Evidence for independence of circadian characters and extent of photoresponsiveness in the Djungarian hamster, Phodopus sungorus.

Djungarian hamsters (Phodopus sungorus) exposed to a short-day photoperiod generally respond with a syndrome of physiological and behavioral changes, such as body weight loss and molt to a white pelage. The extent of the short-day-induced responses differs among individuals. Furthermore, some hamsters show no photoresponse. In this study, we sought to determine whether variation in the photoresponse would be associated with circadian function: whether phase angle or free-running period (tau) would differ between responsive and nonresponsive hamsters; and whether changes in these circadian characters would correlate with the extent of weight loss and molt (and the timing of molt onset) in photoresponsive hamsters. Adult hamsters were kept in a short-day photoperiod (9 hr light, 15 hr dark) for 14 weeks, during which time body weight and molt were measured biweekly. Hamsters were then transferred to cages equipped with running wheels; we measured the phase angle of activity onset under a short-day photoperiod and tau in constant dark. Hamsters exhibiting a short-day-induced molt had a significantly shorter tau and a less negative phase angle than nonmolting animals. Hamsters that exhibited weight loss also had a significantly less negative phase angle, but no difference in tau. No significant Pearson's or Spearman's correlation coefficients were found between extent (or timing) of the photoresponse and the circadian characters in responsive hamsters. Although these results indicate that threshold for photoresponsiveness is related to circadian function, the extent (and timing) of the photoresponse may not be.     

Regulation by estrogen through the 5'-flanking region of the transforming growth factor alpha gene.

Expression of transforming growth factor alpha (TGF alpha) mRNA and protein can be stimulated by estrogens such as 17 beta-estradiol (E2) in estrogen-responsive rodent and human breast cancer cells. To ascertain if E2 can directly regulate TGF alpha expression through the 5'-flanking region of the human TGF alpha gene, E2-responsive MCF-7 or ZR-75-1 human breast cancer cells or E2-nonresponsive MDA-MB-231 breast cancer cells were transiently transfected with a plasmid containing an 1140-base pair (bp) Sac-I fragment of the TGF alpha 5'-flanking region ligated to the chloramphenicol acetyltransferase (CAT) gene. Cells that were transfected and subsequently treated with physiological concentrations of E2 (10(-11)-10(-8) M) for 24 h exhibited a 2- to 10-fold increase in CAT activity. The E2 stimulation of CAT activity was dose-dependent with an increase first found at 10(-10) M E2. The increase in CAT activity could be detected within 24-36 h after the addition of E2. There was no significant change in CAT activity in transiently transfected MDA-MB-231 cells as mediated through the TGF alpha 5'-flanking region after E2 treatment. MCF-7 cells were also transiently transfected with different fragments of the TGF alpha 5'-flanking region ligated to the luciferase gene. In the absence of E2 treatment, no detectable luciferase activity was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Murine retrovirus-induced spongiform encephalopathy: productive infection of microglia and cerebellar neurons in accelerated CNS disease.

We have examined the pathological lesions and sites of infection in mice inoculated with a highly neurovirulent recombinant wild mouse ecotropic retrovirus (FrCasE). The spongiform lesions appeared initially as swollen postsynaptic neuronal processes, progressing to swelling in neuronal cell bodies, all in the absence of detectable gliosis. Infection of neurons in regions of vacuolation was not detected. However, high level infection of cerebellar granule neurons was observed in the absence of cytopathology, wherein viral protein was found associated with both axons and dendrites. Infection of ramified and amoeboid microglial cells was associated with cytopathology in the brain stem, and endothelial cell-pericyte infection was found throughout the CNS. No evidence of defective retroviral expression was observed. These results are consistent with an indirect mechanism of retrovirus-induced neuropathology.     

MUTATION LOAD AND THE SURVIVAL OF SMALL POPULATIONS

Previous attempts to model the joint action of selection and mutation in finite populations have treated population size as being independent of the mutation load. However, the accumulation of deleterious mutations is expected to cause a gradual reduction in population size. Consequently, in small populations random genetic drift will progressively overpower selection making it easier to fix future mutations. This synergistic interaction, which we refer to as a mutational melt-down, ultimately leads to population extinction. For many conditions, the coefficient of variation of extinction time is less than 0.1, and for species that reproduce by binary fission, the expected extinction time is quite insensitive to population carrying capacity. These results are consistent with observations that many cultures of ciliated protozoans and vertebrate fibroblasts have characteristic extinction times. The model also predicts that clonal lineages are unlikely to survive more than 10⁴ to 10⁵ generations, which is consistent with existing data on parthenogenetic animals. Contrary to the usual view that Muller's ratchet does more damage when selection is weak, we show that the mean extinction time declines as mutations become more deleterious. Although very small sexual populations, such as self-fertilized lines, are subject to mutational meltdowns, recombination effectively eliminates the process when the effective population size exceeds a dozen or so. The concept of the effective mutation load is developed, and several procedures for estimating it are described. It is shown that this load can be reduced substantially when mutational effects are highly variable.     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Organic acids from the anaerobic decomposition of Agropyron repens rhizomes

Phytotoxicity originating from the anaerobic decomposition of couch grass rhizomes has been studied. Short chain aliphatic (acetic, propionic and butyric) acids appear to be mainly responsible but hexanoic, succinic, phenylacetic, cinnamic, p-coumaric, 4-hydroxyphenylpropionic and 3,4-dihydroxyphenylpropionic acids are also present in the phytotoxic solutions formed during the decomposition.     

Postneonatal mortality in children from abusing families.

The postneonatal death rate was studied for 332 infants from 160 families, ascertained through an abused proband. There were nine deaths compared with 2.9 expected from the legitimacy, social class, age, and parity distribution (p = 0.003). All but one of the babies died at home, and all were referred to a coroner or procurator fiscal. No adequate explanation of death could be found in four cases. Bonding problems probably existed in most of the nine families before death occurred.     

The differential distribution of vasoactive intestinal polypeptide in the normal human female genital tract

Summary VIP-like immunoreactive material is present in the female reproductive tract, with a distinct pattern of distribution. The highest concentrations of extractable material and immunoreactive nerve fibres were found in the cervix and vagina. In the cervix these fibres were seen below the surface epithelium and around cervical glands as well as in association with blood vessels and smooth muscle bundles. In the vagina the nerve fibres were most abundant in the superficial regions of the lamina propria. Scattered fibres were also present in the rest of the uterus and in the fallopian tubes. Chromatographic evidence indicates that this VIP-like material is of a similar molecular size to that extracted from other organs. Possible roles for VIP in the regulation of myometrial activity and of cervical and vaginal dilation and secretion are proposed.     

Evidence for messenger ribonucleic acid of an ammonium-inducible glutamate dehydrogenase and synthesis, covalent modification, and degradation of enzyme subunits in uninduced Chlorella sorokiniana cells.

The cells of Chlorella sorokiniana cultured in nitrate medium contain no detectable catalytic activity of an ammonium-inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH). However, several lines of experimental evidence indicated that the NADP-GDH messenger ribonucleic acid was present at high levels and was being translated in uninduced cells. First, binding studies with 125I-labeled anti-NADP-GDH immunoglobulin G and total polysomes isolated from uninduced and induced cells showed that NADP-GDH subunits were being synthesized on polysomes from both types of cells. Second, when polyadenylic acid-containing ribonucleic acid was extracted from polysomes from uninduced and induced cells and placed into a messenger ribonucleic acid-dependent in vitro translation system, NADP-GDH subunits were synthesized from the ribonucleic acid from both sources. Third, when ammonia was added to uninduced cells, NADP-GDH antigen accumulated without an apparent induction lag. Fourth, by use of a specific immunoprecipitation procedure coupled to pulse-chase studies with [35S]sulfate, it was shown that the NADP-GDH subunits are rapidly synthesized, covalently modified, and then degraded in uninduced cells.