Precipitation regulates the responses of xylem phenology of two dominant tree species to temperature in arid and semi-arid forest of the southern Altai Mountains.

Arid and semi-arid forests are important carbon sinks, with implications for the global carbon balance. However, the impacts of climate warming on the growth of arid and semi-arid forest tree species and ecosystem carbon sink dynamics remain uncertain because the effects of the complex interactions between precipitation and temperature on xylem phenology are not clearly understood. Here, we monitored xylem formation over two years in two dominant tree species (Siberian larch, Larix sibirica Ledeb.; Siberian spruce, Picea obovata Ledeb.) along the arid and semi-arid southern Altai Mountains of Central Asia. We determined that temperature interaction with precipitation plays a key role in regulating xylem phenology of these two species, with differences between species. Under rising mean annual temperatures, the growth of L. sibirica advanced as the onset of xylem formation was not limited by early season water availability. However, the earlier cessation of cell enlargement, likely due to legacy effects, compensated for such advancement. In contrast, water stress constrained the advancement of xylem formation under rising temperatures in P. obovata. Nevertheless, water stress was seemingly relieved later in the growing season and consequently did not lead to the earlier cessation of xylem formation. Our results demonstrate that precipitation drives species-specific response to rising temperatures and thus is a key driver of growing season length and carbon sink dynamics in arid and semi-arid forests under climate warming. Integrating the effects of temperature and precipitation on xylem phenology in climate models may improve estimates of climate-carbon feedback in arid and semi-arid forests under future warming scenarios.

Tropical volcanoes synchronize eastern Canada with Northern Hemisphere millennial temperature variability.

Although global and Northern Hemisphere temperature reconstructions are coherent with climate model simulations over the last millennium, reconstructed temperatures tend to diverge from simulations at smaller spatial scales. Yet, it remains unclear to what extent these regional peculiarities reflect region-specific internal climate variability or inadequate proxy coverage and quality. Here, we present a high-quality, millennial-long summer temperature reconstruction for northeastern North America, based on maximum latewood density, the most temperature-sensitive tree-ring proxy. Our reconstruction shows that a large majority (31 out of 44) of the coldest extremes can be attributed to explosive volcanic eruptions, with more persistent cooling following large tropical than extratropical events. These forced climate variations synchronize regional summer temperatures with hemispheric reconstructions and simulations at the multidecadal time scale. Our study highlights that tropical volcanism is the major driver of multidecadal temperature variations across spatial scales.

Discrete Element Modeling of Instability Mechanisms of Unbound Permeable Aggregate Base Materials in Triaxial Compression.

Unbound permeable aggregate base (UPAB) materials with strong load-transmitting skeleton yet adequate inter-connected pores are desired for use in the sponge-city initiative. However, the micro-scale fabric evolution and instability mechanism of macroscopic strength behavior of such UPAB materials still remain unclear. In this study, virtual monotonic triaxial compression tests were conducted by using the discrete element method (DEM) modeling approach on specimens with different gradations quantified by the parameter of gravel-to-sand ratio (G/S). The realistic aggregate particle shape and inter-particle contact behavior were properly considered in the DEM model. The micromechanical mechanisms of the shearing failure of such UPAB materials and their evolution characteristics with G/S values were disclosed from contact force chains, microstructures, and particle motion. It was found that the proportion of rotating particles in the specimens decreased and the proportion of relative sliding between particles increased as the content of fine particles decreased. The plastic yielding of the specimens originated from the failure of contact force chains and the occurrence of the relative motion between particles, while the final instability was manifested by the large-scale relative motion among particles along the failure plane (i.e., changes in the internal particle topology). By comparing the macroscopic strength, microstructure evolution, and particle motion characteristics of the specimens with different G/S values, it was found that the specimens with G/S value of 1.8 performed the best, and that the G/S value of 1.8 could be regarded as the threshold for separating floating dense and skeletal gap type packing structures. The variation of Euler angles of rotating particles was significantly reduced in the particle size range of 4.75 mm to 9.50 mm, indicating that this size range separates most of the particles from rolling and sliding. Since particle rolling and sliding behavior are directly related to shear strength, this validates the rationality of the parameter G/S for controlling and optimizing gradations from the perspective of particle movement. The findings could provide theoretical basis and technical guidance for the effective design and efficient utilization of UPAB materials.

[Radial growth of dominant coniferous species and their responses to climate changes in the Altay Mountains, China]. / é˜¿å°”æ³°å±±ä¸»è¦é’ˆå¶æ ‘ç§æ ‘æœ¨å¾„å‘ç”Ÿé•¿åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Based on the standard method of dendrochronology, we examined the tree-ring width index of two dominant tree species in the Altay Mountains, China, including Picea obovata and Larix sibirica. We analyzed the basal area increments (BAI) of those two species and the relationships between their radial growth and the climatic factors, which were compared in similar habitats. The results showed that the BAI of P. obovata was greater than L. sibirica, but the radial growth rate of L. sibirica was greater. In recent 60 years, the radial growth of P. obovata negatively correlated with high temperature in the fast growing stage of previous year, while the high temperature in June of current year promoted the radial growth of L. sibirica. There was a significantly negative correlation between radial growth of L. sibirica with temperature in January of current year. The sensitivity of tree growth to climate showed an obvious increase after an abrupt climate change under the background of recent warming and wetting trend in mid-1980s. Results of the moving correlation analysis showed that the response of the radial growth of P. obovata and L. sibirica to temperature and precipitation were enhanced under the background of climate change in the study area.

[Tree-ring reconstruction of March-August drought variability over the past 567 years in the Yajiang region of West Sichuan Plateau, China]. / å·è¥¿é› æ±Ÿåœ°åŒºè¿‡åŽ»567å¹´3­8æœˆå¹²æ—±å˜åŒ–çš„æ ‘è½®é‡å»º.

We constructed standard tree-ring-width chronology of Picea likiangensis var. rubescens for the Larima sampling site in the Ganzi Prefecture, Sichuan Province, by the single-free detren-ding method. The results showed that there was significant and positive correlation between the tree-ring chronology and March-August 1-month scale standardized precipitation and evapotranspiration index (SPEI1) of Yajiang region. The variation of the March-August SPEI1 sequence for 1942-2008 was reconstructed based on the current and last year sequences of the tree-ring chronology, with an explained variation of 42.8%. The newly reconstructed series mainly represented the variation of SPEI1 in the low-frequency domain over the historical period. Three wet periods were found in 1442-1465, 1516-1601 and 1836-2008, while the two intervals were dry periods for the March-August SPEI1 reconstruction in the Yajiang region of West Sichuan Plateau. There was a significant drying trend in 1456-1762 for the reconstructed sequence, a significant wetting trend in 1455-1762, while the wetting trend was the most significant in 1959-2008. Mutation test showed that the sudden changes from dry to wet for the March-August SPEI1 reconstructions occurred in 1512, 1733, 1767, 1831, 1941, 1957 and 1975, while that in 1684 and 1961 was the opposite. The comparison with surrounding region showed a good coherence of variations in the low-frequency domain among the SPEI1 reconstruction for the Yajiang region, the annual precipitation reconstruction for the northeastern Tibetan Plateau, and the SPEI05 reconstruction for the northern slope of the eastern Qilian Mountains. The reconstructed sequence well represented the variation of the March-August SPEI1 in the northeastern Tibetan Plateau and the southern Qinhai Province.

SET Domain-Containing Protein 5 Enhances the Cell Stemness of Non-Small Cell Lung Cancer via the PI3K/Akt/mTOR Pathway.

BACKGROUND: SET domain-containing protein 5 (SETD5) could promote non-small cell lung cancer (NS-CLC) cell invasion, but the effect of SETD5 on NSCLC cell stemness characteristics is unknown. Thus we attempted to evaluate the effect of SETD5 on NSCLC stemness and its mechanism. METHODS: The expressions of SETD5 and stemness-related genes (SOX2, OCT4, ABCG2) were detected in NSCLC tissues by immunohistochemistry assay, qRT-PCR, and western blot. A SETD5 knockdown cell model was constructed by siRNA transfection in A549 and H1299 cells. A CCK8 assay was used to examine cell viability. A sphere-forming assay and side population cell assay were conducted to measure the cancer cell stem properties. The cells with SETD5 deletion were treated with an activator of AKT, SC79, and the protein expressions of Akt, p-Akt, mTOR, and p-mTOR were assessed. RESULTS: SETD5 and cancer stem-related genes SOX2, OCT4, and ABCG2 were co-expressed and co-localized in tumor tissues and cell lines of NSCLC. The deletion of SETD5 significantly reduced the cell viability, cancer stem properties, and activity of the PI3K/Akt/mTOR pathway, while the decreased SETD5-induced effects were partially restored with SC79 treatment. CONCLUSION: In this study, SETD5 promoted the cancer stem cell property of NSCLC through mitigating the activation of the PI3K/Akt/mTOR pathway, suggesting a candidate target role for SETD5 in NSCLC treatment.

Characteristics of tree-ring density at different stem heights and their climatic responses.

Taking windfall woods of Picea schrenkiana in the southern mountainous area of the Ili Prefecture as the research object, tree-ring density chronologies were developed from the discs for maximum density (MXD), minimum density (MID), mean earlywood density (EWD), and mean latewood density (LWD) at five different stem heights (1.3, 5, 10, 15 and 20 m) to examine the climatic responses of tree-ring density by correlation analysis with local meteorological data. The results showed that there was a good coherence among the four types of tree-ring density chronologies for the same stem height, which was relatively significant for the data from 10, 15 and 20 m. The LWD had good coherence among different stem heights, while the climatic responses of tree-ring density at different stem heights varied. The MXD and LWD at 15 m were sensitive to mean tempera-ture from July to September in the previous year and from May to September in the current year. It might underestimate the response of P. schrenkiana to temperature if we sample tree-ring at 1.3 m.

Pre-culture Sudan Black B treatment suppresses autofluorescence signals emitted from polymer tissue scaffolds.

In tissue engineering, autofluorescence of polymer scaffolds often lowers the image contrast, making it difficult to examine cells and subcellular structures. Treating the scaffold materials with Sudan Black B (SBB) after cell fixation can effectively suppress autofluorescence, but this approach is not conducive to live cell imaging. Post-culture SBB treatment also disrupts intracellular structures and leads to reduced fluorescence intensity of the targets of interest. In this study, we introduce pre-culture SBB treatment to suppress autofluorescence, where SBB is applied to polymeric scaffold materials before cell seeding. The results show that the autofluorescence signals emitted from polycaprolactone (PCL) scaffolds in three commonly used fluorescence channels effectively decrease without diminishing the fluorescence signals emitted from the cells. The pre-culture SBB treatment does not significantly affect cell viability. The autofluorescence suppressive effect does not substantially diminish during the culturing period up to 28 days. The results also show that cell migration, proliferation, and myogenic differentiation in pre-culture SBB-treated groups do not exhibit statistical difference from the non-treated groups. As such, this approach greatly improves the fluorescence image quality for examining live cell behaviors and dynamics while the cells are cultured within autofluorescent polymer scaffolds.

Validation of research trajectory 1 of an Exposome framework: Exposure to benzo(a)pyrene confers enhanced susceptibility to bacterial infection.

The exposome provides a framework for understanding elucidation of an uncharacterized molecular mechanism conferring enhanced susceptibility of macrophage membranes to bacterial infection after exposure to the environmental contaminant benzo(a)pyrene, [B(a)P]. The fundamental requirement in activation of macrophage effector functions is the binding of immunoglobulins to Fc receptors. FcγRIIa (CD32a), a member of the Fc family of immunoreceptors with low affinity for immunoglobulin G, has been reported to bind preferentially to IgG within lipid rafts. Previous research suggested that exposure to B(a)P suppressed macrophage effector functions but the molecular mechanisms remain elusive. The goal of this study was to elucidate the mechanism(s) of B(a)P-exposure induced suppression of macrophage function by examining the resultant effects of exposure-induced insult on CD32-lipid raft interactions in the regulation of IgG binding to CD32. The results demonstrate that exposure of macrophages to B(a)P alters lipid raft integrity by decreasing membrane cholesterol 25% while increasing CD32 into non-lipid raft fractions. This robust diminution in membrane cholesterol and 30% exclusion of CD32 from lipid rafts causes a significant reduction in CD32-mediated IgG binding to suppress essential macrophage effector functions. Such exposures across the lifespan would have the potential to induce immunosuppressive endophenotypes in vulnerable populations.

Precipitation reconstruction for the northwestern Chinese Altay since 1760 indicates the drought signals of the northern part of inner Asia.

Based on the significant positive correlations between the regional tree-ring width chronology and local climate data, the total precipitation of the previous July to the current June was reconstructed since AD 1760 for the northwestern Chinese Altay. The reconstruction model accounts for 40.7 % of the actual precipitation variance during the calibration period from 1959 to 2013. Wet conditions prevailed during the periods 1764-1777, 1784-1791, 1795-1805, 1829-1835, 1838-1846, 1850-1862, 1867-1872, 1907-1916, 1926-1931, 1935-1943, 1956-1961, 1968-1973, 1984-1997, and 2002-2006. Dry episodes occurred during 1760-1763, 1778-1783, 1792-1794, 1806-1828, 1836-1837, 1847-1849, 1863-1866, 1873-1906, 1917-1925, 1932-1934, 1944-1955, 1962-1967, 1974-1983, 1998-2001, and 2007-2012. The spectral analysis of the precipitation reconstruction shows the existence of some cycles (15.3, 4.5, 3.1, 2.7, and 2.1 years). The significant correlations with the gridded precipitation dataset revealed that the precipitation reconstruction represents the precipitation variation for a large area of the northern part of inner Asia. A comparison with the precipitation reconstruction from the southern Chinese Altay shows the high level of confidence for the precipitation reconstruction for the northwestern Chinese Altay. Precipitation variation of the northwestern Chinese Altay is positively correlated with sea surface temperatures in tropical oceans, suggesting a possible linkage of the precipitation variation of the northwestern Chinese Altay to the El Niño-Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO). The synoptic climatology analysis reveals that there is the relationship between anomalous atmospheric circulation and extreme climate events in the northwestern Chinese Altay.

Revealing Behavioral Learning Deficit Phenotypes Subsequent to In Utero Exposure to Benzo(a)pyrene.

To characterize behavioral deficits in pre-adolescent offspring exposed in utero to Benzo(a)pyrene [B(a)P], timed-pregnant Long Evans Hooded rats were treated with B(a)P (150, 300, 600, and 1200 µg/kg BW) or peanut oil (vehicle) on E14, 15, 16, and 17. Following birth, during the pre-weaning period, B(a)P metabolites were examined in plasma and whole brain or cerebral cortex from exposed and control offspring. Tissue concentrations of B(a)P metabolites were (1) dose-dependent and (2) followed a time-dependence for elimination with ∼60% reduction by PND5 in the 1200 µg/kg BW experimental group. Spatial discrimination-reversal learning was utilized to evaluate potential behavioral neurotoxicity in P40-P60 offspring. Late-adolescent offspring exposed in utero to 600 and 1200 µg/kg BW were indistinguishable from their control counterparts for ability to acquire an original discrimination (OD) and reach criterion. However, a dose-dependent effect of in utero B(a)P-exposure was evident upon a discrimination reversal as exposed offspring perseverated on the previously correct response. This newly characterized behavioral deficit phenotype for the first reversal was not apparent in either the (1) OD or (2) subsequent reversal sessions relative to the respective control offspring. Furthermore, the expression of activity related-cytoskeletal-associated protein (Arc), an experience-dependent cortical protein marker known to be up-regulated in response to acquisition of a novel behavior, was greater in B(a)P-exposed offspring included in the spatial discrimination cohort versus home cage controls. Collectively, these findings support the hypothesis that in utero exposure to B(a)P during critical windows of development representing peak periods of neurogenesis results in behavioral deficits in later life.

Application of Citizen Science Risk Communication Tools in a Vulnerable Urban Community.

A public participatory geographical information systems (PPGIS) demographic, environmental, socioeconomic, health status portal was developed for the Stambaugh-Elwood (SE) community in Columbus, OH. We hypothesized that soil at SE residences would have metal concentrations above natural background levels. Three aims were developed that allowed testing of this hypothesis. Aim 1 focused on establishing partnerships between academia, state agencies and communities to assist in the development of a community voice. Aim 2 was to design and conduct soil sampling for residents of the SE community. Aim 3 was to utilize our interactive, customized portal as a risk communication tool by allowing residents to educate themselves as to the potential risks from industrial sources in close proximity to their community. Multiple comparisons of means were used to determine differences in soil element concentration by sampling location at p < 0.05. The results demonstrated that eight metals (As, Cd, Cu, Pb, Mo, Se, Tl, Zn) occurred at statistically-significantly greater levels than natural background levels, but most were below risk-based residential soil screening levels. Results were conveyed to residents via an educational, risk-communication informational card. This study demonstrates that community-led coalitions in collaboration with academic teams and state agencies can effectively address environmental concerns.

Preparation and optical properties of YH2:Er2+ and Y2O3:Er3+ nanoparticles.

The rare earth hydride nanoparticles have been prepared successfully by a novel method of hydrogen plasma-metal reaction. The YH2:Er2+ nanoparticles of 40-50 nm were polycrystalline and in hexagonal shape. The Y2O3:Er3+ nanoparticles were fabricated by annealing the hydride nanoparticles in air at 300, 500 and 700 degrees C, respectively. The influence of the sintering temperature on the size, crystal structure and optical properties of these nanoparticle samples were investigated. After annealing, the Y2O3:Er3+ nanoparticles became single crystalline and spherical shape, and the mean particle size of these particles did not change apparently upon the annealing temperature up to 700 degrees C. With the increase of the annealing temperature, the absorption intensity of YH2 in the Fourier transform infrared spectroscopy spectra decreased and the peak position moved to high-frequency, whereas the absorption intensity of Y2O3 was enhanced. The intensity of the near-IR fluorescence spectra of the Y2O3:Er3+ nanoparticles increased remarkably with the increase of the annealing temperature from 300 to 700 degrees C. The Y2O3:Er3+ sample sintered at 700 degrees C exhibited a strong photoluminescent intensity at the wavelength of about 1535 nm, with a narrow full width of 6 nm at the half maximum. This makes the Y2O3:Er3+ nanoparticles promising for the applications in the optical communication devices.

Expression of centrosomal tubulins associated with DNA ploidy in breast premalignant lesions and carcinoma.

The centrosome plays an essential role in chromosomal segregation during cell division. Centrosome dysfunction might lead to aneuploidy and chromosomal instability. Invasive breast tumors with centrosome amplification often show aneuploidy. Flow cytometry (FCM) was used to examine the aneuploidy rate in 30 cases of each of the following seven tissue types: normal breast tissue, usual ductal hyperplasia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ, high-grade ductal carcinoma in situ, low-grade invasive ductal carcinoma, and high-grade invasive ductal carcinoma. Centrosomal α, γ-tubulin expression was examined by FCM immunofluorescence and compared between diploid and aneuploid cells. The aneuploidy rate was 0, 6.7%, 26.7%, 30.0%, 46.7%, 56.7%, and 86.7%, respectively, in the seven tissue types. The percentage of cells expressing α- and γ-tubulins was significantly different between the seven groups, and the positive rate of α- and γ-tubulin expression in ADH, DCIS and IDC was higher than that in NBT and UDH. The percentage of cells expressing α- and γ-tubulins in the diploid state was significantly lower than that in the aneuploid state. Expression of centrosomal α- and γ-tubulins seems to be associated with DNA ploidy in breast premalignant lesions and carcinoma during the progression of breast cancer.

Evidence of associations of APOBEC3B gene deletion with susceptibility to persistent HBV infection and hepatocellular carcinoma.

APOBEC3s are a family of cytidine deaminases involved in innate cellular immunity against virus including hepatitis B virus (HBV). A germline deletion across APOBEC3A and APOBEC3B (A3B) genes results in complete removal of the A3B coding region and destroys A3B expression. To determine whether this deletion affects susceptibility to HBV infection and HBV-related hepatocellular carcinoma (HCC), A3B genotypes were analyzed in 1124 individuals with HCC, 510 individuals with persistent HBV infection and 826 healthy controls and the association was estimated by odds ratio (OR) and 95% confidence interval (CI) computed by logistic regression. We also examined the effects of A3B on HBV genome hypermutation and replication in HCC cells. We observed a significantly higher frequency of the A3B deletion allele in persistent HBV carriers (33.3%; P = 0.0015) and HCC patients (37.9%; P = 1.28 × 10(-11)) compared with that in controls (27.5%). An increased risk for persistent HBV infection (OR = 1.35, 95% CI: 1.03-1.77) and HCC development (OR = 1.90, 95% CI: 1.58-2.28) was associated with at least one A3B deletion allele (+/- or -/- genotype) compared with the +/+ genotype. Transfection of A3B in HepG2 cells caused a substantial reduction of HBV RNA levels and G → A hypermutation in the HBV genome. Interestingly, a cytidine deaminase null mutant of A3B (E255A) also inhibited HBV RNA production although it was unable to edit HBV. These results suggest that the deletion of A3B attenuates HBV clearance, which in turn may result in persistent HBV infection and increased risk for developing HCC. Further studies are needed to verify our findings.

Association between genetic variations in tumor necrosis factor receptor genes and survival of patients with T-cell lymphoma.

The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the clinical characteristics of patients. However, there is little knowledge of whether genetic variations also affect the prognosis of TCL. This study investigated the associations between single nucleotide polymorphisms(SNPs) in tumor necrosis factor receptor superfamily(TNFRSF) genes and the survival of patients with TCL. A total of 38 tag SNPs in 18 TNFRSF genes were genotyped using Sequenom platform in 150 patients with TCL. Kaplan-Meier survival estimates were plotted and significance was assessed using log-rank tests. Cox proportional hazard models were used to analyze each of these 38 SNPs with adjustment for covariates that might influence patient survival, including sex and international prognostic Index score. Hazard ratios (HRs) and their 95% confidence intervals(CIs) were calculated. Among the 38 SNPs tested, 3 were significantly associated with the survival of patients with TCL. These SNPs were located at LTßR (rs3759333C>T) and TNFRSF17(rs2017662C>T and rs2071336C>T). The 5-year survival rates were significantly different among patients carrying different genotypes and the HRs for death between the different genotypes ranged from 0.45 to 2.46. These findings suggest that the SNPs in TNFRSF genes might be important determinants for the survival of TCL patients.

Cytokine BAFF gene variation is associated with survival of patients with T-cell lymphomas.

PURPOSE: Cytokine BAFF is a potent molecule for the activation and survival of B cells, and it also plays an important role in T-cell function. Genetic polymorphism (rs9514828C>T) in BAFF has been associated with elevated BAFF transcription. We sought to determine whether rs9514828 is associated with T-cell lymphoma (TCL) survival. EXPERIMENTAL DESIGN: BAFF rs9514828 genotypes and survival of TCL were analyzed in the discovery group including 150 patients, and the results were replicated in an independent validation group of 120 patients. Kaplan-Meier analysis was conducted to compare survival among different genotypes. Cox proportional hazard models were used to identify independent significant variables. Luciferase reporter gene assays were conducted to examine the function of rs9514828 variant. RESULTS: We found that BAFF rs9514828 polymorphism was significantly associated with TCL survival. In pooled analysis of two independent groups, the favorable rs9514828 TC and TT genotypes had significantly better five-year survival rates compared with the CC genotype (47% and 53% vs. 22%, P = 2.27 × 10(-5) for log-rank test). Multivariate Cox regression analysis showed that rs9514828 was an independent prognostic factor, with HRs for patient death being 0.48 [95% confidence interval (CI), 0.32-0.71] for the CT and 0.47 (95% CI, 0.23-0.93) for the TT genotypes. Reporter gene assays indicated that the rs9514828T allele had significantly higher promoter activity than the rs9514828C counterpart. CONCLUSION: These findings suggest that functional polymorphism in BAFF might be a genetic determinant for the survival of patients with TCL.

Tree-ring-based reconstruction of precipitation in the Changling Mountains, China, since A.D.1691.

Seven different tree-ring parameters were obtained from Chinese pine (Pinus tabulaeformis) in the Changling Mountains, China. The chronologies were analyzed individually and then compared with each other. The climate response analysis shows that total precipitation (September-July) is the main factor limiting the radial growth of Chinese pine in the Changling Mountains. Thus, the residual earlywood width chronology was used to estimate precipitation (September-July) for the period AD 1691-2006, and explained 46.9% of the precipitation variance. Drought events in our reconstruction are compared to historical archives for Gansu and north-central China. The results reveal the climatic extremes over much of Gansu. Some events have had profound impacts on the Gansu people over the past several centuries. Spatial analysis shows that the precipitation reconstruction has strong common signals for North-central China. The reconstructed series is correlated significantly with Helan Mountains Palmer drought severity index (PDSI), as well as with previous results from Jiuquan, Shandan, Huashan, Luya Mountains, and even the state of Mongolia. Our results suggest that some dry periods are coincident with solar minima over the past several hundred years. Multitaper spectral analysis reveals the existence of significant 24.4-year, 12.2-year, and 2.4- to 3.4-year periods of variability.

Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis.

Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the development and progression of various types of human cancer and serum miRNAs are potential biomarkers. This study examined whether some commonly deregulated miRNAs in hepatocellular carcinoma (HCC) are presented in serum of patients with HCC and can serve as diagnostic markers. Serum miRNAs (miR-21, miR-122, and miR-223) were quantified by real-time quantitative RT-PCR in 101 patients with HCC and 89 healthy controls. In addition, 48 patients with chronic type B hepatitis were also analyzed for comparison. We found that the median levels of miR-21, miR-122, and miR-223 were significantly higher in patients with HCC than those in healthy controls (P = 7.48 x 10⁻¹³, P = 6.93 x 10⁻9, and P = 3.90 x 10⁻¹², respectively). However, these elevated serum miRNAs were also detected in patients with chronic hepatitis (P = 2.05 x 10⁻¹², P = 4.52 x 10⁻¹6, and P = 1.65 x 10⁻¹¹, respectively). Moreover, serum miR-21 and miR-122 in patients with chronic hepatitis were higher than in patients with HCC (P = 3.99 x 10⁻4 and P = 4.97 x 10⁻8), although no such significant difference was found for miR-223. Receiver-operator characteristic (ROC) curve analyses suggest that these serum miRNAs may be useful markers for discriminating patients with HCC or chronic hepatitis from healthy controls, but not patients with HCC from patients with chronic hepatitis. Our results indicate that serum miR-21, miR-122 and miR-223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC.

Genome-wide interrogation identifies YAP1 variants associated with survival of small-cell lung cancer patients.

Although most patients with small-cell lung cancer respond to chemotherapy, the survival time is highly diverse. We conducted a genome-wide analysis to examine whether germline genetic variations are prognostic factors in small-cell lung cancer patients treated with the same chemotherapy regimen. Genome-wide scan of single nucleotide polymorphisms (SNP) was performed using blood DNA to identify genotypes associated with overall survival in 245 patients treated with platinum-based chemotherapy, and the results were replicated in another independent set of 305 patients. Associations were estimated by Cox models and function of the variants was examined by biochemical assays. We found that rs1820453 T>G SNP within the promoter region of YAP1 on chromosome 11q22 and rs716274 A>G SNP in the region of downstream of DYNC2H1 on chromosome 11q22.3 are associated with small-cell lung cancer survival. In pooled analysis of 2 independent cohorts, the adjusted hazard ratio for patients with the rs1820453 TG or GG genotype was 1.49 (95% CI, 1.19-1.85; P = 0.0004) and 1.65 (95% CI, 1.36-2.01; P = 4.76 × 10(-7)), respectively, compared with the TT genotype; and for patients with the rs716274 AG or GG genotype was 1.83 (95% CI, 1.47-2.29; P = 8.74 × 10(-8)) and 2.96 (95% CI, 1.90-4.62; P = 1.59 × 10(-6)), respectively, compared with the AA genotype. Functional analysis showed that the rs1820453 T>G change creates a transcriptional factor binding site and results in downregulation of YAP1 expression. These results suggest that YAP1 may play an important role in prognosis of small-cell lung cancer patients treated with platinum-based chemotherapy.