bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription initiation RNAs are associated with chromatin activation mark H3K4me3
Authors: Hobbs Matthew , Ender Christine , Baillie Gregory J. , Crawford Joanna , Ru Kelin , Taft Ryan J. , Taft Ryan J. , Mattick John S. 
Published: February 2018

AbstractTranscription initiation RNAs (tiRNAs) are small, predominantly 18 nt, RNAs whose biogenesis is associated with nucleosomes adjacent to active transcription initiation sites. These loci usually contain modified histones associated with transcription initiation, including histone H3 trimethylated at lysine 4 (H3K4me3). To further characterize the relationship of tiRNAs and H3K4me3 marked nucleosomes, H3K4me3-targeted RNA:chromatin immunoprecipitations were performed in a murine macrophage cell line, and small RNA sequence libraries were constructed and subjected to deep sequencing. The H3K4me3 libraries exhibited a distinct profile of read lengths with a noticeable enrichment of sequences 17-26 nt in length, with a peak at ∼18nt that included tiRNAs. These RNAs show clear enrichment of sequences that map to genomic features known to be associated with transcription initiation, including CAGE transcription initiation sites (TSSs), sites of RNAPII occupancy, and H3K4me3 sites. The distribution of sequences that map in the vicinity of TSSs is consistent with previous descriptions of tiRNAs; viz. a major peak at approximately 40 nt downstream of the TSS, and a minor broader peak approximately 150-200 nt upstream of, and on the opposite strand to, the TSS. These results show that tiRNAs are physically associated with H3K4me3-marked chromatin. tiRNAs may be markers of RNAPII pausing and it remains a possibility that their association with H3K4me3 is part of an epigenetic signaling system.
A common goodness-of-fit framework for neural population models using marked point process time-rescaling
Authors: Tao Long , Weber Karoline E. , Arai Kensuke , Eden Uri T. 
Published: February 2018

AbstractA critical component of any statistical modeling procedure is the ability to assess the goodness-of-fit between a model and observed data. For neural spike train models of individual neurons, many goodness-of-fit measures rely on the time-rescaling theorem to assess the statistical properties of rescaled spike times. Recently, there has been increasing interest in statistical models that describe the simultaneous spiking activity of neuron populations, either in a single brain region or across brain regions. Classically, such models have used spike sorted data to describe relationships between the identified neurons, but more recently clusterless modeling methods have been used to describe population activity using a single model. Here we develop a generalization of the time-rescaling theorem that enables comprehensive goodness-of-fit analysis for either of these classes of population models. We use the theory of marked point processes to model population spiking activity, and show that under the correct model, each spike can be rescaled individually to generate a uniformly distributed set of events in time and the space of spike marks. After rescaling, multiple well-established goodness-of-fit procedures and statistical tests are available. We demonstrate the application of these methods both to simulated data and real population spiking in rat hippocampus.
Ablation ofEzh2in neural crest cells leads to Hirschsprung's disease-like phenotype in mice
Authors: Kim Hana , Langohr Ingeborg M. , Faisal Mohammad , McNulty Margaret , Thorn Caitlin , Kim Joomyeong 
Published: February 2018

AbstractIn the current study, we examined the role ofEzh2as an epigenetic modifier for the enteric neural crest cell development through H3K27me3.Ezh2conditional null mice were viable up to birth, but died within the first hour of life. In addition to craniofacial defects,Ezh2conditional null mice displayed reduced number of ganglion cells in the enteric nervous system. RT-PCR and ChIP assays indicated aberrant up-regulation ofZic1,Pax3, andSox10and loss of H3K27me3 marks in the promoter regions of these genes in the myenteric plexus. Overall, these results suggest thatEzh2is an important epigenetic modifier for the enteric neural crest cell development through repression ofZic1,Pax3, andSox10.
H3K4 methylation dependent and independent chromatin regulation by JHD2 and SET1 in budding yeast
Authors: Lee Kwan Yin , Chen Ziyan , Jiang River , Meneghini Marc D. 
Published: February 2018

AbstractSet1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me) through their opposing methyltransferase and demethylase activities in the budding yeast Saccharomyces cerevisiae. H3K4me associates with actively transcribed genes and, like both SET1 and JHD2 themselves, is known to regulate gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act solely through H3K4me. Relevantly, Set1 methylates lysine residues in the kinetochore protein Dam1 while genetic studies of the S. pombe SET1 ortholog suggest the existence of non-H3K4 Set1 targets relevant to gene regulation. We interrogated genetic interactions of JHD2 and SET1 with essential genes involved in varied aspects of the transcription cycle. Our findings implicate JHD2 in genetic inhibition of the histone chaperone complexes Spt16-Pob3 (FACT) and Spt6-Spn1. This targeted screen also revealed that JHD2 inhibits the Nrd1-Nab3-Sen1 (NNS) transcription termination complex. We find that while Jhd2’s impact on these transcription regulatory complexes likely acts via H3K4me, Set1 governs the roles of FACT and NNS through opposing H3K4-dependent and -independent functions. We also identify diametrically opposing consequences for mutation of H3K4 to alanine or arginine, illuminating that caution must be taken in interpreting histone mutation studies. Unlike FACT and NNS, detailed genetic studies suggest an H3K4me-centric mode of Spt6-Spn1 regulation by JHD2 and SET1. Chromatin immunoprecipitation and transcript quantification experiments show that Jhd2 opposes the positioning of a Spt6-deposited nucleosome near the transcription start site of SER3, a Spt6-Spn1 regulated gene, leading to hyper-induction of SER3. In addition to confirming and extending an emerging role for Jhd2 in the control of nucleosome occupancy near transcription start sites, our findings suggest some of the chromatin regulatory functions of Set1 are independent of H3K4 methylation.
A new paradigm for personalized cancer screening
Authors: Walker Rachel , Enderling Heiko 
Published: February 2018

AbstractA series of distinct histologic lesions precedes the onset of malignancy in many common cancers, yet early detection remains a major challenge. Many patients still experience late (stage IV) diagnoses and thus poor prognosis and limited options for therapeutic intervention. For cancers with known biomarkers of premalignant progression, optimized patient-specific screening protocols would minimize the risk of undetected progression to advanced stage disease. Here, we propose simple, cost-effective mathematical and statistical approaches to forecasting disease progression that could guide the personalization of optimal screening times for high-risk patients.
Evolution transforms pushed waves into pulled waves
Authors: Erm Philip , Phillips Ben L. 
Published: February 2018

AbstractUnderstanding the dynamics of biological invasions is crucial for managing numerous phenomena, from invasive species to tumours. While Allee effects (where individuals in low-density populations suffer lowered fitness) are known to influence both the ecological and evolutionary dynamics of invasions, the possibility that an invader’s susceptibility to the Allee effect might itself evolve on an invasion front has received almost no attention. Since invasion fronts are regions of perpetually low population density, selection should favour vanguard invaders that are resistant to Allee effects. Evolution in response to this pressure could cause invasions to transition from pushed waves, propelled by dispersal from behind the invasion front, to pulled waves, driven by the invasion vanguard. To examine this possibility, we construct an individual-based model in which a trait that governs resistance to the Allee effect is allowed to evolve during an invasion. We find that vanguard invaders rapidly evolve resistance to the Allee effect, causing invasions to accelerate. This also results in invasions transforming from pushed waves into pulled waves, an outcome with consequences for predictions of invasion speed, the population’s genetic structure, and other important behaviours. These findings underscore the importance of accounting or evolution in invasion forecasts, and suggest that evolution has the capacity to fundamentally alter invasion dynamics.
Anamorphic development and extended parental care in a 520 million-year-old stem-group euarthropod from China
Authors: Fu Dongjing , Ortega-Hernández Javier , Daley Allison C. , Zhang Xingliang , Shu Degan 
Published: February 2018

AbstractExtended parental care (XPC) is a complex reproductive strategy in which progenitors actively look after their offspring up to – or beyond – the first juvenile stage in order to maximize their fitness. Although the euarthropod fossil record has produced several examples of brood-care, the appearance of XPC within this phylum remains poorly constrained given the scarcity of developmental data for Palaeozoic stem-group representatives that would link juvenile and adult forms in an ontogenetic sequence. Here, we describe the post-embryonic growth ofFuxianhuia protensafrom the early Cambrian Chengjiang Lagerstätte, and show parental care in this stem-group euarthropod. We recognize fifteen distinct ontogenetic stages based on the number and shape of the trunk tergites, and their allocation between the morphologically distinct thorax and abdomen. Our data demonstrate anamorphic post-embryonic development inF. protensa, in which tergites were sequentially added from a posterior growth zone. A life assemblage consisting of a sexually matureF. protensaadult alongside four ontogenetically coeval juveniles, constitutes the oldest occurrence of XPC in the panarthropod fossil record. These findings provide the most phylogenetically basal evidence of anamorphosis in the evolutionary history of total-group Euarthropoda, and reveal a complex post-embryonic reproductive ecology for its early representatives.
The integrated stress response regulates BMP signaling through effects on translation
Authors: Malzer Elke , Dominicus Caia S. , Chambers Joseph E. , Mookerjee Souradip , Marciniak Stefan J. 
Published: February 2018

AbstractDevelopmental pathways must be responsive to the environment. Phosphorylation of eIF2α enables a family of stress sensing kinases to trigger the integrated stress response (ISR), which has pro-survival and developmental consequences. Mutations of the ISR kinase GCN2 have been implicated in the development of pulmonary arterial hypertension, a disorder known to be associated with defects of BMP signaling, but how the ISR and BMP signaling might interact is unknown. Here we show inDrosophilathat GCN2 antagonises BMP signaling through direct effects on translation and indirectly via the transcription factorcrc(dATF4). Expression of a constitutively active GCN2 or loss of the eIF2α phosphatase dPPP1R15 impair developmental BMP signaling in flies. In cells, inhibition of translation by GCN2 blocks downstream BMP signaling. Moreover, loss of d4E-BP, a target ofcrc, augments BMP signalingin vitroand rescues tissue developmentin vivo. These results identify a novel mechanism by which the ISR modulates BMP signaling during development. Since abnormalities of both GCN2 and BMP signaling lead to pulmonary hypertension, these findings may have wider relevance for the development of therapies for this disease.
Longitudinal Epidemiological Study of Autism Subgroups Using Autism Treatment Evaluation Checklist (ATEC) Score
Authors: Mahapatra Shreyas , Khokhlovich Edward , Martinez Samantha , Kannel Benjamin , Edelson Stephen M , Vyshedskiy Andrey 
Published: February 2018

AbstractHere we report the results of the subgroup analyses of an observational cohort of children whose parents completed the Autism Treatment Evaluation Checklist (ATEC) over the period of several years. A linear mixed effects model was used to evaluate longitudinal changes in ATEC scores within different patient subgroups. All groups decreased their mean ATEC score over time indicating improvement of symptoms, however there were significant differences between the groups. Younger children improved more than the older children. Children with milder ASD improved more than children with more severe ASD in the Communication subscale. There was no difference in improvement between females vs. males. One surprising finding was that children from developed English-speaking countries improved less than children from non-English-speaking countries.
Rab-mediated trafficking in the secondary cells of Drosophila male accessory glands and its role in fecundity
Authors: Prince E. , Brankatschk M. , Kroeger B. , Gligorov D. , Wilson C. , Eaton S. , Karch F. , Maeda R.K. 
Published: February 2018

AbstractIt is known that the male seminal fluid contains factors that affect female post-mating behavior and physiology. InDrosophila,most of these factors are secreted by the two epithelial cell types that make up the male accessory gland: the main and secondary cells. Although secondary cells represent only 4% of the cells of the accessory gland, their contribution to the male seminal fluid is essential for sustaining the female post-mating response. To better understand the function of the secondary cells, here we investigate their molecular organization, particularly with respect to the intracellular membrane transport machinery. We determined that large vacuole-like structures found in the secondary cells are trafficking hubs labeled by Rab6, 7, 11 and 19. Furthermore, these cell-specific organelles are essential for the long-term post-mating behavior of females and that their formation is directly dependent upon Rab6. Our discovery adds to our understanding of Rab proteins function in secretory cells. We have created an online, open-access imaging resource as a valuable tool for the intracellular membrane and protein traffic community.
Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo
Authors: Freitas Caroline S. de , Higa Luiza M. , Sacramento Carolina , Ferreira André C. , Reis Patrícia A. , Delvecchio Rodrigo , Monteiro Fabio Lima , Barbosa-Lima Giselle , Vieira Yasmine Rangel , Mattos Mayara , Hoelz Lucas Villas Bôas , Leme Rennan Papaleo Paes , Bastos Mônica M. , Bozza Fernando A. , Bozza Patrícia T. , Boechat Nubia , Tanuri Amilcar , Souza Thiago Moreno L. 
Published: February 2018

AbstractYellow fever virus (YFV) is a member of the Flaviviridae family, that causes major mortality. In Brazil, YFV activity increased in the last years. It has been registered that sylvatic, instead of urban, yellow fever (YF) leads our contemporary public health concern. Low vaccinal coverage leaves the human population near the jangle vulnerable to the outbreak, making it necessary to identify therapeutic options. Repurposing of clinically approved antiviral drugs represents an alternative for such identification. Other Flaviviruses, such Zika (ZIKV) and dengue (DENV) viruses, are susceptible to Sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Moreover, sofosbuvir has a safety record on critically ill hepatic patients, making it an attractive option. Our data show that YFV RNA polymerase uses conserved amino acid resides for nucleotide binding to dock sofosbuvir. This drug inhibited YFV replication in different lineages of human hepatoma cells, Huh-7 and HepG2, with EC50 value of 4.8 µM. Sofosbuvir protected YFV-infected neonatal Swiss mice from mortality and weight loss. Our pre-clinical results indicate that sofosbuvir could represent an option against YFV.
Engineering bacteria for biogenic synthesis of chalcogenide nanomaterials
Authors: Chellamuthu Prithiviraj , Tran Frances , Silva Kalinga Pavan T. , El-Naggar Moh , Boedicker James Q. 
Published: February 2018

SummaryMicrobes naturally build nanoscale structures, including structures assembled from inorganic materials. Here we combine the natural capabilities of microbes with engineered genetic control circuits to demonstrate the ability to control biological synthesis of chalcogenide nanomaterials in a heterologous host. We transferred reductase genes from both Shewanella sp. ANA-3 and Salmonella enterica serovar Typhimurium into an heterologous host (Escherichia coli) and examined the mechanisms that regulate the properties of biogenic nanomaterials. Expression of arsenic reductase genes and thiosulfate reductase genes in E. coli resulted in the synthesis of arsenic sulfide nanomaterials. In addition to processing the starting materials via redox enzymes, cellular components also nucleated the formation of arsenic sulfide nanomaterials. The shape of the nanomaterial was influenced by the bacterial culture, with the synthetic E. coli strain producing nanospheres and conditioned media or cultures of wild type Shewanella sp. producing nanofibers. The diameter of these nanofibers also depended on the biological context of synthesis. These results demonstrate the potential for biogenic synthesis of nanomaterials with controlled properties by combining the natural capabilities of wild microbes with the tools from synthetic biology.
The adoption of balanced scorecard: an exploration of its antecedents and consequences
Authors: Singh Reetesh K. , Arora Simple Sethi 
Published: February 2018

PurposeThe purpose of this paper is to study the adoption of balanced scorecard (ABSC) as performance management system (PMS). It also proposes a framework for empirically validating the antecedents and consequences of the ABSC as PMS.Design/methodology/approachThrough the extensive review of BSC literature, the antecedents and consequences factors of BSC adoption as PMS are explored. A conceptual model is derived which hypothesises the relationship between the antecedents and consequences of the ABSC. The data collected by surveying perception of 128 bank employees is empirically tested. Confirmatory factor analysis is used to test the validity of the proposed measurement model, and hypothesised relationships are tested using structural equation modelling.FindingsThe findings confirmed the hypothesised conceptual model. They indicate that top management involvement and interdepartmental communication are the two prime antecedent factors which significantly lead to ABSC as PMS. In addition to this, the findings validate a strong causal relationship between ABSC and three consequence factors, namely, employees’ behaviour, organisational capabilities and perceived performance.Research limitations/implicationsThe current study broadens the understanding of the notion of BSC as PMS in a considerable manner. It overcomes the inadequacy of the previous studies which failed to explore the antecedents and consequences of ABSC in a comprehensive way. The studies’ key limitation is that it is based on the perception of employees which can be overcome by using multiple methods to collect data in future studies.Originality/valueThe current study makes a significant contribution to the BSC literature. It is a first of its kind study to provide empirical validation to the conceptual model of antecedents and consequences of the ABSC as PMS. The research finding offers key implications for both researchers and practitioners.
Reverse technology transfer from the East to the West
Authors: Wolfram Pierre , Agarwal Nivedita , Brem Alexander 
Published: February 2018

Purpose
The approach of Western companies to internationalise their R&D by establishing R&D sites in emerging markets (EMs) has led to a discussion about the role of R&D in home markets and host markets. The purpose of this paper is to shed light on the evolution of foreign R&D sites of Western companies in EMs and their role using China as the empirical context.

Design/methodology/approach
The study uses the State Intellectual Property Office database, and investigates about 2,000 patent families of the top 14 Western patent applicants in China.

Findings
The results indicate a gradual shift from an exploitative to an exploratory role of R&D sites in China. The study also shows evident learning effects on Western R&D from local counterparts.

Research limitations/implications
The paper motivates further research of R&D internationalisation approaches within EMs, and explores the changing role of local subsidiaries. While the study is only focussed on China, the applicability of the results is limited in context of other countries, due to cultural, economic and legislative differences.

Practical implications
This study shows the increasing importance of EMs such as China and how these markets, known for imitations and cheap resources, are gradually moving towards innovations and creating new technologies locally.

Originality/value
Based on the patent analysis, this study shows the growing importance of the local R&D subsidiaries of Western multinationals in China.
Consequences of workplace violence behaviors in Jordanian public hospitals
Authors: Al-Shiyab Ahmed Abdelhalim , Ababneh Raed Ismail 
Published: February 2018

Purpose
The purpose of this paper is to examine the consequences of workplace violence against healthcare staff in Jordanian public hospitals.

Design/methodology/approach
A convenient sample included 334 physicians and nurses employed in eight different public hospitals, different departments and different working shifts were surveyed by filling the designed questionnaire.

Findings
The findings indicated workplace violence had a clear moderate impact on the respondents’ interaction with patients, performing work responsibilities, ability of making decisions, and professional career. The most frequent workplace violence consequences were damaging staff’s personality and prestige, increasing laziness and unwillingness to serve patients. Workplace violence consequences also included aggressive behavior, fear while dealing with patients, increase job insecurity, and lack of professional responsibility. In addition, demographic variables such as gender, education, job title, working shift, and income showed statistical significant differences in the attitudes of participants toward the consequences of workplace violence.

Practical implications
This study highlighted the necessity of healthcare policy makers and hospital administrators to establish violence free and safe working environments in order to retain qualified healthcare staff that in turn improves the health services quality.

Originality/value
There is a lack of research and documentation on violence in the healthcare settings in developing countries. This study is one of the first to examine the consequences of workplace violence that affect public physicians and nurses.