bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative apical membrane proteomics reveals vasopressin-induced actin dynamics in collecting duct cells
Authors: Loo Chin-San , Chen Cheng-Wei , Wang Po-Jen , Chen Pei-Yu , Lin Shu-Yu , Khoo Kay-Hooi , Fenton Robert A. , Knepper Mark A. , Yu Ming-Jiun 
Published: October 2013

Significance
Vasopressin is a peptide hormone that regulates renal water excretion to maintain whole-body water balance. It does so by regulating trafficking of a molecular water channel, aquaporin-2, to and from the plasma membrane of collecting duct cells. This study uses two state-of-the-art methods (protein mass spectrometry of affinity-isolated apical plasma membrane proteins and live-cell imaging of actin dynamics) to uncover the central role of the actin dynamics in the trafficking of aquaporin-2–containing vesicles. The results coupled with prior data produce a model in which vasopressin signaling triggers actin accumulation near the tight junction and concomitant depletion of actin from the central regions of the apical plasma membrane, thereby providing access of aquaporin-2–containing vesicles to the apical plasma membrane.
Receptive field focus of visual area V4 neurons determines responses to illusory surfaces
Authors: Cox Michele A. , Schmid Michael C. , Peters Andrew J. , Saunders Richard C. , Leopold David A. , Maier Alexander 
Published: October 2013

Significance
Visual information is often fragmented, such as when objects block each other from view, and our brain must actively deduce missing parts of an image to perceive key features of the world. This study asks whether neurons in cortical area V4 can infer the presence of an object’s surface when visual clues are limited. Indeed, our experiments reveal that certain V4 neurons enhance their responses to an array of stimuli only when they are configured to give rise to an illusory surface. Intriguingly, this effect exhibited unexpected spatial precision relative to the inducing components of the illusion. These findings provide important clues about how the brain overcomes a fundamental challenge of vision.
MMAD: microarray microdissection with analysis of differences is a computational tool for deconvoluting cell type-specific contributions from tissue samples
Authors: Liebner David A. , Huang Kun , Parvin Jeffrey D. 
Published: October 2013

Abstract
Background: One of the significant obstacles in the development of clinically relevant microarray-derived biomarkers and classifiers is tissue heterogeneity. Physical cell separation techniques, such as cell sorting and laser-capture microdissection, can enrich samples for cell types of interest, but are costly, labor intensive and can limit investigation of important interactions between different cell types.
Results: We developed a new computational approach, called microarray microdissection with analysis of differences (MMAD), which performs microdissection in silico. Notably, MMAD (i) allows for simultaneous estimation of cell fractions and gene expression profiles of contributing cell types, (ii) adjusts for microarray normalization bias, (iii) uses the corrected Akaike information criterion during model optimization to minimize overfitting and (iv) provides mechanisms for comparing gene expression and cell fractions between samples in different classes. Computational microdissection of simulated and experimental tissue mixture datasets showed tight correlations between predicted and measured gene expression of pure tissues as well as tight correlations between reported and estimated cell fraction for each of the individual cell types. In simulation studies, MMAD showed superior ability to detect differentially expressed genes in mixed tissue samples when compared with standard metrics, including both significance analysis of microarrays and cell type-specific significance analysis of microarrays.
Conclusions: We have developed a new computational tool called MMAD, which is capable of performing robust tissue microdissection in silico, and which can improve the detection of differentially expressed genes. MMAD software as implemented in MATLAB is publically available for download at http://sourceforge.net/projects/mmad/.
Contact: david.liebner@gmail.com
Supplementary Information: Supplementary data are available at Bioinformatics online.
Exogenous Gibberellins Induce Wheat Spike Development under Short Days Only in the Presence of VERNALIZATION1
Authors: Pearce Stephen , Vanzetti Leonardo S. , Dubcovsky Jorge 
Published: October 2013

Abstract
The activation of the meristem identity gene VERNALIZATION1 (VRN1) is a critical regulatory point in wheat (Triticum spp.) flowering. In photoperiod-sensitive wheat varieties, VRN1 is expressed only under long days (LDs), but mutants carrying deletions in a regulatory element in its promoter show VRN1 transcription and early spike development under short days (SDs). However, complete spike development is delayed until plants are transferred to LDs, indicating the existence of an additional regulatory mechanism dependent on LDs. We show here that exogenous gibberellin (GA) application accelerates spike development under SDs, but only in wheat lines expressing VRN1. The simultaneous presence of GA and VRN1 results in the up-regulation of the floral meristem identity genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1-1 and LEAFY, whereas inhibition of GA biosynthesis with paclobutrazol precludes the LD induction of these two genes. The inductive role of GA on wheat flowering is further supported by the up-regulation of GA biosynthetic genes in the apices of plants transferred from SDs to LDs and in photoperiod-insensitive and transgenic wheat plants with increased FLOWERING LOCUS T transcription under SDs. The up-regulation of GA biosynthetic genes was not observed in the leaves of the same genetic stocks. Based on these observations, we propose a model in which FLOWERING LOCUS T is up-regulated in the leaves under LDs and is then transported to the shoot apical meristem, where it simultaneously induces the expression of VRN1 and GA biosynthetic genes, which are both required for the up-regulation of the early floral meristem genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1-1 and LEAFY and the timely development of the wheat spike.
Winter is coming: Miocene and Quaternary climatic shifts shaped the diversification of Western‐Mediterranean Harpactocrates (Araneae, Dysderidae) spiders
Authors: Bidegaray‐Batista Leticia , Ferrández Miguel Á. , Arnedo Miquel A. 
Published: September 2013

AbstractPast climatic shifts have played a major role in generating and shaping biodiversity. Quaternary glacial cycles are the better known examples of dramatic climatic changes endured by ecosystems in temperate regions. Although still a matter of debate, some authors suggest that glaciations promoted speciation. Here we investigate the effect of past climatic changes on the diversification of the ground‐dwelling spider genus Harpactocrates, distributed across the major mountain ranges of the western Mediterranean. Concatenated and species‐tree analyses of multiple mitochondrial and nuclear loci, combined with the use of fossil and biogeographic calibration points, reveal a Miocene origin of most nominal species, but also unravel several cryptic lineages tracing back to the Pleistocene. We hypothesize that the Miocene Climatic Transition triggered major extinction events in the genus but also promoted its subsequent diversification. Under this scenario, the Iberian mountains acted as an island‐like system, providing shelter to Harpactocrates lineages during the climate shifts and favouring isolation between mountain ranges. Quaternary glacial cycles contributed further to the diversification of the group by isolating lineages in peripheral refugia within mountain ranges. In addition, we recovered some unique biogeographic patterns, such as the colonization of the Alps and the Apennines from the Iberian Peninsula.
On the Use of Auxiliary and Paradata for Dealing With Non‐sampling Errors in Household Surveys
Authors: Zhang Li‐Chun , Thomsen Ib , Kleven Øyvin 
Published: October 2013

RésuméDans cet article, nous considérons l'utilisation de paradonnées pour traiter la non‐réponse et les erreurs de mesure dans les enquêtes auprès des ménages. Trois propriétés fondamentales sont mises en évidence: l'amélioration des taux de réponses, l'ajustement statistique et l'analyse du biais. Nous portons une attention particulière à plusieurs aspects durant les différentes phases de la production statistique à partir de la collecte des données, en passant par l'analyse des données et la manière de sélectionner et d'utiliser l'information auxiliaire disponible et les paradonnées. Les données de registres administratifs fournissent la source d'information auxiliaire pertinente la plus riche et s'ajoutent aux données collectées par les enquêtes et recensements antérieurs. Comme il est important de les utiliser efficacement pour traiter les erreurs qui ne sont pas dues à l'échantillonnage, on doit faire tous les efforts possibles pour augmenter leur disponibilité dans le système statistique et, en même temps, pour développer des méthodes statistiques efficaces qui permettent de mettre à profit l'intégration de données de sources différentes.
Objective Bayes Factors for Inequality Constrained Hypotheses
Authors: Hoijtink Herbert 
Published: October 2013

RésuméCe travail présente un facteur Bayésien pour la comparaison entre une hypothèse d'intérêt définie par des inégalités et son complément d'une part, l'hypothèse non contrainte d'autre part. Des ensembles équivalents d'hypothèses forment la base d'une quantification de la complexité d'une hypothèse d'intérêt. Nous montrons qu'une distribution a priori peut tre choisie de façon que l'un des termes composant le facteur Bayésien représente cette quantification. L'autre terme constitue une mesure de la qualité de l'adéquation à cette hypothèse. Si un a priori vague est utilisé, cette mesure d'adéquation est essentiellement déterminée par les observations. Le résultat est un facteur Bayésien objectif.
Advances in Joint Modelling: A Review of Recent Developments with Application to the Survival of End Stage Renal Disease Patients
Authors: McCrink Lisa M. , Marshall Adele H. , Cairns Karen J. 
Published: October 2013

RésuméL'approche mixte, pour la modélisation des processus de survie et des processus longitudinaux, connait de nos jours un succès grandissant, en particulier lorsqu';il existe une interdépendance entre ceux‐ci. Réputés pour leur efficacité, les modèles mixtes sont moins biaisés par rapport aux méthodes classiques naïves, d'où une littérature abondante sur le sujet. L'objet de cette étude est de présenter une revue de la littérature récente sur les modèles mixtes, en l'occurrence ceux utilisés pour l'estimation du temps d'échec dans les processus de survie. Nous présenterons une analyse détaillée de la gamme de modèles de survie utilisés pour la construction des modèles mixtes. Une attention particulière sera accordée aux progrès récents dans le développement des logiciels dédiés à la construction de ces modéles. Une illustration sur l'utilisation des progiciels JM et JoineR, développés dans l'environnement R, sera présentée pour le cas de l'analyse de survie des patients souffrant d'insuffisance rénale en phase terminale. Finalement, nous concluons avec une discussion sur plusieurs pistes de recherche potentielles dans le domaine.
Statistical Disclosure Risk: Separating Potential and Harm
Authors: Skinner Chris 
Published: October 2013

RésuméLes agences statistiques ont à coeur la mise au point de procédés permettant l'accès à leurs données dans le respect de la confidentialité de ces dernières. Bien que les méthodes d'évaluation du risque de divulgation soient désormais bien établies dans la littérature statistique, l'intégration de ces méthodes à la pratique des instituts sur des bases scientifiques se révèle encore difficile. Cet article vise à examiner, tout en le clarifiant, le rôle de la statistique dans les fondements conceptuels de l'évaluation du risque de divulgation dans le cadre des activités des instituts. Ce risque comporte deux composantes: la mesure de la possibilité d'une réelle divulgation, et le dommage potentiellement associéà celle‐ci. Nous développons l'idée que la statistique est bien adaptée à l'évaluation de la première de ces deux composantes, et proposons un cadre pour une telle évaluation. Nous soutenons que le comportement liéà une éventuelle intrusion malveillante peut être considéré indépendamment de ce cadre pourvu qu'il soit tenu compte de façon appropriée de la nature des tentatives d'attaques dans la définition du potentiel de divulgation.
Traceable Regressions
Authors: Wermuth Nanny 
Published: October 2013

RésuméDans cet article, nous définitions et étudions le concept de traçabilité des régressions et l'appliquer á quelques exemples. Régressions traçables sont des séquences de distributions conditionnelles dans les réponses individuelles ou conjointes pour lesquelles un graphe correspondant capte non seulement une structure indépendance, mais représente, en outre, dépendances conditionnelles qui permettent le traçage des voies de la dépendance. Nous donnons les propriétés nécessaires pour transformer ces graphes et des critères graphiques de décider si un chemin dans le graphe induit une dépendance. Les contraintes beaucoup plus fortes sur les distributions qui sont fidèles á un graphe sont comparés á ceux nécessaires pour les régressions traçables.
Ordered Kinetochore Assembly in the Human-Pathogenic Basidiomycetous Yeast Cryptococcus neoformans
Authors: Kozubowski Lukasz , Yadav Vikas , Chatterjee Gautam , Sridhar Shreyas , Yamaguchi Masashi , Kawamoto Susumu , Bose Indrani , Heitman Joseph , Sanyal Kaustuv 
Published: October 2013

ABSTRACT

Kinetochores facilitate interaction between chromosomes and the spindle apparatus. The formation of a metazoan trilayered kinetochore is an ordered event in which inner, middle, and outer layers assemble during disassembly of the nuclear envelope during mitosis. The existence of a similar strong correlation between kinetochore assembly and nuclear envelope breakdown in unicellular eukaryotes is unclear. Studies in the hemiascomycetous budding yeasts
Saccharomyces cerevisiae
and
Candida albicans
suggest that an ordered kinetochore assembly may not be evolutionarily conserved. Here, we utilized high-resolution time-lapse microscopy to analyze the localization patterns of a series of putative kinetochore proteins in the basidiomycetous budding yeast
Cryptococcus neoformans
, a human pathogen. Strikingly, similar to most metazoa but atypical of yeasts, the centromeres are not clustered but positioned adjacent to the nuclear envelope in premitotic
C. neoformans
cells. The centromeres gradually coalesce to a single cluster as cells progress toward mitosis. The mitotic clustering of centromeres seems to be dependent on the integrity of the mitotic spindle. To study the dynamics of the nuclear envelope, we followed the localization of two marker proteins, Ndc1 and Nup107. Fluorescence microscopy of the nuclear envelope and components of the kinetochore, along with ultrastructure analysis by transmission electron microscopy, reveal that in
C. neoformans
, the kinetochore assembles in an ordered manner prior to mitosis in concert with a partial opening of the nuclear envelope. Taken together, the results of this study demonstrate that kinetochore dynamics in
C. neoformans
is reminiscent of that of metazoans and shed new light on the evolution of mitosis in eukaryotes.

IMPORTANCE
Successful propagation of genetic material in progeny is essential for the survival of any organism. A proper kinetochore-microtubule interaction is crucial for high-fidelity chromosome segregation. An error in this process can lead to loss or gain of chromosomes, a common feature of most solid cancers. Several proteins assemble on centromere DNA to form a kinetochore. However, significant differences in the process of kinetochore assembly exist between unicellular yeasts and multicellular metaozoa. Here, we examined the key events that lead to formation of a proper kinetochore in a basidiomycetous budding yeast,
Cryptococcus neoformans
. We found that, during the progression of the cell cycle, nonclustered centromeres gradually clustered and kinetochores assembled in an ordered manner concomitant with partial opening of the nuclear envelope in this organism. These events have higher similarity to mitotic events of metazoans than to those previously described in other yeasts.
Navigating the Therapeutic Complexity of PI3K Pathway Inhibition in Melanoma
Authors: Kwong Lawrence N. , Davies Michael A. 
Published: October 2013

Abstract
Melanoma is entering into an era of combinatorial approaches to build upon recent clinical breakthroughs achieved by novel single-agent therapies. One of the leading targets to emerge from the growing understanding of the molecular pathogenesis, heterogeneity, and resistance mechanisms of melanomas is the phosphoinositide 3-kinase (PI3K)–AKT pathway. Multiple genetic and epigenetic aberrations that activate this pathway have been identified in melanomas de novo and in acquired resistance models. These developments have been paralleled by the establishment of models for preclinical testing and the availability of compounds that target various effectors in the pathway. Thus, in addition to having a strong rationale for targeting, the PI3K–AKT pathway presents an immediate clinical opportunity. However, the development of effective strategies against this pathway must overcome several key challenges, including optimizing patient selection, overcoming feedback loops, and pathway cross-talk that can mediate resistance. This review discusses the current understanding and ongoing research about the PI3K–AKT pathway in melanoma and emerging strategies to achieve clinical benefit in patients by targeting it. Clin Cancer Res; 19(19); 5310–9. ©2013 AACR.
Rinne Revisited: Steel versus Aluminum Tuning Forks
Authors: MacKechnie Cheryl A. , Greenberg Jesse J. , Gerkin Richard C. , McCall Andrew A. , Hirsch Barry E. , Durrant John D. , Raz Yael 
Published: October 2013

Objective(1) Determine whether tuning fork material (aluminum vs stainless steel) affects Rinne testing in the clinical assessment of conductive hearing loss (CHL). (2) Determine the relative acoustic and mechanical outputs of 512‐Hz tuning forks made of aluminum and stainless steel.Study DesignProspective, observational.SettingOutpatient otology clinic.Subjects and MethodsFifty subjects presenting May 2011 to May 2012 with negative or equivocal Rinne in at least 1 ear and same‐day audiometry. Rinne test results using aluminum and steel forks were compared and correlated with the audiometric air‐bone gap. Bench top measurements using sound‐level meter, microphone, and artificial mastoid.ResultsPatients with CHL were more likely to produce a negative Rinne test with a steel fork than with an aluminum fork. Logistic regression revealed that the probability of a negative Rinne reached 50% at a 19 dB air‐bone gap for stainless steel versus 27 dB with aluminum. Bench top testing revealed that steel forks demonstrate, in effect, more comparable air and bone conduction efficiencies while aluminum forks have relatively lower bone conduction efficiency.ConclusionWe have found that steel tuning forks can detect a lesser air‐bone gap compared to aluminum tuning forks. This is substantiated by observations of clear differences in the relative acoustic versus mechanical outputs of steel and aluminum forks, reflecting underlying inevitable differences in acoustic versus mechanical impedances of these devices, and thus efficiency of coupling sound/vibratory energy to the auditory system. These findings have clinical implications for using tuning forks to determine candidacy for stapes surgery.
The Impact of Mild Cognitive Impairment on Sexual Activity
Authors: Momtaz Yadollah Abolfathi , Hamid Tengku Aizan , Ibrahim Rahimah 
Published: October 2013

Objective: The aim of this study was to identify the unique impact of mild cognitive impairment (MCI) on sexual activity among older adults. Methods: Data for the study were drawn from a national survey entitled the “Determinants of Wellness among Older Malaysians: A Health Promotion Perspective” conducted in 2010. Results: According to the Mini-Mental State Examination education-adjusted cutoff points, 15.6% of the 1046 respondents were identified as having MCI. Older adults with MCI had a significantly lower level of sexual activity than the healthy cognitive group (chi-square = 50.20, P < .001, 32.5% vs 62.3%). The results of 3-step hierarchical logistic regression model revealed that MCI is significantly associated with decreased sexual activity in community-dwelling older adults, over and beyond demographic factors, and age-related medical conditions affecting sexual activity (odds ratio 0.33, P < .001, 95% confidence interval 0.23-0.49). Conclusion: Findings from the present study support the significant role of cognitive functioning to perform sexual activity in later life.
Characterization of squamous cell carcinoma in an organotypic culture via subsurface non-linear optical molecular imaging
Authors: Scanlon Christina S , Van Tubergen Elizabeth A , Chen Leng-Chun , Elahi Sakib F , Kuo Shiuhyang , Feinberg Stephen , Mycek Mary-Ann , D’Silva Nisha J 
Published: October 2013

Tristetraprolin (TTP) is an RNA-binding protein which downregulates multiple cytokines that mediate progression of head and neck squamous cell carcinoma (HNSCC). We previously showed that HNSCC cells with shRNA-mediated knockdown of TTP are more invasive than controls. In this study, we use control and TTP-deficient cells to present a novel subsurface non-linear optical molecular imaging method using a three-dimensional (3D) organotypic construct, and compare the live cell imaging data to histology of fixed tissue specimens. This manuscript describes how to prepare and image the novel organotypic system that closely mimics HNSCC in a clinical setting. The oral cancer equivalent (OCE) system allows HNSCC cells to stratify and invade beyond the basement membrane into underlying connective tissue prepared from decellularized human dermal tissue. The OCE model was inspired by tissue engineering strategies to prepare autologous transplants from human keratinocytes. Advantages of this method over previously used in vitro cancer models include the simulation of the basement membrane and complex connective tissue in the construct, in addition to the ability to track the 3D movement of live invading cells and quantify matrix destruction over time. The OCE model and novel live cell imaging strategy may be applied to study other types of 3D tissue constructs.
Heart failure patients’ attitudes, beliefs, expectations and experiences of self-management strategies: A qualitative synthesis
Authors: Wingham Jennifer , Harding Geoff , Britten Nicky , Dalal Hayes 
Published: October 2013

Objectives To develop a model of heart failure patients’ attitudes, beliefs, expectations, and experiences based on published qualitative research that could influence the development of self-management strategies. Methods A synthesis of 19 qualitative research studies using the method of meta-ethnography. Results This synthesis offers a conceptual model of the attitudes, beliefs, and expectations of patients with heart failure. Patients experienced a sense of disruption before developing a mental model of heart failure. Patients’ reactions included becoming a strategic avoider, a selective denier, a well-intentioned manager, or an advanced self-manager. Patients responded by forming self-management strategies and finally assimilated the strategies into everyday life seeking to feel safe. Discussion This conceptual model suggests that there are a range of interplaying factors that facilitate the process of developing self-management strategies. Interventions should take into account patients’ concepts of heart failure and their subsequent reactions.