Phytoestrogen action in Leydig cells of Biłgoraj ganders (Anser anser)

The mechanism of phytoestrogen action in gonadal cells of ganders has not been elucidated. The aim of the study was to investigate in Bi?goraj ganders the possibility of phytoestrogen action via estrogen or androgen receptors or via protein tyrosine kinase pathways in Leydig cells. Genistein and daidzein (5 and 50 microM) as well as equol (50 microM) inhibited testosterone (T) secretion by incubated Leydig cells (1x10(5)/ml; 20 h; 37 degrees C). The effects of hydroxytamoxifen (estrogen receptor inhibitor) and cyproterone acetate (androgen receptor antagonist) on phytoestrogen inhibition of T release by Leydig cells were not observed. Lavendustin A (protein tyrosine kinases inhibitor) did not change T production. The influence of phytoestrogens seems not to be conducted via estrogen and androgen receptors or protein tyrosine kinases system in these cells, but further studies are required to completely examine the mechanism of phytoestrogens action in testes of ganders.     

Triazolyl tryptoline derivatives as β-secretase inhibitors

Tryptoline, a core structure of ochrolifuanine E, which is a hit compound from virtual screening of the Thai herbal database against BACE1 was used as a scaffold for the design of BACE1 inhibitors. The tryptoline was linked with different side chains by 1,2,3-triazole ring readily synthesized by catalytic azide-alkyne cycloaddition reactions. Twenty two triazolyl tryptoline derivatives were synthesized and screened for the inhibitory action against BACE1. JJCA-140 was the most potent inhibitor (IC(50)=1.49 μM) and was 100 times more selective for BACE1 than for Cat-D.     

A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus

Background

Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the ‘bush-meat’ trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.

Methodology/Principal Findings

We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a ‘proof-of-concept’ for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a CD8⁺ T cell epitope from the nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NP_CTL). MCMV/ZEBOV-NP_CTL induced high levels of long-lasting (>8 months) CD8⁺ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.

Conclusions/Significance

This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for ‘disseminating’ CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.     

Miliolipora species (Foraminifera,Miliolina) from the Rhaetian Dachstein Limestone of Karavanke Mts (Slovenia): Palaeoecological and palaeobiogeographic implications

The Carnian-Rhaetian genus Miliolipora (Soritoidea, Milioliporidae) is characterised by a coarsely perforated porcelaneous wall and a quinqueloculinoid arrangement of semi-tubular chambers. Miliolipora tamarae nov. sp. has been documented in the Rhaetian Dachstein reef limestone of Mt. Begunj??ica (Karavanke Mts., northern Slovenia). This new species differs from Miliolipora cuvillieri Brönnimann and Zaninetti in its costate outer chambers and evolute coiling. Both species are abundant in an oncoid rudstone/grapestone facies located immediately behind the central reef zone. In this depositional context, Miliolipora spp. were subjected to mechanical sorting and are believed to have been transported a short distance from their habitat. The costae and the overall less rounded shape of the test helped to stabilize M. tamarae nov. sp. on the sea floor. Both species were widely spread in the Tethyan realm confirming the broad palaeobiogeographic distribution of the Late Triassic foraminifera.     

High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions

Celiac disease is an immune-mediated disorder in which mucosal autoantibodies to the enzyme transglutaminase 2 (TG2) are generated in response to the exogenous antigen gluten in individuals who express human leukocyte antigen HLA-DQ2 or HLA-DQ8 (ref. 3). We assessed in a comprehensive and nonbiased manner the IgA anti-TG2 response by expression cloning of the antibody repertoire of ex vivo-isolated intestinal antibody-secreting cells (ASCs). We found that TG2-specific plasma cells are markedly expanded within the duodenal mucosa in individuals with active celiac disease. TG2-specific antibodies were of high affinity yet showed little adaptation by somatic mutations. Unlike infection-induced peripheral blood plasmablasts, the TG2-specific ASCs had not recently proliferated and were not short-lived ex vivo. Altogether, these observations demonstrate that there is a germline repertoire with high affinity for TG2 that may favor massive generation of autoreactive B cells. TG2-specific antibodies did not block enzymatic activity and served as substrates for TG2-mediated crosslinking when expressed as IgD or IgM but not as IgA1 or IgG1. This could result in preferential recruitment of plasma cells from naive IgD- and IgM-expressing B cells, thus possibly explaining why the antibody response to TG2 bears signs of a primary immune response despite the disease chronicity.     

New approach in studies of microalgal cell lysis

A new approach to the studies of the microalgal cell lysis by utilizing a combination of two complementary methods is presented. Delayed fluorescence (DF) is a measure of the living algal biomass, detecting only cells with active photosynthesis. Thermal lens spectrometry (TLS) detects the total pigment amount released from lysed cells. Both methods select for photosynthetic organisms, reducing possible background from other sources (e.g. heterotrophic bacteria, zooplankton, and abiotic substances). The DF/TLS method was tested with a laboratory Skeletonema costatum culture exposed to a geometric dilution series of the lysing factor poly- APS. The exposure resulted in similar EC₅0 values for DF intensity, TLS and dissolved esterase activity of 0.8±0.2, 1.77±0.35, and 1.25±0.1 mg poly-APS l⁻¹, respectively. The combined DF/TLS method enabled a rapid evaluation of the living vs. dead cells without any sample pretreatment or manipulation.