Metabolic and physiological response of the rabbit to continuous and intermittent treadmill exercise

Our knowledge of the effects of exercise on the heart is limited by the predominant use of rats as an animal model. The rabbit has many advantages over the rat as an animal model to study. However, little work has characterized its capacity to exercise. The purposes of the present study were to determine if the rabbit could (i) learn to run on a motor-driven treadmill at relatively high speeds using different exercise protocols, and (ii) characterize the various physiological and metabolic responses of the rabbit to acute bouts of exercise. We found that female New Zealand white rabbits had the capacity to run continuously on the treadmill for up to 21 min at 20 m/min until exhausted. Continuous, endurance-type exercise resulted in significant elevations in body temperature, heart rate, and plasma lactate levels. Plasma triglyceride concentration decreased as a function of this type of running whereas plasma glucose levels were unchanged. Twenty-four hours after a bout of running, plasma creatine phosphokinase activity was significantly elevated. The rabbits also had the capacity to learn to run using an intermittent, higher speed protocol. These physically untrained animals could achieve speeds of up to 70 m/min for 10 bouts of 15 s run/30 s rest. Their metabolic and physiological responses to this protocol were similar to those of continuous running with the following exceptions. The decrease in plasma triglyceride was less marked and the increase in plasma lactate was greater after intermittent exercise. Glycogen content of the rabbit vastus lateralis muscle was also significantly depleted after exhaustive, intermittent exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology     

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.     

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA^Glu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA^Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC^Glu) to BLA^Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD^Glu) to BLA^Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the IC^Glu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD^Glu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC^Glu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD^Glu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC^Glu→BLA and MD^Glu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.     

植物核DNA含量在全球尺度上的纬度变异式样及其气候适应意义——以菊科植物为例

核DNA含量是重要的生物学概念,涉及DNA C-值和基因组大小。前人有关植物核DNA含量在纬度梯度上的变异规律存在着矛盾的报道,而且多数将核DNA含量与纬度、海拔、气候等因素之间的关系描述成线性关系。核DNA含量是否具有环境适应上的意义,也还存在争议。先前有关核DNA含量与环境因素间关系的矛盾性报道可能与取样过小、地理范围过窄、研究对象遗传背景差异过大有关。如果对一个遗传背景相近的类群在全球范围内进行取样,核DNA含量会呈现有规律的纬度梯度变化,可能与大的气候因素之间存在非线性关系。菊科(Asteraceae)是被子植物的最大科,是一个广泛认可的自然分类群。为揭示全球空间尺度上植物核DNA含量在纬度梯度上的变异规律,以及这种变异是否具有环境适应意义,以菊科为对象开展了核DNA含量与纬度、生物气候因素关系的统计分析。从"植物DNA C-值数据库"检索到822种菊科植物的核DNA含量数据;在全球范围内,沿经度方向上设立10条样带,每条样带横跨15个经度,每条样带又均分成22个样块,每个样块纵跨7.5个纬度;其次,从"世界气候数据网站"下载1950—2000年时间段14个生物气候因子数据,应用Arc GIS 9.3获得每个样块14个生物气候因子的平均值;根据"全球生物多样性信息网站"记录,计算每个样块菊科植物平均的核DNA含量数据。为避免气候变量之间的多重共线性对数据分析的影响,应用主成分分析对数据进行了降维,发现最冷季度平均温度、最干季度雨量分别是第一、二主成分上荷载最大的因子,去除与它们相关性在-0.7至+0.7之间的其他气候因子后获得了最冷季度平均温度、最干季度雨量和最湿月份雨量三个变量用于进一步数据分析。结果发现,菊科植物在全球10个样带上的核DNA含量与纬度关系密切,与最冷季度平均温度、最干季度雨量和最湿月份雨量呈现极显著的单峰型的非线性关系,可以用二项式进行拟合。因此,全球空间尺度上植物核DNA含量沿着纬度梯度有规律性的非线性变化,这种变化具有很强的气候适应意义。     

Response of physiologic metabolism and cell structures in mango fruit to exogenous methyl salicylate under low-temperature stress

We explored the effects of exogenous methyl salicylate (MeSA) on the development of chilling injury symptom, and the structure and composition of the pericarp, in mango ( Mangifera indica L. cv. 'Red 6') fruit under low-temperature stress using histochemical analysis and scanning electron microscopy together with Fourier transform infrared (FTIR) analysis. The results indicated that chilling injury symptom was remarkably limited in the fruit treated with MeSA at 0.1 m M as compared to the 5°C control, demonstrating the positive effects of MeSA in reducing chilling injury of mango fruit in low-temperature storage. In MeSA-treated fruit, the pericarp wax surface showed many cracks, and exocarp cells exhibited normal separation. The cell wall of exocarp contained lower amounts of pectic substances, aliphatics and phenolics in MeSA-treated fruit. In addition, MeSA-treated fruit contained more esterified substances and less carboxylate and carboxyl substances. Our work revealed the importance of MeSA in enhancing fruit tolerance to low-temperature stress and suggested a contribution of cellular structure and composition to this effect, which has not been reported previously.     

Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers

Human embryonic stem (hES) cells are typically maintained on mouse embryonic fibroblast (MEF) feeders or with MEF-conditioned medium. However, these xenosupport systems greatly limit the therapeutic applications of hES cells because of the risk of cross-transfer of animal pathogens. Here we showed that the bone morphogenetic protein antagonist noggin is critical in preventing differentiation of hES cells in culture. Furthermore, we found that the combination of noggin and basic fibroblast growth factor (bFGF) was sufficient to maintain the prolonged growth of hES cells while retaining all hES cell features. Since both noggin and bFGF are expressed in MEF, our findings suggest that they may be important factors secreted by MEF for maintaining undifferentiated pluripotent hES cells. Our data provide new insight into the mechanism how hES cell self-renewal is regulated. The newly developed feeder-free culture system will provide a more reliable alternative for future therapeutic applications of hES cells.     

海洋氮循环中细菌的厌氧氨氧化

细菌厌氧氨氧化过程是在一类特殊细菌的厌氧氨氧化体内完成的以氨作为电子供体硝酸盐作为电子受体的一种新型脱氮反应.厌氧氨氧化菌的发现,改变人们对传统氮的生物地球化学循环的认识:反硝化细菌并不是大气中氮气产生的唯一生物类群.而且越来越多的证据表明,细菌厌氧氨氧化与全球的氮物质循环密切相关,估计海洋细菌的厌氧氨氧化过程占到全球海洋氮气产生的一半左右.由于氮与碳的循环密切相关,因此可以推测,细菌的厌氧氨氧化会影响大气中的二氧化碳浓度,从而对全球气候变化产生重要影响.另外,由于细菌厌氧氨氧化菌实现了氨氮的短程转化,缩短了氮素的转化过程,因此为开发更节约能源、更符合可持续发展要求的废水脱氮新技术提供了生物学基础.     

P38MAPK信号通路与心血管疾病关系的研究进展

P38MAPK信号通路是细胞内主要的信息传递途径之一,与其他信号通路相互联系,共同调节细胞增殖、分化、凋亡、细胞骨架重构及细胞周期,在多种心血管疾病发生发展和转归中均起着重要作用。通过阻断和调控P38MAPK的表达和活性,探索防治心血管疾病的新的治疗手段具有重大临床意义。本文拟将P38MAPK与心血管疾病的关系的研究进展做一综述。