Global trends in emerging infectious diseases

Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID 'events' (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease 'hotspots'). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.     

Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies.

The study of complex genetic traits in humans is limited by the expense and difficulty of ascertaining populations of sufficient sample size to detect subtle genetic contributions to disease. Here we introduce an application of a somatic cell hybrid construction strategy called conversion that maximizes the genotypic information from each sampled individual. The approach permits direct observation of individual haplotypes, thereby eliminating the need for collecting and genotyping DNA from family members for haplotype-based analyses. We describe experimental data that validate the use of conversion as a whole-genome haplotyping tool and evaluate the theoretical efficiency of using conversion-derived haplotypes instead of conventional genotypes in the context of haplotype-frequency estimation. We show that, particularly when phenotyping is expensive, conversion-based haplotyping can be more efficient and cost-effective than standard genotyping.     

PARAMAP vs. Isomap: A Comparison of Two Nonlinear Mapping Algorithms

Dimensionality reduction techniques are used for representing higher dimensional data by a more parsimonious and meaningful lower dimensional structure. In this paper we will study two such approaches, namely Carroll’s Parametric Mapping (abbreviated PARAMAP) (Shepard and Carroll, 1966) and Tenenbaum’s Isometric Mapping (abbreviated Isomap) (Tenenbaum, de Silva, and Langford, 2000). The former relies on iterative minimization of a cost function while the latter applies classical MDS after a preprocessing step involving the use of a shortest path algorithm to define approximate geodesic distances. We will develop a measure of congruence based on preservation of local structure between the input data and the mapped low dimensional embedding, and compare the different approaches on various sets of data, including points located on the surface of a sphere, some data called the "Swiss Roll data", and truncated spheres.     

TUSC3: functional duality of a cancer gene

Two decades ago, following a systematic screening of LOH regions on chromosome 8p22, TUSC3 has been identified as a candidate tumor suppressor gene in ovarian, prostate and pancreatic cancers. Since then, a growing body of evidence documented its clinical importance in various other types of cancers, and first initial insights into its molecular function and phenotypic effects have been gained, though the precise role of TUSC3 in different cancers remains unclear. As a part of the oligosaccharyltransferase complex, TUSC3 localizes to the endoplasmic reticulum and functions in final steps of N-glycosylation of proteins, while its loss evokes the unfolded protein response. We are still trying to figure out how this mechanistic function is reconcilable with its varied effects on cancer promotion. In this review, we focus on cancer-related effects of TUSC3 and envisage a possible role of TUSC3 beyond endoplasmic reticulum.     

Least squares algorithms for constructing constrained ultrametric and additive tree representations of symmetric proximity data

A mathematical programming algorithm is developed for fitting ultrametric or additive trees to proximity data where external constraints are imposed on the topology of the tree. The two procedures minimize a least squares loss function. The method is illustrated on both synthetic and real data. A constrained ultrametric tree analysis was performed on similarities between 32 subjects based on preferences for ten odors, while a constrained additive tree analysis was carried out on some proximity data between kinship terms. Finally, some extensions of the methodology to other tree fitting procedures are mentioned.The first author is supported as Bevoegdverklaard Navorser of the Belgian Nationaal Fonds voor Wetenschappelijk Onderzoek.     

Ontogenetic and habitat-related changes in diet of late larval and juvenile suckers (Catostomidae) in Upper Klamath Lake, Oregon

We describe ontogenetic patterns in the diets of shortnose and Lost River suckers (15.8–92.8 mm standard length) from Upper Klamath Lake in summer 1999. Both species made a transition from surface and planktonic prey to benthic prey at about 20–30 mm standard length, corresponding to the approximate size of the juvenile morphological transition. Surface prey was dominated by adult chironomids and undigestable pollen, while benthic prey was dominated by larval chironomids, chydorids, and ostracods. In the 15–20-mm size class, pollen made up >75% of food particles in 68% of specimens, and only 2 specimens in this size class lacked any pollen grains. A better understanding of the prey selection process in larval suckers is needed to determine the importance of this potential source of starvation. The planktonic prey eaten during the surface-to-benthic feeding transition were widely distributed in the lake, suggesting that larvae use emergent vegetation primarily as a refuge from predators. On a numerical basis, crustaceans and larval chironomids contributed most to the diets of larger juveniles. In specimens >40 mm, shortnose suckers ate more Tanytarsini and Lost River suckers ate more chironomid pupae and chydorids. In specimens >40 mm there was a strong habitat-related difference in diet: specimens collected in offshore samples ate more chironomid larvae and pupae, harpacticoid copepods, and chydorids, whereas onshore specimens ate more cyclopoid copepods and invertebrate eggs. The transition from onshore to offshore habitat appears to occur over a broad size range of about 40–90 mm.