Combinatorial inhibition of Angiotensin converting enzyme, Neutral endopeptidase and Aminopeptidase N by N-methylated peptides alleviates blood pressure and fibrosis in rat model of dexamethasone-induced hypertension

Angiotensin converting enzyme (ACE), neutral endopeptidase (NEP) and aminopeptidase N (APN) are responsible for generation of vasoactive peptides that regulates vasoconstriction, vasodilation and natriuresis, which altogether regulate blood pressure. Cumulative inhibition of ACE, NEP and APN effectively blocks the progression of respective pathways. In this study, N-methylated peptide inhibitors F-N(Me)H-L, V-N(Me)F-R and R-N(Me)V-Y were synthesized against ACE, NEP and APN respectively, using their respective physiological substrates. F-N(Me)H-L inhibited ACE activity with an IC50 of 83 nmol/L, V-N(Me)F-R inhibited NEP activity with an IC50 of 1.173 mu mol/L and R-N(Me)V-Y inhibited APN activity with an IC50 of 3.94 nmol/L respectively. Further, the anti-hypertensive effect of N-methylated peptides was evaluated using rat model of dexamethasone-induced hypertension. Individual peptides and their cocktail treatment were started from day 6 of the study period and blood pressure was measured on every alternate day during 15 day study. Administration of F-N(Me) H-L (138 +/- 3 mmHg) and cocktail of all the three peptides at a dose of 100 mg/kg significantly reduced systolic blood pressure (SBP) compared to dexamethasone group (SBP of Groups-dexamethasone; (167 +/- 5 mmHg), F-N (Me)H-L (138 +/- 3 mmHg), and Cocktail (122 +/- 3 mmHg). Anti-hypertensive, anti-hypertrophic and anti-fibrotic effects of N-methylated peptides and cocktail was further reflected by the decreased levels of circulating Ang II and increased ANP levels in sera of hypertensive rats along with decrease in collagen deposition in heart and kidney. Though, ACE inhibition is adequate to reduce SBP, targeting NEP and APN along with ACE is beneficial in tackling hypertension and associated fibrosis of heart

Sociobiological Control of Plasmid copy number

Background:
All known mechanisms and genes responsible for the regulation of plasmid replication lie with the plasmid rather than the chromosome. It is possible therefore that there can be copy-up mutants. Copy-up mutants will have within host selective advantage. This would eventually result into instability of bacteria-plasmid association. In spite of this possibility low copy number plasmids appear to exist stably in host populations. We examined this paradox using a computer simulation model.

Model:
Our multilevel selection model assumes a wild type with tightly regulated replication to ensure low copy number. A mutant with slightly relaxed replication regulation can act as a “cheater” or “selfish” plasmid and can enjoy a greater within-host-fitness. However the host of a cheater plasmid has to pay a greater cost. As a result, in host level competition, host cell with low copy number plasmid has a greater fitness. Furthermore, another mutant that has lost the genes required for conjugation was introduced in the model. The non-conjugal mutant was assumed to undergo conjugal transfer in the presence of another conjugal plasmid in the host cell.

Results:
The simulatons showed that if the cost of carrying a plasmid was low, the copy-up mutant could drive the wild type to extinction or very low frequencies. Consequently, another mutant with a higher copy number could invade the first invader. This process could result into an increasing copy number. However above a certain copy number within-host selection was overcompensated by host level selection leading to a rock-paper-scissor (RPS) like situation. The RPS situation allowed the coexistence of high and low copy number plasmids. The non-conjugal “hypercheaters” could further arrest the copy numbers to a substantially lower level.

Conclusions:
These sociobiological interactions might explain the stability of copy numbers better than molecular mechanisms of replication regulation alone

Problems in Public Distribution System

To minimize the poverty level among general public, Government of India promoted Public distribution system for extending basic necessary goods at subsidized rates. But their primary motto has not been fulfilled due to numerous problems prevailing in PDS. Thus, an attempt has been made in this study to ascertain the Problems prevailing in PDS. The result of the study indicates that Adulteration, Distribution of inferior quality goods, Under Weighment are the common problems found in Public distribution system

Electrochemistry at nanoscale electrodes : individual single-walled carbon nanotubes (SWNTs) and SWNT-templated metal nanowires

Individual nanowires (NWs) and native single-walled carbon nanotubes (SWNTs) can be readily used as well-defined nanoscale electrodes (NSEs) for voltammetric analysis. Here, the simple photolithography-free fabrication of submillimeter long Au, Pt, and Pd NWs, with sub-100 nm heights, by templated electrodeposition onto ultralong flow-aligned SWNTs is demonstrated. Both individual Au NWs and SWNTs are employed as NSEs for electron-transfer (ET) kinetic quantification, using cyclic voltammetry (CV), in conjunction with a microcapillary-based electrochemical method. A small capillary with internal diameter in the range 30–70 μm, filled with solution containing a redox-active mediator (FcTMA+ ((trimethylammonium)methylferrocene), Fe(CN)64–, or hydrazine) is positioned above the NSE, so that the solution meniscus completes an electrochemical cell. A 3D finite-element model, faithfully reproducing the experimental geometry, is used to both analyze the experimental CVs and derive the rate of heterogeneous ET, using Butler–Volmer kinetics. For a 70 nm height Au NW, intrinsic rate constants, k0, up to ca. 1 cm s–1 can be resolved. Using the same experimental configuration the electrochemistry of individual SWNTs can also be accessed. For FcTMA+/2+ electrolysis the simulated ET kinetic parameters yield very fast ET kinetics (k0 > 2 ± 1 cm s–1). Some deviation between the experimental voltammetry and the idealized model is noted, suggesting that double-layer effects may influence ET at the nanoscale

Phytochemical constituents of Cadaba Trifoliata Roxb. root extract

Cadaba trifoliata Roxb is belongs to the family Capparaceae, important medicinal plant of Indian medicinal plants. The methanol, ethanol, ethyl acetate and aqueous extracts along with dry powder of root were screened for the presence of phytochemicals. The phytochemical constituents were analyzed by qualitative and GC-MS method. Preliminary studies showed that the presence of Tannins, Steroids, Alkaloids, Glycosides, Flavonoids and Phenolic compounds. In the GC-MS analysis, 17 bioactive phytochemical compounds were identified in the alcoholic extract. The identification of phytochemical compounds in very high peak area, 1, 2-Benzenedicarboxylic acid, diisooctyl ester (C24H38O4) with RT 24.95 has peak area 51.86% and 1-Methyl-pyrrolidine-2-carboxylic acid (C6H11NO2) with RT 6.89 has peak area 20.58%. The main important compound phytol (C20H40O) with RT 18.95 ranks with peak area 1.21%. A nature compound contains diterpene activity anti-cancer, anti-diabetic, anti-inflammatory, anti-oxidant activity and antimicrobial activity

Tris(2,4-di-tert-butyl­phen­yl) phosphate

The title compound, C42H63O4P, was isolated from the leaves of Vitex negundo. Two of the tert-butyl groups are disordered over two orientations with occupancy ratios of 0.57 (1):0.43 (1) and 0.67 (1):0.33 (1). Several intra­molecular C—H⋯O inter­actions are observed in the mol­ecular structure

The Scenario of Groundwater Pollution after Implementation of Zero Liquid Discharge: An Agricultural Economic Perspective

Groundwater pollution is hard to remediate in the Noyyal river region even after the implementation of Zero Liquid Discharge process. Hence, to study the status and extent of groundwater pollution in the Noyyal river region, Tiruppur district of Tamil Nadu was purposively selected and classified into 3 regions based on the distance from the river and 120 farms were selected. Tools of analysis viz., Cost benefit analysis, Resource use efficiency and decomposition analysis were undertaken to study the status of groundwater pollution and its effect on agriculture. The results showed that intensity and severity of pollution is high in the region closer to Noyyal river (less than 1 km). Income from agriculture is also low in that region due to the use of polluted groundwater for irrigation. The study revealed that Zero Liquid Discharge ensures stoppage of industrial effluents into the river and hence, river pollution is stopped. Similarly, a suitable policy is required to revamp groundwater. Hence, the suggested policy includes water storage structures like tanks, lakes, ponds etc are to be used for groundwater recharge purpose alone

1-Methyl-3-(2-methyl­phen­yl)-3a-nitro-1,2,3,3a,4,9b-hexa­hydro­chromeno[4,3-b]pyrrole

The asymmetric unit of the title compound, C19H20N2O3, contains two independent mol­ecules in both of which the pyrrolidine ring adopts an envelope conformation, but with a C atom as the flap in one mol­ecule and the N atom in the other. The pyran ring adopts a half-chair conformation in both mol­ecules. In the crystal, mol­ecules are linked via C—H⋯O hydrogen bonds and C—H⋯π inter­actions