THE EFFECT OF CLIMATE ON TOTAL PHENOLICS IN MACROTYLOMA UNIFLORUM, VIGNA UNGUICULATA, CINNAMOMUM ZEYLANICUM AND MENTHA PIPERITA USING SPECTROPHOTOMETER

Objective: Polyphenolic compound which is proven as antioxidants and possesses a chemo - protective potential are found in leaves, flowers, fruits,and bark. The aim of the study was to estimate the amount of tannins present in these drugs using Folin-Denis method. This study was conductedto evaluate the variations in the total amount of secondary metabolites (poly-phenolic) during summer and winter seasons in the leaves of fourimportant valuable medicinal plants, viz., Macrotyloma uniflorum, Vigna unguiculata, Cinnamomum zeylanicum, and Mentha piperita using ultravioletvisible spectrophotometry.Methods: Tannin contents of plants were measured by Folin-Denis method. Tannin-like compounds reduce phosphotungstomolybdic acid in alkalinesolution to produce a highly colored blue solution, the intensity of which is proportional to the amount of tannins present. The intensity is measuredin a spectrophotometer at 650 nm.Results: The concentration was almost same for Mu1 and Mu2 plant with little effect of seasonal variations and at the same place it was found to bemaximum in Cz1. The concentration curve for tannic acid was determined, and the correlation coefficient was calculated and was found to be 1 whichindicates the good linearity between the concentration and the absorbance.Conclusion: The maximum amounts of secondary metabolites (poly-phenolic) were observed during summer, while minimum in winter season with an exception of Mu2 plant. Thus, this study was used as one of the parameters for standardization of medicinal plants.Keywords: Macrotyloma uniflorum, Vigna unguiculata, Cinnamomum zeylanicum, Mentha piperita tannins, Total phenolics, Folin-Denis method

ALOE VERA ATTENUATES GENTAMICIN-INDUCED NEPHROTOXICITY IN WISTAR ALBINO RATS: HISTOPATHOLOGICAL AND BIOCHEMICAL CHANGES

Objectives: To evaluate the nephroprotective properties of ethanol extract of leaves of Aloe vera against gentamicin-induced nephrotoxicity in rats.Methods: Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of gentamicin 40 mg/kg/days for 5 days. Effect of concurrentadministration of ethanol extract of leaves of A. vera at a dose of 20 ml/kg/day given by oral route was determined using serum creatinine and bloodurea nitrogen as biochemical indicators of renal damage; after 10, 20, and 30 days. The study included a control group which received oral saline only,gentamicin treated group, received gentamicin and oral saline and A. vera group, received oral A. vera prior to gentamicin administration. Each grouphad six rats.Results: It was observed that in A. vera treated rats, prevented elevation of the biochemical indicators of nephrotoxicity and significantly reducedhistopathological scores.Conclusion: Ethanol extract of A. vera contains constituents with nephroprotective activities.Keywords: Gentamicin-induced nephrotoxicity, Aloe vera, Wister rats, Histopathological change

Histone deacetylase inhibitors: pharmacotherapeutic implications as epigenetic modifier

Epigenetic modifications such as acetylation and deacetylation of histone proteins play a decisive role in transcriptional alteration and expression of genes. Acetylation is catalysed by the histone acetyl transferases enzymes and activates expression of genes by converting chromatin into a less compact, transcriptionally active state. Histone deacetylases enzymes catalyze deacetylation that condenses chromatin into a closed structure .Consequently transcriptional factors are unable to access DNA and gene expression is suppressed. Balanced activity of HATs and HDACS is essential for normal gene expression. Increased HDAC activity can lead to imbalance in protein acetylation resulting in hypoacetylation, tight chromatin structure and suppression of various genes. This aberrant suppression of genes is the hallmark of several malignant and other diseases including neurodegenerative disorders. Histone Deacetylase Inhibitors (HDACIs) have potential to restore the balance of histone acetylation that reverses the silencing of pathological genes. Thus HDACIs modify expression of genes without affecting sequence of DNA and act as epigenetic modifiers. Vorinostat and romidepsin are FDA approved HDACIs. Valproic acid, belinostat and many others are in different phases of clinical trials. This review article explores the target based epigenetic mechanisms as well as existing and potential therapeutic role of HDACIs in various malignant and non-malignant diseases. Data sources were articles published in medical journals and bibliographic database Medline

Auxetic regions in large deformations of periodic frameworks

In materials science, auxetic behavior refers to lateral widening upon stretching. We investigate the problem of finding domains of auxeticity in global deformation spaces of periodic frameworks. Case studies include planar periodic mechanisms constructed from quadrilaterals with diagonals as periods and other frameworks with two vertex orbits. We relate several geometric and kinematic descriptions.Comment: Presented at the International Conference on "Interdisciplinary Applications of Kinematics" (IAK18), Lima, Peru, March 201

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development

After acquiring competence for selected cell fates, embryonic primordia may remain plastic for variable periods before tissue identity is irrevocably determined (commitment). We investigated the chromatin basis for these developmental milestones in mouse endoderm, a tissue with recognizable rostro-caudal patterning and transcription factor (TF)-dependent interim plasticity. Foregut-specific enhancers are as accessible and active in early midgut as in foregut endoderm, and intestinal enhancers and identity are established only after ectopic cis-regulatory elements are decommissioned. Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Thus, midgut endoderm is primed for heterologous cell fates, and TFs act on a background of shifting chromatin access to determine intestinal at the expense of foregut identity. Similar principles likely govern other fate commitments

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

No Adverse Effect of Genetically Modified Antifungal Wheat on Decomposition Dynamics and the Soil Fauna Community – A Field Study

The cultivation of genetically modified (GM) plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b) and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C∶N ratio, lignin, cellulose, hemicellulose) were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina), springtails (Isotomidae), annelids (Enchytraeidae) and Diptera (Cecidomyiidae larvae). Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM wheat on the composition and the activity of the soil fauna community

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes