Multivariate meta-analysis of QTL mapping studies

A large number of quantitative trait loci (QTLs) for milk production and quality traits in dairy cattle has been reported in literature. The large amount of information available could be exploited by meta-analyses to draw more general conclusions from results obtained in different experimental conditions (animals, statistical methodologies). QTL meta-analyses have been carried out to estimate the distribution of QTL effects in livestock and to find consensus on QTL position. In this study, multivariate dimension reduction techniques are used to analyse a database of dairy cattle QTL published results, in order to extract latent variables able to characterise the research. A total of 92 papers by 72 authors were found on 25 scientific Journals for the period January 1995-February 2008. More than thirty parameters were picked up from the articles. To overcome the problem of different map location, the flanking markers were mapped on release 4.1 of the Bos taurus genome sequence (www.ensembl. org). Their position was retrieved from public databases and, when absent, was calculated in silico by blasting (http://blast.wustl.edu/) the markers’ nucleotide sequence against the genomic sequence. Records were discarded if flanking markers or P-values were not available. After these edits, the final archive consisted of 1,162 records. Seven selected variables were analysed both with the Factor Analysis (FA), combined with the varimax rotation technique, and Principal Component Analysis (PCA). FA was able to explain 68% of the original variability with 3 latent factors: the first factor extracted was highly associated (factor loading of 0.98) to marker location along the chromosome and could be considered as a marker map index; the second factor showed factor loadings of 0.74 and 0.84 related to the variable number of animals involved and year of the experiment, respectively, and it can be regarded as an indicator of the dimension of the study; the third factor was correlated to the significance level of the statistical test (0.78), number of families (0.63), and, negatively, to the marker density (-0.43). It can be named as index of power of the experiment. Same patterns can be observed in the eigenvectors of PCA. Four PCs were able to explain about 80% of the original variance. The first two PCs basically underlined accurately the same structure found with the first two factors in FA, whereas PC3 and PC4 summarized the structure of F3. The score that each QTL gets on each Factor or PC could be useful to classify the original QTL records and make them more comparable once that the redundancy of information has been removed

p38 regulates expression of osteoblast-specific genes by phosphorylation of osterix

Osterix, a zinc finger transcription factor, is specifically expressed in osteoblasts and osteocytes of all developing bones. Because no bone formation occurs in Osx-null mice, Osterix is thought to be an essential regulator of osteoblast differentiation. We report that, in several mesenchymal and osteoblastic cell types, BMP-2 induces an increase in expression of the two isoforms of Osterix arising from two alternative promoters. We identified a consensus Sp1 sequence (GGGCGG) as Osterix binding regions in the fibromodulin and the bone sialoprotein promoters in vitro and in vivo. Furthermore, we show that Osterix is a novel substrate for p38 MAPK in vitro and in vivo and that Ser-73 and Ser-77 are the regulatory sites phosphorylated by p38. Our data also demonstrate that Osterix is able to increase recruitment of p300 and Brg1 to the promoters of its target genes fibromodulin and bone sialoprotein in vivo and that it directly associates with these cofactors through protein-protein interactions. Phosphorylation of Osterix at Ser-73/77 increased its ability to recruit p300 and SWI/SNF to either fibromodulin or bone sialoprotein promoters. We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial

In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses

Objective: The aim of this study was to identify the risk factors associated with fragility fracture (FF) development in glucocorticoid (GC)-treated patients. Methods: 127 patients (aged 62±18 years, 63% women) on GC-treatment (mean dose 14.5±14.1 mg/day and duration 47.7±69 months) were included. The clinical data collected included bone metabolism study (including gonadal axis), GC-treatment, disease activity, dual-energy X-ray absorptiometry analysis (evaluating densitometric osteoporosis (OP) and trabecular bone score (TBS) degraded microarchitecture values (DMA)), X-ray (assessing vertebral fractures (VF)), FRAX risk (GC-adjusted) and previous FF. Results: 17% of the patients had VF, 28% FF (VF and/or non-VF), 29% OP and 52% DMA. Patients with VF received more GC boluses (57.1% vs 29.5%, p=0.03), were older (68±13 vs 60±19 years, p=0.02), postmenopausal (100% vs 67%, p=0.02), had low testosterone levels (57% vs 11%, p=0.02), lower TBS values (1.119±0.03 vs 1.237±0.013, p100, p=0.01) and having received GC boluses (OR 3.45; 95% CI 1.04 to 12.15, p=0.01) were the main factors related to VF. Hypogonadism (OR 7.03; 95% CI 1.47 to 38.37, p=0.01) and FRAX >20 (OR 7.08; 95% CI 1.28 to 53.71, p=0.02) were factors related to FF. Conclusion: Hypogonadism is the principal risk factor for developing fractures in GC-treated men and women, whereas receiving GC boluses is a major factor for VF. These results indicate the importance of evaluating the gonadal axis in these patients

Recent developments in oxidative esterification and amidation of aldehydes

Esters and amides, which are functional groups of fundamental importance in organic chemistry are traditionally prepared by reacting carboxylic acid derivatives (carboxylic halides, anhydrides and activated esters) with alcohols and amines, often implying multistep processes. Recently the oxidative esterification and amidation of aldehydes have been raised as sustainable and efficient alternatives to classical synthesis. This digest reports more recent advances in this emergent field