bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying ecological responses to amplified water level fluctuations in standing waters: an experimental approach
Authors: Evtimova Vesela V. , Donohue Ian
Published: May 2014

Global freshwater demand is increasing dramatically, with water withdrawal rates more than tripling in the last five decades. Consequently, alteration of water level regimes, particularly in the form of amplified water level fluctuations (WLF), is rapidly becoming one of the major disturbances of aquatic ecosystems globally. However, even though the impacts of WLF are likely to be strongest in littoral zones, little is known about their effects on the structure and functioning of littoral assemblages in standing water systems.

We established an experiment in large outdoor pond mesocosms to examine the effects of WLF on littoral assemblages and explore the potential for development of ecological indicators of WLF.

Water level fluctuations reduced benthic algal biomass and the density and taxonomic distinctness of benthic invertebrate assemblages. Both the taxonomic and trophic structure of benthic assemblages were altered significantly in ponds with WLF and homogenized along the depth gradient.

Synthesis and applications. Our results indicate that water level fluctuations (WLF) can reduce considerably the productivity and biological diversity of lake littoral zones. Given that the problem is likely to be exacerbated by predicted increases in climatic variability and enhanced demand for water and hydropower, our findings have important implications for the conservation and management of global aquatic biodiversity. We identified several specific ways that WLF modify littoral assemblages along the depth gradient. This ability to identify separate pressures is an important requirement of robust ecological assessment tools. This study confers potential for development of ecological indicators of WLF in standing waters, provides indication of sampling strategies to be employed and demonstrates the need to mitigate the most extreme water withdrawals.
REVIEW: China's transboundary waters: new paradigms for water and ecological security through applied ecology
Authors: He Daming , Wu Ruidong , Feng Yan , Li Yungang , Ding Chengzhi , Wang Wenling , Yu Douglas W.
Published: May 2014

China is Asia's most important upstream riparian country, sharing 110 rivers and lakes with 18 downstream countries. Consequently, China's management of transboundary water resources must consider both environmental and geopolitical risks.

The major threats to and conflicts over international rivers in China revolve around biotic homogenisation due to the installation of transport links, water allocation, water pollution, alteration of natural flow patterns and disruption of fisheries due to the installation of hydropower dams, and droughts and floods exacerbated by climate change. Because these problems have an international component, they fall under China's Peaceful Rise strategy, mandating that transboundary conflicts be resolved amicably as part of the overarching goal of increasing regional economic growth with as little conflict as possible.

Science‐backed policy is more likely to result in long term, mutually agreeable solutions; the results of applied ecological research have already resulted in a number of mitigation measures, including setting operational thresholds to reduce the downstream impact of dams, designating protected areas along key river stretches where dams cannot be installed (one dam in a critical location has been cancelled), and the installation of terrestrial protected‐area networks.

Synthesis and applications. Applied ecology will continue to play an important role in the diagnosis and resolution of environmental threats to China's transboundary waters. More importantly, applied ecology can inform the development of a transboundary environmental compensation mechanism and regional consultative mechanisms that support informed, cooperative decision‐making for China and its riparian neighbours.
Small RNA deep sequencing‐based detection and further evidence of DNA viruses infecting sweetpotato plants in Tanzania
Authors: Mbanzibwa D.R. , Tugume A.K. , Chiunga E. , Mark D. , Tairo F.D.
Published: May 2014

Small interfering RNA deep sequencing (SRDS) was used to detect viruses in 23 sweetpotato plants, collected from various locations in Tanzania. Alignment of small RNA reads using a MAQ program recovered genomes of viruses from five families, namely Geminiviridae (2), Closteroviridae (1), Betaflexiviridae (1), Caulimoviridae (1) and Potyviridae (1). This was in agreement with the variation of symptoms observed on sweetpotato plants in fields and screen house, which included leaf curl, vein yellowing, chlorosis, stunted growth and brown blotches. PCR was also used to confirm the occurrence of viruses associated with leaf curl and symptomless infections. A complete genome (2768 nucleotides) was obtained for a sweepovirus that was 89.9% identical to the strain of Sweet potato leaf curl Sao Paulo virus (SPLCSPV; Begomovirus) reported in South Africa. Sweepoviruses are known to undergo frequent recombinations and evidence for this was found in the SPLCSPV sequence studied. The SRDS‐based results indicated occurrence of the poorly studied Sweet potato badnavirus B (SPBV‐B) and Sweet potato badnavirus A (collectively known as Sweet potato pakakuy virus; SPPV; Caulimoviridae) in sweetpotato plants in Tanzania. A 5′‐end partial sequence (3065 nucleotides), encoding hypothetical, movement and coat proteins, was obtained and found to be 86.3% and 73.1% identical to SPBV‐B and SPBV‐A, respectively. A survey for the distribution of SPPV and Sweet potato symptomless mastrevirus 1 (SPSMV‐1) showed that these viruses were wide spread and co‐infecting sweetpotato plants in Tanzania. The importance of East Africa as a hot spot for the diversity and evolution of sweet potato viruses is discussed.
Monitoring of occupational and environmental aeroallergens – EAACI Position Paper
Authors: Raulf M. , Buters J. , Chapman M. , Cecchi L. , de Blay F. , Doekes G. , Eduard W. , Heederik D. , Jeebhay M. F. , Kespohl S. , Krop E. , Moscato G. , Pala G. , Quirce S. , Sander I. , Schlünssen V. , Sigsgaard T. , Walusiak‐Skorupa J. , Wiszniewska M. , Wouters I. M. , Annesi‐Maesano I.
Published: June 2014

Exposure to high molecular weight sensitizers of biological origin is an important risk factor for the development of asthma and rhinitis. Most of the causal allergens have been defined based on their reactivity with IgE antibodies, and in many cases, the molecular structure and function of the allergens have been established. Significant information on allergen levels that cause sensitization and allergic symptoms for several major environmental and occupational allergens has been reported. Monitoring of high molecular weight allergens and allergen carrier particles is an important part of the management of allergic respiratory diseases and requires standardized allergen assessment methods for occupational and environmental (indoor and outdoor) allergen exposure. The aim of this EAACI task force was to review the essential points for monitoring environmental and occupational allergen exposure including sampling strategies and methods, processing of dust samples, allergen analysis, and quantification. The paper includes a summary of different methods for sampling and allergen quantification, as well as their pros and cons for various exposure settings. Recommendations are being made for different exposure scenarios.
Low‐grade prostate cancer diverges early from high grade and metastatic disease
Authors: VanderWeele David J. , Brown Christopher D. , Taxy Jerome B. , Gillard Marc , Hatcher David M. , Tom Westin R. , Stadler Walter M. , White Kevin P.
Published: May 2014

Understanding the developmental relationship between indolent and aggressive tumors is central to understanding disease progression and making treatment decisions. For example, most men diagnosed with prostate cancer have clinically indolent disease and die from other causes. Overtreatment of prostate cancer remains a concern. Here we use laser microdissection followed by exome sequencing of low‐ and high‐grade prostate cancer foci from four subjects, and metastatic disease from two of those subjects, to evaluate the molecular relationship of coincident cancer foci. Seventy of 79 (87%) high‐confidence somatic mutations in low‐grade disease were private to low‐grade foci. In contrast, high‐grade foci and metastases harbored many of the same mutations. In cases in which there was a metastatic focus, 15 of 80 (19%) high‐confidence somatic mutations in high‐grade foci were private. Seven of the 80 (9%) were shared with low‐grade foci and 65 (82%) were shared with metastatic foci. Notably, mutations in cancer‐associated genes and the p53 signaling pathway were found exclusively in high‐grade foci and metastases. The pattern of mutations is consistent with early divergence between low‐ and high‐grade foci and late divergence between high‐grade foci and metastases. These data provide insights into the development of high‐grade and metastatic prostate cancer.
Impression management during evaluation and psychological reactions post‐donation of living kidney donors
Authors: Hildebrand Lee , Melchert Timothy P. , Anderson Rebecca C.
Published: May 2014

Many healthcare providers have been concerned about the extent to which potential kidney donors use impression management or concealment of important information regarding their medical history, current functioning, or other circumstances that could affect whether they are accepted as donors. To date, however, there has been very little empirical examination of these questions. It is also not known whether donors' use of impression management pre‐donation is related to their reactions and adjustment post‐donation.

Methods

This study surveyed 76 individuals who had donated a kidney one to six yr previously regarding their use of impression management and their concealing of information during their psychological evaluations. They were also asked about their reactions to the donation and whether they would make the same decision again. In addition, 21 of these donors participated in focus groups that explored these questions in depth.

Results

Many of the kidney donors reported that they possessed very strong motivation to donate and consequently used impression management in their interactions with medical professionals pre‐donation. Very few donors, however, indicated that they concealed information during their pre‐donation evaluations. The donors' psychological reactions post‐donation were generally positive, and nearly all indicated that they would make the same decision again.
Applying evolutionary concepts to wildlife disease ecology and management
Authors: Vander Wal Eric , Garant Dany , Calmé Sophie , Chapman Colin A. , Festa‐Bianchet Marco , Millien Virginie , Rioux‐Paquette Sébastien , Pelletier Fanie
Published: May 2014

Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio‐economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host–pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco‐evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment–disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management.
Does therapeutic intervention in atopic dermatitis normalize epidermal Notch deficiency?
Authors: Melnik Bodo C.
Published: May 2014

This viewpoint presents a unifying concept for the treatment of atopic dermatitis (AD) that is based on the improvement of deficient Notch signalling, which appears to represent the fundamental epithelial defect of AD resulting in epidermal and immunological barrier dysfunction. One study of AD patients demonstrated a marked epidermal deficiency of Notch receptors and several mouse models with genetically suppressed Notch signalling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and Th2 cell‐mediated immunological changes closely resembling human AD. Notch signalling is critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in the repression of activating protein‐1 (AP‐1), the regulation of late epidermal differentiation associated with filaggrin‐ and stratum corneum barrier lipid processing, in aquaporin 3‐ and claudin‐1 expression and in keratinocyte‐mediated release of thymic stromal lymphopoietin (TSLP), which promotes Th2‐driven immune responses with TSLP‐ and IL‐31‐mediated stimulation of cutaneous sensory neurons involved in the induction of itch. Translational evidence will be provided that all major therapeutic regimens employed for the treatment of AD such as glucocorticoids, calcineurin inhibitors and UV radiation may converge in the upregulation of impaired Notch signalling, the proposed pathogenic defect of AD.
Topical application of the adenosine A2A receptor agonist CGS‐21680 prevents phorbol‐induced epidermal hyperplasia and inflammation in mice
Authors: Arasa Jorge , Martos Patricio , Terencio María Carmen , Valcuende‐Cavero Francisca , Montesinos María Carmen
Published: May 2014

The nucleoside adenosine is a known regulator of immunity and inflammation that mediates, at least in part, the anti‐inflammatory effect of methotrexate, an immunosuppressive agent widely used to treat autoimmune inflammatory diseases. Adenosine A2A receptors play a key role in the inhibition of the inflammatory process besides promoting wound healing. Therefore, we aimed to determine the topical effect of a selective agonist, CGS‐21680, on a murine model of skin hyperplasia with a marked inflammatory component. Pretreatment with either CGS‐21680 (5 μg per site) or the reference agent dexamethasone (200 μg/site) prevented the epidermal hyperplasia and inflammatory response induced by topical application of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA, 2 nmol/site) for three consecutive days. The histological analysis showed that both CGS‐21680 and dexamethasone produced a marked reduction of inflammatory cell infiltrate, which correlated with diminished myeloperoxidase (MPO) activity in skin homogenates. Both treatments reduced the levels of the chemotactic mediators LTB4 and CXCL‐1, and the inflammatory cytokine TNF‐α, through the suppression of NFκB phosphorylation. The immunohistochemical analysis of the hyperproliferative markers cytokeratin 6 (CK6) and Ki67 revealed that while both agents inhibit the number of proliferating cells in the epidermis, CGS‐21680 treatment promoted dermal fibroblasts proliferation. Consistently, increased collagen deposition in dermis was observed in tissue sections from agonist‐treated mice. Our results showed that CGS 21680 efficiently prevents phorbol‐induced epidermal hyperplasia and inflammation in mice without the deleterious atrophic effect of topical corticosteroids.
Employee post‐training behaviour and performance: evaluating the results of the training process
Authors: Diamantidis Anastasios D. , Chatzoglou Prodromos D.
Published: May 2014

Despite the fact that firms invest in training, there is considerable evidence to show that training programmes often fail to achieve the intended result of improving worker and organization performance. The purpose of this paper is to examine the medium‐ to long‐term effects of training programmes on firms by means of an integrated research model combining the principal factors that the existing literature has shown to be related to training transfer and also by examining the relationship between training transfer and operational performance. The transfer factors chosen are training design, trainee self‐efficacy and work environment. The validity of this model is tested by applying the structural equation modelling approach to data from 126 employees who have participated in various training programmes in a number of Greek organizations. The results indicate that the design of a training programme has the strongest impact on post‐training job performance, along with trainees' self‐efficacy and post‐training behaviour.
The serodominant secreted effector protein of Salmonella, SseB, is a strong CD4 antigen containing an immunodominant epitope presented by diverse HLA class II alleles
Authors: Reynolds Catherine J. , Jones Claire , Blohmke Christoph J. , Darton Thomas C. , Goudet Amelie , Sergeant Ruhena , Maillere Bernard , Pollard Andrew J. , Altmann Daniel M. , Boyton Rosemary J.
Published: May 2014

Detailed characterization of the protective T‐cell response in salmonellosis is a pressing unmet need in light of the global burden of human Salmonella infections and the likely contribution of CD4 T cells to immunity against this intracellular infection. In previous studies screening patient sera against antigen arrays, SseB was noteworthy as a serodominant target of adaptive immunity, inducing significantly raised antibody responses in HIV‐seronegative compared with seropositive patients. SseB is a secreted protein, part of the Espa superfamily, localized to the bacterial surface and forming part of the translocon of the type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2. We demonstrate here that SseB is also a target of CD4 T‐cell immunity, generating a substantial response after experimental infection in human volunteers, with around 0·1% of the peripheral repertoire responding to it. HLA‐DR/peptide binding studies indicate that this protein encompasses a number of peptides with ability to bind to several different HLA‐DR alleles. Of these, peptide 11 (p11) was shown in priming of both HLA‐DR1 and HLA‐DR4 transgenic mice to contain an immunodominant CD4 epitope. Analysis of responses in human donors showed immunity focused on p11 and another epitope in peptide 2. The high frequency of SseB‐reactive CD4 T cells and the broad applicability to diverse HLA genotypes coupled with previous observations of serodominance and protective vaccination in mouse challenge experiments, make SseB a plausible candidate for next‐generation Salmonella vaccines.
miR‐155 deficiency protects mice from experimental colitis by reducing T helper type 1/type 17 responses
Authors: Singh Udai P. , Murphy Angela E. , Enos Reilly T. , Shamran Haidar A. , Singh Narendra P. , Guan Honbing , Hegde Venkatesh L. , Fan Daping , Price Robert L. , Taub Dennis D. , Mishra Manoj K. , Nagarkatti Mitzi , Nagarkatti Prakash S.
Published: May 2014

Inflammatory bowel disease (IBD), a chronic intestinal inflammatory condition that affects millions of people worldwide, results in high morbidity and exorbitant health‐care costs. The critical features of both innate and adaptive immunity are to control inflammation and dysfunction in this equilibrium is believed to be the reason for the development of IBD. miR‐155, a microRNA, is up‐regulated in various inflammatory disease states, including IBD, and is a positive regulator of T‐cell responses. To date, no reports have defined a function for miR‐155 with regard to cellular responses in IBD. Using an acute experimental colitis model, we found that miR‐155−/− mice, as compared to wild‐type control mice, have decreased clinical scores, a reversal of colitis‐associated pathogenesis, and reduced systemic and mucosal inflammatory cytokines. The increased frequency of CD4+ lymphocytes in the spleen and lamina propria with dextran sodium sulphate induction was decreased in miR‐155−/− mice. Similarly, miR‐155 deficiency abrogated the increased numbers of interferon‐γ expressing CD4+ T cells typically observed in wild‐type mice in this model. The frequency of systemic and mucosal T helper type 17‐, CCR9‐expressing CD4+ T cells was also reduced in miR‐155−/− mice compared with control mice. These findings strongly support a role for miR‐155 in facilitating pro‐inflammatory cellular responses in this model of IBD. Loss of miR‐155 also results in decreases in T helper type 1/type 17, CD11b+, and CD11c+ cells, which correlated with reduced clinical scores and severity of disease. miR‐155 may serve as a potential therapeutic target for the treatment of IBD.
25‐hydroxyvitamin D and increased all‐cause mortality in very old women: the Newcastle 85+ study
Authors: Granic A. , Aspray T. , Hill T. , Davies K. , Collerton J. , Martin‐Ruiz C. , von Zglinicki T. , Kirkwood T. B. L. , Mathers J. C. , Jagger C.
Published: May 2014

Objective

To investigate the associations between low and high concentrations of baseline serum 25‐hydroxyvitamin D [25(OH)D] and all‐cause mortality in very old (≥85 years) men and women over 6 years.

Design, setting and subjects

Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season‐specific quartiles and predefined cut‐off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D‐containing supplements and medication) cohorts.

Results

For the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season‐specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01–1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12–1.85, P = 0.004] compared with the combined middle quartiles (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06–1.77, P = 0.02) and was seen only in women in sex‐specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut‐off values, the highest 25(OH)D concentration (≥75 nmol L−1) was associated with a 2.4‐fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates.

Conclusion

Low and high season‐specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D‐containing supplements/medication.
Existence and Extent of Operations and Supply Management Departmental Thought Worlds: An Empirical Study
Authors: Niranjan Tarikere T. , Rao Shashank , Sengupta Sourav , Wagner Stephan M.
Published: May 2014

Operations and supply chain management (OSM) solutions typically assume that the decision makers in different organizational roles know the key supply chain parameters equally well. Our research questions this assumption by employing two detailed case studies. Study 1 develops the OSM departmental thought worlds (DTW) construct and examines how and why they occur, with reference to supply chain breakdown. Study 2 measures the extent of OSM DTW with reference to total cost of ownership (TCO) of bought parts. We find that organizational roles indeed shape perceptions of the task environment, and these perceptions follow a predictable pattern. An insight into this influence of DTW is essential for OSM tools to work in practice. In particular, model‐based approaches must consider that even if different departments agree on the objective function, the parameter values may differ across departments, leading to divergent solutions.
Short‐term variations in gene flow related to cyclic density fluctuations in the common vole
Authors: Gauffre Bertrand , Berthier Karine , Inchausti Pablo , Chaval Yannick , Bretagnolle Vincent , Cosson Jean‐François
Published: May 2014

In highly fluctuating populations with complex social systems, genetic patterns are likely to vary in space and time due to demographic and behavioural processes. Cyclic rodents are extreme examples of demographically instable populations that often exhibit strong social organization. In such populations, kin structure and spacing behaviour may vary with density fluctuations and impact both the composition and spatial structure of genetic diversity. In this study, we analysed the multiannual genetic structure of a cyclic rodent, Microtus arvalis, using a sample of 875 individuals trapped over three complete cycles (from 1999 to 2007) and genotyped at 10 microsatellite loci. We tested the predictions that genetic diversity and gene flow intensity vary with density fluctuations. We found evidences for both spatial scale‐dependant variations in genetic diversity and higher gene flow during high density. Moreover, investigation of sex‐specific relatedness patterns revealed that, although dispersal is biased toward males in this species, distances moved by both sexes were lengthened during high density. Altogether, these results suggest that an increase in migration with density allows to restore the local loss of genetic diversity occurring during low density. We then postulate that this change in migration results from local competition, which enhances female colonization of empty spaces and male dispersal among colonies.
Effects of long‐term differential fertilization on eukaryotic microbial communities in an arable soil: a multiple barcoding approach
Authors: Lentendu Guillaume , Wubet Tesfaye , Chatzinotas Antonis , Wilhelm Christian , Buscot François , Schlegel Martin
Published: May 2014

To understand the fine‐scale effects of changes in nutrient availability on eukaryotic soil microorganisms communities, a multiple barcoding approach was used to analyse soil samples from four different treatments in a long‐term fertilization experiment. We performed PCR amplification on soil DNA with primer pairs specifically targeting the 18S rRNA genes of all eukaryotes and three protist groups (Cercozoa, Chrysophyceae‐Synurophyceae and Kinetoplastida) as well as the ITS gene of fungi and the 23S plastid rRNA gene of photoautotrophic microorganisms. Amplicons were pyrosequenced, and a total of 88 706 quality filtered reads were clustered into 1232 operational taxonomic units (OTU) across the six data sets. Comparisons of the taxonomic coverage achieved based on overlapping assignment of OTUs revealed that half of the eukaryotic taxa identified were missed by the universal eukaryotic barcoding marker. There were only little differences in OTU richness observed between organic‐ (farmyard manure), mineral‐ and nonfertilized soils. However, the community compositions appeared to be strongly structured by organic fertilization in all data sets other than that generated using the universal eukaryotic 18S rRNA gene primers, whereas mineral fertilization had only a minor effect. In addition, a co‐occurrence based network analysis revealed complex potential interaction patterns between OTUs from different trophic levels, for example between fungivorous flagellates and fungi. Our results demonstrate that changes in pH, moisture and organic nutrients availability caused shifts in the composition of eukaryotic microbial communities at multiple trophic levels.
Gene expression plasticity evolves in response to colonization of freshwater lakes in threespine stickleback
Authors: Morris Matthew R. J. , Richard Romain , Leder Erica H. , Barrett Rowan D. H. , Aubin‐Horth Nadia , Rogers Sean M.
Published: May 2014

Phenotypic plasticity is predicted to facilitate individual survival and/or evolve in response to novel environments. Plasticity that facilitates survival should both permit colonization and act as a buffer against further evolution, with contemporary and derived forms predicted to be similarly plastic for a suite of traits. On the other hand, given the importance of plasticity in maintaining internal homeostasis, derived populations that encounter greater environmental heterogeneity should evolve greater plasticity. We tested the evolutionary significance of phenotypic plasticity in coastalBritishColumbian postglacial populations of threespine stickleback (Gasterosteus aculeatus) that evolved under greater seasonal extremes in temperature after invading freshwater lakes from the sea. Two ancestral (contemporary marine) and two derived (contemporary freshwater) populations of stickleback were raised near their thermal tolerance extremes, 7 and 22 °C. Gene expression plasticity was estimated for more than 14 000 genes. Over five thousand genes were similarly plastic in marine and freshwater stickleback, but freshwater populations exhibited significantly more genes with plastic expression than marine populations. Furthermore, several of the loci shown to exhibit gene expression plasticity have been previously implicated in the adaptive evolution of freshwater populations, including a gene involved in mitochondrial regulation (PPARAa). Collectively, these data provide molecular evidence that highlights the importance of plasticity in colonization and adaptation to new environments.
Genome diversity in Brachypodium distachyon: deep sequencing of highly diverse inbred lines
Authors: Gordon Sean P. , Priest Henry , Des Marais David L. , Schackwitz Wendy , Figueroa Melania , Martin Joel , Bragg Jennifer N. , Tyler Ludmila , Lee Cheng‐Ruei , Bryant Doug , Wang Wenqin , Messing Joachim , Manzaneda Antonio J. , Barry Kerrie , Garvin David F. , Budak Hikmet , Tuna Metin , Mitchell‐Olds Thomas , Pfender William F. , Juenger Thomas E. , Mockler Todd C. , Vogel John P.
Published: May 2014

Brachypodium distachyon is small annual grass that has been adopted as a model for the grasses. Its small genome, high‐quality reference genome, large germplasm collection, and selfing nature make it an excellent subject for studies of natural variation. We sequenced six divergent lines to identify a comprehensive set of polymorphisms and analyze their distribution and concordance with gene expression. Multiple methods and controls were utilized to identify polymorphisms and validate their quality. mRNA‐Seq experiments under control and simulated drought‐stress conditions, identified 300 genes with a genotype‐dependent treatment response. We showed that large‐scale sequence variants had extremely high concordance with altered expression of hundreds of genes, including many with genotype‐dependent treatment responses. We generated a deep mRNA‐Seq dataset for the most divergent line and created a de novo transcriptome assembly. This led to the discovery of >2400 previously unannotated transcripts and hundreds of genes not present in the reference genome. We built a public database for visualization and investigation of sequence variants among these widely used inbred lines.
Respiratory modulation of muscle sympathetic nerve activity in obstructive sleep apnoea
Authors: Fatouleh Rania , McKenzie David K. , Macefield Vaughan G.
Published: May 2014

New Findings

What is the central question of this study?

Muscle sympathetic nerve activity (MSNA) is increased in obstructive sleep apnoea (OSA), leading to hypertension. Is this due to an increase in respiratory–sympathetic coupling, as has been demonstrated in the spontaneously hypertensive rat?

What is the main finding and its importance?

Using direct microelectrode recordings of MSNA in hypertensive OSA patients and normotensive control subjects, we show that the magnitude of respiratory modulation is not increased in OSA, arguing against an amplified respiratory–sympathetic coupling as the underlying cause of the neurogenic hypertension, although the temporal coupling of MSNA to respiration was stronger in OSA.

Obstructive sleep apnoea (OSA) is associated with elevated muscle sympathetic nerve activity (MSNA) during normoxic daytime wakefulness, leading to hypertension. We tested the hypothesis that respiratory–sympathetic coupling, postulated to be the underlying cause of neurogenic hypertension, is increased in OSA. Muscle sympathetic nerve activity, blood pressure, ECG and respiration were recorded in 21 normotensive control subjects and 21 newly diagnosed patients with OSA before and after 6 and 12 months of treatment with continuous positive airway pressure. Muscle sympathetic nerve activity was recorded via tungsten microelectrodes inserted percutaneously into the peroneal nerve. Cardiac and respiratory modulation of MSNA was quantified from the cross‐correlation histograms constructed between the sympathetic spikes and either ECG or respiration. Muscle sympathetic nerve activity was significantly elevated in newly diagnosed OSA patients compared with control subjects (53 ± 2 versus 28 ± 2 bursts min−1). There was a significant fall in MSNA after 6 months of continuous positive airway pressure (37 ± 2 bursts min−1), with no further change after 12 months (37 ± 2 bursts min−1). There were no significant differences in the magnitude of respiratory modulation of MSNA between the OSA patients and control subjects (40 ± 3.1 versus 39 ± 3.4%). However, when considering the normalized temporal profile there were changes in the respiratory patterning of MSNA in OSA, with more activity occurring in postinspiration and less in inspiration and expiration. This was largely reversed following long‐term continuous positive airway pressure.
The degree of acute descending control of spinal nociception in an area of primary hyperalgesia is dependent on the peripheral domain of afferent input
Authors: Drake Robert A. R. , Hulse Richard P. , Lumb Bridget M. , Donaldson Lucy F.
Published: May 2014

Key points

Acute inflammation engages various descending control systems in the brain that alter the resulting inflammatory pain, usually by inhibiting it.

In this study we looked at the differences in inhibition of acute (up to 3 h) inflammatory pain from smooth (glabrous) and hairy skin in the rat hind foot.

In hairy skin, inflammatory pain is rapidly inhibited by descending systems that release noradrenaline, but not opiates, into the spinal cord.

In glabrous skin, neither descending noradrenergic nor opioidergic controls affect inflammatory pain.

These results tell us that the controls on the spinal processing of cutaneous inflammatory pain differ according to the skin type affected.

Descending controls of spinal nociceptive processing play a critical role in the development of inflammatory hyperalgesia. Acute peripheral nociceptor sensitization drives spinal sensitization and activates spino–supraspinal–spinal loops leading to descending inhibitory and facilitatory controls of spinal neuronal activity that further modify the extent and degree of the pain state. The afferent inputs from hairy and glabrous skin are distinct with respect to both the profile of primary afferent classes and the degree of their peripheral sensitization. It is not known whether these differences in afferent input differentially engage descending control systems to different extents or in different ways. Injection of complete Freund's adjuvant resulted in inflammation and swelling of hairy hind foot skin in rats, a transient thermal hyperalgesia lasting <2 h, and longlasting primary mechanical hyperalgesia (≥7 days). Much longer lasting thermal hyperalgesia was apparent in glabrous skin (1 h to >72 h). In hairy skin, transient hyperalgesia was associated with sensitization of withdrawal reflexes to thermal activation of either A‐ or C‐nociceptors. The transience of the hyperalgesia was attributable to a rapidly engaged descending inhibitory noradrenergic mechanism, which affected withdrawal responses to both A‐ and C‐nociceptor activation and this could be reversed by intrathecal administration of yohimbine (α‐2‐adrenoceptor antagonist). In glabrous skin, yohimbine had no effect on an equivalent thermal inflammatory hyperalgesia. We conclude that acute inflammation and peripheral nociceptor sensitization in hind foot hairy skin, but not glabrous skin, rapidly activates a descending inhibitory noradrenergic system. This may result from differences in the engagement of descending control systems following sensitization of different primary afferent classes that innervate glabrous and hairy skin.
Nociceptive primary afferents: they have a mind of their own
Authors: Carlton Susan M.
Published: May 2014

Nociceptive primary afferents have three surprising properties: they are highly complex in their expression of neurotransmitters and receptors and most probably participate in autocrine and paracrine interactions; they are capable of exerting tonic and activity‐dependent inhibitory control over incoming nociceptive input; they can generate signals in the form of dorsal root reflexes that are transmitted antidromically out to the periphery and these signals can result in neurogenic inflammation in the innervated tissue. Thus, nociceptive primary afferents are highly complicated structures, capable of modifying input before it is ever transmitted to the central nervous system and capable of altering the tissue they innervate.
Diet‐dependent modulation of gastro‐oesphageal vagal afferent mechanosensitivity by endogenous nitric oxide
Authors: Kentish Stephen J. , O'Donnell Tracey A. , Wittert Gary A. , Page Amanda J.
Published: May 2014

Key points

Nitric oxide (NO) is an important signalling molecule found in the gastrointestinal tract, which can modulate the mechanosensitivity of gastro‐oesophageal vagal afferents.

It is known that the effects of NO on food intake depend on feeding status, but the effect of NO on gastro‐oesophageal vagal afferents in different feeding conditions is unknown.

We show that in the fed state endogenous NO inhibits mucosal afferents through a pathway involving nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.

In mice fasted overnight endogenous NO potentiates the response of mucosal stroking‐ and tension‐sensitive afferents to mechanical stimuli via a mechanism involving hyperpolarisation‐activated cyclic nucleotide‐gated 3 (HCN3) channels.

These results show the role of NO in the peripheral modulation of gastro‐oesophageal vagal afferents is dynamic and dependent on feeding status.

Neuronal nitric oxide (NO) plays an important role in gastric motor activity and modulates the mechanosensitivity of gastro‐oesophageal vagal afferents. Effects of NO on food intake are dependent on feeding status. We sought to determine the effect of NO on gastro‐oesophageal vagal afferent activity in the normally fed and food‐restricted states and the second messenger pathways mediating these effects. Eight week old female C56BL/6 mice were fed ad libitum or food restricted for 14 h. An in vitro preparation was used to determine the functional effects of NO and the second messenger pathways involved. Expression of NO signal transduction molecules in vagal afferents was determined by reverse‐transcription polymerase chain reaction (RT‐PCR). Endogenous NO and the NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP) inhibited vagal mucosal afferent responses to tactile stimuli in mice fed ad libitum. After a 14 h fast endogenous NO and SNAP potentiated tension and mucosal afferent responses to mechanical stimulation. The excitatory effect of NO was blocked by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin. After a 14 h fast expression of NADPH oxidase 2 (NOX2) mRNA in whole nodose ganglia was significantly reduced and the excitatory effect of NO on gastro‐oesophageal vagal afferents was lost. Under fasting conditions the inhibitory effect of NO was blocked with the hyperpolarisation‐activated cyclic nucleotide‐gated (HCN) channel blocker ivabradine and mRNA expression of HCN3 in the nodose ganglia was elevated. In conclusion, the role of NO in the peripheral modulation of gastro‐oesophageal vagal afferents is dynamic and dependent on feeding status.
Cholinergic circuit modulation through differential recruitment of neocortical interneuron types during behaviour
Authors: Poorthuis Rogier B. , Enke Leona , Letzkus Johannes J.
Published: May 2014

Acetylcholine is a crucial neuromodulator for attention, learning and memory. Release of acetylcholine in primary sensory cortex enhances processing of sensory stimuli, and many in vitro studies have pinpointed cellular mechanisms that could mediate this effect. In contrast, how cholinergic modulation shapes the function of intact circuits during behaviour is only beginning to emerge. Here we review recent data on the recruitment of identified interneuron types in neocortex by cholinergic signalling, obtained with a combination of genetic targeting of cell types, two‐photon imaging and optogenetics. These results suggest that acetylcholine release during basal forebrain stimulation, and during physiological recruitment of the basal forebrain, can strongly and rapidly influence the firing of neocortical interneurons. In contrast to the traditional view of neuromodulation as a relatively slow process, cholinergic signalling can thus rapidly convey time‐locked information to neocortex about the behavioural state of the animal and the occurrence of salient sensory stimuli. Importantly, these effects strongly depend on interneuron type, and different interneuron types in turn control distinct aspects of circuit function. One prominent effect of phasic acetylcholine release is disinhibition of pyramidal neurons, which can facilitate sensory processing and associative learning.
Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal muscle
Authors: Tan Nhi , Lansman Jeffry B.
Published: May 2014

Key points

Loss of the cytoskeletal protein dystrophin leads to muscle degeneration in Duchenne muscular dystrophy. The mdx mouse lacks dystrophin but muscle disease is mild, in part because upregulation of utrophin compensates for dystrophin. Evidence suggests that Ca2+ entry through mechanosensitive (MS) ion channels contributes to disease pathogenesis, but the role of utrophin in regulating Ca2+ entry has not been studied.

Depletion of utrophin in mdx mice produces a gene dose‐dependent increase in MS channel open probability, single‐channel conductance in some patches, and an increase in the pressure required to MS channels. The overall effect of loss of utrophin is increased Ca2+ entry.

The results suggest utrophin organizes local membrane microdomains containing MS channels. Disruption of these domains causes changes in membrane composition, which favour channel open states and subunit aggregation. Utrophin‐replacement therapies may act by correcting MS channel gating, and specific MS channel inhibitors have the potential to prevent disease progression.

Dystrophin is a large, submembrane cytoskeletal protein, absence of which causes Duchenne muscular dystrophy. Utrophin is a dystrophin homologue found in both muscle and brain whose physiological function is unknown. Recordings of single‐channel activity were made from membrane patches on skeletal muscle from mdx, mdx/utrn+/– heterozygotes and mdx/utrn–/– double knockout mice to investigate the role of these cytoskeletal proteins in mechanosensitive (MS) channel gating. We find complex, gene dose‐dependent effects of utrophin depletion in dystrophin‐deficient mdx muscle: (1) increased MS channel open probability, (2) a shift of MS channel gating to larger pressures, (3) appearance of modal gating of MS channels and small conductance channels and (4) expression of large conductance MS channels. We suggest a physical model in which utrophin acts as a scaffolding protein that stabilizes lipid microdomains and clusters MS channel subunits. Depletion of utrophin disrupts domain composition in a manner that favours open channel area expansion, as well as allowing diffusion and aggregation of additional MS channel subunits.
Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high‐density diamond ultra‐microelectrode arrays
Authors: Gosso Sara , Turturici Marco , Franchino Claudio , Colombo Elisabetta , Pasquarelli Alberto , Carbone Emilio , Carabelli Valentina
Published: May 2014

Key points

A planar nanocrystalline diamond array with nine ultra‐microelectrodes (9‐Ch NCD‐UMEA) has been designed for high spatial resolution of amperometric recordings in single chromaffin cells.

The 9‐Ch NCD‐UMEA operates in voltammetric and amperometric mode to reveal low doses of adrenaline, dopamine and serotonin. The lowest detectable concentration of adrenaline is ∼5 μm.

Using mouse and bovine chromaffin cells, single quantal exocytotic events are recorded from nine microareas of 12–27 μm2. We found an excellent correspondence with recordings from the cell apex using carbon fibre electrodes.

In the bovine, secretion is heterogeneous. There are areas of high and medium activity covering 54% of the cell surface and areas of low and no activity covering the remainder. The ‘non‐active zones’ (silent) cover 24% of the cell surface and persist for minutes as the ‘active zones’.

The 9‐Ch NCD‐UMEA brings new insights into the spatial mapping of secretory sites in chromaffin cells.

Here we describe the ability of a high‐density diamond microelectrode array targeted to resolve multi‐site detection of fast exocytotic events from single cells. The array consists of nine boron‐doped nanocrystalline diamond ultra‐microelectrodes (9‐Ch NCD‐UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose–response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl‐enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9‐Ch NCD‐UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12–27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The ‘non‐active’ (‘silent’) zones covered 24% of the total and persisted for 6–8 min, indicating stable location. The 9‐Ch NCD‐UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution.