Efficacy of two lion conservation programs in Maasailand, Kenya.

Lion (Panthera leo) populations are in decline throughout most of Africa. The problem is particularly acute in southern Kenya, where Maasai pastoralists have been spearing and poisoning lions at a rate that will ensure near term local extinction. We investigated 2 approaches for improving local tolerance of lions: compensation payments for livestock lost to predators and Lion Guardians, which draws on local cultural values and knowledge to mitigate livestock-carnivore conflict and monitor carnivores. To gauge the overall influence of conservation intervention, we combined both programs into a single conservation treatment variable. Using 8 years of lion killing data, we applied Manski's partial identification approach with bounded assumptions to investigate the effect of conservation treatment on lion killing in 4 contiguous areas. In 3 of the areas, conservation treatment was positively associated with a reduction in lion killing. We then applied a generalized linear model to assess the relative efficacy of the 2 interventions. The model estimated that compensation resulted in an 87-91% drop in the number of lions killed, whereas Lion Guardians (operating in combination with compensation and alone) resulted in a 99% drop in lion killing.

Data-poor management of African lion hunting using a relative index of abundance.

Sustainable management of terrestrial hunting requires managers to set quotas restricting offtake. This often takes place in the absence of reliable information on the population size, and as a consequence, quotas are set in an arbitrary fashion, leading to population decline and revenue loss. In this investigation, we show how an indirect measure of abundance can be used to set quotas in a sustainable manner, even in the absence of information on population size. Focusing on lion hunting in Africa, we developed a simple algorithm to convert changes in the number of safari days required to kill a lion into a quota for the following year. This was tested against a simulation model of population dynamics, accounting for uncertainties in demography, observation, and implementation. Results showed it to reliably set sustainable quotas despite these uncertainties, providing a robust foundation for the conservation of hunted species.

Non-adaptive phenotypic evolution of the endangered carnivore Lycaon pictus.

Decline in wild populations as a result of anthropogenic impact is widely considered to have evolutionary consequences for the species concerned. Here we examine changes in developmental stability in the painted hunting dog (Lycaon pictus), which once occupied most of sub-Saharan Africa but has undergone a dramatic population decline in the last century. Fluctuating asymmetry (FA) was used as an indicator of developmental stability and measured in museum skull specimens spanning a hundred year period. A comparison with the more ubiquitous black-backed jackal (Canis mesomelas) revealed FA in L. pictus to be high. Furthermore, the data indicate a temporal increase in FA over time in L. pictus, corresponding to the period of its population decline. The high rate of change is compatible with genetic drift although environmental factors are also likely to be important. Lowering developmental stability over time may have direct fitness consequences and as such represents an unacknowledged threat to future resilience of the population.

Incentivizing monitoring and compliance in trophy hunting.

Conservation scientists are increasingly focusing on the drivers of human behavior and on the implications of various sources of uncertainty for management decision making. Trophy hunting has been suggested as a conservation tool because it gives economic value to wildlife, but recent examples show that overharvesting is a substantial problem and that data limitations are rife. We use a case study of trophy hunting of an endangered antelope, the mountain nyala (Tragelaphus buxtoni), to explore how uncertainties generated by population monitoring and poaching interact with decision making by 2 key stakeholders: the safari companies and the government. We built a management strategy evaluation model that encompasses the population dynamics of mountain nyala, a monitoring model, and a company decision making model. We investigated scenarios of investment into antipoaching and monitoring by governments and safari companies. Harvest strategy was robust to the uncertainty in the population estimates obtained from monitoring, but poaching had a much stronger effect on quota and sustainability. Hence, reducing poaching is in the interests of companies wishing to increase the profitability of their enterprises, for example by engaging community members as game scouts. There is a threshold level of uncertainty in the population estimates beyond which the year-to-year variation in the trophy quota prevented planning by the safari companies. This suggests a role for government in ensuring that a baseline level of population monitoring is carried out such that this level is not exceeded. Our results illustrate the importance of considering the incentives of multiple stakeholders when designing frameworks for resource use and when designing management frameworks to address the particular sources of uncertainty that affect system sustainability most heavily. Incentivando el Monitoreo y el Cumplimiento en la Caza de Trofeos.

Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.

Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1-specific CTLs in vivo. We estimate that only 2% of productively infected CD4+ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 10(7)) per day but are not responsible for the majority of infected cell death.

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1.

BACKGROUND: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear. RESULTS: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission. CONCLUSION: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.

Sexual transmission of single human immunodeficiency virus type 1 virions encoding highly polymorphic multisite cytotoxic T-lymphocyte escape variants.

Antigenic variation inherent in human immunodeficiency virus type 1 (HIV-1) virions that successfully instigate new infections transferred by sex has not been well defined. Yet this is the viral "challenge" which any vaccine-induced immunity must deal with. Closely timed comparisons of the virus circulating in the "donor" and that which initiates new infection are difficult to carry out rigorously, as suitable samples are very hard to get in the face of ethical hurdles. Here we investigate HIV-1 variation in four homosexual couples where we sampled blood from both parties within several weeks of the estimated transmission event. We analyzed variation within highly immunogenic HIV-1 internal proteins encoding epitopes recognized by cytotoxic T lymphocytes (CTLs). These responses are believed to be crucial as a means of containing viral replication. In the donors we detected virions capable of evading host CTL recognition at several linked epitopes of distinct HLA class I restriction. When a donor transmitted escape variants to a recipient with whom he had HLA class I molecules in common, the recipient's CTL response to those epitopes was prevented, thus impeding adequate viral control. In addition, we show that even when HLA class I alleles are disparate in the transmitting couple, a single polymorphism can abolish CTL recognition of an overlapping epitope of distinct restriction and so confer immune escape properties to the recipient's seroconversion virus. In donors who are themselves controlling an early, acute infection, the precise timing of onward transmission is a crucial determinant of the viral variants available to compose the inoculum.

Intrapatient escape in the A*0201-restricted epitope SLYNTVATL drives evolution of human immunodeficiency virus type 1 at the population level.

The hypothesis that the intrapatient emergence of cytotoxic T-lymphocyte escape variants contributes to the evolution of human immunodeficiency virus type 1 at the population (interpatient) level was tested using the HLA-A*0201-restricted gag p17 epitope SLYNTVATL. Using a simple experimental design, we investigated the evolutionary processes operating within this epitope among patients while compensating for the confounding influence of intrapatient natural selection. Using this approach, we revealed a pattern of A*0201-driven escape within patients, followed by the sustained transmission of these escape variants among patients irrespective of their HLA type.

Assessment of doxylamine influence on mixed function oxidase activity upon multiple dose oral administration to normal volunteers.

The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5 mg of doxylamine succinate, placebo, or 30 mg of phenobarbital administered orally every 6 h for 17 days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 micrograms) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.

Antisecretory and antiinflammatory properties of bismuth subsalicylate.

The antisecretory properties of Pepto-Bismol (PB) and its active ingredient, bismuth subsalicylate (BSS), were studied in ligated (rabbit and pig) and unligated (rat) intestinal-segment models. When PB was administered to segments before intestinal inoculation with heat-labile (LT) Escherichia coli or Vibrio cholerae enterotoxins, the inhibition of fluid accumulation was 74%-94% and 60%-91%, respectively. In the pig, the percentages of inhibition by PB of fluid accumulation produced by organisms or toxins were 69% for E. coli P57 producing heat-stable enterotoxin (ST), 89%-95% for E. coli P155 producing ST and LT, 52% for ST alone, 95% for LT alone, and 73% for ST and LT. When PB was administered to the pig immediately after inoculation with E. coli P57, E. coli P155, ST alone, LT alone, or ST and LT, the percentages of inhibition of fluid accumulation were 76%, 80%, 56%, 97%, and 69%, respectively. However, in the rabbit and rat, PB failed to inhibit fluid accumulation when it was administered 5-60 minutes after inoculation of cholera or E. coli LT enterotoxins. In the rabbit the combination of BSS and the vehicle of PB was synergistic in preventing the fluid accumulation normally produced by cholera toxin. Finally, when PB or BSS was administered 30 minutes before intestinal inoculation with arachidonic acid in a rat model of inflammatory diarrhea, the percentages of inhibition of fluid accumulation ranged, in a dose-responsive fashion, from 16% to 113% for PB and from 25% to 111% for BSS.