Miracle-dz/UniFAR-FTUs huggingface dataset:
High glucose promotes nascent nephron apoptosis via NF- (cid:1) B and p53 pathways

High glucose promotes nascent nephron apoptosis via NF- (cid:1) B and p53 pathways. Am J Physiol Renal Physiol 300: F147–F156, 2011. 2010; hyperglycemic environment in utero reduces kidney size and nephron number due to nascent nephron apoptosis. However, the underlying mechanisms are incompletely understood. The present study investigated whether the nascent nephron apoptosis promoted by high glucose is mediated via the transcription factor NF- (cid:1) B and p53 signaling pathways. Neonatal mouse kidneys from the offspring of nondiabetic, diabetic, and insulin-treated diabetic dams were used for in vivo studies, and MK4 cells, an embryonic metanephric mesenchymal (MM) cell line, were used for in vitro studies. Neonatal kidneys of the offspring of diabetic mothers exhibited an increased number of apoptotic cells and reactive oxygen species (ROS) generation, enhanced NF- (cid:1) B activation, and nuclear translocation of its subunits (p50 and p65 subunits) as well as phosphorylation (Ser 15) of p53 compared with kidneys of offspring of nondiabetic mothers. Insulin treatment of diabetic dams normalized these parameters in the offspring. In vitro, high-glucose (25 mM) induced ROS generation and signiﬁcantly increased MK4 cell apoptosis and caspase-3 activity via activation of NF- (cid:1) B pathway, with p53 phosphorylation and nuclear translocation compared with normal glucose (5 mM). These changes in a high-glucose milieu were prevented by transient transfection of small interfering RNAs for dominant negative I (cid:1) B (cid:2) or IKK or p53. Our data demonstrate that high glucose-induced nascent nephron apoptosis is mediated, at least in part, via ROS generation and the activation of NF- (cid:1) B and p53 pathways.
The influence of perceived talker differences on the talker variability effect under cochlear implant simulation

Speech recognition is harder when communicating with multiple talkers. This “talker variability effect” has not been extensively examined for cochlear implant (CI) users, who have difficulty discriminating same-gender talkers but not different-gender talkers. A shadowing task was conducted with normal hearing listeners (N=19) under CI simulation. The test consisted of a single-talker condition (ST), and two multi-talker conditions with different male and female voices (MT-M) or only different female voices (MT-F). Response times were longer and accuracy was lower in MT-M compared to MT-F. Thus, the talker variability effect was observed only when talkers were perceptible under CI simulation.
COMPARISON BETWEEN ENDOSCOPIC SURGERY AND CALCANEAL PERFORATION IN THE MANAGEMENT OF PLANTAR FASCIITIS AND CALCANEAL

Background: Ignoring plantar fasciitis may result in chronic heel pain that hinders the regular activities. Prolonged standing, decreased range of ankle dorsiflexion, an intense running regime and obesity are all risk factors for plantar fasciitis. Surgery including endoscopic surgery or calcaneal perforation is considered only after 12 months of aggressive nonsurgical treatment. Aim of study: To evaluate the clinical outcome of endoscopic plantar fascia release in comparison to calcaneal drilling. Patients and Methods: A comparative study conducted in the Orthopedic unit in two Teaching Hospitals in Iraq during a period of three years from Feb, 2014 – Jan, 2017. It involved 70 feet (60 patients) with plantar fasciitis; 35 feet (30 patients) by endoscopic release of planter fascia in addition to spur removal (Group 1) and other 35 feet were treated by calcaneal perforation (Group 2) after more than six months of conservative treatment without relieve of their symptoms. Postoperative Evaluation was assessed by Ankle-Hind Foot Scale before surgery and at 18th month after surgery, duration until full weight bearing after surgery, and duration until returning to full activity. Patients with systemic cause of heel pain such as gout, pseudo gout, rheumatoid arthritis, ankylosing spondylitis or patients with mechanical abnormality, history of heavy smoking, diabetes mellitus or peripheral vascular insufficiency were excluded from the study. Results: No statistically significant difference in the mean of age between the study groups (42.9 versus 44.3 years, P=0.465). No statistical significant differences between study groups regarding postoperative complications (P=0.16). Mean of Ankle-Hind Foot Score was significantly higher in group (2) than that in group (1) (98.2 versus 93.5, P=0.001). Regarding duration until full activity, patients in group (2) were needed significantly lower duration than patients of group (1) to reach full activity (6.12 versus 9.9 weeks, P= 0.003). Conclusion: Calcaneal perforation is superior in the management of plantar fasciitis compared to endoscopic release of planter fascia.
Role of Angiotensin II in the Periovulatory Epidermal Growth Factor-Like Cascade in Bovine Granulosa Cells In Vitro 1

Angiotensin II (AGT-2) induces follicular prostaglandin release in a number of species and ovulation in rabbits. Conversely, AGT-2 antagonists block ovulation in cattle. To determine the mechanism of action of AGT-2, we used a bovine granulosa cell model in which luteinizing hormone (LH) increased the expression of genes essential for ovulation in a time- and dose-dependent manner. The addition of AGT-2 to LH-stimulated cells significantly increased abundance of prostaglan-din-endoperoxide synthase 2 (PTGS2) mRNA and protein, whereas AGT-2 alone had no effect. Upstream of PTGS2, AGT-2 increased abundance of mRNA encoding the epidermal growth factor-like ligands amphiregulin ( AREG ) and epiregulin ( EREG ) at 6 h posttreatment and abundance of a disintegrin and metalloprotease 17 ( ADAM17 ), a sheddase, within 3 h of treatment. Inhibiting sheddase activity abolished the stimulatory effect of AGT-2 on AREG , EREG , and PTGS2 mRNA. The addition of selective AGT-2 antagonists to cells stimulated with LH plus AGT-2 demonstrated that AGT-2 did not act through the type 1 receptor and did not increase mitogen-activated protein kinase 3/1 phosphorylation. Combined with previous data from studies in vitro, we conclude that AGT-2 is an essential cofactor for LH in the early increase of ADAM expression/activity that induces the cascade of events leading to ovulation.
Simulation Model for the Analysis of Patient Pathways and Delivery of Medical Services for Coronary Heart Disease in the Swiss Population

The Swiss health system is sound, but expensive and the discussion on how to curb rising costs without compromising quality of health care is controversial. This controversy pertains to the definition of an appropriate supply and to the design of adequate policy interventions. To address these issues, needs-based approaches are favored, but to date only few attempts have been made to adopt this approach. We propose and assess a simulation model as an instrument for a needs-based health care planning for an exemplary case. Our study is focused on coronary heart disease in Switzerland, following the patient pathway from the onset of symptoms to diagnostic and therapeutic interventions. We suggest that the proposed model is a valuable framework to explain empirical data and to test hypotheses with regard to potential overuse of diagnostic interventions. Moreover, it provides a generic cohort model structure to analyze a chronic disease in a population, where prognosis depends on age and time since first event (or the onset of the chronic disease). We identify relevant knowledge gaps and present suggestions for further model development.
Theoretical Nuclear Physics

A semi-empirical basis is used to describe and correlate the known nuclear properties including the theoretical concepts, methods, and considerations which have been devised in order to interpret the experimentsl material and to advance the ability to predict and control nuclear phenomena. General properties, two-body problems at low energies, nuclear forces, two-body problems at high energies, three- and four-body problems, nuclear spectroscopy, nuclear reactions, spontaneous decay of nuclei, interaction of nuclei with electromagnetic radiation, and beta decay are treated. 1200 references. (JFP)
Cells More Rapidly Than the Bulk of the Splenic Marginal Zone Generate Effector Lymphocytes Enriched in high CD21 high IgM

2 Ag encounter will recruit Ag-speciﬁc cells from the pool of mature B lymphocytes in the spleen and activate them to perform effector functions: generation of Ab-forming cells (plasma cells) and presentation of Ag to T cells. We have compared the ability of mature follicular and marginal zone cells to develop into effector B cells. The generation of marginal zone B cells and their localization in the marginal sinus area are T cell and CD40 ligand independent, suggesting that they do not represent a postgerminal center population. Compared with mature recirculating follicular B cells, they express several characteristics of previous antigenic experience, including higher levels of B7.1 (CD80) and B7.2 (CD86) when freshly isolated and following in vitro stimulation. After a brief 6- to 8-h in vitro stimulation with LPS or anti-CD40 Abs, marginal zone B cells become potent APCs. In addition, their ability to proliferate and differentiate into plasma cells in response to low doses of T-independent polyclonal stimuli (LPS) is far greater than that of follicular B cells. These ﬁndings indicate a functional heterogeneity within splenic mature B lymphocytes, with marginal zone B cells having the capacity to generate effector cells in early stages of the immune response against particulate Ags scavenged efﬁciently in this special anatomical site. The Journal of Immunology, 1999, 162: 7198–7207. certain Ig heavy chain transgenic (TG) proportionally larger MZ compartments that may constitute up to 50% of splenic B cells, and that the development of this is indeed independent of T cells. We have used these TG mice as a source of large quantities of puriﬁed MZ B cells to facilitate the analysis of their functional potential in early stages of in vitro activation. We show that MZ B cells respond better than FO B cells with respect to early in vitro activation events, resulting in up-regulation of T cell costimulatory molecules and a concomitant ability to function as APCs. We also show that MZ B cells proliferate much faster in response to very low doses of polyclonal mitogens and terminally differentiate into plasma cells within hours of activation. Collectively, these ﬁndings suggest that MZ B cells have unique signaling and subsequent differentiative poten-tials that might permit them to react faster than the majority of splenic B cells (FO) in the earliest stages of an in vivo immune response. These functional differences apply to both Ag presentation and the production of short-lived IgM Ab-forming cells that are involved in the early defense against blood-borne pathogens.
FibrosisDual Roles of IL-4 in Lung Injury and

Increased lung IL-4 expression in pulmonary ﬁbrosis suggests a potential pathogenetic role for this cytokine. To dissect this role, bleomycin-induced pulmonary inﬂammation and ﬁbrosis were analyzed and compared in wild type (IL-4 (cid:1) / (cid:1) ) vs IL-4-deﬁcient (IL-4 (cid:2) / (cid:2) ) mice. Lethal pulmonary injury after bleomycin treatment was higher in IL-4 (cid:2) / (cid:2) vs IL-4 (cid:1) / (cid:1) mice. By administration of anti-CD3 Abs, we demonstrated that this early response was linked to the marked T lymphocyte lung inﬁltration and to the overproduction of the proinﬂammatory mediators such as TNF- (cid:3) , IFN- (cid:4) , and NO in IL-4 (cid:2) / (cid:2) mice. In contrast to this early anti-inﬂammatory/immunosuppressive role, during later stages of ﬁbrosis, IL-4 played a proﬁbrotic role since IL-4 (cid:2) / (cid:2) mice developed signiﬁcantly less pulmonary ﬁbrosis relative to IL-4 (cid:1) / (cid:1) mice. However, IL-4 failed to directly stimulate proliferation, (cid:3) -smooth muscle actin, and type I collagen expression in lung ﬁbroblasts isolated from the wild-type mice. Upon appropriate stimulation with other known ﬁbrogenic cytokines, ﬁbroblasts from IL-4 (cid:2) / (cid:2) mice were relatively deﬁcient in the studied parameters in comparison to ﬁbroblasts isolated from IL-4 (cid:1) / (cid:1) mice. Taken together, these data suggest dual effects of IL-4 in this model of lung ﬁbrosis: 1) limiting early recruitment of T lymphocytes,
Differential Requirement of Histone Acetylase and Deacetylase Activities for IRF5-Mediated Proinflammatory Cytokine Expression

Recent evidence indicates a new role for histone deacetylases (HDACs) in the activation of genes governing the host immune response. Virus, along with other pathogenic stimuli, triggers an antiviral defense mechanism through the induction of IFN, IFN-stimulated genes, and other proinflammatory cytokines. Many of these genes have been shown to be regulated by transcription factors of the IFN regulatory factor (IRF) family. Recent studies from IRF5 knockout mice have confirmed a critical role for IRF5 in virus-induced type I IFN expression and proinflammatory cytokines IL-6, IL-12, and TNF-α; yet, little is known of the molecular mechanism of IRF5-mediated proinflammatory cytokine expression. In this study, we show that both HDACs and histone acetyltransferases (HATs) associate with IRF5, leading to alterations in its transactivation ability. Using the HDAC inhibitor trichostatin A, we demonstrate that ISRE, IFNA, and IL6 promoters require HDAC activity for transactivation and transcription, whereas TNFα does not. Mapping the interaction of corepressor proteins (HDAC1, silencing mediator of retinoid and thyroid receptor/nuclear corepressor of retinoid receptor, and Sin3a) and HATs to IRF5 revealed distinct differences, including the dependence of IRF5 phosphorylation on HAT association resulting in IRF5 acetylation. Data presented in this study support a mechanism whereby virus triggers the dynamic conversion of an IRF5-mediated silencing complex to that of an activating complex on promoters of target genes. These data provide the first evidence, to our knowledge, of a tightly controlled transcriptional mechanism whereby IRF5 regulates proinflammatory cytokine expression in conjunction with HATs and HDACs.
Effect of liquid formulations of Rhizobium inoculation on growth and yield of mung bean

The mung bean ( Vigna radiata ) belongs to group of the legume family (Fabaceae). This family is a wide spread as it occupies the third largest family of flowering plants, with approximately 650 genera and nearly 20,000 species. The present study was to check the effect of liquid formulations of Rhizobium inoculation on Soil microbial population dynamics at periodic intervals in soil, nitrogen and phosphorus uptake by mung bean, growth and yield of mung bean as influenced by application of liquid Rhizobium. After considering all the parameters, inference could be drawn that Rhizobium application enhance the growth leading to increase in yield of mung bean. It was observed that T 3 : S.T. L. liquid Rhizobium @ 25 ml/kg of seed each had higher arithmetic value for growth parameters including germination, plant height, number of branches, number of leaves, LAI, root nodules and yield parameters pods/ plant, 1000 seed weight ultimately yield/ ha. Other parameters including chemical and microbial parameters showed significant increase over the absolute control. Above investigation concluded that inoculation of liquid formulation of Rhizobium enhanced growth as well as yield of mung bean. Population of Rhizobium as influenced by inoculation of liquid formulations significantly was enhanced. Total N and P uptake by plant and grain sample was found to be significantly higher due microbial inoculations.
Reply to Bouchiat et al

1. Kwiecinski J, Jacobsson G, Karlsson M, et al. Staphylokinase promotes the establishment of Staphylococcus aureus skin infections while decreasing disease severity. J Infect Dis 2013; 208:990–9. 2. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30:633–8. 3. Monecke S, Slickers P, Ehricht R. Assignment of Staphylococcus aureus isolates to clonal complexes based on microarray analysis and pattern recognition. FEMS Immunol Med Microbiol 2008; 53:237–51. 4. Kwiecinski J, Josefsson E, Mitchell J, et al. Activation of plasminogen by staphylokinase reduces the severity of Staphylococcus aureus systemic infection. J Infect Dis 2010; 202:1041–9.
ENDOGENOUS BIOTIN AND BACKGROUND STAINING IN MURINE CARDIAC TISSUE USING THE AVIDIN-BIOTIN IMMUNOPEROXIDASE TECHNIQUE by

Previous investigations have shown that there is an increased expression of major histocompatibility complex (MHC) molecules during allograft rejection due to cytokines secreted by lymphocytes and monocytes following stimulation by alloantigens or viral infection. In order to investigate the expression of H-2 molecules in allografted cardiac tissue, we used a modified direct peroxidase staining method based on the avidin-biotin reaction. Immunoperoxidase staining based on the avidin-biotin reaction is sensitive and widely used. This study reports the problems encountered when we applied this technique or staining fresh frozen BALB/c strain mouse heart tissue, the mechanisms responsible for the difficulties, as well as modifications to the procedures which eventually allowed successful staining and identification ofMHC molecules on allograft tissue. The commercially available hybridoma cells that produce anti-H-2 Kdnd monoclonal antibodies needed to demonstrate MHC antigen on BALB/c tissue are generated by fusion of mouse myeloma cells and mouse spleen cells. In an indirect staining protocol, secondary antibodies to be used are customarily elicited by injecting mouse IgG into animals of a different species, such as rabbit or goat; the resultant anti-mouse IgG antibody will tend to react not only with the specific primary IgG attached to target cells, but also to any IgG already present in the target pnor to application of the primary antibody. Therefore, a false positive staining may result because of the same species origin of primary antibodies generated in the tissue to be stained. Furthermore, in a direct staining procedure which avoided the secondary antibody problem described above, the reagent avidin-horseradish-peroxidase also caused excessive staining. To avoid the application of mouse antibody to mouse tissue in the indirect staining method, a modified direct staining method involving biotinylated anti-H-2 monoclonal antibodies was used. Endogenous biotin in mouse heart tissue was found to be a major cause of excessive staining in the avidin-biotin based immunoperoxidase staining technique. It was overcome by pretreatment of the tissue with free avidin solution and followed by free biotin solution. The free avidin combined with endogenous biotin, and the free biotin applied thereafter saturated any remaining avidin binding sites. Normal inbred mouse BALBlc heart tissue treated with anti-H-2 KdDd antibody showed little staining of myocyte plasma and intercalated discs, but definitive staining of nuclear membranes, myocyte membranes and the endothelium of arterioles and capillaries. Syngeneically grafted BALBI c inbred mouse heart tissue given the same treatment showed staining similar to that of a normal BALBI c heart. In contrast, allografted heart tissue, harvested and stained day 4 posttransplantation, showed increased staining on myocyte membranes and discs
Cardiac Syndrome X: assessment of endothelial function by peripheral arterial tonometry

: Background: Cardiac Syndrome X (CSX) is characterized by the presence of typical chest pain, a positive exercise test result and normal coronary arteries upon angiographic examination. The development of this syndrome is thought to be heterogeneous, involving many pathogenic mechanisms. Among other mechanisms, impaired endothelial function may predominantly contribute to the pathogenesis of symptoms in CSX patients. In this work we prospectively evaluated the role of endothelial function, using non-invasive peripheral arterial tonometry, in a cohort of patients which included healthy patients, patients with coronary artery disease and patients with CSX, from Italian-speaking Switzerland. Methods: We examined systemic endothelial function in a cohort of 37 patients: 8 healthy patients, 15 patients with coronary artery disease and 14 CSX patients. The latter were identified from the Swiss-Italian cohort of the “Italian registry of patients with Cardiac Syndrome X” (“Registro italiano dei pazienti con Sindrome X”). Endothelial function was assessed using peripheral arterial tonometry, a validated and FDA (U.S. Food and Drug Administration) approved tool for the examination of systemic and coronary endothelial function in humans [1-5]. Results: The average values for the two main indexes measured, the “Endopat index” and the “Endopat index according to Bonetti”, were over the discriminatory value of 1.67 for all studied groups. A value of less than 1.67 indicates the presence of endothelial dysfunction. Statistical analysis failed to demonstrate a significant difference between studied groups (p value of 0.442 and 0.417 respectively). Larger differences could be extrapolated in some selected subgroups, but in our study, the number of patients was too small to allow statistical analysis of the significance of the results. Conclusion: Our results, based on a relatively small sample of patients with CSX, do not show a significant difference in endothelial
Block EBV Infection In Vitro Selectively Target B Cells through CD21 and Released by EBV-Transformed B Cells Exosomes Containing Glycoprotein 350

Exosomes are nano-sized membrane vesicles released from a wide variety of cells, formed in endosomes by inward budding of the endosomal limiting membrane. They have immune stimulatory-, inhibitory-, or tolerance-inducing effects, depending on their cellular origin, which is why they are investigated for use in vaccine and immune therapeutic strategies. In this study, we explored whether exosomes of different origins and functions can selectively target different immune cells in human peripheral blood. Flow cytometry, confocal laser scanning microscopy, and multispectral imaging ﬂow cytometry (ImageStream) revealed that exosomes derived from human monocyte-derived dendritic cells and breast milk preferably associated with monocytes. In contrast, exosomes from an EBV-transformed B cell line (LCL1) preferentially targeted B cells. This was not observed for an EBV 2 B cell line (BJAB). Electron microscopy, size-distribution analysis (NanoSight), and a cord blood transformation assay excluded the presence of virions in our LCL1 exosome preparations. The interaction between LCL1-derived exosomes and peripheral blood B cells could be blocked efﬁciently by anti-CD21 or anti-gp350, indicating an interaction between CD21 on B cells and the EBV glycoprotein gp350 on exosomes. The targeting of LCL1-derived exosomes through gp350–CD21 interaction strongly inhibited EBV infection in B cells isolated from umbilical cord blood, suggesting a protective role for exosomes in regulating EBV infection. Our ﬁnding also suggests that exosome-based vaccines can be engineered for speciﬁc B cell targeting by
VOLUMES OF HYPERBOLIC 3-MANIFOLDS

A weldable alloy steel having improved fracture toughness and stress corrosion resistance at very high strength levels in which the essential composition, according to percent by weight is in the range of 0.12 - 0.17% carbon, 1.8 - 3.2% chromium, 0.9 - 1.35% molybdenum, 11.5 - 14.5% cobalt, and 9.5 - 10.5% nickel, the remainder being substantially iron, i.e., with minor amounts of certain impurities and residual elements. Very good stress corrosion resistance and fracture toughness at high strength levels is produced when these elements are alloyed in the percent by weight ranges of 0.15 - 0.17% carbon, 1.8 - 2.2% chromium, 0.9 - 1.1% molybdenum, 13.5 - 14.5% cobalt, and 9.5 - 10.5% nickel. Good fatigue endurance is achieved. Minor amounts of manganese also may be present.