A Pilot Study on the Physiological Effects of Three Essential Oils in Humans.

In the present study, the physiological effects on 32 humans exposed to experimental stress provoked by inhalation of the essential oils of East Indian sandalwood (Santalum album L.), Western Australian sandalwood (Santalum spicatum R.Br.) and lavender (Lavandula angustifolia MILL.) were investigated. During individual testing sessions, several saliva samples were collected, blood pressure was regularly measured and parameters of the autonomic nervous system (heart rate, skin conductance response) were continuously monitored. Salivary cortisol, as an endocrine stress indicator, was determined by time- resolved fluoroimmunoassay. Statistical analyses evidenced that the tested sandalwood essential oils significantly reduced systolic blood pressure, especially during the recreation phase. This finding corresponds with a distinct reduction of salivary cortisol levels during recreation in the Western Australian sandalwood oil compared with the control. In conclusion, the results demonstrate that essential oils can alleviate the physiological reactions to psychological stress and facilitate recovery after exposition to stress.

Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification.

Pancreatic cancer is one of the most lethal of all cancers. The median survival is six months and less than 5% of those diagnosed survive five years. Recurrent genetic deletions and amplifications in 72 pancreatic adenocarcinomas, the largest sample set analyzed to date for pancreatic cancer, were defined using comparative genomic hybridization The recurrent genetic alterations identified target a number of previously well-characterized genes, as well as regions that contain possible new oncogenes and tumor suppressor genes. We have focused on chromosome 19q13, a region frequently found amplified in pancreatic cancer and demonstrate how boundaries of common regions of mutation can be mapped and how a gene, in this case PAK4 amplified on chromosome19q13, can be functionally validated. We show that although the PAK4 gene is not activated by mutation in cell lines with gene amplification, an oncogenic form of the KRAS2 gene is present in these cells and oncogenic KRAS2 can activate PAK4. In fact in the three samples we identified with PAK4 gene amplification, the KRAS2 gene was activated and genomically amplified. The kinase activity of the PAK4 protein is significantly higher in cells with genomic amplification as compared to cells without amplification. Our study demonstrates the utility of analyzing copy number data in a large set of neoplasms to identify genes involved in cancer. We have generated a useful dataset which will be particularly useful for the pancreatic cancer community as efforts are undertaken to sequence the pancreatic cancer genome.

The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion.

The circumsporozoite protein (CSP) is the major surface protein of Plasmodium sporozoites, the infective stage of malaria. Although CSP has been extensively studied as a malaria vaccine candidate, little is known about its structure. Here, we show that CSP is proteolytically cleaved by a papain family cysteine protease of parasite origin. Our data suggest that the highly conserved region I, found just before the repeat region, contains the cleavage site. Cleavage occurs on the sporozoite surface when parasites contact target cells. Inhibitors of CSP processing inhibit cell invasion in vitro, and treatment of mice with E-64, a highly specific cysteine protease inhibitor, completely inhibits sporozoite infectivity in vivo.

Bordetella pertussis acquires resistance to complement-mediated killing in vivo.

In order to initially colonize a host, bacteria must avoid various components of the innate immune system, one of which is complement. The genus Bordetella includes three closely related species that differ in their ability to resist complement-mediated killing. Bordetella parapertussis and Bordetella bronchiseptica resist killing in naïve serum, a characteristic that may aid in efficient respiratory tract colonization and has been attributed to expression of O antigen. Bordetella pertussis lacks O antigen and is sensitive to naïve serum in vitro, yet it also efficiently colonizes the respiratory tract. Based on these observations, we hypothesized that B. pertussis may have an alternate mechanism to resist complement in vivo. While a number of reports on serum sensitivity of the bordetellae have been published, we show here that serum concentration and growth conditions can greatly alter the observed level of sensitivity to complement and that all but one strain of B. pertussis observed were sensitive to some level of naïve serum in vitro, particularly when there was excess complement. However, B. pertussis rapidly acquires increased resistance in vivo to naïve serum that is specific to the alternative pathway. Resistance is not efficiently acquired by B. parapertussis and B. bronchiseptica mutants lacking O antigen. This B. pertussis-specific mechanism of complement resistance does not appear to be dependent on either brkA or other genes expressed specifically in the Bvg(+) phase. This in vivo acquisition of alternative pathway resistance suggests that there is a novel O antigen-independent method by which B. pertussis evades complement-mediated killing.