Genetics of obesity

Considerable attention is currently being paid to the secular changes in food intake and physical activity that underlie the increase in the prevalence of obesity that is apparent in many societies. While this is laudable it would be unwise to view these environmental factors in isolation from the biological factors that normally control body weight and composition and the compelling evidence that inter-individual differences in susceptibility to obesity have strong genetic determinants. This is particularly important, as it is only in the past decade that we have begun to obtain substantive information regarding the molecular constituents of pathways controlling mammalian energy balance and therefore, for the first time, are in a position to achieve a better mechanistic understanding of this disease. Population-based association and linkage studies have highlighted a number of loci at which genetic variation is associated with obesity and related phenotypes and the identification and characterization of monogenic obesity syndromes has been particularly fruitful. While there is widespread acceptance that hereditary factors might predispose to human obesity, it is frequently assumed that such factors would influence metabolic rate or the selective partitioning of excess calories into fat. However, it is notable that, thus far, all monogenic defects causing human obesity actually disrupt hypothalamic pathways and have a profound effect on satiety and food intake. To conclude, the evidence we have to date suggests that the major impact of genes on human obesity is just as likely (or perhaps more likely) to directly impact on hunger, satiety and food intake rather than metabolic rate or nutrient partitioning. At the risk of oversimplification, it seems that from an aetiological/genetic standpoint, human obesity appears less a metabolic than a neuro-behavioural disease.     

Evolutionary trends in Tetrastigma (Vitaceae): Morphological diversity and taxonomic implications

Tetrastigma (Miq.) Planch. (Vitaceae) is a genus with ca. 100 species showing great morphological diversity. Previous molecular phylogenetic studies suggested that traditional classification systems are not consistent with the molecular phylogeny, and Tetrastigma is undergoing further systematic investigation. We traced the evolutionary trends of 20 morphological characters within a robust phylogenetic framework. Our results revealed that many morphological characters show either multiple transitions or few state changes, however, some characters show distinct variation. The two subgenera in Tetrastigma (subgen. Tetrastigma and subgen. Palmicirrata) based on unbranched/bifurcate versus digitately branched tendrils are not supported because subgen. Tetrastigma is paraphyletic. However, the unbranched versus bifurcate/digitately branched tendril is of taxonomic utility to characterize some of the major clades. Inflorescences in Tetrastigma appear axillary, but are leaf‐opposed on a compressed axillary shoot. We found most of the species in Tetrastigma retained the ancestral compound dichasial inflorescence, except those of clade IV that have derived pseudo‐umbellate inflorescences. Other characters including habit, leaf organization, and berry shape provide additional morphological support for the major clades. Our morphological analysis and recent molecular study suggest each of the five major clades within Tetrastigma be treated as distinct taxonomic sections (five sections in the genus).     

A molecular evaluation of dengue virus pathogenesis and its latest vaccine strategies

More than one third of the world’s population living in tropical and subtropical areas of the world is at risk of dengue infections and as many as 100 million people are yearly infected. This disease has reemerged during the past 20 years in the form of an epidemic. Dengue is caused by one of four related serotypes of dengue virus and often leads to severe forms of the disease, resulting commonly from secondary infections. Dengue virus is a mosquito borne virus, belongs to the family Flaviviridae and consists of a single stranded positive sense RNA genome. Like other RNA viruses it escapes defense mechanisms and neutralization attempts by mutations, which make it more resistant and adaptable to its environment. Antiviral strategies and vaccine development is thus impaired and hence to date there is no licensed vaccine available for dengue virus. Here we discuss various efforts made towards the identification of potential vaccine targets for dengue as well as various strategies employed by research groups/pharmaceutical companies towards the development of a successful dengue vaccine.     

Interaction Between Selenium and Mercury in Biological Samples of Pakistani Myocardial Infarction Patients at Different Stages as Related to Controls

It has been speculated that trace elements may a play role in the pathogenesis of heart diseases. In the present study, we aimed to assess the levels of selenium (Se) and mercury (Hg) in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both genders (age range 45–60 years) at the first, second, and third heart attack (n?=?130), hospitalized in a cardiac ward of a civil hospital of Hyderabad City (Pakistan). For comparison, healthy age-matched referent subjects (n?=?61) of both genders were also selected. Se and Hg in biological samples were measured by electrothermal atomic absorption spectrometry and cold vapor atomic absorption spectrometry, prior to microwave acid digestion, respectively. The validity of the methodology was checked by biological certified reference materials. During this study, 78 % of the 32 registered patients of third MI attack (aged >50 years) died. The concentration of Se was decreased in scalp hair and blood samples of MI patients, while Hg was higher in all biological samples as compared to referent subjects. Se concentration was inversely associated with the risk of MI attacks in both genders. These results add to an increasing body of evidence that Se is a protective element for cardiovascular health.     

A non-ionic surfactant reduces the induction time and enhances expression levels of bubaline somatotropin in Pichia pastoris

This study describes a simple approach for enhanced secretory expression of bubaline somatotropin (BbST) in the methylotropic yeast Pichia pastoris. A Mut^s Pichia transformant carrying multi-copy, non-codon optimized BbST cDNA sequence, expressed and secreted the recombinant protein into the culture medium to a level of 25 % of the total proteins in the culture supernatant, after 120 h of induction. Inclusion of polysorbate-80 in the inducing medium resulted in a significant improvement in the BbST expression (up to 45 % of the total culture supernatant proteins) with concomitant reduction in the induction time to 48 h. The amount of BbST obtained was 148 mg/L, which was around fivefold higher than that obtained without the surfactant. BbST was purified to near homogeneity by FPLC on Q-sepharose FF anion-exchange column. Protein authenticity was judged by SDS-PAGE and western blot analyses. A bioassay based on proliferation of Nb2 rat lymphoma cell lines confirmed that the purified, recombinant BbST is biologically active. Use of polysorbate-80 in combination with methanol, during the induction phase, is likely to have general applicability in lowering the induction time and enhancing the secretory expression of other commercially important proteins in Mut^s strains of P. pastoris.     

Tissue culture and genetic analysis of somaclonal variations of Solanum melongena L. cv. Nirrala

The present study was designed to analyze genetically somaclonal variants using biochemical and molecular markers. Efficient tissue culture protocol for Solanum melongena L. cv. Nirrala was developed. Maximum callus induction (100%) was observed for Murashige and Skoog (MS) media supplemented with 2.0 mg L^?1 naphthalene acetic acid +0.5 mg L^?1 6-benzylaminopurine; and nodal explants gave best callusing response (88.8%) as compared to internodes (88.3%) and leaves (87.7%). The best shooting was induced on nodal and internodal callus in the presence of 2.0 mg L^?1 6-benzylaminopurine. Total soluble protein content of callus and regenerated variant plants was estimated for biochemical analysis, and largest amount of soluble protein was found in callus (6.54 mg g^?1 fresh tissue) followed by variant plant grown on 2.0 mg L^?1 6-benzylaminopurine (5.96 mg g^?1 fresh tissue). Random amplification of polymorphic DNA technique was done with five decamer primers (OPC1-OPC5) and maximum polymorphism was detected by OPC 2 (26.99%) among all samples, whereas nodal callus on media containing 1.0 mg L^?1 naphthalene acetic acid +1.0 mg L^?1 6-benzylaminopurine showed highest polymorphism producing 22 bands, out of which 8 bands were polymorphic. The study shows that this marker system can provide better evaluation of genetic variation induced by tissue culture.     

Molecular docking analysis of fluoroquinolones and other natural and synthetic compounds with the HCV NS3 helicase

It is of an interest to document the molecular docking analysis of fluoroquinolones and other natural and synthetic compounds with the HCV NS3 helicase. Data shows that three fluoroquinolones interacted with the NS3 helicase in the catalytic region, targeting some of the amino acids known to play a crucial role in NS3 helicase activity. Similarly, binding energy shows that the fluoroquinolones were comparable to the thiazolpiperazinyl derivatives, while superior to several of the synthetic and natural derivatives. The results show three fluoroquinolones to be potent helicase inhibitors that can be repurposed as supplemental therapy against HCV especially in cases non-responsive to DAAAs.     

Genetic strategies to understand physiological pathways regulating body weight

Body weight is a highly heritable trait across species. In humans, genetic variation plays a major role in determining the inter-individual differences in susceptibility or resistance to environmental factors which influence energy intake and expenditure. In this review, I discuss how genetic studies have contributed to our understanding of the central pathways that govern energy homeostasis. The study of individuals harboring highly penetrant genetic variants that disrupt the leptin–melanocortin pathway has informed our understanding of the physiological pathways involved in mammalian energy homeostasis.