bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual impacts of climate change: forest migration and turnover through life history
Authors: Zhu Kai , Woodall Christopher W. , Ghosh Souparno , Gelfand Alan E. , Clark James S.
Published: September 2013

Tree species are predicted to track future climate by shifting their geographic distributions, but climate‐mediated migrations are not apparent in a recent continental‐scale analysis. To better understand the mechanisms of a possible migration lag, we analyzed relative recruitment patterns by comparing juvenile and adult tree abundances in climate space. One would expect relative recruitment to be higher in cold and dry climates as a result of tree migration with juveniles located further poleward than adults. Alternatively, relative recruitment could be higher in warm and wet climates as a result of higher tree population turnover with increased temperature and precipitation. Using theUSDAForest Service's Forest Inventory and Analysis data at regional scales, we jointly modeled juvenile and adult abundance distributions for 65 tree species in climate space of the eastern United States. We directly compared the optimal climate conditions for juveniles and adults, identified the climates where each species has high relative recruitment, and synthesized relative recruitment patterns across species. Results suggest that for 77% and 83% of the tree species, juveniles have higher optimal temperature and optimal precipitation, respectively, than adults. Across species, the relative recruitment pattern is dominated by relatively more abundant juveniles than adults in warm and wet climates. These different abundance‐climate responses through life history are consistent with faster population turnover and inconsistent with the geographic trend of large‐scale tree migration. Taken together, this juvenile–adult analysis suggests that tree species might respond to climate change by having faster turnover as dynamics accelerate with longer growing seasons and higher temperatures, before there is evidence of poleward migration at biogeographic scales.
Molecular pathology of bone tumours: diagnostic implications
Authors: Puls Florian , Niblett Angela J , Mangham D Chas
Published: September 2013

Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's‐like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed.
Corticomedullary differentiation and maturational arrest in thymomas
Authors: Ströbel Philipp , Hartmann Elena , Rosenwald Andreas , Kalla Jörg , Ott German , Friedel Godehard , Schalke Berthold , Kasahara Masanori , Tomaru Utano , Marx Alexander
Published: September 2013

Aims

Morphological complexity hampers the histological classification of thymomas. Our aim was to determine whether the use of novel differentiation and maturation markers of cortical and medullary thymic epithelial cells (cTECs and mTECs) might provide an approach to understanding the underlying biology of these tumours.

Methods and results

Fifty‐seven thymomas were studied by immunohistochemistry. The cortical markers used were B5T, PRSS16, and cathepsin V. The medullary markers used were CD40, claudin‐4, AIRE, and desmin. Involucrin and cytokeratin 10 were used to study terminal mTEC maturation. Irrespective of histological subtype, most thymomas contained distinct areas with cortical and medullary differentiation. Type B1, type B2 and type AB thymomas showed marked bi‐lineage differentiation, with lack of terminal mTEC maturation in type AB. Type AB thymomas were unique in showing areas where cells with either cortical or medullary differentiation were intimately ‘mixed’ at the single‐cell level. Type B3 and type A thymomas showed only abortive lineage differentiation and maturation.

Conclusions

Thymomas show highly characteristic patterns of bi‐lineage TEC differentiation that reflect the histological subtypes recognized by the WHO classification. We hypothesize that thymomas arise from thymic precursor cells with different cortical and/or medullary maturation defects.
Disentangling the Effects of an Adult Model's Eye Gaze and Head Orientation on Young Infants' Processing of a Previously Attended Object
Authors: Hoehl Stefanie , Wahl Sebastian , Pauen Sabina
Published: September 2013

In order to disentangle the effects of an adult model's eye gaze and head orientation on infants' processing of objects attended to by the adult, we presented 4‐month‐olds with faces that either (1) shifted eye gaze toward or away from an object while the head stayed stationary or (2) that turned their head while maintaining gaze directed straight ahead. Infants' responses to the previously attended and unattended objects were measured using eye‐tracking and event‐related potentials. In both conditions, infants responded to objects that were not cued by the adult's head or eye gaze shift with more visual attention and an increased negative central (Nc) component relative to cued objects. This suggests that cued objects had been encoded more effectively, whereas uncued objects required further processing. We conclude that eye gaze and head orientation act independently as cues to direct infants' attention and object processing. Both head orientation and eye gaze, when presented in motion, even override the effects of incongruent stationary information from the other kind of cue.
Four views of Riehl's melanosis: clinical appearance, dermoscopy, confocal microscopy and histopathology
Authors: Wang L. , Xu A.‐E.
Published: September 2013

Background

Riehl's melanosis often poses a diagnostic challenge because of the variability in clinical morphology. Reflectance confocal microscopy (RCM), similar to dermoscopy, images lesions in an en face plane, thus enabling direct correlations with dermoscopic images. No published data are currently available regarding dermoscopic and RCM findings in Riehl's melanosis.

Objectives

The aim of our study was to correlate the features of Riehl's melanosis across various imaging modalities including dermoscopy, confocal microscopy and histopathological examination to give a more precise description of this disease to improve the accuracy of diagnosis.

Methods

Fifteen patients with a previously established diagnosis of Riehl's melanosis were recruited. All lesions were imaged using dermoscope and in vivo RCM, followed by complete excision for histopathological analysis.

Results

A series of dermoscopic and RCM features of Riehl's melanosis were identified and shown to correlate well with histopathological examination. Pseudonetworks, grey dots/granules, liquefaction of basal cells, incontinence of pigment were the most distinctive characteristic.

Conclusions

This study highlights the clinical, dermoscopic, confocal microscopic and histopathological features of Riehl's melanosis. It is necessary to further define the diagnostic features of clinically difficult lesions with these modalities, but clinical evaluation should not be neglected.
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

Studies 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.

image

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

Objectives

The 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.

Subjects

Two 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.

Design

Factor 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.

Results

Factor 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.

Conclusions

A 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

Background

Impairment 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.

Methods

Blood 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.

Results

The 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.

Conclusion

Comparison 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.
Writing as a sociolinguistic object
Authors: Blommaert Jan
Published: September 2013

Writing has never been a core object of sociolinguistics, and this paper argues for a mature sociolinguistics of writing. Seen from a sociolinguistic viewpoint, writing needs to be seen as a complex of specific resources subject to patterns of distribution, of availability and accessibility. If we take this approach to the field of writing, and unthink the unproductive distinction between ‘language’ and ‘writing’, we can distinguish several specific sets of resources that are required for writing: from infrastructural ones, over graphic ones, linguistic, semantic, pragmatic and metapragmatic ones, to social and cultural ones. These resources form the ‘sub‐molecular’ structure of writing and each of them is subject to different patterns of distribution, leading to specific configurations of writing resources in people's repertoires. Thus, we can arrive at vastly more precise diagnostic analyses of ‘problems’ in writing, and this has a range of important effects.
Texting Africa: Writing as performance
Authors: Deumert Ana , Lexander Kristin Vold
Published: September 2013

This paper discusses African multilingual digital writing, focusing on one digital genre: texting. Our analysis draws on quantitative and qualitative data from five highly multilingual African countries: Côte d'Ivoire, Ghana, Nigeria, Senegal and South Africa. Writers are shown to draw on local as well as global linguistic resources in crafting their messages. Being a good texter requires the performance of ‘textual linguistic dexterity’: the ability to articulate meaning through the skillful use of both global and local forms. Good texters are valued by their audiences not only for the speed with which they reply, but also their ability to ‘play with words’. The quantitative data shows such practices to be widespread, while the qualitative data allows us to understand writers’ motivations and underlying linguistics ideologies. Texting is frequently used in intimate interactions, especially for expressions of love, affection and attraction. Through the juxtaposition of linguistic material, and drawing on the social meanings of different resources within their multilingual repertoires, writers are able to project particular personae and to negotiate various forms of emotional attachment.
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

Although 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

In 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

Parasites 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

Petal 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

Melanoma 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

Paired 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.
Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep
Authors: Koome Miriam E. , Bennet Laura , Booth Lindsea C. , Davidson Joanne O. , Wassink Guido , Gunn Alistair Jan
Published: September 2013

New Findings

What is the central question of this study?

Can power spectral analysis of fetal heart rate variability provide a reliable, objective estimate of autonomic balance before birth?

What is the main finding and its importance?

This study demonstrates that there is a substantial increase in fetal heart rate spectral power over late gestation in chronically instrumented fetal sheep, with changes between sleep states that are consistent with known patterns of autonomic activity. However, parasympathetic blockade with atropine and complete chemical sympathectomy did not support substantial, consistent differences in the frequencies of sympathetic and parasympathetic activity in late gestation, suggesting that this does not provide a reliable index of relative cardiac autonomic activity before birth.

Power spectral analysis of fetal heart rate variability has been proposed to provide a non‐invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0–0.04 Hz), low (0.04–0.15 Hz) and high frequencies (0.15–0.4 Hz), as well as the ratio of low‐ to high‐frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n= 8), 0.7 (n= 7) and 0.8 gestational age (ga; n= 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h−1 for 30 min, n= 6) or 6‐hydroxydopamine (20 mg ml−1 at 2.5 ml h−1 for 3 h; n= 9). Data were analysed by sleep state, defined by low‐voltage–high‐frequency (LV) or high‐voltage–low‐frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P= 0.02). Both atropine (P= 0.05) and 6‐hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late‐gestation fetal sheep.
Characterization of the Bacterial Community of the Chemically Defended Hawaiian Sacoglossan Elysia rufescens
Authors: Davis Jeanette , Fricke W. Florian , Hamann Mark T. , Esquenazi Eduardo , Dorrestein Pieter C. , Hill Russell T.
Published: September 2013

Sacoglossans are characterized by the ability to sequester functional chloroplasts from their algal diet through a process called kleptoplasty, enabling them to photosynthesize. The bacterial diversity associated with sacoglossans is not well understood. In this study, we coupled traditional cultivation-based methods with 454 pyrosequencing to examine the bacterial communities of the chemically defended Hawaiian sacoglossanElysia rufescensand its secreted mucus.E. rufescenscontains a defense molecule, kahalalide F, that is possibly of bacterial origin and is of interest because of its antifungal and anticancer properties. Our results showed that there is a diverse bacterial assemblage associated withE. rufescensand its mucus, with secreted mucus harboring higher bacterial richness than entire-E. rufescenssamples. The most-abundant bacterial groups affiliated withE. rufescensand its mucus areMycoplasmaspp. andVibriospp., respectively. Our analyses revealed that theVibriospp. that were highly represented in the cultivable assemblage were also abundant in the culture-independent community. Epifluorescence microscopy and matrix-assisted laser desorption–ionization mass spectrometry (MALDI-MS) were utilized to detect the chemical defense molecule kahalalide F on a longitudinal section of the sacoglossan.
Survival of Murine Norovirus, Tulane Virus, and Hepatitis A Virus on Alfalfa Seeds and Sprouts during Storage and Germination
Authors: Wang Qing , Hirneisen Kirsten A. , Markland Sarah M. , Kniel Kalmia E.
Published: September 2013

Human norovirus (huNoV) and hepatitis A virus (HAV) have been involved in several produce-associated outbreaks and identified as major food-borne viral etiologies. In this study, the survival of huNoV surrogates (murine norovirus [MNV] and Tulane virus [TV]) and HAV was investigated on alfalfa seeds during storage and postgermination. Alfalfa seeds were inoculated with MNV, TV, or HAV with titers of 6.46 ± 0.06 log PFU/g, 3.87 ± 0.38 log PFU/g, or 7.01 ± 0.07 log 50% tissue culture infectious doses (TCID
50
)/g, respectively. Inoculated seeds were stored for up to 50 days at 22°C and sampled during that storage period on days 0, 2, 5, 10, and 15. Following storage, virus presence was monitored over a 1-week germination period. Viruses remained infectious after 50 days, with titers of 1.61 ± 0.19 log PFU/g, 0.85 ± 0.21 log PFU/g, and 3.43 ± 0.21 log TCID
50
/g for MNV, TV, and HAV, respectively. HAV demonstrated greater persistence than MNV and TV, without a statistically significant reduction over 20 days (<1 log TCID
50
/g); however, relatively high levels of genomic copies of all viruses persisted over the testing time period. Low titers of viruses were found on sprouts and were located in all tissues as well as in sprout-spent water sampled on days 1, 3, and 6 following seed planting. Results revealed the persistence of viruses in seeds for a prolonged period of time, and perhaps of greater importance these data suggest the ease of which virus may transfer from seeds to sprouts and spent water during germination. These findings highlight the importance of sanitation and prevention procedures before and during germination.
Noninvasive Analysis of Microbiome Dynamics in the Fruit Fly Drosophila melanogaster
Authors: Fink Christine , Staubach Fabian , Kuenzel Sven , Baines John F. , Roeder Thomas
Published: September 2013

The diversity and structure of the intestinal microbial community has a strong influence on life history. To understand how hosts and microbes interact, model organisms with comparatively simple microbial communities, such as the fruit fly (
Drosophila melanogaster
), offer key advantages. However, studies of the
Drosophila
microbiome are limited to a single point in time, because flies are typically sacrificed for DNA extraction. In order to test whether noninvasive approaches, such as sampling of fly feces, could be a means to assess fly-associated communities over time on the same cohort of flies, we compared the microbial communities of fly feces, dissected fly intestines, and whole flies across three different
Drosophila
strains. Bacterial species identified in either whole flies or isolated intestines were reproducibly found in feces samples. Although the bacterial communities of feces and intestinal samples were not identical, they shared similarities and obviously the same origin. In contrast to material from whole flies and intestines, feces samples were not compromised by
Wolbachia
spp. infections, which are widespread in laboratory and wild strains. In a proof-of-principle experiment, we showed that simple nutritional interventions, such as a high-fat diet or short-term starvation, had drastic and long-lasting effects on the micobiome. Thus, the analysis of feces can supplement the toolbox for microbiome studies in
Drosophila
, unleashing the full potential of such studies in time course experiments where multiple samples from single populations are obtained during aging, development, or experimental manipulations.
Fatty Alcohols for Wax Esters in Marinobacter aquaeolei VT8: Two Optional Routes in the Wax Biosynthesis Pathway
Authors: Lenneman Eric M. , Ohlert Janet M. , Palani Nagendra P. , Barney Brett M.
Published: September 2013

The biosynthesis of wax esters in bacteria is accomplished by a unique pathway that combines a fatty alcohol and a fatty acyl coenzyme A substrate. Previous
in vitro
enzymatic studies indicated that two different enzymes could be involved in the synthesis of the required fatty alcohol in
Marinobacter aquaeolei
VT8. In this study, we demonstrate through a series of gene deletions and transcriptional analysis that either enzyme is capable of fulfilling the role of providing the fatty alcohol required for wax ester biosynthesis
in vivo
, but evolution has clearly selected one of these, a previously characterized fatty aldehyde reductase, as the preferred enzyme to perform this reaction under typical wax ester-accumulating conditions. These results complement previous
in vitro
studies and provide the first glimpse into the role of each enzyme
in vivo
in the native organism.
Unraveling the Leloir Pathway of Bifidobacterium bifidum: Significance of the Uridylyltransferases
Authors: De Bruyn Frederik , Beauprez Joeri , Maertens Jo , Soetaert Wim , De Mey Marjan
Published: September 2013

The GNB/LNB (galacto-
N
-biose/lacto-
N
-biose) pathway plays a crucial role in bifidobacteria during growth on human milk or mucin from epithelial cells. It is thought to be the major route for galactose utilization in
Bifidobacterium longum
as it is an energy-saving variant of the Leloir pathway. Both pathways are present in
B. bifidum
, and galactose 1-phosphate (gal1P) is considered to play a key role. Due to its toxic nature, gal1P is further converted into its activated UDP-sugar through the action of poorly characterized uridylyltransferases. In this study, three uridylyltransferases (
galT1
,
galT2
, and
ugpA
) from
Bifidobacterium bifidum
were cloned in an
Escherichia coli
mutant and screened for activity on the key intermediate gal1P. GalT1 and GalT2 showed UDP-glucose-hexose-1-phosphate uridylyltransferase activity (EC 2.7.7.12), whereas UgpA showed promiscuous UTP-hexose-1-phosphate uridylyltransferase activity (EC 2.7.7.10). The activity of UgpA toward glucose 1-phosphate was about 33-fold higher than that toward gal1P. GalT1, as part of the bifidobacterial Leloir pathway, was about 357-fold more active than GalT2, the functional analog in the GNB/LNB pathway. These results suggest that GalT1 plays a more significant role than previously thought and predominates when
B. bifidum
grows on lactose and human milk oligosaccharides. GalT2 activity is required only during growth on substrates with a GNB core such as mucin glycans.
Structural and Functional Characterization of the N Terminus of Schizosaccharomyces pombe Cwf10
Authors: Livesay S. Brent , Collier Scott E. , Bitton Danny A. , Bähler Jürg , Ohi Melanie D.
Published: September 2013

The spliceosome is a dynamic macromolecular machine that catalyzes the removal of introns from pre-mRNA, yielding mature message.
Schizosaccharomyces pombe
Cwf10 (homolog of
Saccharomyces cerevisiae
Snu114 and human U5-116K), an integral member of the U5 snRNP, is a GTPase that has multiple roles within the splicing cycle. Cwf10/Snu114 family members are highly homologous to eukaryotic translation elongation factor EF2, and they contain a conserved N-terminal extension (NTE) to the EF2-like portion, predicted to be an intrinsically unfolded domain. Using
S. pombe
as a model system, we show that the NTE is not essential, but cells lacking this domain are defective in pre-mRNA splicing. Genetic interactions between
cwf10
-Δ
NTE
and other pre-mRNA splicing mutants are consistent with a role for the NTE in spliceosome activation and second-step catalysis. Characterization of Cwf10-NTE by various biophysical techniques shows that in solution the NTE contains regions of both structure and disorder. The first 23 highly conserved amino acids of the NTE are essential for its role in splicing but when overexpressed are not sufficient to restore pre-mRNA splicing to wild-type levels in
cwf10
-Δ
NTE
cells. When the entire NTE is overexpressed in the
cwf10
-Δ
NTE
background, it can complement the truncated Cwf10 protein in
trans
, and it immunoprecipitates a complex similar in composition to the late-stage U5.U2/U6 spliceosome. These data show that the structurally flexible NTE is capable of independently incorporating into the spliceosome and improving splicing function, possibly indicating a role for the NTE in stabilizing conformational rearrangements during a splice cycle.
Mutations on the N-Terminal Edge of the DELSEED Loop in either the α or β Subunit of the Mitochondrial F
1
-ATPase Enhance ATP Hydrolysis in the Absence of the Central γ Rotor
Authors: La Thuy , Clark-Walker George Desmond , Wang Xiaowen , Wilkens Stephan , Chen Xin Jie
Published: September 2013

F
1
-ATPase is a rotary molecular machine with a subunit stoichiometry of α
3
β
3
γ
1
δ
1
ε
1
. It has a robust ATP-hydrolyzing activity due to effective cooperativity between the three catalytic sites. It is believed that the central γ rotor dictates the sequential conformational changes to the catalytic sites in the α
3
β
3
core to achieve cooperativity. However, recent studies of the thermophilic
Bacillus
PS3 F
1
-ATPase have suggested that the α
3
β
3
core can intrinsically undergo unidirectional cooperative catalysis (T. Uchihashi et al., Science 333:755-758, 2011). The mechanism of this γ-independent ATP-hydrolyzing mode is unclear. Here, a unique genetic screen allowed us to identify specific mutations in the α and β subunits that stimulate ATP hydrolysis by the mitochondrial F
1
-ATPase in the absence of γ. We found that the F446I mutation in the α subunit and G419D mutation in the β subunit suppress cell death by the loss of mitochondrial DNA (ρ
o
) in a
Kluyveromyces lactis
mutant lacking γ.
In organello
ATPase assays showed that the mutant but not the wild-type γ-less F
1
complexes retained 21.7 to 44.6% of the native F
1
-ATPase activity. The γ-less F
1
subcomplex was assembled but was structurally and functionally labile
in vitro
. Phe446 in the α subunit and Gly419 in the β subunit are located on the N-terminal edge of the DELSEED loops in both subunits. Mutations in these two sites likely enhance the transmission of catalytically required conformational changes to an adjacent α or β subunit, thereby allowing robust ATP hydrolysis and cell survival under ρ
o
conditions. This work may help our understanding of the structural elements required for ATP hydrolysis by the α
3
β
3
subcomplex.