Life Sciences

<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

Molecular characterization of 96 rice germplasm collected from the different rice research centre was done using the panel of 50 SSR markers of the IRRI GCP programme. The aim of the work was to study variations and to select lines that can be used as potential parents in a future breeding program. A total number of 163 loci were amplified from 50 SSR markers; each primer amplified 3.26 loci of which 3.16 were polymorphic. The PIC value of each marker were ranged 0.04 (RM489) to 0.71 (RM 287) with an average PIC value of 0.32. Genetic relatedness among accessions based on SSR molecular marker data was presented in form of a dendrogram using the Un-weighted Pair Group Method with Arithmetic mean (UPGMA). The cluster analysis using the SRR microsatellite data classified ninety six genotypes in to two clusters namely, cluster A (13 genotypes) and large major cluster B (83 genotypes).

(SoNS) School of Natural Sciences

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Plant Archives

Estimation of molecular diversity based on SSR markers in Indian rice germplasm (Oryza sativa L.)

Background: Long-term maintenance of neural stem cells in vitro is crucial for their stage specific roles in neurogenesis. To have an in-depth understanding of optimal conditional microenviron-mental niche for long-term maintenance of neural stem cells (NSCs), we imposed different combinatorial treatment of growth factors to EGF/FGF-responsive cells. We hypothesized, that IGF-1-treatment can provide an optimal niche for long-term maintenance and proliferation of EGF/FGF-responsive NSCs. Objective: This study was performed to investigate the cellular morphology and growth of rat embryonic striatal tissue derived-NSCs in long-term culture under the influence of different combinatorial effects of certain growth factors, such as EGF, bFGF, LIF and IGF-1. Methods: The NSCs were harvested and cultured from striatal tissue of 18 days old rat embryos. We have generated neurospheres from these NSCs and cultured them till passage 7 (28 days in vitro) under four different conditional microenvironments: (A) without growth factor, (B) EGF/bFGF, (C) EGF/bFGF/LIF, (D) EGF/bFGF/IGF-1 and (E) EGF/bFGF/LIF/IGF-1. Isolated NSCs were characterised by Immunoflouroscence for nestin expression. The cell growth and proliferation was evaluated at different time intervals (P1, P3, P5 & P7), assessing the metabolic activity based cell proliferation. Apoptosis was studied in each of these groups by In situ cell death assay. Results: Our results demonstrated certain important findings relevant to long-term culture and maintenance of striatal NSC-derived neurospheres. This suggested that IGF-1 can induce enhanced cell proliferation during early stages of neurogenesis, impose long-term maintenance (up to passage 7) to cultured NSCs and enhance survival efficiency in vitro, in the presence of EGF and FGF. Conclusions: Our findings support the hypothesis that the enforcement of IGF-1 treatment to the EGF/FGF-responsive NSCs, can lead to enhanced cell proliferation during early stages of neurogenesis, and an extended life span in vitro. This information will be beneficial for improving future therapeutic implication of NSCs, by addressing improved in vitro production of NSCs. © Ivyspring International Publisher.

Fulltext

International Journal of Medical Sciences

IGF-1 acts as controlling switch for long-term proliferation and maintenance of EGF/FGF-responsive striatal neural stem cells

The antibody trastuzumab is approved for treatment of patients with HER2 (ERBB2)-overexpressing breast cancer. A significant fraction of these tumors are either intrinsically resistant or acquire resistance rendering the drug ineffective. The development of resistance has been attributed to failure of the antibody to inhibit phosphoinositide 3-kinase (PI3K), which is activated by the HER2 network. Herein, we examined the effects of PI3K blockade in trastuzumab-resistant breast cancer cell lines. Treatment with the pan-PI3K inhibitor XL147 and trastuzumab reduced proliferation and pAKT levels, triggering apoptosis of trastuzumab-resistant cells. Compared with XL147 alone, the combination exhibited a superior antitumor effect against trastuzumabresistant tumor xenografts. Furthermore, treatment with XL147 and trastuzumab reduced the cancer stem-cell (CSC) fraction within trastuzumab-resistant cells both in vitro and in vivo. These effects were associated with FoxO-mediated inhibition of transcription of the antiapoptosis gene survivin (BIRC5) and the CSC-associated cytokine interleukin-8. RNA interference-mediated or pharmacologic inhibition of survivin restored sensitivity to trastuzumab in resistant cells. In a cohort of patients with HER2-overexpressing breast cancer treated with trastuzumab, higher pretreatment tumor levels of survivin RNA correlated with poor response to therapy. Together, our results suggest that survivin blockade is required for therapeutic responses to trastuzumab and that by combining trastuzumab and PI3K inhibitors, CSCs can be reduced within HER2+ tumors, potentially preventing acquired resistance to anti-HER2 therapy. © 2012 American Association for Cancer Research.

Cancer Research

Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors

Bacterial leaf blight of rice, caused by Xanthomonas oryzae pv. oryzae is one of the major constraints limiting rice production and productivity in South East Asia, particularly in Japan, Philippines, Indonesia, China and India. No effective chemical control for the disease is available. It is therefore, important to identify lines resistant to blight, which can then be used as parental lines in breeding programmes. Gene-linked and gene-based molecular markers and well defined donors are available for most of these genes. In the present study, a total of 386 Indian rice germplasm lines including commercially cultivated Indian rice varieties were screened for the presence of four bacterial blight resistance genes i.e. Xa4, xa5, xa13 and Xa21. The rationale behind the study was to identify new hitherto unreported, rice lines carrying BLB resistance genes and studying the allelic distribution of these genes in the germplasm.

Indian Journal of Genetics and Plant Breeding

Identification of Indian rice germplasm lines with bacterial leaf blight (BLB) resistance genes

Closed traumatic brain injury (CTB I) leads to increase mortality rates in developing countries. However, a sustainable therapeutic approach has not been established yet. Therefore, the present study was designed to evaluate the impact of normabaric hyperoxia treatment (NBOT) on striatum associated Locomotor Activity (LA) in IntelliCage after Fluid-Percussion Injury (FPI). Animals were divided in four groups: Group I control (n=24), Group II sham (n=24), Group III FPI (n=24) and Group IV FPI with NBOT (n=24). Animals were habituated in IntelliCage for 4 days following transponder implanted in mice neck region on day 5. Then the LA of all groups was assessed 6hr daily for 5 days before inducing FPI. On day 6, cannula was implanted on the striatum, on day 7 FPI was performed in Group III (kept in normal environment) and IV (immediately exposed to NBOT for 3 hr). LA (in terms of number of visits in all four corners) was assessed 6 hr at days 1, 7, 14, 21 and 28 following FPI. After the animals were sacrificed to study the neuronal damage, dopamine receptors and transporters expression in striatum. The results suggested that the LA of FPI impaired mice as compared to the control and sham showed less number of visits in all four corners in IntelliCage. Morphological results revealed that FPI induced neuronal damage as compared to sham and control. Dopamine receptors and transporters were down regulated in the FPI group as compared to the control. Immediate exposure to NBOT improved LA in terms of increased number of visits in all four corners, reduced number of cell death and improved receptor expression as compared to FPI. In conclusion, NBOT exposure could improve the LA of mice following FPI through prevention of neuronal damage, improved dopamine receptors and transporters. © 2013 Sangu Muthuraju et al.

International Journal of Biomedical Science

Normabaric hyperoxia treatment improved locomotor activity of C57BL/6J mice through enhancing dopamine genes following fluid-percussion injury in striatum

A statistical study of pulsing hiss emissions observed during daytime at low latitude Indian ground stations Jammu (geomag. lat., 22 26′N; L = 1.17) and Srinagar (geomag. lat., 24 10′N; L = 1.28) is presented. From the detailed statistical analysis of the observed data it is found that the reported day time pulsing hiss emissions is a rare phenomena at low latitudes. The spectrograms of pulsing hiss emissions observed during daytime clearly show band limited spectrums regularly pulsing with almost equal period of the order of few seconds in the frequency range of 300 Hz-8 kHz. The intensity and bandwidth of daytime pulsing hiss remain almost constant in the frequency range of 300 Hz-8 kHz in clear contrast to the pulsing hiss emission observed during nighttime at low latitudes. The daytime pulsing hiss time period is about 0.5 s which is small in comparison to time period (~1.43 s) of the low latitude pulsing hiss observed during nighttime. The generation and propagation mechanisms of pulsing hiss emissions are discussed. The micropulsations propagating along the geomagnetic field lines modulate the growth rate of the wave resulting in hiss intensity. © 2013 Indian Association for the Cultivation of Science.

Indian Journal of Physics

A statistical study of daytime pulsing hiss emission at low latitudes

GW2, a grain weight quantitative trait locus (QTL) in rice encodes a ring type E-3 ubiquitin ligase. A single nucleotide deletion at the 346th nucleotide position in the ligase domain of GW2 was earlier reported to result in higher grain weight in rice. The present study aimed at validating the known functional polymorphism and identifying additional natural genetic variation if any, in the region that included the functional domain of GW2 in a set of indica and aromatic genotypes for which ninety three rice genotypes were phenotyped for grain length, grain width and 100 grain weight. A wide range of variation was observed for these traits. PCR amplification and sequencing of GW2 target region revealed absence of insertion/deletion (InDel) at the 346th position which suggested that the genetic variation in grain weight in Basmati and non-Basmati indica genotypes was not explained by this InDel. However, four new single nucleotide polymorphisms (SNPs) were discovered at nucleotide positions 406, 461, 466 and 501 in the fifth exon and one InDel each in second and fourth introns. Only two of these SNPs, at positions 461 and 501 led to amino acid substitutions. A total of 10 haplotypes were constructed based on these four SNPs which could be regrouped into four categories based on their amino acid substitutions. Association genetic analysis of these haplotypes with different grain traits revealed a moderate association with grain width (R2 = 0.18 at P &lt; 0.05). Thirteen haplotypes constructed using both intronic and exonic polymorphisms did not have any association with grain traits. © 2012 Springer Science+Business Media Dordrecht.

Euphytica

Haplotype structure in grain weight gene GW2 and its association with grain characteristics in rice

Histidinolphosphate aminotransferase (HisC; Rv1600) from Mycobacterium tuberculosis was overexpressed in M. smegmatis and purified to homogeneity using nickel-nitrilotriacetic acid metal-affinity and gel-filtration chromatography. Diffraction-quality crystals suitable for X-ray analysis were grown by the hanging-drop vapour-diffusion technique using 30% polyethylene glycol monomethyl ether 2000 as the precipitant. The crystals belonged to the hexagonal space group P3221, with an unusual high solvent content of 74.5%. X-ray diffraction data were recorded to 3.08 {\AA} resolution from a single crystal using in-house Cu K radiation. The structure of HisC was solved by the molecular-replacement method using its Corynebacterium glutamicum counterpart as a search model. HisC is a dimer in the crystal as well as in solution. {\textcopyright} 2013 International Union of Crystallography.

Acta Crystallographica Section F: Structural Biology and Crystallization Communications

Sample preparation, crystallization and structure solution of HisC from Mycobacterium tuberculosis

Purpose: Mutations in receptor tyrosine kinase (RTK) genes can confer resistance to receptor-targeted therapies. A T798M mutation in the HER2 oncogene has been shown to confer resistance to the tyrosine kinase inhibitor (TKI) lapatinib. We studied the mechanisms of HER2-T798M-induced resistance to identify potential strategies to overcome that resistance. Experimental Design: HER2-T798M was stably expressed in BT474 and MCF10A cells. Mutant cells and xenografts were evaluated for effects of the mutation on proliferation, signaling, and tumor growth after treatment with combinations of inhibitors targeting the EGFR/HER2/HER3/PI3K axis. Results: A low3%allelic frequency of the T798M mutant shifted 10-fold the IC50 of lapatinib. In mutantexpressing cells, lapatinib did not block basal phosphorylation of HER2, HER3, AKT, and ERK1/2. In vitro kinase assays showed increased autocatalytic activity of HER2-T798M. HER3 association with PI3K p85 was increased in mutant-expressing cells. BT474-T798M cells were also resistant to the HER2 antibody trastuzumab. These cells were sensitive to the pan-PI3K inhibitors BKM120 and XL147 and the irreversible HER2/EGFR TKI afatinib but not the MEK1/2 inhibitor CI-1040, suggesting continued dependence of the mutant cells on ErbB receptors and downstream PI3K signaling. BT474-T798M cells showed increased expression of the EGFR ligands EGF, TGFa, amphiregulin, and HB-EGF. Addition of the EGFR neutralizing antibody cetuximab or lapatinib restored trastuzumab sensitivity of BT474-T798M cells and xenografts, suggesting that increased EGFR ligand production was causally associated with drug resistance. Conclusions: Simultaneous blockade of HER2 and EGFR should be an effective treatment strategy against HER2 gene-amplified breast cancer cells harboring T798M mutant alleles. © 2013 American Association for Cancer Research.

Clinical Cancer Research

Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2

Summary Cicer arietinum L. (chickpea) is the third most important food legume crop. We have generated the draft sequence of a desi-type chickpea genome using next-generation sequencing platforms, bacterial artificial chromosome end sequences and a genetic map. The 520-Mb assembly covers 70% of the predicted 740-Mb genome length, and more than 80% of the gene space. Genome analysis predicts the presence of 27 571 genes and 210 Mb as repeat elements. The gene expression analysis performed using 274 million RNA-Seq reads identified several tissue-specific and stress-responsive genes. Although segmental duplicated blocks are observed, the chickpea genome does not exhibit any indication of recent whole-genome duplication. Nucleotide diversity analysis provides an assessment of a narrow genetic base within the chickpea cultivars. We have developed a resource for genetic markers by comparing the genome sequences of one wild and three cultivated chickpea genotypes. The draft genome sequence is expected to facilitate genetic enhancement and breeding to develop improved chickpea varieties. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.