Network metrics, structural dynamics and density functional theory calculations identified a novel Ursodeoxycholic Acid derivative against therapeutic target Parkin for Parkinson's disease.

Parkinson's disease (PD) has been designated as one of the priority neurodegenerative disorders worldwide. Although diagnostic biomarkers have been identified, early onset detection and targeted therapy are still limited. An integrated systems and structural biology approach were adopted to identify therapeutic targets for PD. From a set of 49 PD associated genes, a densely connected interactome was constructed. Based on centrality indices, degree of interaction and functional enrichments, LRRK2, PARK2, PARK7, PINK1 and SNCA were identified as the hub-genes. PARK2 (Parkin) was finalized as a potent theranostic candidate marker due to its strong association (score > 0.99) with α-synuclein (SNCA), which directly regulates PD progression. Besides, modeling and validation of Parkin structure, an extensive virtual-screening revealed small (commercially available) inhibitors against Parkin. Molecule-258 (ZINC5022267) was selected as a potent candidate based on pharmacokinetic profiles, Density Functional Theory (DFT) energy calculations (ΔE = 6.93 eV) and high binding affinity (Binding energy = -6.57 ± 0.1 kcal/mol; Inhibition constant = 15.35 µM) against Parkin. Molecular dynamics simulation of protein-inhibitor complexes further strengthened the therapeutic propositions with stable trajectories (low structural fluctuations), hydrogen bonding patterns and interactive energies (>0kJ/mol). Our study encourages experimental validations of the novel drug candidate to prevent the auto-inhibition of Parkin mediated ubiquitination in PD.

Microalgal bio-flocculation: present scenario and prospects for commercialization.

The need for sustainable production of renewable biofuel has been a global concern in the recent times. Overcoming the tailbacks of the first- and second-generation biofuels, third-generation biofuel using microalgae as feedstock has emerged as a plausible alternative. It has an added advantage of preventing any greenhouse gas (GHG) emissions with simultaneous carbon dioxide sequestration. Dewatering of microalgal culture is one of the many concerns regarding industrial-scale biofuel production. The small size of microalgae and dilute nature of its growth cultures creates huge operational cost during biomass separation, limiting economic feasibility of algae-based fuels. Considering the recovery efficiency, operation economics, technological feasibility and cost-effectiveness, bio-flocculation is a promising method of harvesting. Moreover, advantage of bio-flocculation over other conventional methods is that it does not incur the addition of any external chemical flocculants. This article reviews the current status of bio-flocculation technique for harvesting microalgae at industrial scale. The various microbial strains that can be prospective bioflocculants have been reviewed along with its application and advantages over chemical flocculants. Also, this article proposes that the primary focus of an appropriate harvesting technique should depend on the final utilization of the harvested biomass. This review article attempts to bring forth the beneficial aspects of microbial aided microalgal harvesting with a special attention on genetically modified self-flocculation microalgae.

Optimization of Chlamydomonas reinhardtii cultivation with simultaneous CO2 sequestration and biofuels production in a biorefinery framework.

Algal biomass is regarded as a sustainable energy feedstock for the future. Enhancement of the biomass and metabolite production of microalgae increases the economic feasibility of the biofuel production process. The present study encompasses on bioethanol production from Chlamydomonas reinhardtii through a biorefinery approach. The biomass and carbohydrate productivity of C. reinhardtii UTEX 90 and CC 2656 were enhanced by optimizing the physico-chemical parameters. The following conditions were found suitable for the improvement of biomass and metabolite content of C. reinhardtii: pH 6.5-7.0, incubation temperature 30 °C, initial acetate and ammonium chloride concentration of 1.56 g L-1 and 100-200 mg L-1, respectively. Under the optimized operational condition biomass and carbohydrate productivity of C. reinhardtii UTEX 90 and CC 2656 were 512 mg L-1 d-1 & 266.24 mg L-1 d-1 and 364 mg L-1 d -1 & 163.80 mg L-1 d-1, respectively. The amount of CO2 sequestered during the cultivation process by UTEX 90 and CC 2656 were 113 mg L-1 d-1 and 74.95 mg L-1 d-1, respectively. The depigmented and defatted carbohydrate rich biomass was considered as raw material for bioethanol production. The bioethanol yield range was 90-94% of the theoretical yield using Saccharomyces cerevisiae INVSC-1 in a double jacket reactor. To improve the viability of the process, the spent media after ethanol fermentation was subsequently used for methane production using mixed microbial consortium. The energy recovery from the process was 40.39% and 39.7% for UTEX 90 and CC 2656, respectively when C. reinhardtii biomass was used as substrate for biofuel production. The present investigation concedes with the potentiality of algae as a favourable 3rd generation feedstock to address the existing challenges of clean energy production with concomitant CO2 sequestration.

Vanadium(V) hydrazido(2-) thiolate imine alkoxide complexes.

The reaction of (Me(3)Si)(2)TIP with V(NNMe(2))(OAr)(3) results in the production of V(NNMe(2))(TIP)(OAr), where TIP is 2-((2-thiolatophenylimino)methylene)phenolate. The aryloxide is readily displaced by ISiMe(3) to form an insoluble iodide complex formulated as V(NNMe(2))(TIP)(I). The iodide was used to prepare three different complexes: [V(NNMe(2))(TIP)(dmpe)]I, [V(NNMe(2))(TIP)(Bu(t)bpy)][OTf], and [V(NNMe(2))(TIP)(Bu(t)bpy)][SbF(6)]. The phosphine derivative, [V(NNMe(2))(TIP)(dmpe)]I, was characterized by X-ray diffraction and shows a quite short N-N distance of 1.293(3) A indicative of a dominant isodiazene resonance form.