The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.     

The effect of prostaglandin F(2α) administration at the time of insemination on the pregnancy rate of dairy cows

This paper addresses the question whether the pregnancy rate of dairy cows and heifers may be affected by administering prostaglandin F_2α at the time of artificial insemination. A field trial involving 1031 dairy cows and heifers distributed to a large number of small dairy farms in an area of extensive farming in central Germany provided evidence that intramuscular administration of 25 mg Dinoprost (Dinolytic^®) at the time of insemination has no effect on pregnancy rate (61% of the cows and heifers were pregnant in both prostaglandin F_2α-treated and saline control groups). On the other hand, deposition of 0.5 mL of a 0.5 mg/mL Dinoprost solution in the uterine lumen immediately after artificial insemination gave rise to a pregnancy rate of 66% as compared with 59% in saline controls. The increase in pregnancy rate of 229 prostaglandin F_2α-treated animals (66% pregnant) over that of 226 saline controls (59% pregnant) amounted to 12%. This improvement was not statistically significant (P = 0.12). Factors exerting a significant effect on pregnancy rate were parity (74% pregnancies in heifers versus 57% in cows, P < 0.01 and 65% pregnancies in first parity-cows versus 55% in older cows, P < 0.01) and season (57% during the barn season versus 64% during the pasture season, P < 0.05), whereas length of service period, level of milk production and serum or milk progesterone level at the time of insemination did not. A follow-up trial involving more animals will have to be conducted aimed at confirming the promising results obtained by intrauterine PGF_2α administration.     

Secreted HHIP1 interacts with heparan sulfate and regulates Hedgehog ligand localization and function

Vertebrate Hedgehog (HH) signaling is controlled by several ligand-binding antagonists including Patched-1 (PTCH1), PTCH2, and HH-interacting protein 1 (HHIP1), whose collective action is essential for proper HH pathway activity. However, the molecular mechanisms used by these inhibitors remain poorly understood. In this paper, we investigated the mechanisms underlying HHIP1 antagonism of HH signaling. Strikingly, we found evidence that HHIP1 non–cell-autonomously inhibits HH-dependent neural progenitor patterning and proliferation. Furthermore, this non–cell-autonomous antagonism of HH signaling results from the secretion of HHIP1 that is modulated by cell type–specific interactions with heparan sulfate (HS). These interactions are mediated by an HS-binding motif in the cysteine-rich domain of HHIP1 that is required for its localization to the neuroepithelial basement membrane (BM) to effectively antagonize HH pathway function. Our data also suggest that endogenous, secreted HHIP1 localization to HS-containing BMs regulates HH ligand distribution. Overall, the secreted activity of HHIP1 represents a novel mechanism to regulate HH ligand localization and function during embryogenesis.     

Influence of nutritional substrates on the development of Diaphania hyalinata L. (Lepidoptera: Crambidae)

The aim of this research was to evaluate the biological behaviour of melonworm at different natural and artificial diets. Squash cultivar jacaré, cucumber, summer squash and an artificial diets developed by Hensley & Hammond for the sugarcane borer were tried. The research was carried out in the Laboratório de Entomologia do Centro de Ciências Agrárias of the Universidade Federal do Espírito Santo, in climatized room at 25 +/- 1 masculineC, relative humidity of 70 +/- 10% and 14h photofase. The caterpillars fed on each substrate during the whole life cycle. Differences in duration of the larval period, larvae and pupae survival, adult longevity and number of eggs were registered between the substrates. The results show that the best diet for rearing is the artificial one. Between the natural diets the cucumber showed the best results.     

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians

Background  

A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3 ) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India.     

Induction of the oxLDL receptor LOX-1 by endothelin-1 in human endothelial cells.

In this study, we analyzed the effect of endothelin-1 (ET-1) on expression of the lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 LOX-1 and on oxLDL uptake in primary cultures of human umbilical vein endothelial cells (HUVEC). LOX-1 mRNA was quantified by standard-calibrated competitive RT-PCR, LOX-1 protein expression by Western analysis and endothelial oxLDL uptake using DiI-labeled oxLDL. ET-1 induces LOX-1 mRNA expression, reaching its maximum after 1 h (160 +/- 14% of control, 100 nM ET-1, P < 0.05). This increased ET-1-mediated LOX-1 mRNA expression could be inhibited by endothelin receptor B antagonist BQ-788. In addition, ET-1 stimulates LOX-1 protein expression and oxLDL uptake in HUVEC. The augmented oxLDL uptake by ET-1 is mediated by endothelin receptor B, but not by protein kinases. These data support a new pathophysiological mechanism how locally and systemically increased ET-1 levels could promote LOX-1-mediated oxLDL uptake in human endothelial cells and the development and progression of endothelial dysfunction and atherosclerosis.     

Effect of insemination of estrus-induced prepuberal gilts on ensuing reproductive performance and body weight

Prepuberal gilts reared and managed to 85-90 kg live weight in a common system were allocated at random to one of three first-mating treatments in an experiment conducted over a period of more than 5 years. In two of the treatments, gilts received a single i.m. injection of 400 IU equine chorionic gonadotropin (eCG) and 200 IU human chorionic gonadotropin (hCG) (PG600; Intervet) and were either inseminated 4 and 5 days later on a fixed-time basis regardless of oestrus (treatment A), or at the second oestrus following treatment (treatment B). The third group of gilts remained untreated and was inseminated on the first spontaneous oestrus (treatment C). Thereafter, all gilts were managed in the same way and those observed in oestrus were re-inseminated. Significantly more gilts returned to oestrus after the first service in treatment A (35%) than in treatment B and C (12 and 17%, respectively; P<0.01). Gilts farrowed to the first or repeat inseminations at a significantly younger age (P<0.01) in treatment A (304 days) than treatment B (324 days) and C (320 days). The age difference at farrowing remained in surviving gilts at the end of their third parity. The first farrowing performance of the gilts was significantly affected by treatment in terms of litter size at birth (A 7.0, B 8.4 and C 8.3 live piglets per gilt; P<0.01), litter size at weaning (A 6.2, B 7.2 and C 7.2 live piglets per gilt, P<0.05), and piglet birth weight (A 1.4, B 1.3 and C 1.3 kg; P<0.05) but piglet survival rate and weaning weight were not affected by treatment. The live weights of the gilts were significantly different between the treatments at first insemination (A 95.7, B 106.5 and C 109.2 kg; P<0.01) but not when the first litter was weaned (A 133.6, B 135.1 and C 136.6; P>0.05). After the first farrowing there were no differences between the treatments in terms of the survival rate, productive or reproductive performance of the gilts/sows and their offspring. Without conducting a detailed cost-benefit-calculation it was deduced that, from an economical point of view, differences between treatment A and treatments B and C are negligible because the savings associated with farrowing at a younger age on this treatment just about compensated for any additional costs associated with the treatment and the lower number of piglets born at the first farrowing.     

UV resonance Raman study of angiotensin II conformation in nonaqueous environments: lipid micelles and acetonitrile

We used 206.5-nm excited resonance Raman measurements to examine the angiotensin II (AII) secondary structure in H(2)O in the presence of dodecylphosphocholine (DPC) micelles, sodium dodecylsulfate (SDS) monomers and micelles, and in a 70% acetonitrile (ACN-d)-30% water solution. Our AII-SDS titration absorption studies indicate the formation of a 1:2 AII:SDS complex in which two negatively charged SDS molecules attach to the AII positively charged N terminus and to Arg(2). Our 206.5-nm excited Raman results indicate that the 1:2 AII:SDS complexation increases the AII beta-turn composition. We also used 228.9-nm Raman excitation to probe the local solvent accessibility of Tyr(4) (AII) in DPC and SDS micelles. Our Tyr (AII) solvent accessibility studies suggest that the Tyr residue is more exposed to the aqueous environment in SDS micelles than in DPC micelles.