Osteocalcin and matrix GLA protein in developing teleost teeth: identification of sites of mRNA and protein accumulation at single cell resolution

In this study, the tissue distribution and accumulation of osteocalcin or bone Gla protein (BGP) and matrix Gla protein (MGP) were determined during tooth development in a teleost fish, Argyrosomus regius. In this species, the presence of BGP and MGP mRNA in teeth was revealed by in situ hybridization. mRNA for BGP was detected in the odontoblasts as well as in its cytoplasmic processes emerging through dentinal tubules, while mRNA for MGP was expressed in the enamel portion within the apical portion of the elongated cell bodies of enameloblasts, adjacent to the root of the teeth as well as in cells within the pulpal space. Immunolocalization of BGP and MGP demonstrated that these proteins accumulate mainly in the mineralized dentin or in enameloblastic processes, confirming in situ hybridization results. In this study, we examined for the first time the localization of both BGP and MGP gene expression and protein accumulation within the different regions of the vertebrate tooth. We clearly demonstrated that although the overall pattern of BGP and MGP gene expression and protein accumulation in A. regius teeth was in general agreement to what is known for other vertebrates such as rats or rodents, our study provided novel information and highlighted some species-differences between fish and higher vertebrates.     

Microcalcifications in breast cancer: From pathophysiology to diagnosis and prognosis

The implementation of mammographic screening programmes in many countries has been linked to a marked increase in early detection and improved prognosis for breast cancer patients. Breast tumours can be detected by assessing several features in mammographic images but one of the most common are the presence of small deposits of calcium known as microcalcifications, which in many cases may be the only detectable sign of a breast tumour. In addition to their efficacy in the detection of breast cancer, the presence of microcalcifications within a breast tumour may also convey useful prognostic information. Breast tumours with associated calcifications display an increased rate of HER2 overexpression as well as decreased survival, increased risk of recurrence, high tumour grade and increased likelihood of spread to the lymph nodes. Clearly, the presence of microcalcifications in a tumour is a clinically significant finding, suggesting that a detailed understanding of their formation may improve our knowledge of the early stages of breast tumourigenesis, yet there are no reports which attempt to bring together recent basic science research findings and current knowledge of the clinical significance of microcalcifications. This review will summarise the most current understanding of the formation of calcifications within breast tissue and explore their associated clinical features and prognostic value.     

New microbial mannan catabolic pathway that involves a novel mannosylglucose phosphorylase

The consecutive genes BF0771–BF0774 in the genome of Bacteroidesfragilis NCTC 9343 were found to constitute an operon. The functional analysis of BF0772 showed that the gene encoded a novel enzyme, mannosylglucose phosphorylase that catalyzes the reaction, 4-O-β-d-mannopyranosyl-d-glucose + Pi → mannose-1-phosphate + glucose. Here we propose a new mannan catabolic pathway in the anaerobe, which involves 1,4-β-mannanase (BF0771), a mannobiose and/or sugar transporter (BF0773), mannobiose 2-epimerase (BF0774), and mannosylglucose phosphorylase (BF0772), finally progressing to glycolysis. This pathway is distributed in microbes such as Bacteroides, Parabacteroides, Flavobacterium, and Cellvibrio.     

Predicting Sediment Toxicity at Former Manufactured Gas Plants Using Equilibrium Partitioning Benchmarks for PAH Mixtures

This study was conducted to examine the application of Equilibrium Partitioning Sediment Benchmarks (ESBs) for assessing the toxicity of polycyclic aromatic hydrocarbons (PAHs) in sediments at former manufactured gas plant (MGP) and coke sites. Samples of freshwater sediment from four MGP and coke sites in the U.S. Northeast and Midwest were analyzed for 34 individual PAHs, total organic carbon, “black” carbon (potentially composed of pitch, soot, and other forms of pyrogenic carbon), and sediment toxicity (28-day Hyalella azteca toxicity test). The sum of the Toxic Units in each sample was calculated from a one-phase model that accounts for sorption of PAHs to total sediment organic carbon, and a two-phase model that accounts for sorption to black carbon as well as to natural organic carbon. Although both the one-phase and two-phase models accurately predicted concentrations of PAHs that were not toxic to aquatic invertebrates, the two-phase model was more often in agreement with results of sediment toxicity tests. While the bioavailability and toxicity of PAHs may vary at other sites, the two-phase model correctly predicted that sediments from these sites with concentrations of total PAHs as high as 52 mg/kg were not toxic to invertebrates.     

文蛤糖肽MGP0501的分离纯化及性质鉴定

文蛤粗提液经超滤、层析等纯化得到分子量为15.878×103、纯度为96.42%、糖和蛋白质含量各占约55.18%和44.82%的糖肽MGP0501。MTT法和流式细胞术检测证实MGP0501对A549细胞具有体外抗肿瘤活性,对小鼠移植瘤S180的体内抗肿瘤实验检测亦证实其对小鼠移植瘤S180具有体内抑制作用,表明MGP0501是一种具有抗肿瘤作用的糖肽。     

Characterization of PAH Sources in Sediments of the Thea Foss/Wheeler Osgood Waterways,Tacoma, Washington

The character of polycyclic aromatic hydrocarbons (PAH) in sediments of the Thea Foss and Wheeler-Osgood Waterways in Tacoma, Washington, were investigated with the objective of determining the general source(s) of these compounds to the waterways. In this study, 42 near-surface sediment samples from the Waterways were collected and analyzed for their (1) concentration of 43 individual or groups of PAH, (2) total extractable hydrocarbon “fingerprint” and concentration, (3) grain size and (4) total organic carbon content. Analysis of the sediment data, including comparisons to standard reference materials, indicates that all but two samples contained PAH derived from a pyrogenic source(s), i.e., a non-petroleum source(s). The high concentrations and characteristic distributions of PAH in some sediment samples were consistent with the occurrence of manufactured gas plant (MGP) derived tar(s) or tar distillate(s), particularly in some sediments proximal to a historic MGP and tar distillate storage operation near the head of the Thea Foss Waterway. Most other sediment samples throughout the Waterways contained PAH distributions and concentration indicating (at least) a greater proportion of PAH are derived from urban runoff/fallout.     

A polymorphism of matrix Gla protein gene is associated with kidney stone in the Chinese Han population

Purpose

Matrix Gla protein (MGP) is a molecular determinant regulating the extracellular matrix calcification. To further confirm whether the MGP genetic polymorphism was universally associated with the risk of kidney stone, we investigated the association of genetic polymorphisms of MGP with kidney stone in the Chinese Han population.

Materials and methods

728 subjects were recruited for the study. We firstly re-sequenced the human genomic MGP gene including the 1500 bp promoter, 5′-UTR, 4 exons and 3′-untranslated regions, identified single nucleotide polymorphisms (SNPs) in MGP, and performed an association analysis with kidney stones in 54 subjects of the Chinese Han population. A candidate tag SNP was genotyped in total subjects using an allele specific PCR, and further analyzed the association with kidney stone.

Results

We identified 18 polymorphisms including four tag SNPs. A tag SNPrs4236 was associated with kidney stones. The G allele carrier had a 1.373-fold reduced kidney stone risk compared with A allele carriers in SNPrs4236 (odds ratios (OR) = 1.373; 95%CI, 1.051–1.793; p = 0.019). However, we did not find an association between the polymorphism and clinical characteristics of kidney stones.

Conclusions

Our findings showed that SNPrs4236 of the MGP gene is associated with kidney stones in the Chinese Han population, and influences the genetic susceptibility to kidney stones. In the future, functional assays of the polymorphism should permit a better understanding of the role of MGP genetic variants and kidney stones.     

Heterotrimeric G Proteins and the Single-Transmembrane Domain IGF-II/M6P Receptor: Functional Interaction and Relevance to Cell Signaling

The G protein-coupled receptor (GPCR) family represents the largest and most versatile group of cell surface receptors. Classical GPCR signaling constitutes ligand binding to a seven-transmembrane domain receptor, receptor interaction with a heterotrimeric G protein, and the subsequent activation or inhibition of downstream intracellular effectors to mediate a cellular response. However, recent reports on direct, receptor-independent G protein activation, G protein-independent signaling by GPCRs, and signaling of nonheptahelical receptors via trimeric G proteins have highlighted the intrinsic complexities of G protein signaling mechanisms. The insulin-like growth factor-II/mannose-6 phosphate (IGF-II/M6P) receptor is a single-transmembrane glycoprotein whose principal function is the intracellular transport of lysosomal enzymes. In addition, the receptor also mediates some biological effects in response to IGF-II binding in both neuronal and nonneuronal systems. Multidisciplinary efforts to elucidate the intracellular signaling pathways that underlie these effects have generated data to suggest that the IGF-II/M6P receptor might mediate transmembrane signaling via a G protein-coupled mechanism. The purpose of this review is to outline the characteristics of traditional and nontraditional GPCRs, to relate the IGF-II/M6P receptor’s structure with its role in G protein-coupled signaling and to summarize evidence gathered over the years regarding the putative signaling of the IGF-II/M6P receptor mediated by a G protein.