The essential role of lipids in Alzheimer's disease

In the absence of efficient diagnostic and therapeutic tools, Alzheimer's disease (AD) is a major public health concern due to longer life expectancy in the Western countries. Although the precise cause of AD is still unknown, soluble β-amyloid (Aβ) oligomers are considered the proximate effectors of the synaptic injury and neuronal death occurring in the early stages of AD. Aβ oligomers may directly interact with the synaptic membrane, leading to impairment of synaptic functions and subsequent signalling pathways triggering neurodegeneration. Therefore, membrane structure and lipid status should be considered determinant factors in Aβ-oligomer-induced synaptic and cell injuries, and therefore AD progression. Numerous epidemiological studies have highlighted close relationships between AD incidence and dietary patterns. Among the nutritional factors involved, lipids significantly influence AD pathogenesis. It is likely that maintenance of adequate membrane lipid content could prevent the production of Aβ peptide as well as its deleterious effects upon its interaction with synaptic membrane, thereby protecting neurons from Aβ-induced neurodegeneration. As major constituents of neuronal lipids, n-3 polyunsaturated fatty acids are of particular interest in the prevention of AD valuable diet ingredients whose neuroprotective properties could be essential for designing preventive nutrition-based strategies. In this review, we discuss the functional relevance of neuronal membrane features with respect to susceptibility to Aβ oligomers and AD pathogenesis, as well as the prospective capacities of lipids to prevent or to delay the disease.     

Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate

Epidemiological, in vitro cell culture, and in vivo animal studies have shown that green tea or its constituent polyphenols, particularly its major polyphenol epigallocatechin-3-gallate (EGCG) may protect against many cancer types. In earlier studies, we showed that green tea polyphenol EGCG causes a G0/G1-phase cell cycle arrest and apoptosis of human epidermoid carcinoma (A431) cells. We also demonstrated that these effects of EGCG may be mediated through the inhibition of nuclear factor kappa B that has been associated with cell cycle regulation and cancer. In this study, employing A431 cells, we provide evidence for the involvement of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery during cell cycle deregulation by EGCG. As shown by immunoblot analysis, EGCG treatment of the cells resulted in significant dose- and time-dependent (i) upregulation of the protein expression of WAF1/p21, KIP1/p27, p16 and p18, (ii) downmodulation of the protein expression of cyclin D1, cdk4 and cdk6, but not of cyclin E and cdk2, (iii) inhibition of the kinase activities associated with cyclin E, cyclin D1, cdk2, cdk4 and cdk6. Taken together, our study suggests that EGCG causes an induction of G1-phase ckis, which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle thereby causing a G0/G1-phase arrest of the cell cycle, which is an irreversible process ultimately resulting in an apoptotic cell death. We suggest that the naturally occurring agents such as green tea polyphenols which may inhibit cell cycle progression could be developed as potent anticancer agents for the management of cancer.     

An 18 kDa Acid Phosphatase from Chicken Heart Possesses Phosphotransferase Activity

A low molecular weight acid phosphatase was purified to homogeneity from chicken heart with a specific activity of 42 U/mg and a recovery of about 1%. Nearly 800 fold purification was achieved. The molecular weight was estimated to be 18 kDa by SDS-polyacrylamide gel electrophoresis. Para-nitrophenyl phosphate, phenyl phosphate and flavin mononucleotide were efficiently hydrolysed by the enzyme and found to be good substrates. Fluoride and tartrate had no inhibitory effect while phosphate, vanadate and molybdate strongly inhibited the enzyme. The acid phosphatase was stimulated in the presence of glycerol, ethylene glycol, methanol, ethanol and acetone, which reflected the phosphotransferase activity. When phosphate acceptors such as ethylene glycol concentrations were increased, the ratio of phosphate transfer to hydrolysis was also increased, demonstrating the presence of a transphosphorylation reaction where an acceptor can compete with water in the rate limiting step involving hydrolysis of a covalent phospho enzyme intermediate. Partition experiments carried out with two substrates, para-nitrophenyl phosphate and phenyl phosphate, revealed a constant product ratio of 1.7 for phosphotransfer to ethylene glycol versus hydrolysis, strongly supporting the existence of common covalent phospho enzyme intermediate. A constant ratio of K _cat/K _m, 4.3×10⁴, found at different ethylene glycol concentrations, also supported the idea that the rate limiting step was the hydrolysis of the phospho enzyme intermediate.     

Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation

Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer’s disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Although the oxidative stress has been anticipated as a main cause in promoting both AD and T2DM, multiple pathways could be involved in ROS production. The focus of this review is to summarize the mechanisms involved in ROS production and their possible association with AD and T2DM pathogenesis and progression. We have also highlighted the role of current treatments that can be linked with reduced oxidative stress and damage in AD and T2DM.     

Effect of host plant on cornucopia of mango fruit flies (Diptera: Tephritidae) and their triumphant management in context of climate change

A study was performed to assess the preference of fourteen mango cultivars for fruit flies and their management by bagging. So the choice of Tephritid flies to mango cultivars during fruiting phase is crucial. Fourteen different cultivars of mango viz., ‘Dusehri’, ‘Malda’, ‘Langra’ early cultivars, ‘Chaunsa’, ‘Fajri Klan’, ‘Sensation’ medium whereas ‘Sanglakhi’, ‘Retaul-12’, ‘Mehmood Khan’, ‘Tukhmi’, ‘Kala Chaunsa’, ‘Chitta Chaunsa’, ‘Dai Wala’ and ‘Sobey De Ting’ late cultivars were assessed for their suitability for fruit flies. The results indicate that the population density of fruit flies was higher on late cultivars like ‘Sanglakhi’ (20.61 percent), ‘Mehmood Khan’ (20.22 percent) and ‘Reutal-12’ (19.92 percent) were proved to be highly susceptible to fruit flies. Among these the cultivar ‘Reutal-12’ was selected being commercial and future cultivar for the management of fruit flies through bagging. The results reported that the attack of tephritid fruit flies and other insect pests were zero in bagged fruits as compared with control. It was further recorded that the bagged fruits has maximum average fruit weight i.e. 203.50 and 197.83 g per fruit was noted in those treatments where butter paper bag and brown paper bag was wrapped with better coloration as compared with un-bagged fruit with 159.5 g per fruit. Similarly, on an average fruit length were more i.e. 90.17, 91.33 mm in bagged fruit and 85.33 in un-bagged fruits. Furthermore, bagged fruits have zero incidence of disease with reduced fruit crack, fruit sunburn, mechanical damage, bird damage, fruit blemished and agrochemical residues on the fruit. So, it is concluded that the special attention should be given on ‘Reutal-12’ for the management of fruit flies when devising an IPM program for the control of fruit flies. Further, bagging has proved to be the good agricultural practices for the production of quality mango.     

The influence of peroxisome proliferator-activated receptor γ(1) during differentiation of mouse embryonic stem cells to neural cells

Peroxisome proliferator activated receptor γ, belongs to PPARs, which exerts various metabolic functions including differentiation process. To testify the importance of PPARγ in neural differentiation of mouse embryonic stem cells (mESCs), its expression level was assessed. Data revealed an elevation in expression level of PPARγ when neural precursors (NPs) are formed upon retinoic acid treatment. Thus, involvement of PPARγ in two stages of neural differentiation of mESCs, during and post-NPs formation was examined by application of its agonist and antagonist. Our results indicated that PPARγ inactivation via treatment with GW9662 during NPs formation, reduced expression of neural precursor and neural (neuronal and astrocytes) markers. However, PPARγ inactivation by antagonist treatment post-NPs formation stage only decreased the expression of mature astrocyte marker (Gfap) suggesting that inactivation of PPARγ by antagonist decreased astrocyte differentiation. Here, we have demonstrated the stage dependent role of PPARγ modulation on neural differentiation of mESCs by retinoic acid treatment for the first time.     

Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

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Failure of spermatozoa from T/t mice to fertilize in vitro is overcome by zona drilling

Failure of epididymal spermatozoa from T/t mutant mice, but not from t/t individuals, to fertilize oocytes in vitro was partially overcome by opening a small aperture in the zona pellucida with acidified Tyrode's solution to permit direct access of the spermatozoon to the vitellus. This study provides a model system to evaluate requirements for successful zona drilling in the treatment of human infertility and further insights into the effects of the t complex on sperm fertility.