bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival in patients with Child–Pugh class C cirrhosis: Analysis of the liver transplant registry in Japan
Authors: Genda Takuya , Ichida Takafumi , Sakisaka Shotaro , Tanaka Eiji , Mochida Satoshi , Ueno Yoshiyuki , Inui Ayano , Egawa Hiroto , Umeshita Koji , Furukawa Hiroyuki , Kawasaki Seiji , Inomata Yukihiro ,   The Assessment Committee of Indication for Transplantation
Published: December 2016

Aim

Aim: To clarify the survival and prognostic factors in patients with Child–Turcotte–Pugh class C (CTP‐C) cirrhosis.

Methods

From all candidates for deceased donor liver transplantation in Japan between 2007 and 2015, 1014 adult patients with CTP‐C cirrhosis were retrospectively enrolled in this study. The hazard ratio (HR) of factors associated with mortality was estimated by the Cox proportional hazard model. The survival probabilities were evaluated by Kaplan–Meier analysis and the log–rank test.

Results

Median survival time of the entire cohort was 475 days. Univariate analysis identified age, CTP, Model for End‐Stage Liver Disease (MELD) score, and primary biliary cholangitis (PBC) as significant variables associated with mortality and hepatitis B virus (HBV) infection as a close‐to‐significant variable. Multivariate analysis revealed that age‐adjusted mortality risk increased by 59% and 12% per 1 score step up in CTP and MELD scores, respectively. The HRs for HBV infection and PBC were significant after adjustment for age and CTP score, and they showed a 26% lower risk and an 83% higher risk than hepatitis C virus (HCV) infection, respectively. After adjustment for age and MELD score, the HR was also significant for HBV infection, but lost statistical significance for PBC. The survival curves were well stratified by both CTP or MELD score and revealed significant difference in both HBV infection and PBC as compared to HCV infection.

Conclusions

In patients with CTP‐C cirrhosis, CTP and MELD scores could well stratify the patients’ survival, and HBV infection and PBC as etiologies have an impact on survival.
Effects of high hydrostatic pressure processing and subsequent storage on phenolic contents and antioxidant activity in fruit and vegetable products
Authors: Zhao Guanghe , Zhang Ruifen , Zhang Mingwei
Published: December 2016

Fresh fruits and vegetables have been reported to possess a variety of bioactivities partly due to their high abundance of phenolics. However, traditional thermal pasteurisation during fruit and vegetable processing typically induces a pronounced loss of phenolic compounds. In contrast, nonthermal pasteurisation techniques, especially high hydrostatic pressure (HHP) processing, are beneficial to the retention of phenolics. In addition to more effectively keeping original freshness, flavour and colour of fruit and vegetable products to the greatest extent, in most cases, HHP processing and subsequent storage more effectively sustain the levels of phenolic compounds and antioxidant activity in fruit and vegetable products compared with thermal pasteurisation. Therefore, HHP processing has a huge potential to preserve fruit and vegetable products rich in phenolic compounds.
Mucilage formation in food: a review on the example of okra
Authors: Ritzoulis Christos
Published: December 2016

Formation of a mucilage is a complex process that involves the initial contact of a solid matrix (e.g. bone with connective tissue, okra fruit, beans) and water; the wetting of the macromolecules that are embedded on the solid matrix, followed by its swelling; their elution (‘extraction’) in the aqueous phase, forming a hydrocolloidal dispersion; the relaxation of the macromolecules in their new environment, leading to the modification of the latter's rheological properties, or their adsorption onto an oil interface, leading to the formation of oil‐in‐water emulsions. This review collects data assembled on a representative case study, that of okra fruit, as to assemble an image of the individual contributions of the previous stages towards the final formation of the hydrocolloidal mucilage.
Review of the NICE guidelines for multiple myeloma
Authors: Pratt G. , Morris T.C.
Published: December 2016

In February 2016, the National Institute for Health and Care Excellence (NICE) published guidelines on multiple myeloma. NICE have published numerous guidelines relating to haematology, but this was the first guideline focusing on a single haematological malignancy. The purpose of this review was to highlight the recommendations made in the guideline and the implications for the management of patients in the UK and also internationally. In addition, we review the NICE process and highlight issues around current guideline development.
Role of interferon‐γ and inflammatory monocytes in driving colonic inflammation during acute Clostridium difficile infection in mice
Authors: McDermott Andrew J. , Falkowski Nicole R. , McDonald Roderick A. , Frank Charles R. , Pandit Chinmay R. , Young Vincent B. , Huffnagle Gary B.
Published: December 2016

The inflammatory response to the colonic pathogen Clostridium difficile is characterized by the induction of inflammatory cytokines including Interleukin‐23 (IL‐23) and interferon‐γ (IFN‐γ) and the recruitment of myeloid cells including Ly6CHigh monocytes. IL‐23 knockout mice showed reduced expression of the monocyte chemokines Ccl4 and Ccl7, but not Ccl2, as well as reduced Ly6CHigh Ly6GMid monocyte recruitment to the colon in response to C. difficile colitis. Clostridium difficile‐infected CCR2−/− (CCR2 KO) mice showed a significant defect in Ly6CHigh Ly6GMid monocyte recruitment to the colon in response to C. difficile. Although there was no decrease in expression of the inflammatory cytokines Il1b, Il6 or Tnf or reduction in the severity of colonic histopathology associated with ablation of monocyte recruitment, Slpi and Inos expression was significantly reduced in the colons of these animals. Additionally, neutralization of IFN‐γ through the administration of anti‐IFN‐γ monoclonal antibody resulted in a significant reduction in the expression of the IFN‐γ‐inducible chemokines Cxcl9 and Cxcl10, but not a reduction in the neutrophil chemokines Cxcl1, Cxcl2 and Ccl3 or the monocyte chemokine Ccl2. Consistently, monocyte and neutrophil recruitment were unchanged following anti‐IFN‐γ treatment. Additionally, Inos and Slpi expression were unchanged following anti‐IFN‐γ treatment, suggesting that Inos and Slpi regulation is independent of IFN‐γ during C. difficile colitis. Taken together, these data strongly suggest that IL‐23 and CCR2 signalling are required for monocyte recruitment during C. difficile colitis. Additionally, these studies also suggest that monocytes, but not IFN‐γ, are necessary for full expression of Inos and Slpi in the colon.
Foxd3 suppresses interleukin‐10 expression in B cells
Authors: Zhang Yu , Wang Zhiding , Xiao He , Liu Xiaoling , Zhu Gaizhi , Yu Dandan , Han Gencheng , Chen Guojiang , Hou Chunmei , Ma Ning , Shen Beifen , Li Yan , Wang Tianxiao , Wang Renxi
Published: December 2016

Interleukin‐10‐positive (IL‐10+) regulatory B (Breg) cells play an important role in restraining excessive inflammatory responses by secreting IL‐10. However, it is still unclear what key transcription factors determine Breg cell differentiation. Hence, we explore what transcription factor plays a key role in the expression of IL‐10, a pivotal cytokine in Breg cells. We used two types of web‐based prediction software to predict transcription factors binding the IL‐10 promoter and found that IL‐10 promoter had many binding sites for Foxd3. Chromatin immunoprecipitation PCR assay demonstrated that Foxd3 directly binds the predicted binding sites around the start codon upstream by −1400 bp. Further, we found that Foxd3 suppressed the activation of IL‐10 promoter by using an IL‐10 promoter report system. Finally, knocking out Foxd3 effectively promotes Breg cell production by up‐regulating IL‐10 expression. Conversely, up‐regulated Foxd3 expression was negatively associated with IL‐10+ Breg cells in lupus‐prone MRL/lpr mice. Hence, our data suggest that Foxd3 suppresses the production of IL‐10+ Breg cells by directly binding the IL‐10 promoter. This study demonstrates the mechanism for Breg cell production and its application to the treatment of autoimmune diseases by regulating Foxd3 expression.
Organizational politics, nurses' stress, burnout levels, turnover intention and job satisfaction
Authors: Labrague L.J. , McEnroe‐Petitte D.M. , Gloe D. , Tsaras K. , Arteche D.L. , Maldia F.
Published: December 2016

Aim

This is a research report examining the influence of organizational politics perceptions on nurses' work outcomes (job satisfaction, work stress, job burnout and turnover intention).

Background

Organizational politics is a phenomenon common in almost all institutions and is linked with undesirable consequences in employees.

Introduction

Despite the plethora of research around the world on this topic, studies describing organizational politics in nursing remain underexplored.

Methods

A cross‐sectional research design was utilized in this study. One hundred sixty‐six (166) nurses participated. Five standardized tools were used: the Job Satisfaction Index, the Job Stress Scale, the Burnout Measure Scale, the Turnover Intention Inventory Scale and the Perception of Organizational Politics Scale.

Results

Nurses employed both in private and government‐owned hospitals perceived moderate levels of organizational politics. Positive correlations were identified between perceived organizational politics and job stress, turnover intention and job burnout. Negative correlations were found between perceived organizational politics and job satisfaction.

Discussion

Perceptions of workplace politics in Filipino nurses were lower when compared to findings in other international studies. A strong link was found between organizational politics perceptions and the four job outcomes (stress and burnout levels, turnover intention and job satisfaction).

Limitations

Use of a self‐reporting questionnaire and exclusion of nurses from other provinces.

Conclusion

Perceived organizational politics predicted nurses’ stress and burnout levels, turnover intention and job satisfaction.

Implications for nursing and/or health policy

The findings of this study may provide a valuable perspective of this organizational issue and could assist policymakers and nurse administrators in formulating interventions that could minimize the effect of workplace politics.
Keloid progression: a stiffness gap hypothesis
Authors: Huang Chenyu , Liu Longwei , You Zhifeng , Wang Bingjie , Du Yanan , Ogawa Rei
Published: December 2016

Keloids are fibroproliferative skin disorders characterised clinically by continuous horizontal progression and post‐surgical recurrence and histologically by the accumulation of collagen and fibroblast ingredients. Till now, their aetiology remains clear, which may cover genetic, environmental and metabolic factors. Evidence in the involvement of local mechanics (e.g. predilection site and typical shape) and the progress in mechanobiology have incubated our stiffness gap hypotheses in illustrating the chronic but constant development in keloid. We put forward that the enlarged gap between extracellular matrix (ECM) stiffness and cellular stiffness potentiates keloid progression. Matrix stiffness itself provides organisational guidance cues to regulate the mechanosensitive resident cells (e.g. proliferation, migration and apoptosis). During this dynamic process, the ECM stiffness and cell stiffness are not well balanced, and the continuously enlarged stiffness gap between them potentiates keloid progression. The cushion factors, such as prestress for cell stiffness and topology for ECM stiffness, serve as compensations, the decompensation of which aggravates keloid development. It can well explain the typical shape of keloids, their progression in a horizontal but not vertical direction and the post‐surgical recurrence, which were evidenced by our clinical cases. Such a stiffness gap hypothesis might be bridged to mechanotherapeutic approaches for keloid progression.
Game‐based assessment: investigating the impact on test anxiety and exam performance
Authors: Mavridis A. , Tsiatsos T.
Published: December 2016

The aim of this study is to assess the impact of a 3D educational computer game on students' test anxiety and exam performance when used in evaluative situations as compared to the traditional method of examination. The participants of the study were students in tertiary education who were examined using game‐based assessment and traditional assessment in a 2 × 2 cross‐over design. The game was flexible, providing the instructor with the opportunity to import and edit exam questions and modify several aspects via an administration panel. Following the collection and analysis of both quantitative and interview data, it was revealed that the students' test anxiety was reduced during the game‐based assessment. Furthermore, the exam performance of the students was significantly better when the game method was used. The results showed that there is a linear negative relationship between the students' test anxiety and exam performance as well as that these variables are correlated in a causal way. Overall, this study provides evidence that game‐based assessment could be potentially beneficial for students.
The effects of the DNA methyltranfserases inhibitor 5‐Azacitidine on ageing, oxidative stress and DNA methylation of adipose derived stem cells
Authors: Kornicka Katarzyna , Marycz Krzysztof , Marędziak Monika , Tomaszewski Krzysztof A. , Nicpoń Jakub
Published: December 2016

Human adipose tissue is a great source of adult mesenchymal stem cells (MSCs) which are recognized from their ability to self‐renew and differentiation into multiple lineages. MSCs have promised a vast therapeutic potential in treatment many diseases including tissue injury and immune disorders. However, their regenerative potential profoundly depends on patients’ age. Age‐related deterioration of MSC is associated with cellular senescence mainly caused by increased DNA methylation status, accumulation of oxidative stress factors and mitochondria dysfunction. We found that DNA methyltransferase (DNMT) inhibitor i.e. 5‐Azacytidine (5‐AZA) reversed the aged phenotype of MSCs. Proliferation rate of cells cultured with 5‐AZA was increased while the accumulation of oxidative stress factors and DNA methylation status were decreased. Simultaneously the mRNA levels of TET proteins involved in demethylation process were elevated in those cells. Moreover, cells treated with 5‐AZA displayed reduced reactive oxygen species (ROS) accumulation, ameliorated superoxide dismutase activity and increased BCL‐2/BAX ratio in comparison to control group. Our results indicates that, treating MSCs with 5‐AZA can be justified therapeutic intervention, that can slow‐down and even reverse aged‐ related degenerative changes in those cells.
Efficacy of an emollient cream in the treatment of xerosis in diabetic foot: a double‐blind, randomized, vehicle‐controlled clinical trial
Authors: Martini J. , Huertas C. , Turlier V. , Saint‐Martory C. , Delarue A.
Published: December 2016

Background

Peripheral neuronal impairment compromises foot health in patients with diabetes. Clinically, xerosis is the most common mild complication, but it should not be underestimated. An effective treatment must be able to restore the cutaneous barrier and prevent water loss, to maintain adequate hydration and protection.

Objective

This study aimed to assess the efficacy of an emollient cream on foot xerosis in patients with diabetes.

Methods

This is a prospective, multicenter, randomized, double‐blind contralateral vehicle‐controlled study in 57 patients with diabetes. Patients were treated twice daily for 27 ± 2 days with the study emollient containing glycerol 15%, liquid and soft paraffin 10%, glycerol monostearate, stearic acid, polydimethylcyclosiloxane, silicone oil, macrogol 600, trolamine, propyl parahydroxybenzoate and purified water (Dexeryl®; Pierre Fabre Medicament, Boulogne, France) or its vehicle (glycerol monostearate, stearic acid, polydimethylcyclosiloxane, silicone oil, macrogol 600, trolamine, propyl parahydroxybenzoate and purified water). Efficacy was assessed after a 28‐day treatment period using a validated score [Xerosis Assessment Scale (XAS) score], instrumental measurements and subjective assessment.

Results

The XAS score decreased to 3.2 ± 2.6 points with the emollient and 4.1 ± 2.3 with the vehicle (P = 0.001). Improvement was observed from day 14 (P = 0.012). Compared with the vehicle, the emollient also significantly improved the overall skin score, hydration index, D‐Squame® (CuDerm Corporation, Dallas, TX, USA) test, skin roughness and patients’ opinions.

Conclusion

Treatment with an emollient is effective for improving foot xerosis in patients with diabetes.
Inner ear development in cetaceans
Authors: Thean Tara , Kardjilov Nikolay , Asher Robert J.
Published: December 2016

Cetaceans face the challenge of maintaining equilibrium underwater and obtaining sensory input within a dense, low‐visibility medium. The cetacean ear represents a key innovation that marked their evolution from terrestrial artiodactyls to among the most fully aquatic mammals in existence. Using micro‐CT and histological data, we document shape and size changes in the cetacean inner ear during ontogeny, and demonstrate that, as a proportion of gestation time, the cetacean inner ear is precocial in its growth compared with that of suid artiodactyls. Cetacean inner ears begin ossifying and reach near‐adult shape as early as at 32% of the gestation period, and near‐adult dimensions as early as at 27% newborn total length. Our earliest embryos with measurable inner ears (13% newborn length) exhibit a flattened cochlea (i.e. smaller distance from cochlear apex to round window) compared with later and adult stages. Inner ears of Sus scrofa have neither begun ossifying nor reached near‐adult dimensions at 55% of the gestation period, but have an adult‐like ratio of cochlear diameters to each other, suggesting an adult‐like shape. The precocial development of the cetacean inner ear complements previous work demonstrating precocial development of other cetacean anatomical features such as the locomotor muscles to facilitate swimming at the moment of birth.
Rap as Korean Rhyme: Local Enregisterment of the Foreign
Authors: Park Jonghyun
Published: December 2016

This article investigates how a “foreign” register of rap is emerging among South Korean rappers through debates and experiments. It focuses on a dispute about the essentiality and translatability of rhyming, a novel verbal‐artistic device, and traces how rhyme has become understood as a defining feature of the register of Korean rap. Korean rappers have grappled with metapragmatic definitions of the semiotic linkage between rhyme and rap and the realization of rhyme at a pragmatic level, performatively bringing into being new forms of rhyming, based on their knowledge of local registers and of the linguistic differences between Korean and English. This ongoing pragmatic/metapragmatic practice contributes to the register‐formation of Korean rap as a dynamic process that remains open to the creation of new strategies for realizing “Korean rhyme” in its genre‐history.
The opsin genes of amazonian cichlids
Authors: Escobar‐Camacho Daniel , Ramos Erica , Martins Cesar , Carleton Karen L.
Published: December 2016

Vision is a critical sense for organismal survival with visual sensitivities strongly shaped by the environment. Some freshwater fishes with a Gondwanan origin are distributed in both South American rivers including the Amazon and African rivers and lakes. These different habitats likely required adaptations to murky and clear environments. In this study, we compare the molecular basis of Amazonian and African cichlid fishes’ visual systems. We used next‐generation sequencing of genomes and retinal transcriptomes to examine three Amazonian cichlid species. Genome assemblies revealed six cone opsin classes (SWS1, SWS2B, SWS2A, RH2B, RH2A and LWS) and rod opsin (RH1). However, the functionality of these genes varies across species with different pseudogenes found in different species. Our results support evidence of an RH2A gene duplication event that is shared across both cichlid groups, but which was probably followed by gene conversion. Transcriptome analyses show that Amazonian species mainly express three opsin classes (SWS2A, RH2A and LWS), which likely are a good match to the long‐wavelength‐oriented light environment of the Amazon basin. Furthermore, analysis of amino acid sequences suggests that the short‐wavelength‐sensitive genes (SWS2B, SWS2A) may be under selective pressures to shift their spectral properties to a longer‐wavelength visual palette. Our results agree with the ‘sensitivity hypothesis’ where the light environment causes visual adaptation. Amazonian cichlid visual systems are likely adapting through gene expression, gene loss and possibly spectral tuning of opsin sequences. Such mechanisms may be shared across the Amazonian fish fauna.
Evidence for microbial local adaptation in nature
Authors: Kraemer Susanne A. , Boynton Primrose J.
Published: December 2016

Local adaptation is an outcome of divergent selection on microbial populations and has been linked to the immense genetic diversity of microbes observed in nature. Because it is difficult to study microbes in their natural habitats, most tests of microbial local adaptation have been performed in model laboratory systems; as a result, microbiologists have limited understanding of local adaptation among natural microbial populations. In this review, we summarize the evidence for microbial local adaptation in nature. Local adaptation has been most frequently studied, and most frequently found, in host–pathogen systems. We argue that more research is needed to understand the prevalence of local adaptation in free‐living microbial populations. However, researchers will need to overcome a variety of logistical and conceptual challenges when studying natural microbial local adaptation, including a lack of solid understanding of many microbes’ natural histories. We propose strategies to facilitate future natural history research on divergent selection. We also summarize laboratory experimental work investigating the ecological and evolutionary processes leading to local adaptation. Microbiologists’ ongoing challenge is to integrate the valuable knowledge gained from laboratory experiments into well‐designed field experiments. Such integration will help us understand the prevalence of, and circumstances leading to, local adaptation among microorganisms.
The on‐again, off‐again relationship between mitochondrial genomes and species boundaries
Authors: Sloan Daniel B. , Havird Justin C. , Sharbrough Joel
Published: December 2016

The study of reproductive isolation and species barriers frequently focuses on mitochondrial genomes and has produced two alternative and almost diametrically opposed narratives. On one hand, mtDNA may be at the forefront of speciation events, with co‐evolved mitonuclear interactions responsible for some of the earliest genetic incompatibilities arising among isolated populations. On the other hand, there are numerous cases of introgression of mtDNA across species boundaries even when nuclear gene flow is restricted. We argue that these seemingly contradictory patterns can result from a single underlying cause. Specifically, the accumulation of deleterious mutations in mtDNA creates a problem with two alternative evolutionary solutions. In some cases, compensatory or epistatic changes in the nuclear genome may ameliorate the effects of mitochondrial mutations, thereby establishing coadapted mitonuclear genotypes within populations and forming the basis of reproductive incompatibilities between populations. Alternatively, populations with high mitochondrial mutation loads may be rescued by replacement with a more fit, foreign mitochondrial haplotype. Coupled with many nonadaptive mechanisms of introgression that can preferentially affect cytoplasmic genomes, this form of adaptive introgression may contribute to the widespread discordance between mitochondrial and nuclear genealogies. Here, we review recent advances related to mitochondrial introgression and mitonuclear incompatibilities, including the potential for cointrogression of mtDNA and interacting nuclear genes. We also address an emerging controversy over the classic assumption that selection on mitochondrial genomes is inefficient and discuss the mechanisms that lead lineages down alternative evolutionary paths in response to mitochondrial mutation accumulation.
Habitat continuity and stepping‐stone oceanographic distances explain population genetic connectivity of the brown alga Cystoseira amentacea
Authors: Buonomo Roberto , Assis Jorge , Fernandes Francisco , Engelen Aschwin H. , Airoldi Laura , Serrão Ester A.
Published: December 2016

Effective predictive and management approaches for species occurring in a metapopulation structure require good understanding of interpopulation connectivity. In this study, we ask whether population genetic structure of marine species with fragmented distributions can be predicted by stepping‐stone oceanographic transport and habitat continuity, using as model an ecosystem‐structuring brown alga, Cystoseira amentacea var. stricta. To answer this question, we analysed the genetic structure and estimated the connectivity of populations along discontinuous rocky habitat patches in southern Italy, using microsatellite markers at multiple scales. In addition, we modelled the effect of rocky habitat continuity and ocean circulation on gene flow by simulating Lagrangian particle dispersal based on ocean surface currents allowing multigenerational stepping‐stone dynamics. Populations were highly differentiated, at scales from few metres up to thousands of kilometres. The best possible model fit to explain the genetic results combined current direction, rocky habitat extension and distance along the coast among rocky sites. We conclude that a combination of variable suitable habitat and oceanographic transport is a useful predictor of genetic structure. This relationship provides insight into the mechanisms of dispersal and the role of life‐history traits. Our results highlight the importance of spatially explicit modelling of stepping‐stone dynamics and oceanographic directional transport coupled with habitat suitability, to better describe and predict marine population structure and differentiation. This study also suggests the appropriate spatial scales for the conservation, restoration and management of species that are increasingly affected by habitat modifications.
Why UV vision and red vision are important for damselfish (Pomacentridae): structural and expression variation in opsin genes
Authors: Stieb Sara M. , Cortesi Fabio , Sueess Lorenz , Carleton Karen L. , Salzburger Walter , Marshall N. J.
Published: December 2016

Coral reefs belong to the most diverse ecosystems on our planet. The diversity in coloration and lifestyles of coral reef fishes makes them a particularly promising system to study the role of visual communication and adaptation. Here, we investigated the evolution of visual pigment genes (opsins) in damselfish (Pomacentridae) and examined whether structural and expression variation of opsins can be linked to ecology. Using DNA sequence data of a phylogenetically representative set of 31 damselfish species, we show that all but one visual opsin are evolving under positive selection. In addition, selection on opsin tuning sites, including cases of divergent, parallel, convergent and reversed evolution, has been strong throughout the radiation of damselfish, emphasizing the importance of visual tuning for this group. The highest functional variation in opsin protein sequences was observed in the short‐ followed by the long‐wavelength end of the visual spectrum. Comparative gene expression analyses of a subset of the same species revealed that with SWS1, RH2B and RH2A always being expressed, damselfish use an overall short‐wavelength shifted expression profile. Interestingly, not only did all species express SWS1 – a UV‐sensitive opsin – and possess UV‐transmitting lenses, most species also feature UV‐reflective body parts. This suggests that damsels might benefit from a close‐range UV‐based ‘private’ communication channel, which is likely to be hidden from ‘UV‐blind’ predators. Finally, we found that LWS expression is highly correlated to feeding strategy in damsels with herbivorous feeders having an increased LWS expression, possibly enhancing the detection of benthic algae.
The metalloprotease SepA governs processing of accumulation‐associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis
Authors: Paharik Alexandra E. , Kotasinska Marta , Both Anna , Hoang Tra‐My N. , Büttner Henning , Roy Paroma , Fey Paul D. , Horswill Alexander R. , Rohde Holger
Published: December 2016

The otherwise harmless skin inhabitant Staphylococcus epidermidis is a major cause of healthcare‐associated medical device infections. The species' selective pathogenic potential depends on its production of surface adherent biofilms. The Cell wall‐anchored protein Aap promotes biofilm formation in S. epidermidis, independently from the polysaccharide intercellular adhesin PIA. Aap requires proteolytic cleavage to act as an intercellular adhesin. Whether and which staphylococcal proteases account for Aap processing is yet unknown. Here, evidence is provided that in PIA‐negative S. epidermidis 1457Δica, the metalloprotease SepA is required for Aap‐dependent S. epidermidis biofilm formation in static and dynamic biofilm models. qRT‐PCR and protease activity assays demonstrated that under standard growth conditions, sepA is repressed by the global regulator SarA. Inactivation of sarA increased SepA production, and in turn augmented biofilm formation. Genetic and biochemical analyses demonstrated that SepA‐related induction of biofilm accumulation resulted from enhanced Aap processing. Studies using recombinant proteins demonstrated that SepA is able to cleave the A domain of Aap at residue 335 and between the A and B domains at residue 601. This study identifies the mechanism behind Aap‐mediated biofilm maturation, and also demonstrates a novel role for a secreted staphylococcal protease as a requirement for the development of a biofilm.
Metabolic adaptation of Chlamydia trachomatis to mammalian host cells
Authors: Mehlitz Adrian , Eylert Eva , Huber Claudia , Lindner Buko , Vollmuth Nadine , Karunakaran Karthika , Goebel Werner , Eisenreich Wolfgang , Rudel Thomas
Published: December 2016

Metabolic adaptation is a key feature for the virulence of pathogenic intracellular bacteria. Nevertheless, little is known about the pathways in adapting the bacterial metabolism to multiple carbon sources available from the host cell. To analyze the metabolic adaptation of the obligate intracellular human pathogen Chlamydia trachomatis, we labeled infected HeLa or Caco‐2 cells with 13C‐marked glucose, glutamine, malate or a mix of amino acids as tracers. Comparative GC‐MS‐based isotopologue analysis of protein‐derived amino acids from the host cell and the bacterial fraction showed that C. trachomatis efficiently imported amino acids from the host cell for protein biosynthesis. FT‐ICR‐MS analyses also demonstrated that label from exogenous 13C‐glucose was efficiently shuffled into chlamydial lipopolysaccharide probably via glucose 6‐phosphate of the host cell. Minor fractions of bacterial Ala, Asp, and Glu were made de novo probably using dicarboxylates from the citrate cycle of the host cell. Indeed, exogenous 13C‐malate was efficiently taken up by C. trachomatis and metabolized into fumarate and succinate when the bacteria were kept in axenic medium containing the malate tracer. Together, the data indicate co‐substrate usage of intracellular C. trachomatis in a stream‐lined bipartite metabolism with host cell‐supplied amino acids for protein biosynthesis, host cell‐provided glucose 6‐phosphate for cell wall biosynthesis, and, to some extent, one or more host cell‐derived dicarboxylates, e.g. malate, feeding the partial TCA cycle of the bacterium. The latter flux could also support the biosynthesis of meso‐2,6‐diaminopimelate required for the formation of chlamydial peptidoglycan.
Structural mechanism for bacterial oxidation of oceanic trimethylamine into trimethylamine N‐oxide
Authors: Li Chun‐Yang , Chen Xiu‐Lan , Zhang Dian , Wang Peng , Sheng Qi , Peng Ming , Xie Bin‐Bin , Qin Qi‐Long , Li Ping‐Yi , Zhang Xi‐Ying , Su Hai‐Nan , Song Xiao‐Yan , Shi Mei , Zhou Bai‐Cheng , Xun Lu‐Ying , Chen Yin , Zhang Yu‐Zhong
Published: December 2016

Trimethylamine (TMA) and trimethylamine N‐oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin‐containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm (RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm. The catalytic process of Tmm consists of a reductive half‐reaction and an oxidative half‐reaction. In the reductive half‐reaction, FAD is reduced and a C4a‐hydroperoxyflavin intermediate forms. In the oxidative half‐reaction, this intermediate attracts TMA through electronic interactions. After TMA binding, NADP+ bends and interacts with D317, shutting off the entrance to create a protected micro‐environment for catalysis and exposing C4a‐hydroperoxyflavin to TMA for oxidation. Sequence analysis suggests that the proposed catalytic mechanism is common for bacterial Tmms. These findings reveal the catalytic process of TMA oxidation by marine bacterial Tmm and first show that NADP+ undergoes a conformational change in the oxidative half‐reaction of FMOs.
Elucidating the role of hyposalivation and autoimmunity in oral candidiasis
Authors: Billings M , Dye BA , Iafolla T , Grisius M , Alevizos I
Published: December 2016

Introduction

Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non‐salivary gland dysfunction controls (NSGD).

Methods

A nested case–control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken.

Results

Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min−1) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P < 0.001) and NSGD (3.8, IQR: 3.8, P < 0.001) but comparable with that of Sicca (1.0, IQR: 1.5, P = 0.777) participants. The median total stimulated salivary flow rate (TSS, ml 15 min−1) was lowest in SS (7.0, IQR: 12.4, P < 0.001) compared to other groups. Of the 45 OC cases in this cohort, 71.1% (n = 32) were from the SS group. The prevalence of OC was highest in the SS group (4.6%, P = 0.008). SS group had twice the risk of OC than NSGD (OR = 2.2, 95%CI: 1.1–4.2, P = 0.02) and Sicca (OR = 2.2, 95% CI: 1.0–4.8, P = 0.03), adjusting for confounders; hyposalivation [WUS (OR = 5.1, 95%CI: 2.5–10.4, P < 0.001), TSS (OR = 1.9, 95%CI: 1.0–3.5, P = 0.04)], history of other autoimmune disorders (OR = 4.4, 95%CI: 1.7–11.3, P = 0.002), medications for extraglandular manifestations (OR = 2.3, 95%CI: 1.1–4.9, P = 0.03), and diabetes mellitus (4.2, 95%CI: 1.2–15.2, P = 0.02) were independent predictors of OC; females had a lower risk than males (OR = 0.29, 95%CI: 0.13–0.67, P = 0.004). Age, race, anti‐SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis.

Conclusion

Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population.
Active Atrial Function and Atrial Scar Burden After Multiple Catheter Ablations of Persistent Atrial Fibrillation
Authors: NÜHRICH JANA M. , GEISLER ANNE C. , STEVEN DANIEL , HOFFMANN BORIS A. , SCHÄFFER BENJAMIN , LUND GUNNAR , STEHNING CHRISTIAN , RADUNSKI ULF K. , SULTAN ARIAN , SCHWARZL MICHAEL , ADAM GERHARD , WILLEMS STEPHAN , MUELLERLEILE KAI
Published: December 2016

Background

Extensive and repeated substrate modification (SM) is frequently performed as an ablation strategy in persistent atrial fibrillation (persAF). The effect of these extended ablation strategies on atrial function has not been investigated sufficiently so far. The purpose was to assess atrial function by cardiac magnetic resonance (CMR) and its association with left atrial (LA) scar burden by electroanatomical voltage‐mapping after multiple persAF ablation procedures.

Methods

We included 16 persAF patients who had ≥2 SM procedures and a control group (CG) of 21 persAF patients without prior ablation. CMR was performed in sinus rhythm at least 4 weeks after the last cardioversion. Active left and right (RA) atrial emptying fractions (AEF) as well as peak active left atrial appendage (LAA) emptying velocities were obtained by CMR flow measurements. Furthermore, LA scar burden was quantified on electroanatomical voltage maps by the portion of points with local voltage amplitude <0.2 mV.

Results

We found median LA‐AEF to be lower (13 [9–22] vs 32 [26–36] %, P < 0.001) and median LA scar burden to be higher (40 [20–68] vs nine [3–18] %, P < 0.05) in the SM group compared with the CG. Furthermore, a significant correlation was found between mean LA voltage and LA‐AEF (r2 = 0.62, P < 0.001). No significant differences were detected with respect to median RA‐AEF (41 [28–48] vs 47 [35–50] %, P = 0.43) and median peak LAA emptying velocities (30 [16–40] vs 17 [13–28] cm/s, P = 0.07).

Conclusions

Active LA function is preserved but significantly impaired and associated with ablation‐related LA scar burden after multiple extensive persAF ablations.
The Effect of Education on the Demographic Dividend
Authors: Rentería Elisenda , Souto Guadalupe , Mejía‐Guevara Iván , Patxot Concepció
Published: December 2016

The impact of population structure on economic growth has been studied in recent decades using different methods to estimate the so‐called demographic dividend. Besides, education has been pointed out as a key factor in economic growth. We propose a decomposition of the demographic dividend, into age and education effects. We illustrate the potentialities of the method, deriving an application to Mexico and Spain over the period 1970‐2100. To that end, we estimate the National Transfer Accounts age profiles by schooling level and apply them to recently available population projections stratified by education level. Our results confirm the role of population age structure in the demographic dividend, but also reveal that education attainment can be even more crucial. Moreover, we find that how both age and education effects finally impact on economic growth depends to a great extent on the specific consumption and labor income age profiles in each country.
Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid‐naive Malay Males
Authors: Zahari Zalina , Lee Chee Siong , Ibrahim Muslih Abdulkarim , Musa Nurfadhlina , Mohd Yasin Mohd Azhar , Lee Yeong Yeh , Tan Soo Choon , Mohamad Nasir , Ismail Rusli
Published: December 2016

Background

Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P‐gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males.

Methods

Cold pain responses, including pain threshold and pain tolerance, were measured using the cold‐pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real‐time polymerase chain reaction.

Results

A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype.

Conclusion

The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.
Chronic Postsurgical Pain Outcomes in Breast Reconstruction Patients Receiving Perioperative Transversus Abdominis Plane Catheters at the Donor Site: A Prospective Cohort Follow‐up Study
Authors: Oh Justin , Pagé M. Gabrielle , Zhong Toni , McCluskey Stuart , Srinivas Coimbatore , O'Neill Anne C. , Kahn James , Katz Joel , Hofer Stefan O.P. , Clarke Hance
Published: December 2016

Background

Chronic postsurgical pain (CPSP) is a debilitating and costly condition. Risk factors for CPSP after autologous breast reconstruction have not been clearly established. Previously, we demonstrated that transversus abdominis plane (TAP) catheters delivering intermittent local anesthetic reduced postoperative morphine consumption. This prospective follow‐up study aimed to (1) compare the incidence of CPSP after autologous breast reconstruction between patients who received postoperative intermittent TAP catheters with bupivacaine or saline boluses and (2) assess the factors that contribute to the development and maintenance of CPSP in this study cohort.

Methods

Ninety‐three patients who underwent deep inferior epigastric artery perforator or muscle‐sparing transverse rectus abdominis breast reconstruction were randomized to receive TAP catheters with bupivacaine or saline postoperatively. Subsequently, patients were followed for a year to assess persistent pain, pain severity, quality of life scores, and functional disability at 6 and 12 months after surgery.

Results

Twenty‐four percent and 23% of patients reported CPSP at 6 and 12 months, respectively. There were no significant differences between groups (bupivacaine vs. placebo) on pain‐related variables, including incidence of CPSP. Patients who reported greater variability in pain scores at rest over the first 48 hours postoperatively were more likely to have CPSP 6 months, but not 12 months, later.

Conclusions

Acute postoperative pain variability may contribute to the development of CPSP up to 6 months after autologous breast reconstruction surgery. Neither postoperative use of bupivacaine vs. saline in the TAP catheters nor acute pain severity influenced the 6‐ or 12‐month incidence of CPSP.
Ectopic expression of specific GA2 oxidase mutants promotes yield and stress tolerance in rice
Authors: Lo Shuen‐Fang , Ho Tuan‐Hua David , Liu Yi‐Lun , Jiang Mirng‐Jier , Hsieh Kun‐Ting , Chen Ku‐Ting , Yu Lin‐Chih , Lee Miin‐Huey , Chen Chi‐yu , Huang Tzu‐Pi , Kojima Mikiko , Sakakibara Hitoshi , Chen Liang‐Jwu , Yu Su‐May
Published: December 2016

A major challenge of modern agricultural biotechnology is the optimization of plant architecture for enhanced productivity, stress tolerance and water use efficiency (WUE). To optimize plant height and tillering that directly link to grain yield in cereals and are known to be tightly regulated by gibberellins (GAs), we attenuated the endogenous levels of GAs in rice via its degradation. GA 2‐oxidase (GA2ox) is a key enzyme that inactivates endogenous GAs and their precursors. We identified three conserved domains in a unique class of C20 GA2ox, GA2ox6, which is known to regulate the architecture and function of rice plants. We mutated nine specific amino acids in these conserved domains and observed a gradient of effects on plant height. Ectopic expression of some of these GA2ox6 mutants moderately lowered GA levels and reprogrammed transcriptional networks, leading to reduced plant height, more productive tillers, expanded root system, higher WUE and photosynthesis rate, and elevated abiotic and biotic stress tolerance in transgenic rice. Combinations of these beneficial traits conferred not only drought and disease tolerance but also increased grain yield by 10–30% in field trials. Our studies hold the promise of manipulating GA levels to substantially improve plant architecture, stress tolerance and grain yield in rice and possibly in other major crops.
Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology
Authors: Tanaka Hideo , Matsuyama Taka‐aki , Takamatsu Tetsuro
Published: December 2016

Cardiac arrhythmias have long been regarded as derangement of electrical impulse initiation and conduction within the heart. However, underlying mechanisms for arrhythmogenesis are not fully understood solely from the electrophysiological viewpoint. This review article discusses pathogenesis of arrhythmias from non‐electrical aspects, which were elucidated by spatiotemporal imaging of functional molecules in combination with morphological analysis of living heart tissues. Intracellular Ca2+ ([Ca2+]i) overload, caused by myocardial injury, provokes Ca2+ waves that could lead to abnormal excitations, i.e., triggered arrhythmias. Depressed Ca2+ release from the sarcoplasmic reticulum, caused by ischemia, heart failure, or T‐tubular remodeling, results in spatiotemporally inhomogeneous [Ca2+]i dynamics that could disturb impulse conduction, leading to reentrant tachyarrhythmias. Impairment of the gap junction‐mediated intercellular communications, which provokes derangement of impulse propagation of the myocardium, also leads to reentrant arrhythmias. Interpositions of non‐cardiomyocytes, especially fibroblasts, in the myocardium could also contribute to arrhythmogenesis via heterocellular gap‐junctional coupling with cardiomyocytes. Furthermore, alterations in myocardial histology, e.g., density and arrangements of myocytes in association with gap‐junctional distributions, could constitute important pathologic bases of atrial fibrillation. Integration of these molecular, functional, and morphological features of the myocardium, unveiled by experimental pathological approaches, would pave a new way for understanding pathogenesis of cardiac arrhythmias.