2,3,7,8-tetrachlorodibenzo-p-dioxin induces lecithin: retinol acyltransferase transcription in the rat kidney

Vitamin A (retinoids) has an essential role in development and throughout life of humans and animals. Consequently, effects of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on retinoid metabolism may be contributory to its toxicity. This study was performed to clarify the mechanism behind dioxin-induced retinyl ester formation in the rat kidney. In addition we investigated the possible role of CYP1A1 in dioxin-induced all-trans-retinoic acid (atRA) formation. Male Sprague-Dawley rats were exposed to a single oral dose of TCDD in a combined dose-response and time-course study, with doses ranging from 0.1 to 100 microg/kg bw and time points from 1 to 28 days. Levels of atRA and the expression of two potentially retinoic acid (RA)-controlled proteins critically involved in retinoid storage regulation, lecithin: retinol acyltransferase (LRAT) and cellular retinol binding protein I (CRBP I), were analyzed in liver and kidney. The expression and activity of cytochrome P4501A1 (assayed as ethoxyresorufin-O-deethylase activity) was assessed to gain insight into its potential role in RA synthesis. There was a significant increase in LRAT mRNA expression in the kidney, whereas no such increase could be observed in the liver, despite significantly increased atRA levels in both tissues. This suggests a tissue-specific regulation of LRAT by TCDD that may be dependent on other factors than atRA. Neither CRBP I mRNA nor protein levels were altered by TCDD. The time-course relationship between CYP1A1 activity and atRA levels in liver and kidney does not exclude a role of CYP1A1 in TCDD-induced RA synthesis. The observed altered regulation of the retinoid-metabolizing enzyme LRAT, together with the low doses and short time required by TCDD to change tissue RA levels, suggest that enzymes involved in retinoid metabolism are specific and/or direct targets of TCDD.     

The ULTRAPETALA gene controls shoot and floral meristem size in Arabidopsis

The regulation of proper shoot and floral meristem size during plant development is mediated by a complex interaction of stem cell promoting and restricting factors. The phenotypic effects of mutations in the ULTRAPETALA gene, which is required to control shoot and floral meristem cell accumulation in Arabidopsis thaliana, are described. ultrapetala flowers contain more floral organs and whorls than wild-type plants, phenotypes that correlate with an increase in floral meristem size preceding organ initiation. ultrapetala plants also produce more floral meristems than wild-type plants, correlating with an increase in inflorescence meristem size without visible fasciation. Expression analysis indicates that ULTRAPETALA controls meristem cell accumulation partly by limiting the domain of CLAVATA1 expression. Genetic studies show that ULTRAPETALA acts independently of ERA1, but has overlapping functions with PERIANTHIA and the CLAVATA signal transduction pathway in controlling shoot and floral meristem size and meristem determinacy. Thus ULTRAPETALA defines a novel locus that restricts meristem cell accumulation in Arabidopsis shoot and floral meristems.     

Gene targeting in primary fetal fibroblasts from sheep and pig

Nuclear transfer offers a new cell-based route for introducing precise genetic modifications in a range of animal species. However, significant challenges, such as establishment of somatic gene targeting techniques, must be overcome before the technology can be applied routinely. In this report, we describe targeted deletion at the GGTA1 (alpha 1,3-galactosyl transferase) and PrP (prion protein) loci in primary fibroblasts from livestock. We place particular emphasis on the growth characteristics of the primary cell cultures, since these are key to determining success.     

How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2)

Background

The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications.

Methods

After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide.

Results

Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients.

Conclusion

Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide.     

Gestational length in the koala, Phascolarctos cinereus

We report a possible case of extended gestation in the koala, Phascolarctos cinereus. Birth of a pouch young was first observed 127 days after the removal of the male from a multi-female colony at Taronga Zoo. No other males were present at that time or had access to the facility. Head measurements and other growth data collected at the time of detection and over the period of pouch life indicates the time from removal of the male and the date of birth to be between 50 and 77 days. DNA fingerprinting using microsatellite loci unambiguously assigned paternity of the pouch young to this male.

These observations suggest either an extended period of gestation of at least 50 days, or activation of a dormant blastocyst from the previous breeding season, as the female entered the period of seasonal oestrus.     

The effects of altitude,aspect, grazing and time on the proportion of cyanogenics in neighbouring populations of Trifolium repens L. (white clover)

The proportion of cyanogenic individuals of white clover amongst 200 individuals in each of 32 neighbouring populations in Northumberland, UK were recorded. Sites differed for four altitude zones, two aspects, and were either sheep pasture or ungrazed meadow. The proportion of cyanogenics showed a striking reduction with increasing altitude. Below 100 m, north-facing sites contained more cyanogenics than south-facing sites, but aspect did not affect higher sites. Grassland management had no effect on the proportion of cyanogenics. A 24-year study of one population showed highly significant changes in the proportion of cyanogenics over time, suggesting that a significant turnover of individuals occurs. In some cases, different size class cohorts varied for the proportion of cyanogenics within a year, and the same cohort varied between years. We conclude that environment at birth may determine the proportion of cyanogenics for that cohort, so that this proportion persists in that cohort as it matures. Comparisons of the proportion of cyanogenics with mean monthly averages for January minimum temperature, July maximum temperature and August rainfall showed a significant association only with mean January minima 2 1/2 years previously. We hypothesise that the 2 to 3-year cohort may predominate in this population. We suggest that winter cold and summer drought may both select against cyanogenics. Grazing by large herbivores does not favour cyanogenesis, but some invertebrate herbivory may do so. Most selection probably occurs at birth and will be greatest in populations with a high turnover.