bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Insights into Negative Cooperativity between Gemin2 and RNA in Sm-class snRNP Assembly
Authors: Zhang Rundong 
Published: November 2019

ABSTRACTSm-class ribonucleoprotein particles (RNPs) are ring-shaped structures (Sm cores) formed by Sm hetero-heptamer around a segment of RNA, containing a nonameric oligoribonucleotide, PuAUUUNUGPu, followed by a stem-loop, and are basic structural modules critical for stability and functions of spliceosomal, telomerase and U7 RNPs. In the chaperones-assisted Sm core assembly, Gemin2 of the SMN complex, not only binds SmD1/D2/F/E/G (5Sm), but also serves as a checkpoint via a negative cooperativity mechanism uncovered in our recent study: Gemin2 constricts the horseshoe-shaped 5Sm in a narrow conformation from outside, preventing non-cognate RNA and SmD3/B from joining; only cognate RNA can bind inside 5Sm and widen 5Sm, dissociating Gemin2 from 5Sm and recruiting SmD3/B. However, the structural mechanics is unknown. Here I describe a coordinate-improved structure of 5Sm bound by Gemin2/SMN. Moreover, via new analysis, comparison of this structure with those of newly coordinate-improved Sm cores reveals the negative cooperativity mechanism between Gemin2 and RNA in binding 5Sm at atomic resolution level and provides structural insights into RNA selection and Gemin2’s release in Sm core assembly. Finally, implications in the evolution of the Sm-core assembly chaperoning machinery and the neurodegenerative disease spinal muscular atrophy caused by SMN deficiency are discussed.
Multi-colour DNA-qPAINT reveals how Csk nano-clusters regulate T-cell receptor signalling
Authors: Simoncelli Sabrina , Griffié Juliette , Williamson David J. , Bibby Jack , Bray Cara , Zamoyska Rose , Cope Andrew P. , Owen Dylan M. 
Published: November 2019

AbstractPhosphorylation of the negative regulatory element of the tyrosine kinase Lck by Csk down-modulates T-cell receptor induced signalling. Being constitutively active, Csk spatial organization is responsible for regulating this signalling interaction. Here, we used stoichiometrically accurate, multiplexed, single-molecule super-resolution microscopy (DNA-qPAINT) to image the nanoscale spatial architecture of Csk and two binding partners implicated in its membrane association – PAG and TRAF3. Combined with a newly developed co-clustering analysis framework, we provide a powerful resource for dissecting signalling pathways regulated by spatio-temporal organisation. We found that Csk forms nanoscale clusters proximal to the plasma membrane that are lost post-stimulation and re-recruited at later time points. Unexpectedly, these clusters do not directly co-localise with PAG at the membrane, but instead provide a ready pool of monomers to down-regulate signalling. By generating CRISPR/Cas9 knock-out T-cells, our data also identify that protein tyrosine phosphatase non-receptor type 22 (PTPN22) is essential for Csk nanocluster re-recruitment and for maintenance of the synaptic PAG population.
Structure and assembly of calcium homeostasis modulator proteins
Authors: Syrjanen Johanna L , Michalski Kevin , Chou Tsung-Han , Grant Timothy , Rao Shanlin , Simorowski Noriko , Tucker Stephen J. , Grigorieff Nikolaus , Furukawa Hiro 
Published: November 2019

AbstractBiological membranes of many tissues and organs contain large-pore channels designed to permeate a wide variety of ions and metabolites. Examples include connexin, innexin, and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), which permeate ions and ATP in a voltage-dependent manner to control neuronal excitability, taste signaling, and pathologies of depression and Alzheimer’s disease. Despite such critical biological roles, the structures and patterns of oligomeric assembly remain unclear. Here, we reveal the first structures of two CALHMs, CALHM1 and CALHM2, by single particle cryo-electron microscopy, which show novel assembly of the four transmembrane helices into channels of 8-mers and 11-mers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore-size, lipid accommodation, and channel activity.
In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection
Authors: Zawawi Ayat , Forman Ruth , Smith Hannah , Mair Iris , Jibril Murtala , Albaqshi Munirah , Brass Andrew , Derrick Jeremy P. , Else Kathryn J. 
Published: November 2019

AbstractTrichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children’s educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). A combined VLP vaccine containing four Trichuris MHC-II T-cell epitopes stimulated dendritic cells and macrophages to produce pro-inflammatory and anti-inflammatory cytokines. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.Author SummaryThe soil transmitted helminth Trichuris trichiura is a major parasite in developing countries; development of a comprehensive vaccine has been elusive. Here we used a systematic approach based on in silico identification of MHC-II T cell epitopes from genome sequences, their incorporation into a virus-like particle (VLP), characterization of the assemblies and testing in an in vivo murine infection model. Animals vaccinated with a preparation of four different VLP-antigen fusions showed significant reductions in intestinal worm burdens and associated antibody responses consistent with protection. The results suggest that a pipeline based on in silico prediction of potent MHC-II T cell epitopes, followed by incorporation into VLPs, could be a strategy which enables rapid translation into a vaccine against Trichuris trichiura.
Why buy new, when used will do?
Authors: Nicholson Michael Robert 
Published: November 2019

Learning outcomes
Students are exposed to debt and equity financing; analysis of company affairs using selected financial statement information; use of ratios in financial analysis; the impact of adequate financing on company performance; and trade-offs companies must make in their day-to-day operations.

Case overview/synopsis
Jetcon Corporation’s business model involved the importation of pre-owned cars from Japan for re-sale in Jamaica. It was a fiercely competitive business as there were over 100 companies involved in this sector. There was also a vibrant new-car sector. Jetcon focused on importing mid to low price Japanese pre-owned models, which were already common on Jamaican roads, and which would be affordable to the larger segment of buyers. Like most small businesses, it experienced difficulty raising financing in the amounts and cost that is required and this contributed to its decision to raise equity capital through an initial public offer. It was the first used-car dealer to list on the Jamaica Stock Exchange.

Complexity academic level
This case is suitable for final-year undergraduate students in finance. By that time they should already have been exposed to debt, equity and stock markets. It helps students to explore some of the issues involved in financing a company’s operations.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 3: Entrepreneurship.
US students interning in New Zealand: how they are challenged; what they learn
Authors: Sligo Frank , Housel Teresa Heinz 
Published: November 2019

Purpose
The purpose of this paper is to explore US students’ experience in for-credit, unpaid internships overseas with particular reference to their personal development, how they mobilised their knowledge across contexts, their learning as acquisition and as participation, and what they contributed. Students were thought likely to encounter three forms of cultural differences: national, workplace and academic.

Design/methodology/approach
In total, 17 students in communication, marketing or related fields from the USA were placed in four-week internships in Wellington, New Zealand. Outcomes for them were assessed first, via weekly discussions in which they described what they had encountered that week, second, via the presentations they gave at the end of the course to internship hosts and university staff on the subject of what they had found challenging and what they had learned and contributed, and third, through assessment of students’ formal written assignments to discover what they said they had learned and what they had contributed.

Findings
Students were surprised at how proactive their internship hosts expected them to be and at how little overt direction they received. While they valued their opportunity to make a contribution to their workplace, they found this challenging. Students gave instances of their learning both as individuals and in groups. No mention was made of academic cultural differences being an issue, but they often described the demanding nature of the national and workplace cultural differences that they encountered.

Research limitations/implications
The study reports on only one cohort of students in one year, so a longitudinal study of further cohorts might provide different findings.

Originality/value
Insights are provided into how students saw themselves as changing from their involvement. Students described the challenges they faced, how they reacted to those challenges and their most important forms of learning.
Locating heritage value in building material reuse
Authors: Arlotta Allison Iris 
Published: November 2019

Purpose
The purpose of this paper is to explore the intersection of building material reuse and heritage value, and raises questions about how “preservation” has traditionally been defined and conceptualized. With a grounding in the realities of global climate change, the paper argues for further research on the topic and for the active engagement of the preservation field in reuse efforts.

Design/methodology/approach
After a review of existing literature, this study takes a descriptive and conceptual approach to explore the heritage values generated through material reuse.

Findings
This paper finds that processes of material reuse are richly embedded with heritage value and offer a conceptual challenge to established modes of heritage practice.

Practical implications
The findings of this paper suggest that heritage practitioners should actively engage with material reuse efforts to better understand the heritage values generated from such processes. Areas of future research and collaboration are identified.

Originality/value
Despite their intrinsic interaction with aged and existing infrastructure, there has been limited engagement in the heritage and preservation field with the topics of deconstruction, building material reuse, or construction and demolition waste practices more generally. This paper thus provides descriptive research on a topic that has been unevenly explored.
Factors affecting the accuracy of cost estimate during various design stages
Authors: Dandan Tala Hassan , Sweis Ghaleb , Sukkari Lilana Salem , Sweis Rateb J. 
Published: November 2019

Purpose
The purpose of this paper is to identify factors affecting cost estimate accuracy in each of five design stages preceding building construction: order of magnitude, conceptual/schematic, detailed design, construction document and bid phase.

Design/methodology/approach
Data were collected using an online survey completed by 138 respondents who work in design consultancy firms in Jordan, including project managers, architects and quantity surveyors (QSs). Survey responses were analyzed using descriptive statistics. Confirmatory interviews and case study comparisons were used to confirm the statistical analysis results.

Findings
The results of this study indicated that each design stage’s cost estimate was affected by several factors. Two significant factors were common across four of the five design stages: client experience and project team experience. In addition, a high level of agreement was observed among the project managers, architects and QSs regarding the factors affecting cost estimate accuracy.

Originality/value
Accurately estimating building construction costs during the design process has posed a challenge for designers and their clients in Jordan. Despite the care and effort involved in preparing cost estimates in each of the five design stages, deviations are commonly observed. Because the accuracy of building construction cost estimates directly affect the success or failure of a project, the results of this study can be used to reduce uncertainties in building construction cost estimation and subsequently increase the likelihood of project success
Understanding how professionals cultures impact implementation of a pediatric oncology genomic test
Authors: Gagnon Justin , Rahimzadeh Vasiliki , Longo Cristina , Nugus Peter , Bartlett Gillian 
Published: November 2019

Purpose
Healthcare innovation, exemplified by genomic medicine, requires increasingly sophisticated understanding of the interdisciplinary-organizational context in which new innovations are implemented. Deliberative stakeholder consultations are public engagement tools that are gaining increasing traction in health care, as a means of maximizing the diversity of roles and interests vested in a particular policy or practice issue. They engage participants from different knowledge systems (“cultures”) in mutually respectful debate to enable group consensus on implementation strategies. Current deliberation analytic methods tend to overlook the cultural contexts of the deliberative process. The paper aims to discuss this issue.

Design/methodology/approach
This conceptual paper proposes adding ethnographic participant observation to provide a more comprehensive account of the process that gives rise to deliberative outputs. To underpin this conceptual paper, the authors draw on the authors’ experience engaging healthcare professionals during implementation of genomics in the care for pediatric oncology patients with treatment-resistant glioblastoma at two tertiary care hospitals.

Findings
Ethnography enabled a deeper understanding of deliberative outcomes by combining rhetorical and non-rhetorical analysis to identify the implementation and coordination of care barriers across professional cultures.

Originality/value
This paper highlights the value of ethnographic methods in enabling a more comprehensive assessment of the quality of engagement across professional cultures in implementation studies.
Exploring the determinants of information adoption
Authors: Luo Chuan , Luo Xin , Ma Ning 
Published: November 2019

Purpose
The purpose of this study is to explore the effects of review group’s content-related and environment-associated attributes on information adoption intention of information readers. In addition, this study further investigates the effects of these determinants in different websites with different commercial attributes (i.e. online stores and third party forums).

Design/methodology/approach
This study used a structured online survey to collect data from an online store and a third party forum in China; totally 302 responses were collected.

Findings
The empirical results confirm that all of the five determinants significantly affect the information adoption intention of information readers. Furthermore, the authors found that four of the determinants have distinct effects in different websites.

Originality/value
The findings of this study validate the significant moderating role of website attributes in readers’ information processing. Information readers use distinct criteria to evaluate the received review information; electronic word-of-mouth determinants have varying effects on different websites with different commercial attributes.
Shifting identities: exploring occupational identity for those in recovery from an eating disorder
Authors: Dark Esther , Carter Sarah 
Published: November 2019

Purpose
The purpose of this paper is to explore the nature, transition and formation of occupational identity for those in recovery from eating disorders (EDs).

Design/methodology/approach
Semi-structured “episodic” interviews were carried out with six women, self-identifying in recovery from an ED. Narrative-type-analysis produced a distilled narrative of participants’ accounts, before use of thematic analysis compared and extracted pertinent themes.

Findings
During recovery from an ED, significant shifts occurred in occupational identities, moving from sole identification with the ED, to a greater understanding of self; facilitated by increased engagement in meaningful occupations, adapting occupational meaning, connecting with self and others and the importance of becoming and belonging.

Originality/value
This is the first known piece of research exploring occupational identity in relation to EDs. The findings are applicable to occupational therapists and add to the growing body of qualitative research into EDs.
The impact of consumers’ positive online recommendations on the omnichannel webrooming experience
Authors: Orús Carlos , Gurrea Raquel , Ibáñez-Sánchez Sergio 
Published: November 2019

Purpose
This purpose of this paper is to analyze how consumers’ online recommendations affect the omnichannel webrooming experience based on the internet, physical and mobile channels.

Design/methodology/approach
Two experimental studies are implemented. Study 1 analyzes the impact of an online review on the physical interaction with the product. Study 2 modifies the moment of receiving the online recommendation and its social tie.

Findings
Webrooming improves the shopping experience. Online recommendations from anonymous customers increase confidence in the product’s adequacy, although this effect depends on the moment of receiving the recommendation and the level of confidence before interacting physically with the product. Friend recommendations reinforce preferences regardless of previous online experiences.

Research limitations/implications
This research examines the effects of different types of online recommendations on offline shopping experiences, choice and confidence. Confidence is stressed as a key variable in omnichannel behavior.

Practical implications
The findings offer practical value for electronic word-of-mouth marketing, omnichannel marketing, as well as online and physical channel management.

Originality/value
This is one of the first studies that examine the impact of online consumer recommendations on shopping experiences combining online, mobile and physical channels. The results reveal the importance of recommendations’ source and moment of reception for determining consumers’ preferences, choice and confidence.
Follicle‐stimulating hormone and estradiol are associated with bone mineral density and risk of fractures in men with type 2 diabetes mellitus
Authors: Jing Yixuan , Wang Xiaofeng , Yu Jingjia , Wang Xiaojing , Zhou Yanman , Tao Bei , Sun Lihao , Liu Jianmin , Zhao Hongyan 
Published: November 2019

AbstractBackgroundType 2 diabetes mellitus (T2DM) is associated with a higher fracture risk. Sex hormones are important for maintaining skeletal health. It is not clear which sex hormone(s) contribute(s) to bone mineral density (BMD) and fracture risk in males with T2DM. This study investigated the relationships of these parameters in males with T2DM.MethodsThis study involved 482 men with T2DM. BMDs at the lumbar spine (L2‐4), femoral neck (FN), and total hip (TH) were measured by dual‐energy X‐ray absorptiometry (DXA). The 10‐year probability of fractures was assessed using the modified Fracture Risk Algorithm (FRAX) tool. Serum levels of sex hormones were measured.ResultsFollicle‐stimulating hormone (FSH) and estradiol (E2) were associated with BMDs at L2‐4 (FSH, β = −.162, P < .05; E2, β = .176, P < .001), and E2 was associated with BMD at FN (β = .137, P < .05) and TH (β = .140, P < .05). FSH was associated with major osteoporotic fractures (β = .288, P < .001) and hip fractures (β = .235, P < .001). Higher FSH was a risk factor for osteoporosis/osteopenia (odds ratios [OR] = 2.92, 95% CI = 1.66‐5.14, P < .001), whereas higher E2 was a protective factor (OR = 0.37, 95% CI = 0.22‐0.60, P < .001). Patients in the higher tertile of FSH and lower tertile of E2 had an increased risk of osteoporosis/osteopenia (OR = 5.05, 95% CI = 1.37‐18.65, P < .05).ConclusionsFor males with T2DM, FSH and E2 are significantly associated with BMD, osteoporosis/osteopenia, and fracture risk.
Mechanism research of miR‐34a regulates Axl in non‐small‐cell lung cancer with gefitinib‐acquired resistance
Authors: Xiong Ran , Sun Xiang‐xiang , Wu Han‐ran , Xu Guang‐wen , Wang Gao‐xiang , Sun Xiao‐hui , Xu Mei‐qing , Xie Ming‐ran 
Published: November 2019

BackgroundTo investigate the regulatory mechanism behind miR‐34a‐altered Axl levels in non‐small‐cell lung cancer (NSCLC) with gefitinib‐acquired resistance.MethodsThe expression of miR‐34a, Axl, Gas6 and related downstream signaling proteins in the EGFR mutant NSCLC cell lines were determined by qRT‐PCR and Western blot; PC9‐Gef‐miR‐34a and HCC827‐Gef‐miR‐34a cells were established by transfecting the parent cells with a miR‐34a overexpressing virus, then the expression of Axl, Gas6 and the downstream channel‐related proteins were also compared in PC9‐Gef‐miR‐34a and HCC827‐Gef‐miR‐34a and drug‐resistant strains. The survival rate of the cells were measured by CCK8 assay. A luciferase reporter detected whether Axl was the target of miR‐34a. Finally, a tumor‐bearing nude mouse model was established to verify the relationship between the expression of miR‐34a, Axl and Gas6 mRNA in vivo.ResultsThe expression levels of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream proteins in PC9‐Gef and HCC827‐Gef cell lines were higher than those in PC9 and HCC827 parental cell lines, while the expression of miR‐34a was lower than it was in the parental cell lines (P < 0.05). The expression of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream signaling proteins in PC9‐Gef and HCC827‐Gef cell lines was higher than the expression in PC9‐Gef‐miR‐34a and HCC827‐Gef‐miR‐34a cells, which overexpressed miR‐34a (P < 0.05).ConclusionThe miR‐34a regulation of Axl plays an important role in NSCLC‐acquired gefitinib resistance, and their expression is inversely correlated, which suggests that they can be used as prognostic markers or potential therapeutic targets for NSCLC.