Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions

Background

Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained.

Methodology/Principal Findings

We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients.

Conclusions/Significance

Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known) congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition.     

A Lithium–Sulfur Cell Based on Reversible Lithium Deposition from a Li2S Cathode Host onto a Hostless‐Anode Substrate

The development of lithium–sulfur batteries necessitates a thorough understanding of the lithium‐deposition process. A novel full‐cell configuration comprising an Li₂S cathode and a bare copper foil on the anode side is presented here. The absence of excess lithium allows for the realization of a truly lithium‐limited Li–S battery, which operates by reversible plating and stripping of lithium on the hostless‐anode substrate (copper foil). Its performance is closely tied to the efficiency of lithium deposition, generating valuable insights on the role and dynamic behavior of lithium anode. The Li₂S full cell shows reasonable capacity retention with a Coulombic efficiency of 96% over 100 cycles, which is a tremendous improvement over that of a similar lithium‐plating‐based full cell with LiFePO₄ cathodes. The exceptional robustness of the Li₂S system is attributed to an intrinsic stabilization of the lithium‐deposition process, which is mediated by polysulfide intermediates that form protective Li₂S and Li₂S₂ regions on the deposited lithium. Combined with the large improvements in energy density and safety by the elimination of a metallic lithium anode, the stability and electrochemical performance of the lithium‐plating‐based Li₂S full cell establish it as an important trajectory for Li–S battery research, focusing on practical realization of reversible lithium anodes.     

Exploiting Phosphate-Starved cells of <Emphasis Type="Italic">Scenedesmus</Emphasis> sp. for the Treatment of Raw Sewage

Phosphate depletion is one of the favorable ways to enhance the sewage water treatment with the algae, however, detailed information is essential with respect to internal phosphate concentration and physiology of the algae. The growth rate of the phosphate-starved Scenedesmus cells was reduced drastically after 48 h. Indicating cells entered in the stationary phase of the growth cycle. Fourier Transform Infrared analysis of phosphate-starved Scenedesmus cells showed the reduction in internal phosphate concentration and an increase in carbohydrate/phosphate and carbohydrate/lipid ratio. The phosphate-starved Scenedesmus cells, with an initial cell density of, 1 × 10⁶ cells mL^?1 shows 87% phosphate and 100 % nitrogen removal in 24 h. The normal Scenedesmus cells need approximately 48 h to trim down the nutrients from wastewater up to this extent. Other microalgae, Ankistrodesmus, growth pattern was not affected due to phosphate starvation. The cells of Ankistrodesmus was able to reduce 71% phosphate and 73% nitrogen within 24 h, with an initial cell density of, 1 × 10⁶ cells mL^?1.     

Nanocrystalline SrS:Ce3+ system for the generation of white light‐emitting diodes

Nanocrystalline SrS phosphors doped with Ce³⁺ ions at different concentrations (0.5, 1, 1.5 and 2 mol%) are synthesized via the solid‐state diffusion method (SSDM), which is suitable for the large‐scale production of phosphors in industrial applications. The as‐prepared samples are characterized using an X‐ray diffraction (XRD) technique, field emission scanning electron microscopy (FESEM), high‐resolution transmission electron microscopy (HRTEM) and energy‐dispersive X‐ray (EDX) analysis. The optical properties of these phosphors are analyzed using reflectance spectra, photoluminescence spectra and afterglow decay curves. The cubic structure of the SrS phosphor is confirmed by XRD analysis and the crystallite size calculated by Scherer's formula using XRD data shows the nanocrystalline nature of the phosphors. No phase change is observed with increasing concentrations of Ce³⁺ ions. The surface morphology of the prepared phosphors is determined by FESEM, which shows a sphere‐like structure and good connectivity of the grains. The authenticity of the formation of nanocrystalline phosphors is examined by HRTEM analysis. Elemental compositional information for the prepared phosphors is gathered by EDX analysis. Photoluminescence studies reveal that the emission spectra of the prepared phosphor shows broad band emission centered at 458 and 550 nm due to the transition of electrons from the 5d → 4f energy levels. The afterglow decay characteristics of different as‐synthesized SrS:Ce³⁺ nanophosphors are conceptually described. Copyright © 2016 John Wiley & Sons, Ltd.     

Endemic Asian Chytrid Strain Infection in Threatened and Endemic Anurans of the Northern Western Ghats,India

The Western Ghats of India harbors a rich diversity of amphibians with more than 77% species endemic to this region. At least 42% of the endemic species are threatened due to several anthropogenic stressors. However, information on amphibian diseases and their impacts on amphibian populations in this region are scarce. We report the occurrence of Batrachochytridium dendrobatidis (Bd), an epidermal aquatic fungal pathogen that causes chytridiomycosis in amphibians, from the Western Ghats. In the current study we detected the occurrence of a native Asian Bd strain from three endemic and threatened species of anurans, Bombay Night Frog Nyctibatrachus humayuni, Leith''s Leaping Frog Indirana leithii and Bombay Bubble Nest Frog Raorchestes bombayensis, for the first time from the northern Western Ghats of India based on diagnostic nested PCR, quantitative PCR, DNA sequencing and histopathology. While, the Bd infected I. leithii and R. bombayensis did not show any external symptoms, N. humayuni showed lesions on the skin, browning of skin and sloughing. Sequencing of Bd 5.8S ribosomal RNA gene, and the ITS1 and ITS2 regions, revealed that the current Bd strain is related to a haplotype endemic to Asia. Our findings confirm the presence of Bd in northern Western Ghats and the affected amphibians may or may not show detectable clinical symptoms. We suggest that the significance of diseases as potential threat to amphibian populations of the Western Ghats needs to be highlighted from the conservation point of view.     

A Cascading Auction Protocol as a Framework for Integrating Process Planning and Heterarchical Shop Floor Control

A new contract net-style auction protocol is proposed as a framework for integrating process planning and shop floor control in heterarchical manufacturing systems. Process planning is partitioned into on-line and off-line activities; off-line process planning decisions are represented in a graph format and used as input for on-line process planning activities performed by machine controllers. Triggered by the opening round of an auction, the final on-line stages of process planning are dovetailed with the resource allocation process in the shop floor control system. The auction process allows final process planning decisions to be based on timely information, relying on the distribution of static process planning information rather than the distribution of a model of dynamic shop floor status and allowing a controller to identify all the primary and secondary resources and operations that must be provided for the incremental processing of a part.     

Molecular modeling,dynamics studies and density functional theory approaches to identify potential inhibitors of SIRT4 protein from Homo sapiens : a novel target for the treatment of type 2 diabetes

Type 2 diabetes is one of the biggest health challenges in the world and WHO projects it to be the 7th leading cause of death in 2030. It is a chronic condition affecting the way our body metabolizes sugar. Insulin resistance is high risk factor marked by expression of Lipoprotein Lipases and Peroxisome Proliferator-Activated Receptor that predisposes to type 2 diabetes. AMP-dependent protein kinase in AMPK signaling pathway is a central sensor of energy status. Deregulation of AMPK signaling leads to inflammation, oxidative stress, and deactivation of autophagy which are implicated in pathogenesis of insulin resistance. SIRT4 protein deactivates AMPK as well as directly inhibits insulin secretion. SIRT4 overexpression leads to dyslipidimeia, decreased fatty acid oxidation, and lipogenesis which are the characteristic features of insulin resistance promoting type 2 diabetes. This makes SIRT4 a novel therapeutic target to control type 2 diabetes. Virtual screening and molecular docking studies were performed to obtain potential ligands. To further optimize the geometry of protein–ligand complexes Quantum Polarized Ligand Docking was performed. Binding Free Energy was calculated for the top three ligand molecules. In view of exploring the stereoelectronic features of the ligand, density functional theory approach was implemented at B3LYP/6-31G* level. 30 ns MD simulation studies of the protein–ligand complexes were done. The present research work proposes ZINC12421989 as potential inhibitor of SIRT4 with docking score (?7.54 kcal/mol), docking energy (?51.34 kcal/mol), binding free energy (?70.21 kcal/mol), and comparatively low energy gap (?0.1786 eV) for HOMO and LUMO indicating reactivity of the lead molecule.     

Clinical proteomics of the neglected human malarial parasite Plasmodium vivax

Recent reports highlight the severity and the morbidity of disease caused by the long neglected malaria parasite Plasmodium vivax. Due to inherent difficulties in the laboratory-propagation of P. vivax, the biology of this parasite has not been adequately explored. While the proteome of P. falciparum, the causative agent of cerebral malaria, has been extensively explored from several sources, there is limited information on the proteome of P. vivax. We have, for the first time, examined the proteome of P. vivax isolated directly from patients without adaptation to laboratory conditions. We have identified 153 proteins from clinical P. vivax, majority of which do not show homology to any previously known gene products. We also report 29 new proteins that were found to be expressed in P. vivax for the first time. In addition, several proteins previously implicated as anti-malarial targets, were also found in our analysis. Most importantly, we found several unique proteins expressed by P. vivax.This study is an important step in providing insight into physiology of the parasite under clinical settings.     

Superoxide dismutase: an industrial perspective

The application of enzyme technologies to industrial research, development, and manufacturing has become a very important field. Since the production of crude rennet in 1874, several enzymes have been commercialized, and used for therapeutic, supplementary, and other applications. Recent advancements in biotechnology now allow companies to produce safer and less expensive enzymes with enhanced potency and specificity. Antioxidant enzymes are emerging as a new addition to the pool of industrial enzymes and are surpassing all other enzymes in terms of the volume of research and production. In the 1990s, an antioxidant enzyme--superoxide dismutase (SOD)--was introduced into the market. Although the enzyme initially showed great promise in therapeutic applications, it did not perform up to expectations. Consequently, its use was limited to non-drug applications in humans and drug applications in animals. This review summarizes the rise and fall of SOD at the industrial level, the reasons for this, and potential future thrust areas that need to be addressed. The review also focuses on other industrially relevant aspects of SOD such as industrial importance, enzyme engineering, production processes, and process optimization and scale-up.