bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of the bacterial cell division determinant GpsB and its interaction with penicillin‐binding proteins
Authors: Rismondo Jeanine , Cleverley Robert M. , Lane Harriet V. , Großhennig Stephanie , Steglich Anne , Möller Lars , Mannala Gopala Krishna , Hain Torsten , Lewis Richard J. , Halbedel Sven
Published: November 2015

Each bacterium has to co‐ordinate its growth with division to ensure genetic stability of the population. Consequently, cell division and growth are tightly regulated phenomena, albeit different bacteria utilise one of several alternative regulatory mechanisms to maintain control. Here we consider GpsB, which is linked to cell growth and division in Gram‐positive bacteria. ΔgpsB mutants of the human pathogen Listeria monocytogenes show severe lysis, division and growth defects due to distortions of cell wall biosynthesis. Consistent with this premise, GpsB interacts both in vitro and in vivo with the major bi‐functional penicillin‐binding protein. We solved the crystal structure of GpsB and the interaction interfaces in both proteins are identified and validated. The inactivation of gpsB results in strongly attenuated virulence in animal experiments, comparable in degree to classical listerial virulence factor mutants. Therefore, GpsB is essential for in vitro and in vivo growth of a highly virulent food‐borne pathogen, suggesting that GpsB could be a target for the future design of novel antibacterials.
Nationwide epidemiology and prognosis of dialysis‐requiring acute kidney injury (NEP‐AKI‐D) study: Design and methods
Authors: Shiao Chih‐Chung , Wu Pei‐Chen , Wu Vin‐Cent , Lin Jui‐Hsiang , Pan Heng‐Chih , Yang Ya‐Fei , Lai Tai‐Shuan , Huang Tao‐Min , Wu Che‐Hsiung , Yang Wei‐Shun , Wu Chih‐Jen , Kao Chih‐Chin , Sun Chiao‐Yin , Huang Chun‐Te , Lee Kuo‐Hua , Lin Chan‐Yu , Chen Te‐Chuan , Hu Fu‐Chang , Liou Hung‐Hsiang , Lu Kuo‐Cheng , Chien Kuo‐Liong , Wang Jian‐Jhong , Kan Wei‐Chih , Kuo Feng‐Chi , Lin Hugo You‐Hsien , Chen Cheng‐Min , You Zi‐hong , Tsai Jen‐Pi , Weng Chih‐Jen , Chen Hung‐Yuan , Chang Chao‐Fu , Hsu Wen‐Ding , Wu Mai‐Szu , Huang Chiu‐Ching , Wu Kwan‐Dun ,   on behalf of the Taiwan Consortium for Acute Kidney Injury Renal Diseases (CAKs)
Published: November 2015

Aim

Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end‐stage renal disease (ESRD) as well as the medical expenses during the post‐AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis‐requiring acute kidney injury (NEP‐AKI‐D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI‐ESRD interaction.

Methods

The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP‐AKI‐D study enrols intensive care unit‐based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on‐site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in‐hospital mortality, dialysis‐dependency and readmission rate within 90 days after discharge.

Conclusion

The NEP‐AKI‐D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.
The extent of whole‐genome copy number alterations predicts aggressive features in primary melanomas
Authors: Gandolfi Greta , Longo Caterina , Moscarella Elvira , Zalaudek Iris , Sancisi Valentina , Raucci Margherita , Manzotti Gloria , Gugnoni Mila , Piana Simonetta , Argenziano Giuseppe , Ciarrocchi Alessia
Published: November 2015

Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP‐array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.
Comparison of Childhood Vitiligo Presenting with or without Associated Halo Nevi
Authors: Cohen Brandon E. , Mu Euphemia W. , Orlow Seth J.
Published: November 2015

Background

Previous studies have characterized differences in vitiligo associated with halo nevi, but the features of vitiligo presenting with halo nevus in children have yet to be fully described.

Aims

We sought to provide an epidemiologic and clinical comparison of cases of childhood vitiligo presenting with or without associated halo nevi.

Materials and Methods

This was a retrospective chart review of children diagnosed with vitiligo in an academic pediatric dermatology practice from January 1990 to November 2014. The characteristics of children with vitiligo with or without associated halo nevi were compared.

Results

Halo nevi were identified in 55 (26%) of 208 children with vitiligo. Patients with halo nevi were significantly more likely to be male and develop vitiligo at a later age. Children with vitiligo associated with halo nevi were more likely to present with generalized vitiligo, defined according to the presence of bilateral macules.

Discussion

There was no significant association between groups in the percentage of body surface area with vitiligo or family history of vitiligo or autoimmune diseases. Patients with halo nevi were no more likely to develop new areas of vitiligo during the follow‐up period, but there was a nonsignificant trend toward a higher rate of repigmentation in vitiligo associated with halo nevus.

Conclusion

Halo nevi are a common finding in children with vitiligo. The presence of a halo nevus in a child with vitiligo is associated with generalized vitiligo. The presence of a halo nevus does not significantly alter the risk of disease progression and rate of treatment.
Acute Effects of Light on Alternative Splicing in Light‐Grown Plants
Authors: Mancini Estefania , Sanchez Sabrina E. , Romanowski Andres , Schlaen Ruben G. , Sanchez‐Lamas Maximiliano , Cerdán Pablo D. , Yanovsky Marcelo J.
Published: November 2015

Light modulates plant growth and development to a great extent by regulating gene expression programs. Here, we evaluated the effect of light on alternative splicing (AS) in light‐grown Arabidopsis thaliana plants using high‐throughput RNA sequencing (RNA‐seq). We found that an acute light pulse given in the middle of the night, a treatment that simulates photoperiod lengthening, affected AS events corresponding to 382 genes. Some of these AS events were associated with genes involved in primary metabolism and stress responses, which may help to adjust metabolic and physiological responses to seasonal changes. We also found that several core clock genes showed changes in AS in response to the light treatment, suggesting that light regulation of AS may play a role in clock entrainment. Finally, we found that many light‐regulated AS events were associated with genes encoding RNA processing proteins and splicing factors, supporting the idea that light regulates this posttranscriptional regulatory layer through AS regulation of splicing factors. Interestingly, the effect of a red‐light pulse on AS of a gene encoding a splicing factor was not impaired in a quintuple phytochrome mutant, providing unequivocal evidence that nonphotosensory photoreceptors control AS in light‐grown plants.
Comparative mitochondrial genome analysis reveals the evolutionary rearrangement mechanism in Brassica
Authors: Yang J. , Liu G. , Zhao N. , Chen S. , Liu D. , Ma W. , Hu Z. , Zhang M.
Published: November 2015

The genus Brassica has many species that are important for oil, vegetable and other food products. Three mitochondrial genome types (mitotype) originated from its common ancestor. In this paper, a B. nigra mitochondrial main circle genome with 232,407 bp was generated through de novo assembly. Synteny analysis showed that the mitochondrial genomes of B. rapa and B. oleracea had a better syntenic relationship than B. nigra. Principal components analysis and development of a phylogenetic tree indicated maternal ancestors of three allotetraploid species in Us triangle of Brassica. Diversified mitotypes were found in allotetraploid B. napus, in which napus‐type B. napus was derived from B. oleracea, while polima‐type B. napus was inherited from B. rapa. In addition, the mitochondrial genome of napus‐type B. napus was closer to botrytis‐type than capitata‐type B. oleracea. The sub‐stoichiometric shifting of several mitochondrial genes suggested that mitochondrial genome rearrangement underwent evolutionary selection during domestication and/or plant breeding. Our findings clarify the role of diploid species in the maternal origin of allotetraploid species in Brassica and suggest the possibility of breeding selection of the mitochondrial genome.
Natural variation in tocochromanols content in Arabidopsis thaliana accessions – the effect of temperature and light intensity
Authors: Gabruk Michał , Habina Iwona , Kruk Jerzy , Dłużewska Jolanta , Szymańska Renata
Published: November 2015

In this study, 25 accessions of Arabidopsis thaliana originating from a variety of climate conditions were grown under controlled circumstances of different light intensity and temperature. The accessions were analyzed for prenyllipids content and composition, as well as expression of the genes involved in tocochromanol biosynthesis (vte1‐5). It was found that the applied conditions did not strongly affect total tocochromanols content and there was no apparent correlation of the tocochromanol content with the origin of the accessions. However, the presented results indicate that the temperature, more than the light intensity, affects the expression of the vte1‐5 genes and the content of some prenyllipids. An interesting observation was that under low growth temperature, the hydroxy‐plastochromanol (PC‐OH) to plastochromanol (PC) ratio was considerably increased regardless of the light intensity in most of the accessions. PC‐OH is known to be formed as a result of singlet oxygen stress, therefore this observation indicates that the singlet oxygen production is enhanced under low temperature. Unexpectedly, the highest increase in the PC‐OH/PC ratio was found for accessions originating from cold climate (Shigu, Krazo‐1 and Lov‐5), even though such plants could be expected to be more resistant to low temperature stress.
Changes in water and soil metals in a Mediterranean restored marsh subject to different water management schemes
Authors: Calvo‐Cubero Juan , Ibáñez Carles , Rovira Albert , Sharpe Peter J. , Reyes Enrique
Published: November 2015

Marsh restoration is an effective tool to remove water and soil metals via plant uptake and soil accumulation. However, few studies have attempted to quantify metal accumulation and removal in Mediterranean restored marshes. This study aimed to assess changes in water and soil metals in an oligohaline‐restored marsh experiment that was set in an abandoned rice field for 3 years. Two freshwater‐type treatments were tested: river irrigation water (IW) and rice field drainage water (DW), as well as three water level management schemes. Differences in water level schemes did not cause significant differences in metal removal and accumulation in soil marshes in either water type treatment. However, results showed that significantly higher Mn, Pb, and Zn input concentrations from DW allowed higher mean percentage of concentration reduction. Higher Cu concentration from IW also allowed higher Cu reduction (85%). Mean values of Co, Cr, Cu, Ni, Pb, V, and Zn in soil were higher in the IW treatment characterized by higher plant biomass, whereas mean accumulation rates of As, Ba, Cr, Cu, Ni, Pb, V, and Zn were higher in the DW treatment with higher accretion rates. Results suggest that wetland plants likely favored soil metal adsorption through soil oxygenation and highlight the utility of restored marshes as pollution filters in coastal wetlands with significant soil accretion and subject to relative sea level rise.
Continental carbonate facies of a Neoproterozoic panglaciation, north‐east Svalbard
Authors: Fairchild Ian J. , Fleming Edward J. , Bao Huiming , Benn Douglas I. , Boomer Ian , Dublyansky Yuri V. , Halverson Galen P. , Hambrey Michael J. , Hendy Chris , McMillan Emily A. , Spötl Christoph , Stevenson Carl T. E. , Wynn Peter M.
Published: November 2015

The Marinoan panglaciation (ca 650 to 635 Ma) is represented in north‐east Svalbard by the 130 to 175 m thick Wilsonbreen Formation which contains syn‐glacial carbonates in its upper 100 m. These sediments are now known to have been deposited under a CO2‐rich atmosphere, late in the glaciation, and global climate models facilitate testing of proposed analogues. Precipitated carbonates occur in four of the seven facies associations identified: Fluvial Channel (including stromatolitic and intraclastic limestones in ephemeral stream deposits); Dolomitic Floodplain (dolomite‐cemented sand and siltstones, and microbial dolomites); Calcareous Lake Margin (intraclastic dolomite and wave‐rippled or aeolian siliciclastic facies); and Calcareous Lake (slump‐folded and locally re‐sedimented rhythmic/stromatolitic limestones and dolomites associated with ice‐rafted sediment). There is no strong cyclicity, and modern analogues suggest that sudden changes in lake level may exert a strong control on facies geometry. Both calcite and dolomite in stromatolites and rhythmites display either primary or early diagenetic replacive growth. Oxygen isotope values (−12 to +15‰VPDB) broadly covary with δ13C. High δ13C values of +3·5 to +4·5‰ correspond to equilibration with an atmosphere dominated by volcanically degassed CO2 with δ13C of −6 to −7‰. Limestones have consistently negative δ18O values, while rhythmic and playa dolomites preserve intermediate compositions, and dolocretes possess slightly negative to strongly positive δ18O signatures, reflecting significant evaporation under hyperarid conditions. Inferred meltwater compositions (−8 to −15·5‰) could reflect smaller Rayleigh fractionation related to more limited cooling than in modern polar regions. A common pseudomorph morphology is interpreted as a replacement of ikaite (CaCO3·H2O), which may also have been the precursor for widespread replacive calcite mosaics. Local dolomitization of lacustrine facies is interpreted to reflect microenvironments with fluctuating redox conditions. Although differing in (palaeo)latitude and carbonate abundance, the Wilsonbreen carbonates provide strong parallels with the McMurdo Dry Valleys of Antarctica.
Public–Private Partnerships in European Old‐Age Pension Provision: An Accountability Perspective
Authors: Sorsa Ville‐Pekka
Published: November 2015

Over the last few decades, the boundary between public and private responsibility in old‐age pension provisions has been redrawn throughout Europe. A new, public–private mix has emerged, not only in pension policy, but also in pension administration. The purpose of this article is to map and conduct a comparative analysis of the administrative design of public–private partnerships (PPPs) in European pension regimes, with a specific focus on how accountabilities are institutionally enforced within the PPP design. Previous literature has recognized accountability as an important factor in promoting trust in mandated pension schemes. However, as the literature on PPPs suggests, institutional arrangements of accountability are more complex in the case of PPPs than has been suggested by previous studies on pension administration. Thus, there is a need for further elaboration of existing comparative models. This study's analysis examines 19 old‐age pension schemes that existed in 18 European countries at the beginning of 2013. The findings suggest that significant variations in accountability structures exist, even among schemes that are similar in terms of their pension policy targets. It is concluded that various schemes suffer from ineffective accountability structures that may compromise the legitimacy and sustainability of PPP‐type pension schemes.
The Cooperative Capacity of Swiss Federalism
Authors: Wasserfallen Fabio
Published: November 2015

The federal structure is a defining feature of the Swiss polity. According to the disenchanted hypothesis, which argues that the Swiss political culture of accommodating competing interests has come under pressures, we should expect that cooperation among the cantons and between the federal and cantonal governments has deteriorated over the last 25 years. However, inter‐cantonal coordination has increased substantially. In addition, the successful negotiation of the NFA shows that the federal and cantonal governments can reach comprehensive agreements. This study provides empirical analyses of the NFA reform and of inter‐cantonal tax competition. The NFA analysis shows that the cantons successfully coordinated their interests vis‐à‐vis the federal government, and the findings of the spatial econometric tax competition investigation suggest that inter‐cantonal coordination in the NFA had an attenuating effect on tax competition. Overall, the problem‐solving capacity of the Swiss federal system is remarkably high—not disenchanted.
Ammonia emissions from urea, stabilized urea and calcium ammonium nitrate: insights into loss abatement in temperate grassland
Authors: Forrestal P. J. , Harty M. , Carolan R. , Lanigan G. J. , Watson C. J. , Laughlin R. J. , McNeill G. , Chambers B. J. , Richards K. G.
Published: November 2015

Fertilizer nitrogen (N) contributes to ammonia (NH3) emissions, which European Union member states have committed to reduce. This study focused on evaluating NH3‐N loss from a suite of N fertilizers over multiple applications, and gained insights into the temporal and seasonal patterns of NH3‐N loss from urea in Irish temperate grassland using wind tunnels. The fertilizers evaluated were calcium ammonium nitrate (CAN), urea and urea with the N stabilizers N‐(n‐butyl) thiophosphoric triamide (NBPT), dicyandiamide (DCD), DCD+NBPT and a maleic and itaconic acid polymer (MIP). 200 (and 400 for urea only) kg N/ha/yr was applied in five equal applications over the growing season at two grassland sites (one for MIP). Mean NH3‐N losses from CAN were 85% lower than urea and had highly variable loss (range 45% points). The effect of DCD on NH3 emissions was variable. MIP did not decrease NH3‐N loss, but NBPT caused a 78.5% reduction and, when combined with DCD, a 74% reduction compared with urea alone. Mean spring and summer losses from urea were similar, although spring losses were more variable with both the lowest and highest losses. Maximum NH3‐N loss usually occurred on the second day after application. These data highlight the potential of stabilized urea to alter urea NH3‐N loss outcomes in temperate grassland, the need for caution when using season as a loss risk guide and that urea hydrolysis in temperate grassland initiates quickly. Micrometeorological measurements focused specifically on urea are needed to determine absolute NH3‐N loss levels in Irish temperate grassland.
The new HLA‐A*24:321 shows one conservative amino acid replacement compared with HLA‐A*24:02:01
Authors: Azkarate M. , Santos S. , Eguizabal C. , Balas A. , Vicario J. L.
Published: November 2015

HLA‐A*24:321 shows one nucleotide difference at codon 49 (GCG>GTG; A49>V49) compared with A*24:02:01.
Human placental renin–angiotensin system in normotensive and pre‐eclamptic pregnancies at high altitude and after acute hypoxia–reoxygenation insult
Authors: Kurlak Lesia O. , Mistry Hiten D. , Cindrova‐Davies Tereza , Burton Graham J. , Pipkin Fiona Broughton
Published: November 2015

Key points

The development of the human placenta occurs in a low oxygen environment which stimulates angiogenesis and vascularization.

Placental expression of the renin angiotensin system (RAS) is highest in early pregnancy. Although both the RAS and oxygen stimulate angiogenesis, it is not known how they interact during placental development.

Pre‐eclampsia (PE), a condition characterized by poor placental development and elevated oxidative stress has increased incidence in populations living at high altitude and thus exposed to hypobaric hypoxia.

This study aimed to investigate the effects of various forms of oxidative stress on the placental RAS.

The results suggest that the placental RAS is activated by oxidative insults but the component type and the degree of activation is dependent on the nature of the insult.

A functioning placental renin–angiotensin system (RAS) appears necessary for uncomplicated pregnancy and is present during placentation, which occurs under low oxygen tensions. Placental RAS is increased in pre‐eclampsia (PE), characterised by placental dysfunction and elevated oxidative stress. We investigated the effect of high altitude hypoxia on the RAS and hypoxia‐inducible factors (HIFs) by measuring mRNA and protein expression in term placentae from normotensive (NT) and PE women who delivered at sea level or above 3100 m, using an explant model of hypoxia–reoxygenation to assess the impact of acute oxidative stress on the RAS and HIFs. Protein levels of prorenin (P = 0.049), prorenin receptor (PRR; P = 0.0004), and angiotensin type 1 receptor (AT1R, P = 0.006) and type 2 receptor (AT2R, P = 0.002) were all significantly higher in placentae from NT women at altitude, despite mRNA expression being unaffected. However, mRNA expression of all RAS components was significantly lower in PE at altitude than at sea level, yet PRR, angiotensinogen (AGT) and AT1R proteins were all increased. The increase in transcript and protein expression of all the HIFs and NADPH oxidase 4 seen in PE compared to NT at sea level was blunted at high altitude. Experimentally induced oxidative stress stimulated AGT mRNA (P = 0.04) and protein (P = 0.025). AT1R (r = 0.77, P < 0.001) and AT2R (r = 0.81, P < 0.001) mRNA both significantly correlated with HIF‐1β, whilst AT2R also correlated with HIF‐1α (r = 0.512, P < 0.013). Our observations suggest that the placental RAS is responsive to changes in tissue oxygenation: this could be important in the interplay between reactive oxygen species as cell‐signalling molecules for angiogenesis and hence placental development and function.
Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system
Authors: Rajendran Pradeep S. , Nakamura Keijiro , Ajijola Olujimi A. , Vaseghi Marmar , Armour J. Andrew , Ardell Jeffrey L. , Shivkumar Kalyanam
Published: November 2015

Key points

Intrinsic cardiac (IC) neurons undergo differential morphological and phenotypic remodelling that reflects the site of myocardial infarction (MI).

Afferent neural signals from the infarcted region to IC neurons are attenuated, while those from border and remote regions are preserved post‐MI, giving rise to a ‘neural sensory border zone’.

Convergent IC local circuit (processing) neurons have enhanced transduction capacity following MI.

Functional network connectivity within the intrinsic cardiac nervous system is reduced post‐MI.

MI reduces the response and alters the characteristics of IC neurons to ventricular pacing.

Autonomic dysregulation following myocardial infarction (MI) is an important pathogenic event. The intrinsic cardiac nervous system (ICNS) is a neural network located on the heart that is critically involved in autonomic regulation. The aims of this study were to characterize structural and functional remodelling of the ICNS post‐MI in a porcine model (control (n = 16) vs. healed anteroapical MI (n = 16)). In vivo microelectrode recordings of basal activity, as well as responses to afferent and efferent stimuli, were recorded from intrinsic cardiac neurons. From control 118 neurons and from MI animals 102 neurons were functionally classified as afferent, efferent, or convergent (receiving both afferent and efferent inputs). In control and MI, convergent neurons represented the largest subpopulation (47% and 48%, respectively) and had enhanced transduction capacity following MI. Efferent inputs to neurons were maintained post‐MI. Afferent inputs were attenuated from the infarcted region (19% in control vs. 7% in MI; P = 0.03), creating a ‘neural sensory border zone’, or heterogeneity in afferent information. MI reduced transduction of changes in preload (54% in control vs. 41% in MI; P = 0.05). The overall functional network connectivity, or the ability of neurons to respond to independent pairs of stimuli, within the ICNS was reduced following MI. The neuronal response was differentially decreased to ventricular vs. atrial pacing post‐MI (63% in control vs. 44% in MI to ventricular pacing; P < 0.01). MI induced morphological and phenotypic changes within the ICNS. The alteration of afferent neural signals, and remodelling of convergent neurons, represents a ‘neural signature’ of ischaemic heart disease.
Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia
Authors: Turner Mark J. , Saint‐Criq Vinciane , Patel Waseema , Ibrahim Salam H. , Verdon Bernard , Ward Christopher , Garnett James P. , Tarran Robert , Cann Martin J. , Gray Michael A.
Published: November 2015

Key points

Raised arterial blood CO2 (hypercapnia) is a feature of many lung diseases.

CO2 has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca2+.

Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO3− transport via pendrin or Na+/HCO3− cotransporters.

These results further support the role of CO2 as a cell signalling molecule and suggests CO2‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs.

Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO2‐induced reduction in anion secretion was not due to a decrease in HCO3− transport given that neither a change in CFTR‐dependent HCO3− efflux nor Na+/HCO3− cotransporter‐dependent HCO3− influx were CO2‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid secretion over 24 h, yet had no effect on the HCO3− content of the secreted fluid. Our data reveal that hypercapnia reduces CFTR‐dependent, electrogenic Cl− and fluid secretion, but not CFTR‐dependent HCO3− secretion, which highlights a differential sensitivity of Cl− and HCO3− transporters to raised CO2 in Calu‐3 cells. Hypercapnia also reduced forskolin‐stimulated CFTR‐dependent anion secretion in primary human airway epithelia. Based on current models of airways biology, a reduction in fluid secretion, associated with hypercapnia, would be predicted to have important consequences for airways hydration and the innate defence mechanisms of the lungs.
The hepatitis C virus protein NS3 suppresses TNF-α–stimulated activation of NF-κB by targeting LUBAC
Authors: Chen Yongzhi , He Liang , Peng Yanan , Shi Xiaodong , Chen Jizheng , Zhong Jin , Chen Xinwen , Cheng Genhong , Deng Hongyu
Published: November 2015

A hepatitis C virus protein blocks NF-κB activation to suppress the antiviral immune response.
Detecting disease before symptoms appear
Authors: Colmone Angela
Published: November 2015

Combining a gene-regulatory network and disease-association data identified early regulators of T cell–associated diseases.
Nlrp6 keeps gut infections in check
Authors: Mueller Kristen L.
Published: November 2015

Control of gut, but not systemic, viral infections in mice requires the protein NLRP6.
Cytosolic functions of ERβ in apoptosis and inflammasome regulation
Authors: Gough Nancy R.
Published: November 2015

Estrogen receptor β and its coregulator SRC-1 interact with cytosolic proteins to inhibit apoptosome activation and promote inflammasome activation.
A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells
Authors: Drummond Coyne G. , Nickerson Cheryl A. , Coyne Carolyn B.
Published: November 2015

Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the epithelium lining the gastrointestinal tract early in infection. The lack of suitable
in vivo
and
in vitro
models to study CVB infection of the gastrointestinal epithelium has limited our understanding of the events that surround infection of these specialized cells. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of human intestinal epithelial cells that better models the gastrointestinal epithelium
in vivo
. By applying this 3-D model, which recapitulates many aspects of the gastrointestinal epithelium
in vivo
, to the study of CVB infection, our work provides a new cell system to model the mechanisms by which CVB infects the intestinal epithelium, which may have a profound impact on CVB pathogenesis.
A rare comorbidity: neurosarcoidosis and cutaneous sarcoidosis
Authors: Akyol Lütfi , Aslan Kerim , Özgen Metin , Sayarlioglu Mehmet
Published: November 2015

We present a case of a neurosarcoidosis patient with skin lesions. A 50-year-old woman was admitted with a 1-year history of violaceous, smooth and shiny plaques on her face and right arm. These lesions were biopsied and the histological examination indicated sarcoidosis. The patient had a history of headache and syncope that lasted for about 1 h. Brain CT showed masses measuring 37×20 mm in both frontal lobes. Thoracic and abdominal CT showed many pathologically enlarged lymph nodes. The patient was diagnosed with cutaneous, lung and neuronal sarcoidosis, and treated with 20 mg/day methylprednisolone, 15 mg/week methotrexate, 10 mg/week folic acid, 400 mg/day hydroxychloroquine and 800 mg/day carbamazepine. One month later, the patient's neurological symptoms had improved and her skin lesions had decreased. At 6-month follow-up, the size of the cranial masses had markedly regressed.
Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study
Authors: Carlsten Chris , Blomberg Anders , Pui Mandy , Sandstrom Thomas , Wong Sze Wing , Alexis Neil , Hirota Jeremy
Published: November 2015

Rationale

Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood.

Objective

To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects.

Methods

18 blinded atopic volunteers were exposed to filtered air or 300 µg PM2.5/m3 of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points.

Results

Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells.

Conclusion

Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.

Trial registration number

NCT01792232.
Structure and charge density distribution of amine azide based hypergolic propellant molecules: a theoretical study
Authors: Kandhakumar Gopal , Kalaiarasi Chinnasamy , Kumaradhas Poomani
Published: November 2015

A quantum chemical calculation and charge density analysis of some amine azide based propellants (DMAZ, DMAEH, ADMCPA, AMCBA and ACPA) have been carried out to understand the geometry, bond topological, electrostatic, and energetic properties. The topological properties of electron density of the molecules were determined using Bader’s theory of atoms in molecules from the wave functions obtained from the density functional method (B3LYP) with the 6-311G** basis set. The electron density distribution of these molecules reveals the nature of chemical bonding in the molecules. The azide group attached C−N bonds of all molecules exhibit the electron density of ρbcp(r) ∼1.639 e Å−3and the Laplacian of electron density ∇2ρbcp(r) is ∼–14.0 e Å−5, in which the corresponding values of the ADMCPA molecule are relatively high, 1.725 e Å–3and –15.2 e Å−5respectively, whereas for the methylamine group attached C–N bonds, these values are found to be higher (1.824 e Å–3and –17.25 e Å−5). The Laplacian of terminal N–N bonds of the azide group is highly negative, indicating that these charges are highly concentrated, whereas the charge concentration of the dimethylamine group attached N–N bond of DMEAH is very much less, confirming that the bond is the weakest bond among the molecules. The energy density has been calculated for each bond of the molecules, which insights the energy density distribution of the molecules. Relatively, the molecules exhibit distinct electrostatic properties that are related to different charge distribution in the molecules. Large negative electrostatic potential regions are found at the vicinity of the amine and azide groups of the molecules. The charge imbalance parameter of the molecules has been determined and shows that the DMAEH molecule is the least sensitive molecule in this series.
The influence of commercial harvesting on parasite infection in the bivalve Austrovenus stutchburyi
Authors: O’Connell-Milne Sorrel , Savage Candida , Rayment William
Published: November 2015

Commercial harvesting often reduces densities of target species, potentially affecting transmission of parasites within the population. Rates of parasitic infection not only impact the hosts directly, but can result in wider ecosystem effects through influences on host behaviour. Commercial harvesting may therefore have important ecological consequences beyond the direct effects of removal of biomass. Clams (Austrovenus stutchburyi) are commonly infected by trematode parasites (Acanthoparyphium spp. and Curtuteria australis) and have been commercially harvested in Otago, New Zealand, since 1983. To assess the effects of harvesting on the abundance of trematodes in A. stutchburyi, the number of parasites per clam was compared in harvested and unharvested areas. The mean number of parasites per clam was 36% higher at commercially harvested sites, suggesting that harvesting enhances the local transmission of parasites. Harvesters may be able to reduce their influence on parasite infection levels in clam populations by harvesting less intensively and allowing more time between harvests for clam biomass to regenerate.
On 1/Z expansion, the critical charge for a two-electron system, and the Kato theorem
Authors: Turbiner A.V. , Vieyra J.C. Lopez
Published: November 2015

The 1/Z expansion for the ground state energy of the Coulomb system of an infinitely massive center of charge Z and two electrons (two-electron ionic sequence) is studied. A critical analysis of the 1/Z coefficients presented in Baker et al. (Phys. Rev. A, 41, 1247 (1990)) is performed and its numerical deficiency is indicated, leading, in particular, to unreliable decimal digits beyond digits 11–12 of the first coefficients. We made a consistency check of the 1/Z-expansion with accurate energies for Z = 1–10: the weighted partial sums of the 1/Z expansion with Baker et al. coefficients reproduce systematically the ground state energies of two-electron ions with Z ≥ 2 up to 12 decimal digits and for Z = 1 up to 10 decimal digits calculated by Nakashima and Nakatsuji (J. Chem. Phys. 127, 224104 (2007)) with unprecedented accuracy. This rules out the presence of non-analytic terms at Z = ∞ contributing to the first 10–12 decimal digits in the ground state energy; it agrees with the Kato theorem about convergence of the 1/Z expansion within that accuracy. The ground state energy of two-electron ions Z = 11 (Na9+) and Z = 12 (Mg10+) is calculated with 12 decimal digits. This study can be considered as the independent confirmation of the correctness of 10 decimal digits in all 401 coefficients of 1/Z-expansion printed in Baker et al. (Phys. Rev. A, 41, 1247 (1990)).
On the sensitivity to partial pressure of oxygen of the mobility in cadmium oxide
Authors: Grado-Caffaro M. A. , Grado-Caffaro M.
Published: November 2015

The partial pressure of oxygen during the deposition process of cadmium oxide is a crucial quantity whose influence on the electrical and optical properties of this material is really very significant (consider, for example, the experimental technique known as activated reactive evaporation). In fact, this paper is a theoretical formulation to evaluate the sensitivity changes of the aforementioned pressure of the electron drift-mobility and velocity in CdO. Indeed, as we will see later, given that the electron relaxation time depends upon the oxygen partial pressure, then the electron drift-mobility, mean free path and velocity also depend on this pressure. Relevant calculations involving the above physical quantities are carried out.
The energy of a unitary Fermi gas in the normal phase including the effect of induced interaction
Authors: Gong Hao , Ruan Xiao-Xia , Pang Hou-Rong , Zong Hong-Shi
Published: November 2015

In this paper, taking into account the effect of the induced interaction, we calculate the energy of ultracold Fermi gases at unitarity in the framework of non-self-consistent T-matrix approximation (nTMA) above the critical temperature and compare the result with the experimental data and other theoretical calculation without induced interaction. Our calculated chemical potential is higher than the experimental data, but our calculated energy obtains a good agreement with Tokyo experiment for temperature range between [Formula: see text] and [Formula: see text].
Approaches to improve the robustness on interdependent networks against cascading failures with load-based model
Authors: Dong Zhengcheng , Fang Yanjun , Tian Meng , Zhang Rong
Published: November 2015

With load-based model, considering the loss of capacity on nodes, we investigate how the coupling strength (many-to-many coupled pattern) and link patterns (one-to-one coupled pattern) can affect the robustness of interdependent networks. In one-to-one coupled pattern, we take into account the properties of degree and betweenness, and adopt four kinds of inter-similarity link patterns and random link pattern. In many-to-many coupled pattern, we propose a novel method to build new networks via adding inter-links (coupled links) on the existing one-to-one coupled networks. For a full investigation on the effects, we conduct two types of attack strategies, i.e. RO-attack (randomly remove only one node) and RF-attack (randomly remove a fraction of nodes). We numerically find that inter-similarity link patterns and bigger coupling strength can effectively improve the robustness under RO-attacks and RF-attacks in some cases. Therefore, the inter-similarity link patterns can be applied during the initial period of network construction. Once the networks are completed, the robustness level can be improved via adding inter-links appropriately without changing the existing inter-links and topologies of networks. We also find that BA–BA topology is a better choice and that it is not useful to infinitely increase the capacity which is defined as the cost of networks.
Exploring Quality Management Practices and Its Pattern Analysis in Indian Service SMEs
Authors: Basu Rana , Bhola Prabha
Published: November 2015

Substantial research exists on quality management practices in context to large organisations with plethora of studies in manufacturing organisations while exiguously aiming service sector SMEs. As more and more organisations strive to remain competitive, the concepts and practices of quality management have received increased attention by Indian industry. The contribution of service sector in Indian economy has increased at a faster rate in comparison with other sectors. Considering the pressing need this research explores the literature for a near exhaustive list of practices in quality management by deploying qualitative and descriptive approach. Thereafter, twenty service organizations were surveyed for comprehending their adoption of the type of quality management practices. On the basis of their prioritization or apportioning weight to those practices, a descriptive pattern analysis has been deployed to detect perceived level of adoption/implementation of quality management practices. The findings represent that out of twenty one quality management practices; thirteen practices substantially have been ranked on priority while others require phenomenal acclimatization towards implementation in the Indian scenario. Analysis also reflects that the strength of service SMEs lies with customer focus, management leadership and customer feedback. Further with the integration of contextual factors, as supported by theory, a conceptual framework has been proposed exhibiting relationship between quality management practices with performance and growth. The methodological approach led to the emergence of unique dimensions culminating into new findings with both managerial and entrepreneurial implications. Directions for future scope of research and suggestions for improvement have also been recommended.
An Exploratory Study on Outcomes of Social Enterprises in South Africa
Authors: Urban Boris
Published: November 2015

This article investigates social enterprises in terms of their outcomes. Few studies focus on social entrepreneurs that incorporate an impact assessment of their social enterprises. The article responds to calls where it has been noted that the rapidly expanding social enterprise sector of the economy is evolving without effective evaluation tools that can provide reliable measurement and impact assessment.

The study is conducted in two major cities in South Africa, where social entrepreneurship has unequivocal application, considering that traditional government initiatives are unable to satisfy the entire social deficit, and where challenges to non-profit accountability are acute. Social outcomes are measured in terms of the following dimensions: impact/reach, innovativeness of solution, replicability/expandability and sustainability. A survey is used to collect data from 165 social enterprises and is interpreted using descriptive statistics.

Results on sample characteristics indicate that a diverse group of individuals are involved in a wide range of social enterprise activities. Descriptive statistics across the dimensions reflect above-average mean scores suggesting favourable perceptions of social outcomes.

By providing an elementary measuring tool for social outcomes, researchers can test its validity across different contexts. Social enterprises need to demonstrate solid impact and reach of their outcomes, so they can replicate interventions, build partnerships, and remain sustainable by meeting the needs of groups who have been failed by previous government attempts in social redress.

The article provides a much needed account of the evaluation of social enterprise outcomes in an emerging market context.
A METHOD FOR COMPARISON OF RADIOCARPAL CARTILAGE T2 RELAXATION TIME MAPS AND CONTACT PRESSURE DISTRIBUTIONS IN NORMAL AND INJURED WRISTS
Authors: Chappell Isaac , Lee Phil , McIff Terence E. , Bruce Toby E. , Fischer Kenneth J.
Published: November 2015

Objective: The goal of this study was to demonstrate a methodology to observe the relationship between joint contact pressure and cartilage T2 relaxation times in three-dimensional space. Methods: One subject diagnosed with unilateral scapholunate dissociation had both injured and uninjured wrists scanned using a Siemens 3T Skyra magnetic resonance imaging (MRI) scanner. Four time echo scans were performed with TE ranging 15–61[Formula: see text]ms with the hand relaxed. T2 maps were constructed using a custom Matlab code, and these maps were registered to anatomical images for the same subject. The anatomical images were used to construct surface contact models and calculate contact pressures for a simple grasp activity in a prior study. Contact pressures and T2 relaxation times were analyzed using regression analysis. Results and Conclusion: This study demonstrates the feasibility of comparing T2 relaxation times and contact pressure data. For this single demonstration subject, it is not surprising that no relationship was found between T2 relaxation times for the articular cartilage and contact pressures in the normal wrist, contact pressures in the wrist with injury, nor contact pressure changes due to injury. However, the method has been demonstrated and may be useful to evaluate the influence of joint injuries or other pathologies on T2 relaxation times in the context of changes in joint contact pressures with larger cohorts of subjects.