A new positive relationship between pCO2 and stomatal frequency in Quercus guyavifolia (Fagaceae): a potential proxy for palaeo-CO2 levels

Background and Aims The inverse relationship between atmospheric CO₂ partial pressure (pCO₂) and stomatal frequency in many species of plants has been widely used to estimate palaeoatmospheric CO₂ (palaeo-CO₂) levels; however, the results obtained have been quite variable. This study attempts to find a potential new proxy for palaeo-CO₂ levels by analysing stomatal frequency in Quercus guyavifolia (Q. guajavifolia, Fagaceae), an extant dominant species of sclerophyllous forests in the Himalayas with abundant fossil relatives.Methods Stomatal frequency was analysed for extant samples of Q. guyavifolia collected from17 field sites at altitudes ranging between 2493 and 4497 m. Herbarium specimens collected between 1926 and 2011 were also examined. Correlations of pCO₂–stomatal frequency were determined using samples from both sources, and these were then applied to Q. preguyavaefolia fossils in order to estimate palaeo-CO₂ concentrations for two late-Pliocene floras in south-western China.Key Results In contrast to the negative correlations detected for most other species that have been studied, a positive correlation between pCO₂ and stomatal frequency was determined in Q. guyavifolia sampled from both extant field collections and historical herbarium specimens. Palaeo-CO₂ concentrations were estimated to be approx. 180–240 ppm in the late Pliocene, which is consistent with most other previous estimates.Conclusions A new positive relationship between pCO₂ and stomatal frequency in Q. guyavifolia is presented, which can be applied to the fossils closely related to this species that are widely distributed in the late-Cenozoic strata in order to estimate palaeo-CO₂ concentrations. The results show that it is valid to use a positive relationship to estimate palaeo-CO₂ concentrations, and the study adds to the variety of stomatal density/index relationships that available for estimating pCO₂. The physiological mechanisms underlying this positive response are unclear, however, and require further research.     

IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity

Background

Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity.

Methods and Findings

Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity.

Conclusions

This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease.     

N-(4-{[4-(1H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors

A novel class of N-(4-{[4-(1H-benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamides are described as inhibitors of the endo-beta-glucuronidase heparanase. Among them are N-(4-{[4-(1H-benzoimidazol-2-yl)-phenylamino]-methyl}-phenyl)-3-bromo-4-methoxy-benzamide (15h), and N-(4-{[5-(1H-benzoimidazol-2-yl)-pyridin-2-ylamino]-methyl}- phenyl)-3-bromo-4-methoxy-benzamide (23) which displayed good heparanase inhibitory activity (IC(50) 0.23-0.29 microM), with the latter showing oral exposure in mice.     

Heme Oxygenase-2 Suppress TNF-α and IL6 Expression via TLR4/MyD88-Dependent Signaling Pathway in Mouse Cerebral Vascular Endothelial Cells

Heme oxygenase (HO) represents an intrinsic antiinflammatory system based on its ability to inhibit expression of proinflammatory cytokines. The constitutive isoform heme oxygenase-2 (HO-2) has high expression and activity in cerebral microvascular endothelial cells (CMVEC). This study was undertaken to evaluate the role of HO-2 in regulation of TLR4/MyD88-dependent signaling and to study the effect of HO-2 on the expression and secretion of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and Interleukin-6 (IL6) in CMVEC. HO-2 short hairpin RNA (shRNA) and HO-2 overexpression plasmids were used to observe the effect of HO-2 on proinflammatory cytokines in CMVEC in vitro, and the results showed that the messenger RNA (mRNA) and protein levels of TNF-α and IL6 were increased and decreased, respectively, compared with control groups. LPS-stimulated TNF-α and IL6 mRNA and protein were also reduced in CMVEC treated with an inhibitor of TLR4 signaling, CLI-095, or HO-2 overexpression. CLI-095 and HO-2 overexpression both reduced TLR4 expression in CMVEC, and HO-2 shRNA blocked these effects of CLI-095. CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation.     

中国荷斯坦牛IL8基因遗传多态性与泌乳性状以及体细胞评分的关联

以上海某奶牛场30个公牛家系的610头中国荷斯坦牛为试验材料,采用聚合酶链式反应-单链构象多态性(PCR-SSCP)技术对Interleukin-8(IL8)基因的遗传多态性进行了分析,采用混合动物模型分析了IL8基因突变位点与测定日产奶量、测定日乳脂率、测定日乳蛋白率、305d校正产奶量、305d乳脂量、305d乳蛋白量及测定日体细胞评分7个性状的相关性,寻找可用于生产实际的分子标记。共检测到KK、KA和AA3种基因型,频率分别为0.187、0.451和0.362,等位基因K和A的频率分别为0.412和0.588。该位点突变对测定日产奶量、305d乳蛋白量、305d校正产奶量和305d乳脂量以及体细胞评分影响达到极显著水平(P0.01),对测定日乳蛋白率的影响达到显著水平(P0.05),对测定日乳脂率影响不显著(P0.05)。多重比较表明:KK基因型对测定日产奶量、305d校正产奶量、305d乳蛋白量和305d乳脂量极显著高于AA和KA基因型(P0.01)。KK基因型的体细胞评分(SCS)最小二乘均值极显著低于KA、AA基因型(P0.01)。对于测定日的乳蛋白率AA基因型显著低于KA、KK型(P0.05)。IL8基因遗传突变对中国荷斯坦牛泌乳性状和乳房炎抗性有较大的遗传效应,可用于中国荷斯坦牛的分子标记辅助选择。     

Cool-dry season depression in gas exchange of canopy leaves and water flux of tropical trees at the northern limit of Asian tropics

Trees on the northern boundary of Asian tropics experience hot-humid and cool-dry seasons, but little is known about their seasonal dynamics in canopy physiology. We used a canopy crane to reach the canopy of nine tropical tree species and measured canopy leaf gas exchange, water status, and trunk sap flux during the hot-humid and cool-dry seasons in Xishuangbanna, China. We found that most tree species exhibited significant reductions in maximum photosynthetic rate (A_max), stomatal conductance (g_smax), predawn and midday leaf water potentials, and maximum sap flux density in the cool-dry season. Compared to the hot-humid season, A_max declined by 19–60%, and maximum water flux declined by ?14% (an increase) to 42%. The cool-dry season decline in A_max of four species can be partly explained by an increased stomatal limitation (decreased g_smax and intercellular CO₂ concentrations). Therefore, a predicted increase in drought in this region may decrease the carbon sequestration and productivity of these forests. We did not find a tradeoff between performance (A_max in the hot-humid season) and persistence through the cool-dry season; species with higher A_max in the hot-humid season did not show higher percent seasonal declines in the cool-dry season. A_max was significantly and positively associated with the trunk sap flux for both seasons, but the association was weaker in the cool-dry season. Thus, our results suggest that some tradeoffs and trait associations are environment dependent. Our results are important for understanding carbon and water fluxes of seasonal tropical forests and their responses to environmental changes.

     

尖锐湿疣样本中HPV病毒的分子检测

调查男性和女性尖锐湿疣样本中人乳头瘤病毒（HPV）的检出率及病毒类型,为研发相关防治疫苗提供依据,以HPV 外壳蛋白DNA序列为模板设计特异引物,SSP－PCR扩增检测样本中HPV的感染率和病毒类型。收集了北京及邯郸市医院门诊尖锐湿疣样本22例,其中男性13例,女性9例。检测发现所有样本中存在着高浓度的HPV病毒DNA。男性样本中有5例感染HPV6型,6例感染HPV11型,2例为HPV6＋HPV11混合感染。女性样本中有3例感染HPV6型,2例感染HPV11型,4例为 HPV6＋HPV11混合感染。被诊断为宫颈湿疣的4位女性还在其含宫颈粘膜脱落细胞的样本中检出了HPV16、HPV18、HPV33、HPV35、HPV45、HPV54、HPV56或HPV58等高危险型病毒类型。所有检测到的HPV病毒DNA片段均TA克隆并将测定的DNA序列存入了国际基因数据库GenBank（DQ003066－DQ003079）。调查没有在单纯的男女尖锐湿疣组织块中检测到除HPV6和HPV11以外的其他HPV类型。该研究建立了灵敏可靠的HPV分子检测及分型方法,尖锐湿疣中HPV的检出率达100％。 本研究初步结果显示导致男女尖锐湿疣的HPV病毒类型没有显著差异,主要为HPV6及HPV11型。     

Challenges in Developing a Validated Biomarker for Angiogenesis Inhibitors: The Motesanib Experience

Purpose

We sought to develop placental growth factor as a predictive pharmacodynamic biomarker for motesanib efficacy as first-line therapy in patients with advanced nonsquamous non–small-cell lung cancer.

Experimental Design

Placental growth factor was evaluated at baseline and study week 4 (after 3 weeks treatment) in an exploratory analysis of data from a randomized phase 2 study of motesanib 125 mg once daily plus carboplatin/paclitaxel and in a prespecified analysis of data from a randomized, double-blind phase 3 study of motesanib 125 mg once daily plus carboplatin/paclitaxel vs placebo plus carboplatin/paclitaxel (MONET1). Associations between fold-change from baseline in placental growth factor and overall survival were evaluated using Cox proportional hazards models.

Results

In the phase 2 study, serum placental growth factor increased from baseline a mean 2.8-fold at study week 4. Patients with ≥2.2-fold change from baseline in placental growth factor (n = 18) had significantly longer overall survival than those with <2.2-fold change (n = 19; 22.9 vs 7.9 months; hazard ratio, 0.30; 95% CI, 0.12–0.74; P = 0.009). Consequently, placental growth factor was investigated as a pharmacodynamic biomarker in the phase 3 MONET1 study. There was no association between log-transformed placental growth factor fold-change from baseline to week 4 (continuous variable) and overall survival (hazard ratio, 0.98; 95% CI, 0.79–1.22; P = 0.868). MONET1 did not meet its primary endpoint of overall survival. Likewise, median overall survival was similar among patients with ≥2.0-fold change in placental growth factor (n = 229) compared with <2.0-fold change (n = 127; 14.8 vs 13.8 months; hazard ratio, 0.88; 95% CI, 0.67–1.15, P = 0.340).

Conclusions

Our results illustrate the challenges of successfully translating phase 2 biomarker results into phase 3 studies.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00460317","term_id":"NCT00460317"}}NCT00460317, {"type":"clinical-trial","attrs":{"text":"NCT00369070","term_id":"NCT00369070"}}NCT00369070     

条石鲷的早期生长发育特征

对条石鲷(Oplegnathus fasciatus)早期生活史阶段生长发育特征进行了观察和测量,描述了胚胎和胚后各发育阶段的生长发育特征。条石鲷成熟卵子为浮性、端黄卵,卵径0.86mm±0.012mm(n=30),单油球,油球径0.18mm-0.22mm。在水温23.5℃±0.5℃、盐度30.5、pH8.0-8.3条件下,受精卵经27.5h孵化出膜。初孵仔鱼消化道细而直,随着仔鱼发育,消化道变得粗大、弯曲,肠道内褶回增多,消化能力增强。3日龄(仔鱼孵化出膜后第一天称为0日龄,以此类推)仔鱼卵黄囊消耗殆尽,开口,肛门与外界相通,油球在6日龄消耗完毕,进入外源性营养阶段。仔稚鱼培育在室内水泥池进行。在水温21℃-24℃、盐度27-33、pH8.0-8.3条件下,仔鱼开口饵料为S型褶皱臂尾轮虫,4日龄仔鱼开始摄食轮虫或轮虫卵,13日龄开始摄食卤虫无节幼体,25日龄开始进行配合饲料转化,30日龄后苗种摄食配合饲料良好。4日龄仔鱼鳔原基形成,7日龄时鳔开始充气变为亮泡状,生活史终生有鳔。色素细胞首先出现在12h50min的胚体上,至18h已在胚体全身分布,随着胚体发育,色素细胞增多。脊椎骨末端弯曲在15日龄开始,至24日龄弯曲过程完成,除腹鳍外其它鳍的鳍条数与成鱼一致,牙齿(硬齿和绒毛齿)生成,可咬食饵料。体表七条横向黑色素带是条石鲷的一个显著体态特征。21日龄鱼体表形成第一条横向黑色素带,23日龄时体表形成第二条色素带,25日龄时形成第三条色素带,29日龄时仔鱼体表第五条色素带形成,至40日龄时第七条色素带形成,此时稚鱼体态除背鳍、尾鳍、腹鳍上色素外与成体相似。60日龄幼鱼鳞片形成,在体态上与成体无明显区别。