Pulsed 86Sr-labeling and NanoSIMS imaging to study coral biomineralization at ultra-structural length scales

A method to label marine biocarbonates is developed based on a concentration enrichment of a minor stable isotope of a trace element that is a natural component of seawater, resulting in the formation of biocarbonate with corresponding isotopic enrichments. This biocarbonate is subsequently imaged with a NanoSIMS ion microprobe to visualize the locations of the isotopic marker on sub-micrometric length scales, permitting resolution of all ultra-structural details. In this study, a scleractinian coral, Pocillopora damicornis, was labeled 3 times with 86Sr-enhanced seawater for a period of 48h with 5days under normal seawater conditions separating each labeling event. Two non-specific cellular stress biomarkers, glutathione-S-transferase activity and porphyrin concentration plus carbonic anhydrase, an enzymatic marker involved in the physiology of carbonate biomineralization, as well as unchanged levels of zooxanthellae photosynthesis efficiency indicate that coral physiological processes are not affected by the 86Sr-enhancement. NanoSIMS images of the 86Sr/44Ca ratio in skeleton formed during the experiment allow for a determination of the average extension rate of the two major ultra-structural components of the coral skeleton: Rapid Accretion Deposits are found to form on average about 4.5 times faster than Thickening Deposits. The method opens up new horizons in the study of biocarbonate formation because it holds the potential to observe growth of calcareous structures such as skeletons, shells, tests, spines formed by a wide range of organisms under essentially unperturbed physiological condition

Plant Genetic Resources and Germplasm Use in India

Plant genetic resource (PGR) scientists now recognize the importance of shifting from a singular focus on conservation to a focus on both conservation and utilization of germplasm in order to meet future challenges. This paper analyzes the patterns of distribution of pearl millet, six small millets, chickpea and pigeonpea germplasm over the last 10 years at the two major genebanks functioning in India: the National Genebank at the National Bureau of Plant Genetic Resources (NBPGR) and a Consultative Group for International Agricultural Research (CGIAR) Genebank at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), as well as the patterns of use of germplasm by millet breeders in India. Between the years of 1999-2009, ICRISAT distributed approximately 48 per cent of all its collections to breeders in India whereas NBPGR distributed 36 per cent of their collection. A total of 20 responses (30 per cent of surveys sent) were collected through this study. Sixty-five percent of respondents said that they rarely (<50 per cent of the time) use germplasm from genebanks in their breeding programs. It is important that both genebanks look into several issues in order to improve levels of distribution and utilization, collection, duplication, engagement of the private sector, access to information, and pre-breeding

Exchange of plant genetic resources: Prospects in India

National Bureau of Plant Genetic Resources has the major responsibility of introducing genetic resources and distributing the same to various research Institutes/organizations within the country. It is involved in enrichment of plant genetic resources through germplasm exchange, procurement and collection from centres of diversity suitable for different agro-climatic conditions. Different biotic and abiotic stresses are the major production constraints in many crops, hence, introduction of crops from the centre of diversity is much needed to bring into superior seeds of various crops with high yield, quality, resistance to pest and diseases and tolerant to abiotic stresses through crop improvements programmes. Future emphasis is to introduce specific genotypes with special characters especially like high quality lines and lines resistant to various biotic and abiotic stresses. During the past five years 211 298 accessions including 467 995 samples of seed/planting material were introduced from 103 countries. Out of theses 116 149 accessions having 138 352 samples were germplasm while 58 024 entries having 329 704 samples were trials/nurseries entries and 1 139 wild species of different agri-horticultural crops were also introduced. During this period a total of 78 298 accessions were exported as per norms/regulation lay down by NBA and with permission of ICAR/DARE, for research purposes only. NBPGR has supplied 50 657 samples of various crops to national users in different institutes/organizations across the country for various crop improvement and breeding programmes

Avapritinib versus regorafenib in locally advanced unresectable or metastatic GI stromal tumor: A randomized, open-label phase III study

PURPOSE Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V–mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS Four hundred seventy-six patients were randomly assigned (avapritinib, n 5 240; regorafenib, n 5 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P 5 .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade $ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST