Increased Inflammatory Response in Cytomegalovirus Seropositive Patients with Alzheimer’s Disease

Alzheimer’s disease (AD) has been associated with increased local inflammation in the affected brain regions, and in some studies also with elevated levels of proinflammatory cytokines in peripheral blood. Cytomegalovirus (CMV) is known to promote a more effector-oriented phenotype in the T-cell compartment, increasing with age. The aim of this study was to investigate the inflammatory response of peripheral blood mononuclear cells (PBMCs) from AD patients and non-demented (ND) controls. Using a multiplex Luminex xMAP assay targeting GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10 and TNF-α, cytokine profiles from PBMCs were analysed after stimulation with anti-CD3/CD28 beads, CMV pp65 peptide mix or amyloid β (Aβ) protofibrils, respectively. CMV seropositive AD subjects presented with higher IFN-γ levels after anti-CD3/CD28 and CMV pp65 but not after Aβ stimulation, compared to CMV seropositive ND controls. When analysing IFN-γ response to anti-CD3/CD28 stimulation on a subgroup level, CMV seropositive AD subjects presented with higher levels compared to both CMV seronegative AD and CMV seropositive ND subjects. Taken together, our data from patients with clinically manifest AD suggest a possible role of CMV as an inflammatory promoter in AD immunology. Further studies of AD patients at earlier stages of disease, could provide better insight into the pathophysiology.     

How Can Inequalities in Mortality Be Reduced? A Quantitative Analysis of 6 Risk Factors in 21 European Populations

Background

Socioeconomic inequalities in mortality are one of the greatest challenges for health policy in all European countries, but the potential for reducing these inequalities is unclear. We therefore quantified the impact of equalizing the distribution of six risk factors for mortality: smoking, overweight, lack of physical exercise, lack of social participation, low income, and economic inactivity.

Methods

We collected and harmonized data on mortality and risk factors by educational level for 21 European populations in the early 2000s. The impact of the risk factors on mortality in each educational group was determined using Population Attributable Fractions. We estimated the impact on inequalities in mortality of two scenarios: a theoretical upward levelling scenario in which inequalities in the risk factor were completely eliminated, and a more realistic best practice scenario, in which inequalities in the risk factor were reduced to those seen in the country with the smallest inequalities for that risk factor.

Findings

In general, upward levelling of inequalities in smoking, low income and economic inactivity hold the greatest potential for reducing inequalities in mortality. While the importance of low income is similar across Europe, smoking is more important in the North and East, and overweight in the South. On the basis of best practice scenarios the potential for reducing inequalities in mortality is often smaller, but still substantial in many countries for smoking and physical inactivity.

Interpretation

Theoretically, there is a great potential for reducing inequalities in mortality in most European countries, for example by equity-oriented tobacco control policies, income redistribution and employment policies. Although it is necessary to achieve substantial degrees of upward levelling to make a notable difference for inequalities in mortality, the existence of best practice countries with more favourable distributions for some of these risk factors suggests that this is feasible.     

The Gut Microbiota and Developmental Programming of the Testis in Mice

Nutrients and environmental chemicals, including endocrine disruptors, have been incriminated in the current increase in male reproductive dysfunction, but the underlying mechanisms remain unknown. The gastrointestinal tract represents the largest surface area exposed to our environment and thereby plays a key role in connection with exposure of internal organs to exogenous factors. In this context the gut microbiome (all bacteria and their metabolites) have been shown to be important contributors to body physiology including metabolism, cognitive functions and immunity. Pivotal to male reproduction is a proper development of the testis, including the formation of the blood-testis barrier (BTB) that encapsulates and protects germ cells from stress induced environmental cues, e.g. pathogenic organisms and xenobiotics. Here we used specific pathogen free (SPF) mice and germ-free (GF) mice to explore whether gut microbiota and/or their metabolites can influence testis development and regulation of BTB. Lumen formation in the seminiferous tubules, which coincides with the development of the BTB was delayed in the testes of GF mice at 16 days postpartum. In addition, perfusion experiments (Evans blue) demonstrated increased BTB permeability in these same mice. Reduced expressions of occludin, ZO-2 and E-cadherin in GF testis suggested that the microbiota modulated BTB permeability by regulation of cell-cell adhesion. Interestingly, exposure of GF mice to Clostridium Tyrobutyricum (CBUT), which secrete high levels of butyrate, restored the integrity of the BTB and normalized the levels of cell adhesion proteins. Moreover, the GF mice exhibited lower serum levels of gonadotropins (LH and FSH) than the SPF group. In addition, the intratesticular content of testosterone was lower in GF compared to SPF or CBUT animals. Thus, the gut microbiome can modulate the permeability of the BTB and might play a role in the regulation of endocrine functions of the testis.     

Allozyme diversity and geographic variation in the widespread coastal sedge, Carex arenaria

Abstract. Allozyme electrophoresis was used to investigate the structure of genetic variation in the rhizomatous coastal sedge, Carex arenaria, throughout its European range — from the SW Iberian peninsula to the Baltic region. Material was sampled from 77 sites in five geographic regions. Nine of the 13 investigated loci were polymorphic in the total material and there were interregional differences in the number of polymorphic loci per site and the percentage of variable sites. In the Scandinavia/Baltic region only 61% of the sites contained at least one locus with more than one allele, whereas all the British and SW Iberian sites were variable. There was a general tendency for the regional frequencies of the less common alleles at individual loci to decline from SW to NE. The mean (over loci and sites) within‐site gene diversity (H _site) was 0.064 (in calculations based on the number of observed multilocus allozyme genotypes within each sampling site). Although there was considerable variation between geographically adjacent sites, within‐site diversity showed a general decrease from SW to NE in Europe. There were significant differences in within‐region gene diversity (H_reg) for the four most variable loci between the five regions. H_reg generally decreased from SW to NE Europe and most loci showed the highest diversity in the SW Iberian peninsula and the Bay of Biscay regions. The mean (over loci) gene diversity in the total material (H_tot) was 0.070 and the levels of diversity in Carex arenaria are substantially lower than is usual in rhizomatous sedges. The within‐site, between‐site and between‐regional components of the total diversity were 92.4%, 2.5% and 5.1%, respectively. The low levels of overall gene diversity in C. arenaria and the successive decrease in diversity from SW to NE are interpreted in terms of the species’ history of postglacial spread into northern Europe. Despite the overall northwards decrease in diversity, the widespread occurrence of less common alleles and the lack of regional deviations from Hardy–Weinberg genotype frequency expectations suggest that C. arenaria is not predominantly self‐fertilized.     

Physiological and molecular diversity of feather moss associative N2-fixing cyanobacteria

Cyanobacteria colonizing the feather moss Pleurozium schreberi were isolated from moss samples collected in northern Sweden and subjected to physiological and molecular characterization. Morphological studies of isolated and moss-associated cyanobacteria were carried out by light microscopy. Molecular tools were used for cyanobacteria identification, and a reconstitution experiment of the association between non-associative mosses and cyanobacteria was conducted. The influence of temperature on N2 fixation in the different cyanobacterial isolates and the influence of light and temperature on N2-fixation rates in the moss were studied using the acetylene reduction assay. Two different cyanobacteria were effectively isolated from P. schreberi: Nostoc sp. and Calothrix sp. A third genus, Stigonema sp. was identified by microscopy, but could not be isolated. The Nostoc sp. was found to fix N2 at lower temperatures than Calothrix sp. Nostoc sp. and Stigonema sp. were the predominant cyanobacteria colonizing the moss. The attempt to reconstitute the association between the moss and cyanobacteria was successful. The two isolated genera of cyanobacteria in feather moss samples collected in northern Sweden differ in their temperature optima, which may have important ecological implications.     

Continuous culture with complete cell recycle to obtain high cell densities in product inhibited cultures; cultivation ofStreptococcus lactis for production of superoxide dismutase

Summary A cultivation system is described for cultivatingStreptococcus lactis in continuous culture with complete cell recycle. The aim was to obtain high cell densities for the production of su-peroxide dismutase (SOD) while avoiding the growth inhibiting effects of the lactic acid produced. This type of cultivation was performed both at constant and at increasing dilution rates. Comparisons made include those between cell mass productivity and SOD productivity in recycling cultivations and batch cultivations. In the recycling cultivation at increasing dilution rates a cell mass of 19 g/1 was obtained after 22 h of cultivation and the SOD productivity was 43.10³ U/1.h which is four times higher than for batch cultivations. The effect of recyclingS. lactis was also considered and no damage of the microorganisms was observed.     

Nigericin insensitive post-illumination reduction in fluorescence yield in Dunaliella tertiolecta (chlorophyte)

Cells of the green alga Dunaliella tertiolecta grown in a light/dark cycle were exposed to high light for about 15 min. In light, energy-dependent quenching reduced fluorescence emission and decreased PS II efficiency. Within 3 minutes after darkening fluorescence quenching largely relaxed. However, PS II fluorescence emission decreased again after further darkening. F_o and F_m decreased to the same relative extent and the PS II efficiency was not reduced. This Reduction in Fluorescence yield in Darkness, termed RFD for the purpose of this paper, lasted about 20 min. The deepoxidation state of xanthophylls remained unchanged during and after the 15-min exposure to high light. We show that RFD is insensitive to the uncoupler nigericin and thus unrelated to energy-dependent quenching. RFD correlated with a reduction of the PQ pool after darkening and low levels of far red or blue light (430 nm more than 460 nm) prevented RFD. This is in contrast to observations in higher plants, where a post-illumination reduction of the PQ pool causes and increase in F_o (Groom et al. (1993) Photosynth Res 36: 205–215). Changes in the adenylate energy charge were not correlated with RFD. Antimycin A and cyanide, both inhibitors of the PQ-oxidase, caused an increase in RFD whereas SHAM, an inhibitor of the chloroplastic glycolate-quinone oxidoreductase, caused a decrease. Low CO₂ concentrations, known to increase the oxygenase activity of Rubisco and to generate glycolate and P-glycolate in light, caused an increase in RFD. We propose that accumulated glycolate and P-glycolate reduce the PQ pool in darkness, leading to the formation of RFD. During RFD, 77 K fluorescence emission from PS II was more reduced than that from PS I, thus resembling a state I, state II transition. However, the reduction in fluorescence yield during RFD is much larger than the reduction previously attributed to state transitions and it is unclear whether RFD and state transitions are identical. The formation and relaxation of RFD increased with higher temperatures and the extent of RFD was largest at the growth temperature (25°C). RFD has to be taken into account when fluorescence is measured after darkening as it may be mistaken for energy-dependent quenching.Abbreviations F_o fluorescence, measured when PS II traps are open - F_o difference between F_o and F_o - F_m fluorescence, measured when PS II traps are temporarily closed - F_m difference between F_m and F_m - FR far red - PFD photosynthetically active photon flux density - PQ plastoquinone - RFD reduction in fluorescence in darkness - SHAM salicylhydroxamic acid - Q_A primary quinone acceptor of PS II