Possible role of metal ionophore against zinc induced cognitive dysfunction in <Emphasis Type="SmallCaps">d-</Emphasis>galactose senescent mice

Metal ionophores are considered as potential anti-dementia agents, and some are currently undergoing clinical trials. Many metals are known to accumulate and distribute abnormally in the aging brain. Alterations in zinc metal homeostasis in the glutaminergic synapse could contribute to ageing and the pathophysiology of Alzheimer’s disease (AD). The present study was designed to investigate the effect of metal ionophores on long term administration of zinc in D-galactose induced senescent mice. The ageing model was established by combined administration of zinc and D-galactose to mice for 6 weeks. A novel metal ionophore, PBT-2 was given daily to zinc-induced d-galactose senescent mice. The cognitive behaviour of mice was monitored using the Morris Water Maze. The anti-oxidant status and amyloidogenic activity in the ageing mouse was measured by determining mito-oxidative parameters and deposition of amyloid β (Aβ) in the brain. Systemic administration of both zinc and D-galactose significantly produced memory deficits, mito-oxidative damage, heightened acetylcholinesterase enzymatic activity and deposition of amyloid-β. Treatment with PBT-2 significantly improved behavioural deficits, biochemical profiles, cellular damage, and curbed the deposition of APP in zinc-induced senescent mice. These findings suggest that PBT-2, acting as a metal protein attenuating compound, may be helpful in the prevention of AD or alleviation of ageing.     

Fluoride affects distribution of absorbed excitation energy more in favour of photosystem 1

The effects of fluoride on the photosynthetic electron transport chain have been studied in spinach thylakoid membranes. Inhibition in photosystem (PS) 2 electron transport rates and a subsequent increase in PS 1 electron transport rate indicated a possibility of state transitions being a mechanism of fluoride action. This hypothesis was further confirmed by the increase in fluorescence emission F_735/685 at 77 K, a decrease in variable to maximum fluorescence ratio (F_v/F_m) at room temperature and increase in the absorption cross section of PS 1 suggesting that fluoride affects distribution of the excitation energy in favour of PS 1 at the expense of PS 2.     

A new species of Limnocnida (Limnomedusae,Coelenterata) from a freshwater aquarium in India

We report the occurrence of a freshwater medusa from a laboratory aquarium in Ranchi, Bihar, India. The consistent emergence of these medussae coincided with sunny days after heavy and prolonged rainfall in the months of August to October. The material showed similarity with Limnocnide indica Annandale and L. nepalensis Dumont but differed in many respects, and is given the status of a distinct species, Limnocnida biharensis n.sp.Author to whom all correspondence should be addressed.Author to whom all correspondence should be addressed.     

Effect of Asparagus racemosus Extract on Transdermal Delivery of Carvedilol: A Mechanistic Study

This study was designed for investigating the effect of Asparagus racemosus (AR) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary–Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with AR extract, CTN, and AR extract–CTN mixture were investigated by using differential scanning calorimetry, transepidermal water loss, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. The permeation of carvedilol across excised rat epidermis was significantly higher (p < 0.05) when AR extract, CTN, or AR extract–CTN mixture was used as donor vehicle as compared to propylene glycol/ethanol (7:3) mixture. Epidermis obtained after 12 h treatment of viable rat skin with AR extract–CTN mixture showed significantly higher (p < 0.05) permeability to CDL as compared to that after treatment with AR extract or CTN alone. Further, the application of patches containing AR extract–CTN mixture resulted in sustained release of CDL which was able to control the hypertension in deoxycorticosterone acetate-induced hypertensive rats through 36 h. Estimation of micro constituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with AR extract–CTN mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure, and corneocyte detachment as observed in SEM and TEM suggested great potential of AR extract for use as percutaneous permeation enhancer. The developed transdermal patches of CDL containing AR extract–CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.     

Regulation of genome edited technologies in India

In India, genetically modified organisms and products thereof are regulated under the “Rules for the manufacture, use, import, export and storage of hazardous microorganisms, genetically engineered organisms or cells, 1989” (referred to as Rules, 1989) notified under the Environment (Protection) Act, 1986. These Rules are implemented by the Ministry of Environment, Forest and Climate Change, Department of Biotechnology and State Governments though six competent authorities. The Rules, 1989 are supported by series of guidelines on contained research, biologics, confined field trials, food safety assessment, environmental risk assessment etc. The definition of genetic engineering in the Rules, 1989 implies that new genome engineering technologies including gene editing technologies like CRISPR/Cas9 and gene drives may be covered under the rules. The regulatory authorities if required, may also review the experiences of other countries in dealing with such new and emerging technologies.

     

Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target

Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly expressed in diverse human carcinomas and certain hematologic malignancies. The oncogenic MUC1 transmembrane C-terminal subunit (MUC1-C) functions in part by transducing growth and survival signals from cell surface receptors. However, little is known about the structure of the MUC1-C cytoplasmic domain as a potential drug target. Using methods for structural predictions, our results indicate that a highly conserved CQCRRK sequence, which is adjacent to the cell membrane, forms a small pocket that exposes the two cysteine residues for forming disulfide bonds. By contrast, the remainder of the MUC1-C cytoplasmic domain has no apparent structure, consistent with an intrinsically disordered protein. Our studies thus focused on targeting the MUC1 CQCRRK region. The results show that L- and D-amino acid CQCRRK-containing peptides bind directly to the CQC motif. We further show that the D-amino acid peptide, designated GO-203, blocks homodimerization of the MUC1-C cytoplasmic domain in vitro and in transfected cells. Moreover, GO-203 binds directly to endogenous MUC1-C in breast and lung cancer cells. Colocalization studies further demonstrate that GO-203 predominantly binds to MUC1-C at the cell membrane. These findings support the further development of agents that target the MUC1-C cytoplasmic domain CQC motif and thereby MUC1-C function in cancer cells.     

Relative Abundance and Plasmodium Infection Rates of Malaria Vectors in and around Jabalpur,a Malaria Endemic Region in Madhya Pradesh State,Central India

BackgroundThis study was undertaken in two Primary Health Centers (PHCs) of malaria endemic district Jabalpur in Madhya Pradesh (Central India).MethodsIn this study we had investigated the relative frequencies of the different anopheline species collected within the study areas by using indoor resting catches, CDC light trap and human landing methods. Sibling species of malaria vectors were identified by cytogenetic and molecular techniques. The role of each vector and its sibling species in the transmission of the different Plasmodium species was ascertained by using sporozoite ELISA.ResultsA total of 52,857 specimens comprising of 17 anopheline species were collected by three different methods (39,964 by indoor resting collections, 1059 by human landing and 11,834 by CDC light trap). Anopheles culicifacies was most predominant species in all collections (55, 71 and 32% in indoor resting, human landing and light trap collections respectively) followed by An. subpictus and An. annularis. All five sibling species of An. culicifacies viz. species A, B, C, D and E were found while only species T and S of An. fluviatilis were collected. The overall sporozoite rate in An. culicifacies and An. fluviatilis were 0.42% (0.25% for P. falciparum and 0.17% for P. vivax) and 0.90% (0.45% for P. falciparum and 0.45% for P. vivax) respectively. An. culicifacies and An. fluviatilis were found harbouring both P. vivax variants VK-210 and VK-247, and P. falciparum. An. culicifacies sibling species C and D were incriminated as vectors during most part of the year while sibling species T of An. fluviatilis was identified as potential vector in monsoon and post monsoon season.ConclusionsAn. culicifacies species C (59%) was the most abundant species followed by An. culicifacies D (24%), B (8.7%), E (6.7%) and A (1.5%). Among An. fluviatilis sibling species, species T was common (99%) and only few specimens of S were found. Our study provides crucial information on the prevalence of An. culicifacies and An. fluviatilis sibling species and their potential in malaria transmission which will assist in developing strategic control measures against these vectors.     

Taxonomic studies on the ant genus Ponera Latreille, 1804 (Hymenoptera,Formicidae), with the description of a new species from India

Four species of the ant genus Ponera Latreille, 1804, are recorded from India. The present study reports one new species Ponera sikkimensis sp. n., a divergent population of Ponera indica Bharti & Wachkoo, 2012 and one new record, Ponera paedericera Zhou, 2001 from India. An identification key and distributions for the four known Indian species of Ponera based on the worker caste are provided.