bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle
Authors: Slaninova Vera , Krafcikova Michaela , Perez-Gomez Raquel , Steffal Pavel , Trantirek Lukas , Bray Sarah J. , Krejci Alena
Published: February 2016

Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling andin vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling inDrosophilawing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.
Comparing maternal genetic variation across two millennia reveals the demographic history of an ancient human population in southwest Turkey
Authors: Ottoni Claudio , Rasteiro Rita , Willet Rinse , Claeys Johan , Talloen Peter , Van de Vijver Katrien , Chikhi Lounès , Poblome Jeroen , Decorte Ronny
Published: February 2016

More than two decades of archaeological research at the site of Sagalassos, in southwest Turkey, resulted in the study of the former urban settlement in all its features. Originally settled in late Classical/early Hellenistic times, possibly from the later fifth century BCE onwards, the city of Sagalassos and its surrounding territory saw empires come and go. The Plague of Justinian in the sixth century CE, which is considered to have caused the death of up to a third of the population in Anatolia, and an earthquake in the seventh century CE, which is attested to have devastated many monuments in the city, may have severely affected the contemporary Sagalassos community. Human occupation continued, however, and Byzantine Sagalassos was eventually abandoned around 1200 CE. In order to investigate whether these historical events resulted in demographic changes across time, we compared the mitochondrial DNA variation of two population samples from Sagalassos (Roman and Middle Byzantine) and a modern sample from the nearby town of Ağlasun. Our analyses revealed no genetic discontinuity across two millennia in the region and Bayesian coalescence-based simulations indicated that a major population decline in the area coincided with the final abandonment of Sagalassos, rather than with the Plague of Justinian or the mentioned earthquake.
Are there statistical links between the direction of European weather systems and ENSO, the solar cycle or stratospheric aerosols?
Authors: Laken Benjamin A. , Stordal Frode
Published: February 2016

The Hess Brezowsky Großwetterlagen (HBGWL) European weather classification system, accumulated over a long period (more than 130 years), provides a rare opportunity to examine the impact of various factors on regional atmospheric flow. We have used these data to examine changes in the frequency (days/month) of given weather systems direction (WSD) during peak phases in the North Atlantic Oscillation (NAO), El Niño Southern Oscillation (ENSO), solar cycle (SC) and peaks in stratospheric aerosol optical depth (AOD) with superposed epoch analysis and Monte Carlo significance testing. We found highly significant responses to the NAO consistent with expectations: this signal confirmed the utility of the HBGWL data for this type of analysis and provided a benchmark of a clear response. WSD changes associated with ENSO, SC and AOD were generally within the ranges expected from random samples. When seasonal restrictions were added the results were similar, however, we found one clearly significant result: an increase in southerly flow of 2.6±0.8 days/month (
p
=1.9×10
−4
) during boreal summertime in association with El Niño. This result supports the existence of a robust teleconnection between the ENSO and European weather.
Kinship as a frequency dependent strategy
Authors: Ji Ting , Zheng Xiu-Deng , He Qiao-Qiao , Wu Jia-Jia , Mace Ruth , Tao Yi
Published: February 2016

Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction.
Effect of microstructure on the mechanical and damping behaviour of dragonfly wing veins
Authors: Rajabi H. , Shafiei A. , Darvizeh A. , Dirks J.-H. , Appel E. , Gorb S. N.
Published: February 2016

Insect wing veins are biological composites of chitin and protein arranged in a complex lamellar configuration. Although these hierarchical structures are found in many ‘venous wings' of insects, very little is known about their physical and mechanical characteristics. For the first time, we carried out a systematic comparative study to gain a better understanding of the influence of microstructure on the mechanical characteristics and damping behaviour of the veins. Morphological data have been used to develop a series of three-dimensional numerical models with different material properties and geometries. Finite-element analysis has been employed to simulate the mechanical response of the models under different loading conditions. The modelling strategy used in this study enabled us to determine the effects selectively induced by resilin, friction between layers, shape of the cross section, material composition and layered structure on the stiffness and damping characteristics of wing veins. Numerical simulations suggest that although the presence of the resilin-dominated endocuticle layer results in a much higher flexibility of wing veins, the dumbbell-shaped cross section increases their bending rigidity. Our study further shows that the rubber-like cuticle, friction between layers and material gradient-based design contribute to the higher damping capacity of veins. The results of this study can serve as a reference for the design of novel bioinspired composite structures.
Coupling all-atom molecular dynamics simulations of ions in water with Brownian dynamics
Authors: Erban Radek
Published: February 2016

Molecular dynamics (MD) simulations of ions (K+, Na+, Ca2+and Cl−) in aqueous solutions are investigated. Water is described using the SPC/E model. A stochastic coarse-grained description for ion behaviour is presented and parametrized using MD simulations. It is given as a system of coupled stochastic and ordinary differential equations, describing the ion position, velocity and acceleration. The stochastic coarse-grained model provides an intermediate description between all-atom MD simulations and Brownian dynamics (BD) models. It is used to develop a multiscale method which uses all-atom MD simulations in parts of the computational domain and (less detailed) BD simulations in the remainder of the domain.
Fast phase randomization via two-folds
Authors: Simpson D. J. W. , Jeffrey M. R.
Published: February 2016

A two-fold is a singular point on the discontinuity surface of a piecewise-smooth vector field, at which the vector field is tangent to the discontinuity surface on both sides. If an orbit passes through an invisible two-fold (also known as a Teixeira singularity) before settling to regular periodic motion, then the phase of that motion cannot be determined from initial conditions, and, in the presence of small noise, the asymptotic phase of a large number of sample solutions is highly random. In this paper, we show how the probability distribution of the asymptotic phase depends on the global nonlinear dynamics. We also show how the phase of a smooth oscillator can be randomized by applying a simple discontinuous control law that generates an invisible two-fold. We propose that such a control law can be used to desynchronize a collection of oscillators, and that this manner of phase randomization is fast compared with existing methods (which use fixed points as phase singularities), because there is no slowing of the dynamics near a two-fold.
Managing marine mollusc diseases in the context of regional and international commerce: policy issues and emerging concerns
Authors: Carnegie Ryan B. , Arzul Isabelle , Bushek David
Published: February 2016

Marine mollusc production contributes to food and economic security worldwide and provides valuable ecological services, yet diseases threaten these industries and wild populations. Although the infrastructure for mollusc aquaculture health management is well characterized, its foundations are not without flaws. Use of notifiable pathogen lists can leave blind spots with regard to detection of unlisted and emerging pathogens. Increased reliance on molecular tools has come without similar attention to diagnostic validation, raising questions about assay performance, and has been accompanied by a reduced emphasis on microscopic diagnostic expertise that could weaken pathogen detection capabilities. Persistent questions concerning pathogen biology and ecology promote regulatory paralysis that impedes trade and which could weaken biosecurity by driving commerce to surreptitious channels. Solutions that might be pursued to improve shellfish aquaculture health management include the establishment of more broad-based surveillance programmes, wider training and use of general methods like histopathology to ensure alertness to emerging diseases, an increased focus on assay assessment and validation as fundamental to assay development, investment in basic research, and application of risk analyses to improve regulation. A continual sharpening of diagnostic tools and approaches and deepening of scientific knowledge is necessary to manage diseases and promote sustainable molluscan shellfish industries.
Managing marine disease emergencies in an era of rapid change
Authors: Groner Maya L. , Maynard Jeffrey , Breyta Rachel , Carnegie Ryan B. , Dobson Andy , Friedman Carolyn S. , Froelich Brett , Garren Melissa , Gulland Frances M. D. , Heron Scott F. , Noble Rachel T. , Revie Crawford W. , Shields Jeffrey D. , Vanderstichel Raphaël , Weil Ernesto , Wyllie-Echeverria Sandy , Harvell C. Drew
Published: February 2016

Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require.
Crystal structure of 2-[(3aS,6R)-3,3,6-trimethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-2-yl]thiazol-4(5H)-one
Authors: Ousidi Abdellah N'ait , Itto My Youssef Ait , Auhmani Aziz , Riahi Abdelkhalek , Daran Jean-Claude , Abdelwahed Auhmani
Published: February 2016

The title compound, C13H19N3OS, is a new thiazolidin-4-one derivative prepared and isolated as the pure (3aS,6R)-diastereisomer from (R)-thiosemicarbazone pulegone. It crystallized with two independent molecules (AandB) in the asymmetric unit. The compound is composed of a hexhydroindazole ring system (viz.a five-membered dihydropyrazole ring fused to a cyclohexyl ring) with a thiazole-4-one ring system attached to one of the pyrazole N atoms (at position 2). The overall geometry of the two molecules differs slightly, with the mean planes of the pyrazole and thiazole rings being inclined to one another by 10.4 (1)° in moleculeAand 0.9 (1)° in moleculeB. In the crystal, theAandBmolecules are linkedviaC—H...O hydrogen bonds, forming slabs parallel to theabplane. There are C—H...π interactions present within the layers, and between the layers, so forming a three-dimensional structure.
An evaluation of the performance of a large scale collaborative procurement initiative in the social housing sector
Authors: Bowles Graeme , Morgan James
Published: February 2016

Purpose

– The purpose of this paper is to understand the factors relating to the implementation of a new procurement initiative that affect performance and value for money (VFM). The study is based on a four-year research project carried out on behalf of the Scottish Government to monitor and evaluate the performance and efficiency of a bulk procurement vehicle for social housing.

Design/methodology/approach

– The researchers had a brief to monitor and evaluate the implementation of the procurement process and its influence on cost and efficiency targets. The study employed a mixed method approach with annual rounds of qualitative and quantitative data collection from project stakeholders including the contractors, consultants, clients and sponsor. Confidential semi-structured interviews were conducted on conclusion of the project to gauge views on how well the procurement process worked from the various perspectives and to reflect on the influence of the process on VFM.

Findings

– The procurement programme failed to achieve the capital cost and efficiency savings targets quantified at the outset and on this measure alone VFM was not demonstrated, although there were a number of reported benefits. A major factor was the extent of process and behavioural change required from the project team and, although a procurement consultant was engaged to facilitate this, the theoretical benefits of “best practice” were not realized. The picture was further complicated by rapidly changing economic conditions experienced, and debate about the robustness of original cost savings targets.

Research limitations/implications

– The findings and conclusions are of relevance and interest to clients and construction organisations undergoing change through adopting novel procurement processes.

Originality/value

– The empirical nature of the study provides a comprehensive evidence base for the performance of a collaborative procurement programme and an understanding of the potential difficulties in attaining the theoretical benefits of procurement innovation.
Sustainable food security futures
Authors: Irani Zahir , Sharif Amir M
Published: February 2016

Purpose

– The purpose of this paper is to signpost the genesis of food security and associated factors such that organisations, enterprises, policy makers and interested stakeholders can seek to explore and understand this important societal issue. The challenges that food security poses are eclectic in nature and cut through country, society, organisation and individual boundaries. Only through identifying these factors – hence identifying underlying factors of food waste and usage of information within food supply chains to untangle them – can we adopt enterprise interventions in order to initiate and mitigate food security risk.

Design/methodology/approach

– As a viewpoint piece, there is no empirical work to report in this paper. An exploratory review of the literature has allowed for the extraction of food security concerns that need the attention of stakeholders across the enterprise to ensure robust food supply chains can be are created, maintained and sustained through a better understanding and usage of information, knowledge and data.

Findings

– This paper articulates six constructs that underpin the challenges of establishing food security. It is suggested that information relating to factors may support decision-makers within communities, organisations and enterprises to better understand these factors that then contribute towards enhanced food security. Relevant strategies or policies can then emerge and be developed such that strategic as well as operational interventions can be prioritised across national, regional or industry level. Underpinning the above, the waste within and across the food supply chain contributes to the six factors, also highlighting where additional focus may need to be applied to sustain food supply chains.

Research limitations/implications

– This paper is a position paper that does not offer factual insight but rather highlights a direction of thought that others can consider exploring as part of wider research agendas in the topical area where enterprise, organisational, and information-based contributions may support the development of strategy-led food security policy.

Practical implications

– This paper provides reassuring insights that will help decision and policy makers assemble their thoughts when it comes to prioritising their communications and interventions amongst organisational/enterprise-level stakeholder groups involved in food security and food supply chain contexts.

Social implications

– This paper has highlighted the need for more research around the human and organisational factors that are identified as both underpinning the need for food security and, as drivers of waste throughout the food supply chain. Indeed, there is further work needed to highlight the inter-relationships that exist and, which then feed into resulting interventions.

Originality/value

– To raise the importance of food security amongst differing stakeholder community groups at the organisational and enterprise level.
Strategic implications of HR role management in a dynamic environment
Authors: Sheehan Cathy , De Cieri Helen , Cooper Brian , Shea Tracey
Published: February 2016

Purpose

– The purpose of this paper is to consider the impact of human resource (HR) role overload and HR role conflict on the HR function’s involvement in strategic decision making and to examine whether conditions of environmental dynamism moderate the impact of HR role conflict and HR role overload in that relationship.

Design/methodology/approach

– The authors collected data from two sources, senior HR and top management team (TMT) executives. A total of 180 HR executives and 109 TMT members completed the survey. In all, 102 organisations were included in the sample with matched HR executive and TMT responses.

Findings

– Results did not support hypothesised negative relationships between HR role management and involvement in strategic decision making but did establish the moderating effect of environmental dynamism, such that these associations were more negative at higher levels of dynamism.

Research limitations/implications

– The cross-sectional nature of the study precludes making inferences about causality and would need to be replicated with a longitudinal design before stronger inferences could be drawn with regard to the relationships between the variables. A strength of the study however is the use of two sources of data to address the issue of common method variance.

Practical implications

– The research has implications for the potential value that HR provides in dynamic environments and the risk that HR role conflict and overload pose to the contribution that HR can make during these periods.

Originality/value

– The research shifts the focus away from the definition of HR roles to considering how these roles are enacted and kept in balance.
The endless opportunity of organizational agility
Authors: Najrani Majed
Published: February 2016

Purpose

– This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies.

Design/methodology/approach

– This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context.

Findings

– Organizational agility could be accomplished by implementing reactive agility, proactive agility or innovative agility.

Practical implications

– The paper provides strategic insights and practical thinking that have influenced some of the world’s leading organizations.

Originality/value

– The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Kawasaki disease and cardiovascular risk: a comprehensive review of subclinical vascular changes in the longer term
Authors: Chen Katherine Y. H. , Curtis Nigel , Dahdah Nagib , Kowalski Remi , Cheung Michael , Burgner David P.
Published: February 2016

Studies of subclinical vascular changes post‐Kawasaki disease indicate that, in general, individuals with a history of coronary artery aneurysms have increased carotid intima–media thickness, evidence of endothelial dysfunction, and increased arterial stiffness, possibly indicative of heightened cardiovascular risk. The results are less consistent for low‐risk groups.

Conclusion

Until data are available from larger prospective studies, it is prudent to advise families of individuals with a history of Kawasaki disease to minimise traditional modifiable cardiovascular risk factors.
Population pharmacokinetic analysis of lenvatinib in healthy subjects and patients with cancer
Authors: Gupta Anubha , Jarzab Barbara , Capdevila Jaume , Shumaker Robert , Hussein Ziad
Published: February 2016

Aims

Lenvatinib was recently approved for the treatment of radioiodine‐refractory differentiated thyroid cancer (RR‐DTC). Here, we characterized the pharmacokinetic (PK) profile of lenvatinib and identified intrinsic and extrinsic factors that explain interindividual PK variability in humans.

Methods

This population PK analysis used pooled data from 15 clinical studies, including eight phase 1 studies in healthy subjects, four phase 1 studies in patients with solid tumours, two phase 2 studies in patients with thyroid cancer and one phase 3 study in patients with RR‐DTC.

Results

The final pooled dataset included data from 779 subjects receiving 3.2–32 mg oral lenvatinib, mainly once daily as tablets or capsules. Lenvatinib PK was best described by a three‐compartment model with linear elimination. Lenvatinib absorption was best described by simultaneous first‐ and zero‐order absorption. The population mean value for lenvatinib apparent clearance (CL/F) was 6.56 l h−1 [percent coefficient of variation (%CV) 25.5], and was independent of dose and time. The relative bioavailability of lenvatinib in capsule form was 90% vs. tablets (%CV 30.2). The final PK model included significant but marginal effects of body weight (2.8% of CL/F variation), liver‐function markers [alkaline phosphatase (−11.7%) and albumin (−6.3%)] and concomitant cytochrome P450 3A4 inducers (+30%) and inhibitors (−7.8%) on lenvatinib CL/F. Lenvatinib PK was unaffected by pH‐elevating agents, dose, age, sex, race, alanine aminotransferase, aspartate aminotransferase or bilirubin levels, or renal function.

Conclusions

The significant effects of several covariates on lenvatinib PK variability were small in magnitude, and therefore were not considered clinically relevant, or to warrant any dose adjustment.
The predictability and magnitude of life‐history divergence to ecological agents of selection: a meta‐analysis in livebearing fishes
Authors: Moore Michael P. , Riesch Rüdiger , Martin Ryan A.
Published: February 2016

Environments causing variation in age‐specific mortality – ecological agents of selection – mediate the evolution of reproductive life‐history traits. However, the relative magnitude of life‐history divergence across selective agents, whether divergence in response to specific selective agents is consistent across taxa and whether it occurs as predicted by theory, remains largely unexplored. We evaluated divergence in offspring size, offspring number, and the trade‐off between these traits using a meta‐analysis in livebearing fishes (Poeciliidae). Life‐history divergence was consistent and predictable to some (predation, hydrogen sulphide) but not all (density, food limitation, salinity) selective agents. In contrast, magnitudes of divergence among selective agents were similar. Finally, there was a negative, asymmetric relationship between offspring‐number and offspring‐size divergence, suggesting greater costs of increasing offspring size than number. Ultimately, these results provide strong evidence for predictable and consistent patterns of reproductive life‐history divergence and highlight the importance of comparing phenotypic divergence across species and ecological selective agents.
Bcl‐2 proteins in development, health, and disease of the hematopoietic system
Authors: Kollek Matthias , Müller Alexandra , Egle Alexander , Erlacher Miriam
Published: February 2016

Members of the Bcl‐2 protein family regulate cell fate decisions following a variety of developmental cues or stress signals, with the outcomes of cell death or survival, thus shaping multiple mammalian tissues. This review describes in detail how anti‐ and proapoptotic Bcl‐2 proteins contribute to the development and functioning of the fetal and adult hematopoietic systems and how they influence the generation and maintenance of different hematopoietic lineages. An overview on how stress signals such as genotoxic stress or inflammation can compromise blood cell production, partially by engaging the intrinsic apoptosis pathway, is presented. Finally, the review describes how Bcl‐2 protein deregulation—either leading to increased apoptosis resistance or excessive cell death—contributes to many hematological disorders, with specific focus on rare disorders of hematopoiesis and how this knowledge may be used therapeutically.
Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma
Authors: Harimoto Norifumi , Yoshizumi Tomoharu , Shimokawa Masahiro , Sakata Kazuhito , Kimura Kouichi , Itoh Shinji , Ikegami Toru , Ikeda Tetsuo , Shirabe Ken , Maehara Yoshihiko
Published: February 2016

Aim

The present study investigated the effect of sarcopenia on short‐ and long‐term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70 years of age and older.

Methods

Patient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70 years, and 70 years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long‐term survival data were analyzed.

Results

Sarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70 years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70 years. Overall survival and disease‐free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70 years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis.

Conclusion

This retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence‐free survival after hepatectomy in patients 70 years of age and older with HCC.
Effect of cocoa in diabetes: the potential of the pancreas and liver as key target organs, more than an antioxidant effect?
Authors: Mellor Duane D. , Naumovski Nenad
Published: February 2016

Increasingly, type 2 diabetes mellitus is being linked to metabolic abnormalities within the liver and pancreas, associated with fat deposition and oxidative stress. Cocoa and chocolate have been seen to improve oxidative stress and enhance insulin sensitivity. Recent in vitro and animal model studies have begun to investigate the potential of cocoa and cocoa extracts in modulating fatty liver and pancreatic function. Evidence from these studies has highlighted a number of mechanisms, which facilitate insulin secretion and enhanced survival in pancreatic beta cells. Whilst in liver, improved effect of insulin was observed with some improvements in fatty infiltration. However, what was seen as a common effect was an increase in endogenous antioxidant capability. The potential of cocoa products in the management of fatty liver and supporting pancreatic function in humans is likely to be limited by their macronutrient and energy profile or palatability, unless taken as cocoa extract supplements.
MicroRNA‐132 and microRNA‐223 control positive feedback circuit by regulating FOXO3a in inflammatory bowel disease
Authors: Kim Hye‐Youn , Kwon Hyeok Yi , Ha Thi Huyen Trang , Lee Ho Jae , Kim Gwang Il , Hahm Ki‐Baek , Hong Suntaek
Published: February 2016

Background and Aim

Although many progresses have been achieved for inflammatory bowel disease (IBD), it is still remained as idiopathic disease to be completely controlled. MicroRNAs (miRNAs) have been identified as key players in many human diseases through degradation or translational inhibition of target genes. Because role of miRNAs in IBD is not completely understood yet, we need to identify miRNAs as novel targets for treatment of IBD.

Methods

Microarray analysis for miRNAs was performed using dextran sulfate sodium‐induced colitis samples and selected differentially regulated miRNAs. Candidate genes were validated using in vitro system and IBD patient samples. Molecular mechanism for regulation of inflammatory signaling was identified using gene modulation system of miRNAs.

Results

We selected 14 upregulated and 15 downregulated miRNAs through microarray analysis. Among candidate miRNAs, significant upregulation of miR‐132 and miR‐223 was confirmed in inflamed mouse tissues as well as human IBD patient tissues. Through bioinformatics analysis, we identified FOXO3a as direct target of miRNAs and confirmed regulatory mechanism using luciferase assay. Expression of miRNAs clearly suppressed the level of IκBα through downregulation of FOXO3a, leading to enhanced NF‐κB signaling to promote the production of pro‐inflammatory cytokines. The downregulation of FOXO3a concurrent with upregulation of cytokines was significantly reversed by sequestration of miRNAs with miRNA sponges.

Conclusions

Our findings provided the evidences that miR‐132 and 223 are critical mediators in positive circuit for pathogenesis of IBD by negatively regulating FOXO3a to enhance the expression of inflammatory cytokines and can be a good therapeutic target for IBD treatment.
Efficacy of an ethanol/guar/triclosan/glycerine gel on bacteria and yeast loads in canine pododermatitis: a pilot study
Authors: Ortalda C. , Noli C. , Cena T.
Published: February 2016

OBJECTIVES

To assess efficacy of a gel compound containing guar, glycerine, triclosan and ethanol (Pawcare®, JOKER Technologies, Kerzers, Switzerland) in decreasing bacterial and yeast loads on the paws of dogs with erythematous, greasy and/or malodorous pododermatitis.

METHODS

In 20 dogs, each with at least two affected paws, semiquantitative Malassezia species counts were performed on 10 oil‐immersion fields (range: 0 to 30) from acetate tapes pressed on the palmar/plantar surface of one paw. Half of the area was sampled before and the other half immediately after the application of Pawcare®. With a similar procedure, swab samples were collected from the other paw for bacterial culture, identification and evaluation of colony‐forming units before and immediately after treatment. Statistical evaluation of pre‐ and posttreatment counts was performed with the Wilcoxon signed‐rank test.

RESULTS

Nine dogs were positive for Malassezia species Mean acetate tape preparation counts decreased significantly from 8·78 (±8·03) to 5·668 (±6·65) (P=0·0039) after treatment. Twenty‐five bacterial isolates of 11 different species were cultured in 19 dogs. Posttreatment cultures were sterile in 8 dogs that had an initial zero or low number (1 to 2 log counts) of colony‐forming units. In cases with a higher pre‐treatment number of colony forming units (2 to 6 log counts), there was a significant decrease – by a mean of 1·16 log counts (pre 3·12 ±1·69, post 1·96 ±1·57) (P=0·0002).

CLINICAL SIGNIFICANCE

The findings of the present study support the use of PawCare ® gel to decrease bacterial and yeast loads in dogs affected by chronic diseases involving the inter‐digital spaces.
The roles of the hybrid cluster protein, Hcp and its reductase, Hcr, in high affinity nitric oxide reduction that protects anaerobic cultures of Escherichia coli against nitrosative stress
Authors: Wang Jing , Vine Claire E. , Balasiny Basema K. , Rizk John , Bradley Charlene L. , Tinajero‐Trejo Mariana , Poole Robert K. , Bergaust Linda L. , Bakken Lars R. , Cole Jeffrey A.
Published: February 2016

The hybrid cluster protein, Hcp, contains a 4Fe‐2S‐2O iron‐sulfur‐oxygen cluster that is currently considered to be unique in biology. It protects various bacteria from nitrosative stress, but the mechanism is unknown. We demonstrate that the Escherichia coli Hcp is a high affinity nitric oxide (NO) reductase that is the major enzyme for reducing NO stoichiometrically to N2O under physiologically relevant conditions. Deletion of hcp results in extreme sensitivity to NO during anaerobic growth and inactivation of the iron‐sulfur proteins, aconitase and fumarase, by accumulated cytoplasmic NO. Site directed mutagenesis revealed an essential role in NO reduction for the conserved glutamate 492 that coordinates the hybrid cluster. The second gene of the hcp‐hcr operon encodes an NADH‐dependent reductase, Hcr. Tight interaction between Hcp and Hcr was demonstrated. Although Hcp and Hcr purified individually were inactive or when recombined, a co‐purified preparation reduced NO in vitro with a Km for NO of 500 nM. In an hcr mutant, Hcp is reversibly inactivated by NO concentrations above 200 nM, indicating that Hcr protects Hcp from nitrosylation by its substrate, NO.
Comparative analysis of growth and physiological traits between the natural hybrid Sphagneticola trilobata × calendulacea and its parental species
Authors: Li Ting , Huang Li‐Xin , Yi Li , Hong Lan , Shen Hao , Ye Wan‐Hui , Wang Zhang‐Ming
Published: February 2016

Biological invasion is a global environmental issue. Hybridization is considered a stimulus for evolution of invasiveness. It is thus essential to evaluate the invasive potential of new hybrids before management strategies are designed and implemented for them, especially, using performance‐related traits. Comparing growth and physiological traits between invasive species and their non‐invasive congeners is an effective way to identify invasive traits and to predict the invasive potential of species. However, few studies have evaluated the invasive potential of new hybrids by comparative analysis of these traits. We examined the invasive potential of a recently confirmed natural hybrid between the invasive Sphagneticola trilobata, one of the 100 worst invasive species worldwide, and its indigenous congener S. calendulacea. We compared growth and physiological responses of the hybrid and its parental species to different light conditions (open, natural light; shade, 25% of natural light) by conducting a common garden experiment. We then used discriminant analysis to identify those growth and physiological traits that are most different between the invasive and the non‐invasive species. We found that S. trilobata had a higher growth rate, photosynthetic capacity and resource use efficiency than S. calendulacea in both the open and the shade environments, and the hybrid was more similar to S. trilobata than to S. calendulacea in these traits. Discriminant analysis suggested that the hybrid is more similar to S. trilobata than to S. calendulacea for a number of traits associated with performance, and that the hybrids had less invasive potential in the shade than in the open environment. These results indicate that the hybrid has a high invasive potential and could be an efficient invader in both open and shade environments.
Aufgaben des Essayisten
Authors: Winde Arne De , Kohns Oliver
Published: February 2016

Dieser Artikel geht nach, inwiefern Spenglers politische Reden nicht zuletzt wegen des okkasionellen und persuasiven diskursiven Kontextes in einem gegenüber dem Hauptwerk Untergang des Abendlandes gesteigerten Sinn vom essayistischen Stil des Autors geprägt sind. Stil ist hier nicht nur eine Frage des rhetorischen decorums, sondern auch der politischen „Aussage“ der oratorischen Texte. Vor allem anhand der Rede „Aufgaben des Adels“ aus dem Jahr 1924 wird dargelegt, wie Adel und Aristokratie bei Spengler als Deutungsmuster funktionieren, in denen sich heterogene, und teils widersprüchliche Tropen und Narrationen verdichten. Dabei argumentieren die Autoren, dass Spenglers Reden ihre ästhetische und politische Energie aus einer fundamentalen Paradoxie beziehen: Die wuchtige und apodiktische Geste einer rhetorischen Weltordnung, die alles, nur keine Rhetorik sein möchte.
Einführung
Authors: de Beun Cyril , De Cauwer Stijn
Published: February 2016

Dieser Artikel fungiert als Einführung zum Sonderheft Schriftstellerreden. Zum einen stellt diese Einführung das Thema der Schriftstellerrede in einen umfassenden makrohistorischen Rahmen, zum anderen bespricht sie die Artikel dieses Sonderheftes unter Berücksichtigung von deren gemeinsamen Schnittstellen sowie deren Facettenreichtum. Der erste Teil dieser Einführung skizziert den geschichtlichen Hintergrund des redenden Schriftstellers und zeigt, dass die schriftstellerische Redetätigkeit im Laufe der Geschichte stark fluktuierte. Bemerkenswerterweise nahm die Zahl der Schriftstellerreden am Ende des neunzehnten Jahrhunderts, im Anfangsstadium der häufig als autonomistisch und antirhetorisch bezeichneten Moderne, wesentlich zu – eine Tendenz, die sich in der ersten Hälfte des zwanzigsten Jahrhunderts fortsetzte. Deshalb stehen im zweiten Teil die gesellschaftlichen, makrogeschichtlichen Faktoren oder Katalysatoren dieses auffälligen Wachstums im Mittelpunkt der Betrachtung. Wie sich dort herausstellt, wurde der (Wieder)aufstieg der Schriftstellerrede von einem komplexen Zusammenspiel politischer, sozialer, technisch‐medialer und mental‐kultureller Impulse nachhaltig geprägt. Auch wird in einer kurzen Überlegung untermauert, warum der Begriff „Schriftstellerrede“ die Omnipräsenz des redenden Autors am besten deckt. Schließlich bespricht der dritte Teil den inhaltlichen Kern der Artikel in diesem Sonderheft und stellt fest, dass die Artikel dank ihrer breit gefächerten Ansätze signifikante gemeinsame Nenner besitzen, zum Beispiel durch ihren Fokus auf dem Schriftsteller als Intellektuellem und auf der Rede‐immanenten Spannung zwischen dem Inhalt einerseits und dessen rhetorisch‐inszenierter Vermittlung andererseits.
Influence of Parenting Behavior on Psychosocial Adjustment in Early Adolescence: Mediated by Anger Regulation and Moderated by Gender
Authors: Rueth Jana Elisa , Otterpohl Nantje , Wild Elke
Published: February 2016

Emotion regulation (ER)—one of the most important developmental tasks in early adolescence—has been proposed to mediate the relation between parenting and adolescents’ psychosocial adjustment. The aim of this study was to examine the influence of parental psychological control and autonomy support on adolescents’ problem and prosocial behavior (Strengths and Difficulties Questionnaire), as well as to examine the mediating role of adolescents’ anger regulation and the moderating effect of gender. We collected three‐year longitudinal questionnaire data from N = 923 parents and their (at first assessment) 9‐ to 13‐year‐old children. Path‐analysis results mainly support the mediating role of adolescents’ adaptive and maladaptive anger regulation and suggest parental autonomy support to be beneficial for regulatory abilities and psychosocial adjustment, whereas the opposite was found for psychological control. Gender differences were found for parent report data, but not for adolescent report data. Practical and theoretical implications are discussed.
A Novel Method for Indirect Estimation of Tire Pressure
Authors: Solmaz Selim
Published: February 2016

In this paper, a novel algorithm for indirect tire failure indication is described. The estimation method is based on measuring changes in the lateral dynamics behavior resulting from certain types of tire failure modes including excessive deflation or significant thread loss in a combination of tires. Given the fact that both failures will notably affect the lateral dynamics behavior, quantifying these changes constitutes the basis of the estimation method. In achieving this, multiple models and switching method are utilized based on lateral dynamics models of the vehicle that are parametrized to account for the uncertainty in tire pressure levels. The results are demonstrated using representative numerical simulations.
Numerical Simulation of the Structural Response of Al/Graphite Composites Using Unit Cell Models and Different Interface Conditions
Authors: Hernández-Rivera J. L. , Medellín-Castillo H. I. , de Lange D. F. , Mejía-Rodríguez Gilberto
Published: February 2016

The advantages of using graphite as reinforcement in aluminum composites have been addressed by several authors, e.g. Warner et al. [1]. The addition of graphite has been demonstrated to improve the relation strength to density ratio because of the low weight of graphite. Also a significant hardening caused by the difference in the thermal expansion coefficient between graphite and Al matrix have been observed [2]. Furthermore, the presence of graphite has been demonstrated to reduce the wear and abrasion of tools. The structural response of metal matrix composites (MMC) has been studied recently to evaluate the elastic and plastic performance by using Finite Element Method (FEM) [3, 4].

In this paper an analysis of the structural response of Al\graphite composites is presented. The analysis is based on the Finite Element Method (FEM) in the elastic and plastic regions. Several Al\graphite composites with different graphite contents were considered. A FEM model based on a unit cell was proposed and two different Al/graphite interface conditions were assumed: 1) strongly bonded interface, and 2) sliding-friction interface. Also, both regular and irregular arrays of graphite particles in the aluminum were considered in the model. The results in the elastic region are evaluated in terms of the effective elastic modulus and compared with some theoretical models in the literature [5]. From these results it has been observed that when a friction-sliding interface is considered, a slightly smaller elastic modulus is obtained, compared with the strongly-bonded interface condition. Regarding the numerical simulation in the plastic region, the results were compared with theoretical models [6] and experimental data obtained from compression tests.
Analytical Solution of the Dilute Strain Concentration Tensor for Coated Cylindrical Inclusions, and Applications for Polymer Nanocomposites
Authors: Wang Zhen , Fisher Frank T.
Published: February 2016

Recently nanoparticle-reinforced polymer nanocomposite materials, comprised of the inclusion, (non-bulk polymer) interphase and the bulk polymer matrix, have received considerable interest. Because of interaction between the nanoinclusion and surrounding polymer matrix, the non-bulk polymer in the vicinity of the nanoinclusion has different properties than the bulk polymer. With tremendous amount of surface area, the interphase may have a large influence on the overall nanocomposite properties and complicate micromechanical predictions of effective properties. Although several micromechanical approaches can provide approximations of the effective elastic modulus, they require one to calculate the dilute concentration tensor using the well-known Eshelby tensor that treat interphase as separate, physically distinct inclusions. However, their elegant solutions are no longer available when the real geometry of the annular interphase must be considered. This work analytically determined the components of the dilute strain concentration tensors for both the inclusion and the interphase by addressing four auxiliary loading cases, which can be directly implemented within standard micromechanical approaches, such as the Mori-Tanaka model, to predict the effective properties of polymer nanocomposites with cylindrical/fibrous nanoinclusions. Comparison of the predictions of the proposed model with predictions based on the traditional Multiphase Mori-Tanaka approach show that differences between the models are largest when the annular interphase region is softer than the matrix material, attributed to the ability of the proposed model to capture the “stress-shielding effect” in the case of the softer annular interphase. In addition, we have examined several sets of experimental data from the literature for both stiff and soft interphase systems to shed further insight on the utility of the proposed model. The model proposed here would provide an important guideline to evaluate the impact of chemical functionalization techniques and other strategies that seek to tailor the properties of the interphase region in nanocomposite materials.
Validation on the Relationship Between J Integral and CTOD for Offshore Structural Steel Weldments by Experimental and Numerical Analyses
Authors: Moon Dong Hyun , Lee Jeong Soo , Lee Jae Myung , Kim Myung Hyun
Published: February 2016

Elastic plastic fracture mechanics (EPFM) is the domain of fracture analysis which considers extensive plastic deformation at crack tip prior to fracture. J integral and crack tip opening displacement (CTOD) have been commonly used as parameters for EPFM analysis. The relationship between these parameters has been extensively studied by industry and academia. The plastic constraint factor can serve as a parameter to characterize constraint effects in fracture involving plastic deformation. Therefore, the characteristics of plastic constraint factor are important in EPFM analysis. In this study, the relationship between J Integral and CTOD was investigated by conducting fracture toughness tests using single edge notched bend (SENB) specimens. Also, plastic constraint factor was investigated by using finite element analysis. Numerical analysis was carried out using ABAQUS elastic-plastic analysis mode.