bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection of Candida albicans Trisomy during Oropharyngeal Infection Results in a Commensal-Like Phenotype
Authors: Forche Anja , Solis Norma V. , Swidergall Marc , Thomas Robert , Guyer Alison , Beach Annette , Cromie Gareth A. , Le Giang T. , Lowell Emily , Pavelka Norman , Berman Judith , Dudley Aimeé M. , Selmecki Anna , Filler Scott G. 
Published: February 2019

AbstractWhen the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr 6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype.
Alzheimer’s disease clinical variants show distinct regional patterns of neurofibrillary tangle accumulation
Authors: Petersen Cathrine , Nolan Amber L , de Paula França Resende Elisa , Ehrenberg Alexander , Spina Salvatore , Miller Bruce L. , Seeley William , Miller Zachary , Grinberg Lea T. 
Published: February 2019

ABSTRACTBackgroundNeurofibrillary tangle (NFT) pathology in Alzheimer’s disease (AD) follows a stereotypic progression well-characterized by Braak staging. However, some AD cases show deviations from the Braak staging scheme. In this study, we tested the hypothesis that these variations in the regional distribution of tau pathology are linked to heterogeneity in the clinical phenotypes of AD.MethodsWe included a clinicopathological cohort of ninety-four AD cases enriched for atypical clinical presentations. Subjects underwent apolipoprotein E (APOE) genotyping and neuropsychological testing. Main cognitive domains (executive, visuospatial, language, and memory function) were assessed using an established composite z-score. We assessed NFT density and distribution from thioflavin S fluorescent microscopy throughout four neocortical and two hippocampal regions. A mathematical algorithm classifying AD cases into typical, hippocampal sparing (HpSp), and limbic predominant (LP) subtypes based on regional NFT burden was compared to unbiased hierarchical clustering for cases with Braak stage > IV.ResultsPatients diagnosed with logopenic primary progressive aphasia showed significantly higher NFT density in the superior temporal gyrus relative to patients diagnosed with Alzheimer-type dementia (p = 0.0091), while patients with corticobasal syndrome showed significantly higher NFT density in the primary motor cortex (p = 0.0205). Hierarchical clustering identified three discrete clusters of patients characterized respectively by low overall NFT burden (n = 18), high overall burden (n = 30), and cortical-predominant burden (n = 24). A regionally specific effect was observed for visuospatial ability; higher NFT density in the angular gyrus (β = - 0.0921, p = 0.0099) and in the CA1 sector of the hippocampus (β = −0.0735, p = 0.0380) was significantly associated with more severe visuospatial dysfunction, modulated by age of death.ConclusionsOur results suggest domain-specific functional consequences of regional NFT accumulation. In particular, we observed focal aggregation of NFT density in clinically relevant regions among different clinical AD variants. Continued work to map the regionally specific clinical consequences of tau accumulation presents an opportunity to increase understanding of disease mechanisms underlying atypical clinical manifestations.
Reduced Plasma Ascorbic Acid Levels in Recipients of Myeloablative Conditioning & Hematopoietic Cell Transplantation
Authors: Rasheed Mahmood , Simmons Gary , Fisher Bernard , Leslie Kevin , Reed Jason , Roberts Catherine , Natarajan Ramesh , Fowler Alpha , Toor Amir 
Published: February 2019

AbstractHematopoietic cell transplantation (HCT) conditioned using myeloablative conditioning (MAC) is complicated by end organ injury due to endothelial dysfunction and graft versus host disease. Mucositis and oxidant injury results in micronutrient deficiency. Ascorbic acid (AA) levels were measured in 15 patients undergoing HCT conditioned with MAC (11 allogeneic and 4 autologous HCT). Ascorbate levels declined post conditioning to 27.3 (±14.1) by day 0 (p <0.05 compared with baseline), reaching a nadir level of 21.5 (±13.8) on day 14 (p <0.05) post-transplant. Patients undergoing allogeneic HCT continued to have low AA levels to day 60 post transplant, whereas recipients of autologous HCT recovered plasma AA levels to normal. The role of AA in maintaining endothelial function and hematopoietic as well as T cell recovery is provided, developing the rationale for repletion of vitamin C following HCT.
Memory-guided microsaccades
Authors: Willeke Konstantin-Friedrich , Tian Xiaoguang , Buonocore Antimo , Bellet Joachim , Ramirez-Cardenas Araceli , Hafed Ziad M. 
Published: February 2019

AbstractMicrosaccades are overwhelmingly described as involuntary eye movements. Here we show in both human subjects and monkeys that individual microsaccades of any direction can easily be triggered: (1) “on demand”, based on an arbitrary instruction, (2) without any special training, (3) without visual guidance by a stimulus, and (4) in a spatially and temporally accurate manner. Subjects voluntarily generated instructed “memory-guided” microsaccades readily, and similarly to how they made normal visually-guided ones. In two monkeys, we also observed midbrain superior colliculus neurons that exhibited movement-related activity bursts exclusively for memory-guided microsaccades, but not for similarly-sized visually-guided movements. Our results demonstrate behavioral and neural evidence for voluntary control over individual microsaccades, supporting recently discovered functional contributions of individual microsaccade generation to visual performance alterations and covert visual selection.
HtrA1 alters endothelial tube formation characteristics in an in vitro model
Authors: Singh Harmeet , Nie Guiying 
Published: February 2019

AbstractHigh temperature requirement factor A1 (HtrA1) is a serine protease of the mammalian HtrA family. It is ubiquitously expressed with high levels in the placenta. Dysregulation of HtrA1 has been linked to a number of diseases, in particular age-related macular degeneration (AMD) and preeclampsia (PE) in which HtrA1 is significantly increased. AMD is the leading cause of irreversible visual impairment in older people, affecting millions across the globe. PE is a life-threatening pregnancy complication, affecting 2-7% of pregnant women worldwide. Although AMD and PE are very different diseases, both are associated with endothelial dysfunction and dysregulation of angiogenesis. Given HtrA1 is up-regulated in both AMD and PE, in this study we examined the impact of excessive HtrA1 on capillary tube formation of HUVECs as an in vitro angiogenesis model. HtrA1 at high concentrations significantly increased the total number of tube branch points and inter-tubular loops, but considerably decreased the mean tube length, resulting in more but much smaller tubes. However, these smaller tubes were incomplete/broken. These data demonstrated that high concentrations of HtrA1 altered endothelial tube formation characteristics of HUVEVs. Our results suggest that HtrA1 over-expression in AMD and PE may directly contribute to the endothelial dysfunction in these diseases.
Computational identification of novel Kir6 channel inhibitors
Authors: Chen Xingyu , Garon Arthur , Wieder Marcus , Houtman Marien J.C. , Zangerl-Plessl Eva-Maria , Langer Thierry , van der Heyden Marcel A.G. , Stary-Weinzinger Anna 
Published: February 2019

AbstractKATP channels consist of four Kir6.x pore–forming subunits and four regulatory sulfonylurea receptor (SUR) subunits. These channels couple the metabolic state of the cell to membrane excitability and play a key role in physiological processes such as insulin secretion in the pancreas, protection of cardiac muscle during ischemia and hypoxic vasodilation of arterial smooth muscle cells. Abnormal channel function resulting from inherited gain or loss-of-function mutations in either the Kir6.x and/or SUR subunits are associated with severe diseases such as neonatal diabetes, congenital hyperinsulinism or Cantú syndrome (CS). CS is an ultra-rare genetic autosomal dominant disorder, caused by dominant gain-of-function mutations in SUR2A or Kir6.1 subunits. No specific pharmacotherapeutic treatment options are currently available for Cantú syndrome. Kir6 specific inhibitors could be beneficial for the development of novel drug therapies for Cantú syndrome, particular for mutations, which lack high affinity for sulfonylurea inhibitor glibenclamide. By applying a combination of computational methods including atomistic MD simulations, free energy calculations and pharmacophore modelling, we identified several novel Kir6.1 inhibitors, which might be possible candidates for drug repurposing. The in silico predictions were confirmed using inside/out patch-clamp analysis. Importantly, Cantú mutation C176S in Kir6.1 and S1020P in SUR2A, retained high affinity towards the novel inhibitors. Summarizing, the inhibitors identified in this study might provide a starting point towards developing novel therapies for Cantú disease.
Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency
Authors: Gardiner Laura-Jayne , Wingen Luzie U. , Bailey Paul , Joynson Ryan , Brabbs Thomas , Wright Jonathan , Higgins James D. , Hall Neil , Griffiths Simon , Clavijo Bernardo J. , Hall Anthony 
Published: February 2019

AbstractSequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. Lack of recombination limits breeding efforts in crops, therefore increasing recombination rates can reduce linkage-drag and generate new genetic combinations. We use computational analysis of 13 recombinant inbred mapping populations to assess crossover and gene conversion frequency in the hexaploid genome of wheat (Triticum aestivum). We observe that high frequency crossover sites are shared between populations and that closely related parental founders lead to populations with more similar crossover patterns. We demonstrate that gene conversion is more prevalent and covers more of the genome in wheat than in other plants, making it a critical process in the generation of new haplotypes, particularly in centromeric regions where crossovers are rare. We have identified QTL for altered gene conversion and crossover frequency and confirm functionality for a novel RecQ helicase gene that belongs to an ancient clade that is missing in some plant lineages including Arabidopsis. This is the first gene to be demonstrated to be involved in gene conversion in wheat. Harnessing the RecQ helicase has the potential to break linkage-drag utilizing widespread gene conversions.
Transmission of human-associated microbiota along family and social networks
Authors: Brito Ilana L. , Gurry Thomas , Zhao Shijie , Huang Katherine , Young Sarah K. , Shea Terrence P. , Naisilisili Waisea , Jenkins Aaron P. , Jupiter Stacy D. , Gevers Dirk , Alm Eric J. 
Published: February 2019

AbstractThe human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans1,2. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively ‘closed’ cohort of 287 people from the Fiji Islands, where common barriers to bacterial transmission are absent, we examine putative bacterial transmission in individuals’ gut and oral microbiomes using strain-level data from both core SNPs and flexible genomic regions. We find a weak signal of transmission, defined by the inferred sharing of genotypes, across many organisms that, in aggregate, reveals strong transmission patterns, most notably within households and between spouses. We find that women harbor strains more closely related to those harbored by their familial and social contacts than men; and that transmission patterns of oral- and gut-associated microbiota need not be the same. Using strain-level data alone, we are able to confidently predict a subset of spouses, highlighting the role of shared susceptibilities, behaviors or social interactions that distinguish specific links in the social network.
Class IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription
Authors: Zhu Yongchuan , Huang Min , Bushong Eric , Uytiepo Marco , Beutter Elizabeth , Boemer Daniel , Ellisman Mark , Maximov Anton 
Published: February 2019

AbstractThe formation of new memories requires transcription. However, the mechanisms that limit signaling of relevant gene programs in space and time for precision of coding and the roles of these programs in specific aspects of information processing remain poorly understood. We found that, during learning, the cellular patterns of expression of early response genes (ERGs) are regulated by class IIa HDACs 4 and 5, transcriptional repressors that transiently enter neuronal nuclei from cytoplasm after sensory input. Mice lacking these repressors in the forebrain have abnormally broad experience-dependent expression of ERGs, altered synaptic architecture and function, elevated anxiety, and severely impaired memory. By acutely manipulating the nuclear activity of class IIa HDACs in behaving animals using a chemical-genetic technique, we further demonstrate that rapid induction of ERG programs is critical for memory acquisition but these programs may become dispensable when a stable memory is formed. These results provide new insights into the molecular basis of memory storage.
Reliability analysis for a hypersonic aircraft’s wing spar
Authors: Wang Yuhui , Shao Peng , Wu Qingxian , Chen Mou 
Published: February 2019

Purpose
This paper aims to present a novel structural reliability analysis scheme with considering the structural strength degradation for the wing spar of a generic hypersonic aircraft to guarantee flight safety and structural reliability.

Design/methodology/approach
A logarithmic model with strength degradation for the wing spar is constructed, and a reliability model of the wing spar is established based on stress-strength interference theory and total probability theorem.

Findings
It is demonstrated that the proposed reliability analysis scheme can obtain more accurate structural reliability and failure results for the wing spar, and the strength degradation cannot be neglected. Furthermore, the obtained results will provide an important reference for the structural safety of hypersonic aircraft.

Research limitations/implications
The proposed reliability analysis scheme has not implemented in actual flight, as all the simulations are conducted according to the actual experiment data.

Practical implications
The proposed reliability analysis scheme can solve the structural life problem of the wing spar for hypersonic aircraft and meet engineering practice requirements, and it also provides an important reference to guarantee the flight safety and structural reliability for hypersonic aircraft.

Originality/value
To describe the damage evolution more accurately, with consideration of strength degradation, flight dynamics and material characteristics of the hypersonic aircraft, the stress-strength interference method is first applied to analyze the structural reliability of the wing spar for the hypersonic aircraft. The proposed analysis scheme is implemented on the dynamic model of the hypersonic aircraft, and the simulation demonstrates that a more reasonable reliability result can be achieved.
The boss and daddy’s little girl: on the construction of gender in Swedish business media
Authors: Hansson Magnus , Gottfridsson Hanna , Raanaes Sandra 
Published: February 2019

Purpose
This paper aims to analyse the construction of gender in business media through identification of media discourses in terms of vocabulary and vocabulary structures.

Design/methodology/approach
The authors conduct critical discourse analysis and linguistic text analysis of media articles in two Swedish business magazines, focussing on vocabulary and vocabulary structures used to describe men and women as managers.

Findings
Media texts fall into traditional, gender-stereotyped patterns. The use of metaphors, choice of words and sentence structures construct and maintain stereotyped models of gender. The linguistic practices and use of specific and gender-biased vocabulary shape discursive practices, contributing to the construction and reconstruction of institutionalised gender-stereotyped patterns of behaviour and established social norms.

Research limitations/implications
The focus on vocabulary and vocabulary structures extends the technique and application of critical discourse analysis, enabling fine-grained analyses, in this case of media texts. This research also indicates a need for future studies that adopt a critical discourse analysis to take into account analytical procedures that shed light on micro-mechanisms that support the materialisations of gender inequalities.

Social implications
Texts that portray both men and women show gender bias that is deeply rooted in the vocabulary and vocabulary structures and thus help to reinforce established discursive practices and gender inequalities. Therefore, there is a need for a fundamental change in the media reports on managers.

Originality/value
The research contributes to the analysis of media texts and representations of men and women as managers by providing a detailed analysis of discursive practices that takes into account vocabulary and vocabulary structures. The findings show the deeply rooted structure of gender-stereotyped patterns in media texts.
Assessment of lean-green practices on the sustainable performance of hotel supply chains
Authors: Hussain Matloub , Al-Aomar Raid , Melhem Hussein 
Published: February 2019

Purpose
The purpose of this paper is to empirically assess the impact of integrated lean and green practices on the sustainable (environmental, economic and social) performance of a hotel supply chain.

Design/methodology/approach
Literature review and previous exploratory studies were used to develop a hypothesized model that characterizes the integrated lean and green (LeGreen) impact on supply chain sustainability. A case study of a large sample of the UAE hotels is used to collect and analyze empirical data, validate the measurement model and test study hypotheses using structural equation modeling (SEM).

Findings
The results showed that three major lean techniques (Kaizen, quality and productive maintenance) and three green techniques (health and safety, waste disposal and green certifications) have substantial impact on the sustainable performance of hotel supply chains. Further results revealed that LeGreen impacts are complementary. Lean techniques have the highest impact on the economic performance of the hotel supply chain and the least impact on the environmental performance. Green practices, on the other hand, have opposite impacts.

Research limitations/implications
Although the study findings may vary in different contexts, study methodology and measurement model can be adapted to assess the LeGreen impact on the sustainable performance of hotel supply chains, as well as other service industries such as banking and health care.

Practical implications
The proposed assessment model is expected to be of great value toward the effective implementation of LeGreen practices across hotel supply chains in the UAE and globally. The study findings also provide guidelines for practitioners within the hospitality sector to undertake the proposed model and to adapt it for assessing and enhancing sustainable performance in other sectors of the service industry.

Originality/value
There is a growing emphasis by practitioners and academics on measuring the impact of LeGreen on the sustainable performance of service supply chains. However, the assessment of LeGreen impacts within the context of a hotel supply chain remains unexplored with a scarcity of comprehensive assessment frameworks. This study aims to fulfill this gap in literature and provide directions for researchers to expand the proposed model and to further analyze the integrated lean-green impact on the sustainability of supply chains of hotels and the service industry.
Quo Vadis, Europa? Four paths and their plausibility
Authors: Héritier Adrienne 
Published: February 2019

Purpose
The purpose of this paper is to assess the plausibility of four different mid-term paths of development of the European Union (EU): first, a political union or a European state; second, a differentiated and flexible integration of the polity; third, a covert and deepening integration of the polity outside of the political arenas; fourth, the disintegration and/or dissolution of the EU through the exit of individual members or a joint decision to terminate the union.

Design/methodology/approach
The paper uses strategic interaction analysis to identify the plausibility of each of these four possible outcomes. By systematically varying the relevant actors’, i.e. European Council’s and member states’, the European Parliament’s, the Commission’s, preferences over outcomes while holding constant institutional rules of decision making on the one hand, and systematically varying institutional rules on the other while holdings actors’ preferences constant, the paper comes to the conclusion that differentiated and flexible integration and covert integration are the most plausible mid-term paths of development.

Findings
The paper finds that neither a European state or deep political union nor a disintegration or even dissolution of the EU is the most plausible path of development. Rather, it concludes that flexible and differentiated integration as well as covert integration outside the political arenas are the most likely developments. However, it also draws attention to the political costs of flexible and differentiated integration which does not allow for an overall view of political and policy issues negotiated at one political table, limiting the scope of compromise formation and even leading to a fragmented polity. Covert integration consisting of mechanisms of hidden integration “invisible” to the wider public may lead to a democratic backlash, once citizens realize that integration has considerably deepened without their being aware of it.

Originality/value
Most publications regarding the future development of the EU are normatively driven, either conjuring an imminent disintegration, or invoking the necessity of a deepening integration leading to a political union. This paper, by contrast, seeks to assess the likely further development based on empirically identified factors and a logical argument.