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.     

Social complexity in bees is not sufficient to explain lack of reversions to solitary living over long time scales

Background  

The major lineages of eusocial insects, the ants, termites, stingless bees, honeybees and vespid wasps, all have ancient origins (≥ 65 mya) with no reversions to solitary behaviour. This has prompted the notion of a 'point of no return' whereby the evolutionary elaboration and integration of behavioural, genetic and morphological traits over a very long period of time leads to a situation where reversion to solitary living is no longer an evolutionary option.     

Cancer gene suppression strategies: issues and potential

Oncogenes are ideal targets for therapies which down-regulate gene expression. However, effective modalities for altering gene expression in vivo have thus far proven to be elusive. Whilst there has been recent success with small molecule inhibitors of oncoprotein function, evolution of resistance to these agents has been observed in the clinical setting, indicating the need for combinations of therapies for cancer treatment. Strategies for in vivo gene down-regulation still hold promise for the treatment of cancer. The technologies relevant to such therapeutic strategies are discussed in terms of molecular action, delivery and choice of target gene. Consideration is given to the pre-clinical and clinical efficacy these agents have demonstrated to date.     

First clinical experience with the R Stent: a new highly flexible stainless steel tube intracoronary stent

BACKGROUND: Coronary stents have been used with increasing frequency and in increasingly complex coronary disease. A new 316 LVM stainless steel coronary stent, the R Stent, has been designed to provide maximum flexibility for tracking and high radial strength post-deployment. PURPOSE: To assess the clinical feasibility of the R Stent in a tertiary referral population of patients with coronary heart disease. Specific objectives are to assess the R Stent's deployment success, angiographic and procedural success (<20% residual stenosis and >TIMI 2 flow), safety (absence of complications), and 30-day clinical success (angiographic/procedural success plus no major adverse coronary events). METHODS: Between April and November 1998, stent deployment was attempted in 27 patients with stable (46%) or unstable (54%) angina pectoris who qualified for percutaneous transluminal coronary angioplasty. Eighty per cent of patients had a pre-existing history of myocardial infarction, coronary bypass surgery or percutaneous transluminal coronary angioplasty, and several of the lesions were anatomically complex (totally occluded, n 32; thrombus present, n 32; heavily calcified, n 33; ostial, n 31; >20 mm long, n 39; angulation >45 degrees, n 37). Lesions in aortocoronary saphenous vein grafts were excluded. Adjunctive medical management included intraprocedural aspirin and heparin and post-procedural aspirin and ticlopidine. After deployment, patients were followed up in the hospital and at 30 days post procedure. RESULTS: Stent deployment was achieved in 32 of 33 attempts (26 of 27 patients). There was one deployment failure in a long, calcified ostial and proximal left coronary lesion. In the 26 successful deployments, TIMI 3 flow was achieved. One other patient experienced a painless increase in creatine kinase to 375 (CK-MB of 59) at 12 h without ECG changes. At 30 days, there were no deaths, no myocardial infarctions, no subacute thromboses, no repeat interventions, no bypass surgeries and no bleeding complications. Only the patient with post-procedural CK-MB elevation experience recurrence of CCS class 2 angina within the 30 days. CONCLUSION: The R Stent is a promising new device for the treatment of complex coronary heart disease. A larger, more broadly-based study is warranted.     

Water relations and leaf expansion: importance of time scale

The role of leaf water relations in controlling cell expansion in leaves of water-stressed maize and barley depends on time scale. Sudden changes in leaf water status, induced by sudden changes in humidity, light and soil salinity, greatly affect leaf elongation rate, but often only transiently. With sufficiently large changes in salinity, leaf elongation rates are persistently reduced. When plants are kept fully turgid throughout such sudden environmental changes, by placing their roots in a pressure chamber and raising the pressure so that the leaf xylem sap is maintained at atmospheric pressure, both the transient and persistent changes in leaf elongation rate disappear. All these responses show that water relations are responsible for the sudden changes in leaf elongation rate resulting from sudden changes in water stress and putative root signals play no part. However, at a time scale of days, pressurization fails to maintain high rates of leaf elongation of plants in either saline or drying soil, indicating that root signals are overriding water relations effects. In both saline and drying soil, pressurization does raise the growth rate during the light period, but a subsequent decrease during the dark results in no net effect on leaf growth over a 24 h period. When transpirational demand is very high, however, growth-promoting effects of pressurization during the light period outweigh any reductions in the dark, resulting in a net increase in growth of pressurized plants over 24 h. Thus leaf water status can limit leaf expansion rates during periods of high transpiration despite the control exercised by hormonal effects on a 24 h basis.