Future change in extreme precipitation in East Asian spring and Mei-yu seasons in two high-resolution AGCMs

Precipitation in the spring and Mei-yu seasons, the main planting and growing period in East Asia, is crucial to water resource management. Changes in spring and Mei-yu extreme precipitation under global warming are evaluated based on two sets of high-resolution simulations with various warming pattern of sea surface temperature (SST'spa). In the spring season, extreme precipitation exhibits larger enhancements over the northern flank of the present-day prevailing rainy region and a tendency of increased occurrence and enhanced intensity in the probability distribution. These changes imply a northward extension of future spring rainband. Although the mean precipitation shows minor change, enhanced precipitation intensity, less total rainfall occurrence, and prolonged consecutive dry days suggest a more challenging water resource management in the warmer climate. The projected enhancement in precipitation intensity is robust compared with the internal variability related to initial conditions (σˆint) and the uncertainty caused by SST'spa (σˆΔSST). In the Mei-yu season, extreme precipitation strengthens and becomes more frequent over the present-day prevailing rainband region. The thermodynamic component of moisture flux predominantly contributes to the changes in the spring season. In the Mei-yu season, both the thermodynamic and dynamic components of moisture flux enhance the moisture transport and intensify the extreme precipitation from southern China to northeast Asia. Compared with spring season, projecting future Mei-yu precipitation is more challenging because of its higher uncertainty associated with 1) the σˆint and σˆΔSST embedded in the projections and 2) the model characteristics of present-day climatology that determines the spatial distribution of precipitation enhancement.publishedVersio

The role of autologous bone graft in surgical treatment of hypertrophic nonunion of midshaft clavicle fractures

AbstractBackgroundThis study was conducted to evaluate the results of treating hypertrophic nonunion of mid-shaft clavicle fracture with a limited contact dynamic compression plate (LC-DCP) without autologous cancellous bone graft.MethodsFrom 1995 to 2008, 51 cases of hypertrophic nonunion of mid-shaft clavicle fracture were managed with open reduction and internal fixation by LC-DCP without bone graft involvement. Of these 51 cases, 30 had nonunion after failure of initial surgical treatment (Group 1), and 21 had nonunion after failure of conservative treatment (Group 2). Preoperative and postoperative case management were the same for both groups, with the average follow-up period being 20.4 months (range 18–36). Our study evaluated the radiographic results and functional outcomes of these cases according to the quick disability of arm, shoulder, and hand score.ResultsAll 51 cases resulted in uneventful unions. There was no statistically significant difference between the two groups regarding patient demography, cause of injury, preoperative and postoperative functional scores, length of operation, union time, and duration of hospitalization (p>0.05).ConclusionLC-DCP fixation is an effective method for treating hypertrophic nonunion of mid-shaft clavicle fracture. Local bone graft is sufficient to achieve necessary union, and autologous bone graft from other sites of the body appears unnecessary

Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model. Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions. Turbidity was identified as the optical density measured using spectroscopy at 405 nm. We also determined the in vivo effects of catalin on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) was applied to analyze the integrity of crystallin samples. Results: PRX at 1,000 μM significantly delayed UVC-induced turbidity formation compared to controls after 4 h of UVC exposure (p<0.05), but not in groups incubated with PRX concentrations of <1,000 μM. Results were further confirmed by SDS–PAGE. The absolute γ-crystallin turbidity induced by 4 h of UVC exposure was ameliorated in the presence of catalin equivalent to 1~100 μM PRX in a concentration-dependent manner. Samples with catalin-formulated vehicle only (CataV) and those containing PRX equivalent to 100 μM had a similar protective effect after 4 h of UVC exposure compared to the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 μM significantly delayed 10 mM selenite- and calcium-induced turbidity formation compared to controls on days 0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 μM PRX) had an initial protective effect against selenite-induced lens protein turbidity on day 1 (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically decreased the mean cataract scores in selenite-induced cataract rats on post-induction day 3 compared to the controls (1.3±0.2 versus 2.4±0.4; p<0.05). However, catalin (equivalent to up to 100 μM PRX) did not inhibit calpain-induced proteolysis activated by calcium, and neither did 100 μM PRX. Conclusions: PRX at micromolar levels ameliorated selenite- and calcium-induced lens protein turbidity but required millimolar levels to protect against UVC irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins by catalin at micromolar concentrations may have been a result of the catalin-formulated vehicle. Transient protection by catalin against selenite-induced turbidity of crystallin solutions in vitro was supported by the ameliorated cataract scores in the early stage of cataractogenesis in vivo by subcutaneously administered catalin. PRX could not inhibit calpain-induced proteolysis activated by calcium or catalin itself, and may be detrimental to crystallins under UVB exposure. Further studies on formulation modifications of catalin and recommended doses of PRX to optimize clinical efficacy by cataract type are warranted

Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (−log10(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (−log10(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population

Activation of Thromboxane A2 Receptor (TP) Increases the Expression of Monocyte Chemoattractant Protein -1 (MCP-1)/Chemokine (C-C motif) Ligand 2 (CCL2) and Recruits Macrophages to Promote Invasion of Lung Cancer Cells

Thromboxane synthase (TXAS) and thromboxane A2 receptor (TP), two critical components for thromboxane A2 (TXA2) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA2 promotes these processes are still unclear. Here we show that TXA2 mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor α isoform (A549-TPα). The induction of MCP-1 was also found in other lung cancer cells H157 and H460 that express relatively high levels of endogenous TP. Using specific inhibitors of several signaling molecules and promoter/luciferase assay, we identified that transcription factor SP1 mediates I-BOP-induced MCP-1 expression. Furthermore, supernatants from I-BOP-treated A549-TPα cells enhanced MCP-1-dependent migration of RAW 264.7 macrophages. Moreover, co-culture of A549 cells with RAW 264.7 macrophages induced expression of MMPs, VEGF and MCP-1 genes, and increased the invasive potential in A549 cells. These findings suggest that TXA2 may stimulate invasion of cancer cells through MCP-1-mediated macrophage recruitment

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Future change in extreme precipitation in East Asian spring and Mei-yu seasons in two high-resolution AGCMs

Precipitation in the spring and Mei-yu seasons, the main planting and growing period in East Asia, is crucial to water resource management. Changes in spring and Mei-yu extreme precipitation under global warming are evaluated based on two sets of high-resolution simulations with various warming pattern of sea surface temperature (SST'spa). In the spring season, extreme precipitation exhibits larger enhancements over the northern flank of the present-day prevailing rainy region and a tendency of increased occurrence and enhanced intensity in the probability distribution. These changes imply a northward extension of future spring rainband. Although the mean precipitation shows minor change, enhanced precipitation intensity, less total rainfall occurrence, and prolonged consecutive dry days suggest a more challenging water resource management in the warmer climate. The projected enhancement in precipitation intensity is robust compared with the internal variability related to initial conditions (σˆint) and the uncertainty caused by SST'spa (σˆΔSST). In the Mei-yu season, extreme precipitation strengthens and becomes more frequent over the present-day prevailing rainband region. The thermodynamic component of moisture flux predominantly contributes to the changes in the spring season. In the Mei-yu season, both the thermodynamic and dynamic components of moisture flux enhance the moisture transport and intensify the extreme precipitation from southern China to northeast Asia. Compared with spring season, projecting future Mei-yu precipitation is more challenging because of its higher uncertainty associated with 1) the σˆint and σˆΔSST embedded in the projections and 2) the model characteristics of present-day climatology that determines the spatial distribution of precipitation enhancement