Consequences of Location-Dependent Organ of Corti Micro-Mechanics

The cochlea performs frequency analysis and amplification of sounds. The graded stiffness of the basilar membrane along the cochlear length underlies the frequency-location relationship of the mammalian cochlea. The somatic motility of outer hair cell is central for cochlear amplification. Despite two to three orders of magnitude change in the basilar membrane stiffness, the force capacity of the outer hair cell’s somatic motility, is nearly invariant over the cochlear length. It is puzzling how actuators with a constant force capacity can operate under such a wide stiffness range. We hypothesize that the organ of Corti sets the mechanical conditions so that the outer hair cell’s somatic motility effectively interacts with the media of traveling waves—the basilar membrane and the tectorial membrane. To test this hypothesis, a computational model of the gerbil cochlea was developed that incorporates organ of Corti structural mechanics, cochlear fluid dynamics, and hair cell electro-physiology. The model simulations showed that the micro-mechanical responses of the organ of Corti are different along the cochlear length. For example, the top surface of the organ of Corti vibrated more than the bottom surface at the basal (high frequency) location, but the amplitude ratio was reversed at the apical (low frequency) location. Unlike the basilar membrane stiffness varying by a factor of 1700 along the cochlear length, the stiffness of the organ of Corti complex felt by the outer hair cell remained between 1.5 and 0.4 times the outer hair cell stiffness. The Y-shaped structure in the organ of Corti formed by outer hair cell, Deiters cell and its phalange was the primary determinant of the elastic reactance imposed on the outer hair cells. The stiffness and geometry of the Deiters cell and its phalange affected cochlear amplification differently depending on the location.     

Single-cell RNA sequencing reveals transcriptional profiles of monocytes in HBV-infected pregnant women during mid-pregnancy

There is a growing body of evidence that innate immunity also plays an important role in the progression of hepatitis B virus (HBV) infection. However, there is less study on systematically elucidating the characteristics of innate immunity in HBV-infected pregnant women. We compared the features of peripheral blood mononuclear cells in three healthy pregnant women and three HBV-infected pregnant women by single-cell RNA sequencing. 10 DEGs were detected between groups and monocytes were the main expression source of most of the DEGs, which involved in the inflammatory response, apoptosis and immune regulation. Meanwhile, qPCR and ELISA were performed to verify above genes. Monocytes displayed immune response defect, reflecting poor ability of response to IFN. In addition, eight clusters were identified in monocytes. We identified molecular drivers in monocytes subpopulations.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes were featured with different gene expression pattern and biological function.TNFSF10+ monocytes and MT1G+ monocytes were characterized by high levels of inflammation response.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes showed decreased response to IFN. Our results dissects alterations in monocytes related to the immune response of HBV-infected pregnant women and provides a rich resource for fully understanding immunopathogenesis and developing effective preventing HBV intrauterine infection strategies.     

Up-regulation of the Cbl family of ubiquitin ligases is involved in ATRA and bufalin-induced cell adhesion but not cell differentiation

The Casitas B-lineage Lymphoma (Cbl) family of ubiquitin ligases is multifunctional proteins that play important roles in different cell signaling pathways. It has been reported that c-Cbl and Cbl-b mRNAs are up-regulated during TPA-induced U937 and HL-60 cell differentiation. But the mechanism of the up-regulation and the roles of the Cbl family of ubiquitin ligases still remain unclear. In the present study, we demonstrated that bufalin enhanced all-trans retinoic acid (ATRA) induced differentiation of HL-60 cells, accompanied by up-regulation of the Cbl family of ubiquitin ligases. CsA, an inhibitor of calcium mobilization, reversed this up-regulation. Pretreatment with CsA and PS-341 did not affect the expression of CD11b, but suppressed the percentage of adherent cells. Lipid raft localization of Cbl-b enhanced cell adhesion, while C-terminal deletion partially suppressed the effect. Moreover, the expression of the adhesion-related kinases Pyk2 and Paxillin was up-regulated in parallel with the increase of Cbl proteins. These results suggested that up-regulation of c-Cbl and Cbl-b was involved in the regulation of ATRA and bufalin-induced HL-60 cell adhesion rather than cell differentiation, which might be mediated by lipid raft localization, ubiquitin ligase activity and C-terminal structure of Cbl proteins. Meanwhile, up-regulation of proline-rich tyrosine kinase (Pyk2) and Paxillin might also be implicated in this regulation.     

中华鳖生态养殖模式的原理、结构和特点

我国中华鳖 (Ｔｒｉｏｎｙｘｓｉｎｅｎｓｉｓ)养殖一般采用冬季加温的养殖模式 ,所以温室设计是中华鳖养殖的关键技术之一。温室设计应考虑以下几个因素 ,鳖的生理生态需求 ,温室的保温采光性能 ,操作管理的便捷以及基建成本等。我们在借鉴各种养鳖温室优点的基础上 ,设计了一种新型温室 ,现就其设计原理和结构特点做一简要介绍。1　联体温室1.1　设计原理中华鳖生长的最适水温是 2 7～ 33℃ ,而且对环境温度的变化极为敏感 ,水温突变± 5℃就可能使其出现生理紊乱 ,甚至引起死亡[2 ] ,因此 ,中华鳖养殖中一般将养殖水体温度控制在 30± 2…     

Cross sections of electron inelastic interactions in DNA

The cross sections of electron inelastic interaction in DNA are calculated using the dielectric response theory and Penn statistical approximation, with the exchange correction included. An empirical approach to obtain optical energy loss function is given for the organic compounds without available optical data. Comparisons of the calculated data with available experimental and theoretical results have been done to show the reliability of the approach proposed in this work. Using this approach, the total inelastic cross sections for five bases: guanine, adenine, thymine, cytosine and uracil have been calculated in the energy range of E10 keV and compared with those recently obtained with the Deutsch-Märk formalism and the Binary-Encounter-Bethe model, respectively. An equivalent unit of the DNA molecule is constructed according to the contents of A-T and G-C base pairs in DNA, and is divided into five constituents, i.e. sugar-phosphate and four bases. The total inelastic cross sections for the constructed unit of the DNA molecule and its constituents have also been calculated.     

The application of tetrahydroisoquinoline-3-carbonyl-TARGD(F)F as an anti-thrombotic agent having dual mechanisms of action

Platelet surface glycoproteins P-selectin and GPIIb/IIIa are implicated in the formation of platelet-fibrin-leukocyte thrombus and platelet-fibrin-platelet thrombus, respectively. In the current study, taking N-(3S-tetrahydroisoquinoline-3-carbonyl)-Thr-Ala-Arg-Gly-Asp-(Phe)-Phe (IQCA-TAFF) as a model compound, the molecular modeling, synthesis, and an evaluation system for a novel anti-thrombotic agent were investigated. The synthesis of IQCA-TAFF was achieved by coupling 3S-tetrahydro-isoquinoline-3-carboxylic acid (IQCA) and Thr-Ala-Arg-Gly-Asp(Phe)-Phe (TAFF). The molecular modeling indicated that IQCA-TAFF was able to occupy the active site pocket of P-selectin with its IQCA moiety and to block GPIIb/IIIa fibrinogen-binding sites with its TAFF moiety, respectively. These are consistent with the dual inhibition of the expressions of P-selectin and GPIIb/IIIa, and with the in vitro anti-platelet aggregation activity of IQCA-TAFF. Besides, the dual suppression of P-selectin and GPIIb/IIIa leads to significant in vivo efficacy of IQCA-TAFF, 500-fold higher than those of IQCA and TAFF, respectively. Transmission electron microscopy (TEM) images indicated that in water, IQCA-TAFF concentration-dependently formed nano-globes. The molecular modeling, in vitro bioassay, in vivo bioassay, action mechanism investigation, and nano-image visualization together constitute a model system to characterize the anti-thrombotic agent capable of simultaneously inhibiting P-selectin and GPIIb/IIIa mediated thrombosis.     

2001-2015年天山北坡植被覆盖对干旱的响应——基于土地利用/土地覆盖分析

天山北坡生态系统脆弱,易受干旱影响,全球变暖和不合理的人类活动加剧了干旱的影响,评估植被覆盖对干旱的响应,为改善生态环境和减轻干旱影响提供科学参考。基于MODIS-NDVI遥感数据以及气象数据,计算了2001-2015年天山北坡多尺度标准化降水蒸散发指数（SPEI）和植被覆盖度,总结出植被覆盖度与多尺度SPEI时空动态变化规律,从土地利用/土地覆盖（LUCC）的角度分析了植被覆盖度对气候干旱的响应。结果表明：（1）天山北坡绝大部分区域呈湿润状态,中部（石河子、呼图壁）、西北部（克拉玛依市）呈轻度干旱。3个月、6个月、12个月时间尺度SPEI均表现出干旱化增强的年际变化趋势;（2）天山北坡植被覆盖度整体上属中低覆盖,总体呈南高北低,天山山区、城市绿洲内部高的分布特点。2001-2015年天山北坡植被覆盖度变化总体呈下降趋势;（3）年尺度天山北坡植被覆盖度与SPEI整体呈正相关关系。不同土地利用/土地覆盖的植被覆盖度与12个月时间尺度SPEI（SPEI 12）的相关性不同,大小依次为：草地 > 未利用地 > 城乡用地 > 林地 > 水域 > 耕地;（4）季节尺度夏季和春季干旱对植被覆盖度的影响最明显,不同季节干旱对不同土地利用/土地覆盖植被覆盖度影响程度不同。     

New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review

Pain is an unpleasant sensory and emotional experience that is commonly associated with actual or potential tissue damage. Despite decades of pain research, many patients continue to suffer from chronic pain that is refractory to current treatments. Accumulating evidence has indicated an important role of protease-activated receptor 4 (PAR4) in the pathogenesis of inflammation and neuropathic pain. Here we reviewed PAR4 expression and activation via intracellular signaling pathways and the role of PAR4 signaling pathways in the development and maintenance of pain. Understanding PAR4 and its corresponding signaling pathways will provide insight to further explore the molecular basis of pain, which will also help to identify new targets for pharmacological intervention for pain relief.