Thermal inhibition of repair of methylmethane sulfonate-damaged DNA in chick embryo fibroblasts

Chick embryo fibroblasts were treated with the monofunctional alkylating agent methylmethane sulfonate at various concentrations for 1 h at 42°C, rinsed and then incubated post-treatment at various temperatures at which the kinetics of alkali-labile bond disappearance was followed. Growth experiments showed that these cells grew similarly at temperatures of either 37°C or 42°C. Repair as assessed by removal of alkali-labile bond was also similar for postincubation in the temperature range 37–42°C for damage due to methylmethane sulfonate treatment at concentrations less than 1.5 mM. When the postincubation temperature was raised higher than 42.5–43°C, this type of repair was stopped. The normal internal body temperature of adult chickens is about 41.6°C. Hence the present finding indicates that chick cells are much more severely restricted in DNA repair at temperatures above normal than are mammalian cells, which can function in this respect for several deg. C above 37°C.     

The value of decreasing the duration of the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R₀) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R₀ 2.0). With R₀ 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R₀ 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration.     

Parelaphostrongylus tenuis in New Brunswick: the parasite in white-tailed deer (Odocoileus virginianus) and moose (Alces alces)

Research was initiated in 1983 to investigate the ecology of Parelaphostrongylus tenuis in New Brunswick. The objectives were to determine the prevalence and intensity of infection in white-tailed deer, and to determine whether or not moose feces contained first stage larvae, signifying the completion of the life cycle of P. tenuis in this host. Forty-nine percent of deer pellet samples were positive and 60% of deer heads contained adults of P. tenuis. None of the moose pellet samples contained first stage larvae.     

Suppression of defective-sporulation phenotypes by mutations in the major sigma factor gene (rpoD) of Bacillus subtilis

Summary Mutations (crsA47 and crsA4) in the major sigma factor gene (rpoD) of Bacillus subtilis RNA polymerase have been found to be powerful intergenic suppressors of spoOB, spoOE, spoOF, spoOK and spoIIG mutations. The crsA47 suppressor restores sporulation of spoOE, spoOF, spoOK and spoIIG mutants to levels near those of wild type bacteria and substantially improves the sporulation of a spoOB strain. The crsA mutations are shown to prevent the induction by aliphatic alcohols of SpoO phenocopies in wild type B. subtilis cells.     

Three theories of stroboscopic motion detection

The three theories derive from three different paradigms. Suprathreshold judgements of perceived quality of motion in multi-flash displays are modelled by space-time Fourier analysis of the motion stimulus. Stroboscopic motion is perceived as being different from real motion to the extent that the additional Fourier components in stroboscopic motion are detectable. Stroboscopic motion of dots along conflicting paths leads to perceptual competition. The theory to describe perceptual I solution derives and proves the uniqueness of strength functions computed only from the time and from the distance between successive points on each path. Time-strength and motion-strength add to determine path-strength; only the strongest path is perceived. Motion-direction detection in continuously drifting two-flash combinations of sinusoidal gratings is described by elaborated Reichardt detectors (ERDs) that compute the covariance of temporal events in two adjacent locations. Other apparently different, detectors that account for direction-detection data are shown to be equivalent to ERDs.     

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular F×1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 ± 198 mg/day compared to a level of 1180 ± 306 seen in the untreated animals (p < 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower doses of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.     

Sulfhydryl Groups in Receptor Binding of Thyrotropin-Releasing Hormone to Rat Amygdala

Abstract: Binding of [³H]-[3-Me-His²]thyrotropin-releasing hormone ([³H]MeTRH) to TRH receptors in rat amygdala was decreased by sulfhydryl reagents in a time-, temperature-, and concentration-dependent manner. A pronounced reduction in receptor density, with little or no change in binding affinity, was apparent following disulfide bond reduction by dithiothreitol (DTT), alkylation of thiol groups by N -ethylmaleimide (NEM), and their oxidation by 5,5'-dithiobis (2-nitrobenzoic acid). Heavy metals (Cd²⁺, Hg²⁺), which complex with reactive -SH residues, also potently inhibited binding. The pharmacological specificity of residual [³H]MeTRH binding in chemically modified amygdala membranes was the same as that in control preparations. Sequential exposure to thiol reagents, in the presence or absence of cations, revealed possible additive effects. Pretreatment of membranes with TRH (10^--⁸-^-10^--⁶ M ), and its continued presence during modification, afforded protection against DTT and NEM. These results indicate the possible importance of thiol groups in the maintenance of TRH receptor conformation.     

Modulation of Receptors for Thyrotropin-Releasing Hormone by Benzodiazepines: Brain Regional Differences

The benzodiazepines (BZDs) chlordiazepoxide (CDE), diazepam (DZM), and flurazepam (FLM) inhibited receptor binding for thyrotropin-releasing hormone (TRH) with low micromolar potency. In contrast, numerous other categories of drugs were previously shown to be inactive. Scatchard analysis of competition data suggested that the BZDs reduced TRH receptor affinity, consistent with competitive inhibition. Receptors from amygdala, retina, and pituitary appeared more sensitive to inhibition by BZDs than those from hypothalamus, hippocampus, spinal cord, or cerebellum. The latter four regions also gave shallower inhibition curves. CDE revealed an apparently biphasic dissociation of [3-Me-His2]TRH([3H]MeTRH) from amygdala membranes at 4 degrees C, with kinetics similar to those with TRH. These results suggest that TRH receptors in the brain are heterogeneous and that certain BZDs in high therapeutic concentrations may exert central effects through actions at TRH receptors or coupled proteins.     

Adrenalectomy of Rats Results in Hypomyelination of the Central Nervous System

The effect of adrenalectomy on CNS myelin accumulation was investigated to determine whether glucocorticoids play a role in regulating myelination. When 14-day-old rats were adrenalectomized and sacrificed 7-8 days later, the amount of bulk-isolated myelin in whole brain, as expressed per gram wet weight of brain or per milligram DNA-phosphate, was reduced to about 75% that of sham-operated controls. Both brain weight and DNA content were unchanged by adrenalectomy. Examination of individual brain regions also revealed decreased amounts of myelin in adrenalectomized animals. Brain glycerol 3-phosphate dehydrogenase specific activity was reduced in adrenalectomized animals to 40-60% that of controls, and serum corticosterone levels were less than 0.6% of control levels. The amount of cerebral myelin in animals adrenalectomized on day 21 and sacrificed 9 days later was not significantly reduced. This suggests a possible role of glucocorticoids during the early period of rapid myelination.     

Organization of the ribosomal ribonucleic acid genes in various wild-type strains and wild-collected strains of Neurospora

Summary The organization of the ribosomal DNA (rDNA) repcat unit in the standard wild-type strain of Neurospora crassa, 74-OR23-1A, and in 30 other wild-type strains and wild-collected strains of N. crassa, N. tetrasperma, N. sitophila, N. intermedia, and N. discreta isolated from nature, was investigated by restriction enzyme digestion of genomic DNA, and probing of the Southern-blotted DNA fragments with specific cloned pieces of the rDNA unit from 74-OR23-1A. The size of the rDNA unit in 74-OR23-1A was shown to be 9.20 kilobase pairs (kb) from blotting data, and the average for all strains was 9.11+0.21 kb; standard error=0.038; coefficient of variation (C.V.)=2.34%. These data indicate that the rDNA repeat unit size has been highly conserved among the Neurospora strains investigated. However, while all strains have a conserved HindIII site near the 5 end of the 25 S rDNA coding sequence, a polymorphism in the number and/or position of HindIII sites in the nontranscribed spacer region was found between strains. The 74-OR23-1A strain has two HindIII sites in the spacer, while others have from 0 to at least 3. This restriction site polymorphism is strain-specific and not species-specific. It was confirmed for some strains by restriction analysis of clones containing most of the rDNA repeat unit. The current restriction map of the 74-OR23-1A rDNA repeat unit is presented.