bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual therapy versus monotherapy of trandolapril and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats
Authors: Rao Ravi P , Jain AK , Srinivasan BP 
Published: March 2011

Objective: To investigate the combination of telmisartan with trandolapril therapy versus monotherapy of trandolapril and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. Material and methods: Neonatal rats (2 days old) were used for inducing type 2 diabetes mellitus. Streptozotocin at a dose of 90 mg/kg, in freshly prepared citrate buffer (0.1M, pH 4.5), was injected intraperitoneally. There were five groups: (1) normal control, (2) diabetic control, (3) diabetic treated with telmisartan, (4) diabetic treated with trandolapril and (5) diabetic treated with telmisartan and trandolapril. Albumin excretion rate, total protein excretion rate, plasma fibronectin, transforming growth factor beta 1(TGF-β1), tumour necrosis factor-α (TNF-α) concentration and renal structural changes were measured. Results: Albumin excretion rate, total protein excretion rate, plasma fibronectin, TGF-β1, TNF-α concentration and renal structural changes increased significantly in untreated diabetic rats compared with normal control rats. Administration of telmisartan, trandolapril, or both decreased these changes. Conclusions: Addition of the telmisartan to trandolapril was more effective in reducing renal structural changes and improvement of renal function than monotherapy with either drug, possibly due to dual inhibitory effect on the renin— angiotensin system, and thus suppression of TGF-β1, TNF-α.
Renin–angiotensin–aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patients
Authors: Mtiraoui Nabil , Ezzidi Intissar , Turki Amira , Chaieb Molka , Mahjoub Touhami , Almawi Wassim Y 
Published: March 2011

Background: The association between renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms with diabetic nephropathy (DN) was investigated in Tunisian type 2 diabetes (T2DM) patients. Methods: Study subjects comprised 917 T2DM patients (405 normoalbuminuric, 329 microalbuminuric and 185 macroalbuminuric). Genotyping was done by PCR-RFLP. Results: Renin C-4063T allele and genotype frequencies were comparable between DN cases and normoalbuminuric controls. Although AGT 235T and -6G allele, and 235T/T and -6G/G genotype frequencies were higher in DN compared to normoalbuminuric patients, they were comparable between microalbuminuric or macroalbuminuric patients. Three-locus AGT haplotype analysis (A-6G/T174M/M235T) identified DN-protective (ATM, AMM, GTM) and DN-susceptible (GTM, ATT, GMT and AMT) haplotypes, and demonstrated enrichment of GTT haplotype in macroalbuminuric compared to microalbuminuric or normoalbuminuric patients. Regression analysis confirmed negative (AMM) and positive (GTM, ATT, GMT, AMT) association of AGT haplotypes with microalbuminuria, and negative (AMM) and positive (GTM and ATT) association of AGT haplotypes with macroalbuminuria. None of the AGT haplotypes was associated with DN severity. Conclusions: Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication.
Study of the mechanisms of aldosterone prothrombotic effect in rats
Authors: Gromotowicz Anna , Szemraj Janusz , Stankiewicz Adrian , Zakrzeska Agnieszka , Mantur Maria , Jaroszewicz Ewa , Rogowski Franciszek , Chabielska Ewa 
Published: March 2011

Introduction: We investigated the role of primary haemostasis, fibrinolysis, nitric oxide (NO) and oxidative stress as well as mineralocorticoid receptors (MR) in acute aldosterone prothrombotic action. Materials and methods: Venous thrombosis was induced by stasis in Wistar rats. Aldosterone (ALDO; 10, 30, 100 µg/kg/h) was infused for 1 h. Eplerenone (EPL; 100 mg/kg, p.o.), a selective MR antagonist, was administered before ALDO infusion. Bleeding time (BT) and platelet adhesion to collagen were evaluated. The expression of nitric oxide synthase (NOS), NADPH oxidase, superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) was measured. NO, malonyl dialdehyde (MDA) and hydrogen peroxide (H2O2) plasma levels were assayed. Results: Significant enhancement of venous thrombosis was observed after ALDO infusion. ALDO shortened BT and increased platelet adhesion. Marked increases were observed in PAI-1, NADPH oxidase and SOD mRNA levels. MDA and H2O2 levels were augmented in ALDO-treated groups, and NOS expression and NO level were decreased. EPL reduced ALDO effects on thrombus formation, primary haemostasis, PAI-1 expression and MDA level. Conclusion: Short-term ALDO infusion enhances experimental venous thrombosis in the mechanism involving primary haemostasis, fibrinolysis, NO and oxidative stress-dependent pathways. The MR antagonist only partially diminished the ALDO effects, suggesting the involvement of additional mechanisms.
Role of the AT2 receptor in modulating the angiotensin II contractile response of the uterine artery at mid-gestation
Authors: Pulgar Victor M , Yamashiro Henry , Rose James C , Moore Lorna G 
Published: March 2011

Introduction: During human pregnancy, circulating concentrations of components of the renin—angiotensin system increase, but pressor refractoriness to angiotensin II (Ang-II) is observed. Given the importance of the Ang-II pressor response in deciding susceptibility to preeclampsia and of the Ang-II system for controlling uterine vasoreactivity, we sought to address the effects of pregnancy on the reactivity of the isolated uterine artery (UA) in mice. Materials and methods : Blood pressure was measured throughout pregnancy in awake C57BL/6J mice. UA segments were isolated from three groups of animals (non-pregnant, mid [day 12—13] and late [day 18—19] gestation) and studied by wire myography. Results: UA diameters, KCl-mediated responses, and acetylcholine-dependent vasorelaxation were greater at mid and late gestation than in non-pregnant animals. Ang-II responses were also greater during pregnancy, with an increased contraction in response to AT2 receptor blockade at mid-gestation. AT1 receptor blockade abolished the Ang-II response in all groups. Conclusions: Study findings are consistent with the possibility that AT2 receptor-mediated vasodilatation plays a role in modulating Ang-II contractile responses in pregnancy.
Characterization and application of anion exchange polymer membranes with non-platinum group metals for fuel cells
Authors: Mamlouk M , Wang X , Scott K , Horsfall J A , Williams C 
Published: March 2011

An investigation of the carbon-supported iron phthalocyanine (Fe-Pc) catalyst for oxygen reduction reaction (ORR) in alkaline media and in hydrogen fuel cells is described. The non-noble metal Fe-Pc catalyst is shown to be a promising alternative to platinum for ORR in alkaline media, with onset potentials of ca. 15 mV higher and double the mass activity than that of Pt. The catalyst also showed lower peroxide generation at lower voltages than Pt when tested at a rotating ring disc electrode. The effect of various parameters such as catalyst loading, catalyst layer thickness, fabrication technique, and ionomer on a hydrogen fuel cell performance using an alkaline electrolyte membrane made by radiation grafting is described. Peak power densities of the fuel cell with Pt/C oxygen reduction catalysts were greater than 100 mW/cm at 60 °C using air. The performance of the fuel cell with the Fe-Pc catalyst was inferior to that with the Pt catalyst giving approximately half the peak power density initially due to the thicker catalyst layer and instability in the quaternary ammonium environment. However, the performance of the Fe-Pc catalyst under fuel cell conditions was found to fall with time due to an interaction of the catalyst with the ion-exchange group of the membrane and the ionomer used in the catalyst layer.
Earth's energy “Golden Zone”: a synthesis from mineralogical research
Authors: Nadeau P. H. 
Published: March 2011

AbstractThe impact of diagenetic processes on petroleum entrapment and recovery efficiency has focused the vast majority of the world's conventional oil and gas resources into relatively narrow thermal intervals, which we call Earth's energy “Golden Zone”. Two key mineralogical research breakthroughs, mainly from the North Sea, underpinned this discovery. The first is the fundamental particle theory of clay mineralogy, which showed the importance of dissolution/precipitation mechanisms in the formation of diagenetic illitic clays with increasing depth and temperature. The second is the surface area precipitation-rate-controlled models for the formation of diagenetic cements, primarily quartz, in reservoirs. Understanding the impacts of these geological processes on permeability evolution, porosity loss, overpressure development, and fluid migration in the subsurface, lead to the realization that exploration and production risks are exponential functions of reservoir temperature. Global compilations of oil/gas reserves relative to reservoir temperature, including the US Gulf Coast, have verified the “Golden Zone” concept, as well as stimulated further research to determine in greater detail the geological/mineralogical controls on petroleum migration and entrapment efficiency within the Earth's sedimentary basins.
Late Cretaceous—Palaeocene mid-latitude climates: inferences from clay mineralogy of continental-coastal sequences (Tremp-Graus area, southern Pyrenees, N Spain)
Authors: Arostegi J. , Baceta J. I. , Pujalte V. , Carracedo M. 
Published: March 2011

AbstractThe origin and distribution of late Maastrichtian–early Palaeocene clay mineral associations were investigated in the Tremp-Graus basin (South Pyrenees, Spain) to assess palaeoclimate changes during that period. The studied succession is made up of expanded continental and transitional terrigeneous and carbonate deposits accumulated in a coastal plain setting. X-ray diffraction, SEM-EDX and TEM-AEM analysis reveal that the main clay components are illite and smectite, but kaolinite, chlorite and illite-smectite mixed layers are present, although irregularly distributed, all of them showing a platy morphology typical of a detrital origin. Persistence of the chemical features of the Al-dioctahedral smectites throughout the whole succession demonstrates the persistence of the same source area during the interval studied. Palygorskite occurs in the late Danian and Selandian, within carbonate tidal flats as sabkha-like facies. In SEM images, the palygorskite displays straight fibre morphologies, both coating and branched curling out, a clear proof of authigenic origin.Physical or chemical weathering (PhW/ChW) determined as illite + chlorite/smectite + kaolinite ratio, smectite/kaolinite ratio and palygorskite distribution have been used as clay proxies for palaeoclimate reconstructions. Such data suggest a shift from temperate subhumid (perennial) conditions in late Maastrichtian times to a warm seasonal climate during early Palaeocene times. This trend, however, was dramatically altered during the late Danian–Selandian interval, when prevailing warm and semi-arid to arid climatic conditions caused intense evaporation and the development of an alkaline environment in which the palygorskite authigenesis took place.The proposed climatic trend partly concurs with that established for earliest Danian time by Domingoet al.(2007), also in the Tremp-Graus basin, from isotopic and geochemical proxies, as well as with the reconstruction of Cojan & Moreau (2006), in which a semiarid Danian phase for the near continental basin of Aix-en-Provence is postulated. However, it is at odds with the notion of a humid Danian state in the Pyrenees, as inferred by Gawendaet al.(1999) from clay mineral proxies of deep marine successions.
Effect of Pakistani bentonite on properties of mortar and concrete
Authors: Ahmad S. , Barbhuiya S. A. , Elahi A. , Iqbal J. 
Published: March 2011

AbstractBentonite is composed primarily of montmorillonite and is useful in a wide range of applications. This paper presents the results of an experimental investigation carried out to evaluate the possibility of using a Pakistani bentonite (from Jehangira, Swabi District) as a cement replacement material in mortar and concrete. The cement in mortar and concrete was replaced with the bentonite at 0%, 20%, 30%, 40% and 50% by cement mass. The strength activity index of bentonite was determined ‘as received’ (20ºC) and ‘heated’ (treatment at 500ºC and 900ºC). The test results indicated that the strength activity index of bentonite conformed to the ASTM Standard C618 specifications, except for the ‘900ºC heated’ bentonite. The water absorption decreased for mortar containing up to 30% bentonite and then steadily increased at higher bentonite loadings. When immersed in 5% Na2SO4 and 2% MgSO4 solution, the greatest compressive strength was observed for mortar containing 30% bentonite. The water demand of concrete increased with increasing bentonite content. Although the compressive strength of concrete decreased progressively as the substitution level of bentonite was increased, the compressive strength of concrete containing 30% ‘as received’ bentonite was found to be 70% of the control concrete, whereas for concrete containing 30% ‘500ºC heated’ bentonite, the strength was found to be 79% of the control concrete. It can be concluded that this Pakistani bentonite can be used to replace up to 30% of cement to produce concrete with sufficient compressive strength for low-cost construction resistant to sulphate attack.
Clonal B cells in patients with hepatitis C virus–associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset
Authors: Charles Edgar D. , Brunetti Claudia , Marukian Svetlana , Ritola Kimberly D. , Talal Andrew H. , Marks Kristen , Jacobson Ira M. , Rice Charles M. , Dustin Lynn B. 
Published: March 2011

Abstract
Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV+MC+ patients have clonal expansions of hypermutated, rheumatoid factor–bearing marginal zone-like IgM+CD27+ peripheral B cells using the VH1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4+ memory B-cell subset and to an “exhausted,” anergic CD21low memory B-cell subset in HIV+ patients. Moreover, HCV+MC+ patients' clonal peripheral B cells are enriched with CD21low, CD11c+, FCRL4high, IL-4Rlow memory B cells. In contrast to the functional, rheumatoid factor–secreting CD27+CD21high subset, the CD27+CD21low subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor–secreting plasmablasts, suggesting that a large proportion of HCV+MC+ patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes. This study was registered at www.clinicaltrials.gov as #NCT00435201.
Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment
Authors: Singbrant Sofie , Russell Megan R. , Jovic Tanja , Liddicoat Brian , Izon David J. , Purton Louise E. , Sims Natalie A. , Martin T. John , Sankaran Vijay G. , Walkley Carl R. 
Published: March 2011

Abstract
Erythropoietin (Epo) has been used in the treatment of anemia resulting from numerous etiologies, including renal disease and cancer. However, its effects are controversial and the expression pattern of the Epo receptor (Epo-R) is debated. Using in vivo lineage tracing, we document that within the hematopoietic and mesenchymal lineage, expression of Epo-R is essentially restricted to erythroid lineage cells. As expected, adult mice treated with a clinically relevant dose of Epo had expanded erythropoiesis because of amplification of committed erythroid precursors. Surprisingly, we also found that Epo induced a rapid 26% loss of the trabecular bone volume and impaired B-lymphopoiesis within the bone marrow microenvironment. Despite the loss of trabecular bone, hematopoietic stem cell populations were unaffected. Inhibition of the osteoclast activity with bisphosphonate therapy blocked the Epo-induced bone loss. Intriguingly, bisphosphonate treatment also reduced the magnitude of the erythroid response to Epo. These data demonstrate a previously unrecognized in vivo regulatory network coordinating erythropoiesis, B-lymphopoiesis, and skeletal homeostasis. Importantly, these findings may be relevant to the clinical application of Epo.
Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation
Authors: Le Robert Quan , Melenhorst J. Joseph , Battiwalla Minoo , Hill Brenna , Memon Sarfraz , Savani Bipin N. , Shenoy Aarthi , Hensel Nancy F. , Koklanaris Eleftheria K. , Keyvanfar Keyvan , Hakim Frances T. , Douek Daniel C. , Barrett A. John 
Published: March 2011

Abstract
After allogeneic stem cell transplantation (SCT), T lymphocyte function is reestablished from the donor's postthymic T cells and through thymic T-cell neogenesis. The immune repertoire and its relation to that of the donor have not been characterized in detail in long-term adult SCT survivors. We studied 21 healthy patients in their second decade after a myeloablative SCT for hematologic malignancy (median follow-up, 12 years). Immune profiles were compared with donor samples cryopreserved at transplant and beyond 10 years from SCT. Only one recipient was on continuing immunosuppression. Compared with the donor at transplant, there was no significant difference in CD4, CD8, natural killer, and B-cell blood counts. However, compared with donors, recipients had significantly fewer naive T cells, lower T-cell receptor excision circle levels, fewer CD4 central memory cells, more effector CD8+ cells, and more regulatory T cells. TCR repertoire analysis showed no significant difference in complexity of TCRVβ spectratype between recipients and donors, although spectratype profiles had diverged with both gain and loss of donor repertoire peaks in the recipient. In conclusion, long-term allogeneic SCT survivors have subtle defects in their immune profile consistent with defective thymic function but compatible with normal health. This study is registered at http://www.clinicaltrials.gov as NCT00106925.
An ENU-induced mouse mutant of SHIP1 reveals a critical role of the stem cell isoform for suppression of macrophage activation
Authors: Nguyen Nhu-Y. N. , Maxwell Mhairi J. , Ooms Lisa M. , Davies Elizabeth M. , Hilton Adrienne A. , Collinge Janelle E. , Hilton Douglas J. , Kile Benjamin T. , Mitchell Christina A. , Hibbs Margaret L. , Jane Stephen M. , Curtis David J. 
Published: March 2011

AbstractIn a recessive ENU mutagenesis screen for embryonic lethality, we identified a mouse pedigree with a missense mutation of SHIP1 (SHIP1el20) leading to an amino acid substitution I641T in the inositol-5′-phosphatase domain that represses phosphatidylinositol-3-kinase signaling. Despite detectable expression of functional SHIP1 protein, the phenotype of homozygous SHIP1el20/el20 mice was more severe than gene-targeted SHIP1-null (SHIP1−/−) mice. Compared with age-matched SHIP1−/− mice, 5-week-old SHIP1el20/el20 mice had increased myeloid cells, serum IL-6 levels, marked reductions in lymphoid cells, and died by 7 weeks of age with infiltration of the lungs by activated macrophages. Bone marrow transplantation demonstrated that these defects were hematopoietic-cell-autonomous. We show that the el20 mutation reduces expression in SHIP1el20/el20 macrophages of both SHIP1 and s-SHIP, an isoform of SHIP1 generated by an internal promoter. In contrast, SHIP1−/− macrophages express normal levels of s-SHIP. Compound heterozygous mice (SHIP1−/el20) had the same phenotype as SHIP1−/− mice, thus providing genetic proof that the more severe phenotype of SHIP1el20/el20 mice is probably the result of concomitant loss of SHIP1 and s-SHIP. Our results suggest that s-SHIP synergizes with SHIP1 for suppression of macrophage activation, thus providing the first evidence for a role of s-SHIP in adult hematopoiesis.
Molecular evolution of a gene cluster of serine proteases expressed in the Anopheles gambiae female reproductive tract
Authors: Mancini Emiliano , Tammaro Federica , Baldini Francesco , Via Allegra , Raimondo Domenico , George Phillip , Audisio Paolo , Sharakhov Igor V , Tramontano Anna , Catteruccia Flaminia , Torre Alessandra della 
Published: March 2011

AbstractBackgroundGenes involved in post-mating processes of multiple mating organisms are known to evolve rapidly due to coevolution driven by sexual conflict among male-female interacting proteins. In the malaria mosquitoAnopheles gambiae- a monandrous species in which sexual conflict is expected to be absent or minimal - recent data strongly suggest that proteolytic enzymes specifically expressed in the female lower reproductive tissues are involved in the processing of male products transferred to females during mating. In order to better understand the role of selective forces underlying the evolution of proteins involved in post-mating responses, we analysed a cluster of genes encoding for three serine proteases that are down-regulated after mating, two of which specifically expressed in the atrium and one in the spermatheca ofA. gambiaefemales.ResultsThe analysis of polymorphisms and divergence of these female-expressed proteases in closely related species of theA. gambiaecomplex revealed a high level of replacement polymorphisms consistent with relaxed evolutionary constraints of duplicated genes, allowing to rapidly fix novel replacements to perform new or more specific functions. Adaptive evolution was detected in several codons of the 3 genes and hints of episodic selection were also found. In addition, the structural modelling of these proteases highlighted some important differences in their substrate specificity, and provided evidence that a number of sites evolving under selective pressures lie relatively close to the catalytic triad and/or on the edge of the specificity pocket, known to be involved in substrate recognition or binding. The observed patterns suggest that these proteases may interact with factors transferred by males during mating (e.g. substrates, inhibitors or pathogens) and that they may have differently evolved in independentA. gambiaelineages.ConclusionsOur results - also examined in light of constraints in the application of selection-inference methods to the closely related species of theA. gambiaecomplex - reveal an unexpectedly intricate evolutionary scenario. Further experimental analyses are needed to investigate the biological functions of these genes in order to better interpret their molecular evolution and to assess whether they represent possible targets for limiting the fertility ofAnophelesmosquitoes in malaria vector control strategies.