The politics of one Oregon: the causes, consequences and prospects of overcoming the rural-urban divide

Presentation and paper from 2008 "Toward One Oregon" Conference

Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs.

OBJECTIVES: Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. METHODS: The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. RESULTS: All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. CONCLUSIONS: TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter

Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs

Objectives Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. Methods The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. Results All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. Conclusions TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporte

Receding ice drove parallel expansions in Southern Ocean penguins

International audienceClimate shifts are key drivers of ecosystem change. Despite the critical importance of Antarctica and the Southern Ocean for global climate, the extent of climate-driven ecological change in this region remains controversial. In particular, the biological effects of changing sea ice conditions are poorly understood. We hypothesize that rapid postglacial reductions in sea ice drove biological shifts across multiple widespread Southern Ocean species. We test for demographic shifts driven by climate events over recent millennia by analyzing population genomic datasets spanning 3 penguin genera ( Eudyptes , Pygoscelis , and Aptenodytes ). Demographic analyses for multiple species (macaroni/royal, eastern rockhopper, Adélie, gentoo, king, and emperor) currently inhabiting southern coastlines affected by heavy sea ice conditions during the Last Glacial Maximum (LGM) yielded genetic signatures of near-simultaneous population expansions associated with postglacial warming. Populations of the ice-adapted emperor penguin are inferred to have expanded slightly earlier than those of species requiring ice-free terrain. These concerted high-latitude expansion events contrast with relatively stable or declining demographic histories inferred for 4 penguin species (northern rockhopper, western rockhopper, Fiordland crested, and Snares crested) that apparently persisted throughout the LGM in ice-free habitats. Limited genetic structure detected in all ice-affected species across the vast Southern Ocean may reflect both rapid postglacial colonization of subantarctic and Antarctic shores, in addition to recent genetic exchange among populations. Together, these analyses highlight dramatic, ecosystem-wide responses to past Southern Ocean climate change and suggest potential for further shifts as warming continues

Community Management of Endemic Scabies in Remote Aboriginal Communities of Northern Australia: Low Treatment Uptake and High Ongoing Acquisition

Like many impoverished areas around the world, Aboriginal communities in Australia experience an unacceptably high burden of scabies, skin infections, and secondary complications. Young children are most at risk. Our study investigated scabies in a remote setting with very high rates of skin disease, a high level of household overcrowding, and limited infrastructure for sanitation and preventive health measures. We assessed uptake of scabies treatment and scabies acquisition following provision of treatment by a community-based skin program. In a household where scabies was present, we found that treatment with topical permethrin cream of all close contacts can significantly reduce a susceptible individual's risk of infection. Our findings also demonstrate the challenges of achieving a high level of treatment participation, with limited permethrin use observed among household contacts. This suggests an urgent need for a more practical treatment option. International efforts to reduce childhood morbidity and mortality have demonstrated the efficacy of numerous child health interventions but have also highlighted the deficits in their delivery and implementation. Experiences like this, where the effectiveness of a coordinated local program delivering an efficacious intervention is hampered by poor treatment uptake and ongoing transmission, are an important and timely message for researchers, program managers, and policy-makers

The Oregon Constitution and the Quest for Party Reform

40 p.In Part I, I provide a history of political parties in Oregon, describing their importance from before statehood to the present. This section explains how the role of political parties has changed over time and why party reform has come to look so appealing. In Part II, I examine three reform proposals that have been discussed in Oregon over the past several years: a nonpartisan legislature, the top-two primary, and fusion voting. I conclude by discussing other factors underlying Oregon’s political problems and some alternative solutions

By the Numbers: The Region Votes its Fate

The author examined how the residents in the five-county region of the metropolitan area (Clackamas, Columbia, Multnomah, Washington, and Yamhill) voted in the 2004 general election on selected ballot measures in order to understand the political values of the neighborhoods in which we live. Using geographic information systems (GIS), we mapped the distribution of votes by election precinct on what we thought were three of the most revealing measures: the constitutional amendment banning same-sex marriages (Measure 36), the initiative requiring state and local governments to pay landowners when land-use restrictions reduce property value (Measure 37), and the constitutional amendment limiting non-economic damages in medical malpractice lawsuits (Measure 35). In general, the maps revealed what most political observers already know about the metropolitan area: there is a polarization of voters in the region, with the more urban areas tending to be more liberal than the rural ones, and with the suburbs falling somewhere in between. Yet the maps reveal that there are important differences from neighborhood to neighborhood, and that the polarization is not as strong on some issues

Introduction: The Enduring Relevance of the State Assemblies

On July 30, 1619, 22 elected representatives convened in a small wooden church along the marshy banks of the James River to consider the laws governing the Virginia Colony. It was unbearably hot and humid during the six days that the assembly was in session and many of those attending were ill, including the colony’s governor and the assembly speaker. One burgess died mid-session. Despite these obstacles, the assembly was successful in ratifying the colony’s new charter, converting past instructions from the company’s leaders in England into law, and adopting several new laws that the burgesses themselves wanted to see enacted. Before adjourning, the assembly passed one final measure: approval of the first tax ever proposed by an American legislature, which required adult colonists to pay one pound of their best tobacco to the colonial government (Kammen 1969, 92–101)

Introduction: The Enduring Relevance of the State Assemblies

On July 30, 1619, 22 elected representatives convened in a small wooden church along the marshy banks of the James River to consider the laws governing the Virginia Colony. It was unbearably hot and humid during the six days that the assembly was in session and many of those attending were ill, including the colony’s governor and the assembly speaker. One burgess died mid-session. Despite these obstacles, the assembly was successful in ratifying the colony’s new charter, converting past instructions from the company’s leaders in England into law, and adopting several new laws that the burgesses themselves wanted to see enacted. Before adjourning, the assembly passed one final measure: approval of the first tax ever proposed by an American legislature, which required adult colonists to pay one pound of their best tobacco to the colonial government (Kammen 1969, 92–101)