Homology modeling, simulation and molecular docking studies of catechol-2, 3-Dioxygenase from Burkholderia cepacia: Involved in degradation of Petroleum hydrocarbons

Catechol 2, 3-dioxygenase is present in several types of bacteria and undergoes degradation of environmental pollutants through an important key biochemical pathways. Specifically, this enzyme cleaves aromatic rings of several environmental pollutants such as toluene, xylene, naphthalene and biphenyl derivatives. Hence, the importance of Catechol 2, 3-dioxygenase and its role in the degradation of environmental pollutants made us to predict the three-dimensional structure of Catechol 2, 3-dioxygenase from Burkholderia cepacia. The 10ns molecular dynamics simulation was carried out to check the stability of the modeled Catechol 2, 3- dioxygenase. The results show that the model was energetically stable, and it attains their equilibrium within 2000 ps of production MD run. The docking of various petroleum hydrocarbons into the Catechol 2,3-dioxygenase reveals that the benzene, O-xylene, Toluene, Fluorene, Naphthalene, Carbazol, Pyrene, Dibenzothiophene, Anthracene, Phenanthrene, Biphenyl makes strong hydrogen bond and Van der waals interaction with the active site residues of H150, L152, W198, H206, H220, H252, I254, T255, Y261, E271, L276 and F309. Free energy of binding and estimated inhibition constant of these compounds demonstrates that they are energetically stable in their binding cavity. Chrysene shows positive energy of binding in the active site atom of Fe. Except Pyrene all the substrates made close contact with Fe atom by the distance ranges from 1.67 to 2.43 Å. In addition to that, the above mentioned substrate except pyrene all other made π-π stacking interaction with H252 by the distance ranges from 3.40 to 3.90 Å. All these docking results reveal that, except Chrysene all other substrate has good free energy of binding to hold enough in the active site and makes strong VdW interaction with Catechol-2,3-dioxygenase. These results suggest that, the enzyme is capable of catalyzing the above-mentioned substrate.     

Projected climate‐driven faunal movement routes

Historically, many species moved great distances as climates changed. However, modern movements will be limited by the patterns of human‐dominated landscapes. Here, we use a combination of projected climate‐driven shifts in the distributions of 2903 vertebrate species, estimated current human impacts on the landscape, and movement models, to determine through which areas in the western hemisphere species will likely need to move to track suitable climates. Our results reveal areas with projected high densities of climate‐driven movements – including, the Amazon Basin, the southeastern United States and southeastern Brazil. Some of these regions, such as southern Bolivia and northern Paraguay, contain relatively intact landscapes, whereas others such as the southeastern United States and Brazil are heavily impacted by human activities. Thus, these results highlight both critical areas for protecting lands that will foster movement, and barriers where human land‐use activities will likely impede climate‐driven shifts in species distributions.     

Fluid replacement drinks during high intensity exercise effects on minimizing exercise-induced disturbances in homeostasis

The purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise. Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments. The work rate was set initially at approximately 85% of VO2max (range 82-88%) with fatigue being defined as a 10% decline in power output below the initial value. During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise: (1) non-electrolyte placebo (NEP; 31 mosmol.kg-1); (2) glucose polymer drink containing electrolytes (GP; 7% CHO, 231 mosmol.kg-1), and (3) electrolyte placebo drink without carbohydrate (EP; 48 mosmol.kg-1). Both the GP and EP beverage contained sodium citrate/citric acid (C) as a flavoring agent while C was not contained in the NEP drink. Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial, the difference was not significant (P greater than 0.05). No differences (P greater than 0.05) existed between the GP and EP treatments in performance time. Exercise changes in rectal temperature, heart rate, delta % plasma volume and plasma concentrations of total protein, free fatty acids, glucose, lactate, potassium, chloride, calcium, and sodium did not differ (P greater than 0.05) between trials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency of heterozygous complete hydatidiform moles,estimated by locus-specific minisatellite and Y chromosome-specific probes

Summary Restriction fragment length polymorphisms identified with three locus-specific minisatellite probes and banding patterns with Y chromosome-specific probes have been examined in 39 cases of complete hydatidiform mole (CHM) and the parents. All 39 cases were shown to be androgenetic. Of the 39 cases, 8 were identified as heterozygous CHM using the minisatellite probes. Estimates for the total number of heterozygous CHM in the series ranged from 23%–29%, higher than previously reported. Of the eight identified heterozygous CHM, six had Y chromosome-specific sequences whereas two were female; this is not significantly different from the 2:1 ratio expected. The low frequency of 46,XX heterozygous CHM in the literature may reflect difficulties in distinguishing them from 46,XX homozygous CHM. Examination of RFLPs with a small panel of locus-specific minisatellite probes provides a powerful method of classifying hydatidiform mole, enabling the rare heterozygous 46,XX CHM to be accurately identified.     

Climbing the vertebrate branch of U1A/U2B″ protein evolution

In the vertebrate lineage of the U1A/U2B″/SNF protein family, the U1A and U2B″ proteins bind to RNA stem–loops in the U1 or U2 snRNPs, respectively. However, their specialization is fairly recent, as they evolved from a single ancestral protein. The progress of their specialization (subfunctionalization) can be monitored by the amino acid sequence changes that give rise to their modern RNA-binding specificity. Using ancestral sequence reconstruction to predict the intermediates on the evolutionary branch, a probable path of sequential changes is defined for U1A and U2B″. The RNA-binding affinity for U1A/U2B″ protein ancestors was measured using modern U1 and U2 snRNA stem–loops and RNA stem–loop variants to understand how the proteins’ RNA specificities evolved.     

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model

Lung cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by hijacking immune system for active growth and aggressive metastasis. Neutrophils, which in their original form should establish immune activities to the tumor as a first line of defense, are undermined by tumor cells to promote tumor invasion in several ways. In this study, we investigate the mutual interactions between the tumor cells and the neutrophils that facilitate tumor invasion by developing a mathematical model that involves taxis-reaction-diffusion equations for the critical components in the interaction. These include the densities of tumor and neutrophils, and the concentrations of signaling molecules and structure such as neutrophil extracellular traps (NETs). We apply the mathematical model to a Boyden invasion assay used in the experiments to demonstrate that the tumor-associated neutrophils can enhance tumor cell invasion by secreting the neutrophil elastase. We show that the model can both reproduce the major experimental observation on NET-mediated cancer invasion and make several important predictions to guide future experiments with the goal of the development of new anti-tumor strategies. Moreover, using this model, we investigate the fundamental mechanism of NET-mediated invasion of cancer cells and the impact of internal and external heterogeneity on the migration patterning of tumour cells and their response to different treatment schedules.     

Preferential breakage of sensitive regions of human chromosomes

Summary Whilst studying the chromosomes of the peripheral blood lymphocytes of normal controls and patients with lymphoproliferative disorders, two examples of preferential breakage of a sensitive chromosomal region were found. A patient with lymphocytic lymphoma had a sensitive region in a C9 chromosome coinciding with the secondary constriction. A healthy woman had one A2 chromosome showing an unusually located secondary constriction in which breakage sometimes occurred.     

The crystal structure of the heparin-binding reelin-N domain of f-spondin

The extracellular matrix protein F-spondin mediates axon guidance during neuronal development. Its N-terminal domain, termed the reelin-N domain, is conserved in F-spondins, reelins, and other extracellular matrix proteins. In this study, a recombinant human reelin-N domain has been expressed, purified, and shown to bind heparin. The crystal structure of the reelin-N domain resolved to 2.0 Å reveals a variant immunoglobulin-like fold and potential heparin-binding sites. Substantial conformational variations even in secondary structure are observed between the two chemically identical reelin-N domains in one crystallographic asymmetric unit. The variations may result from extensive, highly specific interactions across the interface of the two reelin-N domains. The calculated values of buried surface area and the interface's shape complementarity are consistent with the formation of a weak dimer. The homophilic asymmetric dimer can potentially offer advantages in binding to ligands such as glycosaminoglycans, which may, in turn, bridge the two reelin-N domains and stabilize the dimer.