Serum biomarkers in interstitial lung diseases

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.     

Rehydration with glycerol: endocrine, cardiovascular, and thermoregulatory responses during exercise in the heat.

The impact of rehydration with glycerol on cardiovascular and thermoregulatory responses during exercise in the heat was studied in eight highly trained male cyclists. Each subject completed three dehydration-rehydration experimental trials that differed only in the rehydration treatment, each separated by 7 days. Before each experimental day, subjects dehydrated to -4% of their body weight by exercise and water restriction. The experimental treatments were as follows: no fluid (NF), glycerol bolus (1 g/kg body wt) followed by water (G), and water alone (W). Rehydration (3% body weight) was given over an 80-min period. After rehydration, subjects cycled (74% peak O2 uptake) to exhaustion in a hot and wet (37 degrees C and 48% relative humidity) environment. For G, plasma volume was expanded (P < 0.05) during rehydration and remained higher than W (P < 0.05) during exercise. Exercise time to exhaustion during G (33 +/- 4 min) was longer (P < 0.05) compared with both W (27 +/- 3 min) and NF (19 +/- 3 min). Cutaneous vascular conductance was significantly elevated (P < 0.05) during G, but G provided no other thermoregulatory or cardiovascular benefits compared with W and NF. Fluid-regulating hormones (vasopressin, aldosterone, atriopeptin, and plasma renin activity) decreased during rehydration and increased during exercise (except atriopeptin), but there were no differences between G and W. These data indicated that glycerol had little or no major effect on fluid-regulating factors during rehydration or exercise, and the improved exercise capacity in G was likely due to a greater plasma volume during exercise.     

The dynamics of a model of a plankton-nutrient interaction

A stability analysis is given for a model of plankton dynamics introduced by Wroblewskiet al. (Global Biogeochem. Cycles 2, 199–218, 1988). The detailed dependence of the steady-states and their stability on the various model parameters is explicitly presented and analysed. It is shown that under certain conditions the coexistence of phytoplankton and zooplankton occurs in an orbitally stable oscillatory mode. A distinguished parameter is varied and the steady-states computed. The significance of the lack of stable steady-states leading to periodic population levels is investigated and related to certain oceanographic data. Partially supported by NSF Grant DMS-8902712. Supported by New Zealand University Grants Committee Postdoctoral Fellowship.     

Synthesis and biological evaluation of aminothiazoles against Histoplasma capsulatum and Cryptococcus neoformans

The design and synthesis of a library of forty novel 2-aminoazole analogues as well as their evaluation as antifungal compounds against Histoplasma capsulatum and Cryptococcus neoformans is described. These structures were derived from N-[5-(1-naphthalenylmethyl)-2-thiazolyl]cyclohexanecarboxamide (41F5), a fungistatic agent previously identified through phenotypic screening (Antimicrob Agents Chemother. 2013;57:4349). Modifications to improve potency and water-solubility of 41F5 focused primarily on the 5-naphthalenyl group, the thiazole core, and the methylene linker between these two structural elements. In general, compounds with lipophilic [5+6] bicyclic ring systems, such as the 7-benzothiophenyl- and 4-indanyl groups, at the 5-position were 2–3 times more active against both fungal species as compared to 41F5. Also, introduction of a carbonyl group at the methylene linker of 41F5 resulted in a 2–3-fold increase in potency. These highly active compounds also showed generally low toxicities against murine P388D1 macrophages resulting in selectivity indices ranging from 63 to >200. Compounds that were highly active against fluconazole-sensitive C. neoformans strains had almost identical activity against fluconazole-resistant variants of this fungus indicating that 14α-demethylase is not their molecular target. Highly active compounds also retained activity against H. capsulatum phagocytosed into P388D1 macrophages.     

Evidence for Myelin Sheath Remodeling in the CNS Revealed by In Vivo Imaging

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Influence of precipitating agents on thermodynamic parameters of protein crystallization solutions

X‐ray crystallography is the most powerful method for determining three‐dimensional structures of proteins to (near‐)atomic resolution, but protein crystallization is a poorly explained and often intractable phenomenon. Differential Scanning Calorimetry was used to measure the thermodynamic parameters (ΔG, ΔH, ΔS) of temperature‐driven unfolding of two globular proteins, lysozyme, and ribonuclease A, in various salt solutions. The mixtures were categorized into those that were conducive to crystallization of the protein and those that were not. It was found that even fairly low salt concentrations had very large effects on thermodynamic parameters. High concentrations of salts conducive to crystallization stabilized the native folded forms of proteins, whereas high concentrations of salts that did not crystallize them tended to destabilize them. Considering the ΔH and TΔS contributions to the ΔG of unfolding separately, high concentrations of crystallizing salts were found to enthalpically stabilize and entropically destabilize the protein, and vice‐versa for the noncrystallizing salts. These observations suggest an explanation, in terms of protein stability and entropy of hydration, of why some salts are good crystallization agents for a given protein and others are not. This in turn provides theoretical insight into the process of protein crystallization, suggesting ways of predicting and controlling it. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 642–652, 2016.     

Plasmonic Backscattering Effect in High‐Efficient Organic Photovoltaic Devices

A universal strategy for efficient light trapping through the incorporation of gold nanorods on the electron transport layer (rear) of organic photovoltaic devices is demonstrated. Utilizing the photons that are transmitted through the active layer of a bulk heterojunction photovoltaic device and would otherwise be lost, a significant enhancement in power conversion efficiency (PCE) of poly[N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)]:phenyl‐C₇₁‐butyric acid methyl ester (PCDTBT:PC₇₁BM) and poly[[4,8‐bis[(2‐ethylhexyl)oxy]benzo[1,2‐b:4,5‐b′]dithiophene‐2,6‐diyl][3‐fluoro‐2‐[(2‐ethylhexyl)carbonyl]thieno[3,4‐b] thiophenediyl]] (PTB7):PC₇₁BM by ≈13% and ≈8%, respectively. PCEs over 8% are reported for devices based on the PTB7:PC₇₁BM blend. A comprehensive optical and electrical characterization of our devices to clarify the influence of gold nanorods on exciton generation, dissociation, charge recombination, and transport inside the thin film devices is performed. By correlating the experimental data with detailed numerical simulations, the near‐field and far‐field scattering effects are separated of gold nanorods (Au NRs), and confidently attribute part of the performance enhancement to the enhanced absorption caused by backscattering. While, a secondary contribution from the Au NRs that partially protrude inside the active layer and exhibit strong near‐fields due to localized surface plasmon resonance effects is also observed but is minor in magnitude. Furthermore, another important contribution to the enhanced performance is electrical in nature and comes from the increased charge collection probability.