Decreased Proportion of Cytomegalovirus Specific CD8 T-Cells but No Signs of General Immunosenescence in Alzheimer’s Disease

Cytomegalovirus (CMV) has been suggested as a contributing force behind the impaired immune responsiveness in the elderly, with decreased numbers of naïve T-cells and an increased proportion of effector T-cells. Immunological impairment is also implicated as a part of the pathogenesis in Alzheimer’s disease (AD). The aim of this study was to investigate whether AD patients present with a different CMV-specific CD8 immune profile compared to non-demented controls. Blood samples from 50 AD patients and 50 age-matched controls were analysed for HLA-type, CMV serostatus and systemic inflammatory biomarkers. Using multi-colour flow cytometry, lymphocytes from peripheral blood mononuclear cells were analysed for CMV-specific CD8 immunity with MHC-I tetramers A01, A02, A24, B07, B08 and B35 and further classified using CD27, CD28, CD45RA and CCR7 antibodies. Among CMV seropositive subjects, patients with AD had significantly lower proportions of CMV-specific CD8 T-cells compared to controls, 1.16 % vs. 4.13 % (p=0.0057). Regardless of dementia status, CMV seropositive subjects presented with a lower proportion of naïve CD8 cells and a higher proportion of effector CD8 cells compared to seronegative subjects. Interestingly, patients with AD showed a decreased proportion of CMV-specific CD8 cells but no difference in general CD8 differentiation.     

Urinary Excretion of Silicon in Men,Non-pregnant Women,and Pregnant Women: a Cross-sectional Study

Biological Trace Element Research - Silicon is a trace element found mainly in plant-based food and proposed to be beneficial for bone health. Urinary excretion of Si has been shown to be a...     

Feeding of Arapaima sp.: integrating stomach contents and local ecological knowledge

The giant arapaima (Arapaima sp.) has been described as a fish of change in Amazonia because of its important role in the conservation of floodplains, food security and income generation for rural communities. Nonetheless, despite the cultural, ecological and economic importance of arapaima, data on diet are scarce. Aiming to expand knowledge about arapaima diet in western Amazonia, scientific knowledge was integrated with the knowledge of local dwellers. During the low-water period (September 2018) and the falling-water period (June 2019), arapaima stomachs were collected from 11 floodplain lakes in the middle Juruá River. All fishes were measured [TL (total length)] and sexed. Food items from each stomach were categorized as fishes, invertebrates, plants and bone remains and weighed. Also, in the latter period, experienced local fishers were interviewed about arapaima feeding. This integrated approach revealed that young arapaima eat fish and invertebrates but adult arapaima eat fish of a wide range of species, which were mainly of low and intermediate trophic positions. This study reports the first case of cannibalism for arapaima and also shows that during the low-water period, many individuals had empty stomachs or only some small fish-bone remains and/or plant material. Arapaima sex and TL had no influence on the absence of prey in stomach contents. Overall, it can be concluded that local people had consistent ethnobiological knowledge of arapaima feeding ecology that could be useful within management projects in the region.     

Genetic determinants of mortality. Can findings from genome-wide association studies explain variation in human mortality?

Twin studies have estimated the heritability of longevity to be approximately 20–30 %. Genome-wide association studies (GWAS) have revealed a large number of determinants of morbidity, but so far, no new polymorphisms have been discovered to be associated with longevity per se in GWAS. We aim to determine whether the genetic architecture of mortality can be explained by single nucleotide polymorphisms (SNPs) associated with common traits and diseases related to mortality. By extensive quality control of published GWAS we created a genetic score from 707 common SNPs associated with 125 diseases or risk factors related with overall mortality. We prospectively studied the association of the genetic score with: (1) time-to-death; (2) incidence of the first of nine major diseases (coronary heart disease, stroke, heart failure, diabetes, dementia, lung, breast, colon and prostate cancers) in two population-based cohorts of Dutch and Swedish individuals (N = 15,039; age range 47–99 years). During a median follow-up of 6.3 years (max 22.2 years), we observed 4,318 deaths and 2,132 incident disease events. The genetic score was significantly associated with time-to-death [hazard ratio (HR) per added risk allele = 1.003, P value = 0.006; HR 4th vs. 1st quartile = 1.103]. The association between the genetic score and incidence of major diseases was stronger (HR per added risk allele = 1.004, P value = 0.002; HR 4th vs. 1st quartile = 1.160). Associations were stronger for individuals dying at older ages. Our findings are compatible with the view of mortality as a complex and highly polygenetic trait, not easily explainable by common genetic variants related to diseases and physiological traits.     

Oculomotor Deficits after Chemotherapy in Childhood

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects’ self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.     

Fine‐scale habitat heterogeneity explains the local distribution of two Amazonian frog species of concern for conservation

To test the hypothesis that subtle differences in abiotic requirements can result in almost total spatial segregation, we sampled two species of diurnal frogs, Atelopus spumarius and Allobates sumtuosus, in a primary forest reserve in central Brazilian Amazonia. We conducted visual and acoustic surveys on three occasions over 2 months, in 40 streamside (riparian) plots distributed throughout the reserve's two major drainage basins, using a grid system that covers 64 km². On average, drainages differed in the pH of stream water and the number of connected and isolated streamside pools. Differences in abiotic characteristics of drainages were associated with the spatial distribution of frog species. The occurrence and density of Allobates sumtuosus was negatively related to stream pH and discharge and positively related to the number of isolated pools in plots. The occurrence and density of Atelopus spumarius was associated with streams with high discharge and pH near neutral. These results indicate that although very large reserves will probably contain sufficient landscape heterogeneity to accommodate different species of diurnal frogs, due to strongly patchy distributions, in situ studies using fine‐scale species‐distribution models will be necessary to assess the adequacy of small reserves in Amazonia that cover hundreds of square kilometers or less for the conservation of some anuran species.     

Optimization of heterologous production of the polyketide 6-MSA in Saccharomyces cerevisiae

Polyketides are a group of natural products that have gained much interest due to their use as antibiotics, cholesterol lowering agents, immunosuppressors, and as other drugs. Many organisms that naturally produce polyketides are difficult to cultivate and only produce these metabolites in small amounts. It is therefore of general interest to transfer polyketide synthase (PKS) genes from their natural sources into heterologous hosts that can over-produce the corresponding polyketides. In this study we demonstrate the heterologous expression of 6-methylsalicylic acid synthase (6-MSAS), naturally produced by Penicillium patulum, in the yeast Saccharomyces cerevisiae. In order to activate the PKS a 4'-phosphopantetheinyl transferase (PPTase) is required. We therefore co-expressed PPTases encoded by either sfp from Bacillus subtilis or by npgA from Aspergillus nidulans. The different strains were grown in batch cultures. Growth and product concentration were measured and kinetic parameters were calculated. It was shown that both PPTases could be efficiently used for activation of PKS's in yeast as good yields of 6-MSA were obtained with both enzymes.     

Multi-stimulus multi-response posturography

In this study a method for the analysis of simultaneous multiple measurements of kinematics and stabilizing forces related to human postural dynamics is proposed. Each subject in a group of normal subjects (n=10) was tested with eyes-open and eyes-closed with simultaneous but uncorrelated vestibular and proprioceptive stimuli in order to investigate the contributions of individual sensory feedback loops. Statistical analysis was made by means of multi-input multi-output identification of a transfer function from stimuli to stabilizing forces of the feet and the resulting body position, the transfer function being compatible with a biomechanical model formulated as a stabilized segmented inverted pendulum subject to feedback of body sway and position. Each individual model estimated is effective in predicting a subject's response to new stimuli and in describing the interacting effects of stimuli on body kinetics. The proposed methodology responds to the current needs of data analysis of multi-stimulus multi-response experiments.     

Rapid genotyping of the osteoporosis-associated polymorphic transcription factor Sp1 binding site in the COL1A1 gene by pyrosequencing

We describe a novel polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencingbased assay for rapid genotyping of the polymorphic Sp1 binding site in the COL1A1 gene (1). A single nucleotide G-->T substitution polymorphism at this GC-rich site has recently been reported to be a predictive genetic marker for low bone mineral density (BMD). To simplify screening for this marker, we optimized PCR conditions and subjected the amplicons to pyrosequencing, which is a convenient high-throughput sequence analysis technique, readily amenable to automation. The analysis of 200 deidentified convenience DNA samples extracted from blood revealed genotype frequences in Hardy-Weinberg equilibrium (SS 68.0%, Ss 28.5%, and ss 3.5%) in agreement with other studies of European populations. This study demonstrates for the first time that pyrosequencing can be used for rapid identification of the osteoporosis-associated single nucleotide polymorphism (SNP) in the COL1A1 gene.