bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary hypertension: therapeutic targets within the serotonin system
Authors: Dempsie Y , MacLean M R 
Published: June 2008

Pulmonary arterial hypertension (PAH) is characterized by a sustained and progressive elevation in pulmonary arterial pressure and pulmonary vascular remodelling leading to right heart failure and death. Prognosis is poor and novel therapeutic approaches are needed. The serotonin hypothesis of PAH originated in the 1960s after an outbreak of the disease was reported among patients taking the anorexigenic drugs aminorex and fenfluramine. These are indirect serotinergic agonists and serotonin transporter substrates. Since then many advances have been made in our understanding of the role of serotonin in the pathobiology of PAH. The rate‐limiting enzyme in the synthesis of serotonin is tryprophan hydroxylase (Tph). Serotonin is synthesized, through Tph1, in the endothelial cells of the pulmonary artery and can then act on underlying pulmonary arterial smooth muscle cells and pulmonary arterial fibroblasts in a paracrine fashion causing constriction and remodelling. These effects of serotonin can be mediated through both the serotonin transporter and serotonin receptors. This review will discuss our current understanding of ‘the serotonin hypothesis’ of PAH and highlight possible therapeutic targets within the serotonin system.British Journal of Pharmacology(2008)155, 455–462; doi:10.1038/bjp.2008.241; published online 9 June 2008
The failure of torcetrapib: what have we learned?
Authors: Joy T R , Hegele R A 
Published: June 2008

The failure of the cholesterol ester transfer protein (CETP) inhibitor, torcetrapib, has led to questions regarding whether the molecule itself or the mechanism of CETP inhibition was responsible for the adverse cardiovascular outcomes. Given the association with increases in blood pressure and plasma aldosterone levels, torcetrapib has been postulated to have adverse ‘off‐target’ effects. In this issue of British Journal of Pharmacology, Forrest and co‐workers have elegantly investigated these effects, demonstrating two salient points—(1) the pressor effect of torcetrapib is independent of CETP inhibition and (2) although associated with hyperaldosteronism, the pressor effect is likely not mediated by hyperaldosteronism. Anacetrapib, by contrast, did not demonstrate any pressor or off‐target effects. Despite these findings, it remains to be proven whether the adverse cardiovascular outcomes from torcetrapib were indeed related to the pressor effects and whether CETP inhibition by other agents will result in beneficial clinical outcomes. Yet, the studies of Forrest and co‐workers do bring us closer to unravelling the reasons behind the failure of torcetrapib. British Journal of Pharmacology (2008) 154, 1379–1381; doi:fn1; published online 9 June 2008
Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathway
Authors: Sagawa Morihiko , Nakazato Tomonori , Uchida Hideo , Ikeda Yasuo , Kizaki Masahiro 
Published: June 2008

Multiple myeloma is an incurable B‐cell malignancy requiring new therapeutic strategies in clinical settings. Interleukin (IL)–6 signaling pathways play a critical role in the pathogenesis of multiple myeloma. The traditional Chinese medicine cantharidin (CTD) has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of CTD as a novel therapeutic agent for the patients with multiple myeloma. We investigated the in vitro effects of CTD for its antimyeloma activity, and further examined the molecular mechanisms of CTD‐induced apoptosis. CTD inhibited the cellular growth of human myeloma cell lines as well as freshly isolated myeloma cells in patients. Cultivation with CTD induced apoptosis of myeloma cells in a cell‐cycle‐independent manner. Treatment with CTD induced caspase‐3, –8, and –9 activities, and it was completely blocked by each caspase inhibitor. We further examined the effect of CTD on the IL‐6 signaling pathway in myeloma cells, and found that CTD inhibited phosphorylation of STAT3 at tyrosine 705 residue as early as 1 h after treatment and down‐regulated the expression of the antiapoptotic bcl‐xL protein. STAT3 directly bound and activated the transcription of bcl‐xL gene promoter, resulting in the induction of the expression of bcl‐xL in myeloma cells. The essential role of STAT3 in CTD effects was confirmed by transfection with the constitutively active and dominant negative form of STAT3 in U266 cells. In conclusion, we have demonstrated that CTD is a promising candidate to be a new therapeutic agent in signal transduction therapy. (Cancer Sci 2008; 99: 1820–1826)
Expression profiling of the solute carrier gene family in chicken intestine from the late embryonic to early post‐hatch stages
Authors: Li H. , Gilbert E. R. , Zhang Y. , Crasta O. , Emmerson D. , Webb Jr K. E. , Wong E. A. 
Published: June 2008

SummaryIntestinal development during late embryogenesis and early post‐hatch has a long‐term influence on digestive and absorptive capacity in chickens. The objective of this research was to obtain a global view of intestinal solute carrier (SLC) gene family member expression from late embryogenesis until 2 weeks post‐hatch with a focus on SLC genes involved in uptake of sugars and amino acids. Small intestine samples from male chicks were collected on embryonic days 18 (E18) and 20 (E20), day of hatch and days 1, 3, 7 and 14 post‐hatch. The expression profiles of 162 SLC genes belonging to 41 SLC families were determined using Affymetrix chicken genome microarrays. The majority of SLC genes showed little or no difference in level of expression during E18–D14. A number of well‐known intestinal transporters were upregulated between E18 and D14 including the amino acid transporters rBAT, y+LAT‐2 and EAAT3, the peptide transporter PepT1 and the sugar transporters SGLT1, GLUT2 and GLUT5. The amino acid transporters CAT‐1 and CAT‐2 were downregulated. In addition, several glucose and amino acid transporters that are novel to our understanding of nutrient absorption in the chicken intestine were discovered through the arrays (SGLT6, SNAT1, SNAT2 and AST). These results represent a comprehensive characterization of the expression profiles of the SLC family of genes at different stages of development in the chicken intestine and lay the ground work for future nutritional studies.
Anthropometric characteristics as predictors of coronary heart disease in women
Authors: Yang L. , Kuper H. , Weiderpass E. 
Published: June 2008

Abstract.Objectives.  Obesity and other anthropometric measures are clearly related to risk of coronary heart disease (CHD), although debate remains as to which measures are most important and how the impact of obesity varies over the life course.Aim.  We aimed to investigate these issues in a large cohort of Swedish women. The Women’s Lifestyle and Health Cohort Study includes 49 259 women, aged 30–50 years at baseline (1991–1992) when an extensive questionnaire was completed.Methods.  Women were given standard instructions for self‐measurement of anthropometric characteristics. Women were followed through linkages to national registries until December 2003, during which time 256 cases of incident fatal CHD or nonfatal myocardial infarction occurred.Results.  Waist circumference was associated with increased CHD risk after multivariate adjustment for confounders (HR = 1.9; 95% CI:1.1–3.3; highest versus lowest quartile), whereas height, weight and hip circumference were not. Measures of obesity were strongly related to CHD, and after mutual adjustment, waist‐hip ratio (HR = 1.9, 95% CI: 1.2–3.2) was more closely related to CHD risk than BMI (HR = 1.5, 95% CI: 1.0–2.4). Risk of CHD was increased in women who remained heavy, those who were heavy at age 18, and those with low birth weight.Conclusions.  In conclusion, there is strong evidence for supporting control of obesity, in particular avoidance of abdominal obesity, as a strategy to prevent CHD.
Revisiting human primary immunodeficiencies
Authors: Casanova Jean‐Laurent , Fieschi Claire , Zhang Shen‐Ying , Abel Laurent 
Published: June 2008

Abstract.Human primary immunodeficiencies (PIDs) are often thought to be confined to a few rare, familial, monogenic, recessive traits impairing the development or function of one or several leucocyte subsets and resulting in multiple, recurrent, opportunistic and fatal infections in infancy. We highlight here the rapidly growing number of exceptions to each of these conventional qualifications. Indeed, bona fide PIDs include common and sporadic illnesses and may present as dominant, or even polygenic traits; their pathogenesis may involve non haematopoietic cells, and they may result in single episode of illness, with a single or multiple morbid phenotypes, some of which may involve infection, in otherwise healthy adults. We need to increase awareness of the multitude of clinical presentations of human PIDs considerably and rapidly in the medical community. Human PIDs should be considered in a wide range of clinical situations.
The styrene‐responsive StyS/StyR regulation system controls expression of an auxiliary phenylacetyl‐coenzyme A ligase: implications for rapid metabolic coupling of the styrene upper‐ and lower‐degradative pathways
Authors: Del Peso‐Santos Teresa , Shingler Victoria , Perera Julián 
Published: June 2008

Summary Pseudomonas sp. strain Y2 degrades styrene through oxidation to phenylacetic acid via the styABCD operon‐encoded enzymes, whose expression is induced in response to styrene by the StyS/StyR two‐component regulatory system. Further transformation of phenylacetic acid to tricarboxylic acid cycle intermediates is mediated by the enzymes of paa catabolic genes, whose expression is regulated by the PaaX repressor. The first step of this paa degradation pathway is catalysed by paaF‐encoded phenylacetyl‐coenzyme A ligases that produce phenylacetyl‐coenzyme A. This metabolic intermediate, upon being bound by PaaX, inactivates PaaX‐mediated repression of both the paa genes and the styABCD operon. Strain Y2 is unique in having three paaF genes located within two complete copies of the paa gene clusters. Expression of both paaF and paaF3 is controlled by the PaaX repressor. Here we use specific mutants in combination with in vivo and in vitro assays to demonstrate that paaF2, adjacent to the StyS/StyR regulatory genes, belongs to the StyR regulon and is not subject to repression by PaaX. We propose that this unexpected styrene‐responsive regulatory strategy for the otherwise metabolically redundant PaaF2 auxiliary enzyme provides a system for rapid co‐ordinate de‐repression of the two sets of catabolic genes required for styrene degradation.
A new twist on an old pathway – accessory secretion systems
Authors: Rigel Nathan W. , Braunstein Miriam 
Published: June 2008

SummaryThe export of proteins from their site of synthesis in the cytoplasm across the inner membrane is an important aspect of bacterial physiology. Because the location of extracytoplasmic proteins is ideal for host–pathogen interactions, protein export is also important to bacterial virulence. In bacteria, there are conserved protein export systems that are responsible for the majority of protein export: the general secretion (Sec) pathway and the twin‐arginine translocation pathway. In some bacteria, there are also specialized export systems dedicated to exporting specific subsets of proteins. In this review, we discuss a specialized export system that exists in some Gram‐positive bacteria and mycobacteria – the accessory Sec system. The common element to the accessory Sec system is an accessory SecA protein called SecA2. Here we present our current understanding of accessory Sec systems in Streptococcus gordonii, Streptococcus parasanguinis, Mycobacterium smegmatis, Mycobacterium tuberculosis and Listeria monocytogenes, making an effort to highlight apparent similarities and differences between the systems. We also review the data showing that accessory Sec systems can contribute to bacterial virulence.
Paternal effects on seed germination: a barrier to the genetic assimilation of an endemic plant taxon?
Authors: ANDERSSON S. , MÅNSBY E. , PRENTICE H. C. 
Published: June 2008

AbstractWe used a crossing experiment to investigate post‐zygotic barriers that might limit introgression between a pair of closely‐related, gynodioecious plant species – the widespread weedSilene vulgarisand the local Swedish endemicS. uniflorassp.petraea. The study not only considered the effects of hybridization on conventionally‐used (primary) fitness components such as seed set and progeny survival, but also provided a test for the effects of interspecific hybridization on characters with more subtle or habitat‐specific effects on fitness. We detected highly significant paternal effects on seed germination properties, with the germination characteristics of hybrid seed resembling those of the species that served as the pollen donor. These paternal effects on germination represent a potentially strong barrier to interspecific introgression in the two species’ natural habitats, where an inappropriate germination response in the habitat of the maternal parent may lead to the failure of seedling establishment. Interspecific crosses had weak or variable effects on progeny survival, flowering and sex ratio, but these effects could not be interpreted in terms of barriers to introgression. Our results indicate that nuclear restorers inS. vulgarishave the capacity to suppress cytoplasmic male‐sterility genes in its endemic congener.
The Meaning and Meaningfulness of Corporate Social Initiatives
Authors: HESS DAVID , WARREN DANIELLE E. 
Published: June 2008

ABSTRACTIn response to pressures to be more “socially responsible,” corporations are becoming more active in global communities through direct involvement in social initiatives. Critics, however, question the sincerity of these activities and argue that firms are simply attempting to stave off stakeholder pressures without providing a corresponding benefit to society. By drawing on institutional theory and resource dependence theory, we consider what factors influence the adoption of a “meaningful” social initiative—an initiative that is sustainable and has the potential for a significant positive impact on society—as opposed to a symbolic initiative. In addition, we raise the question of how social initiatives—both meaningful and symbolic—participate in the “institutional war” over the meaning of corporate social responsibility.
Reading the Tea Leaves—Did Citigroup Risk Their Reputation During 2004–2005? Presented at ICAA's Second International Conference Globalization – The Good Corporation June 26–28, 2007 Baruch College, New York City
Authors: YORK CHRISTOPHER C. , GUMBUS ANDRA , LILLEY STEPHEN 
Published: June 2008

ABSTRACTIn this paper, we challenge the conventional wisdom that high‐quality news reports of questionable corporate business practices will stimulate various marketplace negative responses, which in turn, will pressure management to undertake actions designed to protect the organization's reputation. Analysis is confined to a relatively brief period of bad news relating to Citigroup, Inc. We conclude that while none of the expected negative marketplace responses are evident in widely available news sources, the CEO did exhibit significant concern and instituted a targeted reputation risk management program. In the absence of a concerned CEO, analysts should not, we suggest, expect a management team to respond with reputation‐enhancing corrective action solely as a reaction to negative publicity regarding questionable business practices.
Transformation Charters in Contemporary South Africa: The Case of the ABSA Group Limited
Authors: ARYA BINDU , BASSI BALBIR , PHIYEGA RIAH 
Published: June 2008

ABSTRACTOver the past decade, strategy and international business scholars have increasingly turned their attention to assessing how alterations in institutional arrangements in former centrally planned economies influence enterprise‐level strategies. Little is known about the strategic responses of organizations operating in countries going through institutional transformation related to social issues. Since the first democratic elections in 1994, the South African government has focused on addressing the inequalities of the past through what is known as Black Economic Empowerment (empowerment of historically disadvantaged black people). In this paper, we investigate the approach used by the Amalgamated Banks of South Africa (ABSA) Group Limited, one of the top four banks and an important player in the South African financial services sector, in formulating and implementing strategy to ensure successful and sustainable organizational transformation. A key component of ABSA's Black Economic Empowerment strategy is incorporation of transformation as a business imperative and not merely as a compliance requirement.
Corporate Services in Poor Areas: A Case Study with Participative Multistakeholder Involvement
Authors: MELÉ DOMENÈC , PALADINO MARCELO 
Published: June 2008

ABSTRACTCorporations that provide services such as water, sewage disposal and electricity in poor countries or deprived areas face political, social and economic problems that make it difficult to simultaneously favor the interests of shareholders and other relevant stakeholders. In this paper a case study is presented in which a company, Aguas Argentinas, promoted innovative and participative multistakeholder involvement that produced benefits for all parties. Key factors in the model employed were the generation of credibility and trust, adaptive management to the specific situation of deprived areas, stakeholder dialogue, and participation. It is argued that understanding corporate citizenship as reciprocity and common effort in solving interdependent problems were fundamental to the success of the company in this case.
Corporate Responses to HIV/AIDS: Experience and Leadership from South Africa
Authors: BOLTON PAMELA L. 
Published: June 2008

ABSTRACTHIV/AIDS harms the viability and competitiveness of African businesses. As a consequence, companies increasingly subscribe to the view that taking a proactive role to combat HIV/AIDS is not simply a question of compassion and good corporate citizenship. Rather, these firms see assertive action against HIV as critical to their long‐term profitability, and some have concluded that it is cost effective even in the short term. The article discusses how South African companies are taking action against HIV in ways that set new benchmarks, enhance the effectiveness of international AIDS advocacy efforts, and spur businesses across Africa and beyond to strengthen their corporate responses to HIV/AIDS.
The Chengzhongcun Land Market in China: Boon or Bane? — A Perspective on Property Rights
Authors: TIAN LI 
Published: June 2008

AbstractWith the rapid expansion of China's cities since the 1978 economic reform, more and more villages have been swallowed up by urban sprawl. The retention of collective land ownership in chengzhongcun has, on the one hand, made low‐rent housing affordable for migrants; on the other hand, however, it has exposed chengzhongcun to many social, economic and environmental problems. Based on a case study of chengzhongcun in Guangzhou, and using an analytical framework of property rights, this article has found that maintaining collective land ownership in chengzhongcun has been socially and economically costly, but a redevelopment strategy without a complementary affordable housing scheme may be problematic. In order to solve the problems of chengzhongcun, an institutional reform of collective land is required.Résumé Les villes chinoises s’étant rapidement étendues depuis la réforme économique de 1978, un grand nombre de villages a été absorbé par les tentacules urbains. La préservation d’une propriété foncière collective dans les chengzhongcun a permis que les migrants accèdent à un logement à loyer modéré, tout en exposant cet habitat à de multiples problèmes sociaux, économiques et environnementaux. S’appuyant sur l’étude de cas du chengzhongcun de Guangzhou et sur un cadre analytique de droits de propriété, cet article montre que le maintien de la propriété foncière collective dans le chengzhongcun s’est révélé coûteux sur le plan social et économique et que, par ailleurs, une stratégie de réaménagement sans un système de logement complémentaire accessible pourrait être problématique. Résoudre les problèmes du chengzhongcun appelle à une réforme institutionnelle des terrains collectifs.
‘Cold spots’ of Urban Infrastructure: ‘Shrinking’ Processes in Eastern Germany and the Modern Infrastructural Ideal
Authors: MOSS TIMOTHY 
Published: June 2008

AbstractThis article explores the unfamiliar, but increasingly prevalent problem of overcapacity in urban infrastructure systems in regions subject to dramatic socio‐economic restructuring. Taking the case of water supply and wastewater disposal systems in Eastern Germany as an example, it examines firstly how infrastructure overcapacities have emerged since reunification in 1990 as a result both of sharply declining water consumption in the wake of ‘shrinking’ processes and of infrastructure expansion. Secondly, the article analyses what impact chronic overcapacity is having on the governance of water infrastructure systems. This empirical analysis is framed conceptually in terms of the current debate on the changing relationship between infrastructures and the localities they serve. It assesses specifically how far and in what ways the phenomenon of overcapacity in technical networks resonates with the ‘splintering urbanism’ thesis developed by Stephen Graham and Simon Marvin. It argues that the serious technical and economic problems posed by overcapacity are intensifying spatial disparities in service quality and price, and — more fundamentally — are challenging the supply‐driven ‘modern infrastructural ideal’ of universal and equitable water services.Résumé Cet article s’intéresse à la question, inhabituelle quoique de plus en plus courante, de la surcapacité des systèmes d’infrastructures urbains dans les régions soumises à une restructuration socio‐économique massive. Prenant comme exemples les réseaux d’alimentation en eau et d’évacuation des eaux usées en Allemagne de l’Est, il examine d’abord comment sont apparues des surcapacités d’infrastructures depuis la réunification de 1990, provoquées à la fois par une nette diminution de la consommation en eau à la suite des processus de ‘rétrécissement’ et par l’expansion des infrastructures. L’article analyse ensuite l’impact d’une surcapacité chronique sur la gouvernance des réseaux d’infrastructure de l’eau. Cette analyse empirique s’articule au plan conceptuel autour du débat actuel sur l’évolution des relations entre les infrastructures et les localités qu’elles desservent. Elle évalue en particulier dans quelle mesure et de quelles manières le phénomène de surcapacité dans les réseaux techniques fait écho à la thèse de ‘la fragmentation urbaine’élaborée par Stephen Graham et Simon Marvin. Les graves problèmes techniques et économiques que pose la surcapacité accentuent actuellement les disparités spatiales en matière de qualité et de tarification des services, mais ce qui est plus essentiel, ils remettent en question ‘l’idéal moderne d’infrastructure’ dynamisé par la demande et caractérisant des services de l’eau universels et équitables.