Antagonists of the human A2A receptor. Part 5: Highly bio-available pyrimidine-4-carboxamides

A novel series of antagonists of the human A_2A receptor have been identified and have been shown to display good potency and high degrees of selectivity over other receptor sub-types. Displaying in vivo potency in commonly used disease models and high oral bio-availability, this class of compounds may serve as clinically useful treatments for the relief of the symptoms associated with Parkinson’s disease.     

Modification of flag leaf senescence and yield characters in barley (Hordeum vulgare L.) by gibberellic acid and kinetin

Barley plants (Hordeum vulgare L.) received foliar applications of 10^–4 M gibberellic acid (GA₃) and Kinetin (KN) individually and in combination at one or more of three growth stages: flag leaf appearance (I), ear emergence (II), and the first stage of senescence initiation in the flag leaf (III). Both plant growth regulators (PGR) hastened onset of senescence when sprayed at Stage I and/or Stage II. Treatment at Stage III, either alone or in combination with treatments at the other stages, tended to postpone senescence. Yield components also showed stage-dependent response: Stage I treatment increased the formation of total and bearing tillers, and Stage III treatment improved grain number and weight. However, while GA₃ proved more effective than KN, the two together acted antagonistically.     

Aerobic Degradation of N-Methyl-4-Nitroaniline (MNA) by Pseudomonas sp. Strain FK357 Isolated from Soil

N-Methyl-4-nitroaniline (MNA) is used as an additive to lower the melting temperature of energetic materials in the synthesis of insensitive explosives. Although the biotransformation of MNA under anaerobic condition has been reported, its aerobic microbial degradation has not been documented yet. A soil microcosms study showed the efficient aerobic degradation of MNA by the inhabitant soil microorganisms. An aerobic bacterium, Pseudomonas sp. strain FK357, able to utilize MNA as the sole carbon, nitrogen, and energy source, was isolated from soil microcosms. HPLC and GC-MS analysis of the samples obtained from growth and resting cell studies showed the formation of 4-nitroaniline (4-NA), 4-aminophenol (4-AP), and 1, 2, 4-benzenetriol (BT) as major metabolic intermediates in the MNA degradation pathway. Enzymatic assay carried out on cell-free lysates of MNA grown cells confirmed N-demethylation reaction is the first step of MNA degradation with the formation of 4-NA and formaldehyde products. Flavin-dependent transformation of 4-NA to 4-AP in cell extracts demonstrated that the second step of MNA degradation is a monooxygenation. Furthermore, conversion of 4-AP to BT by MNA grown cells indicates the involvement of oxidative deamination (release of NH₂ substituent) reaction in third step of MNA degradation. Subsequent degradation of BT occurs by the action of benzenetriol 1, 2-dioxygenase as reported for the degradation of 4-nitrophenol. This is the first report on aerobic degradation of MNA by a single bacterium along with elucidation of metabolic pathway.     

Population Dynamics of the Root-Knot Nematode Meloidogyne Triticoryzae under Five Rice-Based Cropping Systems

Population dynamics of M. triticoryzae in five rice-based cropping systems have revealed that rice was the main host. Most of the population growth which contributed to the peak population density in September occurred in the rice crop. The other crops in the Rabi and summer seasons had a profound influence on the height of the peak in the succeeding rice crop. Some level of reproduction occurred in wheat, greengram and berseem in Rabi which contributed to relatively higher equilibrium densities. The potato variety Pusa Bahar increased the population density while Pusa Badshah decreased it. The lower temperature during the Rabi season also limited the rate of population growth. The incorporation of organic matter into the soil, either as crop residues of greengram or berseem, reduced the population growth of M. triticoryzae .     

Chemical reaction- and particle diffusion-based kinetic modeling of metal biosorption by a Phormidium sp.-dominated cyanobacterial mat

The present study explores the suitability of chemical reaction-based and diffusion-based kinetic models for defining the biosorption of Cu(II), Cd(II) and Pb(II) by Phormidium sp.-dominated mat. The time-course data of metal sorption by the test mat significantly (r² = 0.932-0.999) fitted to the chemical reaction-based models namely pseudo-first-order, -second-order, and the general rate law. However, these models fail to accurately describe the kinetics of metal biosorption due either to prefixed order or unjustifiable change in rate constant and reaction order with varying concentrations of metal and biomass in the solution. The diffusion-based models, namely, the intra-particle diffusion model and the external mass transfer model fitted well to the time-course metal sorption data, thus suggesting involvement of both external and intra-particle diffusion processes in sorption of test metals by mat biomass. However, the Boyd kinetic expression clearly showed that the external mass transfer is the dominant process.     

Overexpression of plastidic maize NADP-malate dehydrogenase (<Emphasis Type="Italic">ZmNADP-MDH</Emphasis>) in <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis> confers tolerance to salt stress

The plastidic C4 Zea mays NADP-malate dehydrogenase (ZmNADP-MDH), responsible for catalysis of oxaloacetate to malate, was overexpressed in Arabidopsis thaliana to assess its impact on photosynthesis and tolerance to salinity stress. Different transgenic lines were produced having ~3–6-fold higher MDH protein abundance and NADP-MDH enzyme activity than vector control. The overexpressors had similar chlorophyll, carotenoid, and protein content as that of vector control. Their photosynthetic electron transport rates, carbon assimilation rate, and consequently fresh weight and dry weight were almost similar. However, these overexpressors were tolerant to salt stress (150 mM NaCl). In saline environment, the Fv/Fm ratio, yield of photosystem II, chlorophyll, and protein content were higher in ZmNADP-MDH overexpressor than vector control. Under identical conditions, the generation of reactive oxygen species (H₂O₂) and production of malondialdehyde, a membrane lipid peroxidation product, were lower in overexpressors. In stress environment, the structural distortion of granal organization and swelling of thylakoids were less pronounced in ZmNADP-MDH overexpressing plants as compared to the vector control. Chloroplastic NADP-MDH in consort with cytosolic and mitochondrial NAD-MDH plays an important role in exporting reducing power (NADPH) and exchange of metabolites between different cellular compartments that maintain the redox homeostasis of the cell via malate valve present in chloroplast envelope membrane. The tolerance of NADP-MDH overexpressors to salt stress could be due to operation of an efficient malate valve that plays a major role in maintaining the cellular redox environment.     

Influence of Feeding Inorganic Vanadium on Growth Performance,Endocrine Variables and Biomarkers of Bone Health in Crossbred Calves

The nutritional essentialities of transition element vanadium (V) as micro-nutrient in farm animals have not yet been established, though in rat model, vanadium as vanadate has been reported to exert insulin-mimetic effect and shown to be needed for proper development of bones. The objective of this study was to determine the effect of V supplementation on growth performance, plasma hormones and bone health status in calves. Twenty-four crossbred calves (body weight 72.83 ± 2.5 kg; age 3–9 months) were blocked in four groups and randomly assigned to four treatment groups (n = 6) on body weight and age basis. Experimental animals were kept on similar feeding regimen except that different groups were supplemented with either 0, 3, 6 or 9 ppm inorganic V/kg DM. Effect of supplementation during 150-day experimental period was observed on feed intake, body weight gain, feed efficiency, body measures, endocrine variables, plasma glucose and biomarkers of bone health status. Supplementation of V did not change average daily gain (ADG), dry matter intake (DMI), feed efficiency and body measures during the experimental period. During the post-V supplementation period plasma insulin-like growth factor-1 (IGF-1), triiodothyronine (T₃) and thyroxin (T₄) concentrations were increased and observed highest in 9 mg V/kg DM fed calves; however, levels of insulin, glucose, parathyroid hormone (PTH) and calcitonin hormones remained similar among calves fed on basal or V-supplemented diets. Bone alkaline phosphatase (Bone-ALP) concentration was increased (P < 0.05); however, plasma protein tyrosine phosphatase (PTP) level decreased (P < 0.05) in 6 and 9 mg V/kg DM supplemented groups. Plasma hydroxyproline (Hyp) and tartrate-resistant acid phosphatase (TRAP) concentration were unchanged by V supplementation. Blood V concentration showed positive correlation with supplemental V levels. These results suggest that V may play a role in modulation of the action of certain endocrine variables and biomarkers of bone health status in growing crossbred calves.     

DNA recognition properties of the N-terminal DNA binding domain within the large subunit of replication factor C.

Replication Factor C (RFC) is a five-subunit protein complex required for eukaryotic DNA replication and repair. The large subunit within this complex contains a C-terminal DNA binding domain which provides specificity for PCNA loading at a primer-template and a second, N-terminal DNA binding domain of unknown function. We isolated the N-terminal DNA binding domain from Drosophila melanogaster and defined the region within this polypeptide required for DNA binding. The DNA determinants most efficiently recognized by both the Drosophila minimal DNA binding domain and the N-terminal half of the human large subunit consist of a double-stranded DNA containing a recessed 5' phosphate. DNA containing a recessed 5' phosphate was preferred 5-fold over hairpined DNA containing a recessed 3' hydroxyl. Combined with existing data, these DNA binding properties suggest a role for the N-terminal DNA binding domain in the recognition of phosphorylated DNA ends.