Are there functional consequences of a reduction in selenium intake in UK subjects?

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status

Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?

Infection with blood-dwelling schistosome worms is a major cause of human disease in many tropical countries. Despite intensive efforts a vaccine has proved elusive, not least because the chronic nature of the infection provides few pointers for vaccine development. The rhesus macaque appears unique among animal models in that adult worms establish but are eventually lost. We investigated whether this was due to pathological or immunological causes by monitoring the fate of a schistosome infection, and were able to rule out escape of worms from the portal system as a result of egg-induced vascular shunts. A substantial worm population established in all animals but there was a wide variation in the numbers recovered at 18 weeks. We observed a strong inverse association between the rapidity and intensity of the IgG response and worm burden. Rather than an acute lethal attack, immune-mediated elimination of worms appeared to be a prolonged process directed against vital components of exposed surfaces, causing worms to starve to death. We suggest that if the mechanisms deployed by the rhesus macaque could be replicated in humans by administration of key recombinant antigens, they would form the basis for a vaccine with both prophylactic and therapeutic properties

Isotopic and spin selectivity of H_2 adsorbed in bundles of carbon nanotubes

Due to its large surface area and strongly attractive potential, a bundle of carbon nanotubes is an ideal substrate material for gas storage. In addition, adsorption in nanotubes can be exploited in order to separate the components of a mixture. In this paper, we investigate the preferential adsorption of D_2 versus H_2(isotope selectivity) and of ortho versus para(spin selectivity) molecules confined in the one-dimensional grooves and interstitial channels of carbon nanotube bundles. We perform selectivity calculations in the low coverage regime, neglecting interactions between adsorbate molecules. We find substantial spin selectivity for a range of temperatures up to 100 K, and even greater isotope selectivity for an extended range of temperatures,up to 300 K. This isotope selectivity is consistent with recent experimental data, which exhibit a large difference between the isosteric heats of D_2 and H_2 adsorbed in these bundles.Comment: Paper submitted to Phys.Rev. B; 17 pages, 2 tables, 6 figure

Porphyromonas gingivalis (W83) infection induces Alzheimer’s disease like pathophysiology in obese and diabetic mice

Periodontal disease and metabolic illnesses negatively impact the quality of life and, eventually, mental health. This study aimed to investigate the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. While no Aβ plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aβ release in the same infection group. In conclusion, P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease

Serotype Distribution and Invasive Potential of Group B Streptococcus Isolates Causing Disease in Infants and Colonizing Maternal-Newborn Dyads

Serotype-specific polysaccharide based group B streptococcus (GBS) vaccines are being developed. An understanding of the serotype epidemiology associated with maternal colonization and invasive disease in infants is necessary to determine the potential coverage of serotype-specific GBS vaccines.Colonizing GBS isolates were identified by vaginal swabbing of mothers during active labor and from skin of their newborns post-delivery. Invasive GBS isolates from infants were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically non-typeable isolates were typed by a serotype-specific PCR method. The invasive potential of GBS serotypes associated with sepsis within seven days of birth was evaluated in association to maternal colonizing serotypes.GBS was identified in 289 (52.4%) newborns born to 551 women with GBS-vaginal colonization and from 113 (5.6%) newborns born to 2,010 mothers in whom GBS was not cultured from vaginal swabs. The serotype distribution among vaginal-colonizing isolates was as follows: III (37.3%), Ia (30.1%), and II (11.3%), V (10.2%), Ib (6.7%) and IV (3.7%). There were no significant differences in serotype distribution between vaginal and newborn colonizing isolates (P = 0.77). Serotype distribution of invasive GBS isolates were significantly different to that of colonizing isolates (P<0.0001). Serotype III was the most common invasive serotype in newborns less than 7 days (57.7%) and in infants 7 to 90 days of age (84.3%; P<0.001). Relative to serotype III, other serotypes showed reduced invasive potential: Ia (0.49; 95%CI 0.31-0.77), II (0.30; 95%CI 0.13-0.67) and V (0.38; 95%CI 0.17-0.83).In South Africa, an anti-GBS vaccine including serotypes Ia, Ib and III has the potential of preventing 74.1%, 85.4% and 98.2% of GBS associated with maternal vaginal-colonization, invasive disease in neonates less than 7 days and invasive disease in infants between 7-90 days of age, respectively

Altered Chromosomal Positioning, Compaction, and Gene Expression with a Lamin A/C Gene Mutation

Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression.To investigate the hypothesis that mutant lamin A/C changes the lamina's ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction.These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)