scholarly journals Promoter-intrinsic and local chromatin features determine gene repression in lamina-associated domains

2018 ◽  
Author(s):  
Christ Leemans ◽  
Marloes van der Zwalm ◽  
Laura Brueckner ◽  
Federico Comoglio ◽  
Tom van Schaik ◽  
...  
Keyword(s):  
General Framework ◽  
Transcription Elongation ◽  
Promoter Sequence ◽  
Gene Repression ◽  
List Type ◽  
Promoter Strength ◽  
Repressive Chromatin ◽  
Systematic Understanding ◽  
Genomic Locations

AbstractIt is largely unclear whether genes that are naturally embedded in lamina associated domains (LADs) are inactive due to their chromatin environment, or whether LADs are merely secondary to the lack of transcription. We show that hundreds of human promoters become active when moved from their native LAD position to a neutral context in the same cells, indicating that LADs form a repressive environment. Another set of promoters inside LADs is able to "escape" repression, although their transcription elongation is attenuated. By inserting reporters into thousands of genomic locations, we demonstrate that these escaper promoters are intrinsically less sensitive to LAD repression. This is not simply explained by promoter strength, but by the interplay between promoter sequence and local chromatin features that vary strongly across LADs. Enhancers also differ in their sensitivity to LAD chromatin. This work provides a general framework for the systematic understanding of gene regulation by repressive chromatin.HighlightsTwo promoter transplantation strategies elucidate the regulatory role of LAD chromatinLADs are generally repressive, but also highly heterogeneousLADs can impede both promoter activity and transcription elongationPromoters vary intrinsically in their sensitivity to LAD repression

scholarly journals Early oxygen levels contribute to brain injury in extremely preterm infants

2021 ◽  
Author(s):  
Krista Rantakari ◽  
Olli-Pekka Rinta-Koski ◽  
Marjo Metsäranta ◽  
Jaakko Hollmén ◽  
Simo Särkkä ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Brain Structures ◽  
High Oxygen ◽  
List Type ◽  
Neurodevelopmental Outcomes ◽  
Oxygen Levels ◽  
Arterial Blood ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Abstract Background Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes. Methods SpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58). Results The ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment. Conclusions Low oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets. Impact This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

scholarly journals 332 The diagnostic role of shunt series radiographs (SSR) in children presenting to the children’s emergency department (CED) with suspected ventriculoperitoneal (VP) shunt failure

2020 ◽  
Vol 37 (12) ◽  
pp. 852.3-853
Author(s):  
Angharad Griffiths ◽  
Ikechukwu Okafor ◽  
Thomas Beattie
Keyword(s):  
Clinical Outcome ◽  
Sensitivity And Specificity ◽  
Clinical Information ◽  
Flow Diagram ◽  
List Type ◽  
Shunt Failure ◽  
Vp Shunt ◽  
Wide Range ◽  
Diagnostic Role

Aims/Objectives/BackgroundVP shunts are used to drain CSF from the cranial vault because of a wide range of pathologies and, like any piece of hardware, can fail. Traditionally investigations include SSR and CT. This project examines the role of SSR in evaluating children with suspected VP shunt failure.Primary outcome: Sensitivity and specificity of SSR in children presenting to the CED with concern for shunt failure.Methods/DesignConducted in a single centre, tertiary CED of the national Irish Neurosurgical(NS) referral centre (ED attendance:>50,000 patients/year). 100 sequential SSR requested by the CED were reviewed. Clinical information was extracted from electronic requests. Shunt failure was defined by the need for NS intervention(Revision).Abstract 332 Figure 1Abstract 332 Figure 2Results/ConclusionsSensitivity and specificity is presented in figure 1 (two by two table).100 radiographs performed in 84 children.22% shunts revised (see flow diagram).7 SSR’s were abnormal.85% (n=6) shunts revised. [5 following abnormal CT].Of the normal SSR’s; 16 had abnormal CT and revised.85/100 received CT.64 of 85 CT’s (75%) were normal.□6 of the 64 had focal shunt concern.SSR’s shouldn’t be used in isolation. NPV&PPV, Sensitivity&Specificity is low.SSR’s are beneficial where there’s concern over focal shunt problems (injury/pain/swelling) or following abnormal CT.VP shunt failure is not well investigated with SSR alone.SSR’s could be omitted where there is no focal shunt concern/after normal CT (without impacting clinical outcome) reducing radiation exposure and reduce impact on CED’s.59 SSR’s could have been avoided without adverse clinical outcome.

Big Data and Sustainable Consumption: A Review and Research Agenda

2021 ◽  
pp. 097226292110225
Author(s):  
Shobhana Chandra ◽  
Sanjeev Verma
Keyword(s):  
Big Data ◽  
Consumer Behaviour ◽  
Business Models ◽  
Sustainable Consumption ◽  
Big Data Analytics ◽  
Consumption Behaviour ◽  
Consumer Experiences ◽  
Systematic Understanding ◽  
The Impact

Big data (BD) is making advances in promoting sustainable consumption behaviour and has attracted the attention of researchers worldwide. Despite the increased focus, the findings of studies on this topic are fragmented, and future researchers need a systematic understanding of the existing literature for identification of the research scope. This study offers a systematic review of the role of BD in promoting sustainable-consumption behaviour with the help of a bibliometric analysis, followed by a thematic analysis. The findings suggest that businesses deploy BD to create sustainable consumer experiences, predict consumer buying patterns, design and alter business models and create nudges for sustainable consumption, while consumers are forcing businesses to develop green operations and supply chains to reduce the latter’s carbon footprint. The major research gaps for future researchers are in the following areas: the impact of big data analytics (BDA) on consumerism, the role of BD in the formation of sustainable habits and consumer knowledge creation for sustainable consumption and prediction of green consumer behaviour.

scholarly journals Beyond feasibility—the role of motivation to implement measures to enhance resilience

2021 ◽  
Vol 26 (5) ◽  
Author(s):  
Luzian Messmer ◽  
Braida Thom ◽  
Pius Kruetli ◽  
Evans Dawoe ◽  
Kebebew Assefa ◽  
...  
Keyword(s):  
Food Security ◽  
Conceptual Framework ◽  
General Framework ◽  
Rural Livelihoods ◽  
Weather Forecast ◽  
Reduced Tillage ◽  
Shade Trees ◽  
The World ◽  
Cocoa Farmers

AbstractMany regions around the world are experiencing an increase in climate-related shocks, such as drought. This poses serious threats to farming activities and has major implications for sustaining rural livelihoods and food security. Farmers’ ability to respond to and withstand the increasing incidence of drought events needs to be strengthened and their resilience enhanced. Implementation of measures to enhance resilience is determined by decisions of farmers and it is important to understand the reasons behind their behavior. We assessed the viability of measures to enhance resilience of farmers to drought, by developing a general framework that covers economic-technical and psychological-cognitive aspects, here summarized under the terms (1) motivation and (2) feasibility. The conceptual framework was applied to cocoa farmers in Ghana and tef farmers in Ethiopia by using questionnaire-based surveys. A portfolio of five specific measures to build resilience (i.e., irrigation, shade trees, fire belts, bookkeeping, mulching, early mature varieties, weather forecast, reduced tillage, improved harvesting) in each country was evaluated with a closed-ended questionnaire that covered the various aspects of motivation and feasibility whereby farmers were asked to (dis)agree on a 5-point Likert scale. The results show that if the motivation mean score is increased by 0.1 units, the probability of implementation increases by 16.9% in Ghana and by 7.7% in Ethiopia. If the feasibility mean score is increased by 0.1 units, the probability of implementation increases by 24.9% in Ghana and by 11.9% in Ethiopia. We can conclude that motivation and feasibility matter, and we improve our understanding of measure implementation if we include both feasibility and motivation into viability assessments.

Introduction

2016 ◽  
Vol 6 (2-3) ◽  
pp. 101-108
Author(s):  
Marc Belissa ◽  
Gary Berton
Keyword(s):  
General Framework ◽  
American English ◽  
Atlantic History ◽  
Thomas Paine ◽  
International Conference ◽  
Opening Up ◽  
Second International

The volume contains six contributions (and an introduction) that have been presented in the Thomas Paine Second International Conference held in Paris Ouest Nanterre in 2014. All scholars involved in the field of research of Atlantic history agree on the fact that the partitioning between ‘national’ historiographies (American, English and French) is detrimental in the understanding of the role of specific transatlantic actors, of which Thomas Paine is one the most spectacular example for the era of the revolutions (1760–1830). This conference gathered American, British and French historians to develop this fruitful approach. The papers presented here participate in the historiographic opening up of studies on Thomas Paine and propose studies, reflexion and specific comments on how Thomas Paine converges within the general framework of Atlantic history and Republicanism history.

Abstract 5858: Role of Oxygen Tension and Oxidative Stress in Human Saphenous Vein Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Binata Joddar ◽  
Rashmeet K Reen ◽  
Michael Firstenberg ◽  
Keith J Gooch
Keyword(s):  
Oxidative Stress ◽  
Oxygen Tension ◽  
Ex Vivo ◽  
Neointimal Hyperplasia ◽  
Fold Increase ◽  
List Type ◽  
Saphenous Veins ◽  
Arterial Po2 ◽  
And Oxidative Stress

Vessels cultured ex vivo maintain viability and vasoactivity for weeks and can remodel in response to mechanical cues. When cultured in the presence of 5% CO2/balance air veins develop neointimal hyperplasia (IH) while arteries do not suggesting that exposure to significant increases in pO2 levels might stimulate IH. Neointimal hyperplasia (IH) is a known mechanism by which saphenous veins have a decreased patency compared to arterial conduits when used for coronary artery bypass. We sought to explore the role of oxygen tension and oxidative stress in IH. Test the hypothesis that exposure of human saphenous veins (HSV) to arterial pO2 stimulates IH via ROS-mediated pathways. Almost 40 HSV remnants acquired following CABG were cultured ex vivo with arterial (~95mmHg) pO2 or venous (~40mmHg) pO2 for 14 days. All differences reported have a p<0.05 via Student’s t-test. Results: HSV cultured at arterial pO2 exhibited significant IH as evidenced by disruption of the IEL, invasion of cells from the media, and a 2.8-fold greater intimal area than fresh HSV, a 5.8-fold increase in cell proliferation compared to fresh HSV, increased ROS levels and oxidative stress as evidenced by 4-fold increase in 4-HNE level (a marker of oxidative stress), increased DHE staining (indicative of superoxide generation), and a progressive increase in total ROS levels with time as assessed by DCF fluorescence, and a 3-fold increase in phosphorylated p38-MAPK, which is implicated in SMC proliferation. In stark contrast vessels culture at arterial pO2, HSV cultured with venous pO2 did not develop increased IH and were indistinguishable from fresh vessels with respect to proliferation, markers of oxidative stress, and MAPK expression levels. Supplementing culture medium with antioxidants including Tiron or NAC blocked the pO2-induced changes. These data indicate that exposure to arterial pO2 increases cellular proliferation and stimulates IH, potentially via oxidative stress or ROS signaling and also suggest that exposure to elevated arterial pO2 might stimulate pathological remodeling of veins grafted into the arterial circulation. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

Quintiles IPO

2017 ◽  
pp. 1-24
Author(s):  
David P. Stowell ◽  
Vishwas Setia
Keyword(s):  
Private Equity ◽  
Life Sciences ◽  
List Type ◽  
Publicly Traded ◽  
Discounted Cash Flow ◽  
Investment Bank ◽  
Strategy Process ◽  
Firm Owners ◽  
A Company

Quintiles Transnational Holdings Inc., the largest global provider of biopharmaceutical development and commercial outsourcing services, grew its revenue at a CAGR of 7.3% and EBITDA at 13.9% between 2008 and 2012.The case is set in December 2012–April 2013, when the majority of the firm was owned by founder Dennis Gillings and four private equity firms (Bain Capital, TPG Capital, 3i Capital and Temasek Life Sciences) after it was taken private in a management-led buyout in 2003 and a subsequent buyout in 2008. Five years after the second buyout, the private equity firm owners were looking to monetize their positions and considered different strategic alternatives: M&A sale to strategic or financial buyers, IPO, or capital restructuring through special dividends.Students will step into the role of an associate at the lead investment bank working with Quintiles. They must consider the case information and determine an IPO strategy, process, potential conflicts, and valuation.After reading and analyzing the case, students will be able to: Apply valuation techniques (discounted cash flow (DCF) and publicly traded comparables) in pricing an IPO Analyze the roles of different parties involved in the transaction Discuss the process of a company filing for an IPO Evaluate different strategic alternatives available to a private equity—backed company Address conflict of interest in management—led buyouts

scholarly journals Da mídia de massa às novas mídias: aspectos evolutivos da comunicação em Marketing

Revista Foco ◽  
2018 ◽  
Vol 11 (2) ◽  
pp. 123
Author(s):  
Cristian Luis Schaeffer ◽  
Fernando Bins Luce
Keyword(s):  
Mass Media ◽  
New Media ◽  
General Framework ◽  
Marketing Mix ◽  
Marketing Area ◽  
The Impact

O objetivo deste artigo consiste em analisar, com base no levantamento de artigos e bibliografias da área, os aspectos evolutivos e o papel da comunicação em marketing com o surgimento das novas mídias. Foram estudados conceitos como Marketing, Mix de Marketing, promoção/comunicação, mídia de massa e novas mídias, além do impacto causado pela tecnologia. A análise dessas informações permitiu traçar um quadro geral com as principais características de ambas as categorias de mídias e os fatores que contribuíram para essa evolução, além de avaliar os desafios para a comunicação em Marketing. As novas mídias exigiram uma mudança no papel e no pensamento do Marketing, já que a comunicação impessoal cedeu espaço para a interatividade. E cabe aqui destacar que a área de Marketing está se esforçando para acompanhar essas mudanças.  The purpose of this article is to analyze, based on the gathering of articles and bibliographies of the area, the evolutive aspects and the role of communication in marketing with the emergence of new media. Concepts such as Marketing, Marketing Mix, promotion/ communication, mass media and new media were studied, as well as the impact caused by technology. The analysis of this information allowed to chart a general framework with the main characteristics of both categories of media and the factors that contributed to this evolution, besides evaluating the challenges for communication in Marketing. The new media required a change in the role and thinking of Marketing, since impersonal communication gave way to interactivity. And it should be noted here that the Marketing area is striving to keep up with these changes.

scholarly journals Psychodynamic approaches to suicide and self-harm

2018 ◽  
Vol 24 (1) ◽  
pp. 37-45
Author(s):  
Jessica Yakeley ◽  
William Burbridge-James
Keyword(s):  
Risk Assessment ◽  
Suicide Attempts ◽  
List Type ◽  
Relational Context ◽  
Transference And Countertransference ◽  
Assessment And Treatment ◽  
Self Harm ◽  
Psychoanalytic Theories ◽  
Risk Assessment And Management

SUMMARYRates of suicide and self-harm are rising in many countries, and it is therapeutically important to explore the personal stories and relationships that underlie this behaviour. In this article psychoanalytic and psychodynamic principles and concepts in relation to violence towards the self are introduced and the various unconscious meanings of suicide and self-harm are explored within a relational context and attachment framework. We describe how a psychodynamic approach may enhance the risk assessment and treatment of patients presenting with self-harm and suicidality, particularly examining the role of transference and countertransference within the therapeutic relationship.LEARNING OBJECTIVES•Understand historical and contemporary psychoanalytic theories and concepts regarding the aetiology of suicide and self-harm•Understand the different meanings and expressions of acts of suicide and self-harm•Understand the use of countertransference in the risk assessment and management of self-harm and suicide attemptsDECLARATION OF INTERESTNone.

scholarly journals STIM1 deficiency is linked to Alzheimer’s disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca2+ entry

2018 ◽  
Vol 96 (10) ◽  
pp. 1061-1079 ◽  
Author(s):  
Carlos Pascual-Caro ◽  
Maria Berrocal ◽  
Aida M. Lopez-Guerrero ◽  
Alberto Alvarez-Barrientos ◽  
Eulalia Pozo-Guisado ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Protein Expression ◽  
Transmembrane Domain ◽  
Neuroblastoma Cell ◽  
Disease Patient ◽  
List Type

Abstract STIM1 is an endoplasmic reticulum protein with a role in Ca2+ mobilization and signaling. As a sensor of intraluminal Ca2+ levels, STIM1 modulates plasma membrane Ca2+ channels to regulate Ca2+ entry. In neuroblastoma SH-SY5Y cells and in familial Alzheimer’s disease patient skin fibroblasts, STIM1 is cleaved at the transmembrane domain by the presenilin-1-associated γ-secretase, leading to dysregulation of Ca2+ homeostasis. In this report, we investigated expression levels of STIM1 in brain tissues (medium frontal gyrus) of pathologically confirmed Alzheimer’s disease patients, and observed that STIM1 protein expression level decreased with the progression of neurodegeneration. To study the role of STIM1 in neurodegeneration, a strategy was designed to knock-out the expression of STIM1 gene in the SH-SY5Y neuroblastoma cell line by CRISPR/Cas9-mediated genome editing, as an in vitro model to examine the phenotype of STIM1-deficient neuronal cells. It was proved that, while STIM1 is not required for the differentiation of SH-SY5Y cells, it is absolutely essential for cell survival in differentiating cells. Differentiated STIM1-KO cells showed a significant decrease of mitochondrial respiratory chain complex I activity, mitochondrial inner membrane depolarization, reduced mitochondrial free Ca2+ concentration, and higher levels of senescence as compared with wild-type cells. In parallel, STIM1-KO cells showed a potentiated Ca2+ entry in response to depolarization, which was sensitive to nifedipine, pointing to L-type voltage-operated Ca2+ channels as mediators of the upregulated Ca2+ entry. The stable knocking-down of CACNA1C transcripts restored mitochondrial function, increased mitochondrial Ca2+ levels, and dropped senescence to basal levels, demonstrating the essential role of the upregulation of voltage-operated Ca2+ entry through Cav1.2 channels in STIM1-deficient SH-SY5Y cell death. Key messages STIM1 protein expression decreases with the progression of neurodegeneration in Alzheimer’s disease. STIM1 is essential for cell viability in differentiated SH-SY5Y cells. STIM1 deficiency triggers voltage-regulated Ca2+ entry-dependent cell death. Mitochondrial dysfunction and senescence are features of STIM1-deficient differentiated cells.

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