Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an ...attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7 − 12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
The ability of roots to penetrate compacted soils can be beneficial in avoiding drought stress. However, breeding for root penetration is hindered by the lack of an efficient, reliable screening ...technique. Our objectives in this study were to develop and evaluate the use of a wax-petrolatum layer system as a reference to measure genotypic variation in root penetration ability of 11 rice (Oryza sativa L.) cultivars from dryland and wetland hydrological origins. The wax-petrolatum layers consisted of 60% wax and 40% petrolatum white, with a penetration resistance strength of 1.4 MPa at 27 degrees C as measured with a soil penetrometer. The wax-petrolatum layers were placed in pots and served as a partial barrier to root growth. Rice cultivars were sown in a randomized complete block design with three replications and grown in a growth chamber. Root penetration ability was measured as the ratio of the number of roots that penetrated the wax-petrolatum layer to the total number of roots. Consistently, rice cultivars from dryland hydrological origins had greater root penetration ability than did cultivars from wetland origins. Root penetration ability ranged from 6 to 26%. Root thickness ranged from 0.9 to 1.5 mm and was positively correlated (r = 0.81, P 0.001) with root penetration ability. Data indicated that the use of wax-petrolatum layers was an effective technique for measuring differences in root penetration ability
Water deficits cause major yield reductions on the world's rainfed riceland. The most severe water deficits occur during the reproductive phase. Differences in canopy temperature among crop cultivars ...are known to be related to drought avoidance characters. In developing a practical field screening system for reproductive phase drought resistance in rice (Oryza sativa L.), we assessed the canopy temperature response of a range of germplasm, and related the results to other plant characters related to drought resistance. Field experiments were conducted on a silty clay loam Typic Hapludoll at the International Rice Research Institute. Planting of the test cultivars was staggered, to synchronize flowering during the water-deficit period. Canopy temperature measurements were made on 12 dates in Trial 1 and 8 dates in Trial 2. Mean canopy temperatures (Tc) increased from 28 to 37 degrees C during the stress period. Grain yield (r2 = -0.63**) and spikelet fertility (r2 = 051**) were related to midday Tc on the day of flowering. Highly significant differences were observed in canopy temperature among entries, with low coefficients of variation (2.0-2.7%). Entries with a history of outstanding vegetative stage drought screening scores consistently remained coolest under stress. Visual drought tolerance scores (r = 0.72**) and leaf rolling scores (r = 0.68**) were correlated with mean canopy temperatures under moderate water stress, but not under severe stress (r = 0.31NS; r = 0.21NS). Infrared thermometry was judged well-suited to monitor the progression of crop water stress development, and to aid in classifying cultivars for relative drought avoidance. However, caution is necessary to assure proper application of the technique and in data interpretation
Water Policy Networks in the United States Heilman, John G.; Johnson, Gerald W.; Morris, John C. ...
Environmental politics,
12/1994, Letnik:
3, Številka:
4
Journal Article
Recenzirano
Evidence suggests that the US water sector is characterised by multiple arrays but not an overarching sector-wide arrangement encompassing all the major decision-making participants. The water policy ...field is marked by considerable fragmentation in structure, as well as by largely-uncoordinated policy. Several forces - including 'metapolicy' shifts, professionalism and alterations in professional dominance, and the tension between advocates of more integrated water policy-making (on the one hand) and interests favouring the status quo (on the other) - have influenced the dynamics of network changes over time. Evidence also suggests that the structure of network organisation in the water sector has impacts on policy outputs. The network idea adds to the understanding of policy change in the US case, but there are also reasons to expect network-based investigations to face limitations in explanatory power in the field of comparative policy.
Purpose: Most neuroblastomas initially respond to therapy but many relapse with chemoresistant disease. p53 mutations are rare in
diagnostic neuroblastomas, but we have previously reported ...inactivation of the p53/MDM2/p14 ARF pathway in 9 of 17 (53%) neuroblastoma cell lines established at relapse.
Hypothesis: Inactivation of the p53/MDM2/p14 ARF pathway develops during treatment and contributes to neuroblastoma relapse.
Methods: Eighty-four neuroblastomas were studied from 41 patients with relapsed neuroblastoma including 38 paired neuroblastomas at
different stages of therapy. p53 mutations were detected by automated sequencing, p14 ARF methylation and deletion by methylation-specific PCR and duplex PCR, respectively, and MDM2 amplification by fluorescent in situ hybridization.
Results: Abnormalities in the p53 pathway were identified in 20 of 41 (49%) cases. Downstream defects due to inactivating missense
p53 mutations were identified in 6 of 41 (15%) cases, 5 following chemotherapy and/or at relapse and 1 at diagnosis, postchemotherapy,
and relapse. The presence of a p53 mutation was independently prognostic for overall survival (hazard ratio, 3.4; 95% confidence
interval, 1.2–9.9; P = 0.02). Upstream defects were present in 35% of cases: MDM2 amplification in 3 cases, all at diagnosis and relapse and p14 ARF inactivation in 12 of 41 (29%) cases: 3 had p14 ARF methylation, 2 after chemotherapy, and 9 had homozygous deletions, 8 at diagnosis and relapse.
Conclusions: These results show that a high proportion of neuroblastomas which relapse have an abnormality in the p53 pathway. The majority
have upstream defects suggesting that agents which reactivate wild-type p53 would be beneficial, in contrast to those with
downstream defects in which p53-independent therapies are indicated. Clin Cancer Res; 16(4); 1108–18
Large-scale climate patterns influenced temperature and weather patterns around the globe in 2011. In particular, a moderate-to-strong La Nina at the beginning of the year dissipated during boreal ...spring but reemerged during fall. The phenomenon contributed to historical droughts in East Africa, the southern United States, and northern Mexico, as well the wettest two-year period (2010-11) on record for Australia, particularly remarkable as this follows a decade-long dry period. Precipitation patterns in South America were also influenced by La Nina. Heavy rain in Rio de Janeiro in January triggered the country's worst floods and landslides in Brazil's history. The 2011 combined average temperature across global land and ocean surfaces was the coolest since 2008, but was also among the 15 warmest years on record and above the 1981-2010 average. The global sea surface temperature cooled by 0.1 degrees C from 2010 to 2011, associated with cooling influences of La Nina. Global integrals of upper ocean heat content for 2011 were higher than for all prior years, demonstrating the Earth's dominant role of the oceans in the Earth's energy budget. In the upper atmosphere, tropical stratospheric temperatures were anomalously warm, while polar temperatures were anomalously cold. This led to large springtime stratospheric ozone reductions in polar latitudes in both hemispheres. Ozone concentrations in the Arctic stratosphere during March were the lowest for that period since satellite records began in 1979. An extensive, deep, and persistent ozone hole over the Antarctic in September indicates that the recovery to pre-1980 conditions is proceeding very slowly. Atmospheric carbon dioxide concentrations increased by 2.10 ppm in 2011, and exceeded 390 ppm for the first time since instrumental records began. Other greenhouse gases also continued to rise in concentration and the combined effect now represents a 30% increase in radiative forcing over a 1990 baseline. Most ozone depleting substances continued to fall. The global net ocean carbon dioxide uptake for the 2010 transition period from El Nino to La Nina, the most recent period for which analyzed data are available, was estimated to be 1.30 Pg C yr(-1), almost 12% below the 29-year long-term average. Relative to the long-term trend, global sea level dropped noticeably in mid-2010 and reached a local minimum in 2011. The drop has been linked to the La Nina conditions that prevailed throughout much of 2010-11. Global sea level increased sharply during the second half of 2011. Global tropical cyclone activity during 2011 was well-below average, with a total of 74 storms compared with the 1981-2010 average of 89. Similar to 2010, the North Atlantic was the only basin that experienced above-normal activity. For the first year since the widespread introduction of the Dvorak intensity-estimation method in the 1980s, only three tropical cyclones reached Category 5 intensity level-all in the Northwest Pacific basin. The Arctic continued to warm at about twice the rate compared with lower latitudes. Below-normal summer snowfall, a decreasing trend in surface albedo, and above-average surface and upper air temperatures resulted in a continued pattern of extreme surface melting, and net snow and ice loss on the Greenland ice sheet. Warmer-than-normal temperatures over the Eurasian Arctic in spring resulted in a new record-low June snow cover extent and spring snow cover duration in this region. In the Canadian Arctic, the mass loss from glaciers and ice caps was the greatest since GRACE measurements began in 2002, continuing a negative trend that began in 1987. New record high temperatures occurred at 20 m below the land surface at all permafrost observatories on the North Slope of Alaska, where measurements began in the late 1970s. Arctic sea ice extent in September 2011 was the second-lowest on record, while the extent of old ice (four and five years) reached a new record minimum that was just 19% of normal. On the opposite pole, austral winter and spring temperatures were more than 3 degrees C above normal over much of the Antarctic continent. However, winter temperatures were below normal in the northern Antarctic Peninsula, which continued the downward trend there during the last 15 years. In summer, an all-time record high temperature of -12.3 degrees C was set at the South Pole station on 25 December, exceeding the previous record by more than a full degree. Antarctic sea ice extent anomalies increased steadily through much of the year, from briefly setting a record low in April, to well above average in December. The latter trend reflects the dispersive effects of low pressure on sea ice and the generally cool conditions around the Antarctic perimeter.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis. The onset of hydronephrosis following unilateral ureteral obstruction is associated with the ...induced expression of RNA and proteins encoded by the SGP-2 gene. SGP-2 expression has been shown to demarcate mammalian cells undergoing apoptosis. Using in situ hybridization, the cellular localization of SGP-2 expression in the obstructed kidney was determined as a means to study the various phases involved in the progression of hydronephrosis. Within 30 minutes of obstruction, SGP-2 mRNA expression was localized to the adventitial layers of the hilar arteries and intrarenal arterioles. Increasing time of obstruction resulted in the notable absence or depletion of this layer. In addition, the pattern of SGP-2 expression changed with time to the collecting ducts and distal tubules. This study identifies the vascular support tissue of the kidney as the initial site of reaction and potential cell death following ureteral obstruction. We believe that this observation may be of importance in explaining the early alterations in blood flow associated with hydronephrosis.
Public Administration: Vitality and Perplexity Toole, Laurence J. O'; Buechner, John C.; Koprowski, Eugene J. ...
Public Administration Review,
09/1978, Letnik:
38, Številka:
5
Book Review, Journal Article
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