bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perturbed functional networks in Alzheimer’s Disease reveal opposing roles for TGIF and EGR3
Authors: Canchi Saranya , Raao Balaji , Masliah Deborah , Rosenthal Sara Brin , Sasik Roman , Fisch Kathleen M. , Jager Philip De , Bennett David A. , Rissman Robert A. 
Published: March 2018

AbstractWhile Alzheimer’s disease (AD) is the most prevalent cause of dementia, complex combinations of the underlying pathologies have led to evolved concepts in clinical and neuropathological criteria in the past decade. Pathological AD can be decomposed into subsets of individuals with significantly different antemortem cognitive decline rates. Using transcriptome as a proxy for functional state, we preselected 414 expression profiles of clinically and neuropathologically confirmed AD subjects and age matched non-demented controls sampled from a large community based neuropathological study. By combining brain tissue specific protein interactome with gene network, we identify functionally distinct composite clusters of genes which reveal extensive changes in expression levels in AD. The average global expression for clusters corresponding to synaptic transmission, metabolism, cell cycle, survival and immune response were downregulated while the upregulated cluster had a large set of uncharacterized pathways and processes that may constitute an AD specific phenotypic signature. We identified four master regulators across all clusters of differentially expressed genes by enrichment analysis includingTGIF1andEGR3.These transcription factors have previously not been associated with AD and were validated in brain tissue samples from an independent AD cohort. We identifyTGIF1,a transcriptional repressor as being neuroprotective in AD by activating co-repressors regulating genes critical for DNA repair, maintaining homeostasis and arresting cell cycle. In addition, we show that loss ofEGR3regulation, mediates synaptic deficits by targeting the synaptic vesicle cycle. Collectively, our results highlight the utility of integrating protein interactions with gene perturbations to generate a comprehensive framework for characterizing the alterations in molecular network as applied to AD.
How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion
Authors: Chao Luke H. , Jang Jaebong , Johnson Adam , Nguyen Anthony , Gray Nathanael S. , Yang Priscilla L. , Harrison Stephen C. 
Published: March 2018

AbstractDengue virus (DV) is a compact, icoshedrally symmetric, enveloped particle, covered by 90 dimers of envelope protein (E), which mediates viral attachment and membrane fusion. Fusion requires a dimer-to-trimer transition and membrane engagement of hydrophobic “fusion loops”. We previously characterized the steps in membrane fusion for the related West Nile virus (WNV), using recombinant, WNV virus-like particles (VLPs) for single-particle experiments. Trimerization and membrane engagement are rate-limiting; fusion requires at least two adjacent trimers; availability of competent monomers within the contact zone between virus and target membrane creates a trimerization bottleneck. We have extended that work to dengue VLPs, from all four DV serotypes, finding an essentially similar mechanism. Small-molecule inhibitors of DV infection that target E block its fusion-inducing conformation change. We show that ∼15 bound molecules per particle (∼8.5 % occupancy) completely prevent fusion, in accord with the proposed mechanism and the likely inhibitor binding site on E.Impact statementSingle-particle studies of dengue-virus membrane fusion and the effect of small-molecule inhibitors of infection clarify the viral fusion mechanism.
Developmental genetics in a complex adaptive structure, the weevil rostrum
Authors: Davis S.R. 
Published: March 2018

AbstractThe rostrum of weevils (Curculionidae) is a novel, complex, adaptive structure that has enabled this huge beetle radiation to feed on and oviposit in a wide spectrum of plant hosts, correlated with diverse life histories and tremendous disparity in rostrum forms. In order to understand the development and evolution of this structure, transcriptomes were produced inde novoassemblies from the developing pre-pupal head tissues of two distantly related curculionids, the rice weevil (Sitophilus oryzae) and the mountain pine beetle (Dendroctonus ponderosae), which have highly divergent rostra. While there are challenges in assessing differences among transcriptomes and in relative gene expression from divergent taxa, tests for differential expression patterns of transcripts yielded lists of candidate genes to examine in future work. RNA interference was performed withS. oryzaefor functional insight into the Hox geneSex combs reduced. Scrhas a conserved function in labial and prothoracic identities, but it also demonstrates a novel role in reduction of ventral head structures, namely the gula, submentum, and associated sulci, in weevils. Ultimately, this study makes strides towards elucidating how the weevil rostrum initially formed and the profound phenotypic diversity it has acquired throughout the curculionoid lineages. It furthermore initiates a better understanding of the genetic framework that permitted the diversification of such an immense lineage as the weevils.Summary statementThis study begins exploring the development of a novel, complex structure in one of the largest families of organisms, the weevils.
Engineering targeted deletions in the mitochondrial genome
Authors: Campbell Jarryd M. , Perales-Clemente Ester , Ata Hirotaka , Vidal-Folch Noemi , Liu Weibin , Clark Karl J. , Xu Xiaolei , Oglesbee Devin , Nelson Timothy J. , Ekker Stephen C. 
Published: March 2018

Summary ParagraphMitochondria are a network of critical intracellular organelles with diverse functions ranging from energy production to cell signaling. The mitochondrial genome (mtDNA) consists of 37 genes that support oxidative phosphorylation and are prone to dysfunction that can lead to currently untreatable diseases. Further characterization of mtDNA gene function and creation of more accurate models of human disease will require the ability to engineer precise genomic sequence modifications. To date, mtDNA has been inaccessible to direct modification using traditional genome engineering tools due to unique DNA repair contexts in mitochondria1. Here, we report a new DNA modification process using sequence-specific transcription activator-like effector (TALE) proteins to manipulate mtDNA in vivo and in vitro for reverse genetics applications. First, we show mtDNA deletions can be induced in Danio rerio (zebrafish) using site-directed mitoTALE-nickases (mito-nickases). Using this approach, the protein-encoding mtDNA gene nd4 was deleted in injected zebrafish embryos. Furthermore, this DNA engineering system recreated a large deletion spanning from nd5 to atp8, which is commonly found in human diseases like Kearns-Sayre syndrome (KSS) and Pearson syndrome. Enrichment of mtDNA-deleted genomes was achieved using targeted mitoTALE-nucleases (mitoTALENs) by co-delivering both mito-nickases and mitoTALENs into zebrafish embryos. This combined approach yielded deletions in over 90% of injected animals, which were maintained through adulthood in various tissues. Subsequently, we confirmed that large, targeted deletions could be induced with this approach in human cells. In addition, we show that, when provided with a single nick on the mtDNA light strand, the binding of a terminal TALE protein alone at the intended recombination site is sufficient for deletion induction. This “block and nick” approach yielded engineered mitochondrial molecules with single nucleotide precision using two different targeted deletion sites. This precise seeding method to engineer mtDNA variants is a critical step for the exploration of mtDNA function and for creating new cellular and animal models of mitochondrial disease.
Cryo-EM structure of the polycystin 2-l1 ion channel
Authors: Hulse Raymond E. , Li Zongli , Huang Rick K. , Zhang Jin , Clapham David E. 
Published: March 2018

ABSTRACTWe report the near atomic resolution (3.1 Å) of the polycystic kidney disease 2-like 1 (polycystin 2-l1) ion channel. Encoded by PKD2L1, polycystin 2-l1 is a calcium and monovalent cation-permeant ion channel in primary cilia and plasma membranes. The related primary cilium-specific polycystin-2 protein, encoded by PKD2, shares a high degree of sequence similarity, yet has distinct permeability characteristics. Here we show that these differences are reflected in the architecture of polycystin 2-l1.
Redefining HR using people analytics: the case of Google
Authors: Shrivastava Shweta , Nagdev Kritika , Rajesh Anupama 
Published: March 2018

Purpose
This paper aims to highlight the importance of analytics and its advantages in the human resource domain using the example of Google, which has extensively used analytics to improve various aspects of people management.

Design/methodology/approach
The paper discusses human resource analytics and illustrates how it has been successfully implemented by Google to enable better decision-making.

Findings
Implementation of analytics in the area of human resources can make people-related decision-making objective, transparent and data-driven and, thus, make the function “quantitative” in nature.

Originality/value
Although analytics has been widely implemented in functions such as finance and marketing, it is yet to gain a strong foothold in the domain of human resources. This paper discusses how Google, a leading organization in the field of technology, has been able to take impactful people-related decisions with the help of analytics.
Volatility spillover between stock and foreign exchange market of China: evidence from subprime Asian financial crisis
Authors: Jebran Khalil 
Published: March 2018

Purpose
This paper aims to examine the volatility spillover dynamics between stock and foreign exchange market of China considering subprime 2007 financial crisis period.

Design/methodology/approach
This study considered daily data from January 2, 2002, to December 31, 2013. The sample period has been further divided into three periods; full sample period (January 2002-December 2013), pre-crisis period (January 2002-October 2007) and post-crisis period (October 2007-December 2013). This study opted Exponential Generalized Autoregressive Heteroskedasticity (EGARCH) model for the purpose of investigating asymmetric volatility spillover.

Findings
The results obtained using the EGARCH model imply that volatility spillover dynamics varies from period to period. In full sample period, the results show evidence of significant unidirectional volatility spillover from foreign exchange market to stock market. In pre-crisis period, the results indicate unidirectional volatility spillover from stock market to foreign exchange market. However, in post-crisis period, the results reveal significant bidirectional volatility spillover between stock and foreign exchange market.

Practical implications
The results of the study are important for policy makers because understanding the behavior of the financial markets, i.e. stock and foreign exchange market, would increase the success of policies implemented in a crisis situation. The results would help investors to formulate efficient portfolios.

Originality/value
This study is an important contribution to the existing literature in terms of analyzing volatility spillover between stock and foreign exchange market in an emerging economy, China. Furthermore, this study explored the volatility spillover dynamics between the two markets by considering the pre and post subprime Asian crisis period.
Workplace empowerment, quality of work life and employee commitment: a study on Indian healthcare sector
Authors: Nayak Tanaya , Sahoo Chandan Kumar , Mohanty Pravat Kumar 
Published: March 2018

PurposeThe purpose of the paper is to explore the relationship between workplace empowerment and employee commitment with quality of work life (QWL) as a mediator in the case of private healthcare employees in India.Design/methodology/approachThe study used a structured questionnaire to collect primary data from 279 employees of private healthcare units in India. AMOS 20 was used to analyse the data.FindingsResults of data analysis confirm that the proposed hypotheses of the study were significant. Structural equation modelling revealed a best-fit model that demonstrated QWL to be a significant partial mediator between workplace empowerment and employee commitment.Practical implicationsThis work provides a pragmatic view about the action mechanism through which workplace empowerment can aid in generating commitment among healthcare employees. The paper also offers insights for healthcare managers, administrators and practitioners.Originality/valueThe research is an attempt to integrate the employees as the core long-term assets of the healthcare system. The study establishes the triadic and symbiotic alliance of workplace empowerment, QWL and employee commitment in the novel context of healthcare.
Packaged scalable energy information systems for hotels
Authors: Singh Reshma , Mathew Paul , Granderson Jessica , Shukla Yash , Behera Amiya Ranjan 
Published: March 2018

Purpose
Building energy information systems (EIS) are performance monitoring software, data acquisition hardware and communication systems used to store, analyze and display building energy data. Some $60bn are spent annually on wasted energy in the US buildings, and actions taken based on EIS data can enable operational energy savings of approximately 10 per cent in the US commercial sector (approximately two quads of primary energy). However, EIS adoption is low because of various technical and market challenges. This paper aims to provide technical specifications for standardized EIS packages that can help overcome barriers and accelerate scale.

Design/methodology/approach
A five-step approach was followed: identifying business drivers as key determinants for hotel sector-specific packages; addressing heterogeneity to develop standardized, tiered packages; determining performance metrics for key stakeholders; recommending streamlined data architecture; and developing visualization enabling insights and actions.

Findings
Technical specifications for two tiers (entry and advanced) of EIS packages for hotels have been developed. EIS vendor, integrator and client organization’s facilities and IT staff have been considered as key stakeholders. Findings from six field demonstrations show benefits of cost-effectiveness, through reduced transactional, first and operational costs, scalability, by accommodating heterogeneity across the building sub-sector, simplicity, by integrating meters, gateways and software in the package and actionability in organizations, across various decision-making levels.

Originality/value
Building owners and operators can use these specifications to ease procurement and installation of EIS in their facilities. EIS software vendors can use them to develop new product offerings for underserved sectors.
Efficiency, stability and asset quality of Islamic vis-à-vis conventional banks
Authors: Prima Sakti Muhammad Rizky , Mohamad Azhar 
Published: March 2018

PurposeThis paper aims to examine how Indonesian Islamic banks differ from conventional banks in terms of their business model, asset quality, stability and efficiency.

Design/methodology/approachBased on data from 2008 to 2012, the authors use t-test, z-score and data envelopment analysis (DEA) to assess the business model, as well as the asset quality, stability and efficiency of both the Islamic and conventional banks.

FindingsThe results indicate that there are significant differences between the two – Islamic banks appear to not follow the conventional business model. Secondly, Islamic banks seem to have better asset quality and to be more stable than their conventional counterparts.

Originality/valueFinally, the DEA results also indicate that Islamic banks are relatively more efficient than conventional banks, as shown by their higher overall efficiency, as well as technical efficiency.
Correlation of epiploic foramen length to height, weight, breed, gender and age in horses
Authors: Alonso J. M. , Rosa G. S. , Marsiglia M. F. , Garcia Alves A. L. , Rodrigues C. A. , Watanabe M. J. , Figueiredo Pantoja J. C. , Hussni C. A. 
Published: March 2018

SummaryEpiploic foramen entrapment (EFE) is one of the most common causes of small intestinal strangulation in horses. Cribbing and previous episodes of colic are suggested as risk factors for its occurrence. The aim of this study was to correlate the height, weight, breed, gender and age to the epiploic foramen (EF) length. Forty‐three horses were submitted to post‐mortem measurement of epiploic foramen with abdominal and thoracic organs positioned in situ. After data collection, linear regression between EF length and the explanatory variables was performed. None of the post‐mortem physical variables was associated with EF length, supporting the hypothesis that there is no association between EF length and age, and that increased intra‐abdominal pressure is the most important factor predisposing to EFE recurrence.
Emerging relationships in a new group of Western lowland gorillas Gorilla gorilla gorilla at Riverbanks Zoo & Garden, Columbia, SC
Authors: Huskisson S. M. , Chism J. L. 
Published: March 2018

Behavioural interactions among members of a newly formed group of Western lowland gorillas Gorilla gorilla gorilla are analysed, from the early stages of group formation through the first several months after introduction. The group consisted of a male, two half‐sisters and an unrelated female. Data were collected in 15 minute focal animal samples for 3 hours twice a week in two 9 week observation blocks for a total of 99·25 observation hours. Hypotheses tested included: frequency of affiliative behaviours would increase over time, with more affiliative interactions between related females; and agonism would decrease over time. Overall, the mean rates of either behaviour type did not change between observation blocks (affiliative: P = 0·075; agonistic: P = 0·116) Total dyadic rates of affiliation were different in female–male dyads (P < 0·001) but not in female–female dyads (P = 0·525). Dyadic mean rates of agonism from both observation blocks were not different in either female–male or female–female dyads (P = 0·210). Using data from approach–withdrawal and grooming interactions, no strong dominance hierarchy was found among females, despite the relatedness of two of the three females. In general, the focal group exhibited group‐wide and intrasex relationships similar to those documented in other gorilla groups in zoos and in the wild, particularly with regard to the lack of consistent female social dominance.
RETRACTED: Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition
Authors: Chen Dehu , Cao Gan , Qiao Chunzhong , Liu Guiyuan , Zhou Haihua , Liu Qinghong 
Published: March 2018

AbstractAlpha B‐crystallin (CRYAB) is overexpressed in a variety of cancers. However, little is known about its specific function and regulatory mechanism in gastric cancer. Here, we first explore the role of CRYAB in gastric cancer progression and metastasis. The expression of CRYAB was determined by western blot and immunohistochemistry in gastric cancer tissues. Besides, methods including stably transfected against CRYAB into gastric cancer cells, western blot, migration and invasion assays in vitro and metastasis assay in vivo were also conducted. The expression of CRYAB is up‐regulated in gastric cancer tissues compared with matched normal tissues. High expression level of CRYAB is closely correlated with cancer metastasis and shorter survival time in patients with gastric cancer. Additionally, CRYAB silencing significantly suppresses epithelial‐mesenchymal transition (EMT), migration and invasion of gastric cancer cells in vitro and in vivo, whereas CRYAB overexpression dramatically reverses these events. Mechanically, CRYAB facilitates gastric cancer cells invasion and metastasis via nuclear factor‐κ‐gene binding (NF‐κB)‐regulated EMT. These findings suggest that CRYAB expression predicts a poor prognosis in patients with gastric cancer. Besides, CRYAB contributes to gastric cancer cells migration and invasion via EMT, mediated by the NF‐κB signalling pathway, thus possibly providing a novel therapeutic target for gastric cancer.
IL‐7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum‐infected mice
Authors: Zhu Jifeng , Zhang Weiwei , Zhang Lina , Xu Lei , Chen Xiaojun , Zhou Sha , Xu Zhipeng , Xiao Ming , Bai Hui , Liu Feng , Su Chuan 
Published: March 2018

AbstractIn schistosomiasis japonica and mansoni, parasite eggs trapped in host liver elicit severe liver granulomatous inflammation that subsequently leads to periportal fibrosis, portal hypertension, haemorrhage or even death. Macrophages are critical for granuloma formation and the development of liver fibrosis during schistosomiasis. However, whether the aberrant regulation of macrophage autophagy has an effect on the development of liver immunopathology in schistosomiasis remains to be elucidated. In this study, we showed that Schistosoma japonicum (S. japonicum) egg antigen (SEA)‐triggered macrophage autophagy limited the development of pathology in host liver. However, engagement of IL‐7 receptor (IL‐7R/CD127) on macrophages by S. japonicum infection‐induced IL‐7 significantly suppressed SEA‐triggered macrophage autophagy, which led to an enhanced liver pathology. In addition, anti‐IL‐7 neutralizing antibody or anti‐CD127 blocking antibody treatment increased macrophage autophagy and suppressed liver pathology. Finally, we demonstrated that IL‐7 protects macrophage against SEA‐induced autophagy through activation of AMP‐activated protein kinase (AMPK). Our study reveals a novel role for IL‐7 in macrophage autophagy and identifies AMPK as a novel downstream mediator of IL‐7‐IL‐7R signalling and suggests that manipulation of macrophage autophagy by targeting IL‐7‐IL‐7R signalling may have the potential to lead to improved treatment options for liver pathogenesis in schistosomiasis.
Comparison of two melphalan protocols and evaluation of outcome and prognostic factors in multiple myeloma in dogs
Authors: Fernández Ricardo , Chon Esther 
Published: March 2018

BackgroundMultiple myeloma (MM) in dogs typically is treated with melphalan. A daily melphalan dosing schedule reportedly is well tolerated and associated with favorable outcome. Although anecdotally a pulse dose regimen has resulted in successful responses, little long‐term outcome and safety data is available regarding this dosing regimen for dogs with MM.Hypothesis/objectives(1) To compare outcome and adverse event profiles between pulse dose and daily dose melphalan schedules and (2) to report prognostic factors in dogs with MM treated with melphalan. We hypothesized that both protocols would have similar outcomes and tolerability.AnimalsThirty‐eight client‐owned dogs diagnosed with MM receiving pulse dose (n = 17) or daily dose (n = 21) melphalan.MethodsRetrospective cohort study assessing outcome and adverse events in dogs receiving either protocol. Risk factors were evaluated for their prognostic relevance.ResultsBoth regimens were well tolerated and similarly effective, with an overall median survival time of 930 days. Renal disease and neutrophil‐to‐lymphocyte ratio (NLR) were negative prognostic factors, whereas hypercalcemia and osteolytic lesions were not prognostic factors in this study population.Conclusions and Clinical ImportancePositive results support the use of either dosing regimen for the treatment of dogs with MM, and renal disease and NLR were negative prognostic factors. Prospective, controlled, and randomized studies are warranted to confirm these findings.