bluuebunny/crossref_metadata_2025 huggingface dataset:
The Latinization of the Central Shenandoah Valley
Authors: Zarrugh Laura
Published: February 2008

Virginia is among a number of southern states in the United States, such as North Carolina, Arkansas and Georgia, which have experienced a sudden growth in Latino immigration during the past decade. Not only is the volume of growth unprecedented, but many of the destinations are new and located in rural areas. Places that have not hosted immigrant populations for generations are quickly becoming multicultural. The small city of Harrisonburg (population 43,500 according to the 2005 estimate), which is located in the rural Central Shenandoah Valley of Virginia, is perhaps the premier example of this new pattern of change. While local advertising once promoted Harrisonburg for its “99.2% American‐born and 93.7% white” population, the area today holds the distinction of hosting the most diverse public school enrollment in the state (in 2006‐2007), with students from 64 countries who speak 44 languages. Among them are Spanish speakers from at least 14 different countries. Drawing on social network theory, the paper examines how social networks among Latino immigrants become activated in new settlement areas. It presents a case history of the historic process of “Latinization” involving the settlement of a number of diverse Latino populations (from Mexico, Guatemala, El Salvador, Honduras, Cuba and Uruguay) in Harrisonburg and the surrounding Central Shenandoah Valley. The study demonstrates how a number of key institutions, including local agricultural industries (apples and poultry), a refugee resettlement office and churches recruited “pioneers” from these immigrant groups to the area and how “pioneers” subsequently engaged in further social network recruitment, thus creating multiple transnational “daughter communities” in the Harrisonburg area. The policy implications of this historical process are explored.
Testing for Equality of Standardized Composite Measures of Linkage Disequilibrium
Authors: Hamilton D. C. , Cole D. E. C.
Published: February 2008

We described the approximate variance for a composite measure of linkage disequilibrium (LD), which depends only on genotype frequencies and allows for departure from Hardy‐Weinberg disequilibrium (Hamilton et al. 2006). Here we extend this work to allow for inferences about differences in composite LD coefficients, as we illustrate with two examples. Simulations demonstrate consistency of type I error rates under most conditions. Calculations for power and sample size are also given.
Mitochondrial DNA Variability in Slovaks, with Application to the Roma Origin
Authors: Malyarchuk B. A. , Perkova M. A. , Derenko M. V. , Vanecek T. , Lazur J. , Gomolcak P.
Published: February 2008

To gain insight into the mitochondrial gene pool diversity of European populations, we studied mitochondrial DNA (mtDNA) variability in 207 subjects from western and eastern areas of Slovakia. Sequencing of two hypervariable segments, HVS I and HVS II, in combination with screening of coding region haplogroup‐specific RFLP‐markers, revealed that the majority of Slovak mtDNAs belong to the common West Eurasian mitochondrial haplogroups (HV, J, T, U, N1, W, and X). However, a few sub‐Saharan African (L2a) mtDNAs were detected in a population from eastern part of Slovakia. In addition, about 3% of mtDNAs from eastern Slovakia encompass Roma‐specific lineages. By means of complete mtDNA sequencing we demonstrate here that the Roma‐specific M‐lineages observed in gene pools of different Slavonic populations (Slovaks, Poles and Russians), belong to Indian‐specific haplogroups M5a1 and M35. Moreover, we show that haplogroup J lineages found in gene pools of the Roma and some Slavonic populations (Czechs and Slovaks) belong to new subhaplogroup J1a, which is defined by coding region mutation at position 8460.
Termination of pregnancy among very preterm births and its impact on very preterm mortality: results from ten European population‐based cohorts in the MOSAIC study
Authors: Papiernik E , Zeitlin J , Delmas D , Draper ES , Gadzinowski J , Künzel W , Cuttini M , Di Lallo D , Weber T , Kollée L , Bekaert A , Bréart G ,   MOSAIC Research Group
Published: February 2008

Objective  To study the impact of terminations of pregnancy (TOP) on very preterm mortality in Europe.

Design  European prospective population‐based cohort study.

Setting  Ten regions from nine European countries participating in the MOSAIC (Models of OrganiSing Access to Intensive Care for very preterm babies) study. These regions had different policies on screening for congenital anomalies (CAs) and on pregnancy termination.

Population or sample  Births 22–31 weeks gestational age.

Methods  The analysis compares the proportion of TOP among very preterm births and assesses differences in mortality between the regions.

Main outcome measures  Pregnancy outcomes (termination, antepartum death, intrapartum death and live birth) and reasons for termination, presence of CAs and causes of death for stillbirths and live births in 2003.

Results  Pregnancy terminations constituted between 1 and 21.5% of all very preterm births and between 4 and 53% of stillbirths. Most terminations were for CAs, although some were for obstetric indications (severe pre‐eclampsia, growth restriction, premature rupture of membranes). TOP contributed substantially to overall fetal mortality rates in the two regions with late second‐trimester screening. There was no clear association between policies governing screening and pregnancy termination and the proportion of CAs among stillbirths and live births, except in Poland, where neonatal deaths associated with CAs were more frequent, reflecting restrictive pregnancy termination policies.

Conclusion  Proportions of TOP among very preterm births varied widely between European regions. Information on terminations should be reported when very preterm live births and stillbirths are compared internationally since national policies related to screening for CAs and the legality and timing of medical terminations differ.
Ranked motives of long‐term care providing family caregivers
Authors: Kolmer Deirdre Beneken genaamd , Tellings Agnes , Gelissen John , Garretsen Henk , Bongers Inge
Published: February 2008

Family caregivers provide long‐term care to their chronically ill loved ones and as a consequence they experience physical, relational and financial problems. This study investigates how long‐term family caregivers rank 12 motives for caregiving. Motives are derived from the views of four philosophical anthropologists and are related to self‐reported stress and joy and to several different background characteristics of respondents. Motives that focus on feelings concerning the relationship between caregiver and care recipient are more popular as a first choice than motives stemming from feelings of obligation or a general feeling of happiness and are also more popular than more self‐directed motives. An analysis of full ranking data shows that two groups can be distinguished, one group of family caregivers with mixed motives and one group of family caregivers with motives that focus on reciprocal mutually equal relationships. The latter are mainly women taking care for a partner or a child, the former report high levels of stress. Implications for intervention programmes and health policy are being discussed.
Functional ability and health complaints among older people with a combination of public and informal care vs. public care only
Authors: Karlsson Staffan , Edberg Anna‐Karin , Westergren Albert , Hallberg Ingalill Rahm
Published: February 2008

The aim of the study was to investigate functional ability and health complaints of people, 65+, living in special accommodation (equivalent to nursing home) and their counterparts who live at home and receive municipal care or a combination of municipal and informal care. Persons (n = 1958) receiving municipal care were assessed in terms of functional ability, health complaints, and level of informal and municipal care and services. The results showed that more home care, services and help with Instrumental Activities of Daily Living (IADL) were provided to those receiving only municipal care at home, while more home care and services associated with Personal Activities of Daily Living (PADL) as well as nursing care were provided to those receiving informal care in addition to formal care. Cohabitation was a predictor of a combination of municipal and informal care in the home (OR: 5.935), while assistance with IADL provided by municipal home care and services predicted municipal care only (OR: 0.344). Care in special accommodation was predicted by advanced age (OR: 1.051), dependency in IADL (OR: 19.883) and PADL (OR: 2.695), and impaired cognitive ability (OR: 3.849) with receiving municipal care only as a reference. Living alone (OR: 0.106), dependency in IADL (OR: 11.348) and PADL (OR: 2.506), impaired cognitive ability (OR: 3.448), impaired vision or blindness (OR: 1.812) and the absence of slowly healing wounds (OR: 0.407) were predictors of special accommodation with a combination of informal and municipal care at home as a reference. The distribution of municipal care divided older people into three distinct groups. The most frail and elderly people who had no cohabitants received care in special accommodation, determined by their level of physical and cognitive dependency. The frailest individuals living at home were cohabiting and received a combination of municipal and informal care, while those who were less dependent mainly had help with IADL from municipal care only. The results indicate that there is a shift from the substitution to the complementary model and highlights that attention to the family carers is needed.
Existential caring in the family health experience: a proposed conceptualization
Authors: Meiers Sonja J. , Brauer Donna J.
Published: February 2008

Empirical realities and technological advances in the clinical practice context continuously call for ethical dialogue among healthcare providers. The nurse’s voice of advocacy for humane caring grounded in an existential understanding of the complexities of the health experience remains a salient responsibility of moral agency. If nurses are to care for families, as society requires, then nurse caring, a phenomenon currently defined and understood primarily at the individual patient–nurse level, must be diligently and broadly explored in terms of its worth to guide nursing service with families. The purpose of this theoretical paper is to explore a conceptualization of care with families in the health experience that emanates from the philosophical tenets of existentialism and underpinnings of symbolic interactionism and is interpreted into action by the ethics of care. Current and classic literature, inclusive of philosophical and empirical works, provide the background for analysis of the following elements: existential caring orientation, family perspective, family–nurse interaction, construction of meaning, family meaning construction, nurse meaning construction, family–nurse co‐construction of meaning and existential advocacy. Existential philosophy is understood as the basic underlying lens guiding the nurse in taking an existential caring orientation as depicted in the resultant conceptualization. Caring in the family health experience is best facilitated by a relational stance where the nurse acknowledges the family’s unique perspective. Through the family–nurse interaction the nurse gains understanding of the family’s perspective being constructed. Nursing practice with families confronting the empirical realities and technological advances of the new millennium will be enriched when moral agency includes ethical dialogue among healthcare providers and families. Existential advocacy with and for families grounded in the nurse’s understanding of the family perspective enhances the context for moral agency.
Leadership and Change at NASA: Sean O’Keefe as Administrator
Authors: Lambright W. Henry
Published: February 2008

Sean O’Keefe was administrator of NASA a little more than three years. In that eventful and turbulent period, he dealt with numerous issues. Appointed to cope with a huge cost overrun on the International Space Station, he was soon engulfed in the Columbia shuttle accident and its investigation. Subsequently, he engineered a presidential decision that NASA return to the moon and go eventually to Mars. He also sought to terminate the immensely popular Hubble Space Telescope. The Moon‐Mars decision was O’Keefe’s most important achievement, as that involving Hubble was his most controversial action. This essay tracks O’Keefe’s role at NASA as a case study in leadership and change.
Performance, Accountability, and the Debate over Rules
Authors: Kassel David S.
Published: February 2008

Does compliance with rules ensure better program performance and accountability? Since the 1980s, many scholars have answered no to this question, arguing that as managers attempt to comply with a growing thicket of rules, they often lose sight of the performance of their agencies and programs. Even the defenders of a rules‐based approach have tended to view it as a necessary, though inconvenient, means of ensuring that democratic values and public rights are protected in the functioning of government. But does compliance with rules inevitably result in a loss of efficiency and effectiveness in the performance of public projects? This essay presents a case study of a public works project and three additional case summaries to demonstrate a theoretical proposition that compliance with rules for contracting and competitive selection of contractors can be an essential element of both a project’s success and its accountability.
Legislative Influences on Performance Management Reform
Authors: Bourdeaux Carolyn , Chikoto Grace
Published: February 2008

The management literature argues that legislative involvement is important to the implementation of performance management reform, but it does not specify how legislatures should be engaged or how different legislative organizational arrangements affect reform. This article blends theories of management and legislative professionalism to better understand the influence of legislatures on the implementation of management reform. Drawing on data from several surveys, it examines the influence of legislative organization on the managerial use of performance measures. The findings suggest that citizen legislatures are associated with better administrative practices than professional legislatures and that the quality of legislative involvement may be more important than its quantity.
Penetrating the Performance Predicament: Communication as a Mediator or Moderator of Organizational Culture’s Impact on Public Organizational Performance
Authors: Garnett James L. , Marlowe Justin , Pandey Sanjay K.
Published: February 2008

The role of communication in public administration has been emphasized over time in public administration theory. Nonetheless, communication—with the exception of political communication—has been neglected in scholarship. Garnett’s performance predicament posits the difficulty of showing linkages between communication and performance. This paper explores the role that communication plays in achieving organizational performance through a review of research that bears on communication’s direct and indirect influences on performance. The primary thrust is communication’s indirect role in achieving performance by mediating or moderating the effects of organizational culture on performance, thereby adding another perspective on the culture–performance relationship. Adapting the typology of Zammuto and Krakower, two types of organizational culture—rule‐oriented culture and mission‐oriented culture—are examined to explore how the relationship between organizational culture and organizational performance is influenced by communication. The analysis supports the claim that communication acts as a meta‐mechanism for shaping and imparting culture in mission‐oriented organizational cultures, thereby influencing performance. In particular, task orientation, feedback, and upward communication have positive effects on perceived organizational performance in mission‐oriented organizations but potentially negative effects on performance in rule‐oriented cultures.
Wicked Problems, Knowledge Challenges, and Collaborative Capacity Builders in Network Settings
Authors: Weber Edward P. , Khademian Anne M.
Published: February 2008

Networks have assumed a place of prominence in the literature on public and private governing structures. The many positive attributes of networks are often featured—the capacity to solve problems, govern shared resources, create learning opportunities, and address shared goals—and a literature focused on the challenges networks pose for managers seeking to realize these network attributes is developing. The authors share an interest in understanding the potential of networks to govern complex public, or “wicked,” problems. A fundamental challenge to effectively managing any public problem in a networked setting is the transfer, receipt and integration of knowledge across participants. When knowledge is viewed pragmatically, the challenge is particularly acute. This perspective, the authors argue, presents a challenge to the network literature to consider the mind‐set of the managers—or collaborative capacity‐builders—who are working to achieve solutions to wicked problems. This mind‐set guides network managers as they apply their skills, strategies, and tools in order to foster the transfer, receipt, and integration of knowledge across the network and, ultimately, to build long‐term collaborative problem‐solving capacity.
Forty‐five years in climatology—a personal odyssey
Authors: ROUSE WAYNE R.
Published: February 2008

This article presents a personal perspective on an academic and research vocation spanning a period of over 45 years. It starts with my early involvement in geography and climatology and terminates with my recent experience in a large interdisciplinary research venture. The presentation highlights, with specific examples, the importance of mentors. Also emphasized is the indispensable input of colleagues and graduate students to successful research endeavours. Most of my career has been centred on McMaster University, and I naturally draw on my experiences there. There have been great changes in the research world over the past few decades. Although the number of faculty and graduate students at McMaster remained relatively constant, the research output per person more than doubled. This is attributed in large part to the accelerating technological advancements in our ability to measure and our ability to process and manipulate data. In the environmental sciences, this has revolutionized the spatial and temporal scope of the scientific questions that can be addressed. Such major changes have stimulated a marked trend towards interdisciplinary research that has evolved from mainly wishful talking to active pursuit in a search to understand complex environmental interactions. Important among these is gaining insights into the processes and feedbacks driving climate change, whether natural or anthropologically induced. Equally important is gaining an understanding of the potential impacts resulting from climate change. My perception of my successes, failures and near misses divides chronologically into three periods that cover research in the early years, research in the central subarctic and research in the Mackenzie River Basin.
The evolving quality of trade between Canada and the United States
Authors: ANDRESEN MARTIN A.
Published: February 2008

This article examines the quality level of trade between Canada and the United States, 1979–2003, to investigate the relevance of staples theory for Canada. After disentangling the quality levels of trade, it is found that the pattern of quality‐level trade changed significantly around the time free trade was established between Canada and the United States. Before free trade, Canada was moving into the lower end of quality, but after the establishment of free trade, Canada is now moving into the higher end of quality trade with the United States. This observation potentially means that Canada is moving out of the staples trap.
Aires de marché et choix des destinations de consommation pour les achats réalisés au cours de la semaine – Le cas de la région de Québec
Authors: BIBA GJIN , THÉRIAULT MARIUS , VILLENEUVE PAUL Y. , DES ROSIERS FRANÇOIS
Published: February 2008

Since the early 1990s, big box stores have profoundly modified the retail structure of Canadian cities. This entails multiple consequences, beyond the mere competition between establishments, for the evolving relationships between diversity of retail forms, consumer behaviour and urban planning. These relationships are explored in the Québec Metropolitan Community, using detailed databases, including establishment directories, mobility surveys and a virtual road network, integrated into a regional GIS. Trade areas of commercial streets, shopping centers and big box stores are delineated and analyzed. Consumers' attributes, such as age, gender, type of household, mode of transport, which putatively influence the probability of patronizing one type of retail cluster compared to another type, are modelled using logistic regression. The influence of the relative location of cluster types on their capacity to attract consumers is also modelled in order to gain some understanding of the competition among and between types. The analysis suggests that, by and large, the growing number of big box stores has more negative consequences for shopping centres than they have for commercial streets. The study also clearly reveals the growing importance of shopping trips in the mobility profile of households and provides a knowledge base useful for urban planning.
Body size, reproductive allocation, and maximum reproductive rate of two species of aphidophagous Coccinellidae exploiting the same resource
Authors: Honek Alois , Dixon Anthony F.G. , Martinkova Zdenka
Published: February 2008

To test the predictions of allometric analyses of laboratory data on aphidophagous ladybirds, a study was carried out on a small [Propylea quatuordecimpunctata (L.); dry female body mass 3.7 mg] and large species (Coccinella septempunctata L.; 15.4 mg) (both Coleoptera: Coccinellidae) of predatory ladybird, which regularly exploit cereal aphids. In 2003–2006, females of C. septempunctata and in 2006 P. quatuordecimpunctata were collected at 2‐ to 5‐day intervals during the 30‐day period around the peak in cereal aphid abundance, and the number of eggs they laid in the following 24 h in the laboratory was recorded. In addition to the number of eggs laid, clutch mass, live weight, and scutum width of ovipositing females and the sizes of the clutches laid in the field were recorded. As predicted, the reproductive allocation in both species was similar. The weight of the eggs of C. septempunctata (0.20 mg) and P. quatuordecimpunctata (0.18 mg) differed little, and the proportion of body mass allocated to daily reproduction (ca. 12%) was identical in both species. In addition, the maximum number of eggs laid per day in the field by the large species was, as predicted, greater than by the small species. Interestingly, the size of the egg clutches laid by C. septempunctata in the field was similar to the daily oviposition of field‐collected adults recorded in the laboratory, whereas for P. quatuordecimpunctata it was significantly smaller. The role of morphology and physiology of ladybirds in structuring aphidophagous ladybird guilds is discussed.
uPA dependent and independent mechanisms of wound healing by C‐phycocyanin
Authors: Madhyastha H. K. , Radha K. S. , Nakajima Y. , Omura S. , Maruyama M.
Published: February 2008

Wound repair requires both recruitment and well co‐ordinated actions of many cell types including inflammatory cells, endothelial cells, epithelial cells and importantly fibroblast cells. Urokinase‐type plasminogen activator (uPA) system plays a vital role in wound healing phenomenon. We have previously demonstrated that C‐phycocyanin (C‐pc), a biliprotein from blue‐green algae, transcriptionally regulates uPA through cAMP‐dependent protein kinase A (PKA) pathway. To date, a role for C‐pc in wound‐healing scenario is not elucidated. This study was designed to examine the wound‐healing property of C‐pc in relation to fibroblast proliferation and migration. C‐pc increased fibroblast proliferation in a dose‐dependent manner. It also enhanced G1 phase of cell cycle and increased the expressions of cyclin‐dependent kinases 1 and 2, which facilitate cell cycle progression, in a uPA‐independent manner. In vitro wound healing and migration assays revealed the pro‐migratory properties of C‐pc. Short‐interference RNA studies demonstrated that uPA was necessary for C‐pc‐induced fibroblast migration. C‐pc also significantly elevated the expressions of chemokines (MDC, RANTES, Eotaxin, GRO α, ENA78 and TARC) and Rho‐GTPases (Cdc 42 and Rac 1) in a uPA‐dependent manner. Pre‐treatment of C‐pc‐stimulated cells with pharmacological inhibitor of PI‐3K (LY294002) annulled the expression of GTPases implying that Rac 1 and Cdc 42 were induced through PI‐3K pathway. C‐pc‐induced cellular migration towards wounded area was also negatively affected by PI‐3K inhibition. In vivo wound‐healing experiments in mice validated our finding that C‐pc accelerates wound healing. Our data provides conclusive evidence of a novel therapeutic usage for C‐pc as a wound‐healing agent. C‐pc is a food and drug administration (FDA)‐approved health supplement. We believe this compound can also be beneficial in healing of internal wounds, such as ulcers.
Decrease in stromal androgen receptor associates with androgen‐independent disease and promotes prostate cancer cell proliferation and invasion
Authors: Li Yirong , Li Caihong X. , Ye Huihui , Chen Fei , Melamed Jonathan , Peng Yi , Liu Jinsong , Wang Zhengxin , Tsou Hui C. , Wei Jianjun , Walden Paul , Garabedian Michael J. , Lee Peng
Published: February 2008

Androgen receptor (AR) is expressed in both stromal and epithelial cells of the prostate. The majority of studies on AR expression and function in prostate cancer is focused on malignant epithelial cells rather than stromal cells. In this study, we examined the levels of stromal AR in androgen‐dependent and ‐independent prostate cancer and the function of stromal AR in prostate cancer growth and invasion. We showed that stromal AR levels were decreased in the areas surrounding cancerous tissue, especially in androgen‐independent cancer. Using two telomerase‐immortalized human stromal cell lines, one AR‐positive and the other AR‐negative, we demonstrated that stromal cells lacking AR stimulated cell proliferation of co‐cultured prostate cancer cells in vitro and enhanced tumour growth in vivo when co‐injected with PC3 epithelial cells in nude mice. In contrast, stromal cells expressing AR suppressed prostate cancer growth in vitro and in vivo. In parallel with cancer growth, in vitro invasion assays revealed that stromal cells lacking AR increased the invasion ability of PC3 cell by one order of magnitude, while stromal cells expressing AR reduced this effect. These results indicate a negative regulation of prostate cancer growth and invasion by stromal AR. This provides potentially new mechanistic insights into the failure of androgen ablation therapy, and the reactivation of stromal AR could be a novel therapeutic approach for treating hormone refractory prostate cancer.
Inhibition of ERK attenuates autophagy and potentiates tumour necrosis factor‐α‐induced cell death in MCF‐7 cells
Authors: Sivaprasad U. , Basu A.
Published: February 2008

The role of autophagy in cell death is under considerable debate. The process of autophagy has been shown to lead to either cell survival or cell death depending on cell type and stimulus. In the present study, we determined the contribution of ERK1/2 signalling to autophagy and cell death induced by tumour necrosis factor‐α (TNF) in MCF‐7 breast cancer cells. Treatment of MCF‐7 cells with TNF caused a time‐dependent increase in ERK1/2 activity. There was an induction of autophagy and cleavage of caspase‐7, ‐8, ‐9 and PARP. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 or PD98059 resulted in a decrease in TNF‐induced autophagy that was accompanied by an increase in cleavage of caspase‐7, ‐8, ‐9 and PARP Furthermore, inhibition of ERK1/2 signalling resulted in decreased clonogenic capacity of MCF‐7 cells. These data suggest that TNF‐induces autophagy through ERK1/2 and that inhibition of autophagy increases cellular sensitivity to TNF.
Development of an animal model for allergic conjunctivitis: influence of genetic factors and allergen concentration on immune response
Authors: Giavina‐Bianchi Pedro , Kalil Jorge , Rizzo Luiz Vicente
Published: February 2008

Purpose:  Animal models of diseases are extremely important in the study of the physiopathogenesis of human diseases and for testing novel therapeutic interventions. The present study aimed to develop an animal model that simulates human allergic conjunctivitis and to study how allergic response may be influenced by the allergen dose used for immunization and by genetic factors.

Methods:  Sixty C57Bl/6 mice and 60 BALB/c mice were immunized with placebo, or 5 μg or 500 μg of allergen derived from Dermatophagoides pteronyssinus. After ocular challenge, the mice were examined in order to clinically verify the occurrence or not of conjunctivitis. Material obtained from animals was used for total and specific IgE and IgG1 dosage, for assays of Der p‐specific lymphocyte proliferation and supernatant cytokine dosage, and for histopathological evaluation of conjunctiva.

Results:  We developed a murine model of allergic conjunctivitis induced by D. pteronyssinus. The model is similar to human disease both clinically and according to laboratory findings. In mouse, conjunctivitis was associated with a Th2 cytokine profile. However, IL‐10 appeared to be involved with disease blockade. Mice of different strains have distinct immune responses, depending on the sensitization dose.

Conclusions:  The murine model developed is suitable for the study of immunopathogenesis and as a template for future therapies. Using BALB/c and C57BL/6 mice, we demonstrated that genetic factors play a role in determining susceptibility and resistance, as well as in establishing the allergen concentration needed to induce or to block disease development.
Protein tyrosine phosphatases: regulatory mechanisms
Authors: Hertog Jeroen den , Östman Arne , Böhmer Frank‐D.
Published: February 2008

Protein‐tyrosine phosphatases are tightly controlled by various mechanisms, ranging from differential expression in specific cell types to restricted subcellular localization, limited proteolysis, post‐translational modifications affecting intrinsic catalytic activity, ligand binding and dimerization. Here, we review the regulatory mechanisms found to control the classical protein‐tyrosine phosphatases.
Protein tyrosine phosphatases: functional inferences from mouse models and human diseases
Authors: Hendriks Wiljan J. A. J. , Elson Ari , Harroch Sheila , Stoker Andrew W.
Published: February 2008

Some 40‐odd genes in mammals encode phosphotyrosine‐specific, ‘classical’ protein tyrosine phosphatases. The generation of animal model systems and the study of various human disease states have begun to elucidate the important and diverse roles of protein tyrosine phosphatases in cellular signalling pathways, development and disease. Here, we provide an overview of those findings from mice and men, and indicate several novel approaches that are now being exploited to further our knowledge of this fascinating enzyme family.
Protein tyrosine phosphatases: dual‐specificity phosphatases in health and disease
Authors: Pulido Rafael , van Huijsduijnen Rob Hooft
Published: February 2008

Dual‐specificity phosphatases (DSPs) constitute a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylates phospho‐Tyr, phospho‐Ser and nonproteinaceous substrates. DSPs are involved in the regulation of both developmental and postnatal essential processes, such as early embryogenesis, placental development and immune responses. Several DSP genes are implicated in familial and sporadic human diseases, including tumor‐related, neurological and muscle disorders, and cardiovascular and inflammatory diseases. This association ranges from disease‐causative mutations to disease‐risk‐prone single‐nucleotide polymorphisms, promoter methylation or gene duplication (most often in cancer). Deconvolution of the role of DSPs in disease is challenging. The enzymes’ activities are regulated at many levels and they form part of extensive, intricate networks with other signaling components. Here, we review current knowledge of the role of cysteine‐based PTP‐domain DSPs in health and disease, and their suitability as putative therapeutic targets for drugs is discussed.
Insect cytokine growth‐blocking peptide signaling cascades regulate two separate groups of target genes
Authors: Ninomiya Yosuke , Kurakake Maiko , Oda Yasunori , Tsuzuki Seiji , Hayakawa Yoichi
Published: February 2008

Growth‐blocking peptide (GBP) is a 25 amino acid insect cytokine found in lepidopteran insects that has diverse biological activities, such as larval growth regulation, paralysis induction, cell proliferation, and stimulation of immune cells. GBP also enhances expression of the tyrosine hydroxylase (TH, EC 1.14.16.2) and 3,4‐dihydroxy‐l‐phenylalanine (Dopa) decarboxylase (DDC, EC 4.1.1.26) genes, which elevate dopamine levels in insect epidermal cells. We used insect epidermis and cultured cells to define the role of the GBP signaling pathway in the enhancement of TH and DDC gene expression. It has been recently reported that robust expression of the DDC gene requires activation of extracellular signal‐regulated kinase (ERK) in epidermal cells of wounded Drosophila embryos. This study confirmed that GBP activates ERK, but this activation is not directly linked to the enhancement of TH and DDC gene expression. One of the GBP pathway components is phospholipase C, whose activation is essential for the activation of ERK and elevation of expression of both enzyme genes. The downstream signaling pathways diverge to ERK activation through activated protein kinase C and expression of the enzyme genes through inositol triphosphate receptor‐mediated Ca2+ influx from extracellular fluid. Our data indicate that the diverged GBP signaling pathways enable GBP to exert completely different biological functions, even in a single cell type.
Isolation and characterization of four type 2 ribosome inactivating pulchellin isoforms from Abrus pulchellus seeds
Authors: Castilho Priscila V. , Goto Leandro S. , Roberts Lynne M. , Araújo Ana Paula U.
Published: February 2008

Abrus pulchellus seeds contain at least seven closely related and highly toxic type 2 ribosome‐inactivating pulchellins, each consisting of a toxic A‐chain linked to a sugar binding B‐chain. In the present study, four pulchellin isoforms (termed P I, P II, P III and P IV) were isolated by affinity, ion exchange and chromatofocusing chromatographies, and investigated with respect to toxicity and sugar binding specificity. Half maximal inhibitory concentration and median lethal dose values indicate that P I and P II have similar toxicities and that both are more toxic to cultured HeLa cells and mice than P III and P IV. Interestingly, the secondary structural characteristics and sugar binding properties of the respective pairs of isoforms correlate well with the two toxicity levels, in that P I/P II and P III/P IV form two specific subgroups. From the deduced amino acids sequences of the four isoforms, it is clear that the highest similarity within each subgroup is found to occur within domain 2 of the B‐chains, suggesting that the disparity in toxicity levels might be attributed to subtle differences in B‐chain‐mediated cell surface interactions that precede and determine toxin uptake pathways.
Structural recognition of DNA by poly(ADP‐ribose)polymerase‐like zinc finger families
Authors: Petrucco Stefania , Percudani Riccardo
Published: February 2008

PARP‐like zinc fingers (zf‐PARPs) are protein domains apt to the recognition of multiple DNA secondary structures. They were initially described as the DNA‐binding, nick‐sensor domains of poly(ADP‐ribose)polymerases (PARPs). It now appears that zf‐PARPs are evolutionary conserved in the eukaryotic lineage and associated with various enzymes implicated in nucleic acid transactions. In the present study, we discuss the functional and structural data of zf‐PARPSs in the light of a comparative analysis of the protein family. Sequence and structural analyses allow the definition of the conserved features of the zf‐PARP domain and the identification of five distinct phylogenetic groups. Differences among the groups accumulate on the putative DNA binding surface of the PARP zinc‐finger fold. These observations suggest that different zf‐PARP types have distinctive recognition properties for DNA secondary structures. A comparison of various functional studies confirms that the different finger types can accomplish a selective recognition of DNA structures.
On the minimum mass of reionization sources
Authors: Choudhury T. Roy , Ferrara A. , Gallerani S.
Published: February 2008

By means of carefully calibrated semi-analytical reionization models, we estimate the minimum mass of star-forming haloes required to match the current data. Models which do not include haloes of total mass M < 109 M⊙ fail at reproducing the Gunn–Peterson and electron scattering optical depths simultaneously, as they contribute too few (many) photons at high (low, z≈ 6) redshift. Marginally acceptable solutions require haloes with M≈ 5 × 107 M⊙ at z≈ 10, corresponding to virial temperatures (∼104 K) for which cooling can be ensured by atomic transitions. However, a much better match to the data is obtained if minihaloes (M∼ 106 M⊙) are included in the analysis. We have critically examined the assumptions made in our model and conclude that reionization in the large-galaxies-only scenario can remain viable only if metal-free stars and/or some other exotic sources at z > 6 are included.
ENZYMATIC PRODUCTION OF CONJUGATED LINOLEIC ACID MONOACYLGLYCEROLS FROM DEHYDRATED ISOMERIZED CASTOR BEAN OIL
Authors: BAROUH NATHALIE , PIOMBO GEORGES , GOLI THIERRY , BARÉA BRUNO , PINA MICHEL , LAGO REGINA , VILLENEUVE PIERRE
Published: February 2008

The goal of this study was to produce conjugated linoleic acid (CLA) monoacylglycerols (MAGs). A chemicoenzymatic process was employed starting from castor bean oil, which was chemically dehydrated and isomerized to obtain new modified triacylglycerols (TAGs) with a very high proportion of CLA fatty acids (>95%). Such TAGs were then used in enzymatic glycerolysis reaction using Candida antarctica B lipase at 55C in tert‐butyl alcohol as a solvent. The effect of enzyme load and substrate molar ratio on the production yield of MAGs was evaluated and optimized using response surface methodology with a two‐factor and three‐level factorial design. A satisfactory linear correlation existed between experimental results and predicted values (R2 = 0.97 and R2adj. = 0.94). Using the contour plot generated from the model for MAG production yield, optimum parameters could be obtained corresponding to an 11/1 glycerol/TAG molar ratio and an enzyme load of 2% (% w/w of both substrates).

PRACTICAL APPLICATIONS

This research work proposes a new route for the synthesis of functional monoacylglycerols combining the emulsifying effect of partial acylglycerols with the nutritional benefits of conjugated linoleic acids, which have been shown to exhibit promising biological properties. The compounds so produced may have potential applications in the food industry.
FATTY ACIDS, TOCOPHEROLS, STEROLS, PHENOLIC PROFILES AND OXIDATIVE STABILITY OF CUCUMIS MELO VAR. AGRESTIS OIL
Authors: MARIOD ABDALBASIT , MATTHÄUS BERTRAND
Published: February 2008

Oil extracted from the seeds of Cucumis melo var. agrestis, collected from Ghibaish (sandy soil) and Gezira (heavy clay soil) provinces in Sudan, was studied in terms of the profile of fatty acids, tocopherols and sterols as well as phenolic compounds and oxidative stability by Rancimat (Metrohm AG, Herisau, Switzerland). The predominant fatty acid was 18:2n‐6, representing 61.3 and 61.4% for Ghibaish and Gezira samples, respectively. There were no variations among the contents of 16:0, 18:0, 18:1n‐9 and 18:2n‐6 between the two samples. γ‐Tocopherol was the predominant tocopherol in both samples, representing 80.7 and 77.6% of the total tocopherols, respectively, followed by α‐tocopherol at 18 and 21%, respectively. Total sterol content was 3,879.0 and 3,785.0 mg/kg for Ghibaish and Gezira samples, respectively. The main sterol of the two oils was β‐sitosterol. The two samples showed an oxidative stability of 5.9 and 5.7 h, respectively. The content of total phenolic compounds was determined in each sample according to the Folin‐Ciocalteau method as 33.0 and 31.9 mg/g of dry product, respectively. The phenolic compounds of the oil were separated using a solid phase extraction. The fractions were studied by high‐performance liquid chromatography with diode‐array detection, which revealed four peaks in the two samples. The major components were catechin, vanillic acid, sinapic acid and callistephin. There was little variability according to location between the two samples.

PRACTICAL APPLICATIONS

Two samples from dried seeds of Cucumis melo var. agrestis were collected. Seeds were crushed and ground using a grinding mill; the oil was extracted from the ground seeds by extraction with petroleum ether in a Soxhlet apparatus, and the physicochemical properties of C. melo var. agrestis oil were determined. The fatty acid and sterol composition were investigated using gas chromatography; the different tocopherol homologs were identified by high‐performance liquid chromatography (HPLC), and the oil oxidative stability was studied by Rancimat (Metrohm AG, Herisau, Switzerland) apparatus. The phenolic compounds were extracted from the obtained oil and then identified by HPLC with diode‐array detection.
SHORT‐ AND LONG‐TERM EFFECTS OF CORN OIL ON SERUM LIPID AND LIPOPROTEIN AND VISCERAL ABDOMINAL FAT PAD PARAMETERS OF RATS
Authors: ASADI FARZAD , SHAHRIARI ALI , POURKABIR MALIHE , MACLAREN ROBIN
Published: February 2008

Obesity, in particular, abdominal obesity, is highly correlated with metabolic disorders and cardiovascular lesions in humans and animal models and may in fact play a role in their pathogenesis. The development of obesity, while partially genetic, is largely affected by environmental and lifestyle factors such as diet. The aim of the present study was to determine the short‐ and long‐term effects of dietary corn oil on the abdominal fat pat morphology and serum lipid and lipoprotein profile. Forty male Wistar rats were randomly separated into two groups. The experimental group was fed a corn oil‐rich diet (CRD), which consisted of 32.5% of kilocalories from corn oil and provided a total number of kcal/kg/day similar to the average western diet. The control group received regular chow (6.5% kilocalories from fat source). In each group, eight rats were sacrificed after 3 weeks and the remaining 12 rats in each group were sacrificed after 10 weeks. Adipocyte size, distribution and adipocyte number per gram of abdominal fat pad were determined. The total weight of the abdominal fat pad from the CRD rats was approximately twice the weight of the pad from the control rats at both time points (5.43 ± 0.93 g versus 11.6 ± 1.98 g after 3 weeks and 6.24 ± 1.38 g versus 11.18 ± 2.17 g after 10 weeks). There was a significant increase (P < 0.001) in adipocyte number per gram of fat and in the total triacylglycerol (TAG) content of the fat pad in the CRD group compared to the control at both short‐term and long‐term time points. However, the adipocyte size distribution showed a similar pattern in both the CRD and control groups. Serum TAG, total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C) and very low‐density lipoprotein cholesterol (VLDL‐C) were also measured. In the long‐term study, higher values of TAG (P = 0.015), TC (P < 0.001), low‐density lipoprotein cholesterol (P < 0.001) and VLDL‐C (P = 0.005) were seen in the CRD group in comparison with the control. These results suggest that the deleterious effects of a CRD are because of serum changes rather than adipocyte morphology changes.

PRACTICAL APPLICATION

Although further research is required, corn oil administration may be associated with the development of cardiovascular disorders.
Discretizing the Fracture‐Matrix Interface to Simulate Solute Transport
Authors: Weatherill Douglas , Graf Thomas , Simmons Craig T. , Cook Peter G. , Therrien Rene , Reynolds David A.
Published: February 2008

This article examines the required spatial discretization perpendicular to the fracture‐matrix interface (FMI) for numerical simulation of solute transport in discretely fractured porous media. The discrete‐fracture, finite‐element model HydroGeoSphere (Therrien et al. 2005) and a discrete‐fracture implementation of MT3DMS (Zheng 1990) were used to model solute transport in a single fracture, and the results were compared to the analytical solution ofTang et al. (1981). To match analytical results on the relatively short timescales simulated in this study, very fine grid spacing perpendicular to the FMI of the scale of the fracture aperture is necessary if advection and/or dispersion in the fracture is high compared to diffusion in the matrix. The requirement of such extremely fine spatial discretization has not been previously reported in the literature. In cases of high matrix diffusion, matching the analytical results is achieved with larger grid spacing at the FMI. Cases where matrix diffusion is lower can employ a larger grid multiplier moving away from the FMI. The very fine spatial discretization identified in this study for cases of low matrix diffusion may limit the applicability of numerical discrete‐fracture models in such cases.
The PTPN22‐1858C>T (R620W) functional polymorphism is associated with generalized vitiligo in the Romanian population
Authors: LaBerge Greggory S. , Birlea Stanca A. , Fain Pamela R. , Spritz Richard A.
Published: February 2008

Generalized vitiligo is an autoimmune disorder of the skin in which autoimmune‐mediated destruction of melanocytes leads to depigmented patches of skin and overlying hair. The 1858C>T (R620W) functional polymorphism of the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (Lyp), has been associated with susceptibility to a number of autoimmune disorders, including generalized vitiligo. The aim of this study was to test genetic association of the PTPN22 1858C>T variant and generalized vitiligo in a Romanian case‐control cohort. We observed significant association of generalized vitiligo with the 1858T risk allele of PTPN22 [P = 0.0138; OR = 2.92 (1.21–7.03)], with significantly different distribution of PTPN22 1858C>T genotypes in cases versus controls [P = 0.036; OR = 2.69 (1.07–6.80)]. Our results provide evidence that the PTPN22 1858T allele contributes to risk of generalized vitiligo in European Caucasian populations, and underscores the importance of a genetically mediated autoimmune mechanism in the pathogenesis of vitiligo.
Symmetrization and norm of the Hardy–Littlewood maximal operator on Lorentz and Marcinkiewicz spaces
Authors: Colzani Leonardo , Laeng Enrico , Morpurgo Carlo
Published: February 2008

We prove that when a function on the real line is symmetrically rearranged, the distribution function of its uncentered Hardy–Littlewood maximal function increases pointwise, while it remains unchanged only when the function is already symmetric. Equivalently, if ℳ is the maximal operator and 𝒮 the symmetrization, then 𝒮ℳf(x)⩽ℳ𝒮f(x) for every x, and equality holds for all x if and only if, up to translations, f(x) = 𝒮 f(x) almost everywhere. Using these results, we then compute the exact norms of the maximal operator acting on Lorentz and Marcinkiewicz spaces, and we determine extremal functions that realize these norms.