Relation between veratridine reaction dynamics and macroscopic Na current in single cardiac cells

Veratridine modification of Na current was examined in single dissociated ventricular myocytes from late-fetal rats. Extracellularly applied veratridine reduced peak Na current and induced a noninactivating current during the depolarizing pulse and an inward tail current that decayed exponentially (tau = 226 ms) after repolarization. The effect was quantitated as tail current amplitude, Itail (measured 10 ms after repolarization), relative to the maximum amplitude induced by a combination of 100 microM veratridine and 1 microM BDF 9145 (which removes inactivation) in the same cell. Saturation curves for Itail were predicted on the assumption of reversible veratridine binding to open Na channels during the pulse with reaction rate constants determined previously in the same type of cell at single Na channels comodified with BDF 9145. Experimental relationships between veratridine concentration and Itail confirmed those predicted by showing (a) half-maximum effect near 60 microM veratridine and no saturation up to 300 microM in cells with normally inactivating Na channels, and (b) half-maximum effect near 3.5 microM and saturation at 30 microM in cells treated with BDF 9145. Due to its known suppressive effect on single channel conductance, veratridine induced a progressive, but partial reduction of noninactivating Na current during the 50-ms depolarizations in the presence of BDF 9145, the kinetics of which were consistent with veratridine association kinetics in showing a decrease in time constant from 57 to 22 and 11 ms, when veratridine concentration was raised from 3 to 10 and 30 microM, respectively. As predicted for a dissociation process, the tail current time constant was insensitive to veratridine concentration in the range from 1 to 300 microM. In conclusion, we have shown that macroscopic Na current of a veratridine-treated cardiomyocyte can be quantitatively predicted on the assumption of a direct relationship between veratridine binding dynamics and Na current and as such can be successfully used to analyze molecular properties of the veratridine receptor site at the cardiac Na channel.     

干旱荒漠区植物生态位对水盐的响应

全球气候变化对生态系统功能的影响决定着种群地位和群落演替,由于干旱区的特殊性成为研究生物响应环境变化的热点地区。为探索艾比湖流域荒漠区植物生态位对土壤水盐梯度的响应,在研究水、盐含量和植物生态位特征的基础上,应用变系数模型,分析了土壤水盐梯度下的群落组成和生态位响应趋势。结果显示:(1)随土壤水盐梯度的降低,艾比湖流域群落的物种组成呈倒"V"型分布,说明土壤水盐交互作用影响着植被分布和群落类型。(2)高水盐环境下,胡杨(Populus euphratica)、琵琶柴(Reaumuria soongorica)和梭梭(Haloxylon ammodendron)等生态位宽度值(B_i)较大,柽柳(Tamarix ramosissima)、骆驼刺(Alhagi sparsifolia)和甘草(Glycyrrhiza uralensis)等B_i较小;中水盐环境下,白刺(Nitraria schoberi)和琵琶柴的B_i较大,铃铛刺(Halimodendron halodendron)、甘草和盐节木(Halocnemum strobilaceum)的B_i较小;低水盐环境下,梭梭、花花柴(Karelinia caspica)和琵琶柴等B_i较大,盐节木的B_i较小;说明土壤水盐环境和物种生态学特性是影响B_i的重要因素。(3)物种水平上,B_i较大的种群与其他物种的生态位重叠(O_(ij))一般较大,但B_i较小的物种间的O_(ij)不一定小(例如:高水盐土壤环境下柽柳和骆驼刺的O_(ij)为1);群落水平上,B_i与O_(ij)具有一定的正相关性;说明由于资源纬度的相似性增大了低B_i物种间的O_(ij),并且B_i和O_(ij)由物种向群落尺度转换时,两者之间的关系存在冗余。(4)土壤水盐梯度与群落生态幅呈现一种非线性相关特征,高水盐格局对群落B_i有一定的促进效应,而低水盐模式对B_i具有一定的限制作用,表明土壤水盐的协同效应影响着物种在群落的地位,并在一定程度上决定了群落向正负两极演替的方向。     

TBK1 Facilitates GLUT1-Dependent Glucose Consumption by suppressing mTORC1 Signaling in Colorectal Cancer Progression

Intestinal inflammation is a vital precipitating factor of colorectal cancer (CRC), but the underlying mechanisms are still elusive. TANK-binding kinase 1 (TBK1) is a core enzyme downstream of several inflammatory signals. Recent studies brought the impacts of TBK1 in malignant disease to the forefront, we found aberrant TBK1 expression in CRC is correlated with CRC progression. TBK1 inhibition impaired CRC cell proliferation, migration, drug resistance and tumor growth. Bioinformatic analysis and experiments in vitro showed overexpressed TBK1 inhibited mTORC1 signaling activation in CRC along with elevated GLUT1 expression without inducing GLUT1 translation. TBK1 mediated mTORC1 inhibition induces intracellular autophagy, which in turn decreasing GLUT1 degradation. As a rescue, blocking of autophagosome and retromer respectively via autophagy-related gene 7 (ATG7) or TBC1 Domain Family Member 5 (TBC1D5) silence diminished the regulation of TBK1 to GLUT1. GLUT1 staining presented that TBK1 facilitated GLUT1 membrane translocation which subsequently enhanced glucose consumption. Inhibitor of TBK1 also decreased GLUT1 expression which potentiated drug-sensitivity of CRC cell. Collectively, TBK1 facilitates glucose consumption for supporting CRC progression via initiating mTORC1 inhibition induced autophagy which decreases GLUT1 degradation and increases GLUT1 membrane location. The adaptive signaling cascade between TBK1 and GLUT1 proposes a new strategy for CRC therapy.     

LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway

Thoracic ossification of the ligamentum flavum (TOLF) is ectopic ossification of the spinal ligaments. Histologically, the development of TOLF can be described as the process of endochondral ossification. However, the underlying aetiology has not been completely clarified. In this investigation, the gene expression profile associated with leucine‐rich repeat‐containing G‐protein‐coupled receptors (LGR) and Wnt signalling pathway in the thoracic ligamentum flavum cells (TLFCs) of different ossification stages was analysed via RNA sequencing. We further confirmed the significant differences in the related gene expression profile by Gene Ontology (GO) enrichment analysis. LGR5 was first identified in primary human TLFCs during osteogenic differentiation. To evaluate the effect of LGR5 on osteogenic differentiation, LGR5 has been knocked down and overexpressed in human TLFCs. We observed that the knockdown of LGR5 inhibited the activity of Wnt signalling and attenuated the potential osteogenic differentiation of TLFCs, while overexpression of LGR5 activated the Wnt signalling pathway and increased osteogenic differentiation. Our results provide important evidence for the potent positive mediatory effects of LGR5 on osteogenesis by enhancing the Wnt signalling pathway in TOLF.     

基于盐分梯度的荒漠植物多样性与群落、种间联接响应

土壤盐分是影响干旱区荒漠植物群落动态的决定因素之一。基于样方调查和不同土壤盐分梯度下植物多样性指数及群落与种间关联的计算结果,分析干旱区荒漠群落植物多样性、群落联接性和种间关联对土壤盐分梯度的响应动态。结果表明,在土壤盐含量为0.03%-0.55% (S1)、0.61%-1.24% (S2)和1.41%-1.79% (S3)的盐分梯度上,(1)随土壤盐含量升高,群落生活型结构改变,草本比例减少,乔木比例增加;(2)植物多样性指数随土壤盐分增加而下降,低盐分梯度下,二者极显著正相关(P<0.01),中盐梯度下二者间呈部分显著负相关(P<0.05),高盐梯度下则转为以正相关为主(P>0.05);(3)群落联接性随土壤盐分梯度转变,在0.61%-1.24%的中度盐含量时正联接性最强(VR=1.89),高盐度含量下群落转为不显著的负联接,稳定性降低;(4)沿盐分升高梯度,种间的负相关种对数增加,正相关种对数减少,种间关联(相关)强度提高,正负相关种对比(PNR)与多样性指数呈显著正相关(P<0.05)。综上可知,干旱区荒漠植物多样性在土壤盐含量达到1.41%-1.79%水平时总体显著降低;土壤盐分水平显著影响植物群落和种间联接性,种间互利性随盐分梯度增加下降,物种趋于独立分布,并最终导致荒漠植物多样性降低。     

荒漠杜加依林冠层水热变化及CO2交换特征

选取新疆艾比湖湿地国家级自然保护区荒漠杜加依林为研究对象,利用通量塔连续观测数据分析新疆艾比湖流域内杜加依林冠层界面水热垂直变化和CO_2交换特征,进一步比较了冠层界面湍流碳通量、植物冠层储存碳通量及净碳交换量,探讨了不同时间和垂直空间序列下杜加依林冠层界面温湿廓线与CO_2交换过程的相互关系。结果表明,新疆艾比湖流域内杜加依林冠层上方大气稳定度生长季的6—9月为中性(z/L=0.009),非生长季为不稳定(z/L=-0.449),全年总体呈不稳定水平(z/L=-0.194);冠层界面上气温垂直变幅小于5℃,随高度呈递增趋势,湿度垂直变幅超过40%;地-气碳通量呈秋冬小春夏大规律,年碳收支高于干旱区平均水平,为-0.026 mg CO_2m~(-2)s~(-1),表现为碳汇;垂直空间尺度上垂直温湿度差与生态系统净碳交换量(NEE,Net Ecosystem Exchange)拟合较好,温度拟合结果为R~2=0.7350(P﹤0.01),湿度拟合结果为R~2=0.3627(P﹤0.01),水热变点分别为5%和1℃,而季节尺度上温度拟合结果较好,温度拟合结果为R~2=0. 5221(P﹤0. 01),湿度拟合结果为R~2=0.1716(P﹤0.01),变点为55%和18℃。生长季较小的冠层垂直温差有利于杜加依林对大气CO_2的吸收,而冠层高湿环境则会抑制杜加依林对CO_2的吸收。     

工业酵母抗逆机理研究进展

工业酵母利用木质纤维素等生物质资源发酵生产醇、酮、醛、酸等各种化合物,是解决人类面临的不可再生资源和能源危机的重要途径,这激发了人们对木质纤维素水解液为原料和环保节能型浓醪发酵技术的极度关注。然而高浓度底物、产物、渗透压、木质纤维素水解液中抑制性物质、发酵过程温度的提高均会抑制微生物生长代谢及发酵性能,这是发酵行业"瓶颈"问题。本文简述了渗透压、温度及抑制性物质对酵母细胞生长的危害,并从胞内稳态平衡、分子水平等方面着重叙述工业酵母对渗透压、温度及抑制性物质的抗逆机制研究进展。     

不同水盐梯度下功能多样性和功能冗余对荒漠植物群落稳定性的影响

功能多样性和功能冗余是物种多样性的两个组成部分,也是影响群落稳定性的两个重要因素。基于不同水盐梯度下植物功能多样性、功能冗余、物种多样性和群落稳定性及其相关关系的计算结果,分析功能多样性和功能冗余对群落稳定性的影响,结果表明:(1)功能多样性、物种多样性和群落稳定性均表现为高水高盐和中水中盐群落显著高于低水低盐群落(P0.05);(2)高水高盐群落,功能多样性与物种多样性的相关系数小于功能冗余与物种多样性的相关系数,且功能多样性与稳定性的相关系数也小于功能冗余与稳定性的相关系数,而中水中盐和低水低盐群落的相关系数则呈现相反的规律;(3)中水中盐和低水低盐群落的功能多样性的标准化偏回归系数均大于功能冗余的标准化偏回归系数;(4)典范对应分析中,土壤含水量可以解释总特征根的22.7%,而土壤含盐量仅可以解释总特征根的1.3%;(5)高水高盐群落的稳定比最接近20/80,稳定性最高;低水低盐群落远离20/80,稳定性最低。改进后的Godron稳定性测定方法与物种种群密度变异系数方法得出的结果相同。综上可知,功能多样性和功能冗余两者中与物种多样性关系更为密切者对群落稳定性的影响也越大,且两者均可提高群落稳定性,也就证明冗余假说在温带干旱荒漠区域的隐域性植物群落中是成立的;群落稳定性、功能多样性、功能冗余及物种多样性主要是受土壤含水量的影响,土壤含盐量对其影响较小。     

苦草对砷的富集作用

为了探求合适的水体砷污染修复植物及砷在食物链中传递、累积的特点,以常见的沉水植物-苦草为研究对象,对受砷污染的水体进行修复,结果表明:苦草对水环境中砷的富集能在较短的时间内(3 d)达到一个较大值,到第14天,不同砷水平(2 mg/L)处理下的苦草对砷富集系数均超过200;苦草中砷浓度随处理时间及外源砷浓度的增加而增加,且与外源砷浓度之间存在极显著地正相关;苦草在不同浓度砷处理下都生长良好,对砷胁迫表现出较强的耐受性。因此,苦草对于水体的砷污染有着很好的去除效果,同时也能很好地反映出一个地区的砷污染水平。