Screened non-bonded interactions in native proteins manipulate optimal paths for robust residue communication

A protein structure is represented as a network of residues whereby edges are determined by intra-molecular contacts. We introduce inhomogeneity into these networks by assigning each edge a weight that is determined by amino-acid pair potentials. Two methodologies are utilized to calculate the average path lengths (APLs) between pairs: To minimize (i) the maximum weight in the strong APL, and (ii) the total weight in the weak APL. We systematically screen edges that have higher than a cutoff potential and calculate the shortest APLs in these reduced networks, while keeping chain connectivity. Therefore, perturbations introduced at a selected region of the residue network propagate to remote regions only along the non-screened edges that retain their ability to disseminate the perturbation. The shortest APLs computed from the reduced homogeneous networks with only the strongest few non-bonded pairs closely reproduce the strong APLs from the weighted networks. The rate of change in the APL in the reduced residue network as compared to its randomly connected counterpart remains constant until a lower bound. Upon further link removal, this property shows an abrupt increase, towards a random coil behavior. Under different perturbation scenarios, diverse optimal paths emerge for robust residue communication.Comment: 21 pages with 6 figure

Perturbation-Response Scanning Reveals Ligand Entry-Exit Mechanisms of Ferric Binding Protein

We study apo and holo forms of the bacterial ferric binding protein (FBP) which exhibits the so-called ferric transport dilemma: it uptakes iron from the host with remarkable affinity, yet releases it with ease in the cytoplasm for subsequent use. The observations fit the “conformational selection” model whereby the existence of a weakly populated, higher energy conformation that is stabilized in the presence of the ligand is proposed. We introduce a new tool that we term perturbation-response scanning (PRS) for the analysis of remote control strategies utilized. The approach relies on the systematic use of computational perturbation/response techniques based on linear response theory, by sequentially applying directed forces on single-residues along the chain and recording the resulting relative changes in the residue coordinates. We further obtain closed-form expressions for the magnitude and the directionality of the response. Using PRS, we study the ligand release mechanisms of FBP and support the findings by molecular dynamics simulations. We find that the residue-by-residue displacements between the apo and the holo forms, as determined from the X-ray structures, are faithfully reproduced by perturbations applied on the majority of the residues of the apo form. However, once the stabilizing ligand (Fe) is integrated to the system in holo FBP, perturbing only a few select residues successfully reproduces the experimental displacements. Thus, iron uptake by FBP is a favored process in the fluctuating environment of the protein, whereas iron release is controlled by mechanisms including chelation and allostery. The directional analysis that we implement in the PRS methodology implicates the latter mechanism by leading to a few distant, charged, and exposed loop residues. Upon perturbing these, irrespective of the direction of the operating forces, we find that the cap residues involved in iron release are made to operate coherently, facilitating release of the ion

Analysis of added value creation process in ready-made clothing sector: "Turkish case"

Turkish ready-made clothing sector is the one of the leading sectors of the Turkish industry. The companies in this sector should produce high added value products to protect their power on the international competition and increase their market shares. Creation of added value depends on various factors like improving the performance in production, producing design products and creating a brand. To analyze the added value process, it is necessary to identify the activities which add value on final product. This study based on the data obtained from three different companies. One of them is in Istanbul, the others are in Izmir and all of them are active in ready-made clothing area. In addition, by considering added value creation process of the other companies in this sector, the added value ratio of each step of added value creation process and the factors which create the added value for the interviewed companies were determined. According to the study data, brand value is the most important factor which determines the added value and sales stage when the final product meets customers is the highest added value step can be said

Which is the best diet to reduce cardiometabolic risk: dietary counseling or home-delivered diet?

Background: Non-compliance with medical nutrition therapy can lead to an increase in cardiometabolic risk factors, resulting in an increase in the frequency of morbidity and mortality. Objective: This study aims to compare the effectiveness of two different medical nutrition therapies designed to reduce cardiometabolic risk factors. Design: The study was conducted on voluntary overweight and obese women who sought services at a specialized Nutrition and Dietary Counseling Clinic. The clinic offered dietary counseling (n = 47) and home-delivered diet (n = 53) services, and the participants themselves decided which method they preferred. Both groups were followed for a period of 4 weeks. The general information, physical activity (PA) status, biochemical findings, blood pressure, anthropometric measurements, and bioelectrical impedance analysis (BIA) of the voluntary participants were evaluated. Taking into consideration the participants’ dietary habits and health status, an appropriate dietary plan (55–60% carbohydrates, 15–20 protein%, 25–30% fat) was prepared. Results: The anthropometric measurements, blood pressure, and biochemical parameters of overweight and obese individuals who received dietary counseling and home-delivered diet services were evaluated before and after the diet. In both groups, cardiometabolic risk factors were found to decrease. It was determined that those who received the home-delivered diet service had a greater reduction in body weight, Body Mass Index values, body fat percentages, and waist circumferences compared to those who received dietary counseling (P < 0.001). Similarly, fasting blood glucose, triglyceride, and blood pressure values were found to decrease more significantly in individuals receiving the home-delivered diet service (P < 0.001). Additionally, both groups showed an increase in High-Density Lipoprotein Cholesterol (HDL-C) levels, with a greater increase observed in those receiving the home-delivered diet service (P < 0.001). Conclusion: According to the findings of this study, participants who received the home-delivered diet service, which is particularly beneficial for individuals who struggle with healthy meal preparation and portion control, exhibited better adherence to medical nutrition therapy and experienced a greater reduction in cardiometabolic risk factors compared to those who received dietary counseling

Cardiac dysrhythmias and autonomic dysfunction in chronic spinal cord injury: A 24-hour Holter monitoring and heart rate variability study

The purpose of this study is to evaluate chronic spinal cord injury (SCI) patients for the incidence of cardiac dysrhythmias and the level of autonomic nervous system (ANS) dysfunction using 24-hour Holter recordings and long term time-domain and frequency domain heart rare variability (HRV) analysis. There was no difference between groups for the frequency of ventricular or supraventricular ectopics, minimal and mean heart rate, and the longest RR intervals. Maximum heart rate was lower in the quadriplegic group compared with controls (124.1 +/- 11.2 vs. 139.4 +/- 10.9, p < 0.05). Frequency-domain spectral analysis of high, low, total frequency powers, and ratio LF/HF showed no significant difference between groups. On time-domain analysis SDANN (94.5 +/- 26.4 vs. 131.1 +/- 15.1, p < 0.01) and SDNN (110.1 +/- 29.2 vs. 143.6 +/- 19.1, p < 0.05) were significantly lower in quadriplegics compared with controls. SDANN (74.0 +/- 17.9 vs. 115.0 +/- 14.2 p < 0.01) and SDNN ( 90.2 +/- 21.1 vs. 130.0 +/- 22.0 p < 0.05) were significantly lower in complete quadriplegics compared with incomplete quadriplegics. When the effect of wake (07-22)-sleep (23-07) cycle on frequency-domain parameters were assessed, HF (12.38 +/- 5.1 vs. 21.18 +/- 8.05, p = 0.001) and TP (35.93 +/- 10.5 vs. 45.68 +/- 12.68, p = 0.004) showed the physiologic increase during sleep in controls, but was unchanged in quadriplegics (10.48 +/- 5.39 vs. 13.35 +/- 8.03, p = 0.205 and 30.67 +/- 10.61 vs. 37.01 +/- 17.59, p = 0.208, respectively). In paraplegics a blunted increase in HF (14.61 +/- 7.69 vs. 19.85 +/- 14.13, p = 0.09) and TP (38.5 +/- 12.77 vs. 47.13 +/- 23.08, p = 0.08) was observed. LF showed no significant change in the three groups. Heart rate circadian rhythm was preserved in all three groups (p < 0.01). We concluded that chronic complete cervical SCI may disrupt modulatory sympathetic flow and downregulates parasympathetic activity but causes no major arrhythmias needing treatment