bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deconvoluting Virome-Wide Antiviral Antibody Profiling Data
Authors: Monaco Daniel R. , Kottapalli Sanjay V. , Yuan Tiezheng , Breitwieser Florian P. , Anderson Danielle E. , Wijaya Limin , Tan Kevin , Chia Wan Ni , Kammers Kai , Caturegli Mario , Waugh Kathleen , Rewers Marian , Wang Lin-Fa , Benjamin Larman H. 
Published: May 2018

AbstractThe ability to comprehensively characterize exposures and immune responses to viral infections will be critical to better understanding human health and disease. We previously described the VirScan system, a phage-display based technology for profiling antibody binding to a comprehensive library of peptides designed to represent the human virome. The previous VirScan analytical approach did not fully account for disproportionate representation of viruses in the library or for antibody cross-reactivity among sequences shared by related viruses. Here we present the ‘AntiViral Antibody Response Deconvolution Algorithm’ (‘AVARDA’), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection at species-level resolution by considering alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. By comparing acute and convalescent sera, AVARDA successfully confirmed or detected antibody responses to human herpesviruses 1, 3, 4, 5, and 6, thereby improving the rate of diagnosing viral encephalitis in this cohort by 62.5%. We further assessed AVARDA’s utility in the setting of an epidemiological study, demonstrating its ability to determine infections acquired in a child followed prospectively from infancy. We consider ways in which AVARDA’s conceptual framework may be further developed in the future and describe how its analyses may be extended beyond investigations of viral infection. AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases.
Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability
Authors: Jing Anqi , Vizeacoumar Frederick S. , Parameswaran Sreejit , Haave Bjorn , Cunningham Chelsea E. , Wu Yuliang , Arnold Roland , Bonham Keith , Freywald Andrew , Han Jie , Vizeacoumar Franco J. 
Published: May 2018

ABSTRACTCan transcriptomic alterations drive the evolution of tumors? We rationalize that expressional changes found in all patients arise earlier in tumor development compared to alterations that occur only in limited subsets of patients. Our analyses of non-mutated genes from the non-amplified regions of the genome of 158 triple negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC. Phylogenetic analyses of these genes predict a “punctuated burst” of multiple gene up-regulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression. Remarkably, this punctuated burst of expressional changes is instigated by hypoxia-related molecular events, predominantly in two groups of genes that control chromosomal instability (CIN) and remodel tumor microenvironment (TME). We conclude that alterations in the transcriptome are not stochastic and that early stage hypoxia induces CIN and TME remodeling to permit further tumor evolution.
xMD-miRNA-seq to generate near in vivo miRNA expression estimates in colon epithelial cells
Authors: Rosenberg Avi Z. , Wright Carrie , Fox-Talbot Karen , Rajpurohit Anandita , Williams Courtney , Porter Corey , Kovbasnjuk Olga , McCall Matthew N. , Shin Joo Heon , Halushka Marc K. 
Published: May 2018

AbstractAccurate, RNA-seq based, microRNA (miRNA) expression estimates from primary cells have recently been described. However, this in vitro data is mainly obtained from cell culture, which is known to alter cell maturity/differentiation status, significantly changing miRNA levels. What is needed is a robust method to obtain in vivo miRNA expression values directly from cells. We introduce expression microdissection miRNA small RNA sequencing (xMD-miRNA-seq), a method to isolate cells directly from formalin fixed paraffin-embedded (FFPE) tissues. xMD-miRNA-seq is a low-cost, high-throughput, immunohistochemistry-based method to capture any cell type of interest. As a proof-of-concept, we isolated colon epithelial cells from two specimens and performed low-input small RNA-seq. We generated up to 600,000 miRNA reads from the samples. Isolated epithelial cells, had abundant epithelial-enriched miRNA expression (miR-192; miR-194; miR-200b; miR-200c; miR-215; miR-375) and overall similar miRNA expression patterns to other epithelial cell populations (colonic enteroids and flow-isolated colon epithelium). xMD-derived epithelial cells were generally not contaminated by other adjacent cells of the colon as noted by t-SNE analysis. xMD-miRNA-seq allows for simple, economical, and efficient identification of cell-specific miRNA expression estimates. Further development will enhance rapid identification of cell-specific miRNA expression estimates in health and disease for nearly any cell type using archival FFPE material.
Identification of a Chimeric M4 Protein and Novel Emm Pattern in Currently Circulating Strains of Emm4 Group A Streptococcus
Authors: DebRoy Sruti , Li Xiqi , Kalia Awdhesh , Galloway Peña Jessica , Shah Brittany J. , Fowler Vance G. , Flores Anthony R. , Shelburne Samuel A. 
Published: May 2018

ABSTRACTGroup A Streptococcus (GAS) is classified by sequence of the gene encoding the M protein (emm) and the patterns into which emm types are grouped. We discovered a novel emm pattern in emm4 GAS, historically considered pattern E, arising from a fusion event between emm and the adjacent enn gene. We identified the emm/enn fusion event in 51/52 emm4 GAS strains isolated by national surveillance in 2015. GAS isolates with an emm/enn fusion event completely replaced pattern E emm4 strains over a 4-year span in Houston (2013-2017). The novel emm/enn gene fusion and new emm pattern has potential vaccine implications.
Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers
Authors: Osmanbeyoglu Hatice U. , Shimizu Fumiko , Rynne-Vidal Angela , Jelinic Petar , Mok Samuel C. , Chiosis Gabriela , Levine Douglas A. , Leslie Christina S. 
Published: May 2018

ABSTRACTEpigenomic data on transcription factor occupancy and chromatin accessibility can elucidate the developmental origin of cancer cells and reveal the enhancer landscape of key oncogenic transcriptional regulators. However, in many cancers, epigenomic analyses have been limited, and computational methods to infer regulatory networks in tumors typically use expression data alone, or rely on transcription factor (TF) motifs in annotated promoter regions. Here, we develop a novel machine learning strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to combine cell line chromatin accessibility data with large tumor expression data sets and model the effect of enhancers on transcriptional programs in multiple cancers. We generated a new ATAC-seq data set profiling chromatin accessibility in gynecologic and basal breast cancer cell lines and applied PSIONIC to 723 RNA-seq experiments from ovarian, uterine, and basal breast tumors as well as 96 cell line RNA-seq profiles. Our computational framework enables us to share information across tumors to learn patient-specific inferred TF activities, revealing regulatory differences between and within tumor types. Many of the identified TF regulators were significantly associated with survival outcome in basal breast, uterine serous and endometrioid carcinomas. Moreover, PSIONIC-predicted activity for MTF1 in cell line models correlated with sensitivity to MTF1 inhibition. Therefore computationally dissecting the role of TFs in gynecologic cancers may ultimately advance personalized therapy.
Aggregation ofVibrio choleraeby cationic polymers enhances quorum sensing but over-rides biofilm dissipation in response to autoinduction
Authors: Perez-Soto Nicolas , Creese Oliver , Fernandez-Trillo Francisco , Krachler Anne-Marie 
Published: May 2018

AbstractVibrio choleraeis a Gram-negative bacterium found in aquatic environments and a human pathogen of global significance. Its transition between host-associated and environmental life styles involves the tight regulation of niche-specific phenotypes such as motility, biofilm formation and virulence.V. cholerae’s transition from the host to environmental dispersal usually involves suppression of virulence and dispersion of biofilm communities. In contrast to this naturally occurring transition, bacterial aggregation by cationic polymers triggers a unique response, which is to suppress virulence gene expression while also triggering biofilm formation byV. cholerae, an artificial combination of traits that is potentially very useful to bind and neutralize the pathogen from contaminated water. Here, we set out to uncover the mechanistic basis of this polymer-triggered bacterial behavior. We found that bacteria-polymer aggregates undergo rapid autoinduction and achieve quorum sensing at bacterial densities far below those required for autoinduction in the absence of polymers. We demonstrate this induction of quorum sensing is due both to a rapid formation of autoinducer gradients and local enhancement of autoinducer concentrations within bacterial clusters, as well as the stimulation of CAI-1 and AI-2 production by aggregated bacteria. We further found that polymers cause an induction of the biofilm specific regulator VpsR and the biofilm structural protein RbmA, bypassing the usual suppression of biofilm during autoinduction. Overall, this study highlights that synthetic materials can be used to cross-wire natural bacterial responses to achieve a combination of phenotypes with potentially useful applications.
LMO7 deficiency reveals the significance of the cuticular plate for hearing function
Authors: Du Ting-Ting , Dewey James B. , Wagner Elizabeth L. , Francis Shimon P. , Perez-Reyes Edward , Xu Wenhao , Oghalai John S , Shin Jung-Bum 
Published: May 2018

AbstractSensory hair cells, the mechanoreceptors of the auditory and vestibular system, harbor two specialized organelles, the hair bundle and the cuticular plate. Both subcellular structures have adapted to facilitate the remarkable sensitivity and speed of hair cell mechanotransduction. While the mechanosensory hair bundle is extensively studied, the molecules and mechanisms mediating the development and function of the cuticular plate are poorly understood. The cuticular plate is believed to provide a rigid foundation for stereociliar pivot movements, but specifics about its function, especially the significance of its integrity for long-term maintenance of hair cell mechanotransduction, are not known. In this study, we describe the discovery of a hair cell protein called LIM only protein 7 (LMO7). In the hair cell, LMO7 is specifically localized in the cuticular plate.Lmo7 KOmice suffer multiple deficiencies in the cuticular plate, including reduced filamentous actin density and abnormal length and distribution of stereociliar rootlets. In addition to the cuticular plate defects, olderLmo7 KOmice develop abnormalities in inner hair cell stereocilia. Together, these defects affect cochlear tuning and sensitivity and give rise to late-onset progressive hearing loss.
Hepatitis B Virus Inhibits Neutrophil Extracellular Traps Release by Modulating Reactive Oxygen Species Production and Autophagy
Authors: Hu Shengnan , Liu Xiaowen , Gao Ying , Zhou Rongfang , Wei Muyun , Yan Huili , Zhao Yueran 
Published: May 2018

AbstractNeutrophils, an important component of the innate immune system, release extracellular traps (NETs) to eliminate invaded pathogens by trapping and killing microbes. A dysfunctional innate immune response is a major cause of persistent hepatitis B virus (HBV) infection. HBV has been shown to reduce neutrophil responses. The objectives of the present study were to determine whether HBV influenced NETs release and to identify the underlying mechanisms. Primary neutrophils and circulating blood samples were collected from 40 patients with a chronic hepatitis B infection (CHB) and 40 healthy controls to detect NETs release using a Quant-iT Pico Green dsDNA assay and to determine the levels of HBV-DNA and HBV markers. NETs release was decreased in patients with a CHB infection, and hepatitis B surface antigen, hepatitis B e antigen and hepatitis B core antibody levels negatively correlated with NETs release. The Quant-iT Pico Green dsDNA assay and western blotting were used to examine the effect of HBV proteins (HBV X protein, HBV C protein, HBV E protein and HBV S protein) on NETs releasein vitro. Based on the flow cytometry and western blot data, HBV C protein and HBV E protein inhibited NETs release by decreasing reactive oxygen species (ROS) production and autophagy. Overall, HBV may inhibit NETs release by modulating ROS production and autophagy to escape the immune system and promote the establishment of a chronic infection.
The RASSF6 tumor suppressor protein regulates apoptosis and the cell cycle progression via Retinoblastoma protein
Authors: Hossain Shakhawoat , Iwasa Hiroaki , Sarkar Aradhan , Maruyama Junichi , Arimoto-Matsuzaki Kyoko , Hata Yutaka 
Published: May 2018

ABSTRACTRASSF6 is a member of the tumor suppressor Ras-association domain family (RASSF) proteins. RASSF6 is frequently suppressed in human cancers and its low expression is associated with poor prognosis. RASSF6 regulates cell cycle arrest and apoptosis and plays a tumor suppressor role. Mechanistically, RASSF6 blocks MDM2-mediated p53 degradation and enhances p53 expression. However, RASSF6 also induces cell cycle arrest and apoptosis in the p53-negative background, which implies that the tumor suppressor function of RASSF6 does not depend solely on p53. In this study, we have revealed that RASSF6 mediates cell cycle arrest and apoptosis via pRb. RASSF6 enhances the interaction between pRb and protein phosphatase. RASSF6 also enhances P16INK4A and P14ARF expression through suppressing BMI1. In this way, RASSF6 increases unphosphorylated pRb and augments the interaction between pRb and E2F1. Moreover, RASSF6 induces TP73-target genes via pRb and E2F1 in the p53-negative background. Finally, we confirmed that RASSF6 depletion induces polypoid cells in p53-negative HCT116 cells. In conclusion, RASSF6 behaves as a tumor suppressor in cancers with the loss-of-function of p53, and pRb is implicated in this function of RASSF6.
Attenuated beta rebound to proprioceptive afferent feedback in Parkinson’s disease
Authors: Vinding Mikkel C. , Tsitsi Panagiota , Piitulainen Harri , Waldthaler Josefine , Jousmäki Veikko , Ingvar Martin , Svenningsson Per , Lundqvist Daniel 
Published: May 2018

AbstractMotor symptoms are defining traits in the diagnosis of Parkinson’s disease (PD). A crucial component in motor function and control of movements is the integration of efferent signals from the motor network to the peripheral motor system, and afferent proprioceptive sensory feedback. Previous studies have indicated abnormal movement-related cortical oscillatory activity in PD, but the role of the proprioceptive afference on abnormal oscillatory activity in PD has not been elucidated. In the present study, we examine the role of proprioception by studying the cortical processing of proprioceptive stimulation in PD patients, ON/OFF levodopa medication, as compared to that of healthy controls (HC). We used a proprioceptive stimulator that generated precisely controlled passive movements of the index finger and measured the induced cortical oscillatory responses following the proprioceptive stimulation using magnetoencephalography (MEG). Both PD patients and HC showed a typical initial mu/beta-band (8–30 Hz) desynchronization during the passive movement. However, the subsequent beta rebound after the passive movement that was apparent in HC was much attenuated and almost absent in PD patients. Furthermore, we found no difference in the degree of beta rebound attenuation between patients ON and OFF levodopa medication. Our results hence demonstrate a disease-related deterioration in cortical processing of proprioceptive afference in PD, and further suggest that such disease-related loss of proprioceptive function is due to processes outside the dopaminergic system affected by levodopa medication.
Variation in expression of the HECT E3 ligase UPL3 modulates LEC2 levels, gene expression, seed size and crop yields in Brassica napus
Authors: Miller Charlotte , Wells Rachel , McKenzie Neil , Trick Martin , Ball Joshua , Fatihi Abdelhak , Debreuq Bertrand , Chardot Thierry , Lepiniec Loic , Bevan Michael W 
Published: May 2018

AbstractIdentifying genetic variation that increases crop yields is a primary objective in plant breeding. We have used association analyses of Brassica napus (oilseed rape/canola) accessions to identify variation in the expression of a HECT E3 ligase gene, BnaUPL3.C03, that influences seed size and final yield. We establish a mechanism in which UPL3 mediates the proteasomal degradation of LEC2, a master regulator of seed maturation. Reduced UPL3 expression increases LEC2 protein levels and prolongs expression of lipid biosynthetic genes and seed maturation. Natural variation in BnaUPL3.C03 expression has not yet been exploited in current Brassica napus breeding lines and can therefore be used as a new approach to maximize future yields in this important oil crop.
Identifying do’s and don’ts using the integrated business process management framework
Authors: Malinova Monika , Mendling Jan 
Published: May 2018

Purpose
The authors observe that actionable guidelines are missing from many reference works on business process management (BPM). Also, success factors are mostly not contextualized in the different phases and concerns of a BPM initiative. The purpose of this paper is to address this research gap.

Design/methodology/approach
The research design builds on a literature survey for building an integrated framework for BPM that is referred to as integrated BPM. It integrates lifecycle phases, capability areas and governance aspects. Then, the authors consolidate insights from expert interviews.

Findings
As a result, the authors provide a list of various activities that are associated with the different elements of BPM. Furthermore, the authors describe pitfalls for each of the elements that have been avoided in order to make the BPM initiative a success.

Research limitations/implications
The findings emphasize the potential to study BPM success and its factors on a more fine-granular activity level.

Practical implications
The list of activities and the list of pitfalls are directly applicable for practitioners.

Originality/value
The research on the integrated BPM framework consolidates insights from prior research and extends it with an expert perspective on pitfalls.
Brand gender-bending
Authors: Azar Salim L. , Aimé Isabelle , Ulrich Isabelle 
Published: May 2018

Purpose
Mixed-target brands with strong gender identities, whether it be feminine or masculine, are not always successful at targeting both men and women, particularly in symbolic product categories. While attempting to maximize their sales for both targets, managers often struggle to capitalize on a single brand, and they hesitate between different naming strategies. This paper aims to build on brand gender literature and understand these brands’ (i.e. brands targeting both men and women) potential to adopt an endorsed brand strategy rather than a branded house strategy.

Design/methodology/approach
The paper uses a before/after experimental design to examine the effect that introducing a gender-incongruent endorsed brand (i.e. feminine endorsed brand name of masculine master brands and masculine endorsed brand name of feminine master brands) can have on consumers’ brand attitude.

Findings
First, adopting an endorsed brand strategy increases the perceived brand femininity of masculine master brands, but there is no increase in feminine master brands’ perceived brand masculinity. Second, this strategy has a negative impact on consumer attitude toward the master brand, with a stronger negative effect for feminine master brands than for masculine master brands, which is mediated by the brand gender perception change. Third, a negative feedback effect on the brand’s gender-congruent users is revealed.

Research limitations/implications
One limitation of this work is that the focus is on one sole extrinsic brand characteristic (i.e. brand name) in our experimental design, which artificially influences the relative brand name importance for consumers. Moreover, the studies offered a short text to introduce the renaming. This may have made the respondents focus on the brand more than they would have in real-world conditions.

Practical implications
This research provides many insights for masculine or feminine mixed-target brands managers in symbolic product categories, as it shows that changing from a branded house strategy to an endorsed brand strategy appears to be unsuccessful in the short run, regardless of master brand’s gender. Moreover, the study reveals negative feedback effects on the attitude toward the initial master brand, following its renaming, in the short run.

Originality/value
This research provides a warning to managers trying to gender-bend their existing brands because it can lead to brand dilution. It also emphasizes the asymmetrical evaluation of masculine vs feminine master brands, as manipulating a brand’s perceived masculinity appears very difficult to do successfully.
High-performance teams and job involvement: exploring the linkage to augment quality in Indian education and research
Authors: Paul Happy , Bamel Umesh Kumar , Stokes Peter 
Published: May 2018

PurposeIndian higher education (HE) is arguably “in the doldrums.” Conformity to minimum standards and requirements combined with ever-eroding quality is the serious threats. Many researchers have suggested adopting a functional approach in universities and developing greater autonomy and accountability to improve the situation. The purpose of this paper is to deliberate on the introduction of an integrated way of making teachers more involved in their profession with the intention of enhancing the quality of education and research.Design/methodology/approachThe paper’s argument conceptualizes the possibilities of the Indian HE system benchmarking the concept of high-performance teams (HTPs) as practiced in the industry.FindingsTaking the support from the extant literature, it is proposed that working in HTPs have the potential to elevate the involvement level of the faculty. Furthermore, it is suggested that through the implementation of HTPs in educational settings, teachers would also be able to develop their competencies in relation to research activities.Originality/valueThe model presented in the study has the potential to be empirically tested for its validity and reliability, which opens vistas for future research.