Blood lipid profile and myocardial superoxide dismutase in swim-trained young and middle-aged rats: comparison between left and right ventricular adaptations to oxidative stress

Region-wise interactive effects of age, swim intensity, and duration on exercise performance in the myocardium and serum lipid profile in young (4 months) and middle-aged (12 months) rats were examined. Animals were allocated to the sedentary control (SE-C) or one of the nine trainee groups. Swim training was for 6 days/week and for 4 weeks at 3 durations (20, 40, and 60 min/day) and intensities (2%, low; 3%, medium; 5%, high). Swim velocity and external work showed an age-related decline with low-intensity of 20 min/day in the middle aged. Reduction in serum cholesterol, low-density lipoproteins (LDLs), and triglycerides were accompanied by elevated levels in high-density lipoprotein in the low-to-moderately trained ones for 20 and 40 min/day. Training at 2%, intensity for 20 min/day was sufficient to alter the blood lipid profile and improve swim performance, and endurance in terms of blood lactate. A concomitant increase in Mn-superoxide dismutase (Mn-SOD) activity and reduced malondialdehyde in the left ventricle (LV) and right ventricle (RV) were evident. Lipofuscin was higher in the LV compared to RV. Our results reflect the minimization of free radical generation through appropriate exercise protocols. Our findings on improved blood lipid profile could be related to lower free radicals, which would otherwise oxidize LDLs. Further, swim training when initiated in the young and middle age for as low as 20 min/day at 2% intensity improves the Mn-SOD in the LV and RV. However, the adaptive response of the LV was weaker when compared to the RV, more so in the middle aged.     

A synthetic recursive "+1" pathway for carbon chain elongation

Nature uses four methods of carbon chain elongation for the production of 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling, protein-substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis for use as a synthetic "+1" recursive metabolic pathway to extend the carbon chain of 2-ketoacids. This modified pathway preferentially selects longer-chain substrates for catalysis, as compared to the non-recursive natural pathway, and can recursively catalyze five elongation cycles to synthesize bulk chemicals, such as 1-heptanol, 1-octanol, and phenylpropanol directly from glucose. The "+1" chemistry is a valuable metabolic tool in addition to the "+5" chemistry and "+2" chemistry for the biosynthesis of isoprenoids, fatty acids, or polyketides.     

Biological pretreatment of sugarcane trash for its conversion to fermentable sugars

Pretreatment of lignocellulosic biomasses, the first step in their conversion to utilizable molecules requires very high energy (steam and electricity), corrosion resistant high-pressure reactors and high temperatures. These severe conditions not only add to the cost component of the entire process but also lead to the loss of sugars to the side reactions. Microbial pretreatments have been reported to be associated with reducing the cost factors as well as the severities of the reactions. Eight bioagents, including fungi and bacteria, were screened for their pretreatment effects on sugarcane trash. They narrowed down the C:N ratio of trash from 108:1 to a varying range of approximately 42:1 to 60:1.The maximum drop in C:N ratio of 61% was observed using Aspergillus terreus followed by Cellulomonas uda (52%) and Trichoderma reesei and Zymomonas mobilis (49%). The bioagents helped in degradation of sugarcane trash by production of cellulases, the maximum being produced by A. terreus, (12 fold) followed by C. uda (10 fold), Cellulomonas cartae (9 fold) and Bacillus macerans (8 fold). The microbial pretreatment of trash rendered the easy accessibility of sugars for enzymatic hydrolysis, which can be directed for production of alcohol.     

Purification and partial characterization of polygalacturonase from Streptomyces lydicus

Polygalacturonase produced by Streptomyces lydicus was purified to homogeneity by ultrafiltration and a combination of ion exchange and gel filtration chromatographic procedures. The purified enzyme was an exo-polygalacturonase with a molecular weight of 43 kDa. It was optimally active at 50 degrees C and pH 6.0. The enzyme was stable from pH 4.0 to 7.0 and at or below 45 degrees C for 90 min. K(m) value for polygalacturonic acid was 1.63 mg/mL and the corresponding V(max) was 677.8 microM min(-1) mg(-1). The inhibition constant (K(i)) for gluconic acid d-lactone was 20.75 mM. Purified enzyme had been inhibited by N-bromosuccinimide, while l-tryptophan could induce enzyme activity, indicating the involvement of tryptophan at the active site.     

Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates

A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC₅₀=4.0–30.0 μΜ) and moderate ability for inhibition of Aβ_1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ₄₂ aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ_1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties.