Elaeocarpus reticulatus fruit extracts reduce viability and induce apoptosis in pancreatic cancer cells in vitro

Molecular Biology Reports - Treatment options for pancreatic cancer (PC) are severely limited due to late diagnosis, early metastasis and the inadequacy of chemotherapy and radiotherapy to combat...     

Influenza Nucleoprotein Delivered with Aluminium Salts Protects Mice from an Influenza A Virus That Expresses an Altered Nucleoprotein Sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes.     

Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors

Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses.     

Cardiovascular responses to central administration of mu and kappa opioid receptor agonist and antagonist in normal rats

The response to centrally administered beta-endorphin has been characterized by decreasing sympathetic nervous activity and decreased cardiovascular tone. We investigated the effect of the central administration of both mu and kappa opioid receptor agonist and antagonists on cardiovascular responses. The administration of the mu agonist, DAMGO (0.2nmol) increased the mean arterial pressure (MAP) and stimulated iliac vasoconstriction while higher doses (2 and 20nmol) decreased MAP and stimulated iliac vasodilation. The administration of the kappa receptor agonist, Dynorphin decreased the MAP and stimulated superior mesenteric vasodilation. beta-Funaltrexamine reduced MAP and superior mesenteric vasodilation while nor-binaltorphimine increased MAP and iliac and superior mesenteric vasoconstriction. We conclude that mu receptor activation decrease or increase MAP depending on the mu agonist concentration. However, kappa receptor activation is consistently associated with a decrease in MAP.     

Frequent occurrence of the human-specific Bacteroides fecal marker at an open coast marine beach: relationship to waves, tides and traditional indicators

Molecular genetic markers, such as those from fecal Bacteroides microorganisms, can link microbial pollution with its source, and have been used successfully in studies of sheltered aquatic environments. Their applicability to wave-driven, open coast environments has not been tested. We assessed the contribution of a tidal outlet to surf zone water quality in coastal Orange County, California, USA by measuring three traditional culture-based fecal indicator bacteria (FIB) as well as the human-specific Bacteroides molecular marker (HF marker) at four shoreline locations. We found that total and fecal coliform levels were higher during low tides than high tides at two of the four stations, and that this effect was strongest at the mouth of the tidal lagoon and decayed with distance from the outlet. The HF marker was detected in 23% and 47% of samples from the tidal outlet and 26% and 41% of samples from an adjacent recreational beach in 2005 and 2006 respectively. Surprisingly, the station farthest from the tidal outlet had the highest occurrence of the HF marker. We found no relationship between FIB abundance and occurrence of the HF marker for individual samples, but that when the data were considered together by year, higher FIB abundance was correlated with a higher incidence of the HF marker. DNA sequences of the HF marker recovered from this site were > 99% similar to those recovered from other states and countries, suggesting low global diversity of this marker. These data provide strong support for the idea that multiple time points and physical conditions should be considered when assessing coastal water quality.