Silicon: A neglected micronutrient essential for bone health

Bone matrix is predominantly made up of collagen, and in vitro and in animal models studies have shown that silicon is linked to glycosaminoglycans and plays an important role in the formation of cross-links between collagen and proteoglycans, determining the beneficial effects on strength, composition, and mechanical properties of bone. However, there are still no precise indications regarding a possible role of silicon on bone health in humans. Given this background, the aim of this narrative review was to consider the effectiveness of silicon dietary intake and silicon dietary supplementation (alone or with other micronutrients), in order to suggest a daily dosage of Si supplementation, on bone mineral density in humans. This review included eight eligible studies: four regarding dietary intake and four considering supplementation with silicon alone or with other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (10012) and the results are interesting. Although to date the available scientific evidences are not considered valid enough to allow to establish an adequate level of Silicon intake, based on extrapolations from the data obtained with studies on animal and human models, it has been suggested that an adequate intake in order to promote beneficial effects for bone could be considered to be around 25 mg silicon/day. As for silicon dietary supplements, it has been shown that the combined treatment with orthosilicic acid (6 mg), calcium, and vitamin D has a potentially beneficial effect on femoral BMD compared to only use of calcium and vitamin D.     

Oxime-based inhibitors of glucose transporter 1 displaying antiproliferative effects in cancer cells

An analysis of the main pharmacophoric features present in the still limited number of inhibitors of glucose transporter GLUT1 led to the identification of new oxime-based inhibitors, which proved to be able to efficiently hinder glucose uptake and cell growth in H1299 lung cancer cells. The most important interactions of a representative inhibitor were indicated by a novel computational model of GLUT1, which was purposely developed to explain these results and to provide useful indications for the design and the development of new and more efficient GLUT1 inhibitors.     

Implicit associative learning engages the hippocampus and interacts with explicit associative learning

The hippocampus is crucial for conscious, explicit memory, but whether it is also involved in nonconscious, implicit memory is uncertain. We investigated with functional magnetic resonance imaging whether implicit learning engages the hippocampus and interacts with subsequent explicit learning. The presentation of subliminal faces-written profession pairs for implicit learning was followed by the explicit learning of supraliminal pairs composed of the same faces combined with written professions semantically incongruous to those presented subliminally (experiment 1), semantically congruous professions (experiment 2), or identical professions (experiment 3). We found that implicit face-profession learning interacted with explicit face-profession learning in all experiments, impairing the explicit retrieval of the associations. Hippocampal activity increased during the subliminal presentation of face-profession pairs versus face-nonword pairs and correlated with the later impairment of explicit retrieval. These findings suggest that implicit semantic associative learning engages the hippocampus and influences explicit memory.     

Increased postcopulatory sexual selection reduces the intramale variation in sperm design

Sperm competition is an important force driving the evolution of sperm design and function. Inter- and intraspecific variation in sperm design are strongly influenced by the risk of sperm competition in many taxa. In contrast, the variation among sperm of one male (intramale variation) is less well understood. We investigated intramale variation in sperm design in passerine birds and found that risk of sperm competition is negatively associated with intramale variation. This result is the first clear evidence that variation among sperm within an individual male is influenced by postcopulatory sexual selection. Our finding has important implications for male traits under pre- and postcopulatory sexual selection.     

On Hill et al's conjecture for calculating the subtree prune and regraft distance between phylogenies

Background  

Recently, Hill et al. [1] implemented a new software package--called SPRIT--which aims at calculating the minimum number of horizontal gene transfer events that is needed to simultaneously explain the evolution of two rooted binary phylogenetic trees on the same set of taxa. To this end, SPRIT computes the closely related so-called rooted subtree prune and regraft distance between two phylogenies. However, calculating this distance is an NP-hard problem and exact algorithms are often only applicable to small- or medium-sized problem instances. Trying to overcome this problem, Hill et al. propose a divide-and-conquer approach to speed up their algorithm and conjecture that this approach can be used to compute the rooted subtree prune and regraft distance exactly.     

Microsomal epoxide hydrolase expression in the endometrial uterine corpus is regulated by progesterone during the menstrual cycle

We have shown previously that high expression levels of microsomal epoxide hydrolase (mEH) correlate with a poor prognosis of breast cancer patients receiving tamoxifen, suggesting that enhanced mEH expression could lead to antiestrogen resistance (Fritz et al. in J Clin Oncol 19:3–9, 2001). Thus, the purpose of this study was to gain insights into the role of mEH in hormone-responsive tissues. We analyzed biopsy samples of the endometrium by immunohistochemical staining, pointing to a regulation of mEH during the menstrual cycle: during the first half mEH expression was low, increased during the second half and reached highest levels during pregnancy. Additionally, the progesterone receptor (PR) positive human endometrial cell lines IKPRAB-36 (estrogene receptor α [ERα] negative) and ECC1-PRAB72 (ERα positive) were chosen to further investigate the hormonal regulation of mEH expression. Western Blot and quantitative RT-PCR analysis revealed an increase of mEH expression after treatment with medroxy-progesterone 17-acetate (MPA) in the ERα containing ECC1-PRAB72 cells. In contrast our results suggest that MPA had no influence on the mEH protein level in the ERα- IKPRAB-36 cells. In conclusion, mEH expression is regulated by progesterone in the presence of both PRs and ERα.     

DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells

Within 2–3 months of in vitro culture-expansion, mesenchymal stromal cells (MSC) undergo replicative senescence characterized by cell enlargement, loss of differentiation potential and ultimate growth arrest. In this study, we have analyzed DNA methylation changes upon long-term culture of MSC by using the HumanMethylation27 BeadChip microarray assessing 27 578 unique CpG sites. Furthermore, we have compared MSC from young and elderly donors. Overall, methylation patterns were maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites. Many of these differences were observed in homeobox genes and genes involved in cell differentiation. Methylation changes were verified by pyrosequencing after bisulfite conversion and compared to gene expression data. Notably, methylation changes in MSC were overlapping in long-term culture and aging in vivo . This supports the notion that replicative senescence and aging represent developmental processes that are regulated by specific epigenetic modifications.     

The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants

Background

The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences.

Methodology/Principal Findings

Genomic DNA from 2700 Caucasians including 812 patients with Crohn''s disease (CD), 442 patients with ulcerative colitis (UC), and 1446 healthy controls was analyzed for the NOD2 SNPs rs2066843 and rs2076756 and the three main CD-associated NOD2 variants p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847). Haplotype and genotype-phenotype analyses were performed. The SNPs rs2066843 (p = 3.01×10⁻⁵, OR 1.48, [95% CI 1.23-1.78]) and rs2076756 (p = 4.01×10⁻⁶; OR 1.54, [95% CI 1.28-1.86]) were significantly associated with CD but not with UC susceptibility. Haplotype analysis revealed a number of significant associations with CD susceptibility with omnibus p values <10⁻¹⁰. The SNPs rs2066843 and rs2076756 were in linkage disequilibrium with each other and with the three main CD-associated NOD2 mutations (D''>0.9). However, in CD, SNPs rs2066843 and rs2076756 were more frequently observed than the other three common NOD2 mutations (minor allele frequencies for rs2066843 and rs2076756: 0.390 and 0.380, respectively). In CD patients homozygous for these novel NOD2 variants, genotype-phenotype analysis revealed higher rates of a penetrating phenotype (rs2076756: p = 0.015) and fistulas (rs2076756: p = 0.015) and significant associations with CD-related surgery (rs2076756: p = 0.003; rs2066843: p = 0.015). However, in multivariate analysis only disease localization (p<2×10⁻¹⁶) and behaviour (p = 0.02) were significantly associated with the need for surgery.

Conclusion/Significance

The NOD2 variants rs2066843 and rs2076756 are novel and common CD susceptibility gene variants.