Network Approaches to Elucidate the Determinants of Protein Topology and Stability

Predicting three-dimensional structures of proteins from sequence information alone, remains one of the most profoundly challenging and intensely studied problems in basic science. It has uniquely garnered the interdisciplinary efforts of biologists, biochemists, computer scientists, mathematicians and physicists. The advancement of computational methods to study fundamental features of proteins also enables insights that are either difficult to explore experimentally or complimentary to further interpret experimental data. In the present research and through the combined development and application of molecular dynamics and network science approaches we aimed to elucidate the role of geographically important amino acids and evolutionarily conserved long-range interactions which are proposed to be key to protein stability and topology. Using a model system of nine proteins that share a Greek-key topology, the proteins were unfolded under high temperature with molecular dynamics simulations. The unfolded trajectories were analyzed by calculating root-mean-square-deviation, contact distances, root-mean-square-fluctuation and fraction of remaining contacts. The results indicated that the conserved long-range interactions are significantly more persistent over time than the non-conserved long-range interactions thus dominant contributors to topological stability. The behavior of the conserved long-range interactions in the folding of our model proteins was also tested using simulated annealing and the formation of giant network clusters. The results demonstrated that the conserved interactions play a dominant role in folding by governing the native topology and facilitating rapid formation of the native network. In a third study, the role of the residues with high betweeness centrality scores in maintaining the protein network and in governing the Greek-key topology were examined by fragmentation and diameter tests. Here we found a subset of selected residues in similar geographical positions in all model proteins, which demonstrates the role of these specific residues and regions in governing the Greek-key topology from a network perspective. In conclusion, we can say that the determination of protein topology in terms of a network structure will facilitate predicting the folding and stability of proteins

Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review

The term “metabolic syndrome” (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting β cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS

Capacitive Sensing of Intercalated H2O Molecules Using Graphene

Understanding the interactions of ambient molecules with graphene and adjacent dielectrics is of fundamental importance for a range of graphene-based devices, particularly sensors, where such interactions could influence the operation of the device. It is well-known that water can be trapped underneath graphene and its host substrate, however, the electrical effect of water beneath graphene and the dynamics of how it changes with different ambient conditions has not been quantified. Here, using a metal-oxide-graphene variable-capacitor (varactor) structure, we show that graphene can be used to capacitively sense the intercalation of water between graphene and HfO2 and that this process is reversible on a fast time scale. Atomic force microscopy is used to confirm the intercalation and quantify the displacement of graphene as a function of humidity. Density functional theory simulations are used to quantify the displacement of graphene induced by intercalated water and also explain the observed Dirac point shifts as being due to the combined effect of water and oxygen on the carrier concentration in the graphene. Finally, molecular dynamics simulations indicate that a likely mechanism for the intercalation involves adsorption and lateral diffusion of water molecules beneath the graphene.Comment: E.J.O. and R.M. made an equal contribution to this wor

Two-Dimensional Black Phosphorus for High Performance Field Effect Transistors

University of Minnesota Ph.D. dissertation. June 2017. Major: Electrical Engineering. Advisor: Steven Koester. 1 computer file (PDF); x, 141 pages.Two-dimensional (2D) materials are a potential platform for scaled logic devices, sensor applications, flexible electronics and other innovative device concepts. Black phosphorus (BP) has recently emerged as a new promising layered semiconductor due to its unique material properties. BP has high electron and hole mobility, tunable band-gap ranging from 0.3 eV (bulk) to 1-2 eV (monolayer) and highly asymmetric effective mass. BP metal-oxide-semiconductor field-effect transistors (MOSFETs) have the potential to outperform other 2D semiconductors mainly due to the lighter effective mass of BP, which leads to higher mobility, and narrower band gap, which can reduce contact resistance due to the Schottky barrier height lowering. In this dissertation, BP n- and p-type MOSFETs with record performance are demonstrated. A comprehensive experimental and theoretical evaluation of the design and operating parameters that limit the off-state performance and subthreshold slope in BP MOSFETs is performed. Next, for the first time, the effect of asymmetric crystal orientation on BP MOSFET performance is quantified and the anisotropic mobility in a realistic MOSFET geometry is analyzed. Finally, contact engineering is utilized to achieve record-low contact resistance in BP p-MOSFETs

Determination of pediatric poisoning factors in children

Background and Objective: Poisoning is a major public health problem and a serious form of the common causes of hospital emergency visits in many countries. Incidence of toxicity based on cultural and economic characteristics of communities are varied. This study was done to determine the pediatric poisoning factors in children. Methods: This descriptive-cross sectional study was performed on 201 patients younger than 12 years old with posinnig symptoms whom referred to hospitals in Shahroud city of central part of Iran from April 2011 to March 2012. Demogaphic data, posinnig symptoms, posinnig agents, time of hospitalization and outcome of posinnig for each child were recored in quetionare. Results: Opium was the most common consumed material with (51.2%) while metadon considered to be the major opium. 180 (89.6%) and 21 (10.4%) children were poisoned accidentaly by their parant respectively. The clinical manifestation of the affected children were 15 (7.5%), 11 (5.5%), 93 (46.3%), 26 (12.9%), 19 (2.5%) and 22 (10.9%) without any symptoms, neuro-respiratory, nervous, gastrointestinal, gastrointestinal-respriatory and weakness respectively. Two children were died in the course of this project. There was a significant statistical correlation between the reason for poisoning and age parant education level and type of poisoning. Also, there was a relation between the type of poisoning and place of residence (P<0.05). Conclusion: This study shows that the most common cause of poisoning among children was opiums

Effect of Monosodium glutamate on rat cerebellum

Background and Objective: Monosodium glutamate (MSG) is used as a food additive. Several studies have reported the adverse effects of Monosodium glutamate on the testis and brain. This study was performed to determine the effect of Monosodium glutamate in rat cerebellum. Methods: In this experimental study, 24 adult wistar rats randomly allocated into three groups including experiment A, experiment B and control (C). The animals in experiment A and B were received 3g and 6g of MSG thoroughly mixed with their feeds for 14 days, respectively. Animals in control group were received MSG free diet. Food and water for rats to be free in all of experimental time. The rats were sacrificed on fifteen day. The cerebellum dissected and fixed with formalin 10% buffer and stained with hematoxylin and eosin. Results: Disorders and detachment were observed in Purkinje and granular cell layers. Neural cell distribution in granular layer redeuced in the experimental groups. Cellular degenerative changes in the granular layer of the experimental B were more severe than experimental group A. The mean number of neuron of the granular layer in the experimental A, B and control groups were 2750, 2140 and 3150, respectively. Conclusion: The consumption of monosodium glutamate dose dependly causes histopathological changes and reduces the number of the cerebellumllar neurons in adult rat