Synthesis of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones as NMDA glycine-site antagonists

Several members of the 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones (2) have been identified as being potent and selective NMDA glycine-site antagonists. Increasing size of the alkyl substituent on the alpha-carbon led to a progressive decrease in binding affinity. Some of these analogues possess improved drug-like properties such as cellular permeability, solubility and oral absorption.     

Characterization of microsatellite DNA loci for the southern flying squirrel (Glaucomys volans)

Polymerase chain reaction primers for microsatellite DNA loci (one dinucleotide, four tetranucleotide and two compound) and the conditions necessary to amplify each are described for the southern flying squirrel (Glaucomys volans). These primers were tested on 22 or more individuals from a population at the Savannah River Site in South Carolina. These microsatellite primers yielded a high allelic diversity (6–22 alleles/locus), and moderate to high observed heterozygosities (0.318–0.826). Primers developed for the northern flying squirrel (Glaucomys sabrinus) were also tested for use on G. volans, with only two successful cross amplifications from the seven loci.     

Plant architecture

Plant architecture is species specific, indicating that it is under strict genetic control. Although it is also influenced by environmental conditions such as light, temperature, humidity and nutrient status, here we wish to focus only on the endogenous regulatory principles that control plant architecture. We summarise recent progress in the understanding of the basic patterning mechanisms involved in the regulation of leaf arrangement, the genetic regulation of meristem determinacy, i.e. the decision to stop or continue growth, and the control of branching during vegetative and generative development.  Finally, we discuss the basis of leaf architecture and the role of cell division and cell growth in morphogenesis.     

Inactivity, exercise training and detraining, and plasma lipoproteins. STRRIDE: a randomized, controlled study of exercise intensity and amount.

Exercise has beneficial effects on lipoproteins. Little is known about how long the effects persist with detraining or whether the duration of benefit is effected by training intensity or amount. Sedentary, overweight subjects (n = 240) were randomized to 6-mo control or one of three exercise groups: 1) high-amount/vigorous-intensity exercise; 2) low-amount/vigorous-intensity exercise; or 3) low-amount/moderate-intensity exercise. Training consisted of a gradual increase in amount of exercise followed by 6 mo of exercise at the prescribed level. Exercise included treadmill, elliptical trainer, and stationary bicycle. The number of minutes necessary to expend the prescribed kilocalories per week (14 kcal x kg body wt(-1) x wk(-1) for both low-amount groups; 23 kcal x kg body wt(-1) x wk(-1) for high-amount group) was calculated for each subject. Average adherence was 83-92% for the three groups; minutes per week were 207, 125, and 203 and sessions per week were 3.6, 2.9, and 3.5 for high-amount/vigorous-intensity, low-amount/vigorous intensity, and low-amount/moderate-intensity groups, respectively. Plasma was obtained at baseline, 24 h, 5 days, and 15 days after exercise cessation. Continued inactivity resulted in significant increases in low-density lipoprotein (LDL) particle number, small dense LDL, and LDL-cholesterol. A modest amount of exercise training prevented this deterioration. Moderate-intensity but not vigorous-intensity exercise resulted in a sustained reduction in very-low-density lipoprotein (VLDL)-triglycerides over 15 days of detraining (P < 0.05). The high-amount group had significant improvements in high-density lipoprotein (HDL)-cholesterol, HDL particle size, and large HDL levels that were sustained for 15 days after exercise stopped. In conclusion, physical inactivity has profound negative effects on lipoprotein metabolism. Modest exercise prevented this. Moderate-intensity but not vigorous-intensity exercise resulted in sustained VLDL-triglyceride lowering. Thirty minutes per day of vigorous exercise, like jogging, has sustained beneficial effects on HDL metabolism.     

Synthesis and Antioxidant Activity of 3‐(Pyridin‐2‐ylmethyl)‐1,3‐thiazinan(thiazolidin)‐4‐ones

The antioxidant properties of two series of thiazolidinones and thiazinanones were reported. The novel six‐membered thiazinanones were synthesized from the efficient multicomponent reaction of 2‐picolylamine (2‐aminomethylpyridine), arenaldehydes, and the 3‐mercaptopropionic acid in moderate to excellent yields. These novel compounds were fully identified and characterized by NMR and GC‐MS techniques. In vitro antioxidant activities of all compounds were evaluated by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azinobis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) tests. The antioxidant assays of thiobarbituric acid reactive species and total thiol content levels in the cerebral cortex and liver of rats were also performed. Thiazinanone 5a showed the best radical scavenging activity in DPPH and ABTS tests, as well as reduced lipid peroxidation and increased total thiol group in biological systems. Altogether, the results may be considered a good starting point for the discovery of a new radical scavenger.     

On the Localized Nature of the Structural Transformations of Li2MnO3 Following Electrochemical Cycling

Although the Li‐excess layered‐oxide Li₂MnO₃ has a high theoretical capacity, structural transformations within the oxide during electrochemical cycling lead to relatively low experimental capacities, hindering its use in practical applications. Here, aberration‐corrected scanning transmission electron microscopy/electron energy loss spectroscopy and high‐resolution X‐ray diffraction are used to characterize the oxide following electrochemical cycling. Microscopy reveals the coexistence of regions with local monoclinic, spinel, and rock‐salt symmetries, indicating localized and inhomogeneous structural evolutions. Crystal structure transformations are observed both at the particle surface and in the bulk. At the surface, these transformed regions resemble spinel Mn₃O₄ or rock‐salt MnO, consistent with oxygen loss. In the bulk, the regions resemble defect spinels, such as the layered‐spinel Li_xMn_4/3O₄, which suggest a partial phase transformation consistent with oxygen retention. Both microscopy and diffraction data of the cycled sample indicate areas of pristine Li₂MnO₃; the presence of such areas, in close proximity to Li_xMn_4/3O₄ areas, suggests that the layered to spinel structure transformation is partially reversible. Spinel, disordered rock salt, and pristine areas are also observed in Li₂MnO₃ samples intentionally damaged by electron beam irradiation. This observation indicates that the dynamic processes resulting in phase transformations can be studied for a variety of oxide systems by a judicious selection of irradiation conditions.