bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fitness valleys constrainHIV‐1's adaptation to its secondary chemokine coreceptor
Authors: da Silva J. , Wyatt S. K. 
Published: February 2014

AbstractFitness valleys, in which mutations at different loci are singly deleterious but jointly beneficial, arise because of reciprocal sign epistasis. Recent theoretical work provides analytical approximations of times to cross fitness valleys via three mechanisms: sequential fixation, stochastic tunnelling and recombination. These times depend critically on the effective population size (Ne). Human immunodeficiency virus type 1 (HIV‐1) encounters fitness valleys in adapting to its secondary cell‐surface chemokine coreceptor,CXCR4. Adaptation toCXCR4 tends to occur late in infection and only in about 50% of patients and is associated with disease progression. It has been hypothesized that the need to cross fitness valleys may explain the delayed and inconsistent adaptation toCXCR4. We have identified four fitness valleys from a previous study of fitness epistasis in adaptation toCXCR4 and use estimates of the within‐patient varianceNefor different patient treatment statuses and infection stages (conditions) to estimate times to cross the valleys. These valleys may be crossed predominantly by stochastic tunnelling, although mean crossing times are consistently longer than the durations of the conditions for which they are calculated. These results were confirmed with stochastic simulation. Simulations show that crossing times for a given condition are highly variable and that for each condition there is a low probability of crossing each valley. These findings support the hypothesis that fitness valleys constrain the adaptation ofHIV‐1 toCXCR4. This study provides the first detailed analysis of the evolutionary dynamics associated with empirical fitness valleys.
Intra‐axonal protein aggregation in the peripheral nervous system
Authors: Vital Anne , Meissner Wassillios G. , Canron Marie‐Hélène , Martin‐Negrier Marie‐Laure , Bezard Erwan , Tison François , Vital Claude 
Published: February 2014

AbstractIntracellular protein aggregates are common pathological hallmarks of many neurodegenerative disorders, and a defect in axonal transport is also incriminated. Here, we studied intra‐axonal abnormal protein aggregation and axonopathy by using immunohistochemistry and electron microscopy on peripheral nerve biopsies from 12 patients with chronic axonal peripheral neuropathy (PN) of unknown etiology. Among these patients, three had idiopathic Parkinson's disease (PD). Intra‐axonal ubiquitin aggregates were more numerous in the patients with PD. Intra‐axonal aggregates of tau AT8 were found in five patients without PD. Phosphorylated α‐synuclein aggregation was absent in all cases, while intra‐axonal colocalization of 14‐3‐3 β and ubiquitin was observed in two PD cases. Electron microscopy revealed enlarged axons crowded with organelles in six cases, including the three patients with PD, thus attesting a slowing of the axoplasmic flux. The number of ubiquitin aggregates was correlated with features of reduced axonal flux, while no such correlation was found for tau and 14‐3‐3 β. Age did not correlate with the number of tau, ubiquitin, and 14‐3‐3 aggregates. Thus, both ubiquitin and/or abnormal tau intra‐axonal aggregates may be found in chronic axonal PN. Ubiquitin aggregates might reduce the axonal flux or result from a disease producing slowing of axonal transport.
Excessive activation of the alternative complement pathway in autosomal dominant polycystic kidney disease
Authors: Su Z. , Wang X. , Gao X. , Liu Y. , Pan C. , Hu H. , Beyer R. P. , Shi M. , Zhou J. , Zhang J. , Serra A. L. , Wüthrich R. P. , Mei C. 
Published: February 2014

AbstractObjectivesThe complement system is involved in many immune complex‐mediated kidney diseases, yet its role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) has not been examined in detail.Methods and ResultsScreening of the glycoproteome of urine samples from ADPKD patients revealed that levels of complement factor B (CFB), serpin peptidase inhibitor, complement component 1 inhibitor (SERPING1) and complement component 9 (C9) increased, whereas complement component 1, r subcomponent‐like (C1RL), CD55 and CD59 levels decreased with disease progression. Immunostaining and Western blot analysis confirmed the enhanced expression of CFB and C9 in cystic kidneys from ADPKD patients. Immunostaining also showed that the expressions of CFB and C9 in renal biopsy tissues from patients with other types of chronic kidney disease were lower than in tissues from ADPKD patients. The effect of the complement inhibitor rosmarinic acid (RMA) was evaluated in Pkd1−/− mice and Han:SPRD Cy/+ rats. Compared with vehicle‐treated Pkd1−/− animals, RMA‐treated mice had significantly lower serum creatinine (−50%) and blood urea nitrogen (−78%) levels, two kidneys/body weight ratio (−60%) and renal cystic index (−60%). Similar results were found in Cy/+ rats. Lower numbers of Ki67‐positive nuclei and inflammatory cells and reduced fibrosis were observed in both animal models upon treatment with RMA.ConclusionsThese results suggest that excessive activation of the alternative complement pathway is associated with ADPKD progression, probably mediated by cyst‐lining epithelial cell proliferation, tubulointerstitial inflammatory cell infiltration and fibrosis. Targeting the complement system might represent a new therapeutic strategy for ADPKD.
Team work engagement: A model of emergence
Authors: Costa Patrícia L. , Passos Ana M. , Bakker Arnold B. 
Published: February 2014

Research has shown that work engagement, both at the individual and team levels, is relevant to understand employee performance and well‐being. Nonetheless, there is no theoretical model that explains the development of work engagement in teams that takes into consideration what is already known about team dynamics and processes. This study addresses this gap in the literature, presenting a model for the emergence of team work engagement. The model proposes team inputs, outputs, and mediators as predictors of team work engagement and highlights their recursive influences over time. This conceptual work provides a starting point for further research on team work engagement, allowing for distinguishing individual and team constructs.Practitioner points

The degree of energy and enthusiasm of teams depends on the way they interact.

The affective and motivational dynamics of teams have consequences for their performance and well‐being.

The emergence of team work engagement is better understood within the literature of teamwork.
The role of oral flora in the development of chemotherapy‐induced oral mucositis
Authors: Stringer Andrea M. , Logan Richard M. 
Published: February 2014

Chemotherapy‐induced mucositis is considered to be a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy. In the last 10 years, there have been significant advances in the understanding of mucositis pathobiology. At the basic level, it is now well‐understood that it is not just an epithelial process, but rather a complex interaction between epithelial and connective tissue compartments. There is also potential interaction between the oral microenvironment and the development of mucositis. Changes occur in the resident oral flora (commensal) throughout cancer treatment, and it is conceivable that these organisms and changes that occur may have an influence on the development of mucosal toxicity associated with cancer treatment. The aim of this review was to examine the potential contributions of oral microflora in the pathobiology of mucositis and identify pathways and interactions that could be targeted for therapeutic management of mucositis.
Allelopathic effects of Alexandrium fundyense (Dinophyceae) on Thalassiosira cf. gravida (Bacillariophyceae): a matter of size
Authors: Lyczkowski Emily R. , Karp‐Boss Lee 
Published: February 2014

Allelopathic interactions among phytoplankton are well documented. The potency of allelopathic species and responses of target species to allelochemicals are quite variable, however, limiting full understanding of the role these interactions may play in nature. One trait that may influence the sensitivity of an individual to allelochemicals is cell size. The few studies that have examined relationships between cell size and susceptibility to allelochemicals have compared different species and thus could not distinguish between the role of size and species‐specific physiological differences. Culturing an actively sexually reproducing diatom allowed us to focus on the influence of target cell size within a single species. We studied growth and nutrient acquisition by the chain‐forming Thalassiosira cf. gravida Clever in the presence and absence of allelochemicals released by Alexandrium fundyense Balech as a function of T. cf. gravida cell size. Upon exposure to filtrate of A. fundyense, T. cf. gravida cultures “bleached” and both growth and nutrient utilization ceased for up to 4 d. The magnitude of the effect was dependent on filtrate concentration and T. cf. gravida cell surface area:volume ratio. The greatest inhibition was observed on the smallest cells, while T. cf. gravida cultures that had undergone cell enlargement via sexual reproduction were least sensitive to A. fundyense filtrate. These results demonstrate that competitor cell size, independent from taxonomy, may influence the outcome of allelopathic interactions. The findings presented here suggest a potential ecological impact of diatom cell size reduction and sexual reproduction that has not yet been described and that may be important in determining diatom survival and success.
Comparison of a novel non‐contact biomotion sensor with wrist actigraphy in estimating sleep quality in patients with obstructive sleep apnoea
Authors: Pallin Michael , O'hare Emer , Zaffaroni Alberto , Boyle Patricia , Fagan Ciara , Kent Brian , Heneghan Conor , de Chazal Philip , McNicholas Walter T. 
Published: February 2014

SummaryAmbulatory monitoring is of major clinical interest in the diagnosis of obstructive sleep apnoea syndrome. We compared a novel non‐contact biomotion sensor, which provides an estimate of both sleep time and sleep‐disordered breathing, with wrist actigraphy in the assessment of total sleep time in adult humans suspected of obstructive sleep apnoea syndrome. Both systems were simultaneously evaluated against polysomnography in 103 patients undergoing assessment for obstructive sleep apnoea syndrome in a hospital‐based sleep laboratory (84 male, aged 55 ± 14 years and apnoea–hypopnoea index 21 ± 23). The biomotion sensor demonstrated similar accuracy to wrist actigraphy for sleep/wake determination (77.3%: biomotion; 76.5%: actigraphy), and the biomotion sensor demonstrated higher specificity (52%: biomotion; 34%: actigraphy) and lower sensitivity (86%: biomotion; 94%: actigraphy). Notably, total sleep time estimation by the biomotion sensor was superior to actigraphy (average overestimate of 10 versus 57 min), especially at a higher apnoea–hypopnoea index. In post hoc analyses, we assessed the improved apnoea–hypopnoea index accuracy gained by combining respiratory measurements from polysomnography for total recording time (equivalent to respiratory polygraphy) with total sleep time derived from actigraphy or the biomotion sensor. Here, the number of misclassifications of obstructive sleep apnoea severity compared with full polysomnography was reduced from 10/103 (for total respiratory recording time alone) to 7/103 and 4/103 (for actigraphy and biomotion sensor total sleep time estimate, respectively). We conclude that the biomotion sensor provides a viable alternative to actigraphy for sleep estimation in the assessment of obstructive sleep apnoea syndrome. As a non‐contact device, it is suited to longitudinal assessment of sleep, which could also be combined with polygraphy in ambulatory studies.
Models for Seismic Vulnerability Analysis of Power Networks: Comparative Assessment
Authors: Cavalieri Francesco , Franchin Paolo , Buriticá Cortés Jessica A. M. , Tesfamariam Solomon 
Published: February 2014

AbstractElectric power networks are spatially distributed systems, subject to different magnitude and recurrence of earthquakes, that play a fundamental role in the well‐being and safety of communities. Therefore, identification of critical components is of paramount importance in retrofit prioritization. This article presents a comparison of five seismic performance assessment models (M1 to M5) of increasing complexity. The first two models (M1 and M2) approach the problem from a connectivity perspective, whereas the last three (M3 to M5) consider also power flow analysis. To illustrate the utility of the five models, the well‐known IEEE‐118 test case, assumed to be located in the central United States, is considered. Performances of the five models are compared using both system‐level and component‐level measures. Spearman rank correlation ρ is computed between results of each model. Highest ρ values, at both system‐ and component‐level, are obtained, as expected, between M1 and M2, and within models M3 to M5. The ρ values between component‐level measures are relatively high across all models, indicating that simpler ones (M1 and M2) are appropriate for vulnerability assessment and retrofit prioritization. The complex flow‐based models (M3 to M5) are suitable if actual performance of the systems is desired, as it is the case when the power network is considered within a larger set of interconnected infrastructural systems.
Data‐Based Model‐Free Hysteretic Restoring Force and Mass Identification for Dynamic Systems
Authors: Xu Bin , He Jia , Masri Sami F. 
Published: February 2014

AbstractMost of the currently available vibration‐based damage detection approaches identify structural damage in the form of decrease in structural stiffness based on extracted eigenparameters and/or their derivates, and the basic hypothesis behind them is the system should be linear and the mass distribution of the system is usually known. Different from the stiffness degradation, the hysteretic restoring force of a dynamic system provides a more informative and direct description on the initiation and development of damage in structures under dynamic loadings and can be employed to quantitatively evaluate the energy dissipation during vibration. In this study, a data‐based model‐free hysteretic behavior identification approach with incomplete external excitations was proposed for the identification of structural hysteretic restoring force without the prior knowledge of structural mass distribution and the numerical model of the nonlinearity of the structure. The accuracy and feasibility of the approach for both structural mass and hysteretic behavior identification was illustrated: first, via numerical simulation with a lumped‐mass multi‐degree‐of‐freedom structure incorporating nonlinear magnetorheological (MR) dampers and a consistent mass plane truss structure incorporating a pseudo‐elastic shape memory alloy model to mimic the nonlinearity in dynamic systems. Second, a dynamic test on a four‐story frame structure equipped with MR dampers was carried out and the corresponding dynamic response was employed to validate the reliability of the proposed approach for both structural mass and hysteretic behavior identification. The results show that the proposed approach is capable of identifying different types of structural nonlinearity, which numerical model is unknown, with incomplete inputs and unknown mass distribution. The approach provides a promising way for damage detection and monitoring in the form of hysteretic behavior and energy dissipation for engineering structures under dynamic loadings, which should be dealt with as nonlinear systems.
In Defense of the Modal Account of the Progressive
Authors: MAYERHOFER IVAN 
Published: February 2014

AbstractWhen we talk about creation, we use the progressive and verbs of creation as in ‘Mary is building a house’. The modal account of the progressive says that a sentence such as ‘Mary is building a house’ is true just in case Mary eventually builds a house in all worlds in which her house‐building proceeds normally. Recently, the modal account has come under fire from those who claim that it over‐generates modal entailments and those who think the progressive should be treated as a predicate of events. By properly situating the modal account within a contemporary semantic framework for natural language modals, I argue that it gives the best semantic treatment of the progressive.
Itraconazole inhibits TNF‐α‐induced CXCL10 expression in oral fibroblasts
Authors: Ohta K , Ishida Y , Fukui A , Nishi H , Naruse T , Takechi M , Kamata N 
Published: February 2014

ObjectiveItraconazole (ICZ) has a broad spectrum of antifungal activity including a wide range of Candida spp. TNF‐α, an inflammatory cytokine associated with Th1‐mediated oral inflammatory disease, enhances inflammatory mediators, such as CXCR3‐agonistic chemokines including CXCL10. We examined the anti‐inflammatory potential of ICZ against TNF‐α‐induced chemokines in oral fibroblasts.Materials and methodsWe investigated the effects of ICZ on mRNA expressions of various TNF‐α‐induced chemokines in immortalized oral keratinocytes (RT7) and oral fibroblasts (GT1) using quantitative PCR analysis. Subsequently, the effects of ICZ and fluconazole (FLZ) on TNF‐α‐induced CXCL10 proteins in GT1 and primary fibroblasts were examined using enzyme‐linked immunosorbent assays (ELISA). The effect of ICZ on signal transduction protein phosphorylation involved in CXCL10 production from TNF‐α‐stimulated GT1 was examined by western blotting.ResultsICZ inhibited TNF‐α‐induced CXCL10 mRNA in GT1, but not RT7. Although ICZ did not affect TNF‐α‐induced IL‐8 mRNA, the mRNAs of TNF‐α‐induced CXCR3‐agonistic chemokines such as CXCL9 and CXCL11 were inhibited by ICZ in GT1. TNF‐α‐induced CXCL10 protein production in GT1 and primary fibroblasts was inhibited by ICZ, but not FLZ. Finally, ICZ inhibited TNF‐α‐induced phosphorylation of c‐JUN, which is related to CXCL10 production by TNF‐α‐stimulated GT1.ConclusionICZ may be useful as therapy for Th1‐mediated oral inflammatory disease.
Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines
Authors: Young Richard J. , Waldeck Kelly , Martin Claire , Foo Jung H. , Cameron Donald P. , Kirby Laura , Do Hongdo , Mitchell Catherine , Cullinane Carleen , Liu Wendy , Fox Stephen B. , Dutton‐Regester Ken , Hayward Nicholas K. , Jene Nicholas , Dobrovic Alexander , Pearson Richard B. , Christensen James G. , Randolph Sophia , McArthur Grant A. , Sheppard Karen E. 
Published: February 2014

SummaryWe have investigated the potential for the p16‐cyclin D‐CDK4/6‐retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three‐quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma‐specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16INK4A) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance.
Molecular data and ecological niche modelling reveal the phylogeographic pattern ofCotinus coggygria(Anacardiaceae) in China's warm‐temperate zone
Authors: Wang W. , Tian C. Y. , Li Y. H. , Li Y. 
Published: February 2014

AbstractThe phylogeography of common and widespread species helps to elucidate the history of local flora and vegetation. In this study, we selectedCotinus coggygria, a species widely distributed in China's warm‐temperate zone. One chloroplastDNA(cpDNA) region and ecological niche modelling were used to examine the phylogeographic pattern ofC. coggygria. The cpDNAdata revealed two phylogeographic groups (Southern and Northern) corresponding to the geographic regions. Divergence time analyses revealed that divergence of the two groups occurred at approximately 147,000 years before the present (BP), which coincided with the formation of the downstream area of the Yellow River, indicating that the Yellow River was a weak phylogeographic divide forC. coggygria. The molecular data and ecological niche modelling also indicated thatC. coggyriadid not experience population expansion after glaciations. This study thus supports the fact that Pleistocene glacial cycles only slightly affectedC. coggygria, which survivedin situand occupied multiple localised glacial refugia during glaciations. This finding is contrary to the hypothesis of large‐scale range habitat contraction and retreat into a few main refugia.
Electroejaculation Increases Low Molecular Weight Proteins in Seminal Plasma Modifying Sperm Quality inCorriedaleRams
Authors: Ledesma A , Manes J , Cesari A , Alberio R , Hozbor F 
Published: February 2014

ContentsThis study was conducted to evaluate the effect of seminal collection method (artificial vagina or electroejaculation) on the protein composition of seminal plasma and sperm quality parameters inCorriedalerams. To address this question, we assessed the effect of seminal collection method on motility, plasma membrane integrity and functionality, mitochondrial functionality and the decondensation state of nuclear chromatin in sperm cells. Volume,pH, osmolarity, protein concentration, total protein content and protein profile using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS‐PAGE) and 2‐D polyacrylamide electrophoresis of seminal plasma collected with artificial vagina and electroejaculation were also analysed. The main findings from this study were that ejaculates obtained with electroejaculation had (i) a higher number of spermatozoa with intact plasma membrane and functional mitochondria and (ii) a higher proportion of seminal plasma, total protein content and relative abundance of low molecular weight proteins than ejaculates obtained with artificial vagina. Five of these proteins were identified by mass spectrometry: binder of sperm 5 precursor;RSVP14;RSVP22; epididymal secretory protein E1 and clusterin. One protein spot with molecular weight of approximately 31 kDa and isoelectric point of 4.8 was only found in the seminal plasma from electroejaculation.
Multitype Point Process Analysis of Spines on the Dendrite Network of a Neuron
Authors: Baddeley Adrian , Jammalamadaka Aruna , Nair Gopalan 
Published: February 2014

SummaryWe develop methods for analysing the spatial pattern of events, classified into several types, that occur on a network of lines. The motivation is the study of small protrusions called ‘spines’ which occur on the dendrite network of a neuron. The spatially varying density of spines is modelled by using relative distributions and regression trees. Spatial correlations are investigated by using counterparts of the K-function and pair correlation function, where the main problem is to compensate for the network geometry. This application illustrates the need for careful analysis of spatial variation in the intensity of points, before assessing any evidence of clustering.