The selenoamino acids methylselenocysteine (MeSeCys) and selenomethionine (SeMet) have disparate efficacies as anticancer agents. Herein, we use X-ray absorption spectroscopy to determine the ...chemical form of selenium in human neuroblastoma cells. Cells treated with MeSeCys contain a significant diselenide component, which is absent from SeMet-treated cells and suggests that metabolites of MeSeCys are capable of altering the redox status of the cells. The differences in the speciation of Se in the selenoamino acid-treated cells may provide insight into the differing anticancer activities of MeSeCys and SeMet.
Dietary selenium has been implicated in the prevention of cancer and other diseases, but its safety and efficacy is dependent on the supplemented form and its metabolites. In this study, X-ray ...absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM) have been used to investigate the speciation and distribution of Se and Cu in vivo. In kidneys isolated from rats fed a diet containing 5 ppm Se as selenite for 3 weeks, Se levels increased 5-fold. XFM revealed a strong correlation between the distribution of Se and the distribution of Cu in the kidney, a phenomenon that has previously been observed in cell culture (Weekley et al., JBIC, J. Biol. Inorg. Chem., 2014, DOI: 10.1007/s00775-014-1113-x). However, X-ray absorption spectra suggest that most of the Se in the kidney is found as Se-Se species, rather than Cu-bound, and that most of the Cu is bound to S and N, presumably to amino acid residues in proteins. Furthermore, SOD1 expression did not change in response to the high Se diet. We cannot rule out the possibility of some Cu-Se bonding in the tissues, but our results suggest mechanisms other than the formation of Cu-Se species and SOD1 upregulation are responsible for the highly correlated distributions of Se and Cu in the kidneys of rats fed high selenite diets.
Objective
Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and ischemic stroke (IS). We investigated the evidence that shared genetic factors ...underpin the two diseases.
Methods
Using genome‐wide association study (GWAS) data from METASTROKE + (15,916 IS cases and 68,826 controls) and the International Genomics of Alzheimer's Project (IGAP; 17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype‐level data (4,610 IS cases, 1,281 AD cases, and 14,320 controls), we estimated the genome‐wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, and large vessel), using genome‐wide single‐nucleotide polymorphism (SNP) data. We then performed a meta‐analysis and pathway analysis in the combined AD and small vessel stroke data sets to identify the SNPs and molecular pathways through which disease risk may be conferred.
Results
We found evidence of a shared genetic contribution between AD and small vessel stroke (rG standard error = 0.37 0.17; p = 0.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta‐analysis of AD IGAP and METASTROKE + small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1) associated with both diseases (p = 1.8 × 10−8). A pathway analysis identified four associated pathways involving cholesterol transport and immune response.
Interpretation
Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. Ann Neurol 2016;79:739–747
We present a sample of 386 BL Lacertae candidates identified from 2860 deg2 of the Sloan Digital Sky Survey (SDSS) spectroscopic database. The candidates are primarily selected to have ...quasi-featureless optical spectra and low proper motions as measured from SDSS and USNO-B positions; however, our ability to separate Galactic from extragalactic quasi-featureless objects (QFOs) on the basis of proper motion alone is limited by the lack of reliable proper motion measurements for faint objects. Fortunately, high proper motion QFOs, mostly DC white dwarfs, populate a well-defined region of color space, approximately corresponding to blackbodies with temperatures in the range 7000-12,000 K. QFOs with measurable redshifts or X-ray or radio counterparts (i.e., evidence of an extragalactic/active galactic nucleus nature) loosely follow a track in color space that corresponds to power-law continua plus host galaxy starlight, with typical power-law slopes in the range 1 < aopt < 2 (fn {proportional to} n-a). Based largely on this remarkably clean color separation, we subdivide the sample into 240 probable candidates and 146 additional less probable (likely stellar) candidates. The probable BL Lac candidates have multiwavelength properties consistent with the range of previously known BL Lac objects, with an apparent preponderance of objects with synchrotron peaks at relatively high energies (HBL/XBL type). The majority of the 154 objects with measurable redshifts have z < 1, with a median of 0.45; there are also a handful of high-redshift objects extending up to z = 5.03. We identify a small number of potential radio-quiet BL Lac candidates, although more sensitive radio observations are needed to confirm their radio-quiet nature.
Data that can be used to monitor biodiversity through time are essential for conservation and management. The reef-forming worm, Sabellaria alveolata (L. 1767) is currently classed as ‘Data ...Deficient’ due to an imbalance in the spread of data on its distribution. Little is known about the distribution of this species around Ireland. Using data archaeology, we collated past and present distribution records and discovered that S. alveolata has a discontinuous distribution with large gaps between populations. Many regions lack data and should be targeted for sampling. Biodiversity surveys revealed that S. alveolata supported diverse epibiotic algal communities. Retrograding (declining) reefs supported greater infaunal diversity than prograding (growing) reefs or sand, suggesting that S. alveolata is a dynamic ecosystem engineer that has a lasting legacy effect. Similar research should be carried out for other Data Deficient species, habitats and regions. Such data are invaluable resources for management and conservation.
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•Improving the knowledge base of data deficient species will enable greater protection.•We identified knowledge gaps for the distribution of a Data Deficient species in a poorly mapped region.•S. alveolata reefs supported diverse epibiotic algal assemblages.•Retrograding (declining) reefs supported greater infaunal diversity than prograding (growing) reefs.•Such research should be done for other Data Deficient species and habitats.
Selenium compounds exhibit chemopreventative properties at supranutritional doses, but the efficacy of selenium supplementation in cancer prevention is dependent on the chemical speciation of the ...selenium supplement and its metabolites. The uptake, speciation, and distribution of the common selenoamino acid supplements, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys), in A549 human lung cancer cells were investigated using X-ray absorption and fluorescence spectroscopies. X-ray absorption spectroscopy of bulk cell pellets treated with the selenoamino acids for 24 h showed that while selenium was found exclusively in carbon-bound forms in SeMet-treated cells, a diselenide component was identified in MeSeCys-treated cells in addition to the carbon-bound selenium species. X-ray fluorescence microscopy of single cells showed that selenium accumulated with sulfur in the perinuclear region of SeMet-treated cells after 24 h, but microprobe selenium X-ray absorption near-edge spectroscopy in this region indicated that selenium was carbon-bound rather than sulfur-bound. X-ray absorption and X-ray fluorescence studies both showed that the selenium content of MeSeCys-treated cells was much lower than that of SeMet-treated cells. Selenium was distributed homogeneously throughout the MeSeCys-treated cells.
X-ray fluorescence (XRF) was used to image 40 histological cross-sections of bovine ovaries (n=19), focusing on structures including: antral follicles at different stages of growth or atresia, ...corpora lutea at three stages of development (II-IV), and capillaries, arterioles, and other blood vessels. This method identified three key trace elements iron (Fe), zinc (Zn), and selenium (Se) within the ovarian tissue which appeared to be localized to specific structures. Owing to minimal preprocessing of the ovaries, important high-resolution information regarding the spatial distribution of these elements was obtained with elemental trends and colocalizations of Fe and Zn apparent, as well as the infrequent appearance of Se surrounding the antrum of large follicles, as previously reported. The ability to use synchrotron radiation to measure trace element distributions in bovine ovaries at such high resolution and over such large areas could have a significant impact on understanding the mechanisms of ovarian development. This research is intended to form a baseline study of healthy ovaries which can later be extended to disease states, thereby improving our current understanding of infertility and endocrine diseases involving the ovary.
Background
We estimated the proportion and number of female breast cancer cases in Canada attributable to night shift work, a probable cause of breast cancer.
Methods
Levin's equation was used to ...calculate population attributable fractions (PAFs) among Canadian women who ever worked night/rotating shifts from 1961 to 2000, accounting for labor turnover and survival to the year 2011. The calculated PAFs were applied to 2011 Canadian breast cancer incidence statistics to obtain the number of attributable cases.
Results
Approximately 1.5 million women ever worked night/rotating shifts during 1961‐2000 and survived to 2011. The PAFs ranged from 2.0% (95% confidence interval CI: 1.4‐6.2) to 5.2% (95% CI: 3.7‐13.6), and 470 to 1200 incident breast cancer cases in 2011 were likely due to shift work, of which 38% would have been diagnosed among women in health‐related occupations.
Conclusions
More research is needed to increase the certainty of this association, but current evidence supports workplace‐based prevention.
Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that results in damage to myelin sheaths and axons in the central nervous system and which preferentially affects young ...adults. We performed a proteomics-based biomarker discovery study in which cerebrospinal fluid (CSF) from MS and control individuals was analyzed (
n
=
112). Ten candidate biomarkers were selected for evaluation by quantitative immunoassay using an independent cohort of MS and control subjects (
n
=
209). In relapsing–remitting MS (RRMS) patients there were significant increases in the CSF levels of alpha-1 antichymotrypsin (A1AC), alpha-1 macroglobulin (A2MG) and fibulin 1 as compared to control subjects. In secondary progressive MS (SPMS) four additional proteins (contactin 1, fetuin A, vitamin D binding protein and angiotensinogen (ANGT)) were increased as compared to control subjects. In particular, ANGT was increased 3-fold in SPMS, indicating a potential as biomarker of disease progression in MS. In PPMS, A1AC and A2MG exhibit significantly higher CSF levels than controls, with a trend of increase for ANGT. Classification models based on the biomarker panel could identify 70% of the RRMS and 80% of the SPMS patients correctly. Further evaluation was conducted in a pilot study of CSF from RRMS patients (
n
=
36), before and after treatment with natalizumab.
We report about a successful study approach to identify biomarkers in a neurological disease and development of a multiplex immunoassay with further evaluation of the findings.
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The biological activity of selenium is dependent on its chemical form. Therefore, knowledge of Se chemistry in vivo is required for efficacious use of selenium compounds in disease prevention and ...treatment. Using X-ray absorption spectroscopy, Se speciation in the kidney, liver, heart, spleen, testis and red blood cells of rats fed control (∼0.3 ppm Se) or selenite-supplemented (1 ppm or 5 ppm Se) diets for 3 or 6 weeks, was investigated. X-ray absorption spectroscopy revealed the presence of Se-Se and Se-C species in the kidney and liver, and Se-S species in the kidney, but not the liver. X-ray absorption near edge structure (XANES) spectra showed that there was variation in speciation in the liver and kidneys, but Se speciation was much more uniform in the remaining organs. Using principal component analysis (PCA) to interpret the Se K-edge X-ray absorption spectra, we were able to directly compare the speciation of Se in two different models of selenite metabolism--human lung cancer cells and rat tissues. The effects of Se dose, tissue type and duration of diet on selenium speciation in rat tissues were investigated, and a relationship between the duration of the diet (3 weeks versus 6 weeks) and selenium speciation was observed.
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