Diabetes mellitus, an epidemic metabolic disorders characterized by high blood glucose level associated with various macrovascular and microvascular complications, is one of the main causes of human suffering across the globe. Researchers around the world mainly focused on insulin, insulin analogues, oral hypoglycemic agents and various other complementary and alternate medicines to control the blood glucose levels in diabetes. The present review summarizes the disorders associated with elevation of blood glucose level, biochemical & endocrinological aspects and the current strategies to control. The emphasis has been laid in particular on the new potential biological targets and the possible treatment as well as the current ongoing research status on new generation hypoglycemic agents.

protocellular membranes are thought to be composed of mixtures of single chain amphiphiles, such as fatty acids and their derivatives, moieties that would have been part of the complex prebiotic chemical landscape. the composition and physico-chemical properties of these prebiological membranes would have been significantly affected and regulated by their environment. In this study, pertinent properties were systematically characterized, under early Earth conditions. Two different fatty acids were mixed with their respective alcohol and/or glycerol monoester derivatives to generate combinations of binary and tertiary membrane systems. their properties were then evaluated as a function of multiple factors including their stability under varying pH, varying Mg 2+ ion concentrations, dilution regimes, and their permeability to calcein. our results demonstrate how environmental constraints would have acted as important prebiotic selection pressures to shape the evolution of prebiological membranes. the study also illustrates that compositionally diverse membrane systems are more stable and robust to multiple selection pressures, thereby making them more suitable for supporting protocellular life. The earliest forms of cellular life are considered to be entities that comprised of dynamic chemical reactions, encapsulated within amphiphilic compartments 1,2. Unlike the contemporary biological membranes model protocellular membranes are thought to have been relatively simpler and composed of single chain amphiphiles (SCAs) 3. These SCAs could have come about on the early Earth either by endogenous synthesis, in the form of Fisher-Tropsch Type (FTT) reactions, or via exogenous delivery 4,5. In this context, fatty acids and their derivatives have been predominantly studied for their plausible role as early compartments 3,6. Fatty acids are known to possess high critical vesicular concentrations (CVCs), the concentration at which the monomers assemble into higher ordered structures like vesicles 7. Such high CVC requirement poses significant obstacles towards their self-assembly under prebiotic scenarios, wherein meeting this high concentration prerequisite would have been difficult 8,9. The pH of certain terrestrial hydrothermal pools of the early Earth is hypothesized to be neutral to alkaline 10 which can drive prebiotically pertinent reactions, including formose reaction 11 , polymerization of non-activated amino acids 12 , and non-canonical nucleoside or nucleotide formation 13. However fatty acid monomers can assemble only in a narrow pH regime, near to their pKa 6,14. Given this scenario the coexistence of the aforementioned reactions and model protocellular membranes would have been really challenging. Moreover, fatty acids are also cation sensitive moieties 15. On the contrary, RNA molecules, which are thought to be the first biomolecules to have emerged, require divalent cations in order to efficiently replicate and carry out catalytic functions 16-18. Such divalent cation concentrations are not compatible with fa...

Nucleic acid segregation and compartmentalization were likely essential functions that primitive compartment systems resolved during evolution. Recently, polyester microdroplets generated from dehydration synthesis of various α-hydroxy acids (αHA) were suggested as potential primitive compartments. Some of these droplets can differentially segregate and compartmentalize organic dyes, proteins, and nucleic acids. However, the previously studied polyester microdroplets included limited αHA chemical diversity, which may not reflect the chemical diversity available in the primitive Earth environment. Here, we increased the chemical diversity of polyester microdroplet systems by combinatorially adding an αHA monomer with a basic side chain, 4-amino-2-hydroxybutyric acid (4a2h), which was incorporated with different ratios of other αHAs containing uncharged side chains to form combinatorial heteropolyesters via dehydration synthesis. Incorporation of 4a2h in the polymers resulted in the assembly of some polyester microdroplets able to segregate fluorescent RNA or potentially acquire intrinsic fluorescent character, suggesting that minor modifications of polyester composition can significantly impact the functional properties of primitive compartments. This study suggests one process by which primitive chemical systems can increase diversity of compartment "phenotype" through simple modifications in their chemical composition.

bThe incidence of superficial dermatophytoses is high in developed countries, and there remains a need for effective topical antifungals. In this study, we evaluated the in vitro antifungal activity of naftifine hydrochloride, the active ingredient in naftifine hydrochloride cream and gel 1% and 2%, against dermatophytes. The MICs and minimum fungicidal concentrations (MFCs) of naftifine hydrochloride against 350 clinical strains, including Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Epidermophyton floccosum, and Microsporum canis, were determined using the CLSI methodology. Subsets from this test panel were subsequently tested in a time-kill assay at 0.125؋, 0.25؋, 0.5؋, and 1؋ the MFC for each isolate. CFU counts were performed over a period of 48 h of incubation. Additionally, in order to determine the potential for resistance development, six strains were subjected to 15 serial passages in concentrations higher than the MIC for each strain. MICs were determined following each passage. The MIC range against the dermatophyte isolates tested was 0.015 to 1.0 g/ml, with naftifine hydrochloride being fungicidal against 85% of the Trichophyton species. The time-kill assay showed dose-dependent activity, with the greatest reduction in the numbers of CFU corresponding to the highest drug concentration. There was no increase in MIC for any strains following repeated exposure to naftifine hydrochloride. Naftifine hydrochloride demonstrated potent activity against all dermatophytes tested, and none of the isolates within this test panel demonstrated the potential for the development of resistance. Thus, future clinical studies of naftifine hydrochloride against dermatophytes may be warranted for the treatment of superficial dermatophytoses.

White spot disease is a devastating disease of shrimp Penaeus monodon in which the shrimp receptor protein PmRab7 interacts with viral envelop protein VP28 to form PmRab7-VP28 complex, which causes initiation of the disease. The molecular mechanism implicated in the disease, the dynamic behavior of proteins as well as interaction between both the biological counterparts that crafts a micro-environment feasible for entry of virus into the shrimp is still unknown. In the present study, we applied molecular modeling (MM), molecular dynamics (MD) and docking to compute surface mapping of infective amino acid residues between interacting proteins. Our result showed that α-helix of PmRab7 (encompassing Ser74, Ile143, Thr184, Arg53, Asn144, Thr184, Arg53, Arg79) interacts with β-sheets of VP28 (containing Ser74, Ile143, Thr184, Arg53, Asn144, Thr184, Arg53, Arg79) and Arg69-Ser74, Val75-Ile143, Leu73-Ile143, Arg79-Asn144, Ala198-Ala182 bonds contributed in the formation of PmRab7-VP28 complex. Further studies on the amino acid residues and bonds may open new possibilities for preventing PmRab7-VP28 complex formation, thus reducing chances of WSD. The quantitative predictions provide a scope for experimental testing in future as well as endow with a straightforward evidence to comprehend cellular mechanisms underlying the disease.

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Of the total 40 endophytic fungi isolated from foliar tissues of medicinal plant Stevia rebaudiana Bertoni, a fungal isolate, Aspergillus flavipes, was subjected to bioassay guided fractionation. The fractionation was found active against medicinal plant pathogen Sclerotinia sclerotiorum with an inhibition zone of 29 mm in size. Further the metabolite was extracted which shows 20% growth inhibition in 24 h and 46% after 48 h, respectively. Bioassay guided chemical compound was identified as 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. On the basis of morphological characters and rDNA sequencing of ITS region the endophyte was identified as Aspergillus flavipes which showed promising plant growth promotory properties.

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