Fractal nature of protein surface roughness: a note on quantification of change of surface roughness in active sites,before and after binding

Year 2010 marked the 25th year since we came to know that roughness of a protein surface has fractal symmetry. Ever since the publication of Lewis and Rees' paper, hundreds of works from a spectrum of perspectives have established that fractal dimension (FD) can be considered as a reliable marker that describes roughness of protein surface objectively. In this article, we introduce readers to the fundamentals of fractals and present categorical biophysical and geometrical reasons as to why FD‐based constructs can describe protein surface roughness more accurately. We then review the commonality (and the lack of it) between numerous approaches that have attempted to investigate protein surface with fractal measures, before exploring the patterns in the results that they have produced. Apart from presenting the genealogy of approaches and results, we present an analysis that quantifies the difference in surface roughness in stretches of protein surface containing the active site, before and after binding to ligands, to underline the utility of FD‐based measures further. It has been found that surface stretches containing the active site, in general, undergo a significant increment in its roughness after binding. After presenting the entire repertoire of FD‐based surface roughness studies, we talk about two yet‐unexplored problems where application of FD‐based techniques can help in deciphering underlying patterns of surface interactions. Finally, we list the limitations of FD‐based constructs and put down several precautions that one must take while working with them. Copyright © 2013 John Wiley & Sons, Ltd.     

Role of the tumor suppressor IQGAP2 in metabolic homeostasis: possible link between diabetes and cancer

Deficiency of IQGAP2, a scaffolding protein expressed primarily in liver leads to rearrangements of hepatic protein compartmentalization and altered regulation of enzyme functions predisposing development of hepatocellular carcinoma and diabetes. Employing a systems approach with proteomics, metabolomics and fluxes characterizations, we examined the effects of IQGAP2 deficient proteomic changes on cellular metabolism and the overall metabolic phenotype. Iqgap2 ^?/?mice demonstrated metabolic inflexibility, fasting hyperglycemia and obesity. Such phenotypic characteristics were associated with aberrant hepatic regulations of glycolysis/gluconeogenesis, glycogenolysis, lipid homeostasis and futile cycling corroborated with corresponding proteomic changes in cytosolic and mitochondrial compartments. IQGAP2 deficiency also led to truncated TCA-cycle, increased anaplerosis, increased supply of acetyl-CoA for de novo lipogenesis, and increased mitochondrial methyl-donor metabolism necessary for nucleotides synthesis. Our results suggest that changes in metabolic networks in IQGAP2 deficiency create a hepatic environment of a ‘pre-diabetic’ phenotype and a predisposition to non-alcoholic fatty liver disease which has been linked to the development of hepatocellular carcinoma.     

Biochemical, molecular, and functional characterization of PISCF-allatostatin, a regulator of juvenile hormone biosynthesis in the mosquito Aedes aegypti

Aedes aegypti PISCF-allatostatin or allatostatin-C (Ae-AS-C) was isolated using a combination of high performance liquid chromatography and enzyme-linked immunosorbent assay (ELISA). The matrix-assisted laser desorption/ionization time-of-flight (TOF) mass spectrum of positive ELISA fractions revealed a molecular mass of 1919.0 Da, in agreement with the sequence qIRYRQCYFNPISCF, with bridged cysteines. This sequence was confirmed by matrix-assisted laser desorption/ionization tandem TOF/TOF mass spectrometry analysis. The corresponding Ae-AS-C cDNA was amplified by PCR, and the sequence of the peptide was confirmed. An in vitro radiochemical assay was used to study the inhibitory effect of synthetic Ae-AS-C on juvenile hormone biosynthesis by the isolated corpora allata (CA) of adult female A. aegypti. The inhibitory action of synthetic Ae-AS-C was dose-dependent; with a maximum at 10(-9) m. Ae-AS-C showed no inhibitory activity in the presence of farnesoic acid, an immediate precursor of juvenile hormone, indicating that the Ae-AS-C target is located before the formation of farnesoic acid in the pathway. The sensitivity of the CA to inhibition by Ae-AS-C in the in vitro assay varied during the adult life; the CA was most sensitive during periods of low synthetic activity. In addition, the levels of Ae-AS-C in the brain were studied using ELISA and reached a maximum at 3 days after eclosion. These studies suggest that Ae-AS-C is an important regulator of CA activity in A. aegypti.     

Associations of Trunk Fat Depots with Insulin Resistance, β Cell Function and Glycaemia - A Multiple Technique Study

Objective

Central (truncal) adiposity is associated strongly with insulin resistance and diabetes. There are very few reports comparing methods of trunk fat measurement in their ability to predict glycaemia and insulin resistance. We report a comparative analysis of different trunk fat measurements in predicting glycaemia and insulin resistance in middle aged Indian men.

Materials and Methods

Trunk fat measurements were performed using anthropometry, magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) on 128 men. Additional measurements were taken to characterise insulin resistance (Matsuda index) and beta cell function (Insulinogenic Index), glycaemia (fasting and 120 min glucose concentrations). Using residual approach we compared the ability of different trunk fat measurement techniques to predict insulin resistance, beta cell function and glycaemia.

Results

There was a strong association between trunk fat measures from each technique with glycaemia and insulin resistance indices but not with the Insulinogenic Index. Insulin resistance and glycaemia, were best predicted using anthropometric measurements, notably by waist circumference and subscapular skinfold thickness. Neither MRI measures of trunk or visceral fat nor DXA trunk fat added significantly. CT liver density contributed to some extent to predict insulin resistance and 120 min glucose after anthropometric measurements.

Conclusions

Our results suggest that, in Indian men, anthropometric measurements are good predictors of glycaemia and insulin resistance. Other complex measurements such as MRI, DXA and CT make only a small addition to the prediction. This finding supports the application of anthropometry for determining trunk fat in clinical and epidemiological settings.     

Design Considerations for Unconventional Electrochemical Energy Storage Architectures

Batteries have become fundamental building blocks for the mobility of modern society. Continuous development of novel battery chemistries and electrode materials has nourished progress in building better batteries. Simultaneously, novel device form factors and designs with multi‐functional components have been proposed, requiring batteries to not only integrate seamlessly to these devices, but to also be a multi‐functional component for a multitude of applications. Thus, in the past decade, along with developments in the component materials, the focus has been shifting more and more towards novel fabrication processes, unconventional configurations, and additional functionalities. This work attempts to critically review the developments with respect to emerging electrochemical energy storage configurations, including, amongst others, paintable, transparent, flexible, wire or cable shaped, ultra‐thin and ultra‐thick configurations, as well as hybrid energy storage‐conversion, or graphene‐incorporated batteries and supercapacitors. The performance requirements are elaborated together with the advantages, but also the limitations, with respect to established electrochemical energy storage technologies. Finally, challenges in developing novel materials with tailored properties that would allow such configurations, and in designing easier manufacturing techniques that can be widely adopted are considered.     

Preclinical Efficacy and Safety of a Human Embryonic Stem Cell-Derived Midbrain Dopamine Progenitor Product,MSK-DA01

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