Estimates of cusp forms for certain co-compact arithmetic subgroups

In this article, we derive a sub convexity estimate of Hecke eigen cusp forms associated to certain cocompact arithmetic subgroups of SL(2,R). The main result can be considered as the holomorphic version of the estimate of Hecke eigen Maass forms, derived in a famous paper of Iwaniec and Sarnak. A stronger estimate was derived by Khayutin and Steiner in arXiv:2009.07194. However, techniques used in both the papers are very different. <br

Telomere shortening: a marker of atherosclerosis?

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Relating 3D Geometry and Photoelectrochemical Activity of WO3-loaded n-Si Nanowires: Design Rules for Photoelectrodes

Nanostructured electrodes for photoelectrochemical (PEC) applications, such as water splitting, have rather low photocurrent density regarding their highly enlarged surface area compared to plain electrodes. This demands for further understanding of the relation between the 3D geometry and the PEC activity. To this end, we fabricate WO3/Si nanowire array photoanodes with various nanowire lengths (1.3 µm, 2.7 µm, 3.2 µm and 3.8 µm) and different WO3 thicknesses (10 nm, 30 nm and 50 nm) using wet chemical etching for nanostructuring of Si and atomic layer deposition for the deposition of WO3. It is found that by increasing the etching time, the nanowires become longer and the top surface area decreases. The photocurrent density first increases and then decreases with increasing Si etching time. This behaviour can be explained by different and opposite effects regarding absorption, geometry and materials specific properties. Particularly, the decrease of the photocurrent density can be due to: First, the longer the nanowires the heavier the recombination of the photogenerated carriers. Second, the long-time Si etching results in a loss of top part of the nanowire arrays. Because of shadowing, the WO3 located at the top part of the nanowires is more effective than that at the bottom part for the WO3/Si nanowire arrays and therefore the photocurrent is decreased. It reveals a trade-off between the top part surface area and the length of the nanowires. This study contributes to a better understand of the relation between the geometry of nanostructures and the performance of PEC electrodes.</p

Differential gene expression of NADPH oxidase (p22phox) and hemoxygenase-1 in patients with Type 2 diabetes and microangiopathy

Aims: While the downstream effects of increased reactive oxygen species (ROS) in the pathogenesis of diabetes were well studied, only a few studies have explored the cellular sources of ROS. We examined whether protection against oxidative stress is altered in patients with diabetes and microangiopathy by examining changes in NADPH oxidase (p22phox) and hemoxygenase‐1 (HO‐1) levels. Methods: NADPH oxidase (p22phox) and HO‐1 gene expression were probed by RT‐PCR using leucocytes from patients with Type 2 diabetes without (n = 19) and with microangiopathy (n = 20) and non‐diabetic subjects (n = 17). Levels of lipid peroxidation as measured by thiobarbituric reactive substances (TBARS) and protein carbonyl content (PCO) were determined by fluorimetric and spectrophotometric methods, respectively. Results: p22phox gene expression (mean ± se) was significantly (P < 0.05) higher in diabetic patients with (0.99 ± 0.04) and without microangiopathy (0.86 ± 0.05) compared with control subjects (0.66 ± 0.05). Consistent with the mRNA data, the p22phox protein expression and NADPH oxidase activity was also increased in cells from diabetic patients compared with control subjects. However, HO‐1 gene expression was significantly (P < 0.05) lower in patients with (0.73 ± 0.03) and without microangiopathy (0.85 ± 0.02) compared with control subjects (1.06 ± 0.03). The mean (± se) levels of TBARS were significantly (P < 0.05) higher in diabetic patients with (14.36 ± 1.3 nm/ml) and without microangiopathy (12.20 ± 1.3 nm/ml) compared with control subjects (8.58 ± 0.7 nm/ml). The protein carbonyl content was also significantly (P < 0.05) higher in diabetic patients with (1.02 ± 0.04 nmol/mg protein) and without microangiopathy (0.84 ± 0.06 nmol/mg protein) compared with control subjects (0.48 ± 0.02 nmol/mg protein). In diabetic subjects, increased p22phox gene expression was negatively correlated with HO‐1 and positively correlated with TBARS, PCO, HbA1c and diabetes duration. In contrast, HO‐1 gene expression was correlated negatively with p22phox, TBARS, PCO, HbA1c and diabetes duration. Conclusion: Our results indicate that increased oxidative damage is seen in Asian Indians with Type 2 diabetes and microangiopathy and is associated with increased NADPH oxidase (p22phox) and decreased HO‐1 gene expression

Telomere shortening & metabolic/vascular diseases

Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during ageing. Over the past decade, emerging evidence has shown that the telomeres are essential regulators of cellular life span and chromosome integrity in a dynamic fashion. By inducing genomic instability, replicative senescence and apoptosis, shortening of telomeres is thought to contribute to organismal ageing. While the aetiology of cardiovascular diseases and diabetes represent a complex interaction between various risk factors overlaid on different genetic backgrounds, the conventional risk factors often did not explain the inter-individual variability related to predisposition of disease states. This underscores the need for biological indicators of ageing in evaluating the aetiology of several age-related disorders, and recent studies indicate that telomere length could qualify as an ideal marker of biological ageing. Short telomeres have been detected in senescent endothelial cells and vascular smooth muscle cells from human atherosclerotic plaque as well as in myocardial tissue from patients with end-stage heart failure and cardiac hypertrophy. In addition, telomere shortening has been demonstrated in WBCs from patients with coronary heart disease, premature myocardial infarction, hypertension and diabetes mellitus. In this review, we discuss the telomere hypothesis of ageing as well as human studies that address the role of telomeres in cardiovascular, diabetes and other cardio-metabolic pathologies

Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear factor-kappa B signaling in patients with Type 2 diabetes and microangiopathy

Although oxidative stress and the subsequent DNA damage is one of the obligatory signals for poly(ADP-ribose) polymerase (PARP) activation and nuclear factor-kappa B (NFκB) alterations, these molecular aspects have not been collectively examined in epidemiological and clinical settings. Therefore, this study attempts to assess the oxidative DNA damage and its downstream effector signals in peripheral blood lymphocytes from Type 2 diabetes subjects without and with microangiopathy along with age-matched non-diabetic subjects. The basal DNA damage, lipid peroxidation and protein carbonyl content were significantly (p < 0.05) higher in patients with and without microangiopathy compared to control subjects. Formamido Pyrimidine Glycosylase (FPG)-sensitive DNA strand breaks which represents reliable indicator of oxidative DNA damage were also significantly (p < 0.001) higher in diabetic patients with (19.41 ± 2.5) and without microangiopathy (16.53 ± 2.0) compared to control subjects (1.38 ± 0.85). Oxidative DNA damage was significantly correlated to poor glycemic control. PARP mRNA expression and PARP activity were significantly (p < 0.05) increased in cells from diabetic patients with (0.31 ± 0.03 densitometry units; 0.22 ± 0.02 PARP units/mg protein, respectively) and without (0.35 ± 0.02; 0.42 ± 0.05) microangiopathy compared to control (0.19 ± 0.02; 0.11 ± 0.02) subjects. Diabetic subjects with and without microangiopathy exhibited a significantly (p < 0.05) higher (80%) NFκB binding activity compared to control subjects. In diabetic patients, FPG-sensitive DNA strand breaks correlated positively with PARP gene expression, PARP activity and NFκB binding activity. This study provides a comprehensive molecular evidence for increased oxidative stress and genomic instability in Type 2 diabetic subjects even prior to vascular pathology and hence reveals a window of opportunity for early therapeutic intervention

Evidence for Mechanistic Alterations of Ca2+ Homeostasis in Type 2 Diabetes Mellitus

Altered cytosolic Ca2+ is implicated in the aetiology of many diseases including diabetes but there are few studies on the mechanism(s) of the altered Ca2+ regulation. Using human lymphocytes, we studied cytosolic calcium (Cai) and various Ca2+ transport mechanisms in subjects with Type 2 diabetes mellitus and control subjects. Ca2+-specific fluorescent probes (Fura-2 and Fluo-3) were used to monitor the Ca2+ signals. Thapsigargin, a potent and specific inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), was used to study Ca2+- store dependent Ca2+ fluxes. Significant (P < 0.05) elevation of basal Cai levels was observed in lymphocytes from diabetic subjects. Cai levels were positively correlated with fasting, plasma glucose and HbAlc. There was also a significant (P < 0.05) reduction in plasma membrane calcium (PMCA) ATPase activity in diabetic subjects compared to controls. Cells from Type 2 diabetics exhibited an increased Ca2+ influx (as measured both by Fluo-3 fliorescence and C45a assays) as a consequence of of thapsigargin-mediated Ca2+ store depletion. Upon addition of Mn2+ (a surrogate of Ca2+), the fura-2 fluorescence decayed in an exponential fashion and the rate and extent of this decline was steeper and greater in cells from type 2 diabetic patients. There was also a significant (P < 0.05) difference in the Na+/Ca2+ exchange activity in Type 2 diabetic patients, both under resting conditions and after challenging the cells with thapsigargin, when the internal store Ca2+ sequestration was circumvented. Pharmacological activation of protein kinase C (PKC) in cells from patients resulted in only partial inhibition of Ca2+ entry. We conclude that cellular Ca2+ accumulation in cells from Type 2 diabetes results from (a) reduction in PMCA ATPase activity, (b) modulation of Na+/Ca2+ exchange and (3) increased Ca2+ influx across the plasma membrane

Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy

Objective: Shortening of telomere length has been reported in several conditions including Type 2 diabetes and atherosclerosis. The aims of this study were (1) to assess whether telomere shortening occurs at the stage of pre-diabetes, i.e., impaired glucose tolerance (IGT) and (2) whether telomere shortening was greater in Type 2 diabetic subjects with atherosclerotic plaques. Methods: Subjects with impaired glucose tolerance (IGT) (n = 30), non-diabetic control subjects (n = 30), Type 2 diabetic patients without (n = 30) and with atherosclerotic plaques (n = 30) were selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing epidemiological population-based study. Southern-blot analysis was used to determine mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leukocyte DNA. Levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and high sensitive C-reactive protein (hs-CRP) were measured by standard methodologies. Carotid intima-media thickness (IMT) was assessed by high resolution B-mode ultrasonography. Results: The mean (±S.E.) TRF lengths were significantly lower in IGT subjects (6.97 ± 0.3 kb; p = 0.002) and lower still in Type 2 diabetic subjects without plaques (6.21 ± 0.2; p = 0.0001) and lowest in Type 2 diabetic subjects with atherosclerotic plaques (5.39 ± 0.2; p = 0.0001) when compared to control subjects (8.7 ± 0.5). In IGT subjects, TRF length was positively correlated to HDL cholesterol and negatively correlated to glycated hemoglobin (HbA1c), TBARS, PCO, HOMA-IR and IMT. In multiple linear regression analysis, presence of diabetes, HDL cholesterol and increased TBARS levels appear as significant determinants of telomere shortening. Conclusion: Telomere shortening is seen even at the stage of IGT. Among subjects with Type 2 diabetes, those with atherosclerotic plaques had greater shortening of telomere length compared to those without plaques

Genetic structure of a small closed population of the New Zealand white rabbit through pedigree analyses

[EN] The genetic structure of a small population of New Zealand White rabbits maintained at the Sheep Breeding and Research Station, Sandynallah, The Nilgiris, India, was evaluated through pedigree analyses. Data on pedigree information (n=2503) for 18 yr (1995-2012) were used for the study. Pedigree analysis and the estimates of population genetic parameters based on the gene origin probabilities were performed. The analysis revealed that the mean values of generation interval, coefficients of inbreeding and equivalent inbreeding were 1.49 yr, 13.23 and 17.59%, respectively. The proportion of population inbred was 100%. The estimated mean values of average relatedness and individual increase in inbreeding were 22.73 and 3.00%, respectively. The percentage increase in inbreeding over generations was 1.94, 3.06 and 3.98 estimated through maximum generations, equivalent generations and complete generations, respectively. The number of ancestors contributing the majority of 50% genes (fa50) to the gene pool of reference population was only 4, which might have led to reduction in genetic variability and increased the amount of inbreeding. The extent of genetic bottleneck assessed by calculating the effective number of founders (fe) and the effective number of ancestors (fa), as expressed by the fe/fa ratio was 1.1, which is indicative of the absence of stringent bottlenecks. Up to 5th generation, 71.29% pedigree was complete, reflecting the well maintained pedigree records. The maximum known generations were 15, with an average of 7.9, and the average equivalent generations traced were 5.6, indicating a fairly good depth in pedigree. The realized effective population size was 14.93, which is very critical, and with the increasing trend of inbreeding the situation has been assessed as likely to become worse in future. The proportion of animals with the genetic conservation index (GCI) greater than 9 was 39.10%, which can be used as a scale to use such animals with higher GCI to maintain balanced contribution from the founders. From the study, it was evident that the herd was completely inbred, with a very high inbreeding coefficient, and the effective population size was critical. Recommendations were made to reduce the probability of deleterious effects of inbreeding and to improve genetic variability in the herd. The present study can help in carrying out similar studies to meet the demand for animal protein in developing countries.The authors acknowledge the support provided by Tamil Nadu Veterinary and Animal Sciences University (TANUVAS) for successful completion of the study.Sakthivel, M.; Balasubramanyam, D.; Kumarasamy, P.; Raja, A.; Anilkumar, R.; Gopi, H.; Devaki, A. (2018). Genetic structure of a small closed population of the New Zealand white rabbit through pedigree analyses. 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