Dose-response modeling of life shortening in a retrospective analysis of the combined data from the JANUS program at Argonne National Laboratory

Life shortening was investigated in both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse exposed to fission neutrons and 60Co gamma rays. Three basic exposure patterns for both neutrons and gamma rays were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. Ten different dose-response models were fitted to the data for animals exposed to neutrons. The response variable used for all dose-response modeling was mean after-survival. A simple linear model adequately described the response to neutrons for females and males at doses less than or equal to 80 cGy. At higher neutron dose levels a linear-quadratic equation was required to describe the life-shortening response. An effect of exposure pattern was observed prior to the detection of curvature in the dose response for neutrons and emerged as a potentially significant factor at neutron doses in the range of 40-60 cGy. Augmentation of neutron injury with dose protraction was observed in both sexes and began at doses as low as 60 cGy. The life-shortening response for all animals exposed to gamma rays (22-1918 cGy) was linear and inversely dependent upon the protraction period (1 day, 24 weeks, 60 weeks). Depending on the exposure pattern used for the gamma-ray baseline, relative biological effectiveness (RBE) values ranged from 6 to 43. Augmentation, because it occurred only at higher levels of neutron exposure, had no influence on the estimation of RBEm.     

A quantitative comparison of a percentile rule with a 2-fold rule for assessing mutagenicity in the Ames assay

Using a model based on the bivariate normal density function, this paper compares the effectiveness of two commonly employed decision rules for assessing mutagenicity in the standard Ames Salmonella assay. The 2-fold method, which considers a compound significantly mutagenic if its mean number of revertants per plate at any dose is equal to or greater than twice the mean number of revertants per plate in the concurrent control, may be a poor indicator of significant mutagenesis. In the percentile method, the frequency of induced mutations for the test compound is tested against the 95th percentile of the accumulated historical data for the spontaneous mutation frequency. As judged by the higher probability of declaring a compound mutagenic that elevates the reversion rate above background, the percentile rule is more reliable than the 2-fold method.     

Low-kilohertz-water-borne ultrasound

Summary The effects of 25 kHz ultrasound on murine testes was studied, as mimicking possible World WAR II SONAR exposure to swimming maintenance personnel. Very few specimens were found to exhibit morphological tissue alterations, depending upon length of exposure time and proximity of the source to the tissue. Thermal processes seem to be eliminated, but microstreaming may be implicated, as the physical mechanism(s) of interaction.     

Plant regeneration by organogenesis in Glycine max

A procedure for the regeneration of fertile plants by organogenesis from tissue cultures of soybeans, Glycine max is described. Seeds were germinated on reduced inorganic salt MS medium containing 5M BA. Cotyledonary nodes were excised and cultured on the same medium. Presence of BA in the medium during seed germination and culture of nodal explants was required for multiple shoot and shoot-bud formation. Histological analyses established the de novo nature of shoot regeneration. Separate reduction of the concentration of inorganic salts or substitution of sucrose for fructose during culture had minimal effects on the regeneration response. Conversely, if the BA was reduced, the inhibition response could not be overcome by increased salt concentration or altered carbon source.Abbreviations BA benzyladenine - IAA indoleacetic acid - SAS secondary axillary shoots - MS Murashige and Skoog (1962) medium     

The comparative tumorigenic effects of fission neutrons and cobalt-60 gamma rays in the B6CF1 mouse.

In the period from 1971 to 1986, both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse were exposed at 110 +/- 7 days of age to single, 24 once-weekly or 60 once-weekly doses of fission neutrons or 60Co gamma rays. A small group of males was also exposed to gamma rays for 22 h/day, 5 days/week, for either 23 or 59 weeks, the elapsed times for the 24 and 60 once-weekly series. All mice were followed for their natural lifetimes. A gross pathology report is available on 32,000 animals, and a histopathology record is available on about 19,000. About 85% died with or from one or more neoplastic diseases. The principal tumors observed at death were of lymphoreticular (45-60%), vascular (20%), or pulmonary (35-50%) origin. From 4 to 10% died with fibrosarcomas, hepatocellular tumors, ovarian tumors, and tumors of the Harderian, adrenal, and pituitary glands. Dose-response equations (linear and linear-quadratic) were fitted to the data for deaths from and occurrences of eight different individual or groups of tumors. Equations were constrained through the control intercepts and fitted separately for the two sexes, the two radiation qualities, and all exposure patterns for the two intervals of 600-799 days and 800-999 days from first exposure. RBE values were derived from the ratios of linear coefficients of dose-response curves. RBE values increased as dose was protracted, largely due to the reduced effectiveness of protracted gamma irradiation; however, about 28% of the increase can be attributed to the increase in neutron-induced injury caused by dose protraction. Highest RBE values were seen for tumors of epithelial tissue origin and the lowest for tumors of connective tissue origin. The range for significant values was from about 2 to over 50. Nonneoplastic diseases accounted for about 5% of all deaths, and 10% were classified as from unknown causes. Neither category responded to differences in radiation quality or exposure patterns.     

Social Justice and Social Order: Binding Moralities across the Political Spectrum

Two studies explored the relationship between political ideology and endorsement of a range of moral principles. Political liberals and conservatives did not differ on intrapersonal or interpersonal moralities, which require self-regulation. However differences emerged on collective moralities, which involve social regulation. Contrary to Moral Foundations Theory, both liberals and conservatives endorsed a group-focused binding morality, specifically Social Justice and Social Order respectively. Libertarians were the group without a binding morality. Although Social Justice and Social Order appear conflictual, analyses based on earlier cross-cultural work on societal tightness-looseness suggest that countries actually benefit in terms of economic success and societal well-being when these group-based moralities co-exist and serve as counterweights in social regulation.     

Tori lines mitigate seabird bycatch in a pelagic longline fishery

Reviews in Fish Biology and Fisheries - Albatross bycatch has been increasing over the past decade in the US tuna longline fishery of the central North Pacific. A controlled field...     

Pyridostigmine improves cardiac function and rhythmicity through RyR2 stabilization and inhibition of STIM1-mediated calcium entry in heart failure

Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial effects. However, mechanisms of parasympathetic-mediated improvement in cardiac function remain unclear. The present study examined the effects and underpinning mechanisms of chronic treatment with the cholinesterase inhibitor, pyridostigmine (PYR), in pressure overload HF induced by transverse aortic constriction (TAC) in mice. TAC mice exhibited characteristic adverse structural (left ventricular hypertrophy) and functional remodelling (reduced ejection fraction, altered myocyte calcium (Ca) handling, increased arrhythmogenesis) with enhanced predisposition to arrhythmogenic aberrant sarcoplasmic reticulum (SR) Ca release, cardiac ryanodine receptor (RyR2) hyper-phosphorylation and up-regulated store-operated Ca entry (SOCE). PYR treatment resulted in improved cardiac contractile performance and rhythmic activity relative to untreated TAC mice. Chronic PYR treatment inhibited altered intracellular Ca handling by alleviating aberrant Ca release and diminishing pathologically enhanced SOCE in TAC myocytes. At the molecular level, these PYR-induced changes in Ca handling were associated with reductions of pathologically enhanced phosphorylation of RyR2 serine-2814 and STIM1 expression in HF myocytes. These results suggest that chronic cholinergic augmentation alleviates HF via normalization of both canonical RyR2-mediated SR Ca release and non-canonical hypertrophic Ca signaling via STIM1-dependent SOCE.     

Age and anesthetic effects on murine electrocardiography

Murine models offer potential insights regarding human cardiac disease, but efficient and reliable methods for phenotype evaluation are necessary. We employed non-invasive electrocardiography (ECG) in mice, investigating statistical reliability of these parameters with respect to anesthetic and animal age. Mice (C57BL/6, 8 or 48 weeks) were anesthetized by ketamine/xylazine (K/X, 80/10 mg/kg ip) or by inhalation anesthetic (halothane, HAL; sevoflurane, SEV) and 6 lead ECGs were recorded. P wave duration and QT interval was significantly prolonged with K/X compared to HAL and SEV, indicating slowed atrial and ventricular conduction. P-R interval (atrio-ventricular conduction) was significantly increased in aged mice under all anesthetics. Heart rate was inversely correlated to QT interval and P wave duration. We also detected significant age effects with respect to optimal approaches for QT interval corrections. Power analysis showed 4-fold higher number of mice/group, were required for K/X, to achieve identical statistical sensitivity. These data demonstrate the importance of anesthetic selection for relevant and reliable ECG analysis in mice and illustrate the selective influences of anesthetics and age on cardiac conductance in this species.     

Stage-specific effects of the fungicide carbendazim on Sertoli cell microtubules in rat testis

The aim of the present study is to provide a morphological explanation of carbendazim (CBZ)-induced sloughing of germ cells that occurs in a stage-specific manner. Therefore, very early alterations in the seminiferous tubule epithelium were examined histologically in the rat testis after oral administration of CBZ (400mg/kg). Gaps between the elongated and round spermatids, the first indication of germ cell sloughing (pre-sloughing), were observed in stage late VI-early VII seminiferous tubules at 90-min post-treatment. Tubulin immunoreaction in the Sertoli cells was reduced in intensity in tubules with pre-sloughing. However, electron microscopy demonstrated that there were some intact microtubules in these cells. At 120 min, sloughing was seen in stage late VI-early VII and XIII-XIV. Tubulin immunoreaction in the Sertoli cells was greatly decreased in intensity in tubules where cell sloughing was observed. Electron microscopy showed that there were few microtubules in the body region of these cells. Stages II-V and mid-VII-VIII were exempt from the sloughing effect at 180 min. These changes in microtubules were not observed in Sertoli cells that did not exhibit sloughing characteristics, regardless of the post-treatment intervals. The present results suggest that stage specificity of sloughing is due to the stage-specific susceptibility of Sertoli cell microtubules to CBZ.