Isolation, biology and chemistry of the disorazoles: New anti-cancer macrodiolides

The disorazoles comprise a family of 29 closely related macrocyclic polyketides isolated in 1994 from the fermentation broth of the gliding myxobacterium Sorangium cellulosum. Disorazoles A1, E and C 1 have shown exceptional biological activities toward inhibiting the proliferation of human cancer cell lines in picomolar and nanomolar concentrations through the disruption of microtubule polymerization. This review gives a brief introduction describing the biosynthesis and the significance of the disorazoles as a new class of microtubulin disruptors. Another portion of the review focuses on the biology of the disorazoles, specifically disorazole A1 and C1, and their antiproliferative efficacy against animal and human tumor cell lines, as well as the available SAR data. The majority of the discussion addresses synthetic efforts, including partial syntheses of various disorazoles and a summary of the total synthesis of disorazole C1. © 2009 The Royal Society of Chemistry

Likelihood informed dimension reduction for inverse problems in remote sensing of atmospheric constituent profiles

We use likelihood informed dimension reduction (LIS) (T. Cui et al. 2014) for inverting vertical profile information of atmospheric methane from ground based Fourier transform infrared (FTIR) measurements at Sodankyl\"a, Northern Finland. The measurements belong to the word wide TCCON network for greenhouse gas measurements and, in addition to providing accurate greenhouse gas measurements, they are important for validating satellite observations. LIS allows construction of an efficient Markov chain Monte Carlo sampling algorithm that explores only a reduced dimensional space but still produces a good approximation of the original full dimensional Bayesian posterior distribution. This in effect makes the statistical estimation problem independent of the discretization of the inverse problem. In addition, we compare LIS to a dimension reduction method based on prior covariance matrix truncation used earlier (S. Tukiainen et al. 2016)

Chick stem cells: Current progress and future prospects.

Chick embryonic stem cells (cESCs) can be derived from cells obtained from stage X embryos (blastoderm stage); these have the ability to contribute to all somatic lineages in chimaeras, but not to the germ line. However, lines of stem cells that are able to contribute to the germ line can be established from chick primordial germ cells (cPGCs) and embryonic germ cells (cEGCs). This review provides information on avian stem cells, emphasizing different sources of cells and current methods for derivation and culture of pluripotent cells from chick embryos. We also review technologies for isolation and derivation of chicken germ cells and the production of transgenic birds

Incorporation of causality structures to complex network analysis of time-varying behaviour of multivariate time series

This paper presents a new methodology for characterising the evolving behaviour of the time-varying causality between multivariate time series, from the perspective of change in the structure of the causality pattern. We propose that such evolutionary behaviour should be tracked by means of a complex network whose nodes are causality patterns and edges are transitions between those patterns of causality. In our new methodology each edge has a weight that includes the frequency of the given transition and two metrics relating to the gross and net structural change in causality pattern, which we call [Formula: see text] and [Formula: see text]. To characterise aspects of the behaviour within this network, five approaches are presented and motivated. To act as a demonstration of this methodology an application of sample data from the international oil market is presented. This example illustrates how our new methodology is able to extract information about evolving causality behaviour. For example, it reveals non-random time-varying behaviour that favours transitions resulting in predominantly similar causality patterns, and it discovers clustering of similar causality patterns and some transitional behaviour between these clusters. The example illustrates how our new methodology supports the inference that the evolution of causality in the system is related to the addition or removal of a few causality links, primarily keeping a similar causality pattern, and that the evolution is not related to some other measure such as the overall number of causality links

Neurogenic hypothesis and psychiatric disorders

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An electrochemical system for efficiently harvesting low-grade heat energy

Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low figure-of-merit and low-temperature differential. An alternative approach is to explore thermodynamic cycles. Thermogalvanic effect, the dependence of electrode potential on temperature, can construct such cycles. In one cycle, an electrochemical cell is charged at a temperature and then discharged at a different temperature with higher cell voltage, thereby converting heat to electricity. Here we report an electrochemical system using a copper hexacyanoferrate cathode and a Cu/Cu2+ anode to convert heat into electricity. The electrode materials have low polarization, high charge capacity, moderate temperature coefficients and low specific heat. These features lead to a high heat-to-electricity energy conversion efficiency of 5.7% when cycled between 10 and 60 degrees C, opening a promising way to utilize low-grade heat.open121

Glucose enhancement of memory is modulated by trait anxiety in healthy adolescent males

Glucose administration is associated with memory enhancement in healthy young individuals under conditions of divided attention at encoding. While the specific neurocognitive mechanisms underlying this ‘glucose memory facilitation effect’ are currently uncertain, it is thought that individual differences in glucoregulatory efficiency may alter an individual’s sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic–pituitary–adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14–17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic–pituitary–adrenal axis function did not appear to influence the glucose memory facilitation effect; however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety

Reducing complexity and unidentifiability when modelling human atrial cells

Mathematical models of a cellular action potential in cardiac modelling have become increasingly complex, particularly in gating kinetics which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalised medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the action potential. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed

Tempol Improves Xanthine Oxidoreductase-mediated Vascular Responses To Nitrite In Experimental Renovascular Hypertension

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Upregulation of xanthine oxidoreductase (XOR) increases vascular reactive oxygen species (ROS) levels and contributes to nitroso-redox imbalance. However, XOR can generate nitric oxide (NO) from nitrite, and increased superoxide could inactivate NO formed from nitrite. This study tested the hypothesis that XOR contributes to the cardiovascular effects of nitrite in renovascular hypertension, and that treatment with the antioxidant tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) improves XOR-mediated effects of nitrite. Blood pressure was assessed weekly in two-kidney one-clip (2K1C) and control rats. After six weeks of hypertension, the relaxing responses to nitrite were assessed in aortic rings in the presence of the XOR inhibitor oxypurinol (or vehicle), either in the absence or in the presence of tempol. Moreover, in vivo hypotensive responses to nitrite were also examined in the presence of oxypurinol (or vehicle) and tempol (or vehicle). Aortic XOR activity and expression were evaluated by fluorescence and Western blot, respectively. Vascular ROS production was assessed by the dihydroethidium assay. 2K1C hypertensive rats showed increased aortic XOR activity and vascular ROS production compared with control rats. Oxypurinol shifted the nitrite concentration response curve to the right in aortic rings from 2K1C rats (but not in controls). Oxypurinol also attenuated the hypotensive responses to nitrite in 2K1C rats (but not in controls). These functional findings agree with increased aortic and plasma XOR activity found in 2K1C rats. Tempol treatment enhanced oxypurinol-induced shift of the nitrite concentration response curve to the right. However, antioxidant treatment did not affect XOR-mediated hypotensive effects of nitrite. Our results show that XOR is important to the cardiovascular responses to nitrite in 2K1C hypertension, and XOR inhibitors commonly used by patients may cancel this effect. This finding suggests that nitrite treatment may not be effective in patients being treated with XOR inhibitors. Moreover, while tempol may improve the vascular responses to nitrite, antihypertensive responses are not affected. (C) 2016 The Authors. Published by Elsevier B.V.8398406Fundacao de Aparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014-23946-0]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)CAPES (Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES