Design,RNA cleavage and antiviral activity of new artificial ribonucleases derived from mono-, di- and tripeptides connected by linkers of different hydrophobicity

A novel series of metal-free artificial ribonucleases (aRNases) was designed, synthesized and assessed in terms of ribonuclease activity and ability to inactivate influenza virus WSN/A33/H1N1 in vitro. The compounds were built of two short peptide fragments, which include Lys, Ser, Arg, Glu and imidazole residues in various combinations, connected by linkers of different hydrophobicity (1,12-diaminododecane or 4,9-dioxa-1,12-diaminododecane). These compounds efficiently cleaved different RNA substrates under physiological conditions at rates three to five times higher than that of artificial ribonucleases described earlier and displayed RNase A-like cleavage specificity. aRNases with the hydrophobic 1,12-diaminododecane linker displayed ribonuclease activity 3–40 times higher than aRNases with the 4,9-dioxa-1,12-diaminododecane linker. The assumed mechanism of RNA cleavage was typical for natural ribonucleases, that is, general acid-base catalysis via the formation of acid/base pairs by functional groups of amino acids present in the aRNases; the pH profile of cleavage confirmed this mechanism. The most active aRNases under study exhibited high antiviral activity and entirely inactivated influenza virus A/WSN/33/(H1N1) after a short incubation period of viral suspension under physiological conditions.     

Helper factor(s) augment in vitro induction of tumor-specific immunity

Helper factor supernatants derived from alloantigen-activated murine lymphocytes augment the generation of cytolytic effector cells to syngeneic tumor cells. The effects are dose dependent and vary with the syngeneic tumor cell system studied. The effector cells are specific for the tumor-associated antigen(s) utilized for their induction, and are sensitive to lysis with anti-T-cell serum (Thy 1.2), but are insensitive to lysis with an allogeneic anti-NK-cell serum. The helper factor supernatants also augment the production of a “tissue-culture-induced” cytolytic cell (cultured NK cell), which is resistant to treatment with both anti-Thy 1.2 and anti-NK serum.     

The Analysis of Partial Diallel Crosses

The analysis of offsprings from the partial diallel crosses is presented. In considered type of crossing, p parental forms into H separate groups are devided. Single crosses among parental forms, from separate groups only, are performed. The analysis for experiments laid out in efficiency balanced block designs is given.     

Contemporary parasite stress curvilinearly correlates with outgroup trust: Cross-country evidence from 2005 to 2014

General trust is trust extended to people from outside one's immediate social network. Two studies have tested a parasite stress explanation of general trust using cross-cultural data, showing a linear negative correlation between parasite stress and trust in “most people.” However, recent studies suggest that 1) trust in most people as a measure of general trust confounds ingroup trust and outgroup trust in cross-cultural surveys and 2) parasite stress can curvilinearly correlate with variables of ingroup embeddedness and outgroup avoidance. Using data from the World Value Survey (WVS) Waves 5 and 6 (N?=?117,370 from 80 countries and geopolitical regions), we found no evidence that parasite stress—measured either as contemporary non-sexually-transmitted-disease (non-STD) stress or as historical pathogen prevalence—curvilinearly correlated with ingroup trust. However, parasite stress significantly curvilinearly correlated with outgroup trust, and the two-line test confirmed that the correlation was U-shaped. This research extends previous work on parasite stress and trust, informs the recent debate on whether parasite stress relates to outgroup avoidance, and suggests directions for developing the parasite stress theory of values and sociality.     

Cardiac Stress Test Induced by Dobutamine and Monitored by Cardiac Catheterization in Mice

Dobutamine is a β-adrenergic agonist with an affinity higher for receptor expressed in the heart (β₁) than for receptors expressed in the arteries (β₂). When systemically administered, it increases cardiac demand. Thus, dobutamine unmasks abnormal rhythm or ischemic areas potentially at risk of infarction. Monitoring of heart function during a cardiac stress test can be performed by either ecocardiography or cardiac catheterization. The latter is an invasive but more accurate and informative technique that the former.Cardiac stress test induced by dobutamine and monitored by cardiac catheterization accomplished as described here allows, in a single experiment, the measurement of the following hemodynamic parameters: heart rate (HR), systolic pressure, diastolic pressure, end-diastolic pressure, maximal positive pressure development (dP/dtmax) and maximal negative pressure development (dP/dt_min), at baseline conditions and under increasing doses of dobutamine.As expected, in normal mice we observed a dobutamine dose-related increase in HR, dP/dt_max and dP/dt_min. Moreover, at the highest dose tested (12 ng/g/min) the cardiac decompensation of high fat diet-induced obese mice was unmasked.     

A Novel Three-dimensional Flow Chamber Device to Study Chemokine-directed Extravasation of Cells Circulating under Physiological Flow Conditions

Extravasation of circulating cells from the bloodstream plays a central role in many physiological and pathophysiological processes, including stem cell homing and tumor metastasis. The three-dimensional flow chamber device (hereafter the 3D device) is a novel in vitro technology that recreates physiological shear stress and allows each step of the cell extravasation cascade to be quantified. The 3D device consists of an upper compartment in which the cells of interest circulate under shear stress, and a lower compartment of static wells that contain the chemoattractants of interest. The two compartments are separated by porous inserts coated with a monolayer of endothelial cells (EC). An optional second insert with microenvironmental cells of interest can be placed immediately beneath the EC layer. A gas exchange unit allows the optimal CO₂ tension to be maintained and provides an access point to add or withdraw cells or compounds during the experiment. The test cells circulate in the upper compartment at the desired shear stress (flow rate) controlled by a peristaltic pump. At the end of the experiment, the circulating and migrated cells are collected for further analyses. The 3D device can be used to examine cell rolling on and adhesion to EC under shear stress, transmigration in response to chemokine gradients, resistance to shear stress, cluster formation, and cell survival. In addition, the optional second insert allows the effects of crosstalk between EC and microenvironmental cells to be examined. The translational applications of the 3D device include testing of drug candidates that target cell migration and predicting the in vivo behavior of cells after intravenous injection. Thus, the novel 3D device is a versatile and inexpensive tool to study the molecular mechanisms that mediate cellular extravasation.     

硬膜外复合全身麻醉对开胸手术患者血流动力学和应激反应的影响研究

目的:研究硬膜外复合全身麻醉对开胸手术患者血流动力学和应激反应的影响。方法:选取120例我院2015年1月到2016年1月收治的开胸手术患者,按照随机数字表法将患者分为研究组和对照组,对照组给予单纯全麻,研究组给予硬膜外复合全身麻醉,比较两组苏醒时间、苏醒期收缩压、舒张压、心率及烦躁情况,并比较两组术前、术后72 h血糖、皮质醇以及肾上腺素水平。结果:两组苏醒时间比较无统计学意义(P0.05),苏醒期研究组收缩压、舒张压及心率、烦躁发生率均较对照组降低(P0.05);两组术前血糖、皮质醇及肾上腺素比较无统计学差异(P0.05);术后72 h,两组血糖、皮质醇及肾上腺素均升高(P0.05);研究组血糖、皮质醇及肾上腺素均较对照组降低(P0.05)。结论:硬膜外复合全身麻醉应用于开胸手术能显著提高患者苏醒期苏醒质量,稳定血流动力学,改善其应激反应。