bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding atcis-regulatory elements and TAD boundaries
Authors: Kadota Shinichi , Ou Jianhong , Shi Yuming , Sun Jiayu , Yildirim Eda 
Published: February 2020

ABSTRACTThe nuclear pore complex (NPC) components, nucleoporins (Nups), have been proposed to mediate spatial and temporal organization of chromatin during gene regulation. Nevertheless, we have little understanding on the molecular mechanisms that underlie Nup-mediated chromatin structure and transcription in mammals. Here, we show that Nucleoporin 153 (NUP153) interacts with the chromatin architectural proteins, CTCF and cohesin, and mediates their binding acrosscis-regulatory elements and TAD boundaries in mouse embryonic stem (ES) cells. NUP153 depletion results in altered CTCF and cohesin occupancy and differential gene expression. This function of NUP153 is most prevalent at the developmental genes that show bivalent chromatin state. To dissect the functional relevance of NUP153-mediated CTCF and cohesin binding during transcriptional activation or silencing, we utilized epidermal growth factor (EGF)-inducible immediate early genes (IEGs). We found that NUP153 binding at thecis-regulatory elements controls CTCF and cohesin binding and subsequent POL II pausing during the transcriptionally silent state. Furthermore, efficient and timely transcription initiation of IEGs relies on NUP153 and occurs around the nuclear periphery suggesting that NUP153 acts as an activator of IEG transcription. Collectively, these results uncover a key role for NUP153 in chromatin architecture and transcription by mediating CTCF and cohesin binding in mammalian cells. We propose that NUP153 links NPCs to chromatin architecture allowing developmental genes and IEGs that are poised to respond rapidly to developmental cues to be properly modulated.
A new mechanism for a familiar mutation – bovineDGAT1K232A modulates gene expression through multi-junction exon splice enhancement
Authors: Fink Tania , Lopdell Thomas J , Tiplady Kathryn , Handley Renee , Johnson Thomas JJ , Spelman Richard J , Davis Stephen R , Snell Russell G , Littlejohn Mathew D 
Published: February 2020

AbstractTheDGAT1gene encodes an enzyme responsible for catalysing the terminal reaction in mammary triglyceride synthesis, and underpins a well-known pleiotropic quantitative trait locus (QTL) with a large influence on milk composition phenotypes. Since first described over 15 years ago, a protein-coding variant K232A has been assumed as the causative variant underlying these effects, followingin-vitrostudies that demonstrated differing levels of triglyceride synthesis between the two protein isoforms. In the current study, we used a large RNAseq dataset to re-examine the underlying mechanisms of this large milk production QTL, and hereby report novel expression-based functions of the chr14 g.1802265AA>GC variant that encodes theDGAT1K232A substitution. Using expression QTL (eQTL) mapping, we demonstrate a highly-significant mammary eQTL forDGAT1, where the K232A mutation appears as one of the top associated variants for this effect. By conductingin vitroexpression and splicing experiments in bovine mammary cell culture, we further show modulation of splicing efficiency by this mutation, likely through disruption of an exon splice enhancer as a consequence of the allele encoding the 232A variant. Although the relative contributions of the enzymatic and transcription-based mechanisms now attributed to K232A remain unclear, these results suggest that transcriptional impacts contribute to the diversity of lactation effects observed at this locus.
BiGen: Integrative Clinical and Brain-Imaging Genetics Analysis Using Structural Equation Model
Authors: Elsheikh Samar S. M. , Chimusa Emile R. , Crimi Alessandro , Mulder Nicola J. 
Published: February 2020

AbstractThe identification of genetic variants associated with complex brain diseases has evolved in the past decades. Studies in the field have taken different approaches and study designs including genome-wide association studies. Neuroimaging and connectomics have also improved our understanding of the structural connectivity of the human brain and produced reliable measurements. Combining both neuroimaging and genetic characteristics significantly contributes to understand their complex relationship in affecting behaviour and cognition. Throughout this thesis we proposed analysis pipeline to study the association between imaging and genetics of two different types of brain disease, which is, Alzheimer’s disease and glioblastoma. We observe the need for a unified model to study the complex interplay between genetic, environmental and clinical, neuroimaging and phenotype features. In this chapter, we developed BiGen, a mathematical model to measure the inter-correlation structure through the integration of genetic, environmental, neuroimaging and disease measurements. We utilised the structural equation model and used a path construct of latent variables to study the hidden association between genes and brain-related diseases, mediated by connectivity characteristics. We applied BiGen to simulated data and to a dataset from the Alzheimer’s Disease Neuroimaging Initiative.
The cell and stress-specific canonical and non-canonical tRNA cleavage
Authors: Rashad Sherif , Tominaga Teiji , Niizuma Kuniyasu 
Published: February 2020

AbstractFollowing stress, tRNA is cleaved to generate tRNA halves (tiRNAs). These stress-induced small RNAs have been shown to regulate translation during stress. To date, angiogenin is considered the main enzyme that cleaves tRNA at its anti-codon site to generate 35 ~ 45 nucleotide long 5′ and 3′ tiRNA halves, however recent reports indicate the presence of angiogenin-independent cleavage. We previously observed tRNA cleavage pattern occurring away from the anti-codon site. To explore this non-canonical cleavage, we analyze tRNA phenotypical cleavage patterns in rat model of ischemia reperfusion and in two rat cell lines.In vivomitochondrial tRNAs were prone to this non-canonical cleavage pattern.In vitro, however, both cytosolic and mitochondrial tRNAs could be cleaved non-canonically. We also evaluated the roles of angiogenin and its inhibitor, RNH1, in regulating tRNA cleavage during stress. Our results suggest that mitochondrial stress has an important regulatory role in angiogenin-mediated tRNA cleavage. Angiogenin does not appear to regulate the non-canonical cleavage pattern of tRNA, and RNH1 does not affect it as well. Finally, we verified our previous findings of the stress-specific role of Alkbh1 in regulating tRNA cleavage and showed a strong influence of stress type on Alkbh1-mediated tRNA cleavage and that Alkbh1 impacts non-canonical tRNA cleavage.
Sputtered porous Pt for wafer-scale manufacture of low-impedance flexible microelectrodes
Authors: Fan Bo , Rodriguez Alexander V. , Vercosa Daniel G. , Kemere Caleb , Robinson Jacob T. 
Published: February 2020

AbstractRecording electrical activity from individual cells in vivo is a key technology for basic neuroscience and has growing clinical applications. To maximize the number of independent recording channels as well as the longevity, and quality of these recordings, researchers often turn to small and flexible electrodes that minimize tissue damage and can isolate signals from individual neurons. One challenge when creating these small electrodes, however, is to maintain a low interfacial impedance by applying a surface coating that is stable in tissue and does not significantly complicate the fabrication process. Here we use a high-pressure Pt sputtering process to create low-impedance electrodes at the wafer scale using standard microfabrication equipment. Direct-sputtered Pt provides a reliable and well-controlled porous coating that reduces the electrode impedance by 5-9 fold compared to flat Pt and is compatible with the microfabrication technologies used to create flexible electrodes. These porous Pt electrodes show reduced thermal noise that matches theoretical predictions. In addition, we show that these electrodes can be implanted into rat cortex, record single unit activity, and be removed all without disrupting the integrity of the coating. We also demonstrate that the shape of the electrode (in addition to the surface area) has a significant effect on the electrode impedance when the feature sizes are on the order of tens of microns. Overall, porous Pt represents a promising method for manufacturing low-impedance electrodes that can be seamlessly integrated into existing processes for producing flexible neural probes.
Short chain fatty acid butyrate promotes virus infection by repressing interferon stimulated genes
Authors: Chemudupati Mahesh , Smith Anna C. , Fillinger Robert J. , Kenney Adam D. , Zhang Lizhi , Zani Ashley , Liu Shan-Lu , Anderson Matthew Z. , Sharma Amit , Yount Jacob S. 
Published: February 2020

AbstractButyrate is an abundant metabolite produced by the gut microbiota and is known to modulate multiple immune system pathways and inflammatory diseases. However, studies of its effects on virus infection of cells are limited and enigmatic. We found that butyrate increases cellular infection and virus replication in influenza virus, reovirus, and human immunodeficiency virus infections. Further exploring this phenomenon, we found that addition of butyrate to cells deficient in type I interferon (IFN) signaling did not increase susceptibility to virus infection. Accordingly, we discovered that butyrate suppressed levels of specific IFN stimulated gene (ISG) products in human and mouse cells. Butyrate did not inhibit IFN-induced phosphorylation of transcription factors STAT1 and STAT2 or their translocation to the nucleus, indicating that IFN signaling was not disrupted. Rather, our data are suggestive of a role for inhibition of histone deacetylase activity by butyrate in limiting ISG induction. Global transcript analysis revealed that butyrate increases expression of more than 800 cellular genes, but represses IFN-induced expression of 60% of ISGs. Overall, we identify a new mechanism by which butyrate promotes virus infection via repression of ISGs. Our findings also add to the growing body of evidence showing that individual ISGs respond differently to type I IFN induction depending on the cellular environment, including the presence of butyrate.ImportanceButyrate is a lipid produced by intestinal bacteria that can regulate inflammation throughout the body. Here we show for the first time that butyrate influences the innate antiviral immune response mediated by type I IFNs. A majority of antiviral genes induced by type I IFNs were repressed in the presence of butyrate, resulting in increased virus infection and replication in cells. This suggests that butyrate could be broadly used as a tool to increase growth of virus stocks for research and for the generation of vaccines. Our research also indicates that metabolites produced by the gut microbiome can have complex effects on cellular physiology as demonstrated by the dampening of an inflammatory innate immune pathway by butyrate resulting in a pro-viral cellular environment.
Disruption ofAtHAK/KT/KUP9enhances plant cesium accumulation under low potassium supply
Authors: Genies Laure , Martin Ludovic , Kanno Satomi , Chiarenza Serge , Carasco Loïc , Camilleri Virginie , Vavasseur Alain , Henner Pascale , Leonhardt Nathalie 
Published: February 2020

ABSTRACTUnderstanding molecular mechanisms which underlie transport of cesium (Cs+) in plants is important to limit entry of its radioisotopes from contaminated area to the food chain. The potentially toxic element Cs+, which is not involved in any biological process, is chemically closed to the macronutrient potassium (K+). Among the multiple K+carriers, the high-affinity K+transporters family HAK/KT/KUP is thought to be relevant in mediating opportunistic Cs+transport. On the 13KUPidentified inArabidopsis thaliana, onlyHAK5, the major contributor to root K+acquisition under low K+supply, has been functionally demonstrated to be involved in Cs+uptakein planta. In the present study, we showed that accumulation of Cs+increased by up to 30% in twoA. thalianamutant lines lackingKUP9and grown under low K+supply. Since further experiments revealed that Cs+release from contaminated plants to the external medium is proportionally lower in the twokup9mutants, we proposed thatKUP9disruption could impair Cs+efflux. By contrast, we did not measure significant impairment of K+status inkup9mutants suggesting thatKUP9disruption does not alter substantially K+transport in experimental conditions used here. Putative primary role of KUP9 in plants is further discussed.
Differential regulation of lineage commitment in human and mouse primed pluripotent stem cells by NuRD
Authors: Ragheb Ramy , Gharbi Sarah , Cramard Julie , Ogundele Oluwaseun , Kloet Susan , Burgold Thomas , Vermeulen Michiel , Reynolds Nicola , Hendrich Brian 
Published: February 2020

AbstractDifferentiation of mammalian pluripotent cells involves large-scale changes in transcription and, among the molecules that orchestrate these changes, chromatin remodellers are essential to initiate, establish and maintain a new gene regulatory network. The NuRD complex is a highly conserved chromatin remodeller which fine-tunes gene expression in embryonic stem cells. While the function of NuRD in mouse pluripotent cells has been well defined, no study yet has defined NuRD function in human pluripotent cells. We investigated the structure and function of NuRD in human induced pluripotent stem cells (hiPSCs). Using immunoprecipitation followed by mass-spectrometry in hiPSCs and in naive or primed mouse pluripotent stem cells, we find that NuRD structure and biochemical interactors are generally conserved. Using RNA sequencing, we find that, whereas in mouse primed stem cells and in mouse naïve ES cells, NuRD is required for an appropriate level of transcriptional response to differentiation signals, hiPSCs require NuRD to initiate these responses. This difference indicates that mouse and human cells interpret and respond to induction of differentiation differently.Graphical AbstractNuRD acts like a conductor in an orchestra.A.In the presence of NuRD (pink blob figure, centre) differentiation occurs in an ordered fashion in both mouse (left) and human (right) ES cells. Gene expression changes in both cell types are tightly controlled with down-regulation of pluripotency genes and up-regulation of lineage appropriate genes. This is akin to a group of musicians producing musical notes in the right order and at the right amplitude to create a coherent piece of music.B.Loss of “the conductor” NuRD results in increased transcriptional noise in both systems, indicated here as a low-level blanket of sound in both systems. Consequences of MBD3/NuRD loss differs between human and mouse ES cells. In mouse ES cells, differentiation cues lead to some down-regulation of pluripotency genes and incomplete progression along a lineage appropriate pathway. This is like musicians who know that they should be making music but who lose their way without a conductor’s influence. In human iPS cells the background level of noise without NuRD results in a lack of order to gene expression changes in response to differentiation. The noise from these “musicians” would be truly awful.
Causes of delay to public infrastructure projects according to engineers representing different contract parties
Authors: Ahmad Hesham S. , Ayoush Maha D. , Al-Alwan Majed S. 
Published: February 2020

Purpose
The purpose of this paper is to investigate the main causes of delay in public construction projects. This is motivated by feedback from public construction experts concerning substantive delays during the last decade. The study thus seeks to help decision makers in Jordan and elsewhere identify problems and develop mitigating strategies.

Design/methodology/approach
Causes of delay were identified from previous related studies and then augmented after consultation with experts. This resulted in 56 delay factors classified into eight groups. The sampling frame for the study was defined in terms of public construction projects (mostly related to roads) owned by the Ministry of Public Works and Housing in Jordan. A survey was conducted with engineers working as representatives of the owner, contractors or consultants to elicit and evaluate the importance of the 56 delay factors.

Findings
Overall, 113 completed questionnaire responses were returned and analyzed to rank the causes of delay using the relative importance index method. Owners and consultants showed more interest in factors related to themselves, while contractors showed highest interest in an external factor related to the owner of services. Four recommendations are put forward for decision makers to mitigate against delays.

Originality/value
This research investigates a relatively large number of delay factors compared to other studies and these are categorized into groups to facilitate thematic understanding. Further, compared to previous related research, this research fills a gap by exploring the opinions of different contract parties.
Drivers of efficiency and their influence on airline performances in South Africa: a bootstrapped meta-frontier approach
Authors: Mhlanga Oswald 
Published: February 2020

Purpose
This paper aims to identify drivers of efficiency and their influence on airline performances in South Africa. Unfortunately, the methods currently used to measure airline efficiency fail to address the heterogeneity problem, which blurs inefficiency.

Design/methodology/approach
To remedy the heterogeneity problem, this paper adopts the meta-frontier framework to identify drivers of efficiency. The interesting feature of the model is that it ensures that heterogeneous airlines are compared based on one homogeneous technology. The model is tested using a panel data sample of nine South African airlines, which operated from 2015 to 2018.

Findings
The paper demonstrates that structural drivers, namely, “aircraft size”, and “airline ownership” and one executional driver, namely, “the cost structure” significantly influence (p < 0.05) airline efficiency thereby corroborating evidence from some prior studies.

Research limitations/implications
First, because of the small size of the industry, fewer airlines and a lack of detailed data, the study could not consider other important factors such as optimal routing and network structure. Second, a more rigorous analysis over a period of time would yield better understanding about the growth of the industry in South Africa and recognise the variation in the influence of drivers of efficiency on airline performances over time.

Practical implications
The results have potential policy implications. First, as the market in South Africa is too small to operate with a smaller aircraft probably, for airlines that operate with smaller aircraft to operate efficiently they should first identify niche markets where they can have a route monopoly. Second, while all state-owned airlines are perfect statehood symbols that define and represent countries, most state carriers in South Africa are highly inefficient. The researcher recommends policymakers to privatise state airlines or seek equity partners. Many nationalised airlines have turned losses to profits in the run-up to privatisation. British Airways, once a large burden on the British taxpayer, is now one of the world’s most efficient airlines. After the privatisation of Air France and Iberia, all two turned from loss-making concerns into profitable airlines. It, therefore, makes no sense for the South African government to expect state carriers to pursue a commercial mandate with such political interference. The very notion of efficiency itself is at risk.

Originality/value
This paper is a first attempt to identify drivers of operational efficiency using a bootstrapped meta-frontier approach in the airline industry in South Africa. By applying the meta-frontier approach the paper ensures that all heterogeneous airlines are assessed based on their distance from a common and identical frontier.
Can mass media be an obstacle to rationing decisions? A case report from Portugal
Authors: Pinho Micaela , Dias Costa Eva 
Published: February 2020

Purpose
Continuous introduction of advanced health technologies coupled with limited resources force governments to adopt rationing measures in all types of health systems. The mass media can influence the application of these measures by rising people and patients' expectations and demands for new forms of healing. This article intends to find evidence of this influence by reporting two recent cases which occurred in Portugal involving two innovative drugs, one for the treatment of hepatitis C and another for type I spinal muscular atrophy. The new drugs were not publicly funded despite promising excellent overall health outcomes because of their high cost and exaggerated burden on national health system (NHS).

Design/methodology/approach
A qualitative research was used to collect information conveyed by the conventional media and social networks.

Findings
After a strong dissemination through conventional and social media of the nonapproved treatments, the drugs swiftly garnered support among the public and triggered remarkable and relentless advocacy efforts. The findings of this paper suggest that society opinions and, by extension, the decision of policy-makers are very susceptible to the influence of the mass media.

Practical implications
New ways of sharing information are changing health research and public health.

Social implications
These stories raise complex tensions and important questions about resource-allocation decisions involving scientific research or innovative medicine. Societal preferences seem very vulnerable to information conveyed by the mass media.

Originality/value
This study is the first attempt to awaken attention to the influence that Portuguese mass media may exercise on future healthcare rationing decisions.
Challenges of 21st-century health governance
Authors: MacVane Phipps Fiona 
Published: February 2020

PurposeThe purpose of this review is to provide an overview of the articles included within one issue of International Journal of Health Governance (IJHG) together with some commentary and reference to other published works.Design/methodology/approachThe design is a literature review based on the articles in the current issue of IJHG. Other literature studies are referred to for expansion or clarification of the discussion.FindingsFinding ways to provide efficient, equitable and compassionate care continues to occupy the minds of health managers and health professionals.Originality/valueThe originality value lies in the fact that IJHG is the only journal in the Emerald suite of health care–related publications that includes a regular review of this type.