bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and tolerability of intensified, N‐terminal pro brain natriuretic peptide‐guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME‐CHF
Authors: Sanders‐van Wijk Sandra , Muzzarelli Stefano , Neuhaus Michael , Kiencke Stephanie , Maeder Micha , Estlinbaum Werner , Tobler Daniel , Mayer Kurt , Erne Paul , Pfisterer Matthias E. , Brunner‐La Rocca Hans‐Peter ,   for the TIME‐CHF investigators
Published: May 2013

AimsNT‐proBNP‐guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT‐proBNP‐guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT‐proBNP‐guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME‐CHF) was assessed.Methods and resultsA total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT‐proBNP‐guided or symptom‐guided therapy and ≥1 month follow‐up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18‐month trial period. A total of 5212 AEs were noted, 433 of them serious. NT‐proBNP‐guided therapy led to a higher up‐titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient‐year 4.7 (2.8–9.4) vs. 5.4 (2.7–11.4), P = 0.69; number of severe AEs/patient‐year 0.7 (0–2.7) vs. 1.3 (0–3.9), P = 0.21] similar to that of symptom‐guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co‐morbidities were associated with AEs and interacted with the safety profile of NT‐proBNP‐guided therapy: positive effects were more frequent in younger and less co‐morbid patients whereas potential negative effects—although small and related to non‐severe AEs only—were only seen in the older and more co‐morbid patients.ConclusionsNT‐proBNP‐guided therapy is safe in elderly and highly co‐morbid HF patients.Trial registrationISRCTN43596477
Natural regulatory T cells are resistant to calcium release-activated calcium (CRAC/ORAI) channel inhibition
Authors: Jin Shu , Chin Jayne , Kitson Christopher , Woods John , Majmudar Rupal , Carvajal Valerie , Allard John , DeMartino Julie , Narula Satwant , Thomas-Karyat Dori A. 
Published: May 2013

Abstract
Organ transplant patients are often treated with immunosuppressants, such as the calcineurin phosphatase inhibitor, cyclosporin A, to block T cell-mediated graft rejection. The calcium release-activated calcium (CRAC/ORAI) channels, which act upstream of calcineurin, are essential for calcium entry and CD4+ T-cell activation. Although cyclosporine A has also been shown to inhibit FoxP3+ Tregs both in vitro and in vivo, the role of ORAI channel inhibition in natural Tregs (nTregs) or inducible Tregs (iTregs) has not been investigated. We found that, despite inhibition of calcium influx through the ORAI channels, ORAI channel inhibitors were unable to repress FoxP3 expression in mouse and human nTregs, whereas FoxP3 expression was inhibited in iTregs. In contrast, cyclosporin A inhibited FoxP3 expression in both nTregs and iTregs. We also generated mice with a T cell-specific, conditional knockout of ORAI1 and found that the mice have normal nTreg development and suppressive activity. Moreover, iTregs derived from ORAI1 conditional knockout mice develop normally and are still susceptible to ORAI channel inhibition. Our data indicate that unlike CD4+ T cells and iTregs, nTregs are resistant to ORAI-mediated inhibition. Targeting ORAI channels potentially offers a novel way to inhibit pathologic T cells, while sparing nTreg-mediated tolerance.
Advanced Proteomic Analyses Yield a Deep Catalog of Ubiquitylation Targets in Arabidopsis
Authors: Kim Do-Young , Scalf Mark , Smith Lloyd M. , Vierstra Richard D. 
Published: May 2013

Abstract
The posttranslational addition of ubiquitin (Ub) profoundly controls the half-life, interactions, and/or trafficking of numerous intracellular proteins. Using stringent two-step affinity methods to purify Ub-protein conjugates followed by high-sensitivity mass spectrometry, we identified almost 950 ubiquitylation substrates in whole Arabidopsis thaliana seedlings. The list includes key factors regulating a wide range of biological processes, including metabolism, cellular transport, signal transduction, transcription, RNA biology, translation, and proteolysis. The ubiquitylation state of more than half of the targets increased after treating seedlings with the proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-Leu-al), strongly suggesting that Ub addition commits many to degradation by the 26S proteasome. Ub-attachment sites were resolved for a number of targets, including six of the seven Lys residues on Ub itself with a Lys-48&gt;Lys-63&gt;Lys-11&gt;&gt;&gt;Lys-33/Lys-29/Lys-6 preference. However, little sequence consensus was detected among conjugation sites, indicating that the local environment has little influence on global ubiquitylation. Intriguingly, the level of Lys-11–linked Ub polymers increased substantially upon MG132 treatment, revealing that they might be important signals for proteasomal breakdown. Taken together, this proteomic analysis illustrates the breadth of plant processes affected by ubiquitylation and provides a deep data set of individual targets from which to explore the roles of Ub in various physiological and developmental pathways.
The α/β Hydrolase CGI-58 and Peroxisomal Transport Protein PXA1 Coregulate Lipid Homeostasis and Signaling in Arabidopsis
Authors: Park Sunjung , Gidda Satinder K. , James Christopher N. , Horn Patrick J. , Khuu Nicholas , Seay Damien C. , Keereetaweep Jantana , Chapman Kent D. , Mullen Robert T. , Dyer John M. 
Published: May 2013

Abstract
COMPARATIVE GENE IDENTIFICATION-58 (CGI-58) is a key regulator of lipid metabolism and signaling in mammals, but its underlying mechanisms are unclear. Disruption of CGI-58 in either mammals or plants results in a significant increase in triacylglycerol (TAG), suggesting that CGI-58 activity is evolutionarily conserved. However, plants lack proteins that are important for CGI-58 activity in mammals. Here, we demonstrate that CGI-58 functions by interacting with the PEROXISOMAL ABC-TRANSPORTER1 (PXA1), a protein that transports a variety of substrates into peroxisomes for their subsequent metabolism by β-oxidation, including fatty acids and lipophilic hormone precursors of the jasmonate and auxin biosynthetic pathways. We also show that mutant cgi-58 plants display changes in jasmonate biosynthesis, auxin signaling, and lipid metabolism consistent with reduced PXA1 activity in planta and that, based on the double mutant cgi-58 pxa1, PXA1 is epistatic to CGI-58 in all of these processes. However, CGI-58 was not required for the PXA1-dependent breakdown of TAG in germinated seeds. Collectively, the results reveal that CGI-58 positively regulates many aspects of PXA1 activity in plants and that these two proteins function to coregulate lipid metabolism and signaling, particularly in nonseed vegetative tissues. Similarities and differences of CGI-58 activity in plants versus animals are discussed.
Temporal dynamics of direct reciprocal and indirect effects in a host–parasite network
Authors: Pilosof Shai , Fortuna Miguel A. , Vinarski Maxim V. , Korallo‐Vinarskaya Natalia P. , Krasnov Boris R. 
Published: May 2013

SummaryTemporal variation in the direct and indirect influence that hosts and parasites exert on each other is still poorly understood. However, variation in species' influence due to species and interactions turnover can have important consequences for host community dynamics and/or for parasite transmission dynamics, and eventually for the risk of zoonotic diseases.We used data on a network of small mammals and their ectoparasites surveyed over 6 years to test hypotheses exploring (i) the temporal variability in direct and indirect influences species exert on each other in a community, and (ii) the differences in temporal variability of direct/indirect influences between temporally persistent (TP) and temporally intermittent species.We modelled the temporal variation in (i) direct reciprocal influence between hosts and parasites (hosts providing resources to parasites and parasites exploiting the resources of hosts), using an asymmetry index, and (ii) indirect influence among species within a community (e.g. facilitation of parasite infestation by other parasites), using betweenness centrality. We also correlated asymmetry and centrality to examine the relationship between them.Network dynamics was determined by TP species but even those species had strong among‐species heterogeneity in the temporal variation of the direct/indirect effects they exerted. In addition, there was a significant positive linear correlation between asymmetry and centrality.We conclude that the temporal dynamics of host–parasite interactions is driven by TP hosts. However, even within this group of persistent species, some exhibit large temporal variation, such that the functional roles they play (e.g. in promoting parasite transmission) change over time. In addition, parasites having a large negative impact on hosts are also those facilitating the spread of other parasites through the entire host community. Our results provide new insights into community dynamics and can be applied in the management of antagonistic networks aimed at preventing disease outbreaks.
Extrarenal roles of the with‐no‐lysine[K] kinases (WNKs)
Authors: Siew Keith , O'Shaughnessy Kevin M 
Published: May 2013

Summary

Identified over a decade ago, the with‐no‐lysine[K] kinases (WNKs) have been the subsequent focus of intense research into the renal handling of Na+, Cl− and K+ and several rare monogenetic diseases. However, the potential extrarenal roles for WNKs have been less well explored.

Thiazides and Gordon syndrome are known to have effects on bone mineral density, Ca2+ and PO43− homeostasis, which were originally assumed to be an indirect effect through the kidney. However, current data suggest a complex and direct role for WNKs in the physiology of bone.

The WNKs also modulate systemic blood pressure at several levels, including the vascular resistance vessels, where they cause vasoconstriction by altering the abundance of the transient receptor potential canonical channel 3 and/or phosphorylation of the Na+−K+−2Cl− cotransporter 1 in vascular smooth muscle cells.

The WNKs and many of the cation‐coupled Cl− cotransporters they regulate are highly expressed in the central nervous system and recent work suggests that WNK dysfunction may have a role in the development of autism, schizophrenia and hereditary sensory and autonomic neuropathy Type 2.

Finally, the WNK–sterile 20 kinase signalling axis represents an evolutionarily ancient mechanism for maintaining osmotic homeostasis, but a rapidly expanding body of evidence also shows a role in immunity and cellular regulation.
Impact of non‐cardiovascular surgery on reactive hyperaemia and arterial endothelial function
Authors: Hu Yan Jun , Wei An Ning , Chook Ping , Yin Yuehui , Cheng William , Wu Meng Jun , Celermajer David S , Woo Kam Sang 
Published: May 2013

Summary

Vascular reactivity is a surrogate marker for atherosclerosis and is predictive of cardiovascular outcome. Non‐cardiovascular surgery is associated with perioperative cardiovascular complications in high‐risk patients.

To evaluate the impact of non‐cardiovascular surgery on reactive hyperaemia and arterial endothelial function and to investigate the relationships between endothelial dysfunction and invasive (laparotomy) or minimally invasive (laparoscopic) surgery, we prospectively evaluated 106 patients undergoing abdominal surgery under general anaesthesia (71 laparotomy, 35 laparoscopy). Measurements of blood pressure, heart rate and pain (on a visual analogue scale (VAS)) were undertaken. Brachial endothelium‐dependent flow‐mediated dilation (FMD), endothelium‐independent dilation, nitroglycerin (NTG)‐induced dilation and reactive hyperaemia were measured with high‐resolution B‐mode ultrasound on preoperative Day 1 (baseline), as well as 2 h and 1 and 7 days postoperatively.

Blood pressure and heart rate were significantly higher 2 h postoperatively. Pain, as measured on the VAS, was higher (P < 0.01) and reactive hyperaemia and FMD were significantly lower (P < 0.001) at 2 h and 1 day postoperatively compared with values at baseline and on postoperative Day 7. By postoperative Day 7, FMD had recovered to baseline levels. Patients undergoing laparoscopic surgery had less FMD reduction on Days 1 and 7 (7.5 ± 1.5% and 7.9 ± 1.5%, respectively) compared with those undergoing laparotomy (6.4 ± 1.6% (P = 0.001) and 7.0 ± 1.6% (P = 0.006), respectively), consistent with potential cardiovascular benefit. Responses to NTG were stable throughout. Backward multivariate linear regression analysis indicated that FMD was independently related to age and VAS (model R = 0.486; F = 6.4; P < 0.001).

Reactive hyperaemia and arterial endothelial function are significantly reduced in the early postoperative period, particularly after laparotomy compared with laparoscopy, which may be related to postoperative cardiovascular events.
DNAbarcoding commercially important fish species ofTurkey
Authors: Keskİn Emre , Atar Hasan H. 
Published: May 2013

AbstractDNAbarcoding was used in the identification of 89 commercially important freshwater and marine fish species found in Turkish ichthyofauna. A total of 1765DNAbarcodes using a 654‐bp‐long fragment of the mitochondrial cytochrome c oxidase subunit I gene were generated for 89 commercially important freshwater and marine fish species found in Turkish ichthyofauna. These species belong to 70 genera, 40 families and 19 orders from class Actinopterygii, and all were associated with a distinctDNAbarcode. Nine and 12 of theCOIbarcode clusters represent the first species records submitted to theBOLDand GenBank databases, respectively. AllCOIbarcodes (except sequences of first species records) were matched with reference sequences of expected species, according to morphological identification. Average nucleotide frequencies of the data set were calculated asT = 29.7%,C = 28.2%,A = 23.6% andG = 18.6%. Average pairwise genetic distance among individuals were estimated as 0.32%, 9.62%, 17,90% and 22.40% for conspecific, congeneric, confamilial and within order, respectively. Kimura 2‐parameter genetic distance values were found to increase with taxonomic level. For most of the species analysed in our data set, there is a barcoding gap, and an overlap in the barcoding gap exists for only two genera. Neighbour‐joining trees were drawn based onDNAbarcodes and all the specimens clustered in agreement with their taxonomic classification at species level. Results of this study supportedDNAbarcoding as an efficient molecular tool for a better monitoring, conservation and management of fisheries.
Curve Fit: a pixel‐level raster regression tool for mapping spatial patterns
Authors: De Jager Nathan R. , Fox Timothy J. 
Published: May 2013

Summary

Despite the fact that pixels (i.e. picture elements) are the basic sampling units of maps, we are aware of no software package or tool that allows users to model changes that may occur at such fine spatial resolutions over broad geographic extents.

Curve Fit is an extension to the application ArcMap that allows users to conduct linear or nonlinear regression analysis on the range of values found within input raster data sets (geo‐referenced images), independently for each pixel.

Outputs consist of raster surfaces of regression model parameter estimates, standard errors, goodness‐of‐fit estimates and multimodel inference measures.

Curve fit outputs characterize continuous spatial or temporal change across a series of raster data sets.
The neurobiological correlates of childhood adversity and implications for treatment
Authors: Tyrka A. R. , Burgers D. E. , Philip N. S. , Price L. H. , Carpenter L. L. 
Published: May 2013

ObjectiveThis article provides an overview of research on the neurobiological correlates of childhood adversity and a selective review of treatment implications.MethodFindings from a broad array of human and animal studies of early adversity were reviewed.ResultsTopics reviewed include neuroendocrine, neurotrophic, neuroimaging, and cognitive effects of adversity, as well as genetic and epigenetic influences. Effects of early‐life stress on treatment outcome are considered, and development of treatments designed to address the neurobiological abnormalities is discussed.ConclusionEarly adversity is associated with abnormalities of several neurobiological systems that are implicated in the development of psychopathology and other medical conditions. Early‐life stress negatively impacts treatment outcome, and individuals may require treatments that are specific to this condition.
Genetics of serum and muscle lipids in pigs
Authors: Casellas J. , Vidal O. , Pena R. N. , Gallardo D. , Manunza A. , Quintanilla R. , Amills M. 
Published: May 2013

SummaryPork meat is one of the most important sources of animal protein in the human diet. Its nutritional properties are partly determined by intramuscular fat content and composition, with existing general consensus about the detrimental effects of cholesterol and saturated fat on cardiovascular health in humans. Because of their physiological resemblance, pigs can be also used as a valuable animal model to study the genetics of human diseases such as atherosclerosis, obesity and dyslipidaemias. Heritability estimates and QTL maps of porcine muscle and serum lipid traits evidence that a considerable amount of genetic variance determining these phenotypes exists, but its molecular basis remains mostly unknown. The recent advent of high‐throughput genotyping and sequencing technologies has revolutionised the field of animal genomics. With these powerful tools, finding needles in the genomic haystack has become increasingly feasible. However, these methodological advances should not be deemed as magic bullets. The goal of identifying the many polymorphisms that shape the variability of lipid phenotypes is so challenging that success can be achieved only under the scope of large international consortia.
Investigating gene expression differences in two chicken groups with variable propensity to feather pecking
Authors: Wysocki Michal , Preuss Siegfried , Stratz Patrick , Bennewitz Jörn 
Published: May 2013

SummaryFeather pecking is a major welfare problem in egg production. It may be caused by genetic, physiological and environmental factors. The main aim of this study was to uncover gene expression variability in brain tissue between individuals from high feather pecking and low feather pecking groups using the Chicken Gene Expression Microarray. In total, 313 signals were initially identified as significant (P ≤ 0.05) for the fold change higher than two. A subset of functional candidate genes including downregulated (GLUL, TSPO, MAOA) and upregulated (HTR1B, SIP1, PSEN1) transcripts was subjected to quantitative PCR validation. The significance level and direction of the fold change in gene expression observed by the microarray analysis were confirmed for four genes (HTR1B, SIP1, PSEN1 and GLUL). Newly identified candidate genes play an important role in neurotransmission and psychopathological disorders and can be considered as potential genetic components involved in complex feather pecking behavior. It can be concluded that this study has revealed some interesting differences in gene expression between high and low feather pecking groups and helped to approach elucidation of the genetic foundations of feather pecking.
Design, Synthesis, and Evaluation of Indolebutylamines as a Novel Class of Selective Dopamine D3 Receptor Ligands
Authors: Du Peng , Xu Lili , Huang Jiye , Yu Kunqian , Zhao Rui , Gao Bo , Jiang Hualiang , Zhao Weili , Zhen Xuechu , Fu Wei 
Published: May 2013

A series of indolebutylamine derivatives were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine 3 receptor. The most potent compound 11q binds to dopamine 3 receptor with a Ki value of 124 nm and displays excellent selectivity over the dopamine 1 receptor and dopamine 2 receptor. Investigation based on structural information indicates that site S182 located in extracellular loop 2 may account for high selectivity of compounds. Interaction models of the dopamine 3 receptor‐11q complex and structure‐activity relationships were discussed by integrating all available experimental and computational data with the eventual aim to discover potent and selective ligands to dopamine 3 receptor.
PON1‐108 TT and PON1‐192 RR genotypes are more frequently encountered in Greek PCOS than non‐PCOS women, and are associated with hyperandrogenaemia
Authors: Paltoglou George , Tavernarakis George , Christopoulos Panagiotis , Vlassi Margarita , Gazouli Maria , Deligeoroglou Efthimios , Creatsas George , Mastorakos George 
Published: May 2013

SummaryObjectiveTo investigate the frequencies of three paraoxonase (PON)1 polymorphisms in Greek polycystic ovary syndrome (PCOS) and non‐PCOS women, and their genotypes association with hyperandrogenaemia and insulin resistance.DesignCase–control genetic association study.SettingUniversity Hospital Endocrine Unit.PatientsA total of 142 PCOS cases (NIH criteria) and 112 controls.Main Outcome MeasureGenotyping of the c.–108C>T (PON1‐108), the c.163T>A (PON1‐55) and the c.575A>G (PON1‐192) polymorphisms and measurement of baseline androgen and insulin resistance profile.ResultsThe PON1‐108 TT and PON1‐192 RR genotypes were more frequently encountered in the PCOS than in the control group. The PON1‐192 R allele frequency was greater in the PCOS than in the control group. Comparing the PCOS and the control groups, statistical significances favoured a recessive and a dominant genetic model, respectively, for the single PON1‐108 T and PON1‐192 R alleles. Free Androgen Index (FAI) levels were higher in patients with PON1‐108 TT, whereas Testosterone, FAI and Dehydroepiandrosterone sulphate (DHEAS) levels were higher in patients with PON1‐192 RR than patients with the wild or the heterozygous genotype.ConclusionsThe decreased PON1 activity‐associated PON1‐108 TT and the PON1‐192 RR genotypes are more frequently found in Greek PCOS women and are associated with hyperandrogenaemia. Hyperandrogenaemia must depend also on other genetic factors because the same genotypes were not associated with hyperandrogenaemia in the control group. Through identification of the involved polymorphisms, women with PCOS could potentially have a better therapeutic screening.