Isomeric triterpenoids from Peritassa campestris

An investigation of the MeOH extract from the roots of Peritassa campestris (Hippocrateaceae) afforded two isomeric seco-A-ring quinonemethide triterpenoids, campestrine-I (1) and -II (2). This appears to be the first report of a C26,-type triterpene carbon skeleton from the Celastraceae or Hippocrateaceae families. The structures were elucidated on the basis of spectral data, particularly HMQC, HMBC and NOE experiments.     

Origin and Population Dynamics of a Novel HIV-1 Subtype G Clade Circulating in Cape Verde and Portugal

The human immunodeficiency virus type 1 (HIV-1) subtype G is the most prevalent and second most prevalent HIV-1 clade in Cape Verde and Portugal, respectively; but there is no information about the origin and spatiotemporal dispersal pattern of this HIV-1 clade circulating in those countries. To this end, we used Maximum Likelihood and Bayesian coalescent-based methods to analyze a collection of 578 HIV-1 subtype G pol sequences sampled throughout Portugal, Cape Verde and 11 other countries from West and Central Africa over a period of 22 years (1992 to 2013). Our analyses indicate that most subtype G sequences from Cape Verde (80%) and Portugal (95%) branched together in a distinct monophyletic cluster (here called G_CV-PT). The G_CV-PT clade probably emerged after a single migration of the virus out of Central Africa into Cape Verde between the late 1970s and the middle 1980s, followed by a rapid dissemination to Portugal a couple of years later. Reconstruction of the demographic history of the G_CV-PT clade circulating in Cape Verde and Portugal indicates that this viral clade displayed an initial phase of exponential growth during the 1980s and 1990s, followed by a decline in growth rate since the early 2000s. Our data also indicate that during the exponential growth phase the G_CV-PT clade recombined with a preexisting subtype B viral strain circulating in Portugal, originating the CRF14_BG clade that was later disseminated to Spain and Cape Verde. Historical and recent human population movements between Angola, Cape Verde and Portugal probably played a key role in the origin and dispersal of the G_CV-PT and CRF14_BG clades.     

Spatiotemporal Aspects of Hendra Virus Infection in Pteropid Bats (Flying-Foxes) in Eastern Australia

Hendra virus (HeV) causes highly lethal disease in horses and humans in the eastern Australian states of Queensland (QLD) and New South Wales (NSW), with multiple equine cases now reported on an annual basis. Infection and excretion dynamics in pteropid bats (flying-foxes), the recognised natural reservoir, are incompletely understood. We sought to identify key spatial and temporal factors associated with excretion in flying-foxes over a 2300 km latitudinal gradient from northern QLD to southern NSW which encompassed all known equine case locations. The aim was to strengthen knowledge of Hendra virus ecology in flying-foxes to improve spillover risk prediction and exposure risk mitigation strategies, and thus better protect horses and humans. Monthly pooled urine samples were collected from under roosting flying-foxes over a three-year period and screened for HeV RNA by quantitative RT-PCR. A generalised linear model was employed to investigate spatiotemporal associations with HeV detection in 13,968 samples from 27 roosts. There was a non-linear relationship between mean HeV excretion prevalence and five latitudinal regions, with excretion moderate in northern and central QLD, highest in southern QLD/northern NSW, moderate in central NSW, and negligible in southern NSW. Highest HeV positivity occurred where black or spectacled flying-foxes were present; nil or very low positivity rates occurred in exclusive grey-headed flying-fox roosts. Similarly, little red flying-foxes are evidently not a significant source of virus, as their periodic extreme increase in numbers at some roosts was not associated with any concurrent increase in HeV detection. There was a consistent, strong winter seasonality to excretion in the southern QLD/northern NSW and central NSW regions. This new information allows risk management strategies to be refined and targeted, mindful of the potential for spatial risk profiles to shift over time with changes in flying-fox species distribution.     

Illegal hunting and law enforcement during a period of economic decline in Zimbabwe: A case study of northern Gonarezhou National Park and adjacent areas

Illegal hunting of wildlife, or top-down harvesting, is a major issue in today's society, particularly in tropical ecosystems. There has been widespread concern about increasing illegal hunting of wildlife in most conservation areas in Zimbabwe following the political instability and economic decline the country faced since 2000. In this study, we focused on the northern Gonarezhou National Park (GNP), a large and unfenced protected area, and adjacent communal areas in southern Zimbabwe. We hypothesised that illegal hunting activities would (1) be perceived to have increased due to economic collapse and (2) vary with law enforcement efforts. A total of 236 local residents from eight villages adjacent to the northern GNP were interviewed using semi-structured questionnaires from December 2010 to May 2011, and law enforcement data for northern GNP between 2000 and 2010 were retrieved from the park law enforcement database. A total of 26 animal species were reportedly hunted. Bushmeat consumption and the need for local trade to raise income were reported as the main reasons behind illegal hunting. Contrary to the first hypothesis, the majority of respondents (n = 156, 66%) reported that illegal hunting activities had declined between 2000 and 2010 largely due to increased park protection as also supported by law enforcement data. A total of 22 animal species were recorded as having been illegally hunted in northern GNP. The number of illegal hunters arrested declined with increased law enforcement efforts although the number of wire snares recovered and hunting dogs shot appeared to increase following increased law enforcement efforts. These results partly support the second hypothesis that illegal hunting activities would vary with law enforcement efforts.     

Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism

Gemcitabine (GEM, 2′,2′-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of < 20%. The purpose of our work was to improve GEM activity by addition of cannabinoids. Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments. The antiproliferative synergism is prevented by the radical scavenger N-acetyl--cysteine and by the specific NF-κB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-κB by GEM is required for this effect. In addition, we report that neither apoptotic nor cytostatic mechanisms are responsible for the synergistic cell growth inhibition, which is strictly associated with the enhancement of endoplasmic reticulum stress and autophagic cell death. Noteworthy, the antiproliferative synergism is stronger in GEM-resistant pancreatic cancer cell lines compared with GEM-sensitive pancreatic cancer cell lines. The combined treatment strongly inhibits growth of human pancreatic tumor cells xenografted in nude mice without apparent toxic effects. These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells.