bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleic acid oxidation: an early feature of Alzheimer's disease
Authors: Bradley‐Whitman Melissa A. , Timmons Michael D. , Beckett Tina L. , Murphy Michael P. , Lynn Bert C. , Lovell Mark A. 
Published: September 2013

AbstractStudies of oxidative damage during the progression of Alzheimer's disease (AD) suggest its central role in disease pathogenesis. To investigate levels of nucleic acid oxidation in both early and late stages of AD, levels of multiple base adducts were quantified in nuclear and mitochondrial DNA from the superior and middle temporal gyri (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of age‐matched normal control subjects, subjects with mild cognitive impairment, preclinical AD, late‐stage AD, and non‐AD neurological disorders (diseased control; DC) using gas chromatography/mass spectrometry. Median levels of multiple DNA adducts in nuclear and mitochondrial DNA were significantly (p ≤ 0.05) elevated in the SMTG, IPL, and CER in multiple stages of AD and in DC subjects. Elevated levels of fapyguanine and fapyadenine in mitochondrial DNA suggest a hypoxic environment early in the progression of AD and in DC subjects. Overall, these data suggest that oxidative damage is an early event not only in the pathogenesis of AD but is also present in neurodegenerative diseases in general.
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Levels of oxidized nucleic acids in nDNA and mtDNA were found to be significantly elevated in mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late‐stage AD (LAD), and a pooled diseased control group (DC) of frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) subjects compared to normal control (NC) subjects. Nucleic acid oxidation peaked early in disease progression and remained elevated. The study suggests nucleic acid oxidation is a general event in neurodegeneration.
Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease
Authors: Huang X. , Sjögren P. , Ärnlöv J. , Cederholm T. , Lind L. , Stenvinkel P. , Lindholm B. , Risérus U. , Carrero J. J. 
Published: September 2013

AbstractObjectivesThe causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD.SubjectsTwo population‐based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C‐estimated glomerular filtration rate <60 mL min−1/1.73 m2: the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively.DesignFactor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp.ResultsFactor analyses generated two fatty acid patterns of (i) low linoleic acid (LA)/high saturated fatty acid (SFA) or (ii) high n‐3 polyunsaturated fatty acid (n‐3 PUFA) levels. In both surveys, the low LA/high SFA pattern increased the odds of having MetS [adjusted odds ratio 0.60 [95% confidence interval (CI) 0.44–0.81] and 0.45 (95% CI 0.30–0.67) per SD decrease in factor score in the ULSAM and PIVUS surveys, respectively] and was directly associated with both IR and C‐reactive protein. The n‐3 PUFA pattern was not consistently associated with these risk factors.ConclusionsA serum fatty acid pattern reflecting low LA and high SFA was strongly associated with MetS, IR and inflammation in two independent surveys of elderly individuals with CKD. At present, there are no specific dietary guidelines for individuals with CKD; however, these findings indirectly support current recommendations to replace SFAs with PUFAs from vegetable oils.
Prognostic impact of renal function in precapillary pulmonary hypertension
Authors: Kaiser R. , Seiler S. , Held M. , Bals R. , Wilkens H. 
Published: September 2013

AbstractBackgroundImpairment of renal function is associated with adverse outcome in various diseases. Patients with pulmonary hypertension (PH) show diminished cardiac function and organ perfusion. The aim of this study was to investigate the associations between renal function and both haemodynamic parameters and long‐term survival in patients with PH.MethodsBlood was collected from 64 patients with PH (Dana Point class 1, 3 and 4) during right heart catheterization, and plasma was prepared. Creatinine, blood urea nitrogen (BUN), cystatin C, neutrophil‐gelatinase‐associated lipocalin (NGAL), fibroblast growth factor 23 (FGF‐23) and α‐Klotho levels were determined, and glomerular filtration rate (GFR) was estimated (eGFR). Parameters were evaluated using c‐statistics and dichotomized for survival analysis based on receiver operating characteristic curves.ResultsThe median follow‐up time was 9.92 years with all‐cause mortality as the primary end‐point. Elevated BUN, cystatin C and creatinine levels were associated with decreased survival, with hazard ratios (HRs) of 3.237, 4.514 and 2.006, respectively, and equivalent performance according to c‐statistics. Estimating GFR by CKD‐EPI, MDRD and Cockcroft–Gault formulas resulted in HRs of 2.942, 2.694 and 3.306, respectively. Amongst these formulas, eGFR (Cockcroft–Gault) had the highest c‐statistics of 0.674. There was a correlation between BUN and both cardiac index (τ = −0.39) and pulmonary vascular resistance index (τ = 0.249), whereas eGFR (CKD‐EPI) was correlated with cardiac index (τ = 0.225). No correlations between either BUN or eGFR and right atrial pressure (RAP) were observed. NGAL, FGF‐23 and α‐Klotho had no prognostic impact or association with haemodynamic parameters.ConclusionComparison of markers of renal function for prognosis in PH demonstrated superiority of creatinine, cystatin C and BUN over NGAL, FGF‐23 and α‐Klotho. Minor decreases in eGFR influence long‐term prognosis, and measurement of cystatin C levels might be useful to detect renal impairment in patients with a normal serum concentration of creatinine. Renal function in patients with PH is linked to cardiac index rather than RAP.
Consolidation through the looking‐glass: sleep‐dependent proactive interference on visuomotor adaptation in children
Authors: Urbain Charline , Houyoux Emeline , Albouy Geneviève , Peigneux Philippe 
Published: September 2013

SummaryAlthough a beneficial role of post‐training sleep for declarative memory has been consistently evidenced in children, as in adults, available data suggest that procedural memory consolidation does not benefit from sleep in children. However, besides the absence of performance gains in children, sleep‐dependent plasticity processes involved in procedural memory consolidation might be expressed through differential interference effects on the learning of novel but related procedural material. To test this hypothesis, 32 10–12‐year‐old children were trained on a motor rotation adaptation task. After either a sleep or a wake period, they were first retested on the same rotation applied at learning, thus assessing offline sleep‐dependent changes in performance, then on the opposite (unlearned) rotation to assess sleep‐dependent modulations in proactive interference coming from the consolidated visuomotor memory trace. Results show that children gradually improve performance over the learning session, showing effective adaptation to the imposed rotation. In line with previous findings, no sleep‐dependent changes in performance were observed for the learned rotation. However, presentation of the opposite, unlearned deviation elicited significantly higher interference effects after post‐training sleep than wakefulness in children. Considering that a definite feature of procedural motor memory and skill acquisition is the implementation of highly automatized motor behaviour, thus lacking flexibility, our results suggest a better integration and/or automation or motor adaptation skills after post‐training sleep, eventually resulting in higher proactive interference effects on untrained material.
Carving out turf in a biodiversity hotspot: multiple, previously unrecognized shrew species co‐occur onJavaIsland,Indonesia
Authors: Esselstyn Jacob A. , Maharadatunkamsi  , Achmadi Anang S. , Siler Cameron D. , Evans Ben J. 
Published: September 2013

AbstractIn theory, competition among species in a shared habitat results in niche separation. In the case of small recondite mammals such as shrews, little is known about their autecologies, leaving open questions regarding the degree to which closely related species co‐occur and how or whether ecological niches are partitioned. The extent to which species are able to coexist may depend on the degree to which they exploit different features of their habitat, which may in turn influence our ability to recognize them as species. We explored these issues in a biodiversity hotspot, by surveying shrew (genusCrocidura) diversity on theIndonesian island ofJava. We sequenced portions of nine unlinked genes in 100–117 specimens ofJavan shrews and incorporated homologous data from most knownCrociduraspecies from other parts of islandSouth‐EastAsia. Current taxonomy recognizes fourCrociduraspecies onJava, including two endemics. However, our phylogenetic, population genetic and species delimitation analyses identify five species on the island, and all are endemic toJava. While the individual ranges of these species may not overlap in their entirety, we found up to four species living syntopically and all five species co‐occurring on one mountain. Differences in species' body size, use of above ground‐level habitats by one species and habitat partitioning along ecological gradients may have facilitated species diversification and coexistence.
Biogeography and host‐related factors trump parasite life history: limited congruence among the genetic structures of specific ectoparasitic lice and their rodent hosts
Authors: Toit Nina du , van Vuuren Bettine J. , Matthee Sonja , Matthee Conrad A. 
Published: September 2013

AbstractParasites and hosts interact across both micro‐ and macroevolutionary scales where congruence among their phylogeographic and phylogenetic structures may be observed. Within southernAfrica, the four‐striped mouse genus,Rhabdomys, is parasitized by the ectoparasitic sucking louse,Polyplax arvicanthis. Molecular data recently suggested the presence of two cryptic species withinP. arvicanthisthat are sympatrically distributed across the distributions of four putativeRhabdomysspecies. We tested the hypotheses of phylogeographic congruence and cophylogeny among the two parasite lineages and the four host taxa, utilizing mitochondrial and nuclear sequence data. Despite the documented host‐specificity ofP. arvicanthis,limited phylogeographic correspondence and nonsignificant cophylogeny was observed. Instead, the parasite–host evolutionary history is characterized by limited codivergence and several duplication, sorting and host‐switching events. Despite the elevated mutational rates found forP. arvicanthis,the spatial genetic structure was not more pronounced in the parasite lineages compared with the hosts. These findings may be partly attributed to larger effective population sizes of the parasite lineages, the vagility and social behaviour ofRhabdomys, and the lack of host‐specificity observed in areas of host sympatry. Further, the patterns of genetic divergence within parasite and host lineages may also be largely attributed to historical biogeographic changes (expansion‐contraction cycles). It is thus evident that the association betweenP. arvicanthisandRhabdomyshas been shaped by the synergistic effects of parasite traits, host‐related factors and biogeography over evolutionary time.
RhNAC3, a stress‐associated NAC transcription factor, has a role in dehydration tolerance through regulating osmotic stress‐related genes in rose petals
Authors: Jiang Xinqiang , Zhang Changqing , Lü Peitao , Jiang Guimei , Liu Xiaowei , Dai Fanwei , Gao Junping 
Published: September 2013

SummaryPetal cell expansion depends on cell wall metabolism, changes in cell turgor pressure and restructuring of the cytoskeleton, and recovery ability of petal cell expansion is defined as an indicator of dehydration tolerance in flowers. We previously reported that RhNAC2, a development‐related NAC domain transcription factor, confers dehydration tolerance through regulating cell wall‐related genes in rose petals. Here, we identify RhNAC3, a novel rose SNAC gene, and its expression in petals induced by dehydration, wounding, exogenous ethylene and abscisic acid (ABA). Expression studies in Arabidopsis protoplasts and yeast show that RhNAC3 has transactivation activity along its full length and in the carboxyl‐terminal domain. Silencing RhNAC3 in rose petals by virus‐induced gene silencing (VIGS) significantly decreased the cell expansion of rose petals under rehydration conditions. In total, 24 of 27 osmotic stress‐related genes were down‐regulated in RhNAC3‐silenced rose petals, while only 4 of 22 cell expansion‐related genes were down‐regulated. Overexpression of RhNAC3 in Arabidopsis gave improved drought tolerance, with lower water loss of leaves in transgenic plants. Arabidopsis ATH1 microarray analysis showed that RhNAC3 regulated the expression of stress‐responsive genes in overexpressing lines, and further analysis revealed that most of the RhNAC3‐up‐regulated genes were involved in the response to osmotic stress. Comparative analysis revealed that different transcription regulation existed between RhNAC3 and RhNAC2. Taken together, these data indicate that RhNAC3, as a positive regulator, confers dehydration tolerance of rose petals mainly through regulating osmotic adjustment‐associated genes.
Melanoma‐associated leukoderma – immunology in black and white?
Authors: Naveh Hadas Prag , Rao Uma N. M. , Butterfield Lisa H. 
Published: September 2013

SummaryMelanoma is an ‘immunogenic tumor’, often highly infiltrated with lymphocytes, which are capable of inducing regression of the primary tumor. The commonly observed phenomenon of regression suggests substantial cross‐talk between immune cells and transformed melanocytes. An immune response to melanocyte differentiation antigens common to transformed and normal melanocytes manifests clinically at distant sites as melanoma‐associated vitiligo or halo nevi. Despite similar antigenic targets, the pathogenesis and prognosis differ between the different melanoma‐associated leukodermas. Understanding immunologic cross‐talk between melanocytes and the immune system will aid the development of approaches to combat melanoma.
A melanoma immune response signature including Human Leukocyte Antigen‐E
Authors: Tremante Elisa , Ginebri Agnese , Lo Monaco Elisa , Benassi Barbara , Frascione Pasquale , Grammatico Paola , Cappellacci Sandra , Catricalà Caterina , Arcelli Diego , Natali Pier Giorgio , Di Filippo Franco , Mottolese Marcella , Visca Paolo , Benevolo Maria , Giacomini Patrizio 
Published: September 2013

SummaryPaired cultures of early‐passage melanoma cells and melanocytes were established from metastatic lesions and the uninvolved skin of five patients. In this stringent autologous setting, cDNA profiling was used to analyze a subset of 1477 genes selected by the Gene Ontology term ‘immune response’. Human Leukocyte Antigen E (HLA‐E) was ranked 19th among melanoma‐overexpressed genes and was embedded in a transformation signature including its preferred peptide ligand donors HLA‐A, HLA‐B, HLA‐C, and HLA‐G. Mostly undetectable in normal skin and 39 nevi (including rare and atypical lesions), HLA‐E was detected by immunohistochemistry in 17/30 (57%) and 32/48 (67%) primary and metastatic lesions, respectively. Accordingly, surface HLA‐E was higher on melanoma cells than on melanocytes and protected the former (6/6 cell lines) from lysis by natural killer (NK) cells, functionally counteracting co‐expressed triggering ligands. Although lacking HLA‐E, melanocytes (4/4 cultures) were nevertheless (and surprisingly) fully protected from NK cell lysis.
Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression
Authors: Garvin Nathan M. , Levine Benjamin D. , Raven Peter B. , Pawelczyk James A. 
Published: September 2013

New Findings
What is the central question of this study?What is the mechanism by which pneumatic antishock garments increase blood pressure?
What is the main finding and its importance?Direct recordings of sympathetic nerve activity revealed that pneumatic antishock garments activate a sympathetically mediated reflex increase in blood pressure by compressing the abdomen, but not the leg. This mechanism has never been shown previously.
Pneumatic antishock garments (PASG) have been proposed to exert their blood pressure‐raising effect mechanically, i.e. by increasing venous return and vascular resistance of the lower body. We tested whether, alternatively, PASG inflation activates the sympathetic nervous system. Five men and four women wore PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the abdominal bladder (ABD) of the trousers were inflated individually and in combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of inflation, conditions that included the ABD region caused significant increases in MAP in a dose‐dependent fashion (7 ± 2, 8 ± 3, 14 ± 4 and 13 ± 5 mmHg for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise, inflation that included ABD caused significant increases in total MSNA compared with control values [306 ± 70, 426 ± 98 and 247 ± 79 units for ABD60, ABD90 and ABD+LEG90, respectively, P < 0.05 (units = burst frequency × burst amplitude]. There were no changes in MAP or MSNA in the LEG‐alone conditions. The ABD inflation also caused a significant decrease in stroke volume (−11 ± 3 and −10 ± 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no change in cardiac output. Neither cardiopulmonary receptor deactivation nor mechanical effects can account for a slowly developing rise in both sympathetic activity and blood pressure during ABD inflation. Rather, these data provide direct evidence that PASG inflation activates the sympathetic nervous system secondarily to abdominal, but not leg, compression.
Vagal modulation of cardiac ventricular arrhythmia
Authors: Ng G. André 
Published: September 2013

New findings
What is the topic of this review?
This article addresses the relationship between vagus nerve activity and malignant ventricular arrhythmias. It focuses on the clinical association of an impaired vagal tone in cardiac disease states with high mortality from sudden cardiac death and the potential underlying mechanisms.
What advances does it highlight?
The article summarizes the mounting evidence that vagal innervation in the cardiac ventricle plays a key direct role in the prevention of the initiation of ventricular fibrillation. Data are presented on the role that nitric oxide plays in mediating the effects of vagal protection against ventricular fibrillation, supporting the notion that a separate non‐muscarinic, nitrergic population of vagal neurons is responsible for this protection.
Sudden cardiac death remains a significant unresolved clinical problem, with many of the deaths being due to malignant ventricular arrhythmias. Markers of abnormal autonomic function have been shown to be strong prognostic predictors, highlighting the important relationship between reduced vagal tone and malignant ventricular arrhythmias, such as ventricular fibrillation, in cardiac patients. Exploring the mechanisms underlying the autonomic modulation of ventricular fibrillation, my group has shown that vagus nerve stimulation protects against ventricular fibrillation in the innervated isolated heart preparation. We have provided direct evidence that nitric oxide is released in the ventricle with cervical vagus nerve stimulation and NO mediates the antifibrillatory actions of vagus nerve stimulation in the ventricle. Classical physiology teaches that vagal postganglionic nerves modulate the heart via acetylcholine acting at muscarinic receptors and, dogmatically, that there is little vagal effect in the ventricle, as innervation was believed to be sparse. Mounting evidence from many species now supports the presence of a rich vagal innervation in the ventricle. Data from my group showing that the protective actions of vagus nerve stimulation against ventricular fibrillation and NO release are preserved in the presence of muscarinic block support the notion that a population of nitrergic neurons could be responsible. This potentially exploitable downstream pathway together with the availability of vagus nerve stimulators make it an exciting time to investigate the development of an effective strategy of vagal protection against ventricular fibrillation in the clinical setting.
Effect of inspiratory muscle fatigue on exercise performance taking into account the fatigue‐induced excess respiratory drive
Authors: Wüthrich Thomas U. , Notter Dominic A. , Spengler Christina M. 
Published: September 2013

New findings
What is the central question of this study?Inspiratory muscle fatigue (IMF) limits exercise performance and can augment ventilatory drive, which could per se impair performance due to greater respiratory muscle work. Using magnetic nerve stimulation to assess fatigue, we tested whether the IMF‐induced decrease in exercise performance results from increased respiratory muscle work alone and/or a metaboreflex‐mediated increase in quadriceps muscle fatigue.
What is the main finding and its importance?We found that IMF increased quadriceps muscle fatigue and perception of exertion and reduced performance in face of similar respiratory muscle work. This impairment is likely to result from increased metaboreflex activation. These findings support a reduction in metaboreflex as the mechanism leading to improved performance after respiratory muscle training.
Inspiratory muscle fatigue (IMF) is suggested to compromise exercise performance, possibly via a respiratory muscle metaboreflex that impairs blood flow to working muscles, thereby accelerating the development of fatigue in these muscles. Cycling with IMF has also been associated with an excess ventilatory response, which could per se impair performance. Therefore, the present study investigated whether prior‐induced IMF would affect subsequent cycling performance via increased quadriceps muscle fatigue alone and whether fatigue‐induced excess ventilation would contribute to this impairment. Fourteen healthy male subjects (peak oxygen uptake, 57.0 ± 5.5 ml min−1 kg−1) cycled to exhaustion at 85% of their maximal work output with prior‐induced IMF (PF‐EX) and without prior‐induced IMF (C‐EX). Subjects then cycled twice for the duration of PF‐EX but without prior IMF, once with spontaneous breathing (C‐ISO) and once with breathing coached to match PF‐EX ventilation (MATCH‐ISO). Inspiratory muscle (Ptw) and quadriceps muscle contractility (Qtw) was assessed via magnetic nerve stimulation before and after exercise. The time to exhaustion in the PF‐EX conditions was significantly reduced by 14% compared with C‐EX. The reduction in Ptw and Qtw was greater after PF‐EX (Ptw, 17.3 ± 9.7%; Qtw, 32.0 ± 10.8%) than after MATCH‐ISO (Ptw, 10.8 ± 10.3%; Qtw, 23.3 ± 15.2%; P < 0.05), which may explain the increased perception of exertion and earlier task failure with prior‐induced IMF. The augmented ventilatory drive had no effect on reductions in Ptw and Qtw after MATCH‐ISO compared with C‐ISO. Thus, prior‐induced IMF reduces exercise performance, probably as a result of the increased quadriceps muscle fatigue and thus greater perception of exertion independent of the excess respiratory drive when cycling with fatigued inspiratory muscles.