Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway

The result of our previous study has shown that the K-ras mutant (pK568MRSV) transfected human adrenocortical cells can significantly increase cortisol production and independently cause cell transformation. The aim of this study is to investigate the effect of the active K-ras oncogene on the cortisol production in normal human adrenocortical cells. First we used isopropyl thiogalactoside to induce the inducible mutant K-ras expression plasmid, pK568MRSV, in the stable transfected human adrenocortical cells. The result showed that the increase of RasGTP levels in transfected cells was time-dependent after isopropyl thiogalactoside induction. Additionally, results from Western blot analysis revealed significant elevation in phosphorylation of c-Raf-1 and Mitogen-activated protein kinase. We also detected the levels of mRNA encoding Cholesterol side-chain cleavage enzyme (P450SCC), 17α-Hydroxylase/17,20-lyase (P450c17) and 3β-Hydroxysteroid dehydrogenase (3βHSD) were increased in human adrenocortical cells transfected with mutant K-ras after IPTG treatment. The increase of mRNA amount in P450scc P450c17 and 3βHSD and the elevation of cortisol level were inhibited with a pretreatment of PD098059, a specific extracellular signal-regulated kinase inhibitor. In our previous report, we proved that lovastatin, a pharmacological inhibitor of p21ras function, also reversed the increase of cortisol level in mutant K-ras stably transfected human adrenocortical cells. Taken together, these findings proved that the active mutant Ras enhanced not only cell proliferation but also steroidogenesis in steroidogenic phenotype cells by activating Raf-MEK-MAPK related signal transduction pathway. Therefore, we believe that K-ras mutants influence regulation of steroidogenesis in adrenocortical cells through RAF-MEK-MAPK pathway

Predation and the Maintenance of Color Polymorphism in a Habitat Specialist Squamate

Multiple studies have addressed the mechanisms maintaining polymorphism within a population. However, several examples exist where species inhabiting diverse habitats exhibit local population-specific polymorphism. Numerous explanations have been proposed for the maintenance of geographic variation in color patterns. For example, spatial variation in patterns of selection or limited gene flow can cause entire populations to become fixed for a single morph, resulting in separate populations of the same species exhibiting separate and distinct color morphs. The mottled rock rattlesnake (Crotalus lepidus lepidus) is a montane species that exhibits among-population color polymorphism that correlates with substrate color. Habitat substrate in the eastern part of its range is composed primarily of light colored limestone and snakes have light dorsal coloration, whereas in the western region the substrate is primarily dark and snakes exhibit dark dorsal coloration. We hypothesized that predation on high contrast color and blotched patterns maintain these distinct color morphs. To test this we performed a predation experiment in the wild by deploying model snakes at 12 sites evenly distributed within each of the two regions where the different morphs are found. We employed a 2×2 factorial design that included two color and two blotched treatments. Our results showed that models contrasting with substrate coloration suffered significantly more avian attacks relative to models mimicking substrates. Predation attempts on blotched models were similar in each substrate type. These results support the hypothesis that color pattern is maintained by selective predation

Parametric design optimisation of proximal humerus plates based on finite element method

Optimal treatment of proximal humerus fractures remains controversial. Locking plates offer theoretical advantages but are associated with complications in the clinic. This study aimed to perform parametric design optimisation of proximal humerus plates to enhance their mechanical performance. A finite element (FE) model was developed that simulated a two-part proximal humerus fracture that had been treated with a Spatial Subchondral Support (S3) plate and subjected to varus bending. The FE model was validated against in vitro biomechanical test results. The predicted load required to apply 5 mm cantilever varus bending was only 0.728% lower. The FE model was then used to conduct a parametric optimisation study to determine the orientations of inferomedial plate screws that would yield minimum fracture gap change (i.e. optimal stability). The feasible design space was automatically identified by imposing clinically relevant constraints, and the creation process of each FE model for the design optimisation was automated. Consequently, 538 FE models were generated, from which the obtained optimal model had 4.686% lower fracture gap change (0.156 mm) than that of the manufacturer’s standard plate. Whereas its screws were oriented towards the inferomedial region and within the range of neck-shaft angle of a healthy subject. The methodology presented in this study promises future applications in patient-specific design optimisation of implants for other regions of the human body

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System

<p>Abstract</p> <p>Background</p> <p>While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair.</p> <p>Methods</p> <p>A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors.</p> <p>Results</p> <p>Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis.</p> <p>Conclusions</p> <p>Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not.</p

Dissolved inorganic radiocarbon in the North Pacific Ocean and Sargasso Sea

We present radiocarbon measurements of dissolved inorganic carbon (DIC) in depth profiles from reoccupations of our central North Pacific Ocean and Sargasso Sea (SS) sites. From 1985 to 1999, an increase in Delta C-14 values of 6-17 parts per thousand was measured between 1150 and 2400m depth in the North Central Pacific. Natural changes in deep circulation are likely responsible for variability of Delta C-14 signatures in the deep ocean, though we cannot rule out the presence of bomb C-14 at this depth range. Bomb C-14 had increased in the deep SS from 1989 to 2000; this is the result of southward transport of North Atlantic Deep Water (NADW) to this site. (c) 2007 Elsevier Ltd. All rights reserved.X1114sciescopu

Variability of monthly radiocarbon during the 1760s in corals from the Galapagos Islands

Radiocarbon (Delta(14)C) measurements of monthly samples from a Galapagos surface coral are among the first data sets from the new Keck Carbon Cycle Accelerator Mass Spectrometry laboratory at the University of Califomia, Irvine. An average Delta(14)C value of -62parts per thousand is obtained for 144 measurements of samples from monthly coral bands that lived from about AD 1760-1771 (+/-6 yr). High Delta(14)C values were found during January through March, when upwelling was weak or absent at the Galapagos Islands. Low Delta(14)C values were obtained mid-year during strong upwelling. The average seasonal variability of Delta(14)C was 15-25parts per thousand, which is greater than that at other tropical and subtropical locations in the Pacific Ocean because of intense seasonal upwelling at this site. Periods of sustained high Delta(14)C values were found during 1762-1763 and 1766. A spectral analysis revealed that the spectral density for the Delta(14)C data displays most of its variance at the 5-yr cycle, which is reflective of El Nino periodicity during the 20th century.X1118sciescopu

Variability of radiocarbon during the 1760s in monthly corals from the Galapagos Islands

. Radiocarbon (∆14C) measurements of monthly samples from a Galapagos surface coral are among the first data sets from the new Keck Carbon Cycle Accelerator Mass Spectrometry laboratory at the University of California, Irvine. An average ∆14C value of –62‰ is obtained for 144 measurements of samples from monthly coral bands that lived from about AD 1760–1771 (±6 yr). High ∆14C values were found during January through March, when upwelling was weak or absent at the Galapagos Islands. Low ∆14C values were obtained mid-year during strong upwelling. The average seasonal variability of ∆14C was 15–25‰, which is greater than that at other tropical and subtropical locations in the Pacific Ocean because of intense seasonal upwelling at this site. Periods of sustained high ∆14C values were found during 1762–1763 and 1766. A spectral analysis revealed that the spectral density for the ∆14C data displays most of its variance at the 5-yr cycle, which is reflective of El Niño periodicity during the 20th century

Variability of radiocarbon during the 1760s in monthly corals from the Galapagos Islands

. Radiocarbon (∆14C) measurements of monthly samples from a Galapagos surface coral are among the first data sets from the new Keck Carbon Cycle Accelerator Mass Spectrometry laboratory at the University of California, Irvine. An average ∆14C value of –62‰ is obtained for 144 measurements of samples from monthly coral bands that lived from about AD 1760–1771 (±6 yr). High ∆14C values were found during January through March, when upwelling was weak or absent at the Galapagos Islands. Low ∆14C values were obtained mid-year during strong upwelling. The average seasonal variability of ∆14C was 15–25‰, which is greater than that at other tropical and subtropical locations in the Pacific Ocean because of intense seasonal upwelling at this site. Periods of sustained high ∆14C values were found during 1762–1763 and 1766. A spectral analysis revealed that the spectral density for the ∆14C data displays most of its variance at the 5-yr cycle, which is reflective of El Niño periodicity during the 20th century