Topics in cancer genomics

Large-scale projects such as the The Cancer Genome Atlas (TCGA) have generated extensive exome libraries across several disease types and populations. Detection of somatic changes in HLA genes by whole-exome sequencing (WES) has been complicated by the highly polymorphic nature of these loci. We developed a method POLYSOLVER (POLYmorphic loci reSOLVER) for accurate inference of class I HLA-A, -B and -C alleles from WES data, and achieved 97% accuracy at protein level resolution when this was applied to 133 HapMap samples of known HLA type. By applying POLYSOLVER in conjunction with somatic change detection tools to 2688 tumor/normal pairs TCGA that were previously analyzed by conventional approaches, we re-discovered 37 of 56 (66%) HLA mutations, while further identifying 23 new events. An analysis of WES data from a larger set of 3768 tumor/normal pairs by POLYSOLVER revealed 131 class I mutations with an enrichment for potentially loss-of-function events. 3% of samples had at least one HLA event with 95 of 131 mutations in the T cell interacting and peptide binding domains. Recurrent hotspot sites of missense, nonsense and splice site mutations were discovered that suggest positive selection, and support immune evasion as an important pathway in cancer. Exome sequencing has also revealed a large number of shared and personal somatic mutations across human cancers. In principle, any genetic alteration affecting a protein-coding region has the potential to generate mutated peptides that are presented by surface HLA class I proteins that might be recognized by cytotoxic T cells. Utilizing POLYSOLVER in conjunction with knowledge of mutations in other genetic loci inferred from exome data, we developed a pipeline for the prediction and validation of such neoantigens derived from individual tumors and presented by patient-specific alleles of the HLA proteins. We applied our computational pipeline to 91 chronic lymphocytic leukemias (CLL) that had undergone whole-exome sequencing. We predicted ~22 mutated HLA-binding peptides per leukemia (derived from ~16 missense mutations), and experimentally confirmed HLA binding for ~55% of such peptides. Finally, we computationally predicted HLA-binding peptides with missense or frameshift mutations for several cancer types and predicted dozens to thousands of neoantigens per individual tumor, suggesting that neoantigens are frequent in most tumors. The neoantigen prediction pipeline can also elucidate the neoantigens unique to a particular cancer patient and help in the design of personalized immune vaccines. MicroRNAs (miRs) are a class of non-coding small RNAs that regulate gene expression by promoting mRNA degradation or by inhibiting mRNA translation. Context Likelihood of Relatedness (CLR) is genetic network reconstruction method that considers the local network context in assessing the significance of connections while also allowing for detection of non-linear associations. Leveraging TCGA multidimensional data in glioblastoma, we inferred the putative regulatory network between microRNA and mRNA using the CLR algorithm. Interrogation of the network in context of defined molecular subtypes identified 8 microRNAs with a strong discriminatory potential between proneural and mesenchymal subtypes. Integrative in silico analyses, a functional genetic screen, and experimental validation identified miR-34a as a tumor suppressor in proneural subtype glioblastoma. Mechanistically, in addition to its direct regulation of platelet-derived growth factor receptor-alpha (PDGFRA), promoter enrichment analysis of CLR-inferred mRNA nodes established miR-34a as a novel regulator of a SMAD4 transcriptional network. Clinically, miR-34a expression level is shown to be prognostic, where miR-34a low-expressing glioblastomas exhibited better overall survival. This work illustrates the potential of comprehensive multidimensional cancer genomic data combined with computational and experimental models to enable mechanistic exploration of relationships among different genetic elements across the genome space in cancer

Use of Electronic Information Resources by Social Scientists of Banaras Hindu University

The dependency on e-resources in every sphere of intellectual activity is increasing day by day. This study investigates the use of electronic information resources by social scientists of Banaras Hindu University with regard to the advocacy of electronic resources. The study revealed that electronic resources available are fairly accessible to the social scientists. Findings revealed that social scientists fairly used the library for their research and other academic purposes

Relationship between ionic radius and pressure dependence of ionic conductivity in water

Experimental measurements of ionic conductivity in water are analysed in order to obtain insight into the pressure dependence of limiting ionic conductivity of individual ions (λ0) for ions of differing sizes. Conductivities of individual ions, λ0 do not exhibit the same trend as a function of pressure for all ions. Our analysis suggests that the effect of pressure on ionic conductivity depends on the temperature. At low temperatures, the effect of pressure on relatively small ions such as Li+ exhibit an increase in conductivity with pressure. Intermediate sized ions exhibit an increase in conductivity with increase in pressure initially and then at still higher pressures, a decrease in ionic conductivity is observed. Although there are data at low temperatures for ions of large radius, the effect of increased pressure is expected to lower conductivity with increase in pressure over the whole range. At higher temperatures, the dependence of conductivity on pressure changes and these changes are discussed. Divalent ions such as SO2−4 exhibit different trends as a function of pressure at different temperatures. Both the divalent ions (Ca2+ and SO2−4 ) for which experimental data exists, exhibit an increase with pressure at lower temperatures. At slightly higher temperatures, a maximum in conductivity is seen as a function of pressure over the same range of pressure

New lithium-ion conductors based on the NASICON structure

Lithium-ion conduction in mixed-metal phosphates, LiMVMIII(PO4)3 [MV=Nb, Ta; MIII=Al, Cr, Fe], possessing the rhombohedral (R3c) NASICON structure has been investigated. Among the phosphates investigated, LiTaAl(PO4)3 exhibits the highest conductivity, σ ≈ 1.0×10-2 S cm-1 at 350°C (Ea=0.47 eV), comparable to the conductivity of LiTi2(PO4)3. Unlike LiTi2(PO4)3 which contains lithium-reducible TiIV, LiTaAl(PO4)3 contains stable TaV and AlIII oxidation states and hence deserves further attention towards tailoring new lithium-ion conductors for application as electrolytes in solid state lithium batteries

Effect of Arbuscular Mycorrhizae on Nutrient Content and Seedling Quality of Important Fodder Tree Species of Central India

Acacia nilotica, Albizia procera, Dalbergia sissoo and Leucaena leucocephala are important multipurpose tree species (MPTs). These are being utilized in agroforestry systems at ICAR-Central Agroforestry Research Institute (ICARCAFRI), Jhansi and are also being utilized in reforestation programme in Central India. The success of any agroforestry model and/or reforestation programme depends upon the quality seedling materials. Nursery-produced seedlings can be an effective means of ensuring successful establishment of agroforestry models and/or reforestation programme. However, such seedlings sometimes fail to establish themselves in the fields. The poor performance of planted seedlings is often associated with transplant shocks and low seedling quality. The preconditioning of young seedlings with efficient arbuscular mycorrhizal fungi (AMF), an important soil microorganism improves plant health and helps in their establishment in fields (Jha et al., 2014). However, before utilizing these fungi for inoculation purpose, the suitable AMF species must be identified. Therefore, to find out the efficient AMF species for inoculations of above mentioned plant species, present study was carried out

Unipolar resistive switching in cobalt titanate thin films

We report giant resistive switching of an order of 104, long-time charge retention characteristics up to 104 s, non-overlapping SET and RESET voltages, ohmic in low resistance state (LRS) and space charge limited current (SCLC) mechanism in high resistance state (HRS) properties in polycrystalline perovskite Cobalt Titanate (CoTiO3 ~ CTO) thin films. Impedance spectroscopy study was carried out for both LRS and HRS states which illustrates that only bulk resistance changes after resistance switching, however, there is a small change (<10% which is in pF range) in the bulk capacitance value in both states. These results suggest that in LRS state current filaments break the capacitor in many small capacitors in a parallel configuration which in turn provides the same capacitance in both states even there was 90 degree changes in phase-angle and an order of change in the tangent loss.Comment: 7 pages, 4 figure

Effect of Arbuscular Mycorrhize on Growth and Productivity of \u3cem\u3eStylosanthes seabrana\u3c/em\u3e

Stylosanthes seabrana, an important range legume was introduced in India in the year 1998 through ACIAR-ICAR joint project. It has given good results under agroforestry/silvopastoral systems and can be grown as sole pasture crop or along with compatible grasses/legumes on a variety of soils. For its year round production, intensive cutting approach is generally employed. Under such conditions, plant demands large amount of soil nutrients for better productivity, which are generally applied as inorganic fertilizers (Chandra et al., 2006). In soils with low nutrient contents especially phosphorus (P), large amount of phosphatic fertilizers are required for establishment and growth of legumes. P is often a growth-limiting factor for plant growth and legumes are poor scavengers of P. In soils, P may present in sufficient amounts but much of it is poorly available to plants because of less solubility of phosphates of calcium, aluminum and iron. Arbuscular mycorrhizae (AM), an important soil microorganism mobilize phosphates and make available to the plants, which indirectly increases their growth (Jha et al., 2012). AM fungi have proved their usefulness in plant production, How even the efficiency of AM inoculants can be affected by properties and texture of the potting substrates (Herrera-Peraza et al., 2011). Since, reports on effect of AM inoculations on growth and productivity of S. seabrana are very scarce in literature; hence, present study was carried out to identify the suitable AM inoculants for S. seabrana

Adverse effects of antiretroviral treatment at a tertiary care hospital in India: a prospective observational study

Background: Data on adverse drug reactions (ADRs) related to antiretroviral (ARV) use in public health practice are few indicating the need for antiretroviral therapy (ART) safety surveillance in clinical care.Methods: 143 patients on ART were studied prospectively over a period of two years. All patients were asked to visit the clinic if they developed any symptoms or on a monthly basis. They were screened clinically and investigated suitably for any ADRs.Results: 143 HIV positive patients were analyzed. At least one ADR was seen in 87 (60.83%) subjects. The most common ADR observed was peripheral neuropathy in 54 (37.76%) patients, followed by lipodystrophy (13.98%), anemia (10.48%) and hyperlipidemia (6.29%). Patients with peripheral neuropathy and lipodystrophy were mainly on stavudine based regimes, while patient with anemia and hyperlipidemia were on zidovudine based regimes. Conclusions: In spite of high ADRs, highly active antiretroviral therapy (HAART) is the only answer to HIV/AIDS. To optimize adherence and thus, efficacy of ART, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious

A retrospective (2004-2013) and prospective (2014-2015) study of new born with special reference to anorectal malformations over a period of 10 years at a tertiary care centre

Background:A surgical audit of neonates with anorectal malformation in advanced tertiary neonatal care unit.Methods: A retrospective (2004-2013) and prospective (2014-2015) audit of medical records of newborn with GIT disorders admitted in a tertiary care center of central India. The trends analyzed for the duration based on gender, region and birth weight and data base was generated depicting the burden of disease in the region. The data base for the prospective study was also compared with a tertiary center from Nigeria.Results:Total 3309 admission included 73.56% (2438) patients of GIT diseases. Congenital anomalies were the most common cause in each category, major part being anorectal malformation (727) and trachea-esophageal fistula (730). Out of 727 admissions, 651 neonates were operated & total 1194 deaths recorded during this audit year 2004 to July 2015. Majority of new born admitted with were low birth weight male from rural skirts of this region. 509 have associated anomalies and 218 isolated ARM.  Conclusions:There is significant increase in admissions in last decade with triple fold increase in GIT disorder and twice rate in anorectal malformation substantially increasing onwards. The quality of management has to continue further to achieve parity with international standards, as there is lack of antenatal screening and details of any antenatal checkup are scarce, for congenital anomalies at primary level. Early recognition, risk stratification of the baby and timely referral to higher pediatric surgery units is the way forward