bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of divergent selection for drought and cold tolerance at landscape and local scales in Abies alba Mill. in the French Mediterranean Alps
Authors: Roschanski Anna M. , Csilléry Katalin , Liepelt Sascha , Oddou‐Muratorio Sylvie , Ziegenhagen Birgit , Huard Frédéric , Ullrich Kristian K. , Postolache Dragos , Vendramin Giovanni G. , Fady Bruno 
Published: December 2015

AbstractUnderstanding local adaptation in forest trees is currently a key research and societal priority. Geographically and ecologically marginal populations provide ideal case studies, because environmental stress along with reduced gene flow can facilitate the establishment of locally adapted populations. We sampled European silver fir (Abies alba Mill.) trees in the French Mediterranean Alps, along the margin of its distribution range, from pairs of high‐ and low‐elevation plots on four different mountains situated along a 170‐km east–west transect. The analysis of 267 SNP loci from 175 candidate genes suggested a neutral pattern of east–west isolation by distance among mountain sites. FST outlier tests revealed 16 SNPs that showed patterns of divergent selection. Plot climate was characterized using both in situ measurements and gridded data that revealed marked differences between and within mountains with different trends depending on the season. Association between allelic frequencies and bioclimatic variables revealed eight genes that contained candidate SNPs, of which two were also detected using FST outlier methods. All SNPs were associated with winter drought, and one of them showed strong evidence of selection with respect to elevation. QST–FST tests for fitness‐related traits measured in a common garden suggested adaptive divergence for the date of bud flush and for growth rate. Overall, our results suggest a complex adaptive picture for A. alba in the southern French Alps where, during the east‐to‐west Holocene recolonization, locally advantageous genetic variants established at both the landscape and local scales.
Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy
Authors: MAGNUSSON PETER , GADLER FREDRIK , LIV PER , MÖRNER STELLAN 
Published: December 2015

BackgroundRisk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is mainly based on evaluations from patients at highly specialized centers.AimTo evaluate risk markers for appropriate implantable cardioverter defibrillator (ICD) therapy in an unselected, nationwide cohort of HCM.MethodsPatients with an ICD due to HCM were identified from the Swedish ICD Registry since its start in 1995, merged with Patient Register data, and medical records were retrieved. Risk markers for ventricular arrhythmias leading to appropriate ICD therapy were analyzed using Cox proportional hazard ratio (HR).ResultsOf 321 patients (70.1% males), at least one appropriate therapy occurred in 77 (24.0%) during a mean follow‐up of 5.4 years (5.3% per year; primary prevention 4.5%, secondary prevention 7.0%). Cumulative incidences at 1 year, 3 years, and 5 years were 8.1%, 15.3%, and 21.3%, respectively. Cardioversion effectively restored rhythm in 52% of the first episode and antitachycardia pacing was sufficient in the remaining. For the whole cohort, ejection fraction (EF) <50% (HR 2.63; P < 0.001) was associated with appropriate ICD therapy. In primary prevention, patients with established risk markers experienced appropriate therapy; atrial fibrillation (AF; HR 2.54; P = 0.010), EF < 50% (HR 2.78; P = 0.004), and nonsustained ventricular tachycardia (HR 1.80; P = 0.109) had the highest HR, and wall thickness ≥30 mm, syncope, exercise blood pressure response, or family history of SCD had weaker associations.ConclusionICD therapy successfully terminates ventricular arrhythmias in HCM. In addition to conventional risk markers, a history of AF or EF < 50% may be considered in risk stratification.
Short- and Long-Run Estimates of The Local Effects of Retirement on Health
Authors: Fé Eduardo , Hollingsworth Bruce 
Published: December 2015

SummaryWe explore the existence of short- and long-term effects of retirement on health. Short-term effects are estimated with a regression discontinuity design which is robust to weak instruments and where the underlying assumptions of continuity of potential outcomes are uncontroversial. To identify the long-term effects we propose a parametric model which, under strong assumptions, can separate normal deterioration of health from the causal effects of retirement. We apply our framework to the British Household Panel Survey and find that retirement has little effect on health. However, our estimates suggest that retirement opens the gate to a sedentary life with an impoverished social component and this is a channel through which retirement could indirectly affect health in the long run.
Autonomic nervous activity of patients with gagging problems during dental mirror insertion
Authors: Sakamoto Toyoaki , Fukuda Ken‐ichi , Saita Naoko , Koukita Yoshihiko , Yamashita Shuichirou , Koizumi Jun‐ichi , Ichinohe Tatuya 
Published: December 2015

ABSTRACTObjectiveTo investigate autonomic nervous activities in patients with gagging problem.MethodsSubjects were 12 and 12 individuals, graded as Group G2 (mild gagging problem) and Group G3 (middle gagging problem), respectively, according to the Classification of Gagging Problem index (CGP) and compared with 15 normal patients. Heart rate (HR), low‐frequency/high‐frequency ratio (L/H), the coefficient of component variation for high frequency (CCVHF), and the coefficient of variation of R‐R intervals (CVRR) were assessed by heart rate variability on electrocardiogram. The measurement was recorded continuously for 1 min before and after dental mirror insertion.ResultsThe insertion did not affect HR, L/H, CCVH, and CVRR in Group G2. HR did not change despite both increases in L/H and CCVHF after the insertion in Group G3.ConclusionsPatients with a gagging problem in G3, dental mirror insertion increased both parasympathetic and sympathetic nervous activities, despite no change in HR.
Plant cell wall imaging by metabolic click‐mediated labelling of rhamnogalacturonan II using azido 3‐deoxy‐d‐manno‐oct‐2‐ulosonic acid
Authors: Dumont Marie , Lehner Arnaud , Vauzeilles Boris , Malassis Julien , Marchant Alan , Smyth Kevin , Linclau Bruno , Baron Aurélie , Mas Pons Jordi , Anderson Charles T. , Schapman Damien , Galas Ludovic , Mollet Jean‐Claude , Lerouge Patrice 
Published: December 2015

SummaryIn plants, 3‐deoxy‐d‐manno‐oct‐2‐ulosonic acid (Kdo) is a monosaccharide that is only found in the cell wall pectin, rhamnogalacturonan‐II (RG‐II). Incubation of 4‐day‐old light‐grown Arabidopsis seedlings or tobacco BY‐2 cells with 8‐azido 8‐deoxy Kdo (Kdo‐N3) followed by coupling to an alkyne‐containing fluorescent probe resulted in the specific in muro labelling of RG‐II through a copper‐catalysed azide–alkyne cycloaddition reaction. CMP‐Kdo synthetase inhibition and competition assays showing that Kdo and D‐Ara, a precursor of Kdo, but not L‐Ara, inhibit incorporation of Kdo‐N3 demonstrated that incorporation of Kdo‐N3 occurs in RG‐II through the endogenous biosynthetic machinery of the cell. Co‐localisation of Kdo‐N3 labelling with the cellulose‐binding dye calcofluor white demonstrated that RG‐II exists throughout the primary cell wall. Additionally, after incubating plants with Kdo‐N3 and an alkynated derivative of L‐fucose that incorporates into rhamnogalacturonan I, co‐localised fluorescence was observed in the cell wall in the elongation zone of the root. Finally, pulse labelling experiments demonstrated that metabolic click‐mediated labelling with Kdo‐N3 provides an efficient method to study the synthesis and redistribution of RG‐II during root growth.
CoxIter – Computing invariants of hyperbolic Coxeter groups
Authors: Guglielmetti R. 
Published: December 2015

CoxIter is a computer program designed to compute invariants of hyperbolic Coxeter groups. Given such a group, the program determines whether it is cocompact or of finite covolume, whether it is arithmetic in the non-cocompact case, and whether it provides the Euler characteristic and the combinatorial structure of the associated fundamental polyhedron. The aim of this paper is to present the theoretical background for the program. The source code is available online as supplementary material with the published article and on the author’s website (http://coxiter.rgug.ch).Supplementary materials are available with this article.
The Dual Nature of Nek9 in Adenovirus Replication
Authors: Jung Richard , Radko Sandi , Pelka Peter 
Published: December 2015

ABSTRACT

To successfully replicate in an infected host cell, a virus must overcome sophisticated host defense mechanisms. Viruses, therefore, have evolved a multitude of devices designed to circumvent cellular defenses that would lead to abortive infection. Previous studies have identified Nek9, a cellular kinase, as a binding partner of adenovirus E1A, but the biology behind this association remains a mystery. Here we show that Nek9 is a transcriptional repressor that functions together with E1A to silence the expression of p53-inducible
GADD45A
gene in the infected cell. Depletion of Nek9 in infected cells reduces virus growth but unexpectedly enhances viral gene expression from the E2 transcription unit, whereas the opposite occurs when Nek9 is overexpressed. Nek9 localizes with viral replication centers, and its depletion reduces viral genome replication, while overexpression enhances viral genome numbers in infected cells. Additionally, Nek9 was found to colocalize with the viral E4 orf3 protein, a repressor of cellular stress response. Significantly, Nek9 was also shown to associate with viral and cellular promoters and appears to function as a transcriptional repressor, representing the first instance of Nek9 playing a role in gene regulation. Overall, these results highlight the complexity of virus-host interactions and identify a new role for the cellular protein Nek9 during infection, suggesting a role for Nek9 in regulating p53 target gene expression.

IMPORTANCE
In the arms race that exists between a pathogen and its host, each has continually evolved mechanisms to either promote or prevent infection. In order to successfully replicate and spread, a virus must overcome every mechanism that a cell can assemble to block infection. On the other hand, to counter viral spread, cells must have multiple mechanisms to stifle viral replication. In the present study, we add to our understanding of how the human adenovirus is able to circumvent cellular roadblocks to replication. We show that the virus uses a cellular protein, Nek9, in order to block activation of p53-regulated gene
GADD45A
, which is an important player in stress response and p53-mediated cell cycle arrest. Importantly, our study also identifies Nek9 as a transcriptional repressor.
Primary care consultation rates among people with and without severe mental illness: a UK cohort study using the Clinical Practice Research Datalink
Authors: Kontopantelis Evangelos , Olier Ivan , Planner Claire , Reeves David , Ashcroft Darren M , Gask Linda , Doran Tim , Reilly Siobhan 
Published: December 2015

ObjectivesLittle is known about service utilisation by patients with severe mental illness (SMI) in UK primary care. We examined their consultation rate patterns and whether they were impacted by the introduction of the Quality and Outcomes Framework (QOF), in 2004.DesignRetrospective cohort study using individual patient data collected from 2000 to 2012.Setting627 general practices contributing to the Clinical Practice Research Datalink, a large UK primary care database.ParticipantsSMI cases (346 551) matched to 5 individuals without SMI (1 732 755) on age, gender and general practice.Outcome measuresConsultation rates were calculated for both groups, across 3 types: face-to-face (primary outcome), telephone and other (not only consultations but including administrative tasks). Poisson regression analyses were used to identify predictors of consultation rates and calculate adjusted consultation rates. Interrupted time-series analysis was used to quantify the effect of the QOF.ResultsOver the study period, face-to-face consultations in primary care remained relatively stable in the matched control group (between 4.5 and 4.9 per annum) but increased for people with SMI (8.8–10.9). Women and older patients consulted more frequently in the SMI and the matched control groups, across all 3 consultation types. Following the introduction of the QOF, there was an increase in the annual trend of face-to-face consultation for people with SMI (average increase of 0.19 consultations per patient per year, 95% CI 0.02 to 0.36), which was not observed for the control group (estimates across groups statistically different, p=0.022).ConclusionsThe introduction of the QOF was associated with increases in the frequency of monitoring and in the average number of reported comorbidities for patients with SMI. This suggests that the QOF scheme successfully incentivised practices to improve their monitoring of the mental and physical health of this group of patients.
Correlation between symptoms and objective findings may improve the symptom-based diagnosis of chronic rhinosinusitis for primary care and epidemiological studies
Authors: Park Do-Yang , Lee Eun Jung , Kim Ji Hoon , Kim Yoo Suk , Jung Chan Min , Kim Kyung-Su 
Published: December 2015

BackgroundIn primary care and epidemiological studies of chronic rhinosinusitis (CRS), symptom-based diagnosis is common, yet limited, because endoscopic and radiological signs are not considered.ObjectivesTo evaluate the correlation between symptoms and objective findings of CRS to improve its symptom-based diagnosis for primary care and epidemiological studies by using data from a large-scale nationwide epidemiological study, the Korean National Health and Nutrition Examination Survey (KNHANES).DesignCross-sectional study.SettingData from 2008 to 2012 KNHANES.Participants29 225 Adults aged >19 years.Outcome measuresQuestionnaires targeted two major (nasal blockage and anterior/posterior nasal drip) and two minor (facial pain/pressure and reduction or loss of smell) symptoms. Nasal polyps or mucopurulent discharge from the middle meatus was defined as positive endoscopic findings for diagnosing CRS.ResultsOf the four symptoms, reduction or loss of smell was the symptom most significantly related to positive endoscopic findings in multivariable analysis (OR=1.936 (95% CI 1.604 to 2.337)). The combinations of symptoms showed higher ORs than individual symptoms and combinations of reduction or loss of smell with other symptoms were statistically more reliable for positive endoscopic findings than other combinations.ConclusionsOur results show that reduction or loss of smell was the symptom most significantly related to positive nasal endoscopic findings. Therefore, symptom-based diagnosis of CRS can be improved by considering reduction or loss of smell as an important symptom for positive endoscopic findings of CRS.
A partial plesiosaurian braincase from the Upper Cretaceous of Sweden
Authors: Sachs Sven , Lindgren Johan , Siversson Mikael 
Published: December 2015

Abstract

A partial exoccipital–opisthotic from the uppermost lower Campanian (Upper Cretaceous) of the Åsen locality, Kristianstad Basin, southernmost Sweden, is described and illustrated. The fossil represents the first braincase element of a plesiosaur found in Sweden. It includes the chamber for the ampulla and utriculus, openings for the caudal vertical and horizontal semicircular canals, and four foramina for cranial nerves. The incomplete braincase can be referred to an elasmosaurid plesiosaur, and closely resembles the exoccipital–opisthotic of
Libonectes morgani
and a referred specimen of
Aristonectes parvidens
. Although we discuss putative postcranial material of the elasmosaurid subfamily Aristonectinae in the uppermost lower Campanian of southernmost Sweden, the exoccipital–opisthotic from Åsen most likely belongs to a juvenile individual of a non-aristonectine elasmosaur.
Application of outcrop analogues in successful exploration of a sand injection complex, Volund Field, Norwegian North Sea
Authors: Hurst Andrew , Huuse Mads , Duranti Davide , Vigorito Mario , Jameson Eric , Schwab Anne 
Published: December 2015

Abstract
Identification and exploration drilling of the Volund Field as part of a sand injection complex is the first example of deliberate targeting of sandstone intrusions in oil exploration. Outcrop data were an important element in the process of constraining the uncertainty associated with reservoir presence and connectivity. A strong lobby against the relevance of sand injectites as exploration targets, and significant uncertainty associated with sub-surface sand injectite analogues associated with existing oil fields, combined to discourage and down-grade Volund's prospectivity. Few outcrop studies provided data of relevance to exploration of sandstone intrusions and original outcrop data were utilized in evaluation of Volund. Sills and saucer-shaped sandstone intrusions are the most common reservoir units observed at outcrop and similar features were identified in the 3D seismic across the Volund Field prospect. A large-scale sand injection origin rather than a depositional origin was proposed. Outcrops of sandstone intrusions demonstrated excellent reservoir quality in composite sandstone bodies that cross-cut depositional bedding. High-quality reservoirs with excellent vertical and lateral connectivity are observed and used to support the prediction of similar quality reservoirs in the Volund prospect.
Personalized Preclinical Trials in BRAF Inhibitor–Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies
Authors: Krepler Clemens , Xiao Min , Sproesser Katrin , Brafford Patricia A. , Shannan Batool , Beqiri Marilda , Liu Qin , Xu Wei , Garman Bradley , Nathanson Katherine L. , Xu Xiaowei , Karakousis Giorgos C. , Mills Gordon B. , Lu Yiling , Ahmed Tamer A. , Poulikakos Poulikos I. , Caponigro Giordano , Boehm Markus , Peters Malte , Schuchter Lynn M. , Weeraratna Ashani T. , Herlyn Meenhard 
Published: December 2015

Abstract
Purpose: To test second-line personalized medicine combination therapies, based on genomic and proteomic data, in patient-derived xenograft (PDX) models.
Experimental Design: We established 12 PDXs from BRAF inhibitor–progressed melanoma patients. Following expansion, PDXs were analyzed using targeted sequencing and reverse-phase protein arrays. By using multi-arm preclinical trial designs, we identified efficacious precision medicine approaches.
Results: We identified alterations previously described as drivers of resistance: NRAS mutations in 3 PDXs, MAP2K1 (MEK1) mutations in 2, BRAF amplification in 4, and aberrant PTEN in 7. At the protein level, re-activation of phospho-MAPK predominated, with parallel activation of PI3K in a subset. Second-line efficacy of the pan-PI3K inhibitor BKM120 with either BRAF (encorafenib)/MEK (binimetinib) inhibitor combination or the ERK inhibitor VX-11e was confirmed in vivo. Amplification of MET was observed in 3 PDX models, a higher frequency than expected and a possible novel mechanism of resistance. Importantly, MET amplification alone did not predict sensitivity to the MET inhibitor capmatinib. In contrast, capmatinib as single agent resulted in significant but transient tumor regression in a PDX with resistance to BRAF/MEK combination therapy and high pMET. The triple combination capmatinib/encorafenib/binimetinib resulted in complete and sustained tumor regression in all animals.
Conclusions: Genomic and proteomic data integration identifies dual-core pathway inhibition as well as MET as combinatorial targets. These studies provide evidence for biomarker development to appropriately select personalized therapies of patients and avoid treatment failures. Clin Cancer Res; 22(7); 1592–602. ©2015 AACR.
See related commentary by Hartsough and Aplin, p. 1550
Transgenic Overexpression of Tissue‐Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification
Authors: Savinov Alexei Y. , Salehi Maryam , Yadav Manisha C. , Radichev Ilian , Millán José Luis , Savinova Olga V. 
Published: December 2015

Background

Ectopic vascular calcification is a common condition associated with aging, atherosclerosis, diabetes, and/or chronic kidney disease. Smooth muscle cells are the best characterized source of osteogenic progenitors in the vasculature; however, recent studies suggest that cells of endothelial origin can also promote calcification. To test this, we sought to increase the osteogenic potential of endothelial cells by overexpressing tissue‐nonspecific alkaline phosphatase (
TNAP
), a key enzyme that regulates biomineralization, and to determine the pathophysiological effect of endothelial
TNAP
on vascular calcification and cardiovascular function.

Methods and Results

We demonstrated previously that mice transgenic for

ALPL

(gene encoding human
TNAP
) develop severe arterial medial calcification and reduced viability when
TNAP
is overexpressed in smooth muscle cells. In this study, we expressed the

ALPL

transgene in
endothelial cells
following endothelial‐specific
Tie2‐Cre
recombination. Mice with endothelial
TNAP
overexpression survived well into adulthood and displayed generalized arterial calcification. Genes associated with osteochondrogenesis (
Runx2, Bglap, Spp1, Opg, and Col2a1
) were upregulated in the aortas of
endothelial TNAP
animals compared with controls. Lesions in coronary arteries of
endothelial TNAP
mice showed immunoreactivity to Runx2, osteocalcin, osteopontin, and collagen
II
as well as increased deposition of sialoproteins revealed by lectin staining. By 23 weeks of age,
endothelial TNAP
mice developed elevated blood pressure and compensatory left ventricular hypertrophy with preserved ejection fraction.

Conclusions

This study presented a novel genetic model demonstrating the osteogenic potential of
TNAP
‐positive endothelial cells in promoting pathophysiological vascular calcification.
Tropical Temperature and Precipitation Responses to Large Volcanic Eruptions: Observations and AMIP5 Simulations
Authors: Meyer A. , Folini D. , Lohmann U. , Peter T. 
Published: December 2015

Abstract
Tropical land mean surface air temperature and precipitation responses to the eruptions of El Chichón in 1982 and Pinatubo in 1991, as simulated by the atmosphere-only GCMs (AMIP) in phase 5 of the Coupled Model Intercomparison Project (CMIP5), are examined and compared to three observational datasets. The El Niño–Southern Oscillation (ENSO) signal was statistically separated from the volcanic signal in all time series. Focusing on the ENSO signal, it was found that the 17 investigated AMIP models successfully simulate the observed 4-month delay in the temperature responses to the ENSO phase but simulate somewhat too-fast precipitation responses during the El Niño onset stage. The observed correlation between temperature and ENSO phase (correlation coefficient of 0.75) is generally captured well by the models (simulated correlation of 0.71 and ensemble means of 0.61–0.83). For precipitation, mean correlations with the ENSO phase are −0.59 for observations and −0.53 for the models, with individual ensemble members having correlations as low as −0.26. Observed, ENSO-removed tropical land temperature and precipitation decrease by about 0.35 K and 0.25 mm day−1 after the Pinatubo eruption, while no significant decrease in either variable was observed after El Chichón. The AMIP models generally capture this behavior despite a tendency to overestimate the precipitation response to El Chichón. Scatter is substantial, both across models and across ensemble members of individual models. Natural variability thus may still play a prominent role despite the strong volcanic forcing.