The effect of aluminum exposure on reproductive ability in the Bank Vole (Myodes glareolus)

Human impact on the environment is steadily increasing the amounts of aluminum in the ecosystems. This element accumulates in plants and water, potentially exposing herbivores to its harmful effect. In heavily polluted sites, a decrease in the density of small rodent populations has been observed. This decline may be caused by many factors, including decreased fertility. The aim of the presented research was to determine how aluminum, administered at concentrations similar to those recorded in industrial districts (Al I = 3 mg/l, Al II = 200 mg/l), affects the reproductive abilities of small rodents. As the indicators of reproductive abilities, body weight, weight of the testes and accessory sex glands of males, and uterus weight of females were estimated. In females, the number of matured follicles (types 6, 7, and 8) was analyzed, while in males, the quantity and quality (matured, viable, swollen, motile, head abnormalities) of epididymal sperm cells were assessed. Moreover, the development of testes, measured by spermatogenic index, was determined. The model species was the bank vole. Our results have proven that aluminum impairs adult individuals’ reproductive abilities by decreasing the quality and quantity of sperm cells and by causing morphologically abnormal development of the gonads. However, no difference in male organometric parameters was found, and only in females treated with 3 mg/l Al, the uterus weight was higher than control. No differences were found in the total number of matured follicles. These results suggest that the decline in rodent numbers in industrial districts is due, at least in part, to poorer males’ reproductive abilities, resulting from exposure to aluminum contamination

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients

Background: Allergic rhinitis affects 10–30 % of the global population and this number is likely to increase in the forthcoming years. Moreover, it commonly co-exists with allergic asthma as a chronic allergic respiratory syndrome. While the involvement of Th2 cells in allergy is well understood, alterations of pro-inflammatory Th17 responses remain poorly characterized. The aim of our study was to determine whether natural seasonal allergen exposure causes changes in T cell subset characteristics in patients with allergic rhinitis and asthma. Methods: Sixteen patients with allergic rhinitis/atopic asthma (9M, 7F; age 31.8 ± 12.1) and 16 healthy controls were recruited into the study (9M, 7F; age 31.2 ± 5.3). Blood samples were collected from the patients 1–3 months before pollen season (visit 1), within 7 days of the appearance of pollen/initiation of allergic symptoms (visit 2) and 2 weeks after visit 2 following the introduction of symptomatic treatment with antihistamines (visit 3). Flow cytometry was used to assess major T cell subsets (naïve, central memory, effector memory and CD45RA+ effector) and key T cell cytokine production (IFNγ, IL-17A, TNF and IL-4) using intracellular staining. Data were analyzed using repeated measures ANOVA and paired t test. Results: As expected, an increase in the percentage of IL‐4+ CD4+ cells was observed during natural pollen exposure in patients with allergic respiratory syndrome. No significant changes were observed in the production of other cytokines, including Th17 cells, which tended to be lower than in the control population but unchanged during pollen exposure. Introduction of antihistamine treatment led to only moderate changes in cytokine production from CD4 and CD8 T cells. Selective changes in CD8+ T cells were observed during natural pollen exposure including a decrease in transient cells (with features of CD45RA+ and CD45RO+ cells) and a decrease in the percentage of central memory cells in the peripheral circulation. Within the CD4 cell group the total percentage of CD45RA positive CD4 cells was increased during pollen exposure. Conclusions: Th1 and Th17 responses are not altered during pollen season but allergen exposure affects T cell activation and memory cell status in patients with allergic respiratory syndrome

Microvascular dysfunction in ankylosing spondylitis is associated with disease activity and is improved by anti-TNF treatment.

Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recent studies indicate that microvascular dysfunction may underlie cardiovascular risk in AS. We hypothesized, that microvascular morphology and dysfunction is linked to AS activity and is modifiable by TNF-α inhibitor (TNFi) treatment. Functional Laser Doppler Flowmetry with post-occlusive reactive hyperemia, and structural nailfold capillaroscopy were performed in 54 patients with AS and 28 matched controls. Active AS was diagnosed based on BASDAI ≥ 4 (n = 37). Effects of 3-month TNFi on microcirculation in active AS were studied. AS was associated with prolonged time to peak hyperemia compared to healthy controls. High disease activity was associated with increased time to peak hyperemia and decreased peak hyperemia when compared to patients with inactive AS. In capillaroscopy, AS was associated with morphological abnormalities indicating increased neoangiogenesis and pericapillary edema compared to controls. Microvascular function improved following 3 months of TNFi in reference to basal flow as well as post-occlusive parameters. TNFi reduced pericapillary edema, while other parameters of capillary morphology remained unchanged. Microvascular dysfunction and capillary neovascular formation are associated with disease activity of AS. Anti-TNF-α treatment may restore microcirculation function and capillary edema but does not modify microvascular structural parameters

1,2,3,4,6 penta-O -galloyl-β-D-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension

Background and Purpose: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6 Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. Experimental Approach: PGG was administered every two days in a dose of 10 mg·kg‐1 i.p during 14‐days of Ang II infusion and was used in a final concentration of 20 μM for in vitro studies. Key Results: Ang II administration increased leukocyte and T cell content in perivascular adipose tissue (pVAT) and administration of PGG significantly decreased total leukocyte and T cell infiltration in pVAT (1640±150 vs. 1028±57, p<0.01; 321±22 vs 158±18, cells/mg; p<0.01, respectively). This effect was observed in relation to all T cell subsets. PGG also decreased the content of T cells bearing CD25, CCR5 and CD44 receptors and the expression of both MCP‐1 in aorta and RANTES in pVAT. PGG administration decreased the content of TNF+ and IFN‐γ+ CD8 T cells and IL‐17A+ CD4+ and CD3+CD4‐CD8‐ cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II‐infused animals independently of blood pressure increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T cells. It also decreased the content of IFN‐γ+ by CD8+ and CD3+CD4‐CD8‐ cells and IL‐17A+ by CD3+CD4‐CD8‐ cells. Conclusion and Implication: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension

Careers in context: An international study of career goals as mesostructure between societies’ career-related human potential and proactive career behavior

Careers exist in a societal context that offers both constraints and opportunities for career actors. Whereas most studies focus on proximal individual and/or organisational‐level variables, we provide insights into how career goals and behaviours are understood and embedded in the more distal societal context. More specifically, we operationalise societal context using the career‐related human potential composite and aim to understand if and why career goals and behaviours vary between countries. Drawing on a model of career structuration and using multilevel mediation modelling, we draw on a survey of 17,986 employees from 27 countries, covering nine of GLOBE's 10 cultural clusters, and national statistical data to examine the relationship between societal context (macrostructure building the career‐opportunity structure) and actors' career goals (career mesostructure) and career behaviour (actions). We show that societal context in terms of societies' career‐related human potential composite is negatively associated with the importance given to financial achievements as a specific career mesostructure in a society that is positively related to individuals' proactive career behaviour. Our career mesostructure fully mediates the relationship between societal context and individuals' proactive career behaviour. In this way, we expand career theory's scope beyond occupation‐ and organisation‐related factors

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe