Spatial distribution of lead in the roots of human primary teeth

Lead remains one of the most hazardous metals in our environment. The concentrations of lead in coronal dentine and enamel have previously been reported but limited information is available regarding lead levels in radicular dentine and cementum. This study reports the distribution of lead in 26 roots of 16 human maxillary primary teeth from seven individuals. In addition, calcium and phosphorous concentrations were also measured to detect any variations in the degree of mineralization in different regions of the roots. The mean lead concentration in these roots was 1.67 +/- 1.43 microg/g, which is comparable to other studies. In all cases there were higher lead concentrations in the apices of non-resorbed roots of primary maxillary teeth relative to middle and cervical regions. The findings reported here are of potential significance during the process of physiological root resorption whence periapical tissue may be exposed to higher levels of lead.     

Actinomycin-Producing Endophytic Streptomyces parvulus Associated with Root of Aloe vera and Optimization of Conditions for Antibiotic Production

Endophytic actinomycetes are a rich source of novel antimicrobial compounds. The aim of this study was to evaluate the production of antimicrobial compound by endophytic Streptomyces sp. Av-R5 associated with root of Aloe vera against multidrug-resistant human pathogens. The 16S rRNA sequence of the isolate Av-R5 has been identified as Streptomyces parvulus NBRC 13193^T (AB184326) and the sequence was submitted to the National Center for Biotechnology Information (NCBI) GenBank database (accession number KY771080). Streptomyces parvulus Av-R5 grown under submerged fermentation condition optimized by central composite design (glucose 11.16 g/L, soybean meal 10.25 g/L, sodium chloride 11.18 g/L, calcium carbonate 1.32 g/L at pH 7.19 at 31.42 °C with 6.04% seed inoculum for 10 days of incubation) exhibited the highest activity against multidrug-resistant Staphylococcus aureus JNMC-3, Staphylococcus epidermidis JNMC-4, Klebsiella pneumoniae MTCC-3384, Klebsiella pneumoniae JNMC-6, Pseudomonas aeruginosa MTCC-741, Proteus vulgaris JNMC-7, Candida albicans MTCC-183, and Aspergillus niger MTCC-872. The structures of the active compounds were elucidated by UV-Vis spectroscopy, ¹H and ¹³C NMR, FT-IR, and ESIMS. Actinomycin D and actinomycin X_0β were detected in crude extracts and major components were eluted by HPLC at 10.96 and 6.81 min, respectively. In this case, a high yield of actinomycin D and actinomycin X_0β (400 mg/L) was achieved with Streptomyces parvulus Av-R5, fermented in glucose soybean meal broth media, which can be used in industrial fermentation process to obtain high yields.

     

The collaborative study on the genetics of alcoholism: Brain function

Alcohol use disorder (AUD) and related health conditions result from a complex interaction of genetic, neural and environmental factors, with differential impacts across the lifespan. From its inception, the Collaborative Study on the Genetics of Alcoholism (COGA) has focused on the importance of brain function as it relates to the risk and consequences of alcohol use and AUD, through the examination of noninvasively recorded brain electrical activity and neuropsychological tests. COGA's sophisticated neurophysiological and neuropsychological measures, together with rich longitudinal, multi-modal family data, have allowed us to disentangle brain-related risk and resilience factors from the consequences of prolonged and heavy alcohol use in the context of genomic and social-environmental influences over the lifespan. COGA has led the field in identifying genetic variation associated with brain functioning, which has advanced the understanding of how genomic risk affects AUD and related disorders. To date, the COGA study has amassed brain function data on over 9871 participants, 7837 with data at more than one time point, and with notable diversity in terms of age (from 7 to 97), gender (52% female), and self-reported race and ethnicity (28% Black, 9% Hispanic). These data are available to the research community through several mechanisms, including directly through the NIAAA, through dbGAP, and in collaboration with COGA investigators. In this review, we provide an overview of COGA's data collection methods and specific brain function measures assessed, and showcase the utility, significance, and contributions these data have made to our understanding of AUD and related disorders, highlighting COGA research findings.     

Localisation du récepteur des androgènes dans le testicule

Whether or not germ cells contain the androgen receptor remains a matter of controversy. In the present study we performed biotinstreptavidin immunoperoxidase using an affinity purified rabbit polyclonal antibody made to a 21 amino acid peptide of the amino terminus of the rat AR to determine androgen receptor (AR) distribution in the rat and mouse testes. Specificity of the antibody was confirmed as follows: 1) Western immunoblots rendered a specific band at approximately 110 kD; 2) preadsorption of the antibody with the 21 amino acid peptide eliminated specifice immunostaining; 3) the intensity of staining in all AR positive cells diminished as a function of antisera dilution; 4) tissues known to express abundant AR (e.g., epididymis, prostate, seminal vesicles) all rendered a robust, nuclear AR immunostaining pattern in the epithelial cells; 5) prostate cell lines known to express AR immunostained positive with the antibody; 6) AR negative COS-7 cells became AR immunopositive when transfected with a vector expressing the rat AR and intracellular AR distribution was a function of androgens. AR immunostaining results revealed the following: Within the interstitial compartment of adult rats, AR was detected in some Leydig cells and all smooth muscle cells forming the walls of blood vessels, but endothelial cells were negative. In the seminiferous tubules AR was observed in all peritubular myoid cell nuelei, but not in the distal layer of Iymphatic endothelial cells. In Sertoli cells, nuclear AR immunostaining was stage specific; moderate AR immunostaining became evident at late stage IV of the cycle, reached a robust peak at stages VII-VIII, and then disappeared completely. Specific AR immunostaining was also discerned in the nuclei of stage XI elongated spermatids, in which nuclear elongation is apparent but chromatin condensation has not yet begun. With onset of chromatin condensation, nuclear AR immunostaining in elongated spermatids was not discerned concomitant with its detection in the cytoplasm. In general, similar observations have now been confirmed in the adult mouse testis, except that an Leydig cells were strongly AR positive. Nucleic acid in situ hybridization studies for AR were performed in adult rat testis using a 236 bp antisense cRNA probe (rat AR cDNA was provided by Dr. C. Chang, U. Wisconsin, Madison, WI) to confirm the AR immunostaining. A prominent hybridization signal at the base of the seminiferous epithelium was observed, in the area occupied by Sertofi and spermatogonia. This led us to re-examine the immunostaining results to determine if spermatogonia were also AR positive. Preliminary results are consistent with the interpretation that AR is present in certain spermatogonial populations. Taken together, these results concur with prior observations suggesting that AR is present in the somatic cells of the testis; thus, it is these cell types that likely respond to circulating androgens to control spermatogenesis. However, they raise anew the controversy of whether germ cells respond directly to androgens.     

Predicting bone turnover following tobacco exposure using bone alkaline phosphatase and N-telopeptide biomarkers and possible variability and effect modification of these markers by race/ethnicity

Abstract

Introduction: This study investigated the systemic response of serum bone alkaline phosphatase (SBAP) and urinary N-telopeptide (UNTX) to tobacco exposure and environmental tobacco smoke (ETS) and the possible effect modification (and variability) of this response by racial/ethnic origin.

Methods: Data (n?=?5411) were obtained from the National Health and Nutrition Examination Survey, with data analysis done on adults aged ≥ 20?years. Outcome variables were SBAP and UNTX. Independent variable was tobacco exposure measured using serum cotinine levels and adjusted for covariates. Generalized linear models were used to explore associations.

Results: A percentage increase in log transformed serum cotinine was associated with a 0.005 percentage increase in log transformed SBAP (CI: 0.002, 0.008) and 0.02 percentage increase in log transformed UNTX (CI: ?0.01, 0.04) with interaction between cotinine and race/ethnicity (p?=?0.01). Stratifying by race/ethnicity, tobacco exposure was associated with significant decreases in UNTX among non-Hispanic Whites – 0.008(?0.014, ?0.002) and Mexican Americans ?0.014 (?0.025, ?0.002) only. Categories of serum cotinine were associated with a monotonic increase in SBAP (p for trend <0.001) and monotonic non-linear decrease in UNTX (p for trend?>?0.05).

Conclusions: Tobacco and environmental tobacco exposure are associated with SBAP and increased bone formation. The response of UNTX to these exposures is modified by race/ethnicity with non-Hispanic Whites and Mexican-Americans less sensitive to the resorptive effects of tobacco exposure on bone.     

Effect of permeabilization on the thermostability of catalase in immobilized yeast cells

Summary Catalase in yeast cells is rendered thermolabile on permeabilization using organic solvents or any process of immobilization that eventually permeabilizes the cells. A stable immobilized catalase preparation can be obtained only if yeast cells are immobilized in an intact or viable form.     

Modulation of SETDB1 activity by APQ ameliorates heterochromatin condensation,motor function,and neuropathology in a Huntington’s disease mouse model

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington’s disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined in silico and in vitro cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD.     

Roles of the two type II NADH dehydrogenases in the survival of Mycobacterium tuberculosis in vitro

Most bacteria are able to generate sufficient amounts of ATP from substrate level phosphorylation, thus rendering the respiratory oxidative phosphorylation non-critical. In mycobacteria, including Mycobacterium tuberculosis, ATP generation by oxidative phosphorylation is an essential process. Of the two types of NADH dehydrogenases (type I and type II), the type II NADH dehydrogenase (Ndh) which is inhibited by phenothiazines has been thought to be essential. In M. tuberculosis there are two Ndh isozymes (Ndh and NdhA) coded by ndh and ndhA genes respectively. Ndh and NdhA share a high degree of amino acid similarity. Both the enzymes have been shown to be enzymatically active and are inhibited by phenothiazines, suggesting a functional similarity between the two. We attempted gene knockout of ndh and ndhA genes in wild type and merodiploid backgrounds. It was found that ndh gene cannot be inactivated in a wild type background, though it was possible to do so when an additional copy of ndh was provided. This showed that in spite of its apparent functional equivalence, NdhA cannot complement the loss of Ndh in M. tuberculosis. We also showed that NdhA is not essential in M. tuberculosis as the ndhA gene could be deleted in a wild type strain of M. tuberculosis without causing any adverse effects in vitro. RT-PCR analysis of in vitro grown M. tuberculosis showed that ndhA gene is actively transcribed. This study suggests that despite being biochemically similar, Ndh and NdhA play different roles in the physiology of M. tuberculosis.