bluuebunny/crossref_metadata_2025 huggingface dataset:
An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference
Authors: Rees S. D. , Islam M. , Hydrie M. Z. I. , Chaudhary B. , Bellary S. , Hashmi S. , O’Hare J. P. , Kumar S. , Sanghera D. K. , Chaturvedi N. , Barnett A. H. , Shera A. S. , Weedon M. N. , Basit A. , Frayling T. M. , Kelly M. A. , Jafar T. H.
Published: February 2011

Diabet. Med. 28, 673–680 (2011)

Aims  A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity‐related traits and Type 2 diabetes in South Asian individuals, and to use meta‐analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.

Methods  We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥ 40 years from the Karachi population‐based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta‐analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies.

Results  In the 4411 Pakistani individuals from this study, the age‐, sex‐ and diabetes‐adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24–0.67) kg/m2 per A‐allele (P = 3.0 × 10−5) and with waist circumference was 0.88 (95% CI 0.36–1.41) cm per A‐allele (P = 0.001). The A‐allele (30% frequency) was also significantly associated with Type 2 diabetes [per A‐allele odds ratio (95% CI) 1.18 (1.07–1.30); P = 0.0009]. A meta‐analysis of four South Asian studies with 8091 subjects showed that the FTO A‐allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14–1.31); P = 1.07 × 10−8] even after adjusting for BMI [1.18 (95% CI 1.10–1.27); P = 1.02 × 10−5] or waist circumference [1.18 (95% CI 1.10–1.27); P = 3.97 × 10−5].

Conclusions  The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.
Blood glucose control and quality of health care in non‐insulin‐treated patients with Type 2 diabetes in Spain: a retrospective and cross‐sectional observational study
Authors: Rodríguez A. , Calle A. , Vázquez L. , Chacón F. , Polavieja P. , Reviriego J. ,   on behalf of the CADiNI Study Group
Published: February 2011

Diabet. Med. 28, 731–740 (2011)

Aims  To assess blood glucose control and quality of health care provided to non‐insulin‐treated patients with Type 2 diabetes mellitus in routine clinical practice in Spain.

Methods  In this observational, retrospective, cross‐sectional study, patients were grouped as either having good or suboptimal blood glucose control according to International Diabetes Federation or American Diabetes Association HbA1c goals. Clinical and socio‐demographic data and compliance with the main standard level of care recommendations of the International Diabetes Federation were recorded during a routine visit. Correlates of glucose control were analysed by logistic regression.

Results  Many patients were grouped as having suboptimal control under International Diabetes Federation (61.9%) or American Diabetes Association (45.0%) criteria. The mean number of accomplished International Diabetes Federation recommendations (7.3 out of 11) was higher for endocrinologists (than for internists or primary care physicians), and significantly more patients under their care were in the good glucose control group (than with primary care physicians). More recommendations were associated with blood glucose control using International Diabetes Federation than American Diabetes Association criteria, demanding higher quality of health care for achieving stricter goals. Some recommendations were poorly observed, particularly those concerning patients’ education on diabetes, the prompt prescription of effective treatments and monitoring of complications. Diabetes complications were associated with being in the suboptimal control group. Patients’ education on diabetes and HbA1c monitoring were associated with being in the good control group.

Conclusions  These results demonstrate the need for improvement in the management of patients with non‐insulin‐treated Type 2 diabetes in actual clinical practice in Spain. Such improvement would entail a stricter adherence to International Diabetes Federation recommendations.
Development and evaluation of a standardized registry for diabetes in pregnancy using data from the Northern, North West and East Anglia regional audits1
Authors: Holman N. , Lewis‐Barned N. , Bell R. , Stephens H. , Modder J. , Gardosi J. , Dornhorst A. , Hillson R. , Young B. , Murphy H. R. ,   on behalf of the NHS Diabetes in Pregnancy Dataset Development Group
Published: February 2011

Diabet. Med. 28, 797–804 (2011)

Objectives  To develop and evaluate a standardized data set for measuring pregnancy outcomes in women with Type 1 and Type 2 diabetes and to compare recent outcomes with those of the 2002–2003 Confidential Enquiry into Maternal and Child Health.

Methods  Existing regional, national and international data sets were compared for content, consistency and validity to develop a standardized data set for diabetes in pregnancy of 46 key clinical items. The data set was tested retrospectively using data from 2007–2008 pregnancies included in three regional audits (Northern, North West and East Anglia). Obstetric and neonatal outcomes of pregnancies resulting in a stillbirth or live birth were compared with those from the same regions during 2002–2003.

Results  Details of 1381 pregnancies, 812 (58.9%) in women with Type 1 diabetes and 556 (40.3%) in women with Type 2 diabetes, were available to test the proposed standardized data set. Of the 46 data items proposed, only 16 (34.8%), predominantly the delivery and neonatal items, achieved ≥ 85% completeness. Ethnic group data were available for 746 (54.0%) pregnancies and BMI for 627 (46.5%) pregnancies. Glycaemic control data were most complete—available for 1217 pregnancies (88.1%), during the first trimester. Only 239 women (19.9%) had adequate pregnancy preparation, defined as pre‐conception folic acid and first trimester HbA1c≤ 7% (≤ 53 mmol/mol). Serious adverse outcome rates (major malformation and perinatal mortality) were 55/1000 and had not improved since 2002–2003.

Conclusions  A standardized data set for diabetes in pregnancy may improve consistency of data collection and allow for more meaningful evaluation of pregnancy outcomes in women with pregestational diabetes.
Potential of education‐based insulin therapy for achievement of good metabolic control: a real‐life experience
Authors: Albrecht D. , Puder J. , Keller U. , Zulewski H.
Published: February 2011

Diabet. Med. 28, 539–542 (2011)

Aims  Achievement of good metabolic control in Type 1 diabetes is a difficult task in routine diabetes care. Education‐based flexible intensified insulin therapy has the potential to meet the therapeutic targets while limiting the risk for severe hypoglycaemia. We evaluated the metabolic control and the rate of severe hypoglycaemia in real‐life clinical practice in a centre using flexible intensified insulin therapy as standard of care since 1990.

Methods  Patients followed for Type 1 diabetes (n = 206) or those with other causes of absolute insulin deficiency (n = 17) in our outpatient clinic were analysed in a cross‐sectional study. Mean age (± standard deviation) was 48.9 ± 15.7 years, with diabetes duration of 21.4 ± 14.4 years. Outcome measures were HbA1c and frequency of severe hypoglycaemia.

Results  Median HbA1c was 7.1% (54 mmol/mol) [interquartile range 6.6–7.8 (51–62 mmol/mol)]; a good or acceptable metabolic control with HbA1c < 7.0% (53 mmol/mol) or 7.5% (58 mmol/mol) was reached in 43.5 and 64.6% of the patients, respectively. The frequency of severe hypoglycaemic episodes was 15 per 100 patient years: 72.3% of the patients did not experience any such episodes during the past 5 years.

Conclusions  Good or acceptable metabolic control is achievable in the majority of patients with Type 1 diabetes or other causes of absolute insulin deficiency in routine diabetes care while limiting the risk for severe hypoglycaemia.
Integrating the Dynamics of Personality and Close Relationship Processes: Methodological and Data Analytic Implications
Authors: Graber Elana C. , Laurenceau Jean‐Philippe , Carver Charles S.
Published: February 2011

A common theme that has emerged from classic and contemporary theoretical work in both the fields of personality and relationship science is a focus on process. Current process‐focused theories bearing on personality invoke a view of the individual in ongoing action and interaction with the environment, reflecting a flow of experience rather than a static depiction. To understand the processes by which personality interacts with the social environment (particularly dyads), investigations must capture individuals interacting in multiple interpersonal situations, which likely necessitates complex study designs and corresponding data analytic strategies. Using an illustrative simulated data set, we focus on diary methods and corresponding individual and dyadic multilevel models to capture person‐situation interaction within the context of processes in daily close relationship life. Finally, we consider future directions that conceptualize personality and close relationship processes from a dynamical systems theoretical and methodological perspective.
A Process‐Content Approach to Adolescent Identity Formation: Examining Longitudinal Associations Between Identity Styles and Goal Pursuits
Authors: Duriez Bart , Luyckx Koen , Soenens Bart , Berzonsky Michael
Published: February 2011

Research on identity focuses on the processes involved (e.g., identity style) or its content (e.g., goals and values), but limited research has addressed both issues simultaneously. The present study investigates cross‐lagged relations between identity styles (i.e., informational, normative, and diffuse‐avoidant) and goals (i.e., intrinsic vs. extrinsic and openness to change vs. conservation) in a 3‐wave adolescent sample (N = 806). Results support a reciprocal model, with process and content influencing each other. As for process effects, the informational and diffuse‐avoidant style predicted decreases in conservation goals, and the normative style predicted increases in conservation and extrinsic goals. As for content effects, conservation goals increased the normative style, and extrinsic goals decreased the informational and increased the diffuse‐avoidant style.
The curriculum for children with severe and profound learning difficulties at Stephen Hawking School
Authors: RAYNER MATTHEW
Published: February 2011

The increasing number of children with profound and multiple learning difficulties means that many schools for children with severe learning difficulties are having to review the curriculum that they offer. In addition, these schools are continuing to question whether a subject‐based approach, in line with the National Curriculum, is the most appropriate way of meeting the educational needs of children working at the earliest stages of development. The staff at Stephen Hawking School, in east London, have been reviewing their curriculum over the past two years to try and meet the needs of their changing population, the needs of the National Curriculum and the suggestions and proposals in both the Rose and Cambridge reviews.
RENMINBISING CHINA'S FOREIGN ASSETS
Authors: Cheung Yin‐Wong , Ma Guonan , McCauley Robert N.
Published: February 2011

Since the 2008 global financial crisis, China has rolled out a number of initiatives to actively promote the international role of the renminbi and to denominate more of its international claims away from the US dollar and into the renminbi. The present paper discusses the factors shaping the prospects of internationalising the renminbi from the perspective of the currency composition of China's international assets and liabilities. These factors include, among others, underlying valuation and management of the renminbi.
Iraqi refugees and the humanitarian costs of the Iraq war: What role for social work?
Authors: Harding Scott , Libal Kathryn
Published: February 2011

Harding S, Libal K. Iraqi refugees and the humanitarian costs of the Iraq war: what role for social work?

The US‐led invasion and war in Iraq has created one of the most significant refugee crises in recent decades. International nongovernmental organizations have partnered with local organizations in Jordan and Syria to provide humanitarian aid to some two million displaced Iraqis. Field research indicates that, as with other humanitarian crises, few trained social workers have contributed to policy and practice with displaced Iraqis. The case of Iraq provides an opportunity to consider how the social work profession can shape comprehensive global refugee policies and programs. This role is appropriate, given mandates for the profession to promote social justice and human rights. Using the case of Iraqi displacement, we illustrate the complexities of humanitarian services provision and the need for trained social workers to participate in humanitarian relief and development programs. We argue that a variety of social work institutions and actors should become more robust advocates for shaping just refugee policy and practice.
Democracy on the Edge: Limits and Possibilities in the Implementation of an Urban Reform Agenda in Brazil
Authors: ROLNIK RAQUEL
Published: February 2011

The 1990s in Brazil were a time of institutional advances in the areas of housing and urban rights following the signing of the new constitution in 1988 that incorporated the principles of the social function of cities and property, recognition of the right to ownership of informal urban squatters and the direct participation of citizens in urban policy decision processes. These propositions are the pillars of the urban reform agenda which, since the creation of the Ministry of Cities by the Lula government, has come under the federal executive branch. This article evaluates the limitations and opportunities involved in implementing this agenda on the basis of two policies proposed by the ministry — the National Cities Council and the campaign for Participatory Master Plans — focusing the analysis on government organization in the area of urban development in its relationship with the political system and the characteristics of Brazilian democracy.

Au Brésil, les années 1990 ont été marquées par des progrès institutionnels en matière de logement et de droits urbains, dans le sillage de la Constitution de 1988 qui intègre les principes d'une fonction sociale de la ville et de la propriété urbaine, ainsi que la reconnaissance du droit à la propriété pour les squatters urbains et la participation directe des citoyens aux processus d'élaboration des politiques urbaines. Ce sont également les piliers du programme de réforme urbaine qui relève de l'exécutif fédéral depuis la création d'un ministère des Villes par le gouvernement Lula. Pour évaluer les limites et potentiels liés à la mise en place de ce programme, cet article s'appuie sur deux politiques publiques proposées par le ministère, le Conseil national des villes et la campagne en faveur des Plans directeurs participatifs, en analysant plus particulièrement l'organisation gouvernementale en matière d'urbanisme par rapport au système politique et aux caractéristiques de la démocratie brésilienne.
Fine‐scale population genetic structuring of bottlenose dolphins in Irish coastal waters
Authors: Mirimin L. , Miller R. , Dillane E. , Berrow S. D. , Ingram S. , Cross T. F. , Rogan E.
Published: February 2011

The identification of localized discrete populations is particularly important to the management and conservation of animal species, especially in the marine environment, where potential for dispersal is high but barriers to gene flow are often not clear. We investigated population genetic structuring of bottlenose dolphinsTursiops truncatusfound along the west coast of Ireland, with particular attention to the Shannon Estuary, which is the only candidate Special Area of Conservation designated for this species in Irish waters. A genetic structure analysis using 62 biopsy samples from free ranging dolphins and 23 necropsies from stranded dolphins revealed fine‐scale population structure among three distinct populations. The Shannon Estuary population appears to be genetically isolated from adjacent coastal areas, with the exception of four animals sampled from a small group of six dolphins that are now resident in Cork Harbour (south coast) indicating ongoing gene flow or recent dispersal between these two areas. A second genetically distinct aggregation was identified in the Connemara–Mayo region, where recent photo‐identification studies have suggested that dolphins found in this area show a degree of site fidelity. We found moderate nuclear (15 microsatellites) and low mitochondrial (544 bp of the control region) gene diversity in dolphins using the Shannon Estuary and the Connemara–Mayo region, while dolphins that stranded along the coast showed markedly higher levels of gene diversity at both classes of markers. Specifically, these stranded dolphins formed a third genetically distinct cluster, which may be part of a larger pelagic population, as also suggested by the high levels of gene diversity. These results provide new insights into population structure of bottlenose dolphins in Irish waters and will aid future management and conservation of the species in the eastern North Atlantic.
Sensitivity of leaf size and shape to climate: global patterns and paleoclimatic applications
Authors: Peppe Daniel J. , Royer Dana L. , Cariglino Bárbara , Oliver Sofia Y. , Newman Sharon , Leight Elias , Enikolopov Grisha , Fernandez‐Burgos Margo , Herrera Fabiany , Adams Jonathan M. , Correa Edwin , Currano Ellen D. , Erickson J. Mark , Hinojosa Luis Felipe , Hoganson John W. , Iglesias Ari , Jaramillo Carlos A. , Johnson Kirk R. , Jordan Gregory J. , Kraft Nathan J. B. , Lovelock Elizabeth C. , Lusk Christopher H. , Niinemets Ülo , Peñuelas Josep , Rapson Gillian , Wing Scott L. , Wright Ian J.
Published: February 2011

See also the Commentary by Burnham and Tonkovich
Units of nature or processes across scales? The ecosystem concept at age 75
Authors: Currie William S.
Published: February 2011

The ecosystem has served as a central organizational concept in ecology for nearly a half century and continues to evolve. As a level in the biotic hierarchy, ecosystems are often viewed as ecological communities integrated with their abiotic environments. This has always been imperfect because of a mismatch of scales between communities and ecosystem processes as they are made operational for field study. Complexity theory has long been forecasted to provide a renewed foundation for ecosystem theory but has been slow to do so. Partly this has arisen from a difficulty in translating theoretical tenets into operational terms for testing in field studies. Ecosystem science has become an important applied science for studying global change and human environmental impacts. Vigorous and important directions in the study of ecosystems today include a growing focus on human‐dominated landscapes and development of the concept of ecosystem services for human resource supply and well‐being. Today, terrestrial ecosystems are viewed less as well‐defined entities or as a level in the biotic hierarchy. Instead, ecosystem processes are being increasingly viewed as the elements in a hierarchy. These occur alongside landscape processes and socioeconomic processes, which combine to form coupled social–ecological systems across a range of scales.

ContentsSummary21I.An organizational concept22II.An imperfect marriage22III.A type of complex adaptive system?25IV.A component of social–ecological systems28V.Conclusions and future research30Acknowledgements31References32
The social field of the European corporate elite: a network analysis of interlocking directorates among Europe's largest corporate boards
Authors: HEEMSKERK EELKE M.
Published: February 2011

In this article I investigate the emerging patterns of the European corporate elite network as an example of a European social field, as described by Fligstein. The findings confirm that interlocking directorates form a European corporate network. However, the intercorporate network rests on a very small group of European corporate elite members: it remains the playground of a select few pan‐European ‘big linkers’. Although financial institutions and bankers appear in the upper echelons of the network, they do not occupy crucial positions. Rather, (former) CEOs of Europe's largest big non‐financial businesses knit together the network of interlocking directorates. The network rests on a coalescence of finance and industry, rather than on the dominance of the one over the other. Although the project of European unification has been quite successful in organizing the formal institutional structures, it has not yet led to reproduction of a European business community reminiscent of the national communities.
Polygynandry, face‐to‐face copulation and sperm competition in the HihiNotiomystis cincta(Aves: Meliphagidae)
Authors: Castro I. , Minot E. O. , Fordham R. A. , Birkhead T. R.
Published: February 2011

The Hihi or StitchbirdNotiomystis cinctabreeding system is highly variable and includes monogamy, polyandry, polygyny and polygynandry. Males have large testes (4.2% of body mass), very large numbers (1460 × 106) of sperm in their seminal glomera and an unusually enlarged cloacal protuberance. These features are also found in other species with highly variable mating systems where males are under intense sperm competition. Hihi copulate in two different positions: face to face and, more conventionally, with the male on the female's back. Face‐to‐face copulation is unique among birds and appears to be a form of forced copulation. The presence of enlarged cloacas in both sexes could aid the transfer of sperm. Both male and female Hihi appear to benefit from a mixed reproductive strategy where a female Hihi can solicit copulations from males other than her partner and male Hihi can perform extra‐pair copulations both with willing females or by forced copulation.
Impact of family functioning on quality of life in patients with psychogenic nonepileptic seizures versus epilepsy
Authors: Curt LaFrance, Jr. W. , Alosco Michael L. , Davis Jennifer Duncan , Tremont Geoffrey , Ryan Christine E. , Keitner Gabor I. , Miller Ivan W. , Blum Andrew S.
Published: February 2011

Purpose:  To evaluate different contributions of aspects of family functioning (FF) on health‐related quality of life (HRQOL) in patients with psychogenic nonepileptic seizures (PNES) versus epileptic seizures (ES).

Methods:  Forty‐five participants with PNES and 32 with ES completed self‐report measures of FF (Family Assessment Device; FAD), HRQOL (Quality of Life in Epilepsy‐31), and depression (Beck Depression Inventory‐II; BDI‐II). The FAD is a self‐report questionnaire that assesses FF along six dimensions and general functioning. Regression analyses were used to evaluate the contribution of FF to HRQOL above and beyond the effects of disease severity and depression.

Key Findings:  Mean Family General Functioning fell in the unhealthy range in participants with ES or PNES. On further analysis, male participants in each group endorsed unhealthy levels of FF compared to female participants. Patients with PNES reported poorer HRQOL and greater depressive symptoms compared to ES participants; there were no gender differences in HRQOL. Regression analyses indicated that the FAD Roles subscale predicted reduced HRQOL in patients with PNES after controlling for illness duration, seizure frequency, and depression. After controlling for the same factors, Communication and Affective Involvement subscales scores predicted HRQOL in ES participants.

Significance:  Family dysfunction was reported in both ES and PNES participants, but greater family dysfunction was experienced by male participants in both groups. Aspects of FF predicted HRQOL in patients with PNES and ES differentially. FF may be an important treatment target to enhance coping in these groups, although the treatments may need to target different aspects of FF in PNES versus ES.
Hippocampal damage after prolonged febrile seizure: One case in a consecutive prospective series
Authors: Tanabe Takuya , Hara Keita , Shimakawa Shuichi , Fukui Miho , Tamai Hiroshi
Published: February 2011

The factors that contribute to hippocampal damage as a sequela, and its frequency, in patients experiencing febrile status epilepticus, remain unknown. Of the 472 patients with febrile seizures admitted to our hospital between February 2004 and August 2008, 77 had prolonged seizures. Among them, 59 underwent magnetic resonance imaging (MRI). A 21‐month‐old girl showed hippocampal changes after her first episode of febrile status epilepticus. The seizure lasted about 35 min, with eye deviation to the right and ictal rhythmic discharges in the left hemisphere. MRI at 72 h after the seizure revealed high‐signal intensities in T2 and fluid‐attenuated inversion recovery (FLAIR) images of the left hippocampus. Left hippocampal volume diminished over the next several months suggesting the occurrence of neuronal cell death. In no other cases, not even those with longer seizure durations, did significant hippocampal changes develop. The frequency of hippocampal damage was 1.7% in this case series. The involvement of factors other than seizure duration merits further study.
How Much Is Enough? Examining the Public's Beliefs About Consumption
Authors: Markowitz Ezra M. , Bowerman Tom
Published: February 2011

Relatively little public opinion research has explored beliefs about consumption. This lack of research is surprising given the increasing attention paid by many commentators to the relationship between consumption and ecological sustainability. Reporting on data collected from a series of five statewide surveys of Oregonians conducted between 2008 and 2009, we find that a strong majority (74–88%) of the Oregon public supports reducing consumption and believes doing so would improve societal and individual well‐being. These findings appear to challenge conventional wisdom about our collective and never‐ending need for consumption of material goods. Our results reveal broad agreement on the consumption issue across traditional ideological divides. We also conducted in‐depth qualitative interviews, which allowed us to explore what “consumption” means to Oregonians and why people think our country would be better off if we reduced consumption. Our findings suggest that populist attitudes toward reducing consumption may fill a role that policymakers avoid for a variety of reasons. We discuss the relevance of consumption beliefs to public policy aimed at reducing greenhouse gas (GHG) emissions, as well as directions for future research.
Viewpoint: An extended class of instrumental variables for the estimation of causal effects
Authors: Chalak Karim , White Halbert
Published: February 2011

Abstract We examine how structural systems can yield observed variables instrumental in identifying and estimating causal effects. We provide an exhaustive characterization of potentially identifying conditional exogeneity relationships and demonstrate how structural relations determine exogeneity and exclusion restrictions that yield moment conditions supporting identification. This provides a comprehensive framework for constructing instruments and covariates. We introduce notions of conditioning and conditional extended instrumental variables (XIVs). These permit identification but need not be traditional instruments, as they may be endogenous. We distinguish between observed XIVs and proxies for unobserved XIVs. A main message is the importance of sufficiently specifying causal relations governing the unobservables.
Congestion pricing of Canadian airports
Authors: Daniel Joseph I.
Published: February 2011

Abstract Under congestion pricing, Canadian airports would annually save between $72 and $105 million. Social costs per landing and takeoff decrease about $300 at Toronto and Vancouver and $50 at Calgary and Montreal. Slot constraints fail to eliminate this airport congestion. Congestion prices are lower on average than existing weight‐based prices. Current airport capacity accommodates at least five more years of traffic growth before congestion reaches current levels. Substantial welfare gains occur even if dominant airlines already internalize their self‐imposed delays. This article calculates equilibrium congestion pricing schedules, traffic rates, queuing delays, layover times, and connection times by time of day.
The Microcirculation: A Target for Developmental Priming
Authors: CLOUGH GERALDINE F. , NORMAN MIKAEL
Published: February 2011

Please cite this paper as: Clough and Norman (2011). The Microcirculation: A Target for Developmental Priming. Microcirculation 18(4), 286–297.

There is increasing evidence that the early life environment, of which nutrition is a key component, acts through developmental adaptations to set the capacity of cardiovascular and metabolic pathways, and ultimately the limits to physiological challenges in later life. Suboptimal maternal nutrition and fetal growth result in reduced microvascular perfusion and functional dilator capacity, which are strongly associated with later development of obesity, type 2 diabetes, and hypertension. These conditions are also linked to microvascular rarefaction and remodeling that together limit capillary recruitment, reduce exchange capacity and increase diffusion distances of metabolic substrates, and increase local and overall peripheral resistance. Changes in small vessel structure and function may be seen very early, long before the onset of overt cardiovascular and metabolic disease, and may thus be a target for early therapeutic and lifestyle intervention strategies. This article explores how a disadvantageous microvascular phenotype may result from perinatal priming and how developmental plasticity may become an important and additional risk determinant in susceptibility to cardiometabolic disease in adult life.
Impact of Dietary Soy Isoflavones in Pregnancy on Fetal Programming of Endothelial Function in Offspring
Authors: BONACASA BARBARA , SIOW RICHARD C.M. , MANN GIOVANNI E.
Published: February 2011

Please cite this paper as: Bonacasa, Siow and Mann (2011). Impact of Dietary Soy Isoflavones in Pregnancy on Fetal Programming of Endothelial Function in Offspring. Microcirculation 18(4), 270–285.

Epidemiological evidence suggests that soy‐based diets containing phytoestrogens (isoflavones) afford protection against cardiovascular diseases (CVDs); however, supplementation trials have largely reported only marginal health benefits. The molecular mechanisms by which the isoflavones genistein, daidzein, and equol afford protection against oxidative stress remain to be investigated in large scale clinical trials. Isoflavones are transferred across the placenta in both rodents and humans, yet there is limited information on their actions in pregnancy and the developmental origins of disease. Our studies established that feeding a soy isoflavone‐rich diet during pregnancy, weaning, and postweaning affords cardiovascular protection in aged male rats. Notably, rats exposed to a soy isoflavone‐deficient diet throughout pregnancy and adult life exhibited increased oxidative stress, diminished antioxidant enzyme and eNOS levels, endothelial dysfunction, and elevated blood pressure in vivo. The beneficial effects of refeeding isoflavones to isoflavone‐deficient rats include an increased production of nitric oxide and EDHF, an upregulation of antioxidant defense enzymes and lowering of blood pressure in vivo. This review focuses on the role that isoflavones in the fetal circulation may play during fetal development in affording protection against CVD in the offspring via their ability to activate eNOS, EDHF, and redox‐sensitive gene expression.
Synthesis of Single Crystalline Anatase TiO2 (001) Tetragonal Nanosheet‐Array Films on Fluorine‐Doped Tin Oxide Substrate
Authors: Feng Shuanglong , Yang Junyou , Zhu Hu , Liu Ming , Zhang Jiansheng , Wu Jin , Wan Jiayu
Published: February 2011

Single crystalline anatase TiO2 tetragonal nanosheet‐array film on a transparent conductive fluorine‐doped tin oxide (FTO) substrate was successfully prepared by hydrothermal method. The products were characterized with XRD, SEM, and transmission electron microscopy measurements. The formation mechanism of the tetragonal (001) TiO2 nanosheets is discussed and the effect of growth parameters, such as acidity, growth time, growth temperature, initial reactant concentration, and additives, are investigated. This work demonstrates a clean and effective route to the morphology‐controlled preparation of large area single‐crystalline TiO2 nanostructured array films on FTO glass.
Interactions in Calcium Aluminate Cement (CAC)‐Based Castables Containing Magnesia. Part I: Hydration–Dehydration Behavior of MgO in the Absence of CAC
Authors: Durán Teresa , Pena Pilar , De Aza Salvador , Gómez‐Millán Jesus , Alvarez Margarita , De Aza Antonio H.
Published: February 2011

Several technological problems arise on adding MgO to castable systems, due to its high tendency to react with water and the subsequent great volumetric expansion promoted by this reaction. Nevertheless, very few basic researches have been systematically carried out related to these castables behavior during the hydration and dehydration process. In the current manuscript (Part I), a novel approach based on the combined use of exothermic profiling andin situtime‐resolved laboratory X‐ray diffraction (LXRD) has been used to evaluate, as a first step, the hydration behavior of two MgO varieties (dead burned and reactive grade) in the absence of calcium aluminate cement (CAC). On the other hand, the dehydration behavior has been followed by conventional LXRD, differential thermal analysis, thermogravimetric, and dilatometric analyses. The results obtained and their implications have been discussed and compared in order to facilitate the understanding of the interactions in CAC‐based castables containing magnesia, which is studied in Part II of the paper.
Tolerance and Economic Performance in American Metropolitan Areas: An Empirical Investigation1
Authors: Chen Xinxiang
Published: February 2011

This article exploits differences in the Gay Index representing diversity and tolerance to estimate the effect of talent on economic performance in U.S. metropolitan areas, and proposes a theory of mechanism of talent distribution and its economic consequences. The index shows there were different degrees of tolerance in early years in different metropolitan areas, with different associated talent. Areas that had high tolerance in early years are more likely tolerant and diverse currently, and can attract more talent. Exploiting differences in the Gay Index as an instrument for current talent, this study estimates a large effect of talent on income per capita. Findings also suggest that other factors, such as high technology and amenities, do not affect regional development directly but do so indirectly by attracting talent.
The Impact of Intersecting Dimensions of Inequality and Identity on the Racial Status of Eastern African Immigrants1
Authors: Guenther Katja M. , Pendaz Sadie , Songora Makene Fortunata
Published: February 2011

In this article, we examine how immigrants from eastern Africa to the Minneapolis and St. Paul metropolitan area understand and navigate the U.S. color line and its implications for nonwhites. Although these immigrants are subject to constraints based on their racial status as black, they mobilize other intersecting aspects of their identities to manipulate racial classifications in the hopes of attaining upward mobility in the United States, even when doing so creates other social costs for them. Eastern African immigrants draw on their ethnicity and, among Muslim immigrants, their religion to differentiate themselves from African Americans, who occupy the lowest position in the U.S. racial hierarchy. In challenging their categorization as racially black and seeking to move up the racial hierarchy, Eastern African immigrants refine the color line to distinguish between African‐American blacks and non‐African‐American blacks.
Motor performance and haptic perception in preschool boys with specific impairment of expressive language
Authors: Müürsepp Iti , Aibast Herje , Pääsuke Mati
Published: February 2011

Aim:  The aim of this study was to investigate motor performance and haptic object recognition (HOR) in 5‐year‐old boys with minor to moderate specific impairment of expressive language (expressive‐SLI).

Methods:  Twenty‐eight boys with expressive‐SLI and 26 boys with typical language development as controls were recruited from ordinary kindergartens. An assessment of the voluntary isometric force production and relaxation capacity of the leg extensor muscles, manual dexterity, ball skills, balance and HOR was performed and the results were compared with those for age‐matched control group.

Results:  Reaction times to voluntary contraction and relaxation of the leg extensor muscles as well as manual dexterity did not differ significantly in the measured groups. Boys with expressive‐SLI demonstrated poorer results in ball skills (p < 0.01), balance (p < 0.01), less leg extensors strength (p < 0.05) and made considerably more (p < 0.001) errors in haptic perception test when compared to controls.

Conclusions:  Deviations in gross‐motor performance and haptic perception are very common in children with minor to moderate expressive‐SLI, being embodied especially in less muscle strength of lower extremities, poorer ball skills, balance and HOR.
Starch‐binding domains in the CBM45 family – low‐affinity domains from glucan, water dikinase and α‐amylase involved in plastidial starch metabolism
Authors: Glaring Mikkel A. , Baumann Martin J. , Hachem Maher Abou , Nakai Hiroyuki , Nakai Natsuko , Santelia Diana , Sigurskjold Bent W. , Zeeman Samuel C. , Blennow Andreas , Svensson Birte
Published: February 2011

Starch‐binding domains are noncatalytic carbohydrate‐binding modules that mediate binding to granular starch. The starch‐binding domains from the carbohydrate‐binding module family 45 (CBM45, http://www.cazy.org) are found as N‐terminal tandem repeats in a small number of enzymes, primarily from photosynthesizing organisms. Isolated domains from representatives of each of the two classes of enzyme carrying CBM45‐type domains, the Solanum tuberosumα‐glucan, water dikinase and the Arabidopsis thaliana plastidial α‐amylase 3, were expressed as recombinant proteins and characterized. Differential scanning calorimetry was used to verify the conformational integrity of an isolated CBM45 domain, revealing a surprisingly high thermal stability (Tm of 84.8 °C). The functionality of CBM45 was demonstrated in planta by yellow/green fluorescent protein fusions and transient expression in tobacco leaves. Affinities for starch and soluble cyclodextrin starch mimics were measured by adsorption assays, surface plasmon resonance and isothermal titration calorimetry analyses. The data indicate that CBM45 binds with an affinity of about two orders of magnitude lower than the classical starch‐binding domains from extracellular microbial amylolytic enzymes. This suggests that low‐affinity starch‐binding domains are a recurring feature in plastidial starch metabolism, and supports the hypothesis that reversible binding, effectuated through low‐affinity interaction with starch granules, facilitates dynamic regulation of enzyme activities and, hence, of starch metabolism.
Active site residue involvement in monoamine or diamine oxidation catalysed by pea seedling amine oxidase
Authors: Di Paolo Maria Luisa , Lunelli Michele , Fuxreiter Monika , Rigo Adelio , Simon Istvan , Scarpa Marina
Published: February 2011

The structures of copper amine oxidases from various sources show good similarity, suggesting similar catalytic mechanisms for all members of this enzyme family. However, the optimal substrates for each member differ, depending on the source of the enzyme and its location. The structural factors underlying substrate selectivity still remain to be discovered. With this in view, we examined the kinetic behaviour of pea seedling amine oxidase with cadaverine and hexylamine, the first bearing two, and the second only one, positively charged amino group. The dependence of Km and catalytic constant (kc) values on pH, ionic strength and temperature indicates that binding of the monoamine is driven by hydrophobic interactions. Instead, binding of the diamine is strongly facilitated by electrostatic factors, controlled by polar side‐chains and two titratable residues present in the active site. The position of the docked substrate is also essential for the participation of titratable amino acid residues in the following catalytic steps. A new mechanistic model explaining the substrate‐dependent kinetics of the reaction is discussed.
Binding Site Analysis of CCR2 Through In Silico Methodologies: Docking, CoMFA, and CoMSIA
Authors: Kothandan Gugan , Gadhe Changdev G. , Madhavan Thirumurthy , Cho Seung J.
Published: February 2011

Chemokine receptor (CCR2) is a G protein‐coupled receptor that contains seven transmembrane domains. CCR2 is targeted for diseases like arthritis, multiple sclerosis, vascular disease, obesity and type 2 diabetes. Herein, we report on a binding site analysis of CCR2 through docking and three‐dimensional quantitative structure–activity relationship (3D‐QSAR). The docking study was performed with modeled receptor (CCR2) using β2‐andrenergic receptor structure as a template. Comparative molecular field analysis (CoMFA)‐ and comparative molecular similarity indices analysis (CoMSIA)‐based 3D‐QSAR models were developed using two different schemes: ligand‐based (CoMFA; q2 = 0.820, r2 = 0.966,  = 0.854 and CoMSIA; q2 = 0.762, r2 = 0.846,  = 0.684) and receptor‐guided (CoMFA; q2 = 0.753, r2 = 0.962,  = 0.786, CoMSIA; q2 = 0.750, r2 = 0.800,  = 0.797) methods. 3D‐QSAR analysis revealed the contribution of electrostatic and hydrogen bond donor parameters to the inhibitory activity. Contour maps suggested that bulky substitutions on the para position of R1 substituted phenyl ring, electronegative and donor substitutions on meta (5′) and ortho (2′) position of R2 substituted phenyl ring were favorable for activity. The results correlate well with previous results and newly report additional residues that may be crucial in CCR2 antagonism.
Transferred NOESY NMR Studies of Biotin Mimetic Peptide (FSHPQNT) Bound to Streptavidin: A Structural Model for Studies of Peptide–Protein Interactions
Authors: Gizachew Dawit , Dratz Edward
Published: February 2011

Protein–protein interactions control signaling, specific adhesion, and many other biological functions. The three‐dimensional structures of the interfaces and bound ligand can be approached with transferred nuclear Overhauser effect spectroscopy NMR, which can be applied to much larger proteins than conventional NMR and requires less concentrated protein. However, it is not clear how accurately the structures of protein‐bound peptides can be determined by transferred nuclear Overhauser effect spectroscopy. We studied the structure of a biotin mimetic peptide (FSHPQNT) bound to streptavidin, because the X‐ray structure of the complex is available to 1.74 Å resolution, and we found that conditions could be adjusted so that the off‐rates were fast enough for transferred nuclear Overhauser effect spectroscopy NMR. The off‐rate was determined with 19F NMR, using a para‐fluoro‐phenylalanine analog of the peptide. A new criterion for a lower limit on kinetic off‐rate was found, which allowed accurate structure determination at a slower off‐rate. Non‐specific binding of the peptide to streptavidin was not significant, because biotin blocked the peptide transferred nuclear Overhauser effect spectroscopy. Protein mediation for the long‐range peptide transferred nuclear Overhauser effect spectroscopy cross‐peaks was corrected by a transferred nuclear Overhauser effect spectroscopy/ROESY averaging procedure. The protein‐bound structure of the peptide was determined by transferred nuclear Overhauser effect spectroscopy constrained and simulated annealing. The structure deduced from the NMR was close to the X‐ray structure.
Increased Diversity of Libraries from Libraries: Chemoinformatic Analysis of Bis‐Diazacyclic Libraries
Authors: López‐Vallejo Fabian , Nefzi Adel , Bender Andreas , Owen John R. , Nabney Ian T. , Houghten Richard A. , Medina‐Franco José L.
Published: February 2011

Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity‐oriented synthetic libraries. Herein, we report a comprehensive characterization of 15 bis‐diazacyclic combinatorial libraries obtained through libraries from libraries, which is a diversity‐oriented synthetic approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI diversity, and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity <0.5 for any fingerprint representation). In particular, bis‐cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug‐like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of diversity‐oriented synthetic libraries with existing drugs or any other compound collection.