Screened nonbonded 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 intramolecular 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 nonscreened edges that retain their ability to disseminate the perturbation. The shortest APLs computed from the reduced homogeneous networks with only the strongest few nonbonded 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 toward a random coil behavior. Under different perturbation scenarios, diverse optimal paths emerge for robust residue communication.     

Tactile sensitivity of normal and autistic children

Many children with autistic spectrum disorders have unusual reactions to certain sensory stimuli. These reactions vary along a hyper- to hypo-responsivity continuum. For example, some children overreact to weak sensory input, but others do not respond negatively to even strong stimuli. It is typically assumed that this deviant responsivity is linked to sensitivity, although the particular stage of sensory processing affected is not known. Psychophysical vibrotactile thresholds of six male children (age: 8-12) who were diagnosed to have autistic spectrum disorders and six normal male children (age: 7-11) were measured by using a two-alternative forced-choice task. The tactile stimuli were sinusoidal displacements and they were applied on the terminal phalanx of the left middle finger of each subject. By using a forward-masking paradigm, 40- and 250-Hz thresholds of the Pacinian tactile channel and 40-Hz threshold of the Non-Pacinian I tactile channel were determined. There was no significant difference between the thresholds of autistic and normal children, and the autistic children had the same detection and masking mechanisms as the normal children. The sensory responsivity of each subject was tested by clinical questionnaires, which showed again no difference between the two subject groups. Furthermore, no significant correlations could be found between the questionnaire data and the psychophysical thresholds. However, there was a high correlation between the data from the tactile and emotional subsets of the questionnaires. These results support the hypothesis that the hyper- and hypo-responsivity to touch, which is sometimes observed in autistic spectrum disorders, is not a perceptual sensory problem, but may probably be emotional in origin.     

The effect of chemical and biological treatment on root and crown rot disease caused by Phytophthora cryptogea Pethybr. & Lafferty in Gerbera

Phytophthora root and crown rot (Phytophthora cryptogea) on gerbera is difficult to manage because most gerbera cultivars are susceptible to P. cryptogea. This study was conducted in order to determine the in vivo (pot experiment) efficacy of some fungicides and biofungicides. In pot experiments, fungicides were applied 7 days after inoculation with P. cryptogea, while biofungicide was applied 7 days before inoculation. In this study, soil drenches of five fungicides were tested. “Ametoctradin+dimethomorph (100 ml/day),” “mandipropamid+difenoconazole (60 ml/day),” “propamocarb+fosetyl‐Al (200 ml/day),” “mancozeb+metalaxyl‐M (250 g/day)” and “azoxystrobin+difenoconazole (100 ml/day)” active substances were used. Similarly, one biofungicide Bacillus amyloliquefaciens syn. MBI 600 (50 g/100 L) was applied by soil drenching. Efficacy of treatments was assessed according to the percentage of the root system which was visibly rotten at the end of the experiment. Root and crown rot severity was rated on a scale of 0 = 0% root system necrotic, 1 = 1%‐25% necrotic, 2 = 26%‐50% necrotic, 3 = 51%‐75% necrotic and 4 = 76%‐100% necrotic from 12 to 21 days. In this experiment, “azoxystrobin 200 g/L + difenoconazole 125 g/L” exhibited the highest efficacy against P. cryptogea with a ratio of 43.75%. The other fungicides and biofungicides ametoctradin 300 g/L + dimethomorph 225 g/L, mandipropamid 250 g/L + difenoconazole 250 g/L, propamocarb 530 g/L + fosety‐Al 310 g/L, mancozeb 64%+metalaxyl‐M 4% and Bacillus amyloliquefaciens syn. MBI 600 11% were ineffective. Importance should be given to management strategies of P. cryptogea of and more experiments should be carried out for a better understanding of the use of registered fungicides and biofungicides.     

Comparative Evaluation of Nimesulide-Loaded Nanoparticles for Anticancer Activity Against Breast Cancer Cells

Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future.     

Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice

Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100?mg/kg gentamicin (i.p; intraperitoneally) and 200?mg/kg alpha-linolenic acid (gavage) are administered to mice for 9?days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation.     

Man alpha1-2 Man alpha-OMe-concanavalin A complex reveals a balance of forces involved in carbohydrate recognition.

We have determined the crystal structure of the methyl glycoside of Man alpha1-2 Man in complex with the carbohydrate binding legume lectin concanavalin A (Con A). Man alpha1-2 Man alpha-OMe binds more tightly to concanavalin A than do its alpha1-3 and alpha1-6 linked counterparts. There has been much speculation as to why this is so, including a suggestion of the presence of multiple binding sites for the alpha1-2 linked disaccharide. Crystals of the Man alpha1-2 Man alpha-OMe-Con A complex form in the space group P2(1)2(1)2(1) with cell dimensions a = 119.7 A, b = 119.7 A, c = 68.9 A and diffract to 2. 75A. The final model has good geometry and an R factor of 19.6% (Rfree= 22.8%). One tetramer is present in the asymmetric unit. In three of the four subunits, electron density for the disaccharide is visible. In the fourth only a monosaccharide is seen. In one subunit the reducing terminal sugar is recognized by the monosaccharide site; the nonreducing terminal sugar occupies a new site and the major solution conformation of the inter-sugar glycosidic linkage conformation is adopted. In contrast, in another subunit the non reducing terminal sugar sits in the so called monosaccharide binding site; the reducing terminal sugar adopts a different conformation about its inter-sugar glycosidic linkage in order for the methyl group to access a hydrophobic pocket. In the third subunit, electron density for both binding modes is observed. We demonstrate that an extended carbohydrate binding site is capable of binding the disaccharide in two distinct ways. These results provide an insight in to the balance of forces controlling protein carbohydrate interactions.