Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

© The Royal Society of Chemistry 2015. Selenoproteins play important roles in antioxidant mechanisms, and are thus hypothesised to have some involvement in the pathology of certain types of dementia. Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are both thought to involve impaired biological activity of certain selenoproteins. Previously, supplementation with a selenium-rich Brazil nut (Bertholletia excelsa) has shown potential in reducing cognitive decline in MCI patients, and could prove to be a safe and effective nutritional approach early in the disease process to slow decline. Here, we have conducted a pilot study that examined the effects of a range of single nucleotide polymorphisms (SNPs) in genes encoding the selenoproteins glutathione peroxidase (GPX1) and selenoprotein P (SEPP) in response to selenium supplementation via dietary Brazil nuts, including selenium status, oxidative stress parameters and GPX1 and SEPP gene expression. Our data suggest that GPX1 Pro198Leu rs1050450 genotypes may differentially affect the selenium status and GPx activity. Moreover, rs7579 and rs3877899 SNPs in SEPP gene, as well as GPX1 rs1050450 genotypes can influence the expression of GPX1 and SEPP mRNA in response to Brazil nuts intake. This small study gives cause for larger investigations into the role of these SNPs in both the selenium status and response to selenium dietary intake, especially in chronic degenerative conditions like MCI and AD

Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox

This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results

The Novel Object and Unusual Name (NOUN) database: a collection of novel images for use in experimental research

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects’ novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects’ colors. Results from a similarity sorting task (and subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprise both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in language, categorization, perception, visual memory and related domains

NMRDyn: A Program for NMR Relaxation Studies of Protein Association

Self-association is an important biological phenomenon that is associated with many cellular processes. NMR relaxation measurements provide data about protein molecular dynamics at the atomic level and are sensitive to changes induced by self-association. Thus, measurements and analysis of NMR relaxation data can provide structurally resolved information on self-association that would not be accessible otherwise. Here, we present a computer program, NMRdyn, which analyses relaxation data to provide parameters defining protein self-association. Unlike existing relaxation analysis software, NMRdyn can explicitly model the monomer-oligomer equilibrium while fitting measured relaxation data. Additionally, the program is packaged with a user-friendly interface, which is important because relaxation data can often be large and complex. NMRdyn is available from http://research1t.imb.uq.edu.au/nmr/NMRdyn

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer

<p>Abstract</p> <p>Background</p> <p>The transcription factor SOX2, which is involved in the induction of pluripotent stem cells and contributes to colorectal carcinogenesis, is associated with a poor prognosis in colon cancer (CC). Furthermore, SOX2 is a repressor of the transcriptional activity of β-catenin in vitro. Since the majority of CC develop via an activation of the Wnt/β-catenin signalling pathway, indicated by nuclear expression of β-catenin, we wanted to investigate the expression patterns of SOX2 and β-catenin and correlate them with the occurrence of lymph node and distant metastases as indicators of malignant progression.</p> <p>Methods</p> <p>The expression of SOX2 and β-catenin was investigated in a case control study utilizing a matched pair collection (N = 114) of right-sided CCs with either corresponding distant metastases (N = 57) or without distant spread (N = 57) by applying immunohistochemistry.</p> <p>Results</p> <p>Elevated protein expression of SOX2 significantly correlated with the presence of lymph node- (<it>p </it>= 0.006) and distant metastases (<it>p </it>= 0.022). Nuclear β-catenin expression correlated significantly only with distant metastases (<it>p </it>= 0.001). Less than 10% of cases showed a coexpression of high levels of β-catenin and SOX2. The positivity for both markers was also associated with a very high risk for lymph-node metastases (<it>p </it>= 0.007) and distant spread (<it>p </it>= 0.028).</p> <p>Conclusion</p> <p>We demonstrated that increased expression of either SOX2 or nuclear β-catenin are associated with distant metastases in right-sided CC. Additionally, SOX2 is also associated with lymph-node metastases. These data underline the importance of stemness-associated markers for the identification of CC with high risk for distant spread.</p

A fatal case of AIDS-defining meningoencephalitis by C. Neoformans, sensitive to antifungal therapy

Cryptococcus neoformans is the most common cause of life threatening meningoencephalitis in HIV-infected patients. Diagnosis is based on tests for cryptoccocal antigen in serum and cerebrospinal fluid, and on culture of the organism. We present a case of AIDS-related cryptococcal meningoencephalitis unresponsive to antifungal combination therapy, despite of evidence of fungal susceptibility in vitro. Significant decreases in cryptococcal antigen titers in serum and cerebrospinal fluid did not correlate with progress in disease and fatal outcome

Drosophila Lipophorin Receptors Mediate the Uptake of Neutral Lipids in Oocytes and Imaginal Disc Cells by an Endocytosis-Independent Mechanism

Lipids are constantly shuttled through the body to redistribute energy and metabolites between sites of absorption, storage, and catabolism in a complex homeostatic equilibrium. In Drosophila, lipids are transported through the hemolymph in the form of lipoprotein particles, known as lipophorins. The mechanisms by which cells interact with circulating lipophorins and acquire their lipidic cargo are poorly understood. We have found that lipophorin receptor 1 and 2 (lpr1 and lpr2), two partially redundant genes belonging to the Low Density Lipoprotein Receptor (LDLR) family, are essential for the efficient uptake and accumulation of neutral lipids by oocytes and cells of the imaginal discs. Females lacking the lpr2 gene lay eggs with low lipid content and have reduced fertility, revealing a central role for lpr2 in mediating Drosophila vitellogenesis. lpr1 and lpr2 are transcribed into multiple isoforms. Interestingly, only a subset of these isoforms containing a particular LDLR type A module mediate neutral lipid uptake. Expression of these isoforms induces the extracellular stabilization of lipophorins. Furthermore, our data indicate that endocytosis of the lipophorin receptors is not required to mediate the uptake of neutral lipids. These findings suggest a model where lipophorin receptors promote the extracellular lipolysis of lipophorins. This model is reminiscent of the lipolytic processing of triglyceride-rich lipoproteins that occurs at the mammalian capillary endothelium, suggesting an ancient role for LDLR–like proteins in this process

Identification of a delta5-like fatty acyl desaturase from the cephalopod Octopus vulgaris (Cuvier 1797) involved in the biosynthesis of essential fatty acids

Long-chain polyunsaturated fatty acids (LC-PUFA) have been identified as essential compounds for common octopus (Octopus vulgaris), but precise dietary requirements have not been determined due in part to the inherent difficulties of performing feeding trials on paralarvae. Our objective is to establish the essential fatty acid (EFA) requirements for paralarval stages of the common octopus through characterisation of the enzymes of endogenous LC-PUFA biosynthetic pathways. In this study we isolated a cDNA with high homology to fatty acyl desaturases (Fad). Functional characterisation in recombinant yeast showed the octopus Fad exhibited ∆5 desaturation activity towards saturated and polyunsaturated fatty acyl substrates. Thus, it efficiently converted the yeast&rsquo;s endogenous 16:0 and 18:0 to 16:1n-11 and 18:1n-13, respectively, and desaturated exogenously added PUFA substrates, 20:4n-3 and 20:3n-6, to 20:5n-3 (EPA) and 20:4n-6 (ARA), respectively. Although the ∆5 Fad enables common octopus to produce EPA and ARA, the low availability of its adequate substrates 20:4n-3 and 20:3n-6, either in the diet or by limited endogenous synthesis from C18 PUFA, might indicate that EPA and ARA are indeed EFA for this species. Interestingly, the octopus ∆5 Fad can also participate in the biosynthesis of non-methylene interrupted FA, PUFA that are generally uncommon in vertebrates but that have been found previously in marine invertebrates including molluscs, and now also confirmed to be present in specific tissues of common octopus