bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil extracellular trap stabilization leads to improved outcomes in murine models of sepsis
Authors: Gollomp Kandace , Sarkar Amrita , Seeholzer Steven H , Rauova Lubica , Kowalska M. Anna , Poncz Mortimer 
Published: May 2019

AbstractSepsis is characterized by multi-organ system dysfunction that occurs due to infection. It is associated with unacceptably high morbidity and mortality and in need of improved therapeutic intervention. Neutrophils play a crucial role in sepsis, releasing neutrophil extracellular traps (NETs) composed of DNA complexed with histones and toxic antimicrobial proteins that ensnare pathogens but also damage host tissues. At presentation, patients likely have a significant NET burden contributing to the multi-organ damage. Therefore, interventions that prevent NET release would likely be ineffective at preventing NET-based injury. Treatments that enhance NET degradation may liberate captured bacteria and toxic NET degradation products (NDPs) and therefore be of limited therapeutic benefit. We propose that interventions that stabilize NETs and sequester NDPs may be protective in sepsis. Platelet factor 4 (PF4, CXCL4) a platelet-associated chemokine, binds and compacts NETs, increasing their resistance to deoxyribonuclease I. A monoclonal antibody, KKO, which binds to PF4-NET complexes, further enhances this resistance. We now show that PF4 increases NET-mediated bacterial capture in vitro, reduces the release of NDPs, and improves outcome in murine models of sepsis. An Fc-modified KKO further enhances deoxyribonuclease resistance, decreases NDP release, and increases survival in these models, supporting a novel NET-targeting approach to improve outcomes in sepsis.
An epigenetic landscape governs early fate decision in cellular aging
Authors: Li Yang , Jiang Yanfei , Paxman Julie , O’Laughlin Richard , Pillus Lorraine , Tsimring Lev S. , Hasty Jeff , Hao Nan 
Published: May 2019

AbstractChromatin instability and mitochondrial decline are conserved processes that contribute to cellular aging. Although both processes have been explored individually in the context of their distinct signaling pathways, the mechanism that determines which cell fate arises in isogenic cells is unknown. Here, we show that interactions between the chromatin silencing and mitochondrial pathways lead to an epigenetic landscape with multiple equilibrium states that represent different types of terminal cellular states. Interestingly, the structure of the landscape drives single-cell differentiation towards one of these states during aging, whereby the fate is determined quite early and is insensitive to intracellular noise. Guided by a quantitative model of the aging landscape, we genetically engineer a new “long-lived” equilibrium state that is characterized by a dramatically extended lifespan.
Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
Authors: Cuomo Anna SE , Seaton Daniel D , McCarthy Davis J , Martinez Iker , Bonder Marc Jan , Garcia-Bernardo Jose , Amatya Shradha , Madrigal Pedro , Isaacson Abigail , Buettner Florian , Knights Andrew , Natarajan Kedar Nath ,   HipSci Consortium, Vallier Ludovic , Marioni John C , Chhatriwala Mariya , Stegle Oliver 
Published: May 2019

AbstractRecent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts.
Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells
Authors: Juárez-Cruz Juan C. , Zuñiga-Eulogio Miriam Daniela , Olea-Flores Monserrat , Castañeda-Saucedo Eduardo , Mendoza-Catalán Miguel Ángel , Ortuño-Pineda Carlos , Moreno-Godínez Ma. Elena , Villegas-Comonfort Sócrates , Padilla-Benavides Teresita , Navarro-Tito Napoleón 
Published: May 2019

ABSTRACTBreast cancer is the most common invasive neoplasia, and the second leading cause of death associated with cancer in women worldwide. Mammary tumorigenesis is severely linked to obesity, the potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloproteases secretion, and invasion. By Western blot we found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Specific inhibitors of FAK and Src showed that the effect exerted by leptin in cell migration, and invasion in breast cancer cells is dependent on these kinases. Moreover, by gelatin zymmography we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9, in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.
Deletion of the CTG Expansion in Myotonic Dystrophy Type 1 Reverses DMPK Aberrant Methylation in Human Embryonic Stem Cells but not Affected Myoblasts
Authors: Yanovsky-Dagan Shira , Bnaya Ester , Diab Manar Abu , Handal Tayma , Zahdeh Fouad , van den Broek Walther J.A.A. , Epsztejn-Litman Silvina , Wansink Derick G. , Eiges Rachel 
Published: May 2019

ABSTRACTMyotonic dystrophy type 1 (DM1) results from a CTG repeat expansion in the 3’-UTR of DMPK. When the repeat extensively expands, this results in DMPK aberrant methylation, reduction in SIX5 transcription and the development of the congenital form of the disease. To explore whether hypermethylation could be reversed in DM1 embryonic stem cells (hESCs) and patient myoblasts, we monitored methylation levels following removal of the expanded repeat by CRISPR/Cas9-mediated editing. Excision of the repeat in undifferentiated hESCs (CTG2000) resets the locus by abolishing abnormal methylation and H3K9me3 enrichment, and rescues SIX5 transcription. In contrast, in affected myoblasts methylation levels remain unchanged following deletion of a large expansion (CTG2600). Altogether, this provides evidence for a transition from a reversible to an irreversible heterochromatin state by the DM1 mutation upon cell differentiation. These findings should be taken into account when considering gene correction in congenital DM1 and potentially other epigenetically regulated disorders.
The structural characterization of a glucosylglycerate hydrolase provides insights into the molecular mechanism of mycobacterial recovery from nitrogen starvation
Authors: Cereija Tatiana Barros , Alarico Susana , Lourenço Eva C. , Manso José António , Ventura M. Rita , Empadinhas Nuno , Macedo-Ribeiro Sandra , Pereira Pedro José Barbosa 
Published: May 2019

Bacteria are challenged to adapt to environmental variations in order to survive. Under nutritional stress, several bacteria are able to slow down their metabolism into a nonreplicating state and wait for favourable conditions. It is almost universal that bacteria accumulate carbon stores to survive during this nonreplicating state and to fuel rapid proliferation when the growth-limiting stress disappears. Mycobacteria are exceedingly successful in their ability to become dormant under harsh circumstances and to be able to resume growth when conditions are favourable. Rapidly growing mycobacteria accumulate glucosylglycerate under nitrogen-limiting conditions and quickly mobilize it when nitrogen availability is restored. The depletion of intracellular glucosylglycerate levels in Mycolicibacterium hassiacum (basonym Mycobacterium hassiacum) was associated with the up-regulation of the gene coding for glucosylglycerate hydrolase (GgH), an enzyme that is able to hydrolyse glucosylglycerate to glycerate and glucose, a source of readily available energy. Highly conserved among unrelated phyla, GgH is likely to be involved in bacterial reactivation following nitrogen starvation, which in addition to other factors driving mycobacterial recovery may also provide an opportunity for therapeutic intervention, especially in the serious infections caused by some emerging opportunistic pathogens of this group, such as Mycobacteroides abscessus (basonym Mycobacterium abscessus). Using a combination of biochemical methods and hybrid structural approaches, the oligomeric organization of M. hassiacum GgH was determined and molecular determinants of its substrate binding and specificity were unveiled.
The development of the Sensory Processing, Aberrant Mealtime Behavior, Motor Inventory for Eating (SAMIE) in children with an ASD
Authors: Withrow Nicole Atkins , Alvidrez Leticia 
Published: May 2019

Purpose
The purpose of this paper is to develop a comprehensive eating screening inventory named the Sensory Processing, Aberrant Mealtime Behaviors, Motor, Inventory for Eating (SAMIE). The SAMIE will accurately screen nutritional risk by identifying the four primary domains that affect eating in children with autism spectrum disorder (ASD).

Design/methodology/approach
The development of the questions was executed in three steps. First, a review of the literature was conducted. Second, expert opinion was acquired which was critical in developing the questions. Third, ten think-aloud protocols were set up to simplify the first draft. Prior to the pilot study, four participants were recruited to complete the SAMIE online.

Findings
A total of 162 participants completed the online demographic questionnaire and the SAMIE. Overall, participants did not differ between groups for demographic characteristics, BMI status and dietary intake. After conducting a series of statistical tests, results illustrated that the SAMIE is a valid measure to screen nutritional risk in children with ASD.

Practical implications
Due to the complexities of problematic eating behaviors in ASD, there is a need for a comprehensive screening inventory that encompasses the four domains that impact eating in an ASD. These domains have been identified as, namely, aberrant mealtime behavior, eating skills, dietary intake, and sensory processing and have yet to be utilized collectively to screen for nutritional risk in children with ASD.

Originality/value
The SAMIE is a novel eating screening inventory that will standardize the methodology for screening nutritional risk that can be used in clinical, community and research settings.
Enhancing organizational health literacy in a rural Missouri clinic: a qualitative case study
Authors: Wray Ricardo , Weaver Nancy , Adsul Prajakta , Gautam Kanak , Jupka Keri , Zellin Stacie , Goggins Kathryn , Vijaykumar Santosh , Hansen Natasha , Rudd Rima 
Published: May 2019

Purpose
The purpose of this paper is to evaluate a collaborative effort between a health care organization and academic institution to strengthen organizational health literacy.

Design/methodology/approach
The intervention took place at a rural, federally qualified health clinic in Missouri between May 2009 and April 2011. Qualitative interviews of key informants were conducted before (n=35) and after (n=23) the intervention to examine program implementation and success in effecting organizational change.

Findings
Intervention activities helped establish a comprehensive understanding of health literacy. The project achieved moderate, fundamental and sustainable organizational change. The program successfully integrated health literacy practices into clinic systems and garnered leadership and organizational commitment, helped the workforce improve interpersonal communication and embedded practices making health education materials more accessible.

Originality/value
The study points to programmatic, conceptual and methodological challenges that must be addressed for organizations to improve health literacy practices, and suggests change management strategies to advance organizational health literacy.
INSPIRE sustainability internships
Authors: Hayles Carolyn Susan 
Published: May 2019

Purpose
This paper aims to explore the outputs of an internship programme, one of a number of campus-based sustainability activities that have been introduced at the University of Wales, Trinity Saint David, to encourage student-led campus-based greening initiatives.

Design/methodology/approach
A case study approach was undertaken, allowing the researcher to investigate the programme in its real-life context. The researcher used multiple sources of evidence to gain as holistic a picture as possible.

Findings
Interns report positive changes in their behaviours towards sustainability, s well as encouraging feedback on their experiential learning, the development of their soft skills and the creation of new knowledge. Moreover, students communicated perceived benefits for their future careers. The reported outcomes reflect mutually beneficial relationships for student and institution, for example, raising the profile of campus greening activities and supporting the University’s aim to embed sustainability throughout its campus, community and culture.

Research limitations/implications
The researcher recognises the limitations of the research, in particular, the small sample size, which has resulted primarily in qualitative results being presented.

Practical implications
Feedback from previous interns will be used to shape future internships. In particular, Institute of Sustainable Practice, Innovation and Resource Effectiveness (INSPIRE) will look for opportunities to work more closely with University operations, departments, faculties and alongside University staff, both academic and support staff.

Social implications
Following student feedback, INSPIRE will give students opportunities for wider involvement, including an opportunity to propose their own projects to shape future internships that meet the needs of student body on campus.

Originality/value
Despite being one case study from one institution, the research highlights the value of such programmes for other institutions.
Promoting green building literacy through online laboratory experiences
Authors: Cole Laura Brianna , Quinn Jerod , Akturk Aysegul , Johnson Briana 
Published: May 2019

PurposeThis study examines a general education, hands-on and 100 per cent online laboratory course to better understand the prospects for fostering green building literacy through experiential online education.Design/methodology/approachThe mixed-methods research design included pre- and post-course surveys (n= 42) together with semi-structured interviews mid-semester (n= 10) and four to six months post-course (n= 5). Data were collected for two semesters.FindingsStudents experienced significant increases in green building knowledge and skills, environmental sensitivity and pro-environmental behaviors from the beginning to the end of the course. Qualitative results indicate that the hands-on laboratory assignments were the primary pedagogical interventions affecting change. Interviews four to six months after the course revealed that motivation, convenience and supportiveness of the context were key factors impacting the pro-environmental behaviors that were maintained versus those that were discontinued by students when the course was over.Practical implicationsThis paper shares effective approaches used to deliver an online course with hands-on laboratories that lead to positive increases in sustainability knowledge and behaviors stretching beyond the semester.Originality/valueWhile online and experiential learning are both well-studied themes in higher education, very little empirical work examines experiential online learning, and this is particularly the case for online laboratory courses. The work here contributes to the understanding of general education online laboratories that are designed to increase knowledge and behavior change through hands-on experiential learning techniques.
An alternative formula for the constant growth model
Authors: Forsyth Juan A. 
Published: May 2019

Purpose
The traditional one-stage constant growth formula has two main underlying assumptions: a company will be able to maintain its competitive advantage for completed investments in perpetuity, and each year in the future, it will be able to generate new investment opportunities with the same competitive advantage, which will also remain in perpetuity. The purpose of this paper is to develop a model that limits the duration of the competitive advantage.

Design/methodology/approach
A new model is developed, and it is used to value a public company.

Findings
In this study, the author introduces an alternative formula considering the duration of the competitive advantage, imposing a restriction on the fact that extraordinary returns cannot be sustained forever, and also separates the part of the value explained by the current investments from the portion of value created by future investments.

Originality/value
The traditional one-stage constant growth model used to determine the continuing value of a company has limitations regarding the duration of the competitive advantage. The developed formula corrects the problem limiting the time extraordinary returns will remain over time.
The role of leader vs organisational credibility in Islamic social enterprise marketing communication
Authors: Hati Sri Rahayu Hijrah , Idris Aida 
Published: May 2019

Purpose
The purpose of this study is to examine the role of leader and organisational credibility in influencing customers’ intention to support Islamic social enterprises.

Design/methodology/approach
The credibility of the leader and that of the social enterprise are exposed through advertising. Ads portraying the six largest Islamic social enterprises in Indonesia and their social entrepreneur leaders were shown to 221 existing customers via online and offline surveys.

Findings
The findings indicate that organisational credibility and organisational branding have much greater influence than leaders’ personal credibility on customers’ intention to support Islamic social enterprises.

Research limitations/implications
The study has highlighted the greater role of organisational credibility and branding over advertising in attracting support for Islamic social entrepreneurship.

Practical implications
Islamic social enterprises need to develop a trusted brand and establish a more effective way to communicate with their stakeholders besides advertising, as the impact of ads on customer support intention is not significant.

Originality/value
The study contributes to the field of marketing and social entrepreneurship by providing empirical results on the Islamic social entrepreneurship phenomenon.
The impact of electronic word of mouth (e-WOM) on the online purchase intention of consumers in the Islamic countries – a case of (UAE)
Authors: Nuseir Mohammed T. 
Published: May 2019

Purpose
The purpose of this paper is to contribute to the marketing literature regarding Islamic countries, in particular the United Arab Emirates (UAE), by assessing the impact of electronic word of mouth (e-WOM) on brand image and on the online purchase intentions of consumers.

Design/methodology/approach
Using a descriptive research approach, this study used quantitative data to assess how the online purchase intentions of consumers in the UAE are influenced by e-WOM and brand image.

Findings
E-WOM has a significant impact on online purchase intentions and brand image among consumers. Brand image significantly influences the online purchase intentions of consumers.

Research limitations/implications
The conclusions may not be generalizable because not all areas of the UAE were represented in this study. In future studies, a larger and more inclusive sample would help to overcome this limitation.

Practical implications
This study will help marketers to understand the power of e-WOM, an important marketing tool, and to use resources more strategically to attract new customers.

Originality/value
E-WOM is the most commonly used and most effective medium of sharing opinions and reviews pertaining to various products and services in the market. Understanding how it influences the purchase intentions of consumers is imperative and has strong implications for marketers.
Trust, power and supply chain integration in Web-enabled supply chains
Authors: Mora-Monge Carlo , Quesada Gioconda , Gonzalez Marvin E. , Davis Joshua M. 
Published: May 2019

PurposeThis study aims to examine the effects of trading partner trust and trading partner power, on supply chain integration, and their impact on business performance in the context of Web-enabled supply chains. In doing so, the authors extend previous studies by exploring this phenomenon by using an integrative theory-driven approach.Design/methodology/approachThis study presents a theoretical model grounded on the resource-based and dynamic capabilities views and the social capital theory. Data collected from 175 firms in the USA are used to test the hypotheses using structural equation modeling.FindingsResults highlight the importance of trust and supply chain integration on business performance, whereas power did not appear to have an effect on supply chain integration in Web-enabled supply chains. The findings are robust to concerns of endogeneity, common method bias and alternative model specification.Practical implicationsCompanies engaged in Web-enabled supply chains need to focus on increasing their integration efforts, and these efforts must also be accompanied by partnerships built on trust. Trading partners who might be inclined to use coercive strategies to influence other members of the supply chain in Web-enabled environments may be better off using cooperative approaches based on trust to achieve their desired goals.Originality/valueThis study integrates the resource-based view, dynamic capabilities view and the social capital theory to explore the dynamic relationships between trading partner trust, trading partner power and supply chain integration in Web-enabled supply chains. In doing so, this paper extends prior studies by examining supply chain integration’s impact on business performance and its mediating role, as it relates to trading partner trust and power in Web-enabled supply chains.