Role of Plasmodium falciparum thrombospondin-related anonymous protein in host-cell interactions

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Assessment of Disease Activity and Complications in Patients of Pulmonary Tuberculosis by High Resolution Computed Tomography

Background: Tuberculosis (TB) is a global health problem and the second most common infectious cause of death. High-resolution computed tomography (HRCT) is far more superior to chest radiography as well as conventional CT for analyzing the pulmonary parenchyma. This study aimed to evaluate the role of HRCT in pulmonary tuberculosis (PTB) with respect to disease activity and complication after anti-tubercular therapy (ATT). Methods: This prospective observational study was conducted in the Department of Radiodiagnosis, Teerthanker Mahaveer Medical College & Research Centre (TMMC&RC) for a period of 1.5 years. A total of 50 cases of newly diagnosed TB were included in the study and a standard six-month ATT was given to the patients. Pulmonary involvement was evaluated by HRCT (128 slice multi-detector PHILIPS INGENUITY CT scanner), twice for each patient (first scan after diagnosis and second after treatment completion). The acquired HRCT images were reconstructed on a highresolution lung algorithm and parenchymal, bronchial, and extra parenchymal findings were recorded systematically. Results: Out of the 50 patients, 5 died within two months of the initiation of treatment and four were lost to follow-up. Thus, post treatment follow-up sample size was reduced to 41 patients. Ill-defined nodules (96%), tree-in-bud pattern (74%), consolidation (86%), cavitary lesions (98%), and ground glass opacities (58%) were the main imaging features of active cases of TB on HRCT. Resolution to thin-walled cavitary lesions (36.5%), bronchiectasis (41.5%), and fibrotic (parenchymal) bands (66%) were common complications or sequelae which were observed after completion of treatment. Conclusion: HRCT thorax is a sensitive modality for evaluation of parenchymal and airway manifestations in cases of PTB and can aid in differentiation of active disease from healed disease. It allows early identification of post-treatment complications and sequelae in patients of PTB

Age-related difference in cardiac adaptation to chronic hypertension in rats, with and without nifedipine treatement

Three myosin isozymes, V1 (αα MHC = Myosin Heavy Chain gene), V2 (αβ MHC) and V3 (ββ MHC) that are identified in the cardiac ventricles of most mammals have been shown to shift to a V3 predominance pattern during cardiac growth and in response to left ventricular pressure overload, and to V1 predominance following anti hypertensive treatment. This study examined whether long-term hypertension impairs the ability of the adult heart to restructure myosin isozyme proportions. Using pyrophosphate gel electrophoresis, we studied proportions of cardiac myosin isozymes (V1 and V3) in young (16 weeks) and adult (36 weeks) spontaneously hypertensive rats (SHR), and following 12 weeks of nifedipine (N) treatment in age-matched SHR rats (SHR-N). The values of V1 and V3 myosin isozymes were derived by adding half of the value of V2 to each isozyme proportion. The V3 proportion in the young SHR control (SHR-C) group (49%) was 34% higher (p < 0.05) than in the young Wistar Kyoto control (WKY-C) group (37%). However, the proportion was similarly high, though not statistically significant, in both the adult SHRC (73%) and WKY-C (71%) groups. The proportion in the young SHR-N group (29%) was 41% lower (p < 0.05) than in the young SHR-C group (49%), and the proportion in the adult SHR-N group (47%) was 34% lower (p < 0.05) than in the adult SHR-C group (73%). The ratio of left ventricular weight to body weight (LVW/BW), which determines left ventricular hypertrophy (LVH), was higher in both young and adult SHR-C (26%, p < 0.05, and 42%, p < 0.05, respectively) than in WKY-C groups. The mean LVW/BW was 27% (p lt; 0.05) greater in adult than in young SHR-C rats. The LVW/BW in both age groups of treated SHR-N was similar to that in age matched WKY-C rats. Conclusion: Our study showed that a rise in the V3 level occurs in young hypertensive rats, but no rise occurs in the V3 level in adult hypertensive rats. High blood pressure seems to contribute to the high V3 level in young hypertensive rats, but in adult hypertensive rats, high blood pressure does not accentuate the V3 rise already acquired due to the aging process. Nifedipine treatment in both young and adult hypertensive rats prevented the V3 rise due to hypertension and to the aging process. This effect of nifedipine seems to be through its antihypertensive action.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45335/1/11010_2004_Article_199277.pd

Sistema Solar: Planetas Clássicos

O conhecimento curricular de Astronomia para surdos, não pode ser empobrecido, subtraído, fragmentado, mas sim formulado para corresponder a sua identidade de cognição, sem distanciar-se, porém, do direito inalienável a tudo que devem conhecer. Métodos de ensino não podem ser únicos para todos e, um sistema educacional que não revela estas diferenças está fadado em provocar a exclusão destes educandos por considerá-los inaptos, intelectualmente. Sendo assim, ao organizar o conteúdo que será trabalhado em sala de aula, o professor terá sempre em mente o tema Sistema Solar /Planetas Clássicos. Este tema está diretamente ligado a outros temas, permitindo ao aluno surdo fazer parte desse todo tão complexo que é o Universo em que vivemo

Vitamin D Receptor Deficit Induces Activation of Renin Angiotensin System Via SIRT1 Modulation in Podocytes

Vitamin D receptor (VDR) deficient status has been shown to be associated with the activation of renin angiotensin system (RAS). We hypothesized that lack of VDR would enhance p53 expression in podocytes through down regulation of SIRT1; the former would enhance the transcription of angiotensinogen (Agt) and angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, and AT1R. In vitro studies, VDR knockout podocytes not only displayed up regulation p53 but also displayed enhanced expression of Agt, renin and AT1R. VDR deficient podocytes also displayed an increase in mRNA expression for p53, Agt, renin, and AT1R. Interestingly, renal tissues of VDR-M as well as VDR heterozygous (h) mice displayed attenuated expression of deacetylase SIRT1. Renal tissues of VDR-M mice showed acetylation of p53 at lysine (K) 382 residues inferring that enhanced p53 expression in renal tissues could be the result of ongoing acetylation, a consequence of SIRT1 deficient state. Notably, podocytes lacking SIRT1 not only showed acetylation of p53 at lysine (K) 382 residues but also displayed enhanced p53 expression. Either silencing of SIRT1/VDR or treatment with high glucose enhanced podocyte PPAR-y expression, whereas, immunoprecipitation (IP) of their lysates with anti-Retinoid X receptor (RXR) antibody revealed presence of PPAR-y. It appears that either the deficit of SIRT1 has de-repressed expression of PPAR-y or enhanced podocyte expression of PPAR-y (in the absence of VDR) has contributed to the down regulation of SIRT1

Disruption of APOL1-miR193a Axis Induces Disorganization of Podocyte Actin Cytoskeleton

Abstract APOL1-miR193a axis participates in the preservation of molecular phenotype of differentiated podocytes (DPDs). We examined the hypothesis that APOL1 (G0) preserves, but APOL1 risk alleles (G1 and G2) disrupt APOL1-miR193a axis in DPDs. DPDG0s displayed down-regulation of miR193a, but upregulation of nephrin expression. DPDG1s/G2s exhibited an increase in miR193a and down-regulation of the expression of adherens complex’s constituents (CD2AP, nephrin, and dendrin). DPDG0s showed decreased Cathepsin L, enhanced dynamin expressions, and the intact actin cytoskeleton. On the contrary, DPDG1s/G2s displayed an increase in Cathepsin L, but down-regulation of dynamin expressions and disorganization of the actin cytoskeleton. APOL1 silencing enhanced miR193a and Cathepsin L, but down-regulated dynamin expressions. DPDG1s/G2s displayed nuclear import of dendrin, indicating an occurrence of destabilization of adherens complexes in APOL1 risk milieu. These findings suggest that DPDG1s and DPDG2s developed disorganized actin cytoskeleton as a consequence of disrupted APOL1-miR193a axis. Interestingly, docking and co-labeling studies suggested an interaction between APOL1 and CD2AP. APOL1 G1/G1 and APOL1 G1/G2 transgenic mice displayed nuclear import of dendrin indicating destabilization of adherens complexes in podocytes; moreover, these mice showed a four-fold increase in urinary albumin to creatinine ratio and development of focal segmental glomerular lesions

Modulation of APOL1-miR193a Axis Prevents Podocyte Dediffrentiation in High Glucose Milieu

The loss of podocyte (PD) molecular phenotype is an important feature of diabetic podocytopathy. We hypothesized that high glucose (HG) induces dedifferentiation in differentiated podocytes (DPDs) through alterations in the apolipoprotein (APO) L1-microRNA (miR) 193a axis. HG-induced DPD dedifferentiation manifested in the form of downregulation of Wilms’ tumor 1 (WT1) and upregulation of paired box 2 (PAX2) expression. WT1-silenced DPDs displayed enhanced expression of PAX2. Immunoprecipitation of DPD cellular lysates with anti-WT1 antibody revealed formation of WT1 repressor complexes containing Polycomb group proteins, enhancer of zeste homolog 2, menin, and DNA methyltransferase (DNMT1), whereas silencing of either WT1 or DNMT1 disrupted this complex with enhanced expression of PAX2. HG-induced DPD dedifferentiation was associated with a higher expression of miR193a, whereas inhibition of miR193a prevented DPD dedifferentiation in HG milieu. HG downregulated DPD expression of APOL1. miR193a-overexpressing DPDs displayed downregulation of APOL1 and enhanced expression of dedifferentiating markers; conversely, silencing of miR193a enhanced the expression of APOL1 and preserved DPD phenotype. Moreover, stably APOL1G0-overexpressing DPDs displayed the enhanced expression of WT1 but attenuated expression of miR193a; nonetheless, silencing of APOL1 reversed these effects. Since silencing of APOL1 enhanced miR193a expression as well as dedifferentiation in DPDs, it appears that downregulation of APOL1 contributed to dedifferentiation of DPDs through enhanced miR193a expression in HG milieu. Vitamin D receptor agonist downregulated miR193a, upregulated APOL1 expression, and prevented dedifferentiation of DPDs in HG milieu. These findings suggest that modulation of the APOL1-miR193a axis carries a potential to preserve DPD molecular phenotype in HG milieu.</jats:p

HIV-1 Promotes Renal Tubular Epithelial Cell Protein Synthesis: Role of mTOR Pathway

Tubular cell HIV-infection has been reported to manifest in the form of cellular hypertrophy and apoptosis. In the present study, we evaluated the role of mammalian target of rapamycin (mTOR) pathway in the HIV induction of tubular cell protein synthesis. Mouse proximal tubular epithelial cells (MPTECs) were transduced with either gag/pol-deleted NL4-3 (HIV/MPTEC) or empty vector (Vector/MPTEC). HIV/MPTEC showed enhanced DNA synthesis when compared with Vector/MPTECs by BRDU labeling studies. HIV/MPTECs also showed enhanced production of β-laminin and fibronection in addition to increased protein content per cell. In in vivo studies, renal cortical sections from HIV transgenic mice and HIVAN patients showed enhanced tubular cell phosphorylation of mTOR. Analysis of mTOR revealed increased expression of phospho (p)-mTOR in HIV/MPTECs when compared to vector/MPTECs. Further downstream analysis of mTOR pathway revealed enhanced phosphorylation of p70S6 kinase and associated diminished phosphorylation of eEF2 (eukaryotic translation elongation factor 2) in HIV/MPTECs; moreover, HIV/MPTECs displayed enhanced phosphorylation of eIF4B (eukaryotic translation initiation factor 4B) and 4EBP-1 (eukaryotic 4E binding protein). To confirm our hypothesis, we evaluated the effect of rapamycin on HIV-induced tubular cell downstream signaling. Rapamycin not only attenuated phosphorylation of p70S6 kinase and associated down stream signaling in HIV/MPTECs but also inhibited HIV-1 induced tubular cell protein synthesis. These findings suggest that mTOR pathway is activated in HIV-induced enhanced tubular cell protein synthesis and contributes to tubular cell hypertrophy

A study of damping characteristics of aluminum-indium alloys and melting transformation of embedded indium inclusions.

Damping of aluminum-indium alloys with up to 16 wt. % indium was characterized. In the nominally strain amplitude-independent regime, the room-temperature damping initially decreased with the addition of indium and showed a minimum at 10 wt. %. For these alloys, the damping was modeled using a diffusion controlled dislocation relaxation model for the high-temperature background and a general expression for multiphase materials was given. For indium contents greater than 10 wt. %, a relaxation peak at 25\sp\circC and 1.0 Hz also contributed to the room-temperature damping. This peak was associated with the indium and an activation energy of 0.6 $\pm$ 0.2 eV was experimentally determined. It was suggested that a critical indium inclusion size is necessary before the relaxation peak becomes appreciable and that this damping mechanism is analogous to that observed for graphite in gray cast irons. Melting transformation of indium particles (1-20 $\mu$m in diameter) embedded in an aluminum matrix was studied using internal friction and differential calorimetry techniques. Two distinct melting peaks in both the internal friction and calorimetry results were observed. Inclusions situated at aluminum grain boundaries melted at the equilibrium melting temperature of 156\sp\circC whereas the inclusions embedded in the grain interiors melted at an elevated temperature of about 160\sp\circC. The difference in melting behavior between the embedded and the grain boundary inclusions was related to differences in the relaxational rates of the transformation stresses. Volume changes at the grain boundaries were rapidly accommodated by diffusional processes, whereas the matrix behaved in a rigid manner with respect to particles embedded within the grains. The unrelaxed stress observed for the inclusions embedded in the grain interiors produced a melting point elevation and thus, two separate peaks were observed. A general theoretical model was proposed that predicted the internal friction associated with a first order transformation of the embedded particles. This model relates the internal friction with the rate of transformation, stresses acting upon the transforming particles, and the relaxational characteristics of the surrounding matrix.Ph.D.Applied SciencesEngineering, Materials scienceMaterials scienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/129140/2/9332129.pd

Internal Friction Study of Melting in Aluminum-indium and Aluminum-lead Alloys

Internal friction studies were performed on two aluminum-based alloys: aluminum-indium and aluminum-lead. Each system was processed to obtain microstructures consisting of an aluminum matrix dispersed with inclusions of nominally pure indium or lead. The inclusion volume fraction was varied from 0.02 to 0.07 (6 to 16% by weight) for aluminum-indium alloys and from 0.01 to 0.02 (4 to 8% by weight) for aluminum-lead alloys. Internal friction was measured as a function of time, temperature, temperature scan rate, frequency, and strain amplitude using a dynamic mechanical analyzer. Sharp internal friction peaks were observed near the melting temperatures of 156 and 327°C for the aluminum-indium and aluminum-lead alloys, respectively. These peaks were associated with a matrix relaxation that accommodated the change in volume associated with the melting transition. The internal friction at the melting transition exhibited many of the internal friction characteristics associated with the polymorphic diffusionless transformations. Internal friction peak height associated with these melting transitions was found to be proportional, but not linear, to the ratio of the heating rate to the frequency of oscillation. Also, the peak height was observed to increase proportionally with the volume fraction of the inclusion. Increasing the applied strain amplitude reduced the internal friction peak height and the peak was observed to disappear completely at strain amplitudes of greater than 0.02 for aluminum-indium and 0.01 for aluminum-lead alloys. An internal friction peak was not observed when a laminate of aluminum and indium was tested. It was postulated that the internal friction peaks observed near the melting transition temperature of the embedded inclusions were related to a matrix relaxation around the inclusion. Only when the volume change of the melting inclusions is fully constrained by the matrix is an internal friction peak observed. Similar effects were observed for cooling experiments where the inclusions solidified