bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic treatment of Pseudomonas aeruginosa biofilms stimulates expression of the magnesium transporter gene mgtE
Authors: Redelman Carly V. , Chakravarty Shubham , Anderson Gregory G.
Published: October 2013

Pseudomonas aeruginosais a Gram-negative opportunistic pathogen with the capacity to cause serious disease, including chronic biofilm infections in the lungs of cystic fibrosis (CF) patients. These infections are treated with high concentrations of antibiotics. Virulence modulation is an important tool utilized byP. aeruginosato propagate infection and biofilm formation in the CF airway. Many different virulence modulatory pathways and proteins have been identified, including the magnesium transporter protein MgtE. We have recently found that isogenic deletion ofmgtEleads to increased cytotoxicity through effects on the type III secretion system. To explore the role of the CF lung environment in MgtE activity, we investigatedmgtEtranscriptional regulation following antibiotic treatment. Utilizing quantitative real-time-PCR, we have demonstrated an increase inmgtEtranscript levels following antibiotic treatment with most of the 12 antibiotics tested. To begin to determine the regulatory network governingmgtEexpression, we screened a transposon-mutant library ofP. aeruginosato look for mutants with potentially alteredmgtEactivity, using cytotoxicity as a readout. In this screen, we observed that AlgR, which regulates production of the biofilm polysaccharide alginate, alters MgtE-mediated cytotoxicity. This cross-talk between MgtE and AlgR suggests that AlgR is involved in linking external inducing signals (e.g. antibiotics) tomgtEtranscription and downstream virulence and biofilm activities. Analysing such interactions may lead to a better understanding of how the CF lung environment shapesP. aeruginosabiofilm infections.
Functional and immunological evaluation of two novel proteins of Leptospira spp.
Authors: Fernandes Luis G. V. , Vieira Monica L. , Alves Ivy J. , de Morais Zenaide M. , Vasconcellos Silvio A. , Romero Eliete C. , Nascimento Ana L. T. O.
Published: October 2013

This work shows the production and characterization of two novel putative lipoproteins encoded by the genes LIC10645 and LIC10731 identified in the genome sequences of Leptospira
interrogans. In silico conservation analysis indicated that the proteins are well conserved among pathogenic leptospiral serovars and species. Recombinant proteins were obtained in Escherichia coli BL21(DE3) Star pLysS strain, purified by metal-affinity chromatography, and used for characterization and immunological evaluations. Recombinant proteins were capable of eliciting a combination of humoral and cellular immune responses in animal models, and could be recognized by antibodies present in human serum samples. The recombinant proteins Lsa44 and Lsa45 were able to bind laminin, and were named Lsa44 and Lsa45 for leptospiral surface adhesins of 44 and 45 kDa, respectively. The attachment to laminin was dose-responsive with K
D values of 108.21 and 250.38 nM for Lsa44 and Lsa45, respectively. Moreover, these proteins interact with plasminogen (PLG) with K
D values of 53.56 and 36.80 nM, respectively. PLG bound to the recombinant proteins could be converted to plasmin (PLA) in the presence of an activator. Cellular localization assays suggested that the Lsa44 and Lsa45 were surface-exposed. These are versatile proteins capable of interacting with laminin and PLG/PLA, and hence could mediate bacterial adhesion and contribute to tissue penetration.
Variation Ontology for annotation of variation effects and mechanisms
Authors: Vihinen Mauno
Published: October 2013

Ontology organizes and formally conceptualizes information in a knowledge domain with a controlled vocabulary having defined terms and relationships between them. Several ontologies have been used to annotate numerous databases in biology and medicine. Due to their unambiguous nature, ontological annotations facilitate systematic description and data organization, data integration and mining, and pattern recognition and statistics, as well as development of analysis and prediction tools. The Variation Ontology (VariO) was developed to allow the annotation of effects, consequences, and mechanisms of DNA, RNA, and protein variations. Variation types are systematically organized, and a detailed description of effects and mechanisms is possible. VariO is for annotating the variant, not the normal-state features or properties, and requires a reference (e.g., reference sequence, reference-state property, activity, etc.) compared to which the changes are indicated. VariO is versatile and can be used for variations ranging from genomic multiplications to single nucleotide or amino acid changes, whether of genetic or nongenetic origin. VariO annotations are position-specific and can be used for variations in any organism.
Linking microhabitat structure, morphology and locomotor performance traits in a recent radiation of dwarf chameleons
Authors: da Silva Jessica M. , Herrel Anthony , Measey G. John , Vanhooydonck Bieke , Tolley Krystal A.
Published: October 2013

Evidence that morphological traits associated with particular environments are functionally adapted to those environments is a key component to determining the adaptive nature of radiations. Adaptation is often measured by testing how organisms perform in diverse habitats, with performance traits associated with locomotion thought to be among the most ecologically relevant.

We therefore explored whether there are relationships between morphology, locomotor performance traits (sprint speed, forefoot and tail grip strength on broad and narrow dowels) and microhabitat use in five phenotypic forms of a recent radiation of dwarf chameleon – theBradypodion melanocephalum–Bradypodion thamnobatesspecies complex – to determine whether morphological differences previously identified between the forms are associated with functional adaptations to their respective habitats, which can be broadly categorized as open or closed‐canopy vegetation.

The results showed significant differences in both absolute and relative performance values between the phenotypic forms. Absolute performance suggests there are two phenotypic groups – strong (B. thamnobatesand TypeB) and weak (B. melanocephalumand Types A and C). Relative performance differences highlighted the significance of forefoot grip strength among these chameleons, with the closed‐canopy forms (B. thamnobates, Types B and C) exceeding their open‐canopy counterparts (B. melanocephalum, Type A). Little to no differences were detected between forms with respect to sprint speed and tail strength. These results indicate that strong selection is acting upon forefoot grip strength and has resulted in morphological adaptations that enable each phenotypic form to conform with the demands of its habitat.

This study provides evidence for the parallel evolution of forefoot grip strength among dwarf chameleons, consistent with the recognition of open and closed‐canopy ecomorphs within the genusBradypodion.
Lasting effects of snow accumulation on summer performance of large herbivores in alpine ecosystems may not last
Authors: Mysterud Atle , Austrheim Gunnar
Published: October 2013

One of the clearest predictions from the IPCC is that we can expect much less snow cover due to global warming in the 21st century, especially in the lower alpine areas. In alpine ecosystems, snow accumulation in depressions gives rise to distinct snow‐bed vegetation types, assumed to play a key role in ecosystem function. A delayed plant phenology yields high‐quality forage in late summer for wild and domestic herbivores. Yet, the mechanistic pathways for how declining snow may affect future performance of large herbivores beyond the effect of phenology remain poorly documented.

Here, we link unique individual‐based data on diet choice, habitat selection and performance of domestic sheep over a 10‐year period to manually GPS‐recorded spatial positions of snow cover in early summer (0·57% to 43·3% in snow beds on 1st of July) in an alpine ecosystem.

Snowy winters gave a higher proportion of easily digestible herbs in the diet and a more variable use of snow‐bed and meadow vegetation types resulting in faster growing lambs. These patterns were consistent between two density treatment levels although slightly more marked for diet at low density, suggesting that effects of simple mitigation efforts such as managing population numbers will be meagre.

Our study thus yields novel insight into the strong impact of melting snow on ecosystem function in alpine habitats, which are likely to affect productivity of both domestic and wild ungulate populations.
Subtype diversity and reassortment potential for co‐circulating avian influenza viruses at a diversity hot spot
Authors: Barton Heather D. , Rohani Pejman , Stallknecht David E. , Brown Justin , Drake John M.
Published: October 2013

Biological diversity has long been used to measure ecological health. While evidence exists from many ecosystems that declines in host biodiversity may lead to greater risk of disease emergence, the role of pathogen diversity in the emergence process remains poorly understood. Particularly, because a more diverse pool of pathogen types provides more ways in which evolutionary innovations may arise, we suggest that host–pathogen systems with high pathogen diversity are more prone to disease emergence than systems with relatively homogeneous pathogen communities. We call this prediction thediversity‐emergence hypothesis.

To show how this hypothesis could be tested, we studied a system comprised of North American shorebirds and their associated low‐pathogenicity avian influenza (LPAI) viruses. These viruses are important as a potential source of genetic innovations in influenza. A theoretical contribution of this study is an expression predicting the rate of viral subtype reassortment to be proportional to both prevalence and Simpson's Index, a formula that has been used traditionally to quantify biodiversity. We then estimated prevalence and subtype diversity in host species at Delaware Bay, a North AmericanAIVhotspot, and used our model to extrapolate from these data.

We estimated that 4 to 39 virus subtypes circulated at Delaware Bay each year between 2000 and 2008, and that surveillance coverage (percentage of co‐circulating subtypes collected) at Delaware Bay is only about 63·0%. Simpson's Index in the same period varied more than fourfold from 0·22 to 0·93. These measurements together with the model provide an indirect, model‐based estimate of the reassortment rate. A proper test of the diversity‐emergence hypothesis would require these results to be joined to independent and reliable estimates of reassortment, perhaps obtained through molecular surveillance.

These results suggest both that subtype diversity (and therefore reassortment) varies from year to year and that several subtypes contributing to reassortment are going undetected. The similarity between these results and more detailed studies of one host, ruddy turnstone (Arenaria interpres), further suggests that this species may be the primary host for influenza reassortment atDelawareBay.

Biological diversity has long been quantified usingSimpson'sIndex. Our model links this formula to a mechanistic account of reassortment in multipathogen systems in the form of subtype diversity atDelawareBay,USA. As a theory of how pathogen diversity may influence the evolution of novel pathogens, this work is a contribution to the larger project of understanding the connections between biodiversity and disease.
Pollen mixing in pollen generalist solitary bees: a possible strategy to complement or mitigate unfavourable pollen properties?
Authors: Eckhardt Michael , Haider Mare , Dorn Silvia , Müller Andreas
Published: October 2013

Generalist herbivorous insects, which feed on plant tissue that is nutritionally heterogeneous or varies in its content of secondary metabolites, often benefit from dietary mixing through more balanced nutrient intake or reduced exposure to harmful secondary metabolites. Pollen is similarly heterogeneous as other plant tissue in its content of primary and secondary metabolites, suggesting that providing their offspring with mixed pollen diets might be a promising strategy for pollen generalist bees to complement nutrient imbalances or to mitigate harmful secondary metabolites of unfavourable pollen.

In the present study, we compared larval performance of the pollen generalist solitary bee species Osmia cornuta (Megachilidae) on five experimental pollen diets that consisted of different proportions of unfavourable pollen diet of Ranunculus acris (Ranunculaceae) and favourable pollen diet of Sinapis arvensis (Brassicaceae). In addition, we microscopically analysed the pollen contained in the scopal brushes of field‐collected females of O. cornuta and three closely related species to elucidate to what degree these pollen generalist bees mix pollen of different hosts in their brood cells.

In striking contrast to a pure Ranunculus pollen diet, which had a lethal effect on most developing larvae of O. cornuta, larval survival, larval development time and adult body mass of both males and females remained nearly unaffected by the admixture of up to 50% of Ranunculus pollen diet to the larval food.

Between 42% and 66% of all female scopal pollen loads analysed contained mixtures of pollen from two to six plant families, indicating that pollen mixing is a common behaviour in O. cornuta and the three related bee species.

The present study provides the first evidence that the larvae of pollen generalist bees can benefit from the nutrient content of unfavourable pollen without being negatively affected by its unfavourable chemical properties if such pollen is mixed with favourable pollen. We conclude that the widespread pollen mixing by females of pollen generalist bees should also be considered as a possible strategy to exploit flowers with unfavourable pollen and to optimize larval food quality.
Changes in predator community structure shifts the efficacy of two warning signals in Arctiid moths
Authors: Nokelainen Ossi , Valkonen Janne , Lindstedt Carita , Mappes Johanna
Published: October 2013

Polymorphism in warning coloration is puzzling because positive frequency‐dependent selection by predators is expected to promote monomorphic warning signals in defended prey.

We studied predation on the warning‐coloured wood tiger moth (Parasemia plantaginis) by using artificial prey resembling white and yellow male colour morphs in five separate populations with different naturally occurring morph frequencies.

We tested whether predation favours one of the colour morphs over the other and whether that is influenced either by local, natural colour morph frequencies or predator community composition.

We found that yellow specimens were attacked less than white ones regardless of the local frequency of the morphs indicating frequency‐independent selection, but predation did depend on predator community composition: yellows suffered less attacks when Paridae were abundant, whereas whites suffered less attacks when Prunellidae were abundant.

Our results suggest that spatial heterogeneity in predator community composition can generate a geographical mosaic of selection facilitating the evolution of polymorphic warning signals. This is the first time this mechanism gains experimental support. Altogether, this study sheds light on the evolution of adaptive coloration in heterogeneous environments.
Individual‐based analyses reveal limited functional overlap in a coral reef fish community
Authors: Brandl Simon J. , Bellwood David R.
Published: October 2013

Detailed knowledge of a species’ functional niche is crucial for the study of ecological communities and processes. The extent of niche overlap, functional redundancy and functional complementarity is of particular importance if we are to understand ecosystem processes and their vulnerability to disturbances.

Coral reefs are among the most threatened marine systems, and anthropogenic activity is changing the functional composition of reefs. The loss of herbivorous fishes is particularly concerning as the removal of algae is crucial for the growth and survival of corals. Yet, the foraging patterns of the various herbivorous fish species are poorly understood.

Using a multidimensional framework, we present novel individual‐based analyses of species’ realized functional niches, which we apply to a herbivorous coral reef fish community. In calculating niche volumes for 21 species, based on their microhabitat utilization patterns during foraging, and computing functional overlaps, we provide a measurement of functional redundancy or complementarity. Complementarity is the inverse of redundancy and is defined as less than 50% overlap in niche volumes.

The analyses reveal extensive complementarity with an average functional overlap of just 15·2%. Furthermore, the analyses divide herbivorous reef fishes into two broad groups. The first group (predominantly surgeonfishes and parrotfishes) comprises species feeding on exposed surfaces and predominantly open reef matrix or sandy substrata, resulting in small niche volumes and extensive complementarity. In contrast, the second group consists of species (predominantly rabbitfishes) that feed over a wider range of microhabitats, penetrating the reef matrix to exploit concealed surfaces of various substratum types. These species show high variation among individuals, leading to large niche volumes, more overlap and less complementarity.

These results may have crucial consequences for our understanding of herbivorous processes on coral reefs, as algal removal appears to depend strongly on species‐specific microhabitat utilization patterns of herbivores. Furthermore, the results emphasize the capacity of the individual‐based analyses to reveal variation in the functional niches of species, even in high‐diversity systems such as coral reefs, demonstrating its potential applicability to other high‐diversity ecosystems.
Does reduced mobility through fragmented landscapes explain patch extinction patterns for three honeyeaters?
Authors: Harrisson Katherine A. , Pavlova Alexandra , Amos J. Nevil , Radford James Q. , Sunnucks Paul
Published: October 2013

Habitat loss and associated fragmentation are major drivers of biodiversity decline, and understanding how they affect population processes (e.g. dispersal) is an important conservation goal. In a large‐scale test employing 10 × 10 km units of replication, three species of Australian birds, the fuscous honeyeater, yellow‐tufted honeyeater and white‐plumed honeyeater, responded differently to fragmentation. The fuscous and yellow‐tufted honeyeaters are ‘decliners’ that disappeared from suitable habitat in landscapes where levels of tree‐cover fell below critical thresholds of 17 and 8%, respectively. The white‐plumed honeyeater is a ‘tolerant’ species whose likelihood of occurrence in suitable habitat was independent of landscape‐level tree‐cover.

To determine whether the absence of the two decliner species in low tree‐cover landscapes can be explained by reduced genetic connectivity, we looked for signatures of reduced mobility and gene flow in response to fragmentation across agricultural landscapes in the Box‐Ironbark region of north‐central Victoria, Australia.

We compared patterns of genetic diversity and population structure at the regional scale and across twelve 100 km2 landscapes with different tree‐cover extents. We used genetic data to test landscape models predicting reduced dispersal through the agricultural matrix. We tested for evidence of sex‐biased dispersal and sex‐specific responses to fragmentation.

Reduced connectivity may have contributed to the disappearance of the yellow‐tufted honey‐eater from low tree‐cover landscapes, as evidenced by male bias and increased relatedness among males in low tree‐cover landscapes and signals of reduced gene flow and mobility through the agricultural matrix. We found no evidence for negative effects of fragmentation on gene flow in the other decliner, the fuscous honeyeater, suggesting that undetected pressures act on this species. As expected, there was no evidence for decreased movement through fragmented landscapes for the tolerant white‐plumed honeyeater.

We demonstrated effects of habitat loss and fragmentation (stronger patterns of genetic differentiation, increased relatedness among males) on the yellow‐tufted honeyeater above the threshold at which probability of occurrence dropped. Increasing extent and structural connectivity of habitat should be an appropriate management action for this species and other relatively sedentary woodland specialist species for which it can be taken as representative.
let‐7‐repressesed Shc translation delays replicative senescence
Authors: Xu Fang , Pang Lijun , Cai Xiaoyu , Liu Xinwen , Yuan Shuai , Fan Xiuqin , Jiang Bin , Zhang Xiaowei , Dou Yali , Gorospe Myriam , Wang Wengong
Published: October 2013

The p66Shc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post‐transcriptional level by the microRNA let‐7a. The levels of let‐7a correlated inversely with the levels of Shc proteins without affecting Shc mRNA levels. We identified ‘seedless’ let‐7a interaction elements in the coding region of Shc mRNA; mutation of the ‘seedless’ interaction sites abolished the regulation of Shc by let‐7a. Our results further revealed that repression of Shc expression by let‐7a delays senescence of human diploid fibroblasts (HDFs). In sum, our findings link let‐7a abundance to the expression of p66Shc, which in turn controls the replicative lifespan of HDFs.
The total number of lymph nodes in resected colon cancer specimens is affected by several factors but the lymph node ratio is independent of these
Authors: Stanisavljević Luka , Søndenaa Karl , Storli Kristian Eeg , Leh Sabine , Nesvik Idunn , Gudlaugsson Einar , Bukholm Ida , Eide Geir Egil
Published: October 2013

The number of lymph nodes retrieved from the specimen may be a surrogate measure of the adequacy of extensive colon cancer surgery, but many variables may influence the total lymph node yield of any specimen. We examined which variables would be influential both for negative and positive node sampling.The combined results from 428 patients from three hospitals A to C treated in 2007–2009 with single colon cancers having R0 segmental resections were analysed. The surgical technique and pathology staining methods were slightly different between the hospitals.The mean number of lymph nodes was 15.8 (range 1–60). Twelve or more lymph nodes were harvested in 78% of the specimens. In the multivariate Poisson regression analysis of all TNM stages, the factors associated with the total lymph node harvest were age, pathology handling, tumour location and size (p < 0.001), whereas for TNM stage III alone the pathology handling (p < 0.001) and a radical operating technique (p = 0.003) were highly significant. The total number of lymph nodes was the only significant factor for the number of positive lymph nodes (Posln) according to the multivariate negative regression analysis (p = 0.02) but the analysis of the lymph node ratio (LNR) detected no statistically significant variable.Several factors, and especially the specimen processing technique, were important for the total number of harvested lymph nodes. The number of Posln varied between segments and increased with the total number of harvested lymph nodes, but for LNR no variable was important. LNR seemed to abolish the combined effect of tumour location and the total lymph node yield in prognosis assessment.
Stimulation of Suicidal Erythrocyte Death by Ribavirin
Authors: Oswald Gergely , Alzoubi Kousi , Abed Majed , Lang Florian
Published: October 2013

Ribavirin is widely used in the treatment for viral disease such as chronic viral hepatitis. Side effects limiting the use of the drug include haemolytic anaemia. If challenged by stimulators of haemolysis, erythrocytes may enter suicidal death or eryptosis, thus preventing the release of haemoglobin into circulating blood. Eryptosis is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase in cytosolic Ca2+ activity ([Ca2+]i). This study explored whether ribavirin modifies [Ca2+]i and elicits eryptosis. Cell volume has been estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from annexin V binding, haemolysis from haemoglobin release and [Ca2+]i from Fluo‐3 fluorescence. A 48‐hr exposure to ribavirin (≥8 μg/ml) was followed by a significant increase in [Ca2+]i, a significant decrease in forward scatter and a significant increase in annexin V binding. The annexin V binding after ribavirin treatment was significantly blunted but not abolished in the nominal absence of extracellular Ca2+. In conclusion, ribaverin stimulates eryptosis, an effect at least in part due to entry of extracellular Ca2+.
Advances in understanding the pathogenesis of autoimmune disorders: focus on chemokines and lymphocyte trafficking
Authors: Comerford Iain , Kara Ervin E. , McKenzie Duncan R. , McColl Shaun R.
Published: October 2013

Lymphocyte trafficking is a key step in the pathogenesis of various autoimmune diseases. Recruitment of autoreactive lymphocytes to inflamed tissues is a defining feature of numerous persistent organ‐specific autoimmune conditions and various therapies are now used in several of these diseases which appear to specifically block lymphocyte migration. Thus, better understanding of the molecular events involved in homing of autoreactive pathogenic lymphocytes may present novel opportunities for pharmacological intervention in autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, type‐1 diabetes and psoriasis. This review describes recent progress in understanding lymphocyte trafficking in autoimmunity, focusing on the involvement of the chemokine and chemokine receptor superfamily. Possible strategies to improve therapeutics for autoimmune diseases arising from these studies are discussed.
The influence of psychological factors on post‐partum weight retention at 9 months
Authors: Phillips Joanne , King Ross , Skouteris Helen
Published: October 2013

Objectives

Post‐partum weight retention (PWR) has been identified as a critical pathway for long‐term overweight and obesity. In recent years, psychological factors have been demonstrated to play a key role in contributing to and maintaining PWR.

Design

Therefore, the aim of this study was to explore the relationship between post‐partum psychological distress and PWR at 9 months, after controlling for maternal weight factors, sleep quality, sociocontextual influences, and maternal behaviours.

Method

Pregnant women (N = 126) completed a series of questionnaires at multiple time points from early pregnancy until 9 months post‐partum.

Results

Hierarchical regression indicated that gestational weight gain, shorter duration (6 months or less) of breastfeeding, and post‐partum body dissatisfaction at 3 and 6 months are associated with higher PWR at 9 months; stress, depression, and anxiety had minimal influence.

Conclusion

Interventions aimed at preventing excessive PWR should specifically target the prevention of body dissatisfaction and excessive weight gain during pregnancy.

Statement of contribution

What is already known on this subject?

Post‐partum weight retention (PWR) is a critical pathway for long‐term overweight and obesity.

Causes of PWR are complex and multifactorial.

There is increasing evidence that psychological factors play a key role in predicting high PWR.

What does this study add?

Post‐partum body dissatisfaction at 3 and 6 months is associated with PWR at 9 months post‐birth.

Post‐partum depression, stress and anxiety have less influence on PWR at 9 months.

Interventions aimed at preventing excessive PWR should target body dissatisfaction.
A randomized controlled trial of a home and school‐based intervention for selective mutism – defocused communication and behavioural techniques
Authors: Oerbeck Beate , Stein Murray B. , Wentzel‐Larsen Tore , Langsrud Øyvind , Kristensen Hanne
Published: October 2013

Background

Randomized controlled psychosocial treatment studies on selective mutism (SM) are lacking.

Method

Overall, 24 children with SM, aged 3–9 years, were randomized to 3 months treatment (n = 12) or wait list (n = 12). Primary outcome measure was the School Speech Questionnaire.

Results

A significant time by group interaction was found (p = .029) with significantly increased speech in the treatment group (p = .004) and no change in wait list controls (p = .936). A time by age interaction favoured younger children (p = .029). Clinical trail registration: Norwegian Research CouncilNCT01002196.

Conclusions

The treatment significantly improved speech. Greater improvement in the younger age group highlights the importance of an early intervention.
Why are children and adolescents referred for psychiatric assessment without fulfiling diagnostic criteria for any psychiatric disorder?
Authors: Dallos Gyöngyvér , Keresztény Ágnes , Miklósi Mónika , Gádoros Júlia , Balázs Judit
Published: October 2013

Background

Clinicians often experience that children are referred for psychiatric evaluation without fulfiling the diagnostic criteria of any psychiatric disorders. This study investigates factors that might lead children to psychiatric referral without any psychiatric disorder.

Method

Children/adolescents who were referred for psychiatric assessment (referred group) (n = 418, mean age = 10.82 years, SD = 3.81) and a control group (n = 48, mean age = 10.38 years, SD = 3.77) were evaluated by the Mini International Neuropsychiatric Interview Kid (MINI Kid) and the Erfassung der Lebensqualität Kindern und Jugendlichen (Measure of Quality of Life for Children and Adolescents). The referred group was further divided into two subgroups: referred subgroup without MINI Kid diagnosis (n = 61) and referred subgroup with MINI Kid diagnosis (n = 357). Subjects less than 18 years old were included and there was no lower age limit.

Results

Attention‐deficit/hyperactivity disorder (ADHD) symptoms significantly increased the odds for referral as social phobia symptoms significantly decreased the odds for psychiatric referral. Regarding quality of life (QoL), the control group showed significantly less impairment when compared with the referred group; the two referred subgroup with and without diagnosis did not differ significantly.

Conclusions

ADHD symptoms, even in a subthreshold level and impaired QoL represent risk factors for psychiatric referral in children. Secondary prevention of children should target to screen subthreshold ADHD symptoms and QoL.
Biological Activity of Sporolides A and B from Salinispora tropica: in silico Target Prediction Using Ligand‐Based Pharmacophore Mapping and in vitro activity Validation on HIV‐1 Reverse Transcriptase
Authors: Dineshkumar Kesavan , Aparna Vasudevan , Madhuri Kantilal Z. , Hopper Waheeta
Published: October 2013

Sporolides A and B are novel polycyclic macrolides from the obligate marine actinomycetes, Salinispora tropica. The unique and novel structure of sporolides makes them interesting candidates for targeting diverse biological activities. Biological target prediction of sporolides was carried out using ligand‐based pharmacophore screening against known inhibitors and drugs. Validation of pharmacophore screening was carried out for the identified hits. New biological targets predicted for sporolides using this method were HIV‐1 reverse transcriptase, adenosine A3 receptor, endothelin receptor ET‐A, oxytocin receptor, voltage‐gated L‐type calcium channel α‐1C subunit/calcium channel α/Δ subunit 1. Drug‐likeness properties were predicted for the selected compounds using QikProp module. Sporolides A and B showed maximum docking score with HIV‐1 reverse transcriptase. Structural interaction fingerprints analysis indicated similar binding pattern of the sporolides with the HIV‐1 reverse transcriptase. Sporolide B exhibited good inhibitory activity against HIV‐1 reverse transcriptase in in vitro fluorescent assay.
Glia Protein Aquaporin‐4 Regulates Aversive Motivation of Spatial Memory in Morris Water Maze
Authors: Zhang Ji , Li Ying , Chen Zhong‐Guo , Dang Hui , Ding Jian‐Hua , Fan Yi , Hu Gang
Published: October 2013

Aims

Although extensive investigation has revealed that an astrocyte‐specific protein aquaporin‐4 (AQP4) participates in regulating synaptic plasticity and memory, a functional relationship between AQP4 and learning processing has not been clearly established. This study was designed to test our hypothesis that AQP4 modulates the aversive motivation in Morris water maze (MWM).

Methods and Results

Using hidden platform training, we observed that AQP4 KO mice significantly decreased their swimming velocity compared with wild‐type (WT) mice. To test for a relationship between velocities and escape motivation, we removed the platform and subjected a new group of mice similar to the session of hidden platform training. We found that KO mice exhibited a gradual reduction in swimming velocity, while WT mice did not alter their velocity. In the subsequent probe trial, KO mice after no platform training significantly decreased their mean velocity compared with those KO mice after hide platform training. However, all of KO mice were not impaired in their ability to locate a visible, cued escape platform.

Conclusions

Our findings, along with a previous report that AQP4 regulates memory consolidation, implicate a novel role for this glial protein in modulating the aversive motivation in spatial learning paradigm.
Increase in Neuroexcitability of Unmyelinated C‐type Vagal Ganglion Neurons During Initial Postnatal Development of Visceral Afferent Reflex Functions
Authors: Qian Zhao , Liu Dong‐Jie , Liu Yang , Han Li‐Min , Yuan Mei , Li Jun‐Nan , Xu Bing , Lu Xiao‐Long , Cao Pan‐Xiang , Wang Hao‐Yan , Pan Xiao‐Dong , Wang Li‐Juan , Qiao Guo‐Fen , Li Bai‐Yan
Published: October 2013

Background

Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs).

Methods

To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A‐ and C‐type VGNs at different developmental stages using whole‐cell patch clamping.

Results

C‐type VGNs underwent significant age‐dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX‐S and TTX‐R Na+ currents were also confirmed and well simulated by computer modeling. Although 4‐AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4‐AP‐ and iberiotoxin‐sensitive K+ current activity, whereas less developmental changes were verified in A‐types.

Conclusion

These data demonstrate for the first time that the neuroexcitability of C‐type VGNs increases significantly compared with A‐types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function.
Comprehensive health assessment and five‐yr follow‐up of allogeneic islet transplant recipients
Authors: Radosevich D. M. , Jevne R. , Bellin M. , Kandaswamy R. , Sutherland D. E. R. , Hering B. J.
Published: October 2013

In patients with type 1 diabetes mellitus (T1DM) complicated by severe hypoglycemic episodes, fear of hypoglycemia can significantly impact daily life. We evaluated whether restoration of glycemic awareness and prevention of hypoglycemia by islet allotransplant could reduce fear and improve health status. We conducted a comprehensive evaluation of patient‐based outcomes in 48 T1DM subjects screened for allogeneic islet transplant alone (ITA) and 27 subjects who received an ITA. A battery of generic health status and diabetes‐specific measures were used to assess ITA at evaluation, six months, and then annually after ITA. Allogeneic islet transplant was associated with a reduction in behaviors adopted in avoiding hypoglycemia (p Value < 0.001) and attenuation in concerns about hypoglycemic episodes (p Value < 0.001). Changes in hypoglycemia fear tracked most closely with insulin use. While there was a trend toward global improvement in health as measured by the EQ‐5D (p Value = 0.002) and in depression symptoms as measured by the Beck (p Value = 0.003), physical health remained unchanged following ITA. Our findings support the socioemotional benefits of ITA during the five years after ITA, which to some extent remains dependent on preservation of islet graft function.
Urine free light chains as a novel biomarker of acute kidney allograft injury
Authors: Zhang Rubin , Li Min , Chouhan Kanwaljit K. , Simon Eric E. , Hamm Lotuce Lee , Batuman Vecihil
Published: October 2013

Background

We evaluated urine free light chains (FLC) as a potential biomarker for acute kidney allograft injury (AKAI).

Methods

Urine κ and λ FLC were compared with urine β‐2 microglobulin (β2‐M), retinol‐binding protein (RBP), kidney injury molecule 1 (KIM‐1), neutrophil gelatinase‐associated lipocalin (NGAL), and microalbuminuria (MAB) in biopsy‐confirmed acute rejection (AR) and acute tubular necrosis (ATN). Healthy volunteers (normal) and transplant recipients with normal allograft function (control) were used as references.

Results

Compared with control or normal group (N = 15), urine FLC, MAB, and RBP were higher in ATN (N = 29) and AR (N = 41) groups (p < 0.05). There was no difference in KIM‐1, NGAL, or β2‐M between four groups. In the AR group, urine κFLC demonstrated the highest predictive value with sensitivity of 95.12% and specificity of 87.5% (p < 0.0001). Urine κFLC also performed best with a sensitivity of 96.55% and specificity of 93.33% (p < 0.0001) in the ATN group. The area under the receiver operating characteristic (ROC) curves (AUC) by ROC analysis is greatest in urine RBP (100%) and FLC (99%), and lowest in KIM‐1 (53.5%), then NGAL (71.5%) in the AR group. The AUC is also greatest in urine FLC (100%) and RBP (99%), and lowest in urine KIM‐1 (55.6%) and NGAL (69.9%) in the ATN group.

Conclusions

Urine FLC appears sensitive for both AR and ATN, and it may be a novel AKAI biomarker.
Effects of chronic exposure of clonal β‐cells to elevated glucose and free fatty acids on incretin receptor gene expression and secretory responses to GIP and GLP‐1
Authors: Pathak V. , Vasu S. , Flatt P. R. , Irwin N.
Published: October 2013

Aim

The incretin effect, mediated by glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1), is impaired in type 2 diabetes.

Methods

This study examines the effects of prolonged exposure to elevated glucose and free fatty acids in clonal BRIN BD11 cells on GIP and GLP‐1 action.

Results

Glucotoxic conditions (18 h) had no effect on GIP‐ or GLP‐1‐mediated insulinotropic responses. In contrast, 48 h glucotoxic culture impaired (p < 0.05 to p < 0.001) insulin release in response to GLP‐1, and particularly GIP. Culture under lipotoxic conditions (18 h) impaired (p < 0.05 to p < 0.001) the insulin‐releasing effect of GIP, but was without effect on GLP‐1. However, 48 h lipotoxic culture compromised both GIP (p < 0.05 to p < 0.001) and GLP‐1 (p < 0.05 to p < 0.01) insulin‐releasing actions. Glucolipotoxic culture (18 h) completely annulled the insulinotropic action of GIP, whereas GLP‐1 effects were similar to control. However, when glucolipotoxic culture was extended to 48 h, both GIP‐ and GLP‐1‐mediated effects were (p < 0.05 to p < 0.001) impaired. Assessment of cell viability, number and insulin content revealed detrimental (p < 0.05 to p < 0.001) effects under all culture conditions, barring 18 h glucotoxic and lipotoxic culture. Finally, GIP‐R gene and protein expression was increased (p < 0.05 to p < 0.01) under glucotoxic culture, with decreased (p < 0.05 to p < 0.001) expression following glucolipotoxic culture. GLP‐1‐R gene expression followed a similar trend, but protein levels were generally reduced under all culture conditions.

Conclusion

The results indicate that impaired insulinotropic response to GIP and GLP‐1 under diabetic milieu involves mechanisms beyond simple expression of respective receptors.
History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major
Authors: Ang Ai Leen , Tzoulis Ploutarchos , Prescott Emma , Davis Bernard A. , Barnard Maria , Shah Farrukh T.
Published: October 2013

Endocrinopathies are common complications of transfusional hemosiderosis among patients with β thalassemia major (TM). Previous studies had shown associations between some endocrinopathies and iron overload of the myocardium, liver and/or endocrine organs as assessed by MRI techniques. This retrospective analysis of 92 patients with TM (median age 36 yr) from a tertiary adult thalassemia unit in UK aimed to determine independent risk factors associated with endocrinopathies among these patients. Unlike previous studies, longitudinal data on routine measurements of iron load [worst myocardial and liver T2* values since 1999, worst LIC by MRI‐R2 since 2008 and average 10‐yr serum ferritin (SF)] up to April 2010 together with demographic features and age of initiating chelation were analyzed for associations with endocrinopathies. The most common endocrinopathies in this cohort were hypogonadism (67%) and diabetes mellitus (DM) (41%), and these were independently associated with myocardial T2* <20 ms (P < 0.001 and P = 0.008, respectively) and increased age (P = 0.002 and P = 0.016, respectively). DM and hypogonadism were independently associated with average SF >1250 μg/L (P = 0.003) and >2000 μg/L (P = 0.047), respectively. DM was also associated with initial detection of abnormal myocardial T2* at an older age (30 yr vs. 24 yr, P = 0.039). An abnormal myocardial T2* may therefore portend the development of DM and hypogonadism in patients with TM.
Genetic variability of respiratory complex abundance, organization and activity in mouse brain
Authors: Buck K. J. , Walter N. A. R. , Denmark D. L.
Published: October 2013

Mitochondrial dysfunction is implicated in the etiology and pathogenesis of numerous human disorders involving tissues with high energy demand. Murine models are widely used to elucidate genetic determinants of phenotypes relevant to human disease, with recent studies of C57BL/6J (B6), DBA/2J (D2) and B6xD2 populations implicating naturally occurring genetic variation in mitochondrial function/dysfunction. Using blue native polyacrylamide gel electrophoresis, immunoblots and in‐gel activity analyses of complexes I, II, III, IV and V, our studies are the first to assess abundance, organization and catalytic activity of mitochondrial respiratory complexes and supercomplexes in mouse brain. Remarkable strain differences in supercomplex assembly and associated activity are evident, without differences in individual complexes I, II, III or IV. Supercomplexes I1III2IV2–3 exhibit robust complex III immunoreactivity and activities of complexes I and IV in D2, but with little detected in B6 for I1III2IV2, and I1III2IV3 is not detected in B6. I1III2IV1 and I1III2 are abundant and catalytically active in both strains, but significantly more so in B6. Furthermore, while supercomplex III2IV1 is abundant in D2, none is detected in B6. In aggregate, these results indicate a shift toward more highly assembled supercomplexes in D2. Respiratory supercomplexes are thought to increase electron flow efficiency and individual complex stability, and to reduce electron leak and generation of reactive oxygen species. Our results provide a framework to begin assessing the role of respiratory complex suprastructure in genetic vulnerability and treatment for a wide variety of mitochondrial‐related disorders.
Evidence for multiple stressor interactions and effects on coral reefs
Authors: Ban Stephen S. , Graham Nicholas A. J. , Connolly Sean R.
Published: October 2013

Concern is growing about the potential effects of interacting multiple stressors, especially as the global climate changes. We provide a comprehensive review of multiple stressor interactions in coral reef ecosystems, which are widely considered to be one of the most sensitive ecosystems to global change. First, we synthesized coral reef studies that examined interactions of two or more stressors, highlighting stressor interactions (where one stressor directly influences another) and potentially synergistic effects on response variables (where two stressors interact to produce an effect that is greater than purely additive). For stressor‐stressor interactions, we found 176 studies that examined at least 2 of the 13 stressors of interest. Applying network analysis to analyze relationships between stressors, we found that pathogens were exacerbated by more costressors than any other stressor, with ca. 78% of studies reporting an enhancing effect by another stressor. Sedimentation, storms, and water temperature directly affected the largest number of other stressors. Pathogens, nutrients, and crown‐of‐thorns starfish were the most‐influenced stressors. We found 187 studies that examined the effects of two or more stressors on a third dependent variable. The interaction of irradiance and temperature on corals has been the subject of more research (62 studies, 33% of the total) than any other combination of stressors, with many studies reporting a synergistic effect on coral symbiont photosynthetic performance (n = 19). Second, we performed a quantitative meta‐analysis of existing literature on this most‐studied interaction (irradiance and temperature). We found that the mean effect size of combined treatments was statistically indistinguishable from a purely additive interaction, although it should be noted that the sample size was relatively small (n = 26). Overall, although in aggregate a large body of literature examines stressor effects on coral reefs and coral organisms, considerable gaps remain for numerous stressor interactions and effects, and insufficient quantitative evidence exists to suggest that the prevailing type of stressor interaction is synergistic.
Sovereign Default Risk and Banks in a Monetary Union
Authors: Uhlig Harald
Published: October 2013

This study seeks to understand the interplay between banks, bank regulation, sovereign default risk and central bank guarantees in a monetary union. I assume that banks can use sovereign bonds for repurchase agreements with a common central bank, and that their sovereign partially backs up any losses should the banks not be able to repurchase the bonds. I argue that regulators in risky countries have an incentive to allow their banks to hold home risky bonds and risk defaults, whereas regulators in other ‘safe’ countries will impose tighter regulation. As a result, governments in risky countries get to borrow more cheaply, effectively shifting the risk of some of the potential sovereign default losses on the common central bank.