bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating population haplotype frequencies from pooled SNP data using incomplete database information
Authors: Pirinen Matti 
Published: October 2009

Abstract
Motivation: Information about haplotype structures gives a more detailed picture of genetic variation between individuals than single-locus analyses. Databases that contain the most frequent haplotypes of certain populations are developing rapidly (e.g. the HapMap database for single-nucleotide polymorphisms in humans). Utilization of such prior information about the prevailing haplotype structures makes it possible to estimate the haplotype frequencies also from large DNA pools. When genetic material from dozens of individuals is pooled together and analysed in a single genotyping, the overall number of genotypings and the costs of the genetic studies are reduced.
Results: A Bayesian model for estimating the haplotypes and their frequencies from pooled allelic observations is introduced. The model combines an idea of using database information for haplotype estimation with a computationally efficient multinormal approximation. In addition, the model treats the number and structures of the unknown haplotypes as random variables whose joint posterior distribution is estimated. The results on real human data from the HapMap database show that the proposed method provides significant improvements over the existing methods.
Availability: A reversible-jump Markov chain Monte Carlo algorithm for analysing the model is implemented in a program called Hippo (Haplotype estimation under incomplete prior information using pooled observations). For comparisons, an approximate expectation-maximization algorithm (EM-algorithm) that utilizes database information about the existing haplotypes is implemented in a program called AEML. The source codes written in C (using GNU Scientific Library) are available at www.iki.fi/∼mpirinen.
Contact: matti.pirinen@iki.fi
Normal systolic blood pressure and risk of heart failure in US male physicians
Authors: Britton Kathryn A. , Gaziano J. Michael , Djoussé Luc 
Published: October 2009

AimsHeart failure (HF) is a major public health issue and hypertension is a major predictor of HF. Observational studies have demonstrated a continuous and graded relationship between ‘normal’ systolic blood pressure (SBP) and cardiovascular disease. However, limited data are available on the relationship between normotensive SBP and the risk of HF.Methods and resultsTo test the hypothesis that there is a graded relation between SBP and HF risk among subjects with normal SBP, we used data on 18 876 participants who were healthy and were free of HF at baseline. Incident HF cases were ascertained by annual follow‐up questionnaires and validated through a review of medical records. Cox proportional hazard model was used to compute multivariable‐adjusted hazard ratios with corresponding 95% confidence intervals. Between 1982 and 2008, 1098 cases of HF occurred. There was a 35% increased risk of HF among subjects with SBP 130–139 mmHg compared with people with optimal SBP (<120 mmHg). In addition, there was a linear trend in HF risk across the normal range of SBP.ConclusionOur findings suggest a linear relationship between normotensive SBP and HF risk. Strategies to prevent HF, such as lifestyle modification, should be emphasized across all blood pressure ranges.
The Ferroportin Metal Efflux Proteins Function in Iron and Cobalt Homeostasis in Arabidopsis
Authors: Morrissey Joe , Baxter Ivan R. , Lee Joohyun , Li Liangtao , Lahner Brett , Grotz Natasha , Kaplan Jerry , Salt David E. , Guerinot Mary Lou 
Published: October 2009

Abstract
Relatively little is known about how metals such as iron are effluxed from cells, a necessary step for transport from the root to the shoot. Ferroportin (FPN) is the sole iron efflux transporter identified to date in animals, and there are two closely related orthologs in Arabidopsis thaliana, IRON REGULATED1 (IREG1/FPN1) and IREG2/FPN2. FPN1 localizes to the plasma membrane and is expressed in the stele, suggesting a role in vascular loading; FPN2 localizes to the vacuole and is expressed in the two outermost layers of the root in response to iron deficiency, suggesting a role in buffering metal influx. Consistent with these roles, fpn2 has a diminished iron deficiency response, whereas fpn1 fpn2 has an elevated iron deficiency response. Ferroportins also play a role in cobalt homeostasis; a survey of Arabidopsis accessions for ionomic phenotypes showed that truncation of FPN2 results in elevated shoot cobalt levels and leads to increased sensitivity to the metal. Conversely, loss of FPN1 abolishes shoot cobalt accumulation, even in the cobalt accumulating mutant frd3. Consequently, in the fpn1 fpn2 double mutant, cobalt cannot move to the shoot via FPN1 and is not sequestered in the root vacuoles via FPN2; instead, cobalt likely accumulates in the root cytoplasm causing fpn1 fpn2 to be even more sensitive to cobalt than fpn2 mutants.
Structure of exhumed mud volcano feeder complexes, Azerbaijan
Authors: Roberts K. S. , Davies R. J. , Stewart S. A. 
Published: October 2009

ABSTRACTWe report the first structural field mapping of exhumed mud volcano feeder complexes. Three mud volcanoes outcropping onshore in Azerbaijan were selected on the basis of outcrop quality and scale. These examples are all located within 1 km of the axes of NW–SE‐trending folds associated with the southern margin of the Greater Caucasus mountain belt. The mapping shows that the intrusive complexes are 200–800 m wide and roughly circular. These feeder complexes consist of a megabreccia of country rock blocks at a scale of tens of metres, enclosed in a matrix of intrusive mud. Minor structures include grid like fractures sets, sinuous fractures, mud plugs and breccia pipes. The country rock blocks are deformed and rotated relative to surrounding sedimentary strata. Alternative mechanisms to explain the strain history of these large blocks in the feeder complexes are: a. stoping, b. flow rotation and c. caldera collapse. Our mapping indicates that the most likely mechanism involves stoping processes, similar to those identified in igneous systems. This study provides a basis for reservoir distribution in commercial geological models that contain the feeder complexes of mud volcano systems, and also constrains conduit geometry for modelling studies of evolution and flow dynamics.
Comprehensive analyses and characterization of haemophagocytic lymphohistiocytosis in Vietnamese children
Authors: My Lam T. , Lien Le B. , Hsieh Wen‐Chuan , Imamura Toshihiko , Anh Tran N. K. , Anh Phan N. L. , Hung Nguyen T. , Tseng Fan‐Chen , Chi Chia‐Yu , Dao Ngo T. H. , Le Duong T. M. , Thinh Le Q. , Tung Tran T. , Imashuku Shinsaku , Thuong Tang C. , Su Ih‐Jen 
Published: October 2009

SummaryHaemophagocytic lymphohistiocytosis (HLH) is a fatal haematological disorder with diverse aetiology. This prospective study was undertaken to characterize HLH cases in Vietnamese children. Clinical and laboratory data, genetic analyses and outcome of the HLH patients were analysed. A total of 33 patients were enrolled from March 2007 to December 2008, with a median age of 3 years. Mutations of the SH2D1A (SAP) and PRF1 genes were detected in one patient, respectively. The virus association was high, up to 63·6% (21/33), including Epstein–Barr virus (19/33), cytomegalovirus (2/33) and dengue virus (2/33). Five patients had malignant lymphoma and two had autoimmune diseases. Twenty‐eight patients were treated according to the HLH‐2004 protocol. The first response rate was 64·3% (18/28), with an early death rate of 35·7% (10/28). High levels of interferon‐γ, interleukin‐10, MIG and interferon‐inducible protein‐10 (IP‐10) were associated with early mortality (P < 0·05). Reactivation among the responders was high (9/18) and the uneventful resolution was low (3/18) after a median follow‐up of 35 weeks. In conclusion, the majority of HLH cases are associated with virus infections in Vietnamese children. Familial HLH is rare. The frequent reactivation and high mortality demands a more appropriate therapeutic regimen in tropical areas like Vietnam.
‘What should I do with a 60‐year old man with a slightly low serum total testosterone concentration and normal levels of serum gonadotrophins’?
Authors: Hugh Jones T. 
Published: October 2009

SummaryThe fundamental question in assessing an older man with a slightly low total testosterone and normal gonadotrophin levels is to determine whether or not he has clinical hypogonadism. Hypogonadism is defined as a clinical syndrome complex, which comprises both symptoms as well as biochemical testosterone deficiency. As symptoms are nonspecific and there are no clear cut‐off values for testosterone levels this invariably leads to a clinical dilemma. International guidelines have been published which provide recommendations to aid the clinician in making a diagnosis. Late‐onset hypogonadism, the preferred terminology for age‐related hypogonadism, can only be made once other causes have been excluded. Evidence shows that low testosterone levels are associated with several common male conditions including erectile dysfunction, osteoporosis and diabetes. Short‐term studies have shown benefits of testosterone replacement therapy (TRT) on body composition, bone metabolism, insulin resistance, sexual function and quality of life. Recommendations give clear advice on safety monitoring, specifically in relation to prostate health. If a diagnosis of hypogonadism is made with borderline testosterone levels then a 3‐month trial of TRT can be considered. The diagnosis of hypogonadism associated with borderline testosterone levels and the decision to treat should only be made by an experienced clinician.
The role of TASK1 in aldosterone production and its expression in normal adrenal and aldosterone‐producing adenomas
Authors: Nogueira Edson F. , Gerry Daniel , Mantero Franco , Mariniello Barbara , Rainey William E. 
Published: October 2009

SummaryObjectives  Aldosterone production in the adrenal glomerulosa is mainly regulated by angiotensin II and K+. Adrenal glomerulosa cells are uniquely sensitive to extracellular K+. Genetic deletion of subunits of K+‐selective leak‐channels (KCNK), TASK1 and/or TASK3, in mice generates animals with hyperaldosteronism and histological changes in the adrenal cortex. Herein, we studied the expression of TASK1 in human adrenocortical cells, as well as its role in aldosterone production in H295R cells.Design  TASK1 expression was investigated by comparative microarray analysis of aldosterone‐producing adenomas (APA) and normal adrenals (NAs). The effects of TASK1 knockdown by siRNA transfection were investigated in H295R cells. Fluo‐4 fluorescent measurements of intracellular Ca2 + and pharmacological inhibition of Ca2 + ‐dependent calmodulin kinases (CaMK) were performed to better define the effects of TASK1 on Ca2 + signalling pathways.Results  Microarray analysis of APA and NA showed similar expression of TASK1 between these two groups. However, in APA, NA and H295R cells the expression of TASK1 was predominant when compared with other KCNK family members. Knockdown of TASK1 (with siRNA) induced the expression of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2), and also stimulated pregnenolone and aldosterone production. Cells transfected with siTASK1 had increased intracellular Ca2 + , leading to activation of CaMK and increased expression of CYP11B2.Conclusions  Our study reveals the predominant expression of TASK1 over other KCNK family genes in the human adrenal cortex. Herein, we also described the role of TASK1 in the regulation of human aldosterone production through regulation of intracellular Ca2 + and CaMK signalling pathways.
Perforin‐expressing cytotoxic cells contribute to chronic cardiomyopathy in Trypanosoma cruzi infection
Authors: Silverio Jaline Coutinho , De‐Oliveira‐Pinto Luzia Maria , Da Silva Andréa Alice , De Oliveira Gabriel Melo , Lannes‐Vieira Joseli 
Published: October 2009

SummaryUnderstanding the dual participation of the immune response in controlling the invader and at the same time causing tissue damage might contribute to the design of effective new vaccines and therapies for Chagas disease. Perforin, a cytolytic protein product of killer cells, is involved in resistance to acute Trypanosoma cruzi infection. However, the contribution of perforin in parasite control and chronic chagasic cardiomyopathy is unclear. Perforin‐positive cells were detected in the heart tissue during the acute and chronic phases of infection of C57BL/6 mice inoculated with low dose (102 parasites) of the Colombian T. cruzi strain. This protocol led to acute phase survival in both wild‐type and perforin null (pfp−/−) mice lineages. During the chronic infection, parasitism and inducible nitric oxide synthase (iNOS) as well as interleukin (IL)‐4+ and, mainly, interferon (IFN)‐γ+ cells were more elevated in the heart tissue of pfp−/− mice. Higher levels of circulating NO and anti‐parasite immunoglobulin (Ig)G2c and IgG3, paralleled by a prominent frequency of IFN‐γ+ and IL‐10+ splenocytes, were present in pfp−/−‐infected mice. Therefore, although the perforin‐dependent pathway plays a role, it is not crucial for anti‐T. cruzi immunity and acute phase survival of mice infected with a low inoculum. Further, perforin deficiency resulted in lower activity of creatine kinase‐muscle brain isoform (CK‐MB) isoenzyme in serum and a more restricted connexin 43 loss, both of which are markers of the cardiomyocyte lesion. Moreover, perforin deficiency hampered the development of severe electrocardiographic abnormalities. Hence, our results corroborate that perforin‐bearing cytotoxic cells might contribute to cardiomyocyte lesion and heart dysfunction during chronic T. cruzi infection, shedding light on immunopathogenesis of chronic chagasic cardiomyopathy.
Can life‐history traits predict the response of forb populations to changes in climate variability?
Authors: Dalgleish Harmony J. , Koons David N. , Adler Peter B. 
Published: October 2009

Summary 1. Climate change will cause changes in average temperature and precipitation as well as increased fluctuations around the mean, yet few studies have considered the impacts of altered climate variability on plant populations. We tested whether life‐history traits (expected life span, generation time and seed size) can predict plant responses to increased environmental variability across similar plant species sharing the same habitat. 2. We combined long‐term demographic data on 10 prairie forb species with stochastic demography techniques to estimate the effects of potential changes in matrix element means and variances on the long‐term stochastic population growth rate. 3. For all 10 species, recruitment had higher contribution and elasticity values than survival, meaning that climate change is more likely to influence population growth through effects on recruitment than on survival for these relatively short‐lived forbs. Species with longer generation times had lower elasticities to increases in matrix element variability. 4. Synthesis. Our analysis of a unique, long‐term data set suggests that longer‐lived plant species will be less vulnerable to the effects of future increases in climate variability. While this relationship was previously reported for diverse taxa from many locations, our results show that it also applies within a guild of short‐lived species from a single community. The generality of the pattern demonstrates the potential for using life‐history traits to make predictions about which species may be the most vulnerable to climate change.
The Excurrent Ducts of the Testis of the Emu (Dromaius novaehollandiae) and Ostrich (Struthio camelus): Microstereology of the Epididymis and Immunohistochemistry of its Cytoskeletal Systems
Authors: Ozegbe P. C. , Kimaro W. , Madekurozwa M.‐C. , Soley J. T. , Aire T. A. 
Published: October 2009

SummaryThe volumetric proportion of the various ducts of the epididymis of the emu and ostrich and the immunohistochemistry of actin microfilaments, as well as cytokeratin, desmin and vimentin intermediate filaments, were studied in the various ducts of the epididymis of the emu and ostrich. The volumetric proportions of various ducts, which are remarkably different from those of members of the Galloanserae monophyly, are as follows: the rete testis, 5.2 ± 1.4% for the emu and 2.4 ± 1.8% for the ostrich; efferent ducts, 14.2 ± 2.3% (emu) and 11.8 ± 1.8% (ostrich); epididymal duct unit, 25.8 ± 5.8% (emu) and 26.1 ± 4.1% (ostrich) and connective tissue and its content, 54.7 ± 5.8% (emu) and 60.0 ± 4.9% (ostrich). Unlike in mammals and members of the Galloanserae monophyly, only vimentin was immunohistochemically demonstrated in the rete testis epithelium of the emu, and none of the cytoskeletal protein elements in the ostrich rete testis. The epithelium of the efferent ducts of the emu co‐expressed actin, cytokeratin and desmin in the non‐ciliated type I cells, and vimentin in the ciliated cell component. The ostrich demonstrated only cytokeratin in this epithelium. The ratite epididymal duct unit is different from that of mammals in lacking actin (only weaky expression in the ostrich), desmin and cytokeratin, and a moderate/strong immunoexpression of vimentin in the basal cells and basal parts of the NC type III cell in the epididymal duct unit. Immunoexpression of the microfilaments and intermediate filaments varied between the two ratite birds, as has been demonstrated previously in birds of the Galloanserae monophyly, and in mammals.
Morphometric Analysis of the Canal System of Cortical Bone: An Experimental Study in the Rabbit Femur Carried Out with Standard Histology and Micro‐CT
Authors: Pazzaglia U. E. , Zarattini G. , Giacomini D. , Rodella L. , Menti A. M. , Feltrin G. 
Published: October 2009

SummaryThe osteonal pattern of cortical bone is gradually built around the intracortical vessels by the progression of the cutting cones (secondary remodelling); therefore, the central canal size can be used as index of the remodelling activity. An experimental model in the rabbit femur was used to investigate, through central canal morphometry and frequency distribution analysis, the remodelling activity, comparing the middle of the diaphysis (mid‐shaft) with the extremity (distal‐shaft) and at the same level sectors and layers of the cortex in transversal sections. The study documented a higher density of canals in the mid‐shaft than in the distal‐shaft and a higher remodelling in the distal‐shaft. There were no significant differences between dorsal, ventral, medial and lateral sectors at both mid‐shaft and distal‐shaft levels, while the number of canals was higher in the sub‐periosteal layers than in the sub‐endosteal. A lower threshold of 40 μm2 was observed in the central canal area. Sealed osteons in the midshaft were 22.43% of the total number of osteons of the central canal area between 40 and 200 μm2 and 0.44% of those of the distal‐shaft. Micro‐CT allowed a 3D reconstruction of the vascular canal system, which confirmed the branched network pattern rather than the trim architecture of the traditional representation. Some aspects like the lower threshold of the central canal size and the sealed osteons documented the plasticity of the system and its capacity for adaptation to changes in the haemodynamic conditions.
Validation of the Cognitive Appraisal Health Scale with Jordanian patients
Authors: Ahmad Muayyad M. 
Published: October 2009

AbstractThe purpose of this study was to test the psychometric properties and the theoretical structure of the Cognitive Appraisal Health Scale for patients with acute and chronic diseases in medical and surgical wards. Previously, the Scale was validated with patients diagnosed with prostate cancer. However, in order to examine the psychometric properties of the scale with patients diagnosed with health problems other than prostate cancer, this study was conducted. The convenience sample of 140 male and 128 female patients was selected from an educational hospital and three private hospitals in Jordan. The factor structure for the Scale was examined by using confirmatory and exploratory factor analysis. The 13 item model with three factors yielded highly acceptable indices in all respects for patients with acute and chronic diseases and appears most useful for measuring their cognitive appraisal.
Adjuvant chemotherapy for stage C colonic cancer in a multidisciplinary setting
Authors: Chapuis Pierre H. , Bokey E. Leslie , Clarke Stephen , Beale Philip , Dent Owen F. 
Published: October 2009

AbstractBackground:  In this study of patients undergoing adjuvant chemotherapy for clinicopathological stage C colonic cancer after optimal surgery, the aims were: to describe their immediate experience of chemotherapy, to assess disease‐free survival, to compare overall survival with that of a matched untreated historical control group, and to evaluate the associations between previously identified adverse risk factors and survival.Methods:  Data were drawn from a comprehensive, prospective hospital registry of resections for colorectal cancer between 1971 and 2004, with retrospective data on adjuvant chemotherapy. The main end point was overall survival. Statistical analysis employed the chi‐squared test, Kaplan–Meier estimation and proportional hazards regression.Results:  From May 1992 to December 2004, there were 104 patients who received adjuvant chemotherapy. Duration of treatment, withdrawal from treatment, toxicity and other immediate treatment outcomes were similar to those in other equivalent studies. There were no toxicity‐associated deaths. Overall survival was significantly longer in the treated patients than in the control group (3‐year rates 81% and 66%, respectively, P = 0.009). A significant protective effect of adjuvant therapy was found (hazard ratio 0.5, 95% confidence interval 0.3–0.8, P = 0.001) after adjustment for histopathology features previously shown to be negatively associated with survival (high grade, venous invasion, apical node metastasis, free serosal surface involvement).Conclusions:  For patients who have had a curative resection for lymph node positive colonic cancer in a specialist colorectal surgical unit and been managed by a multidisciplinary team, post‐operative adjuvant chemotherapy is safe and provides the same survival advantage as seen in randomized trials.
Colorectal cancer stem cells
Authors: Salama Paul , Platell Cameron 
Published: October 2009

AbstractSomatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special ‘niche’ comprised of intestinal sub‐epithlial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti‐neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.