bluuebunny/crossref_metadata_2025 huggingface dataset:
Conducting case study research in non-profit organisations
Authors: Shekhar Singh Ardhendu
Published: December 2013

Purpose

– The purpose of this paper is to focus on the transactional relationship between retailers and handicrafts suppliers using case study research.

Design/methodology/approach

– Various reports on the handicraft sector were studied. Interactions with industry experts also helped clarify various issues confronting the industry. Preliminary visits to organizations working in this area were undertaken to know the ground realities of the handicraft sector.

Findings

– To prove the reliability of the case study process and enable others to replicate it, the steps and procedures must be clearly explicit and well documented in the final report. In this research, the steps that are followed to collect the data have been described in detail so that other researchers can apply the case study process and achieve similar results.

Originality/value

– Scholarship focussing on organised retail as well as handicrafts production and marketing is well developed. There is vast literature on the former from the developed economies though the Indian context is only beginning to be researched. Similarly, there are a large number of scholarly and popular writings on the latter. Yet, there is a paucity of scholarship on the buyer-supplier transactions.
Does culture tame the bunny? A content analysis of a global adult magazine
Authors: Kusuma Meidiahna
Published: December 2013

Purpose

– Few empirical studies have probed the effects of culture on the standardization/adaptation decision in the context of controversial products. This study aims to investigate the relationship between sociosexuality and the adaptation decision for editorial images and advertisements inPlayboymagazine through content analysis.

Design/methodology/approach

– This study is a qualitative research using content analysis as the research approach. The content analysis is done forPlayboymagazines from four culturally diverse countries conducted for this study.

Findings

– The result shows that editions of the magazine across four culturally diverse countries reveal that sociosexuality is positively correlated to the degree of nudity in photographs and to the usage of advertising for controversial products. Moreover, the paper uses the concept of sociosexuality to gain a better understanding of the empirical discrepancies concerning nudity or sex appeal.

Originality/value

– This research is an empirical study developed by author to confirm the influence of culture on the standardization/adaptation decision in the context of controversial products. This research is originally developed by author and has not been published before.
Mechanization and the spatial distribution of industries in the German Empire, 1875 to 1907
Authors: Gutberlet Theresa
Published: December 2013

The adoption of water, steam, and electric power transformed manufacturing in the nineteenth century. This article studies the relationship between this technological change and the spatial distribution of manufacturing industries in the German Empire during the late nineteenth and early twentieth century. The adoption of steam powered machinery created incentives for manufacturers to form industry clusters near coal mining regions. Specifically, this article shows that a one standard deviation increase in the average size of steam power operations was associated with a rise in geographic concentration of one‐quarter of a standard deviation. In contrast, a one standard deviation increase in the size of water power operations was associated with a drop in geographic concentration of one‐sixth of a standard deviation. This is consistent with the constraint that water powered plants had to be located on a stream with a sufficient gradient and away from other water powered plants to avoid disruption from neighbouring gates and dams. Together the findings indicate that the transition from water to steam powered machinery contributed to the geographic concentration of manufacturing in the nineteenth century.
Sustainable tourism, climate change and sea level rise adaptation policies in Barbados
Authors: Mycoo Michelle
Published: December 2013

The vulnerability of tourism‐dependent communities, coastal tourism facilities, and beaches to climate change demands the use of measures that can urgently minimise vulnerability and in the long term achieve sustainable development. This paper makes policy recommendations to address climate change and sea level rise challenges in small island developing states. Using Barbados as a case study, the paper found that innovations in policies and projects have offset the past ills of mass tourism and fortuitously now serve as pre‐emptive measures in adapting to climate change. The array of methods for combating these changes includes physical planning policies, integrated coastal zone management, and infrastructure projects. Among the key areas for policy innovation are the adoption of protection, accommodation, and retreat strategies, which are informed by rigorous cost‐benefit analysis and stakeholder consultation. Ecosystem‐based adaptation to climate change is also necessary, especially for islands where coral reef protection is urgent. Moreover, policy adjustments are required on building construction, water resources management, sewage treatment, coastal zone management, physical planning, and land management. Institutional constraints, including the lack of capacity to implement, monitor, and enforce measures, must also be addressed if progress is to be made in adapting to climate change. A major conclusion is that the severity of coastal damage, the importance of tourism to sustainable development, and the country's adaptive capacity play a key part in the selection and implementation of climate change adaptation measures.
First manic episode associated with use of human chorionic gonadotropin for obesity: a case report
Authors: Sanches Marsal , Pigott Teresa , Swann Alan C , Soares Jair C
Published: December 2013

Background

Although highly controversial, the treatment of obesity with exogenous human chorionic gonadotropin (HCG) remains popular in the USA. We report the case of a patient whose first manic episode was associated with the use of HCG for weight loss.

Case report

A 32‐year‐old female patient was admitted to our psychiatric inpatient unit due to a two‐week history of manic symptoms. She had no previous history of manic or hypomanic episodes and had completed a 45‐day course of sublingual HCG for weight loss immediately prior to the onset of the manic episode. The patient was treated with lithium carbonate and aripiprazole, and progressed with improvement in the symptoms.

Conclusion

While it is not possible to definitively link the HCG use to the development of mania, available evidence suggests that HCG may have a contributing role in triggering manic symptomatology.
Semiparametric analysis of linear transformation models with covariate measurement errors
Authors: Sinha Samiran , Ma Yanyuan
Published: December 2013

We take a semiparametric approach in fitting a linear transformation model to a right censored data when predictive variables are subject to measurement errors. We construct consistent estimating equations when repeated measurements of a surrogate of the unobserved true predictor are available. The proposed approach applies under minimal assumptions on the distributions of the true covariate or the measurement errors. We derive the asymptotic properties of the estimator and illustrate the characteristics of the estimator in finite sample performance via simulation studies. We apply the method to analyze an AIDS clinical trial data set that motivated the work.
H2S modulates duodenal motility in male rats via activating TRPV1 and KATP channels
Authors: Lu Wen , Li Jing , Gong Liping , Xu Xiaomeng , Han Ting , Ye Yanfang , Che Tongtong , Luo Yan , Li Jingxin , Zhan Renzhi , Yao Wei , Liu Kejing , Cui Shuang , Liu Chuanyong
Published: December 2013

Background and Purpose

H2S induces vasodilatation by opening KATP channels but it may also affect other ion channels. The aim of this study was to investigate the effect of H2S on intestinal motility in rats and its underlying mechanism.

Experimental Approach

The tension of intestinal muscle strips, afferent firing of intestinal mesenteric nerves, length of duodenal smooth muscle cells and whole‐cell membrane potential of dorsal root ganglion (DRG) neurons were monitored. H2S‐producing enzymes were located by immunofluorescence staining.

Key results

NaHS exerted early transient excitation and late long‐lasting inhibition on the intestinal contraction. The excitation was attenuated by TRPV1 antagonists capsazepine, A784168, SB‐366791 and NK1 receptor antagonist L703606, while the inhibition was attenuated by glibenclamide. NaHS increased duodenal afferent nerve firing and depolarized DRG neurons. These effects were reduced by capsazepine and A784168. NaHS relaxed isolated duodenal smooth muscle cells. The KATP channels were expressed in smooth muscle cells. Cystathionine β‐synthase and cystathionine γ‐lyase were expressed in rat duodenal myenteric neurons. L‐cysteine and S‐adenosyl‐L‐methionine increased the contraction of duodenal muscle strips, an effect attenuated by capsazepine and L703606.

Conclusions and Implications

NaHS induces biphasic effects on intestinal motility in rats while endogenous H2S only exerts an excitatory effect. This transient excitatory effect might be mediated by activation of TRPV1 channels in sensory nerve terminals with the consequent release of substance P. The long‐lasting inhibitory effect might be mediated by activation of KATP channels in the smooth muscle cells. These findings reveal a novel mechanism for the excitatory effect of H2S on gastrointestinal motility.
5‐Lipoxygenase and cysteinyl leukotriene receptor 1 regulate epidermal growth factor‐induced cell migration through Tiam1 upregulation and Rac1 activation
Authors: Magi Shigeyuki , Takemoto Yasushi , Kobayashi Hiroki , Kasamatsu Masato , Akita Takahiro , Tanaka Ayako , Takano Kei , Tashiro Etsu , Igarashi Yasuhiro , Imoto Masaya
Published: December 2013

Cell migration is an essential step for tumor metastasis. The small GTPase Rac1 plays an important role in cell migration. Previously, we reported that epidermal growth factor (EGF) induced two waves of Rac1 activation; namely, at 5 min and 12 h after stimulation. A second wave of EGF‐induced Rac1 activation was required for EGF‐induced cell migration, however, the spatiotemporal regulation of the second wave of EGF‐induced Rac1 activation remains largely unclear. In this study, we found that 5‐lipoxygenase (5‐LOX) is activated in the process of EGF‐induced cell migration, and that leukotriene C4 (LTC4) produced by 5‐LOX mediated the second wave of Rac1 activation, as well as cell migration. Furthermore, these effects caused by LTC4 were found to be blocked in the presence of the antagonist of cysteinyl leukotriene receptor 1 (CysLT1). This blockage indicates that LTC4‐mediated CysLT1 signaling regulates the second EGF‐induced wave of Rac1 activation. We also found that 5‐LOX inhibitors, CysLT1 antagonists and the knockdown of CysLT1 inhibited EGF‐induced T cell lymphoma invasion and metastasis‐inducing protein 1 (Tiam1) expression. Tiam1 expression is required for the second wave of EGF‐induced Rac1 activation in A431 cells. Therefore, our results indicate that the 5‐LOX/LTC4/CysLT1 signaling pathway regulates EGF‐induced cell migration by increasing Tiam1 expression, leading to a second wave of Rac1 activation. Thus, CysLT1 may serve as a new molecular target for antimetastatic therapy. In addition, the CysLT1 antagonist, montelukast, which is used clinically for allergy treatment, might have great potential as a novel type of antimetastatic agent.
The impact of early cytomegalovirus infection after kidney transplantation on long‐term graft and patient survival
Authors: Smedbråten Yuliya V. , Sagedal Solbjørg , Leivestad Torbjørn , Mjøen Geir , Osnes Kåre , Rollag Halvor , Reisæter Anna V. , Foss Aksel , Os Ingrid , Hartmann Anders
Published: December 2013

This prospective observational cohort study is an extension of a previous study reporting effects of cytomegalovirus (CMV) on graft and patient survival in 471 patients who underwent kidney transplantation between 1994 and 1997. CMV pp65 antigen was measured every 7–14 d during the first three months after transplantation, given as number of CMV pp65‐positive cells per 105 leukocytes. A positive test was defined as CMV infection. None of the patients received CMV prophylaxis or preemptive treatment. During a median of 13.7 (7.1–14.9) yr, the number of death‐censored graft losses was 118 (25%) and of patient deaths 224 (48%). CMV infection was an independent significant risk factor for mortality in multivariate analysis (HR = 1.453, 95% CI 1.033–2.045, p = 0.032), adjusting for patient and donor age, preemptive transplantation, HLA‐DR and ‐AB mismatches, living donor, acute rejection during the first three months, donor–recipient CMV IgG antibody status and diabetic nephropathy. In univariate analysis, CMV infection was significantly associated with death‐censored graft loss but the association was not significant in multivariate model. CMV infection early after kidney transplantation is a predictor of overall mortality but not of death‐censored graft loss after a median observation period of 13.7 yr.
Clinical outcomes among renal transplant recipients with pre‐transplant weakly reactive donor‐specific antibodies
Authors: Yoo Peter S. , Bonnel Alexander , Kamoun Malek , Levine Matthew H.
Published: December 2013

Background

Alloantibody can lead to antibody‐mediated rejection and graft loss in renal transplantation, necessitating an assessment of cross‐match compatibility. Within the past decade, more specific solid phase assays of alloantibody have been widely adopted, allowing virtual cross‐matching based on unacceptable antigens, the threshold of which is determined by individual centers.

Methods

We examined the clinical outcomes of 482 patients transplanted 2007–2009 in a single center, focusing on 30 patients with weakly reactive donor‐specific antibody (DSA) determined prospectively prior to renal transplant.

Results

Compared with patients without DSA, patients with weakly reactive DSA do not have increased rates of antibody‐mediated rejection, cellular rejection, or graft loss despite conventional immunosuppression utilization.

Conclusions

Using the screening methodology and immunosuppression regimen, we have applied to the patients with weak DSA allows them to be transplanted with equivalent outcomes as those without DSA, despite the overall higher risk characteristics of the patients in the weak DSA group.
Mountain landscapes offer few opportunities for high‐elevation tree species migration
Authors: Bell David M. , Bradford John B. , Lauenroth William K.
Published: December 2013

Climate change is anticipated to alter plant species distributions. Regional context, notably the spatial complexity of climatic gradients, may influence species migration potential. While high‐elevation species may benefit from steep climate gradients in mountain regions, their persistence may be threatened by limited suitable habitat as land area decreases with elevation. To untangle these apparently contradictory predictions for mountainous regions, we evaluated the climatic suitability of four coniferous forest tree species of the western United States based on species distribution modeling (SDM) and examined changes in climatically suitable areas under predicted climate change. We used forest structural information relating to tree species dominance, productivity, and demography from an extensive forest inventory system to assess the strength of inferences made with a SDM approach. We found that tree species dominance, productivity, and recruitment were highest where climatic suitability (i.e., probability of species occurrence under certain climate conditions) was high, supporting the use of predicted climatic suitability in examining species risk to climate change. By predicting changes in climatic suitability over the next century, we found that climatic suitability will likely decline, both in areas currently occupied by each tree species and in nearby unoccupied areas to which species might migrate in the future. These trends were most dramatic for high elevation species. Climatic changes predicted over the next century will dramatically reduce climatically suitable areas for high‐elevation tree species while a lower elevation species, Pinus ponderosa, will be well positioned to shift upslope across the region. Reductions in suitable area for high‐elevation species imply that even unlimited migration would be insufficient to offset predicted habitat loss, underscoring the vulnerability of these high‐elevation species to climatic changes.
Historical assemblage distinctiveness and the introduction of widespread non‐native species explain worldwide changes in freshwater fish taxonomic dissimilarity
Authors: Toussaint Aurèle , Beauchard Olivier , Oberdorff Thierry , Brosse Sébastien , Villéger Sébastien
Published: December 2013

Aim

Taxonomic dissimilarity between assemblages can result from two processes – the replacement of species (turnover) and differences in richness – but it remains unclear how anthropogenic drivers (introductions and extirpations) affect these processes. Here, we investigate how historical patterns and anthropogenic drivers shape the changes in dissimilarity and its turnover component in freshwater fish assemblages both in historical (i.e. pre‐industrial) times and at the present day.

Location

World‐wide.

Methods

We used a global database of fish assemblages in 1054 river basins throughout the world to quantify the change in turnover through its contribution to taxonomic dissimilarity between the two periods. We then used random forests to disentangle the relative roles of historical distinctiveness, species introductions and species extirpations on changes in dissimilarity and on the contribution of its turnover component.

Results

The pairs of basins exhibited a decrease in the contribution of turnover to taxonomic dissimilarity of 82% and 61% in homogenized and differentiated pairs, respectively. The historical number of shared species and its change after species introductions and extirpations accounted for more than 60% of the change in dissimilarity and in the turnover contribution in the six biogeographical realms.

Main conclusions

The historically high distinctiveness between pairs of basins, due to a low number of shared species, has promoted high levels of taxonomic dissimilarity. The world‐wide changes in taxonomic dissimilarity among fish assemblages are to a large extent coupled to a decrease in the contribution of taxonomic turnover to taxonomic dissimilarity. Hence, the dissimilarity between assemblages declines with decreasing species replacement. These changes are mainly explained by introductions of a small set of widespread non‐native species, which promote an increase in the number of shared species. Alongside historical distinctiveness, species introduction processes can determine whether assemblages become more homogenized or more differentiated. Our results suggest that taxonomic differentiation can quickly turn to homogenization as the number of species introductions increase.
Unions, Wage Gaps, and Wage Dispersion: New Evidence from the Americas
Authors: Rios‐Avila Fernando , Hirsch Barry T.
Published: December 2013

Using a common methodology, the effects of unions on wage levels and wage dispersion are estimated for two neighboring countries, Bolivia and Chile, and for the United States. The analysis shows that unions have broadly similar effects on the wage distribution within these three economies. The findings suggest that the political economy of unions, coupled with market constraints on labor costs, produce commonality in union wage effects that transcend other economic and institutional differences.
Wage Discrimination Against Workers with Sensory Disabilities
Authors: Baldwin Marjorie L. , Choe Chung
Published: December 2013

We link information on occupation‐specific job demands to data from the Survey of Income and Program Participation to provide first‐ever estimates of wage discrimination against workers with sensory disabilities. Estimates are derived from wage models that control for job demands related to sensory abilities, and interactions between job demands and workers' sensory limitations. Results indicate approximately one third (one tenth) of the male (female) disability‐related wage differential is potentially attributed to discrimination. The results differ from estimates of discrimination against workers with physical disabilities obtained with similar methods, underscoring the importance of accounting for heterogeneity of the disabled population in discrimination studies.
Informal Institutions and Horizontal Accountability: Protocols in the Chilean Budgetary Process
Authors: Araya Ignacio Arana
Published: December 2013

Studies of executive-legislative relations are usually based only on the analysis of formal institutions, although informal institutions also shape interbranch behavior. This omission leads to questionable results when scholars examine the capacity of state institutions to audit other public agencies and branches of government. This article explores how the protocols, an informal institution that shapes the Chilean budgetary negotiations, have increasingly allowed the congress to have a more relevant budgetary role than what the constitution permits. It argues that protocols accommodate some of the undesired consequences of a charter that is strongly biased toward the central government, and describes how this institution has departed from its stringent budgetary focus to encompass broader executive-legislative agreements that enhance the legislature's capacity to oversee the executive.
Viking Sagas: Six Degrees of Icelandic Separation Social Networks from the Viking Era
Authors: Mac Carron Pádraig , Kenna Ralph
Published: December 2013

The Icelandic sagas are thousand-year-old stories of brave deeds and lives and loves, with a cast of thousands – but how true to life are they? Pádraig Mac Carron and Ralph Kenna analyse the interactions between the characters and find that social networks of the Viking era were very similar to those of today.
Early influences on child satiety‐responsiveness: the role of weaning style
Authors: Brown A. , Lee M. D.
Published: December 2013

Background

Nutrition during infancy may have a long‐term impact upon weight gain and eating style. How infants are introduced to solid foods may be important. Traditionally, infants are introduced to solid foods via spoon‐feeding of purees. However, baby‐led weaning advocates allowing infants to self‐feed foods in their whole form. Advocates suggest this may promote healthy eating styles, but evidence is sparse. The aim of the current study was to compare child eating behaviour at 18–24 months between infants weaned using a traditional weaning approach and those weaned using a baby‐led weaning style.

Methods

Two hundred ninety‐eight mothers with an infant aged 18–24 months completed a longitudinal, self‐report questionnaire. In Phase One, mothers with an infant aged 6–12 months reported breastfeeding duration, timing of solid foods, weaning style (baby‐led or standard) and maternal control, measured using the Child Feeding Questionnaire. At 18–24 months, post‐partum mothers completed a follow‐up questionnaire examining child eating style (satiety‐responsiveness, food‐responsiveness, fussiness, enjoyment of food) and reported child weight.

Results

Infants weaned using a baby‐led approach were significantly more satiety‐responsive and less likely to be overweight compared with those weaned using a standard approach. This was independent of breastfeeding duration, timing of introduction to complementary foods and maternal control.

Conclusions

A baby‐led weaning approach may encourage greater satiety‐responsiveness and healthy weight‐gain trajectories in infants. However, the limitations of a self‐report correlational study are noted. Further research using randomized controlled trial is needed.
Suitability of A European Nuclear Collection of Brassica oleracea L. Landraces to Grow at High Temperatures
Authors: Rodríguez V. M. , Soengas P. , Cartea E. , Sotelo T. , Velasco P.
Published: December 2013

Statistical models predict that global warming will have a negative impact in crop yields in the next decades. Especially vulnerable are winter crops such as kales or cabbages (Brassica oleracea L.). We evaluated the impact of high temperatures in morphological and biochemical traits of a B. oleracea core collection during early development. When grown at 30 °C, plants showed a reduction in chlorophyll content, early vigour and biomass compared with values observed on plants grown at 20 °C. Likewise, the total content of glucosinolates shows a reduction at high temperatures. The alboglabra group showed the best general performance at 30 °C for both morphological traits and glucosinolate content. Based on a cluster analysis, we selected four populations (MBG0072, MBG0464, MBG0535 and HRIGRU5555) as the most promising to be used in further breeding programs for heat tolerance.
Motor neuropathy‐associated mutation impairs Seipin functions in neurotransmission
Authors: Wei Shunhui , Soh Stephanie Li‐Ying , Xia Julia , Ong Wei‐Yi , Pang Zhiping P. , Han Weiping
Published: December 2013

Gain‐of‐toxic‐function mutations in Seipin (Asparagine 88 to Serine (N88S) and Serine 90 to Leucine (S90L) mutations, both of which disrupt the N‐glycosylation) cause autosomal dominant motor neuron diseases. However, the mechanism of how these missense mutations lead to motor neuropathy is unclear. Here, we analyze the impact of disruption of N‐glycosylation of Seipin on synaptic transmission by over‐expressing mutant Seipin in cultured cortical neurons via lentiviral infection. Immunostaining shows that over‐expressed Seipin is partly colocalized with synaptic vesicle marker synaptophysin. Electrophysiological recordings reveal that the Seipin mutation significantly decreases the frequency, but not the amplitudes of miniature excitatory post‐synaptic currents and miniature inhibitory post‐synaptic currents. The amplitude of both evoked excitatory post‐synaptic currents and inhibitory post‐synaptic current is also compromised by mutant Seipin over‐expression. The readily releasable pool and vesicular release probability of synaptic vesicles are both altered in neurons over‐expressing Seipin‐N88S, whereas neither γ‐amino butyric acid (GABA) nor α‐Amino‐3‐hydroxy‐5‐methyl‐4‐ isoxazolepropionic acid (AMPA) induced whole cell currents are affected. Moreover, electron microscopy analysis reveals decreased number of morphologically docked synaptic vesicles in Seipin‐N88S‐expressing neurons. These data demonstrate that Seipin‐N88S mutation impairs synaptic neurotransmission, possibly by regulating the priming and docking of synaptic vesicles at the synapse.

image

Motoneuropathy‐associated endoplasmic reticulum (ER) protein Seipin‐N88S mutation disrupts N‐glycosylation and decreased the frequency of miniature excitatory and inhibitory post‐synaptic currents (PSCs), and the amplitude of evoked excitatory and inhibitory PSCs. The readily releasable pool and synaptic vesicle (SV) release probability were reduced in neurons over‐expressing Seipin‐N88S, along with decreased number of docked vesicles. We propose that Seipin‐N88S mutation impairs synaptic neurotransmission by regulating the docking of synaptic vesicles.
LPS or ethanol triggers clathrin‐ and rafts/caveolae‐dependent endocytosis of TLR4 in cortical astrocytes
Authors: Pascual‐Lucas Maya , Fernandez‐Lizarbe Sara , Montesinos Jorge , Guerri Consuelo
Published: December 2013

Toll‐like receptor 4 (TLR4) activation and signalling in glial cells play critical roles in neurological disorders and in alcohol‐induced brain damage. TLR4 endocytosis upon lipopolysaccharide (LPS) stimulation regulates which signalling pathway is activated, the MyD88‐dependent or the TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF)‐dependent pathway. However, it remains elusive whether ethanol‐induced TLR4 signalling is associated with receptor internalization and trafficking, and which endocytic pathway(s) are used in cortical astrocytes. Using the adenoviral over‐expression of TLR4GFP, confocal microscopy and the imagestream technique, we show that upon ethanol or LPS stimulation, TLR4 co‐localizes with markers of the clathrin and caveolin endocytic pathways, and that this endocytosis is dependent on dynamin. Using chlorpromazin and filipin as inhibitors of the clathrin and rafts/caveolae endocytic pathways, respectively, we demostrate that TRIF‐dependent signalling relies on an intact clathrin pathway, whereas disruption of rafts/caveolae inhibits the MyD88‐ and TRIF‐dependent signalling pathways. Immunofluorescence studies also suggest that lipid rafts and clathrin cooperate for appropriate TLR4 internalization. We also show that ethanol can trigger similar endocytic pathways as LPS does, although ethanol delays clathrin internalization and alters TLR4 vesicular trafficking. Our results provide new insights into the effects of ethanol or LPS on TLR4 signalling in cortical astrocytes, events that may underlie neuroinflammation and brain damage.

image

The results demonstrate that ethanol or lipopolysaccharide (LPS) triggers toll‐like receptor 4 (TLR4) endocytosis by caveolae and clathrin‐dependent pathways in astrocytes. We proposed that while clathrin is the protein responsible for TLR4 internalization, caveolin‐1/lipid rafts membrane microdomains are required for TLR4 signaling. The results provide new insights into the effects of ethanol on TLR4 signalling in astrocytes, events that may underlie neuroinflammation.
Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2
Authors: Vandal Milène , Alata Wael , Tremblay Cyntia , Rioux‐Perreault Christine , Salem Norman , Calon Frédéric , Plourde Mélanie
Published: December 2013

Benefits on cognition from docosahexaenoic acid (DHA, 22 : 6 n‐3) intake are absent in humans carrying apolipoprotein E ε4 allele (APOE4), the most important genetic risk factor for Alzheimer's disease (AD). To test the hypothesis that carrying APOE4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [14C]‐DHA using in situ cerebral perfusion through the blood–brain barrier in 4‐ and 13‐month‐old male and female APOE‐targeted replacement mice (APOE2, APOE3, and APOE4), fed with a DHA‐depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE4 compared to APOE2 mice, respectively. Brain uptake of [14C]‐DHA was 24% lower in APOE4 versus APOE2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice (r2 = 0.21) and AD patients (r2 = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE4 than in APOE2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of AD.

image

Using human APOE2, 3, and 4 isoform‐specific transgenic mice, we found a lower brain uptake of docosahexaenoic acid (DHA) in APOE4 than in APOE2 mice that may limit the biodistribution of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD).
Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth
Authors: Nordman Jacob C. , Phillips Wiktor S. , Kodama Nathan , Clark Sarah G. , Del Negro Christopher A. , Kabbani Nadine
Published: December 2013

Cholinergic signaling plays an important role in regulating the growth and regeneration of axons in the nervous system. The α7 nicotinic receptor (α7) can drive synaptic development and plasticity in the hippocampus. Here, we show that activation of α7 significantly reduces axon growth in hippocampal neurons by coupling to G protein‐regulated inducer of neurite outgrowth 1 (Gprin1), which targets it to the growth cone. Knockdown of Gprin1 expression using RNAi is found sufficient to abolish the localization and calcium signaling of α7 at the growth cone. In addition, an α7/Gprin1 interaction appears intimately linked to a Gαo, growth‐associated protein 43, and CDC42 cytoskeletal regulatory pathway within the developing axon. These findings demonstrate that α7 regulates axon growth in hippocampal neurons, thereby likely contributing to synaptic formation in the developing brain.

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Stages in the development of CA3 neurons illustrate how the α7 nicotinic receptor (nAChR) can contribute to axon growth. Protein expression of α7 and G protein‐regulated inducer of neurite outgrowth 1 (Gprin1) peaks between E18 and P10 in rodents. This time period is characterized by significant changes in synaptic structure and circuit development in the hippocampus. α7‐mediated elevations in intracellular calcium within the growth cone (GC) are proposed to serve as ‘stop’ signal for axon growth, thereby possibly contributing to synaptic pruning. Interaction with Gprin1 ensures localization of α7 at the GC, and mediates coupling to a Gαo, GAP‐43, and CDC42 signaling pathway.
Association Between Inflammatory Markers, Hemostatic Markers, and Traditional Risk Factors on Coronary Artery Spasm in Patients with Normal Coronary Angiography
Authors: MAHEMUTI AILIMAN , ABUDUREHEMAN KAILIBINUER , SCHIELE FRANCOIS , ECARNOT FIONA , ABUDUREYIMU SHAJIDAN , TANG BAOPEN , UPUR HALMURAT , MENEVEAU NICOLAS
Published: December 2013

Background

Coronary artery spasm is an important pathophysiological mechanism in some forms of myocardial ischemic disease. The relationship between inflammatory markers, mean platelet volume (MPV), and coronary artery spasm is unclear.

Methods and Results

During coronary angiography, methylergometrin was injected intravenously to 345 patients with chest pain but without significant coronary disease on angiogram to provoke coronary artery spasm. Based on provocation test results, patients were divided into 2 groups: spasm group (60 patients) and nonspasm group (285 patients). Inflammatory markers (C‐reactive protein, CRP; white blood cells; polymorphonuclear neutrophils, PMN; monocytes, MO; lymphocytes, LY), hemostasis markers (MPV; platelet count; fibrinogen [FIB]; D‐dimers), and traditional risk factors (body mass index; hyperlipidemia; triglycerides [TGs]; total, low‐density, and high‐density lipoprotein cholesterol [TC, LDL‐C, and HDL‐C]) were measured and compared between groups. More male patients experienced spasm (23.56% vs. 11.11%, P = 0.002). CRP, PMN, and MO were significantly higher in the spasm group (P < 0.05). There was no significant difference in serum levels of LDL‐C, HDL‐C, TG, TC, LY, MPV, and FIB between groups. Smoking and hyperlipidemia were more common among patients with spasm; males more frequently were smokers (58.04% vs. 46.78%, P = 0.041). By multivariate analysis, smoking, PMN, and MO were significantly associated with coronary artery spasm with odds ratios of 3.52 (95% CI 1.79–6.90, P = 0.0001), 1.21 (95% CI 1.07–1.46, P = 0.04), and 5.35 (95% CI 1.37–21.07, P = 0.01), respectively.

Conclusions

Inflammation may partake in the pathogenesis of coronary artery spasm. Smoking, PMN count, and MO count appear to be clinical risk factors for coronary artery spasm. Conversely, coronary artery spasm does not seem to be associated with abnormalities in thrombogenesis. (J Interven Cardiol 2014;27:29–35)
Donor information based prediction of early allograft dysfunction and outcome in liver transplantation
Authors: Hoyer Dieter P. , Paul Andreas , Gallinat Anja , Molmenti Ernesto P. , Reinhardt Renate , Minor Thomas , Saner Fuat H. , Canbay Ali , Treckmann Jürgen W. , Sotiropoulos Georgios C. , Mathé Zoltan
Published: December 2013

Background & Aims

Poor initial graft function was recently newly defined as early allograft dysfunction (EAD) [Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010; 16: 943]. Aim of this analysis was to evaluate predictive donor information for development of EAD.

Methods

Six hundred and seventy‐eight consecutive adult patients (mean age 51.6 years; 60.3% men) who received a primary liver transplantation (LT) (09/2003–12/2011) were included. Standard donor data were correlated with EAD and outcome by univariable/multivariable logistic regression and Cox proportional hazards to identify prognostic donor factors after adjustment for recipient confounders. Estimates of relevant factors were utilized for construction of a new continuous risk index to develop EAD.

Results

38.7% patients developed EAD. 30‐day survival of grafts with and without EAD was 59.8% and 89.7% (P < 0.0001). 30‐day survival of patients with and without EAD was 68.5% and 93.1% (P < 0.0001) respectively. Donor body mass index (P = 0.0112), gGT (P = 0.0471), macrosteatosis (P = 0.0006) and cold ischaemia time (CIT) (P = 0.0031) were predictors of EAD. Internal cross validation showed a high predictive value (c‐index = 0.622).

Conclusions

Early allograft dysfunction correlates with early results of LT and can be predicted by donor data only. The newly introduced risk index potentially optimizes individual decisions to accept/decline high risk organs. Outcome of these organs might be improved by shortening CIT.
Role of gap junctions modulating hepatic vascular tone in cirrhosis
Authors: Hernández‐Guerra Manuel , González‐Méndez Yanira , de Ganzo Zaida A. , Salido Eduardo , García‐Pagán Juan C. , Abrante Beatriz , Malagón Antonio M. , Bosch Jaime , Quintero Enrique
Published: December 2013

Background & Aims

Gap junctions are formed by connexins (Cx), a family of proteins that couple endothelial and smooth muscle cells in systemic vessels. In this context, Cx allow the transmission of signals modulating vascular tone. Recently, vascular Cx have been observed in liver cells implicated in liver blood flow regulation. Here, we investigated the role of Cx in the regulation of intrahepatic vascular tone in cirrhosis.

Methods

Livers of Sprague–Dawley control and cirrhotic (common bile duct ligation‐CBDL and CCl4) rats were perfused, and concentration–effect curves in response to acetylcholine (ACh) precontracted with methoxamine were obtained in the presence of the specific Cx inhibitor 18‐alpha‐glycyrrhetinic acid or vehicle. Cx expression was assessed by immunofluorescence, western blot and reverse‐transcription polymerase chain reaction in liver tissue, hepatic stellate cells, sinusoidal endothelial cells and hepatocytes isolated from control and cirrhotic rat livers. Cx protein expression was also determined in cirrhotic human tissue.

Results

Gap junction blockade markedly attenuated relaxation of hepatic vasculature in response to ACh in control (maximal relaxation, −55 ± 10.5% vs. −95.3 ± 10% with vehicle; P < 0.01) and CBDL rats (50.9 ± 18.5% vs. −18.7 ± 5.5% with vehicle; P = 0.01). Livers from CBDL rats and patients with cirrhosis exhibited Cx overexpression. By contrast, CCl4‐cirrhotic rats did not show attenuated relaxation of hepatic vasculature after blockade and Cx expression was significantly lower than in controls.

Conclusions

Gap junctions may contribute to modulating portal pressure and intrahepatic vascular relaxation. Liver gap junctions may represent a new therapeutic target in cirrhotic portal hypertension.
Postoperative recurrence pattern and prognosis of patients with hepatocellular carcinoma, with particular reference to the hepatitis viral infection status
Authors: Naito Shigetoshi , Imamura Hiroshi , Tukada Akira , Matsuyama Yutaka , Yoshimoto Jiro , Sugo Hiroyuki , Ishizaki Yoichi , Kawasaki Seiji
Published: December 2013

Background & Aims

Various modalities have been employed effectively according to the tumour recurrence status in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. Therefore, their overall prognosis depends largely on the pattern of recurrence/treatment. We investigated the patterns of recurrence and prognosis in HCC patients, especially in relation to the hepatitis virus infection status.

Methods

The study population comprised 244 patients with HCC undergoing hepatectomy. Curative treatments, including repeated hepatectomies, were performed for recurrences, whenever possible. Detailed information on recurrences was collected until the recurrences exceeded Milan criteria.

Results

The 5‐year disease‐free survival, survival within the Milan criteria and overall survival were 38.4%, 56.3% and 74.5% respectively. In the comparison between patients with hepatitis C and B virus‐related HCC (HC‐HCC: n = 122; and HB‐HCC: n = 45 respectively), the former showed lower disease‐free (30.2% vs. 40.7% at 5 years, P = 0.061) and overall (65.7% vs. 89.7% at 5 years, P = 0.011) survivals; they also showed a higher incidence of multinodular (≥4) intrahepatic recurrences (19.4% vs. 5.3% at 3 years, P = 0.010). However, the incidences of recurrences exceeding the Milan criteria because of other components were comparable. Patients with HC‐HCC showed a higher incidence of intrahepatic recurrences characterized by multiple lesions and the difference became increasingly more pronounced with time.

Conclusions

Patients with HC‐HCC were associated with a higher carcinogenesis in the background liver than those with HB‐HCC, and this difference was aggravated with time after hepatic resection.
Population size and time since island isolation determine genetic diversity loss in insular frog populations
Authors: Wang Supen , Zhu Wei , Gao Xu , Li Xianping , Yan Shaofei , Liu Xuan , Yang Ji , Gao Zengxiang , Li Yiming
Published: December 2013

Understanding the factors that contribute to loss of genetic diversity in fragmented populations is crucial for conservation measurements. Land‐bridge archipelagoes offer ideal model systems for identifying the long‐term effects of these factors on genetic variations in wild populations. In this study, we used nine microsatellite markers to quantify genetic diversity and differentiation of 810 pond frogs (Pelophylax nigromaculatus) from 24 islands of the Zhoushan Archipelago and three sites on nearby mainland China and estimated the effects of the island area, population size, time since island isolation, distance to the mainland and distance to the nearest larger island on reduced genetic diversity of insular populations. The mainland populations displayed higher genetic diversity than insular populations. Genetic differentiations and no obvious gene flow were detected among the frog populations on the islands. Hierarchical partitioning analysis showed that only time since island isolation (square‐root‐transformed) and population size (log‐transformed) significantly contributed to insular genetic diversity. These results suggest that decreased genetic diversity and genetic differentiations among insular populations may have been caused by random genetic drift following isolation by rising sea levels during the Holocene. The results provide strong evidence for a relationship between retained genetic diversity and population size and time since island isolation for pond frogs on the islands, consistent with the prediction of the neutral theory for finite populations. Our study highlights the importance of the size and estimated isolation time of populations in understanding the mechanisms of genetic diversity loss and differentiation in fragmented wild populations.
Ecological adaptation and reproductive isolation in sympatry: genetic and phenotypic evidence for native host races of Rhagoletis pomonella
Authors: Powell Thomas H. Q. , Forbes Andrew A. , Hood Glen R. , Feder Jeffrey L.
Published: December 2013

Ecological speciation with gene flow may be an important mode of diversification for phytophagous insects. The recent shift of Rhagoletis pomonella from its native host downy hawthorn (Crataegus mollis) to introduced apple (Malus domestica) in the northeastern United States is a classic example of sympatric host race formation. Here, we test whether R. pomonella has similarly formed host races on four native Crataegus species in the southern United States: western mayhaw (C. opaca), blueberry hawthorn (C. brachyacantha), southern red hawthorn (C. mollis var. texana) and green hawthorn (C. viridis). These four southern hosts differ from each other in their fruiting phenology and in the volatile compounds emitted from the surface of their fruits. These two traits form the basis of ecological reproductive isolation between downy hawthorn and apple flies in the north. We report evidence from microsatellite population surveys and eclosion studies supporting the existence of genetically differentiated and partially reproductively isolated host races of southern hawthorn flies. The results provide an example of host shifting and ecological divergence involving native plants and imply that speciation with gene flow may be commonly initiated in Rhagoletis when ecological opportunity presents itself.
Revisiting comparisons of genetic diversity in stable and declining species: assessing genome‐wide polymorphism in North American bumble bees using RAD sequencing
Authors: Lozier J. D.
Published: December 2013

Genetic variation is of key importance for a species’ evolutionary potential, and its estimation is a major component of conservation studies. New DNA sequencing technologies have enabled the analysis of large portions of the genome in nonmodel species, promising highly accurate estimates of such population genetic parameters. Restriction site‐associated DNA sequencing (RADseq) is used to analyse thousands of variants in the bumble bee species Bombus impatiens, which is common, and Bombus pensylvanicus, which is in decline. Previous microsatellite‐based analyses have shown that gene diversity is lower in the declining B. pensylvanicus than in B. impatiens. RADseq nucleotide diversities appear much more similar in the two species. Both species exhibit allele frequencies consistent with historical population expansions. Differences in diversity observed at microsatellites thus do not appear to have arisen from long‐term differences in population size and are either recent in origin or may result from mutational processes. Additional research is needed to explain these discrepancies and to investigate the best ways to integrate next‐generation sequencing data and more traditional molecular markers in studies of genetic diversity.
The bacterial communities in plant phloem‐sap‐feeding insects
Authors: Jing Xiangfeng , Wong Adam C‐N , Chaston John M. , Colvin John , McKenzie Cindy L. , Douglas Angela E.
Published: December 2013

The resident microbiota of animals represents an important contribution to the global microbial diversity, but it is poorly known in many animals. This study investigated the bacterial diversity in plant phloem‐sap‐feeding whiteflies, aphids and psyllids by pyrosequencing bacterial 16S rRNA gene amplicons. After correction for sequencing error, just 3–7 bacterial operational taxonomic units were recovered from each insect sample sequenced to sufficient depth for saturation of rarefaction curves. Most samples were dominated by primary and secondary symbionts, which are localized to insect cells or the body cavity, indicative of a dearth of bacterial colonists of the gut lumen. Diversity indices of the bacterial communities (Shannon's index: 0.40–1.46, Simpson's index: 0.15–0.74) did not differ significantly between laboratory and field samples of the phloem‐feeding insects, but were significantly lower than in drosophilid flies quantified by the same methods. Both the low bacterial content of the phloem sap diet and biological processes in the insect may contribute to the apparently low bacterial diversity in these phloem‐feeding insects.