Homology model of thyroxine binding globulin and elucidation of the thyroid hormone binding site.

The tertiary structure of thyroxine binding globulin (TBG) has been modelled on the basis of its close homology to alpha 1-antitrypsin, the archetype of the serine protease inhibitor (serpin) superfamily. Energy minimization was applied to the model to refine the structure further. The putative thyroid hormone binding region suggested in previous labelling studies was found to exist within a beta-barrel structure of complementary dimensions to the thyroid hormones. The model also revealed that the binding cleft provides the hydrophobic environment and specific ionic interaction sites deemed important for thyroid hormone binding. The model is in good agreement with evidence derived from previously reported T3 and T4 binding, stability and isoelectric focussing studies of TBG and TBG variants. Finally, T4 analogue and drug binding studies have enabled us to postulate the orientation and manner of hormone binding to TBG. This may prove to be of assistance in the development of potent and specific, non-thyroidal ligands and also aid in the understanding of physiological thyroid hormone binding interactions.     

A species of Schellackia (Apicomplexa: Lankesterellidae) parasitising east and southeast Asian lizards

Schellackia orientalis n. sp. parasitises the Japanese lizard Takydromus tachydromoides on Honshu and Takydromus sexlineatus in Thailand. Merogony and gamogony occur in the epithelium of the small intestine, and octonucleate oöcysts form in the lamina propria. In infections induced by inoculation of infected blood, sporozoites appeared in blood cells 17–56 days post-inoculation, initially in any type of white blood cell but most commonly in macrophages and monocytes. Both erythroid and leucocytic cells were parasitised after five days. This haemococcidian is another component of the symbiotic complex found in Takydromus species of eastern and southeastern Asia.     

Disruption of Rhino Demography by Poachers May Lead to Population Declines in Kruger National Park,South Africa

The onslaught on the World’s rhinoceroses continues despite numerous initiatives aimed at curbing it. When losses due to poaching exceed birth rates, declining rhino populations result. We used previously published estimates and growth rates for black rhinos (2008) and white rhinos (2010) together with known poaching trends at the time to predict population sizes and poaching rates in Kruger National Park, South Africa for 2013. Kruger is a stronghold for the south-eastern black rhino and southern white rhino. Counting rhinos on 878 blocks 3x3 km in size using helicopters, estimating availability bias and collating observer and detectability biases allowed estimates using the Jolly’s estimator. The exponential escalation in number of rhinos poached per day appears to have slowed. The black rhino estimate of 414 individuals (95% confidence interval: 343-487) was lower than the predicted 835 individuals (95% CI: 754-956). The white rhino estimate of 8,968 individuals (95% CI: 8,394-9,564) overlapped with the predicted 9,417 individuals (95% CI: 7,698-11,183). Density- and rainfall-dependent responses in birth- and death rates of white rhinos provide opportunities to offset anticipated poaching effects through removals of rhinos from high density areas to increase birth and survival rates. Biological management of rhinos, however, need complimentary management of the poaching threat as present poaching trends predict detectable declines in white rhino abundances by 2018. Strategic responses such as anti-poaching that protect supply from illegal harvesting, reducing demand, and increasing supply commonly require crime network disruption as a first step complimented by providing options for alternative economies in areas abutting protected areas.     

Two new trypanosome species from East African cordylid lizards

Two species ofTrypanosoma are described from East African cordylid lizards.Trypanosoma zonuri n. sp. was found in a disjunct population ofCordylus cordylus on the western slope of Ngorongoro Crater in Arusha Region, northern Tanzania. It has the appearance of a delicate and fragile trypanosome, slightly over half the size of the robust, leaf-likeT. cordyli n. sp. that parasitisesCordylus t. tropidosternum in the Rondo Forest, Lindi Region, southern Tanzania. These are the first trypanosome species recorded from the saurian family Cordylidae in East Africa.     

A Mathematical Framework for Combining Decisions of Multiple Experts toward Accurate and Remote Diagnosis of Malaria Using Tele-Microscopy

We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected). To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing ‘slide-level’ diagnosis by using individual ‘cell-level’ diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform.     

Experimental Evolution of a Bacteriophage Virus Reveals the Trajectory of Adaptation across a Fecundity/Longevity Trade-Off

Life history theory attempts to account for how organisms lead their lives, balancing the conflicting demands of reproduction and survival. Here, we track the genomic and phenotypic evolution of the bacteriophage virus T7 across a postulated fecundity/longevity constraint. We adapted T7 to a challenging survival environment (6M urea). Our evolved strain displayed a significant improvement in propagule survival, coupled with a significant loss of fecundity (reduced growth rate on host cells). However, the increased resistance to urea did not generalise to increased resistance against temperature stress, highlighting that propagule durability is environment dependent. Previous comparative studies predicted that changes in propagule resistance would be mediated by changes in capsid proteins or gene deletions. In contrast, we found that point mutations in internal core protein genes (6.7 and 16) were responsible for the increased urea resistance of our evolved strain. Prior to the emergence of the 6.7 and 16 mutations, a distinct set of 5-point mutations peaked at over 20% prevalence before attenuating, suggestive of negative epistatic interactions during adaptation. Our results illustrate that parasites can adapt to specific transmission environments, and that this adaptation can impose costs on the subsequent ability to exploit host cells, potentially constraining durable parasites to lower virulence.     

Studies on ulcerative dermal necrosis of salmonids

Fourteen fresh run salmon Satmo salar L. with early extant lesions of ulcerative dermal necrosis (UDN) were kept in separate tanks and treated with zinc free malachite green. Ten of the fish were held at 10° C and 4 at 2° C. The treatment precluded infection with Saprolegnia fungus and allowed natural resolution of the lesions. There was a marked difference in rate of healing between warm and cold water conditions.
Histological examination of healing lesions at different stages showed that there was a primary invasion of cuboidal epithelium over the collagen scar followed by a phase of disorganized proliferation which eventually organized itself into normal epithelium. Melanocytes were very obvious in the dermis of healing lesions.