Efflux of T4 from the in situ perfused liver of rainbow trout: effect of T4, dithiothreitol and cysteine in the perfusate

A Cortland saline-perfused rainbow trout (Oncorhynchus mykiss) liver model was used to study aspects of T4 efflux from the intact organ system. There was a consistent efflux of T4 in the absence of T4 in the perfusate, and the T4 efflux was increased in the presence of T4 in the perfusate, but the efflux was not T4-dose dependent. The addition of the thiol-containing compound dithiothreitol (DTT, 2 mM) to the perfusate had no significant effect on the flux of T4 from the liver, whereas the addition of cysteine (2 mM), a thiol-containing amino acid suppressed T4 efflux. The results are consistent with the known mechanisms of thyroid hormone trafficking across cell membranes, and suggest that organ systems, such as the liver, may act as a major reserve of hormone, thus participating in plasma thyroid hormone homeostasis.     

Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in BRCA1 and BRCA2 estimated from multiple-case breast cancer families attending Australian family cancer clinics

If the risk of disease is not the same for all germline mutations in a given gene, or if there are other familial modifiers of risk in carriers, then family-history-based estimates of average risk for detected mutations in that gene will depend on how carriers are sampled. Risk may also depend on the site or type of mutation. We studied 51 families with strong histories of breast cancer who attended Australian family cancer clinics and in which a germline mutation in BRCA1 or BRCA2 had been identified (28 and 23 families, respectively). Breast cancer risk in carriers was estimated under maximum likelihood theory, using information from all family members including those not tested, with adjustment for ascertainment by conditioning on genotype of the proband and family phenotype. The average cumulative risk of breast cancer for mutations in either BRCA1 or BRCA2 was 27% (95% confidence interval 16-43%) to age 50 and 64% (44-83%) to age 70. When grouped, the incidence in carriers was on average 17 (10-30) times that in non-carriers, independent of gene or mutation type (hazard ratios: 11 (4-29) for BRCA1, 23 (12-43) for BRCA2 (P for difference = 0.23); 13 (6-29) for protein-truncating mutations, 30 (9-104) for missense mutations and 30 (10-90) for splice-site mutations). For missense mutations, this was equivalent to a cumulative risk to age 70 of 83% (40-100%) and was due in part, but not totally, to the missense mutations 300 T>G in BRCA1 and 4486 G>T in BRCA2, which were individually found to be associated with high risk (P<0.001). Mutations in the central region of BRCA1 may be associated with a lower risk. The issue of the pathogenicity of specific variants may be addressed analytically providing there are one or more suitably informative families with that mutation.     

RETRACTED: SENSORY SUGGESTIVENESS AND LABELING: DO SOY LABELS BIAS TASTE?1

Can labels suggestively influence sensory perceptions and taste? Using a “ Phantom Ingredient” taste test, we show that the presence or absence of a labeled ingredient (soy) and the presence or absence of a health claim negatively bias taste perceptions toward a food erroneously thought to contain soy. We found a label highlighting soy content made health claims believable but negatively influenced perceptions of taste for certain segments of consumers. Our results and discussion provide better direction for researchers who work with ingredient labeling as well as for those who work with soybean products.     

The Arabidopsis Gene Tardy Asynchronous Meiosis Is Required for the Normal Pace and Synchrony of Cell Division during Male Meiosis

Male meiosis in higher organisms features synchronous cell divisions in a large number of cells. It is not clear how this synchrony is achieved, nor is it known whether the synchrony is linked to the regulation of cell cycle progression. Here, we describe an Arabidopsis mutant, named tardy asynchronous meiosis (tam), that exhibits a phenotype of delayed and asynchronous cell divisions during male meiosis. In Arabidopsis, two nuclear divisions occur before simultaneous cytokinesis yields a tetrad of haploid cells. In tam, cell divisions are delayed, resulting in the formation of abnormal intermediates, most frequently dyad meiotic products, or in rare cases, dyad pollen (two gametophytes within one exine wall). Temperature-shift experiments showed that the percentage of the abnormal intermediates increased at 27 degrees C. Analysis of tam and the tam/quartet1 double mutant showed that most of these abnormal intermediates could continue through the normal rounds of cell divisions and form functional pollen, though at a slower than normal pace. The asynchrony of cell division started at the G2/M transition, with cells entering metaphase at different time points, during both meiosis I and II. In addition, chromosome condensation defects and mis-segregation were sometimes observed in tam. These observations suggest that the TAM protein positively regulates cell cycle progression, perhaps by promoting the G2/M transition. We speculate that there is a signal, perhaps TAM, that couples the normal pace of cell cycle progression with the synchrony of cell division during male meiosis.     

Synthesis and application of a photoaffinity analog of dehydroepiandrosterone (DHEA)

We have synthesized an analog of dehydroepiandrosterone (DHEA, 1) containing both a benzophenone (BP) and a biotin (Bt) group (DHEA–BP–Bt, 8). Compound 8 was prepared by functionalization on C-17 of 1. Biocytin was reacted with 4-benzoylbenzoic acid and the product was condensed with 1 containing a diamine–hexane linker. We detected specific protein bands of approximately 55, 80, and 150 kDa by SDS–PAGE analysis of vascular endothelial cell plasma membranes which had been photoirradiated in the presence of 8.     

Towards translational rodent models of depression

Rodent models of depression have been developed in an effort to identify novel antidepressant compounds and to further our understanding of the pathophysiology of depression. Various rodent models of depression and antidepressant-like behaviour are currently used but, clearly, none of these current models fully recapitulate all features of depression. Moreover, these models have not resulted in the development of novel non-monoaminergic-based antidepressants with clinical efficacy. Thus, a refinement of the current models of depression is required. The present review outlines the most commonly used models of depression and antidepressant drug-like activity and suggests several factors that should be considered when refining these models.