Stratified Deposit Production Schedule Optimisation Considering In-Pit Dumping and Haul Road Selection

In mining operations, selecting a schedule for waste mining and hauling to dump locations including in-pit dumps and ore to plants and stockpiles, through a network of roads, poses a huge combinatorial problem. A mathematical model has been proposed to simultaneously optimise pit and waste dump mining including in-pit dumping, with the selection of shortest haulage from possible haul-road networks. Solution methodologies have been developed using exact and meta-heuristic methods and applied on several cases

Molecular Evolution of Hominoid Primates: Phylogeny and Regulation

The complete mtDNA of one eastern gorilla was sequenced to provide the most accurate date for the mitochondrial divergence of gorillas. The most recent common ancestor of eastern lowland and western lowland gorillas existed about 1.9 million years ago, slightly more recent than that of chimpanzee and bonobo. This study also depicts that the eastern and western gorillas show species level genetic divergence. Hominoid mating systems differ tremendously. The level of sperm competition varies according to the mating system, which presumably imposes unique selective pressures on the seminal proteins of each species. Cartilage acidic protein 1 (CRTAC1) was identified in our lab as the protein with the largest difference in abundance between human and chimpanzee, being found at 142-fold higher in chimpanzee. The coding region of CRTAC1 is extremely conserved with signature of strong purifying selection. Paradoxically, CRTAC1 `promoter\u27 from human drives transcription significantly greater than chimpanzee, with or without androgen stimulation. Analyzing H3K27Ac data, a ~2.2kb region was identified as a possible additional cis-regulatory element. The cis-regulatory region behaved like a silencer and aided in strong transcriptional repression in humans. Although its underlying basis remains elusive, it can be speculated that the differential expression of CRTAC1 between human and chimpanzee seminal plasma results from tissue specific over/under expression of this gene. The unique gains and losses of miRNAs within hominoids have remained understudied. The overall goal of this project was to identify the uniquely gained and lost miRNAs and their targets within hominoids. I found 14 miRNAs uniquely gained in humans. Maximum uniquely gained and lost miRNAs were found to be brain specific. The targets of uniquely gained miRNAs in human are also associated with brain-associated functions. Older miRNAs were found to be more conserved compared to the newer miRNAs gained \u3c15 Mya

MITOCHONDRIAL CONTROL REGION VARIATION AMONG THE SUBSPECIES OF SARUS CRANE (GRUS ANTIGONE)

Sarus cranes (Grus antigone) are the tallest members of the crane family, Gruidae. They are found in four geographically distinct regions: northwest India (Indian Sarus- Grus antigone antigone), southeast Asia (Burmese Sarus- Grus antigone sharpei) and northern Australia (Australian Sarus- Grus antigone gillae). Although the three subspecies are morphologically distinct, their genetic distinctness is unclear. In this study, I focused on control region sequences of mitochondrial DNA (mtDNA) to assess the genetic and phylogeographic distinctness of Sarus subspecies. I used samples from four fragmented populations, seven from India, 16 from southeast Asia, five from Myanmar and eight from Australia. Phylogenetic trees were estimated using two Brolga crane sequences (G. rubicunda) as outgroups. All phylogenetic trees had low resolution, but AMOVA showed that all four Sarus populations are differentiated from each other. Nested clade phylogenetic analysis showed that most of the southeast Asian haplotypes are found at the center, suggesting that the Thai population includes the maximum number of ancestral haplotypes. Sarus cranes probably originated in southeast Asia and migrated both north towards India and south towards Australia during the last glacial maximum

Repression of the alkaline phosphatase of Vibrio cholerae

The synthesis of alkaline phosphatase by two strains of Vibrio cholerae belonging to the Inaba and Ogawa serotypes has been examined in relation to the phosphate concentration of the culture medium. The synthesis of the enzyme in both strains was repressed in cells grown in the presence of a high concentration of inorganic phosphate. Lowering the phosphate content of the growth medium led to a derepression of enzyme activity. The presence of glucose in low phosphate medium stimulated the degree of derepression. The synthesis of the enzyme by strain Inaba 569B was more sensitive to inorganic phosphate than that of strain Ogawa 154. The enzyme was presumably located in the periplasmic space since it was released when the organisms were converted to spheroplasts

Ancestry Specific variation in neuropsychological disorders among the South Asian population

The enormous genetic diversity in South Asia resulting from a long and complex admixture history resulted in the emergence of variation in various traits and variations in disease susceptibility. Neuropsychological disorders are one such example that shows variation at the population level. In this study, we aimed at understanding the variation in neuropsychological disorders at the population level among South Asian populations by curating, comparing and contrasting single nucleotide polymorphisms (SNPs), known to be associated with the same. Whole-genome data comprising of 1662 South Asians, belonging to 241 distinct populations were obtained from the database of Dr. David Reich, Harvard Medical School, USA. Principal Component Analysis (PCA) revealed that the Ancestral Tibeto Burman (ATB) genomes form a distinct and distinguishable cluster for the SNPs known to be associated with neuropsychological disorders. Identical By Descent (IBD) analysis showed that out of the top seven populations in terms of IBD sharing, six are from Southern India indicating that these populations may have undergone a recent selective sweep for these SNPs. Further, out of the top ten genomes, according to the number of genomes fixed for the minor alleles, seven were from Southern India. Furthermore, several indigenous populations from South India depicted high F values (>0.25) for SNPs associated with neuropsychological disorders, indicating higher susceptibility for neuropsychological disorders among these South Indian populations. Interestingly, we found that most of the SNPs, fixed for the alternative alleles, were also found to be fixed among the ancient genomes from Indus Valley Civilization (IVC), indicating that these SNPs likely got transmitted to various modern-day South Indian populations from IVC

Role of Reactive Oxygen Species in Mercapto-Methylimidazole-Induced Gastric Acid Secretion and Stress-Induced Gastric Ulceration

The objective of the present study is to delineate the role of reactive oxygen species in drug-induced gastric hyperacidity and stress-induced gastric ulceration. We reported earlier that mercaptomethylimidazole (MMI), an antithyroid drug, induces gastric acid (HCl) secretion partially through H2receptor activation of the parietal cell by histamine release and partially through an intracellular mechanism. While studying the latter, MMI-induced acid secretion was found to correlate well with the inactivation of the peroxidase, an important H2O2metabolizing enzyme of the mucosa. MMI activates the isolated parietal cell for acid secretion, which is sensitive to omeprazole. Peroxidase and catalase activity of the isolated cell is also irreversibly inactivated by MMI. It thus creates a favourable condition for endogenous accumulation of H2O2. Acid secretion by gastric gland preparation or isolated gastric mucosa is stimulated by exogenous H2O2, which is inhibited by omeprazole. Studies indicate that H2O2inactivates the prostaglandin synthetase and removes the inhibitory influence of prostaglandin on acid secretion. MMI thus stimulates acid secretion not only through H2, receptor activation but also through the stimulation of the parietal cell by intracellular generation of H2O2following inactivation of the peroxidase-catalase system. Among the various factors responsible for gastric ulceration, stress was found to cause severe haemorrhagic lesions mainly through oxidative damage of the mucosa as indicated by increased lipid peroxidation, increased protein carbonyl content, and decreased glutathione level. The severity of ulcer correlates well with the time-dependent induction of superoxide dismutase and inactivation of peroxidase, a condition favourable for accumulation of endogenous H2O2. Desferrioxamine prevents stress ulcer, indicating involvement of transition metal ion in the process. Studies indicate that severity of stress ulcer is dependent on the concurrent generation of hydroxyl radical (•OH) formed through metal-catalysed Haber-Weiss reaction between O2-and H2O2

Using Ancestry Informative Markers (AIMs) to Detect Fine Structures Within Gorilla Populations

The knowledge of ancestral origin is monumental in conservation of endangered animals since it can aid in preservation of population level genetic integrity and prevent inbreeding among related individuals. Despite maintenance of studbook, the biogeographical affiliation of most captive gorillas is largely unknown, which has constrained management of captive gorillas aiming at maximizing genetic diversity at the population level. In recent years, ancestry informative markers (AIMs) has been successfully employed for the inference of genomic ancestry in a wide range of studies in evolutionary genetics, biomedical research, genetic stock identification, and introgression analysis and forensic analyses. In this study, we sought to derive the AIMs yielding the most cohesive and faithful understanding of biogeographical affiliation of query gorillas. To this end, we compared three commonly used AIMs-determining methods namely, Infocalc, FST, and Smart Principal Component Analysis (SmartPCA) with ADMIXTURE, using gorilla genome data available through Great Ape Genome Project database. Our findings suggest that the SNPs that were detected by at least three of the four AIMs-determining approaches (N = 1,531), is likely most suitable for delineation of gorilla AIMs. It recapitulated the finer structure within western lowland gorilla genomes with high degree of precision. We further have validated the robustness of our results using a randomized negative control containing the same number of SNPs. To the best of our knowledge, this is the first report of an AIMs panel for gorillas that may aid in developing cost-effective resources for large-scale demographic analyses, and greatly help in conservation of this charismatic mega-fauna

Enterotoxin production, DNA repair and alkaline phosphatase of Vibrio cholerae before and after animal passage

Summary: Three strains of Vibrio cholerae differing in biotype, serotype and/or toxinogenicity were studied. The capability for dark repair of DNA and stability of alkaline phosphatase decreased concomitantly with toxinogenicity on laboratory passage of highly enterotoxinogenic strain 569B. These properties could be restored by passaging strain 569B once through a guinea-pig