regarding different products.Practical implicationsFood neophobia can be avoided by highlighting hedonic aspects and food neophilia can be activate via normative attributes, so the launch of an innovative food should be accompanied by consumer-oriented marketing strategies.Originality/valueThe present study brings relevant insights regarding food neophobia and neophilia and uses a combination of survey with textual analysis.
Stiffness vs flexibility based triangular spring cell – analysis of performance
Authors: Doltsinis I. St. 
Published: July 2020

Purpose
The purpose of the present study is to explore the incomplete substitution of the simplex triangular finite element by either of two models: one evolving out as part of the element flexibility, and the other as part of the element stiffness.

Design/methodology/approach
The elastic energy stored in each of the units under stress or strain decides on stiffer and weaker responses. The pertaining Rayleigh quotient in terms of the flexibility matrices allows bounding the distance of the spring cell models to the finite element in dependence of the triangle configuration.

Findings
Despite a superiority of the flexibility cell concept observed in computations, the study reveals constellations of shape and stressing of the triangle that favour the stiffness concept. The latter is seen to behave stiffer than its flexibility counterpart and produces results more distant to the finite element in most cases.

Research limitations/implications
The difference between the stiffness and the flexibility approach to spring cells is investigated for triangular elements in dependence of the geometrical configuration under specific conditions of stressing. This suffices to refute an exclusive superiority of the flexibility concept although largely true.

Practical implications
The results of the investigation appear useful in deciding between the spring cell models depending on the case of a spring lattice application.

Originality/value
The flexibility approach to the spring cell is not widely known yet. This cell model deserves a study on performance and comparison to the different, more common stiffness cell model.
Are graduates as good as they think? A discussion of overconfidence among graduates and its impact on employability
Authors: Hack-Polay Dieu 
Published: July 2020

PurposeThe paper aims to critically examine overconfidence in numeracy among higher education (HE) graduates and its impact on their employability. The paper discusses the extent to which graduates, because of higher qualifications, overstate their numerical abilities.Design/methodology/approachThe paper is a review of the academic literature examining the theoretical significance of overconfidence in HE. The review subsequently draws on practice and policy reports that evidence graduates' overconfidence in numeracy and basic skills.FindingsThe article shows a significant interaction between the level of qualification and overstatement of numerical abilities. The analysis found that graduates do not always have an important basic skill such as numeracy whose impact on work performance is significant.Practical implicationsThe findings are momentous for rethinking HE curricula, employee development in organisations and government skills strategy. The article advocates more inclusive and interpretive research for a greater understanding of the issues and offers useful data to policymakers and HE institutions in preparing graduates for work and decision-making. Further research in the field is required to enable the formulation of more authoritative conclusions.Originality/valueA critical contribution of this reflection is to have linked the evidence from the academic literature with employer surveys about graduate basic skills to draw the attention to a vital issue affecting national and organisational productivity, thus substantiating anecdotal evidence about graduate overconfidence. This reinforces the value of systematic literature review in research, as it provides an opportunity for more informed policy formulation as well as extending the body of research.
Stimulating employee learning: the confluence of case-based and self-regulated learning
Authors: Lyons Paul , Bandura Randall Paul 
Published: July 2020

PurposeThe purpose of this paper is to demonstrate the linkage of case-based instruction with the enhancement of self-regulated learning of employees. Specific objectives are to review and describe: some characteristics of adult learning, features and functions of self-regulated learning (SRL) and the instructional approach, case-based learning (CBL), followed by a synthesis of the information in the form of a detailed, CBL approach for practitioner use.Design/methodology/approachThe approach used in this work is represented in the following phases. First, conduct a literature review of each of these areas: characteristics of adult learners, details of SRL and its components, accompanied by the expression of linkages among the concepts and CBL. This includes exploration of metacognition, as it relates to the self-regulation of learning. Also reviewed was CBL, including theory background. Literature reviews were aided by databases: Education Research Complete, Psych Info and ScienceDirect. The second substantive phase was to synthesize the information obtained in the reviews and analysis and create a detailed design presentation for using CBL with trainees.FindingsThe findings of the analysis and synthesis of information enable the expression of a complete, detailed approach to the application of CBL for practitioner use. A review of practices in CBL augmented with examination of important theories of situated cognition and constructivism assist in building a rationale as to how case-based instruction may improve individual and team/group self-regulation of learning.Practical implicationsPresented in the paper is a complete model of case-based instruction for practitioner use and refinement.Originality/valueCase-based instruction has not been directly linked to the self-regulation of learning. This paper makes a contribution to the literature of CBL as well as to situational cognition.