Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.     

Effect of pharmaceuticals on thermoreversible gelation of PEO-PPO-PEO copolymers

Pluronic F127, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), has generated considerable interest as a drug delivery vehicle due to its ability to gel at physiological temperatures. This work examines the gelation behavior of Pluronic F127 in the presence of a series of hydrophobic pharmaceuticals, to determine whether there is any correlation between gelation and physicochemical parameters of drug solutes. The study includes the local anesthetics dibucaine, lidocaine, and tetracaine; the pharmaceutical additives methyl paraben, ethyl paraben, and propyl paraben; the anti-cancer agents paclitaxel and baccatin III; and the anti-inflammatory agent sulindac. The results indicate that the presence of local anesthetics and pharmaceutical additives allows F127 solutions to form gels at lower copolymer concentrations; local anesthetics and pharmaceutical additives also shift gelation down to a lower gelation temperature. This behavior is strongly dependent on drug solubility; poorly soluble drugs (paclitaxel, baccatin III, sulindac) do not change the lower gelation temperature or minimum F127 concentration for gelation. An equation relating the decrease in gelation temperature to drug solubility is presented, and the equation fits the data well. The results have significant positive implications on the toxicity and economic issues related to use of Pluronic F127 in drug delivery.     

Developing CRISPR/Cas9-Mediated Fluorescent Reporter Human Pluripotent Stem-Cell Lines for High-Content Screening

Application of the CRISPR/Cas9 system to knock in fluorescent proteins to endogenous genes of interest in human pluripotent stem cells (hPSCs) has the potential to facilitate hPSC-based disease modeling, drug screening, and optimization of transplantation therapy. To evaluate the capability of fluorescent reporter hPSC lines for high-content screening approaches, we targeted EGFP to the endogenous OCT4 locus. Resulting hPSC–OCT4–EGFP lines generated expressed EGFP coincident with pluripotency markers and could be adapted to multi-well formats for high-content screening (HCS) campaigns. However, after long-term culture, hPSCs transiently lost their EGFP expression. Alternatively, through EGFP knock-in to the AAVS1 locus, we established a stable and consistent EGFP-expressing hPSC–AAVS1–EGFP line that maintained EGFP expression during in vitro hematopoietic and neural differentiation. Thus, hPSC–AAVS1–EGFP-derived sensory neurons could be adapted to a high-content screening platform that can be applied to high-throughput small-molecule screening and drug discovery campaigns. Our observations are consistent with recent findings indicating that high-frequency on-target complexities appear following CRISPR/Cas9 genome editing at the OCT4 locus. In contrast, we demonstrate that the AAVS1 locus is a safe genomic location in hPSCs with high gene expression that does not impact hPSC quality and differentiation. Our findings suggest that the CRISPR/Cas9-integrated AAVS1 system should be applied for generating stable reporter hPSC lines for long-term HCS approaches, and they underscore the importance of careful evaluation and selection of the applied reporter cell lines for HCS purposes.     

Hydromagnetic Stability of a Self-Gravitating Composite Plasma in the Presence of Finite Larmor Radius

The hydromagnetic stability of a self-gravitating composite plasma has been studied to include the effects of ion viscosity and the finiteness of the ion Larmor radius. The whole medium is embedded in a uniform horizontal magnetic field. The F. L. R. effects have been included through the stress tensor. An explicit solution for a semi-infinite plasma of finite depth and with an exponential density variation along the vertical is obtained by means of a variational principle characterizing the problem. Numerical calculations show that the influence of the effects of ion viscosity and F. L. R. is to reduce the growth rate of unstable perturbations. On the other hand the effects of neutral gas collisions have been found to be both stabilizing as well as destabilizing.     

The third and fourth spectra of gallium: Ga III and Ga IV

The third and fourth spectra of gallium have been photographed in the region 6000–400 Å by using a 3-m normal-incidence, vacuum spectrograph and a 3.5-m Ebert spectrograph. A three-electrode vacuum spark and a spark in helium were used as sources. New measurements for the wavelengths have confirmed earlier work and provided material to extend the analysis of Ga III and Ga IV.     

Azimuthal anisotropy and correlations at large transverse momenta in p + p and Au + Au collisions at square root sNN=200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au + Au collisions at square root s(NN)=200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au + Au collisions to those in p + p at the same energy. The elliptic anisotropy v(2) is found to reach its maximum at p(t) approximately 3 GeV/c, then decrease slowly and remain significant up to p(t) approximately 7-10 GeV/c. Stronger suppression is found in the back-to-back high-p(t) particle correlations for particles emitted out of plane compared to those emitted in plane. The centrality dependence of v(2) at intermediate p(t) is compared to simple models based on jet quenching.     

Enzymatic synthesis of oligosaccharides, alkyl and terpenyl glucosides, by recombinant Escherichia coli-expressed Pichia etchellsii β-glucosidase II

The biosynthetic activity of yeast Pichia etchellsii β-glucosidase II (BglII) expressed in recombinant Escherichia coli was utilized for synthesis of cellooligosaccharides, alkyl and terpene glucosides. Cellooligosaccharides with a degree of polymerization of 3 and greater were resolved by thin-layer chromatography (TLC) using an ethyl acetate: 1-propanol:2-propanol:water (8:5:1:1) solvent system followed by visualization with 0.2% naphthoresorcinol reagent. Using 2M cellobiose and 15 IU of partially purified BglII, 57 mmol/L of oligosaccharides (comprising mostly cellotriose and cellopentaose) was synthesized in 16 h. Similarly, alkyl glucosides with chain lengths from 6 to 10 carbons were synthesized and products extracted to near purity by ethylacetate extraction. The same extraction method was employed to separate, to near purity, various monoterpenyl (nerol, geraniol, citronellol) glucosides. A reliable and simple method for separation of cellooligosaccharides using a combination of Bio-Gel P-2 gel filtration and charcoal celite adsorption chromatography was developed. The cellooligosaccharides were separated to purity as confirmed by TLC. The enzyme was among the very few that could synthesize a wide variety of glycoconjugates.     

Wall mediated transport in confined spaces: exact theory for low density

We present a theory for the transport of molecules adsorbed in slit and cylindrical nanopores at low density, considering the axial momentum gain of molecules oscillating between diffuse wall reflections. Good agreement with molecular dynamics simulations is obtained over a wide range of pore sizes, including the regime of single-file diffusion where fluid-fluid interactions are shown to have a negligible effect on the collective transport coefficient. We show that dispersive fluid-wall interactions considerably attenuate transport compared to classical hard sphere theory.     

Versatile and facile synthesis of diverse semisynthetic tetracycline derivatives via Pd-catalyzed reactions

A diverse collection of tetracycline derivatives has been synthesized utilizing Heck, Suzuki, and other palladium-coupling reactions via tetracycline arenediazonium and iodoarene salts. Large numbers of tetracyclines are now possible via these reactions, including numerous upper periphery derivatives of doxycycline, minocycline, sancycline, and methacycline modified at positions C7, C9, and C6-C13 on the tetracycline naphthacene ring. Application of palladium-coupling reactions to the tetracyclines has yielded new tetracycline classes with differing structural attributes, greatly increasing the structural diversity of this family of antibiotics, one of the last of the early antibiotic families to be expanded by organic and medicinal chemistry.     

Thermally Conducting Partially Ionized Plasma in a Variable Magnetic Field

An infinitely extending homogenous partially ionized plasma endowed with several physical mechanisms and permeated by a variable magnetic field is considered. The combined effect of these parameters, namely, Hall currents, finite conductivity, ion viscosity, collision with neutrals and thermal conductivity on the gravitational instability of the plasma is studied. It is found that the several mechanisms play different physical roles in the perturbed problem. Jeans' Criterion is analyzed in the framework of Tsallis' statistics for possible modifications due to the presence of nonextensive effects. A simple generalization of the Jeans' criterion is obtained and the standard values are obtained in the limiting case q = 1, q being the nonextensive parameter. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)