bluuebunny/crossref_metadata_2025_split huggingface dataset:
ChIPSummitDB: A ChIP-seq-based database of human transcription factor binding sites and the topological arrangements of the proteins bound to them
Authors: Czipa Erik , Schiller Mátyás , Nagy Tibor , Kontra Levente , Steiner László , Koller Júlia , Pálné-Szén Orsolya , Barta Endre 
Published: May 2019

ABSTRACTChIP-Seq reveals genomic regions where proteins, e.g. transcription factors (TFs) interact with DNA. A substantial fraction of these regions, however, do not contain the cognate binding site for the TF of interest. This phenomenon might be explained by protein-protein interactions and co-precipitation of interacting gene regulatory elements. We uniformly processed 3,727 human ChIP-Seq data sets and determined the cistrome of 292 TFs, as well as the distances between the TF binding motif centers and the ChIP-Seq peak summits.ChIPSummitDB enables the analysis of ChIP-Seq data using multiple approaches. The 292 cistromes and corresponding ChIP-Seq peak sets can be browsed in GenomeView. Overlapping SNPs can be inspected in dbSNPView. Most importantly, the MotifView and PairShiftView pages show the average distance between motif centers and overlapping ChIP-Seq peak summits and distance distributions thereof, respectively.In addition to providing a comprehensive human TF binding site collection, the ChIPSummitDB database and web interface allows for the examination of the topological arrangement of TF complexes genome-wide. ChIPSummitDB is freely accessible at http://summit.med.unideb.hu/summitdb/. The database will be regularly updated and extended with the newly available human and mouse ChIP-Seq data sets.
Origins, admixture dynamics and homogenization of the African gene pool in the Americas
Authors: Gouveia Mateus H. , Borda Victor , Leal Thiago P. , Moreira Rennan G. , Bergen Andrew W. , Aquino Marla M. , Araujo Gilderlanio S. , Araujo Nathalia M. , Kehdy Fernanda S.G. , Liboredo Raquel , Machado Moara , Magalhaes Wagner C.S. , Michelin Lucas A. , Rodrigues Maíra R. , Rodrigues-Soares Fernanda , Sant Anna Hanaisa P. , Santolalla Meddly L. , Scliar Marília O. , Soares-Souza Giordano , Zamudio Roxana , Zolini Camila , Dean Michael , Gilman Robert H. , Guio Heinner , Rocha Jorge , Pereira Alexandre C. , Barreto Mauricio L. , Horta Bernardo L. , Lima-Costa Maria F. , Mbulaiteye Sam M. , Chanock Stephen J. , Tishkoff Sarah A. , Yeager Meredith , Tarazona-Santos Eduardo 
Published: May 2019

AbstractThe Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed genome-wide analysis of 6,267 individuals from 22 populations and observed an enrichment in West-African ancestry in northern latitudes of the Americas, whereas South/East African ancestry is more prevalent in southern South-America. This pattern results from distinct geographic and geopolitical factors leading to population differentiation. However, we observed a decrease of 68% in the African gene pool between-population diversity within the Americas when compared to the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the US and Southeast-Brazil, respect to historical-demography expectations. Also, in most of the Americas, admixture intensification occurred between 1,750 and 1,850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural and political debate regarding ancestry, race, and admixture in the Americas.Significance StatementDifferently from most genetic studies, that have estimated the overall African ancestry in the Americas, we perform a finer geographic analysis and infer how different African groups contributed to North-, South-American and Caribbean populations, in the context of geographic and geopolitical factors. We also perform a formal comparison of information from demographic history records of the Transatlantic Slave Trade with inferences based on genomic diversity of current populations. Our approach reveals the distinct regional African ancestry roots of different populations from North-, South-America and the Caribe and other important aspects of the historical process of mestizaje and its dynamics in the American continent.
Spatial organization of cells and variable expression of autophagy, apoptosis, and neurodevelopmental genes might underlie selective brain region vulnerability in Attention-Deficit/Hyperactivity Disorder
Authors: Hess Jonathan L. , Radonjić Nevena V. , Patak Jameson , Glatt Stephen J. , Faraone Stephen V. 
Published: May 2019

AbstractGenetically influenced changes in brain organization occur over the course of development. Large-scale brain imaging studies by the ENIGMA Consortium identified structural changes associated with attention-deficit/hyperactivity disorder (ADHD). It is not clear why some brain regions are impaired and others spared by the etiological risks for ADHD. We hypothesized that spatial variation in brain cell organization and/or pathway expression levels contribute to selective brain region vulnerability (SBRV) in ADHD. In this study, we used the largest available collection of imaging results from the ADHD ENIGMA Consortium along with high-resolution postmortem brain microarray data from Allen Brain Atlas from 22 sub-cortical and cortical brain regions to investigate our selective brain region vulnerability (SBRV) hypothesis. We performed deconvolution of the bulk transcriptomic data to determine abundances of neuronal and non-neuronal cells in the brain. We then assessed the relationships between gene set expression levels, cell abundance, and standardized effect sizes representing regional changes in brain sizes in cases of ADHD. Our analysis yielded significant correlations between apoptosis, autophagy, and neurodevelopment genes with reductions in regional brain sizes in ADHD, along with associations to regional abundances of dopaminergic neurons, astrocytes, oligodendrocytes, and neural progenitor cells. This works provides novel mechanistic insights into SBRV in ADHD.
Evolution of Larval Segment Position across 12DrosophilaSpecies
Authors: Kalay Gizem , Atallah Joel , Sierra Noemie C. , Tang Austin M. , Crofton Amanda E. , Murugesan Mohan K. , Wykoff-Clary Sherri , Lott Susan E. 
Published: May 2019

AbstractMany developmental traits that are critical to the survival of the organism are also robust. These robust traits are resistant to phenotypic change in the face of variation. This presents a challenge to evolution. In this paper, we asked whether and how a well-established robust trait,Drosophilasegment patterning, changed over the evolutionary history of the genus. We compared segment position scaled to body length at the first-instar larval stage among 12Drosophilaspecies. We found that relative segment position has changed many times across the phylogeny. Changes were frequent, but primarily small in magnitude. Phylogenetic analysis demonstrated that rates of change in segment position are variable along theDrosophilaphylogenetic tree, and that these changes can occur in short evolutionary timescales. Correlation between position shifts of segments decreased as the distance between two segments increased, suggesting local control of segment position. The posterior-most abdominal segment showed the highest magnitude of change on average, had the highest rate of evolution between species, and appeared to be evolving more independently as compared to the rest of the segments. This segment was exceptionally elongated in the cactophilic species in our dataset, raising questions as to whether this change may be adaptive.
A common molecular basis to the convergent evolution of the selfing syndrome in Capsella
Authors: Woźniak Natalia Joanna , Kappel Christian , Marona Cindy , Altschmied Lothar , Neuffer Barbara , Sicard Adrien 
Published: May 2019

AbstractWhether, and to what extent, phenotypic evolution follows predictable genetic paths, remains an important question in evolutionary biology. Convergent evolution of similar characters provides a unique opportunity to address this question. The transition to selfing and the associated changes in flower morphology are among the most prominent examples of repeated evolution in plants. Yet, to date no studies have directly compared the extent of similarities between convergent adaptations to selfing. In this study, we take advantage of the independent transitions to self-fertilization in the genus Capsella to test the existence of genetic and developmental constraints imposed on flower evolution in the context of the selfing syndrome. While C. rubella and C. orientalis have emerged independently, both have evolved almost identical flower characters. Not only the evolutionary outcome is identical but, in both cases, the same developmental strategies underlie the convergent reduction of flower size. This has been associated with convergent evolution of gene-expression changes. The transcriptomic changes common to both selfing lineages are enriched in genes with low-network connectivity and with organ-specific expression patterns. Comparative genetic mapping also indicates that, at least in the case of petal size evolution, these similarities are largely caused by mutations at the same loci. Together, these results suggest that the limited availability of low-pleiotropy paths predetermine closely related species to similar evolutionary outcomes.
Numerically enhanced adaptive optics-based 3D STED microscopy for deep-tissue super-resolved imaging
Authors: Zdankowski Piotr , Trusiak Maciej , McGloin David , Swedlow Jason R. 
Published: May 2019

AbstractIn stimulated emission depletion (STED) nanoscopy, the major origin of decreased signal-to-noise ratio within images can be attributed to sample photobleaching and strong optical aberrations. This is due to STED utilising both a high power depletion laser (increasing risk of photodamage), while the depletion beam is very sensitive to sample-induced aberrations. Here we demonstrate a custom-built 3D STED microscope with automated aberration correction that is capable of 3D super-resolution imaging through thick, highly aberrating, tissue. We introduce and investigate image denoising by block-matching and collaborative filtering (BM3D) to numerically enhance fine object details otherwise mixed with noise. Numerical denoising provides an increase in the final effective resolution of the STED imaging of 31% using the well-established Fourier ring correlation metric. Experimental validation of the proposed method is achieved through super-resolved 3D imaging of axons in differentiated induced pluripotent stem cells growing under a 80µm thick layer of tissue with lateral and axial resolution of 256nm and 300nm, respectively.
MCH4is a multicopy suppressor of glycine toxicity inSaccharomyces cerevisiae
Authors: Melnykov Artem V. , Elson Elliot L. 
Published: May 2019

AbstractSaccharomyces cerevisiaecan either import amino acids from the surrounding or synthesize inside the cell, and both processes are tightly regulated. Disruption of such regulation can result in amino acid toxicity to the cell through mechanisms that are poorly understood. In this study we make use of a mutant strain with deregulated general amino acid permease gene whose growth is inhibited by low concentrations of several amino acids. We carry out multicopy suppression screen with several toxic amino acids and identifyMCH4as a gene that suppresses inhibitory effects of glycine. We find that expression ofMCH4is regulated by osmotic shock but not other kinds of stress. These findings are discussed in the context of possible mechanisms of amino acid toxicity.
c-Jun Overexpressing CAR-T Cells are Exhaustion-Resistant and Mediate Enhanced Antitumor Activity
Authors: Lynn Rachel C. , Weber Evan W. , Gennert David , Sotillo Elena , Xu Peng , Good Zinaida , Anbunathan Hima , Jones Robert , Tieu Victor , Granja Jeffrey , DeBourcy Charles , Majzner Robbie , Satpathy Ansuman T. , Quake Stephen R. , Chang Howard , Mackall Crystal L. 
Published: May 2019

SUMMARYCAR T cells mediate antitumor effects in a small subset of cancer patients, but dysfunction due to T cell exhaustion is an important barrier to progress. To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system employing a tonically signaling CAR, which induces hallmarks of exhaustion described in other settings. Exhaustion was associated with a profound defect in IL-2 production alongside increased chromatin accessibility of AP-1 transcription factor motifs, and overexpression of numerous bZIP and IRF transcription factors that have been implicated in inhibitory activity. Here we demonstrate that engineering CAR T cells to overexpress c-Jun, a canonical AP-1 factor, enhanced expansion potential, increased functional capacity, diminished terminal differentiation and improved antitumor potency in numerous in vivo tumor models. We conclude that a functional deficiency in c-Jun mediates dysfunction in exhausted human T cells and that engineering CAR T cells to overexpress c-Jun renders them exhaustion-resistant, thereby addressing a major barrier to progress for this emerging class of therapeutics.
Quantifying cell line specific proliferation and migration rates in glioblastoma cells
Authors: Rosén Emil , Gerlee Philip , Nelander Sven 
Published: May 2019

AbstractWe have characterised the migration and proliferation rates of a large number of patient-derived glioblastoma cell lines using an individual-based model coupled to an Approximate Bayesian Computation algorithm. We found that the cell lines exhibited a negative correlation between the rate of migration and rate of division. This observation agrees with the Go or Grow hypothesis and highlights patient-specific differences in migration and proliferation.
Direct care staff knowledge about medication for individuals with intellectual disabilities
Authors: Sawyer Amanda , Lake Johanna , Lunsky Yona 
Published: May 2019

PurposeThe majority of adults with intellectual disabilities (ID) are prescribed at least one, if not multiple medications, with psychotropic medications being the most commonly prescribed. Direct care staff play an important role in psychotropic medication administration and monitoring, yet little is known about their knowledge and comfort with medication. The paper aims to discuss this issue.Design/methodology/approachA 15-item survey, focusing on self-reported knowledge and comfort with psychotropic medication, was completed by 152 direct care staff employed at three agencies providing residential services for individuals with ID across Ontario.FindingsIn total, 62 per cent of staff respondents reported that psychotropic medications were among the top medications regularly taken by the individuals they support, with behaviour listed as the most commonly reported reason for taking this medication. The majority of staff reported monitoring medication, however, the frequency of monitoring varied considerably. Generally, staff reported feeling comfortable and knowledgeable about medication use, but, most reported a desire for additional medication training.Originality/valueThis is the first Canadian study to examine staff knowledge and comfort regarding medication use, and the first study to assess PRN (“as needed”) as well as regularly administered medications.
Redesigning a community-based challenging behaviour intensive support service
Authors: White Jasmin , Symes Matt , Pearce Carrie 
Published: May 2019

Purpose
The purpose of this paper is to discuss outcomes of a service redesign, involving an Intensive Support Team (IST) for adults with learning disabilities and challenging behaviour, working in conjunction with a Community Learning Disability Service (CLDS).

Design/methodology/approach
Two IST staff were physically based as “Inreach workers” within a CLDS for six months. Inreach workers provided support with existing resources and consultation for specific clients presenting with challenging behaviour. CLDS staff confidence, understanding and implementation of existing challenging behaviour resources was evaluated before and after service redesign. An online questionnaire was used to gather further data relating to experiences of the Inreach project.

Findings
CLDS staff confidence, understanding and implementation of existing challenging behaviour resources increased over the six-month inreach period. Questionnaire results indicated CLDS staff found Inreach support to be beneficial, having a perceived positive impact for clients, and providing clarity on the skills and resources provided by the IST.

Research limitations/implications
The long-term effects of this pilot have yet to be established. Consideration is given to how demand characteristics may have influenced CLDS responses.

Practical implications
Careful consideration should be given in terms of how ISTs interface with CLDSs. ISTs may consider being based physically within CLDSs, to provide more readily accessible support.

Originality/value
Providing CLDS staff with more accessible support from ISTs may increase the effective implementation of available resources for adults with learning disabilities and challenging behaviour.
Management competencies, complexities and performance in engineering infrastructure projects of Pakistan
Authors: Khattak Muhammad Sajid , Mustafa Usman 
Published: May 2019

PurposeThe complexity of projects has become a serious issue and obstacle in their successful completion. In order to overcome these complexities, it has become imperative to identify the relevant management competencies of project managers. The purpose of this paper is to address the problem of cost, time and scope in engineering infrastructure projects due to their complexities through management competencies.Design/methodology/approachIn the first phase of the study, 32 experts were interviewed through semi-structured pre-tested questionnaire. In this phase, essential elements of complexities were identified initially. This was followed by finding required dimensions of competencies to counter these complexities and to acquire improved performance. In the final stage, required levels of competencies for specific elements of complexity were identified. In the second phase, 85 “project managers” were also approached to get feedback about their recently completed public sector engineering infrastructure projects in Pakistan.FindingsThe study identified additional dimensions, i.e. honesty, enthusiasm and dedication, in the case of competencies and adverse law and order situation, political instability, land issues, energy crisis and weak authorization of project managers in the case of complexities. Leadership, management skill, communication skill, effectiveness and result orientation were identified as top quality traits required. The study concluded that there is a significant impact of management competencies and complexities on project performance.Originality/valueThe study contributes to a better understanding of how to improve performance in complex engineering infrastructure projects through adopting management competencies. It also empirically illustrates the relations among project management competencies, complexities and project performance. Although the research is grounded on public sector infrastructure projects, its findings may also be helpful for practices in project management of other sectors.
Teaching1984in the surveillance culture of schools
Authors: Gilbert Francis Jonathan , Pitfield Margaret 
Published: May 2019

PurposeThis paper focuses on the affordances of and issues surrounding the teaching of George Orwell’s novel1984(1949) as a set text for General Certificate of Secondary Education (GCSE) English and English Literature in an examination-obsessed and heavily surveilled school system. It considers this by focussing on the classroom practice of a beginning teacher tackling the teaching of this novel for the first time and the newly appointed university tutor who is required to assess her teaching against a prescribed set of national Teachers’ Standards.Design/methodology/approachA case study design is used, drawing on data from classroom observation, records of conversations and textual study. These data are analysed with reference to Perrymanet al.’s (2018) re-evaluation of Foucault’s Panopticon (1995), a concept which explains how institutions set up surveillance systems in which people’s behaviour is shaped by their feelings of being watched.FindingsIn the context of her practicum school the beginning teacher adopts a particular approach to language study as a vehicle for teaching the novel1984. This paper argues that such an approach, which finely focuses on the micro-detail of language, prevents teachers and students from seeing the big picture in Orwell’s novel and is therefore contrary to the spirit of his writing. It also restricts teachers from approaching the novel in ways which draw on students’ lived experiences as participants in the highly surveilled education system.Practical implicationsThe push for performativity in the current era of schooling ensures that, for English teachers, fear of failing to comply with imposed and implied norms contributes to a prevailing sense of unease about their subject. Thus, persistent pressures of exam preparation and inspection-readiness drive a wedge between their subject knowledge/expertise and the classroom practices prevalent in English teaching.Social implicationsEnglish teachers and teacher-educators are subject to a plethora of “guidelines” which filter through at every level of education and operate in a similar way to the totalitarian figurehead of Big Brother, Orwell’s fictional dictator who dominates1984. This paper argues that away from Big Brother’s all-seeing eye there are still, however, opportunities for those professional practices that do not fit within such parameters to be discussed, explored and shared.Originality/valueThis paper offers a unique perspective on the teaching of George Orwell at the levels of school student, beginning teacher and teacher-educator. The Big Brother of this paper is not the Stalinist dictator of Orwell’s dystopia, instead manifesting in many different education-related personas. This Big Brother demands compliance with his fuzzy norms (Courtney, 2016; Perryman et al., 2018), rules which are deliberately vague and shifting and if contravened have far-reaching consequences for all concerned in the teaching and learning of English.