Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Linking genome and proteome by mass spectrometry: Large-scale identification of yeast proteins from two dimensional gels

The function of many of the uncharacterized open reading frames discovered by genomic sequencing can be determined at the level of expressed gene products, the proteome. However, identifying the cognate gene from minute amounts of protein has been one of the major problems in molecular biology. Using yeast as an example, we demonstrate here that mass spectrometric protein identification is a general solution to this problem given a completely sequenced genome. As a first screen, our strategy uses automated laser desorption ionization mass spectrometry of the peptide mixtures produced by in-gel tryptic digestion of a protein. Up to 90% of proteins are identified by searching sequence data bases by lists of peptide masses obtained with high accuracy. The remaining proteins are identified by partially sequencing several peptides of the unseparated mixture by nanoelectrospray tandem mass spectrometry followed by data base searching with multiple peptide sequence tags. In blind trials, the method led to unambiguous identification in all cases. In the largest individual protein identification project to date, a total of 150 gel spots—many of them at subpicomole amounts—were successfully analyzed, greatly enlarging a yeast two-dimensional gel data base. More than 32 proteins were novel and matched to previously uncharacterized open reading frames in the yeast genome. This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.     

Association of the -159 C --> T polymorphism in the CD14 promoter with variations in serum lipoproteins in healthy subjects.

The CD14-159 C --> T polymorphism, a single nucleotide polymorphism (SNP) at position -159 in the promoter region of the gene encoding the pattern recognition receptor CD14, has been associated with elevated plasma concentrations of soluble CD14, lowered serum immunoglobulin E, increased risk for myocardial infarction, and decreased risk for allergy and asthma. In the present study, the CD14-159 C --> T polymorphism has been investigated in order to determine its frequency and association with proinflammatory variables and lipid profile traits of 117 volunteers. The frequency of the CD14 promoter genotype as determined by polymerase chain reaction amplification-restriction fragment length polymorphism analysis was 35.0% (CC), 44.4% (CT), and 20.5% (TT), and the T allele frequency was 42.7%. Compared with the other genotypes, notably CC homozygotes, TT homozygotes were associated with lower total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B-100 (P < 0.01) concentrations in serum. However, no association was found between the investigated SNP and inflammatory mediators such as fibrinogen, interleukin-6, tumor necrosis factor-alpha, tissue factor, C-reactive protein, plasminogen activator inhibitor-1, leukotriene B4, or thromboxane B2. In conclusion, the CD14-159 C --> T polymorphism may be an important genetic trait, related to the ability of CD14 to bind and transport lipids, such as cholesterol.     

Loading deproteinized bovine bone with strontium enhances bone regeneration in rat calvarial critical size defects

Clinical Oral Investigations - To evaluate the effect of grafting with strontium (Sr)-loaded deproteinized bovine bone (DBB) on bone healing in calvarial critical size defects (CSD) in rats. Two...     

Long-Term Exposure to Low-Level Arsenic in Drinking Water and Diabetes Incidence: A Prospective Study of the Diet,Cancer and Health Cohort

Background: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear.Objective: We sought to determine whether long-term exposure to low-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort.Methods: During 1993–1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential addresses of the cohort members and used a geographic information system to link addresses with water-supply areas. We estimated individual exposure to arsenic using all addresses from 1 January 1971 until the censoring date. Cox proportional hazards models were used to model the association between arsenic exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded.Results: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4,304 (8.1%) diabetes cases, and 3,035 (5.8%) cases of diabetes based on the more strict definition. The adjusted incidence rate ratios (IRRs) per 1-μg/L increment in arsenic levels in drinking water were as follows: IRR = 1.03 (95% CI: 1.01, 1.06) and IRR = 1.02 (95% CI: 0.99, 1.05) for all and strict diabetes cases, respectively.Conclusions: Long-term exposure to low-level arsenic in drinking water may contribute to the development of diabetes.Citation: Bräuner EV, Nordsborg RB, Andersen ZJ, Tjønneland A, Loft S, Raaschou-Nielsen O. 2014. Long-term exposure to low-level arsenic in drinking water and diabetes incidence: a prospective study of the Diet, Cancer and Health cohort. Environ Health Perspect 122:1059–1065; http://dx.doi.org/10.1289/ehp.1408198     

Survey of pediatricians in Germany reveals important challenges for possible implementation of meningococcal B vaccination

Incidence of invasive meningococcal disease is low in Germany at 0.5 cases/100,000 inhabitants. Serogroup B (MenB) is most common, causing 70% of cases, with highest incidence in infants (5.9/100,000). In 2013, a MenB vaccine was licensed in Europe. To assess pediatricians’ attitudes towards MenB vaccination and its potential use in Germany we conducted a nationwide cross-sectional survey among 5677 pediatricians. Of 3107 participants (response: 55%), 79.1% would recommend a MenB vaccination to parents, with 66.7% favoring a schedule at 6, 8 and 12 months over 2, 3, 4 and 12 months (13.4%). Administration separately from other vaccines was preferred (63.2%); 38.5% feared that a recommendation would lead to refusal of other recommended vaccinations. In conclusion, pediatricians showed distinct preferences regarding possible integration of MenB vaccination into the existent immunization schedule. As physicians play a crucial role in the implementation, findings will be useful in decision-making regarding potential introduction.