The spatial distributions of randomly coiling polynucleotides

Statistical mechanical averages of vectors and tensors characterizing the allowed configurations of randomly coiling polynucleotides have been calculated for chains of 2⁰–2¹⁰ repeating units. Specifically, the persistence vector p = 〈 r 〉 has been obtained as a function of chain length. Configurational averages of the Cartesian tensors formed from the displacement vector ρ = r – p have been computed up to and including the tensor of seventh rank. From these tensors the three-dimensional spatial distributions of end-to-end vectors have been constructed to provide comprehensive pictures of the directional tendencies of the randomly coiling polynucleotide. The elements of the third and fourth moment tensors, however, give sufficient information to represent accurately the qualitative features of the spatial distributions. For long chains, more than 2⁶ (64) repeating units, the spatial distributions assume spherically symmetric shapes that can be adequately characterized by one-dimensional radial distribution functions. These radial distribution functions agree well with the radial distributions calculated from Monte Carlo samples containing more than 5000 chains. The constraints of fixed bond lengths, fixed bond angles, and hindered internal rotations severely distort the spatial distributions of short polynucleotide chains to mushroom-shaped volumes. These skewed distributions provide information useful to the analysis of small, single-stranded loops, bulges, and circles. The formation of these structures requires the termini of the polynucleotides to lie within specifically delineated volumes with respect to coordinate systems affixed to the first bonds of the chains. The extent to which these loop closure volumes overlap the three-dimensional spatial distributions provides estimates of loop formation that are much more reliable than earlier studies based upon the radial distribution function.     

The superoxide anion and singlet molecular oxygen: their role in the microbicidal activity of the polymorphonuclear leukocyte

Superoxide dismutase was found to partially inhibit both chemiluminescence and nitroblue tetrazolium (NBT) reduction from intact human polymorphonuclear leukocytes. This capacity to reduce NBT was lost when the polymorphonuclear leukocytes were sonicated, but could be regained if exogenous NADPH (or NADH) was added to the system. Superoxide dismutase was found to inhibit this NADPH- and NADH-dependent NBT reduction. A mechanism is proposed that relates superoxide anion generation to the univalent reduction of O₂ by the activated NADPH (and NADH) oxidase. The relationship of superoxide anion production to NBT reduction, singlet molecular oxygen generation, and chemiluminescence is discussed.     

Obesity and Weight Control Practices in 2000 Among Veterans Using VA Facilities

Objective: To examine obesity prevalence and weight control practices among veterans who use Department of Veterans Affairs (VA) medical facilities (VA users). Research Methods and Procedures: Data from the 2000 Behavioral Risk Factor Surveillance System, a telephone survey of 184, 450 adults, were analyzed. Outcome measures included BMI, weight control practices (the intent to manage weight, and diet and physical activity patterns), and receipt of professional weight control advice. Results: Of VA users, 44% were overweight and 25% were obese. After controlling for demographic factors, VA users were somewhat less likely to be overweight (odds ratio, 0.86; 95% confidence interval, 0.74 to 1.00) but equally likely to be obese (odds ratio, 1.08; 95% confidence interval, 0.92 to 1.27), compared with non‐VA users. Among obese VA users, 75% reported trying to lose weight, and another 17% reported trying to maintain weight. Of these, only 40% decreased both calorie and fat intake. Only 27% of obese VA users who reported increasing exercise to lose weight followed recommendations for regular and sustained physical activity. Of obese VA users, 59% were inactive or irregularly active. Only 51% of obese VA users received professional advice to lose weight. Obese VA users were more likely than obese non‐VA users to report trying to lose weight, modifying diet to lose weight by decreasing both calories and fat intake, and receiving professional weight control advice. Discussion: Interventions for weight management programs in VA facilities need to take into account the high prevalence of overweight/obesity among VA users and should emphasize effective weight control practices.     

Chronobiotic activity of N-[2-(2,7-dimethoxyfluoren-9-yl)ethyl]-propanamide. Synthesis and melatonergic pharmacology of fluoren-9-ylethyl amides

A series of fluoren-9-yl ethyl amides (2) were synthesized and evaluated for human melatonin MT(1) and MT(2) receptor binding. N-[2-(2,7-dimethoxyfluoren-9-yl)ethyl]propanamide (2b) was selected and evaluated in functional assays measuring intrinsic activity at the human MT(1) and MT(2) receptors and demonstrated full agonism at both receptors. The chronobiotic properties of 2b were demonstrated in both acute and chronic rat models where 2b produced an acute phase advance of 32 min at 1mg/kg and chronically entrained free-running rats with a mean effective dose of 0.23 mg/kg. Compound 2b is significantly less efficacious than melatonin in constricting human coronary artery.     

Ligand conformation has a definitive effect on 5-HT1A and serotonin reuptake affinity

Conformationally constrained aryl cyclohexanes and cyclohexenes based on aryl cyclohexanols 1 were prepared. Locking the aryl ring in plane with the cyclohexane moiety provided potent SSRIs 3. Conversely, fixing the aryl ring perpendicular to the cyclohexane ring via a spiro lactone provided balanced 5-HT1A antagonists with mid-nanomolar range SSRI potency (compounds 2).     

Acute Toxicity of water-borne dimethylnitrosamine (DMN) to Fundulus heteroclitus (L.)

Acute (120h) toxicity of the water-borne carcinogen, dimethylnitrosamine (DMN) to adult Fundulus heteroclitus (L.) at 20°C and 20.2%₀ salinity in natural seawater was determined. The LC-50 values were 8300 mg/1 at 24 h, 5500 mg/1 at 48 h, 4700 mg/1 at 72 h, 3300 mg/1 at 96 h and 2700 mg/1 at 120 h.
Gross lesions consisted of peritoneal and cephalic ecchymoses. Microscopic lesions included necrosis and sloughing of the gastrointestinal mucosa, haemorrhage and necrosis of the liver, and necrosis of taste buds, with severity and incidence being a function of DMN concentration. Acute pathological effects of DMN on Fundulus heteroclitus conformed closely to those reported in other species exposed to this compound by respiratory, oral or parenteral route. DMN concentrations used in this experiment greatly exceeded those expected to be found under natural conditions, and this report is intended both to improve our understanding of DMN-induced pathology in marine fishes and to provide further evidence of the consistency of acute lesions induced by DMN, regardless of test organism or mode of exposure.     

Black spot gill syndrome of the northern shrimp Pandalus borealis

Northern shrimp, Pandalus borealis, taken in the Gulf of Maine show tissue destruction of gill lamellae. Vacuolated chitin growth over damaged tissue produces macroscopic black spots on the gills. First noticed in 1966, semiquantitative records were kept for four consecutive years. Incidence of infestation for this period is described.