The role of the heat shock proteins (HSP70 and sHSP) in the thermotolerance of freshwater amphipods from contrasting habitats

The aim of this study was to clarify the significance of HSP70 and sHSP for thermotolerance in freshwater amphipods. We compared four amphipod species from different freshwater habitats and biogeographical regions (Central Europe vs. Lake Baikal). Test individuals were exposed to thermal stress generated by a water temperature of 25 °C. The thermotolerance of the species, determined by median lethal time (LT50), followed in decreasing order by Gmelinoides fasciatus, Echinogammarus berilloni, Gammarus pulex, Eulimnogammarus verrucosus. HSP70 and sHSP base level concentrations for the species were determined at control (i.e. non-stress) conditions. For HSP70, the base levels were positively correlated to the species' thermotolerances. For sHSP, however, only thermotolerant G. fasciatus showed a high level. Thermal stress at 25 °C water temperature caused a deferred onset of HSP70 and sHSP expression followed by a subsequent offset, delineating a unimodal response curve. The time lag to the expression onset of HSP70 was shorter in the thermosensitive species, compared to thermotolerant ones. Conversely, the time span until the maximum level of HSP70 was variable, not showing a dependence on the thermotolerance properties of the species. The peak concentration in G. pulex was distinctly higher than in the other species, whereas E. verrucosus did not develop a well-defined response maximum at all. In sHSP, the temporal pattern of expression was even more variable than in HSP70. However, the thermosensitive species E. verrucosus showed a time lag of expression onset significantly shorter than the other species and thermotolerant G. fasciatus developed the most pronounced response maximum. Basing on these results, the cellular response to thermal stress in amphipods is more consistently reflected by HSP70, compared to sHSP.     

Influenza A (H15N4) Virus Isolation in Western Siberia,Russia

The rarely identified influenza A viruses of the H15 hemagglutinin subtype have been isolated exclusively in Australia. Here we report the isolation of an H15N4 influenza A virus (A/teal/Chany/7119/2008) in Western Siberia, Russia. Phylogenetic analysis demonstrated that the internal genes of the A/teal/Chany/7119/2008 strain belong to the Eurasian clade and that the H15 and N4 genes were introduced into the gene pool of circulating endemic avian influenza viruses through reassortment events.     

DNA sequence-specific ligands. XVII. Synthesis,spectral properties,virological and biochemical studies of fluorescent dimeric bisbenzimidazoles DBA(n)

A series of DNA minor groove binding fluorescent dimeric bisbenzimidazoles DBA(n) bearing linkers of various length were synthesized and their biochemical and antiviral activities were evaluated. Their antiviral activity was assessed in model cell systems infected with human herpes simplex virus (HSV-1) and cytomegalovirus (CMV). Compounds DBA(1) and DBA(7) demonstrated in vitro inhibitory properties towards HSV-1, and DBA(7) completely blocked the viral infection. Compound DBA(11) displayed the in vitro therapeutic activity towards both HSV-1 and CMV. All of the DBA(n) could fluoresce, were well soluble in water, not cytotoxic to a concentration of 240?µM, penetrated well into cell nuclei by binding to DNA and could inhibit topo-I at low micromolecular concentrations.     

A transgenic model reveals important roles for the NF-kappa B alternative pathway (p100/p52) in mammary development and links to tumorigenesis

A regulated pattern of nuclear factor kappaB (NF-kappaB) activation is essential for normal development of the mammary gland. An increase in NF-kappaB activity has been implicated in breast cancer. We have generated a novel transgenic mouse model to investigate the role of the alternative NF-kappaB pathway in ductal development and identify possible mediators of tumorigenesis downstream of p100/p52. By overexpressing the NF-kappaB p100/p52 subunit in mammary epithelium using the beta-lactoglobulin milk protein promoter, we found that transgene expression resulted in increased overall NF-kappaB activity during late pregnancy. During pregnancy, p100/p52 expression resulted in delayed ductal development with impaired secondary branching and increased levels of Cyclin D1, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and cyclo-oxygenase-2 (COX-2) in the mammary gland. After multiple pregnancies the p100 transgenics exhibited a ductal thickening accompanied by small hyperplastic foci. In tumors from mice expressing the polyoma middle T oncoprotein (PyVT) in the mammary gland, increased levels of p100/p52 were present at the time of tumor development. These results show that increased p100/p52 disrupts normal ductal development and provides insight into the mechanism by which this may contribute to human breast cancer.     

Androgen Receptor Gene Polymorphism,Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born.     

Chronic HCV-infection and expression of mRNA of CC-chemokines and their receptors

The aim of this study was to evaluate some patterns in expression of CC-chemokines (MIP-1alpha, MIP-1beta, MCP-1, RANTES) and their receptors (CCR1, CCR2, CCR3, CCR5) in peripheral blood leukocytes and liver biopsy samples from 21 patients with chronic hepatitis C. 10 healthy subjects were included in the control group. In patients with chronic HCV-infection significant increase of MCP-1 mRNA in liver tissue was observed as the disease progressed. Moreover, content of MCP-1 mRNA was significantly higher in liver as compared with blood. Level of MCP-1 mRNA in liver was directly related with histological changes. Levels of mRNA of CCR1, CCR2, CCR3, and CCR5 in blood of patients with minimal histological manifestations of chronic HCV-infection were significantly lower than in patients with more marked lesions. Expression of CCR1 and CCR5 mRNA in blood was directly correlated with histological activity index and degree of fibrosis. Conducted study demonstrates that progression of chronic hepatitis C is realized through local activation of MCP-1 mRNA synthesis leading to systemic response which manifested by increase of expression of CCR1, CCR2, CCR3, and CCR5 in peripheral blood leukocytes.     

Effect of redox mediators on the flash-induced membrane potential generation in Mn-depleted photosystem II core particles

An electrometrical technique was used to investigate flash-induced electron transfer reactions between Mn-depleted spinach photosystem II core particles incorporated into liposomes and redox mediators. Besides the fast increase in the transmembrane electric potential difference associated with electron transfer between the redox active tyrosine (Y_Z) and the primary quinone acceptor Q_A, an additional electrogenic phase was observed in the presence of N,N,N′N′-tetramethyl-p-phenylenediamine and 2,6-dichlorophenol-indophenol. The latter phase is attributed to vectorial electron transfer from the redox dye(s) to the protein-embedded Y_Z. The data obtained suggest an electrically isolated location of the Y_Z from the external water phase.     

An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats

Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.