Associations between the K232A polymorphism in the diacylglycerol-O-transferase 1 (DGAT1) gene and performance in Irish Holstein-Friesian dairy cattle

peer-reviewedSelection based on genetic polymorphisms requires accurate quantification of the effect or association of the polymorphisms with all traits of economic importance. The objective of this study was to estimate, using progeny performance data on 848 Holstein-Friesian bulls, the association between a non-conservative alanine to lysine amino acid change (K232A) in exon 8 of the diacylglycerol-O-transferase 1 (DGAT1) gene and milk production and functionality in the Irish Holstein-Friesian population. The DGAT1 gene encodes the diacylglycerol-O-transferase microsomal enzyme necessary to catalyze the final step in triglyceride synthesis. Weighted mixed model methodology, accounting for the additive genetic relationships among animals, was used to evaluate the association between performance and the K232A polymorphism. The minor allele frequency (K allele) was 0.32. One copy of the K allele was associated (P < 0.001) with 77 kg less milk yield, 4.22 kg more fat yield, 0.99 kg less protein yield, and 1.30 and 0.28 g/kg greater milk fat and protein concentration, respectively; all traits were based on predicted 305-day production across the first five lactations. The K232A polymorphism explained 4.8%, 10.3% and 1.0% of the genetic variance in milk yield, fat yield and protein yield, respectively. There was no association between the K232A polymorphism and fertility, functional survival, calving performance, carcass traits, or any conformation trait with the exception of rump width and carcass conformation. Using the current economic values for the milk production traits in the Irish total merit index, one copy of the K allele is worth €5.43 in expected profitability of progeny. Results from this study will be useful in quantifying the cost-benefit of including the K232A polymorphism in the Irish national breeding programme

Solubility of zinc oxide-eugenol and calcium hydroxide cements in simulated dentinal fluid

The solubility of four dental cement bases was measured in simulated dentinal fluid and distilled water to evaluate the relevancy of the American Dental Association solubility test for cement bases in contact with vital dentine. A simulated dentinal fluid was formulated utilizing glucose, distilled water, and sterile human plasma. Cement-base samples were immersed in either distilled water or simulated dentinal fluid at 37°C in a shaker water-bath for 1, 2, or 3 months. Weight loss values were compared utilizing a three-way analysis of variance. Zinc oxide-eugenol cements were significantly more soluble in simulated dentinal fluid than distilled water, while the calcium hydroxide cement bases were significantly more soluble in distilled water than simulated dentinal fluid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73127/1/j.1365-2842.1989.tb01365.x.pd

Cocrystals of spironolactone and griseofulvin based on an in silico screening method

Cocrystal formation is considered as one of the most effective solid-state methods to alter the physicochemical properties of active pharmaceutical ingredients (APIs). In silico methods for cocrystal prediction are mostly based on structural and energetic considerations. We have developed a computational method that ranks the probability of cocrystal formation of APIs with large databases of crystal coformers (CCFs). This approach is based on using molecular electrostatic potential surfaces to assess molecular complementarity between two cocrystal components. The screening tool was applied to two low solubility drugs, namely griseofulvin and spironolactone. Promising coformer candidates were selected from a database of 310 pharmaceutically acceptable CCFs, and experimental screening was carried out. Novel solid forms were obtained by liquid-assisted grinding and were characterised by XRPD, DSC, TGA and IR. One new cocrystal of griseofulvin and two new cocrystals of spironolactone were identified, and the crystal structures were determined from the XRPD patterns. For these systems, phenols tend to act as successful H-bond donors in forming cocrystals, while carboxylic acids only give rise to physical mixtures of the two components

Dark Matter attempts for CoGeNT and DAMA

Recently, the CoGeNT collaboration presented a positive signal for an annual modulation in their data set. In light of the long standing annual modulation signal in DAMA/LIBRA, we analyze the compatibility of both of these signal within the hypothesis of dark matter (DM) scattering on nuclei, taking into account existing experimental constraints. We consider the cases of elastic and inelastic scattering with either spin-dependent or spin-independent coupling to nucleons. We allow for isospin violating interactions as well as for light mediators. We find that there is some tension between the size of the modulation signal and the time-integrated event excess in CoGeNT, making it difficult to explain both simultaneously. Moreover, within the wide range of DM interaction models considered, we do not find a simultaneous explanation of CoGeNT and DAMA/LIBRA compatible with constraints from other experiments. However, in certain cases part of the data can be made consistent. For example, the modulation signal from CoGeNT becomes consistent with the total rate and with limits from other DM searches at 90% CL (but not with the DAMA/LIBRA signal) if DM scattering is inelastic spin-independent with just the right couplings to protons and neutrons to reduce the scattering rate on xenon. Conversely the DAMA/LIBRA signal (but not CoGeNT) can be explained by spin-dependent inelastic DM scattering.Comment: 20 pages, 9 figure

Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis

Background & Aims: Parenteral methotrexate induces clinical remission but not endoscopic improvement of mucosal inflammation in patients with ulcerative colitis (UC). We performed a randomized, placebo-controlled trial to assess the efficacy of parenteral methotrexate in maintaining steroid-free response or remission in patients with UC after induction therapy with methotrexate and steroids. Methods: We performed a 48-week trial, from February 2012 through May 2016, of 179 patients with active UC (Mayo score of 6–12 with endoscopy subscore ≥ 2) despite previous conventional or biological therapy. The study comprised a 16-week open label methotrexate induction period followed by a 32-week double-blind, placebo-controlled maintenance period. Patients were given subcutaneous methotrexate (25 mg/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, n = 44) or were given placebo (n = 40) until week 48. We compared the efficacy of treatment by analyzing the proportion of patients who remained relapse free and were in remission at week 48 without use of steroids or other medications to control disease activity. Results: Ninety-one patients (51%) achieved response at week 16, and 84 patients were included in the maintenance period study. During this period, 60% of patients in the placebo group (24/40) and 66% in the methotrexate group (29/44) had a relapse of UC (P =.75). At week 48, 30% of patients in the placebo group (12/40) and 27% of patients in the methotrexate group (12/44) were in steroid-free clinical remission without need for additional therapies (P =.86). No new safety signals for methotrexate were detected. Conclusions: Parenteral methotrexate (25 mg/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405

Thermocycling as a means of inducing mechanical fatigue in dental composites

The effect of thermocycling on the fatigue behaviour of 5 commercially available dental composites; P50(P)1, Silux Plus(S)2, Heliomolar(H)3, Clearfil Photo Posterior-light activated(CLA)4 and Clearfil Posterior-chemically activated(CC)5 was investigated. One hundred and ten rectangular bar specimens were prepared for each materil and divided into 11 groups of 10 each. Test groups 1-6 were subjected to 0, 250, 500, 750, 1000 and 1000 thermal cycles respectively. Each thermal cycle consisted of 1 minute immersion time of 50 seconds per change. The control groups 7-11 were stored in distilled water at 370c for the equivalent time to complete 250, 500, 750, 1000 and 10000 thermal cycles respectively. All specimens were subjected to a 3 point bend test and loaded at a crosshead speed of 1mm/min on a an Inston Testing Machine. The flexural strength of all materials decreases with the number of cycles and length of water storage except for CC where the flexural strength increases during the earlier stages of thermocycling and water storage. The lowest flexural strength was observed in groups 6 and 11. One way analysis of varience showed that Group 1 was significantly different from groups 6 and 11 (P<.05), however the thermally cycled and water storage groups were not different from each other for all materials tested. The decrease in flexural strength of all materials in the water storage groups (7-11) when compared to the 24 hour group (1) is related to weakening of resin-filler interface bu hydrolysis. While the decrease of the thermally cycled groups can be attributed to debongding of matrix-filler due to variation in coefficient of thermal expansion. It can be concluded that thermal changes does not reduce the flerxural strength of composites

Ex vivo bond strength of adhesive precoated metallic and ceramic brackets.

Compared with conventional adhesive systems, adhesive precoated (APC) brackets are reported to have advantages in clinical use. The ex vivo bond strength to human premolar teeth of metallic and ceramic APC brackets was compared wi1h that of identical brackets bonded with Transbond® (3M Unitek) light cured orthodontic adhesive, and patterns of failure were examined. There was no significant difference (P&gt;0·05) in mean bond strength between metallic brackets bonded with the two systems. Ceramic brackets bonded with Transbond® had significantly higher (P&lt;0·05) mean bond strength and failure more normally occurred at the composite/enamel interface when compared with APC ceramic brackets and metallic brackets. Following debonding no enamel damage was observed with either APC or conventionally bonded ceramic brackets. </jats:p