Population structure and transmission dynamics of Plasmodium vivax in the Republic of Korea based on microsatellite DNA analysis

Background

In order to control malaria, it is important to understand the genetic structure of the parasites in each endemic area. Plasmodium vivax is widely distributed in the tropical to temperate regions of Asia and South America, but effective strategies for its elimination have yet to be designed. In South Korea, for example, indigenous vivax malaria was eliminated by the late 1970s, but re-emerged from 1993. We estimated the population structure and temporal dynamics of transmission of P. vivax in South Korea using microsatellite DNA markers.

Methodology/Principal Findings

We analyzed 255 South Korean P. vivax isolates collected from 1994 to 2008, based on 10 highly polymorphic microsatellite DNA loci of the P. vivax genome. Allelic data were obtained for the 87 isolates and their microsatellite haplotypes were determined based on a combination of allelic data of the loci. In total, 40 haplotypes were observed. There were two predominant haplotypes: H16 and H25. H16 was observed in 9 isolates (10%) from 1996 to 2005, and H25 in 27 (31%) from 1995 to 2003. These results suggested that the recombination rate of P. vivax in South Korea, a temperate country, was lower than in tropical areas where identical haplotypes were rarely seen in the following year. Next, we estimated the relationships among the 40 haplotypes by eBURST analysis. Two major groups were found: one composed of 36 isolates (41%) including H25; the other of 20 isolates (23%) including H16. Despite the low recombination rate, other new haplotypes that are genetically distinct from the 2 groups have also been observed since 1997 (H27).

Conclusions/Significance

These results suggested a continual introduction of P. vivax from other population sources, probably North Korea. Molecular epidemiology using microsatellite DNA of the P. vivax population is effective for assessing the population structure and transmission dynamics of the parasites - information that can assist in the elimination of vivax malaria in endemic areas.     

Effect of Intracellular Glutathione Level on the Production of 6-Methoxymellein in Cultured Carrot (Daucus carota) Cells

To produce phytoalexin, 6-methoxymellein (6-MM) was induced in suspension cultures of carrot (Daucus carota) by buthionine sulfoximine (BSO) and CuCl2. Addition of BSO (a specific inhibitor of glutathione [GSH] synthesis) to the cultures lowered the cellular GSH levels. This depletion of GSH was BSO-concentration dependent, and the extent of 6-MM accumulation was dependent on the GSH depletion. The accumulation of 6-MM induced by BSO was suppressed by exogenous GSH. Exogenous H2O2 stimulated the production of 6-MM when added 1 d after BSO treatment, whereas H2O2 added at time zero or on the 4th d of BSO treatment did not. Moreover, a synergistic effect of simultaneous addition of BSO and CuCl2 was observed. These results suggest that active oxygen species may be involved in the triggering of 6-MM synthesis.     

Phylogenetic diversity of non-nodulating Rhizobium associated with pine ectomycorrhizae

Most Rhizobium species described are symbionts that form nodules on legume roots; however, non-nodulating strains of Rhizobium are also widespread in nature. Unfortunately, knowledge of non-nodulating Rhizobium is quite limited compared with nodulating Rhizobium . Here, we studied the phylogenetic diversity of Rhizobium species that inhabit Japanese red pine roots ( Pinus densiflora ). Because fine roots of pine trees are usually colonized by ectomycorrhizal fungi in nature, we mainly used ectomycorrhizal root tips for bacterial isolation. Out of 1195 bacteria isolated from 75 independent root samples from the field and greenhouse experiments, 102 isolates were confirmed to be Rhizobium following partial 16S rRNA gene analysis. Rhizobium species were occasionally dominant in culturable bacterial communities, whereas no Rhizobium species were isolated from the soil itself. Molecular phylogenetic analyses using 16S rRNA, atpD , and recA gene sequences revealed that isolated Rhizobium strains were phylogenetically diverse and that several were distantly related to known Rhizobium species. Considering that a single species of pine is associated with unique and phylogenetically diverse Rhizobium populations, we should pay more attention to non-nodulating strains to better understand the diversity, ecology, and evolution of the genus Rhizobium and plant– Rhizobium associations.     

Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans

Here we report the cloning of a full-length cDNA encoding the human ortholog (HSulf-1) of the developmentally regulated putative sulfatases QSulf-1 (Dhoot, G. K., Gustafsson, M. K., Ai, X., Sun, W., Standiford, D. M., and Emerson, C. P., Jr. (2001) Science 293, 1663-1666) and RSulfFP1 (Ohto, T., Uchida, H., Yamazaki, H., Keino-Masu, K., Matsui, A., and Masu, M. (2002) Genes Cells 7, 173-185) as well as a cDNA encoding a closely related protein, designated HSulf-2. We have also obtained cDNAs for the mouse orthologs of both Sulfs. We demonstrate that the proteins encoded by both classes of cDNAs are endoproteolytically processed in the secretory pathway and are released into conditioned medium of transfected CHO cells. We demonstrate that the mammalian Sulfs exhibit arylsulfatase activity with a pH optimum in the neutral range; moreover, they can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Taken together, our results establish that the mammalian Sulfs are extracellular endosulfatases with strong potential for modulating the interactions of heparan sulfate proteoglycans in the extracellular microenvironment.     

Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional Study of Patients and Physicians

Background

Decision-making capacity to provide informed consent regarding treatment is essential among cancer patients. The purpose of this study was to identify the frequency of decision-making incapacity among newly diagnosed older patients with hematological malignancy receiving first-line chemotherapy, to examine factors associated with incapacity and assess physicians’ perceptions of patients’ decision-making incapacity.

Methods

Consecutive patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Decision-making capacity was assessed using the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised (SICIATRI-R). Cognitive impairment, depressive condition and other possible associated factors were also evaluated.

Results

Among 139 eligible patients registered for this study, 114 completed the survey. Of these, 28 (25%, 95% confidence interval [CI]: 17%-32%) were judged as having some extent of decision-making incompetency according to SICIATRI-R. Higher levels of cognitive impairment and increasing age were significantly associated with decision-making incapacity. Physicians experienced difficulty performing competency assessment (Cohen’s kappa -0.54).

Conclusions

Decision-making incapacity was found to be a common and under-recognized problem in older patients with cancer. Age and assessment of cognitive impairment may provide the opportunity to find patients that are at a high risk of showing decision-making incapacity.     

Comparative Analysis of kdp and ktr Mutants Reveals Distinct Roles of the Potassium Transporters in the Model Cyanobacterium Synechocystis sp. Strain PCC 6803

Photoautotrophic bacteria have developed mechanisms to maintain K⁺ homeostasis under conditions of changing ionic concentrations in the environment. Synechocystis sp. strain PCC 6803 contains genes encoding a well-characterized Ktr-type K⁺ uptake transporter (Ktr) and a putative ATP-dependent transporter specific for K⁺ (Kdp). The contributions of each of these K⁺ transport systems to cellular K⁺ homeostasis have not yet been defined conclusively. To verify the functionality of Kdp, kdp genes were expressed in Escherichia coli, where Kdp conferred K⁺ uptake, albeit with lower rates than were conferred by Ktr. An on-chip microfluidic device enabled monitoring of the biphasic initial volume recovery of single Synechocystis cells after hyperosmotic shock. Here, Ktr functioned as the primary K⁺ uptake system during the first recovery phase, whereas Kdp did not contribute significantly. The expression of the kdp operon in Synechocystis was induced by extracellular K⁺ depletion. Correspondingly, Kdp-mediated K⁺ uptake supported Synechocystis cell growth with trace amounts of external potassium. This induction of kdp expression depended on two adjacent genes, hik20 and rre19, encoding a putative two-component system. The circadian expression of kdp and ktr peaked at subjective dawn, which may support the acquisition of K⁺ required for the regular diurnal photosynthetic metabolism. These results indicate that Kdp contributes to the maintenance of a basal intracellular K⁺ concentration under conditions of limited K⁺ in natural environments, whereas Ktr mediates fast potassium movements in the presence of greater K⁺ availability. Through their distinct activities, both Ktr and Kdp coordinate the responses of Synechocystis to changes in K⁺ levels under fluctuating environmental conditions.     

Feedback between size balance and consumption strongly affects the consequences of hatching phenology in size‐dependent predator–prey interactions

In many size‐dependent predator–prey systems, hatching phenology strongly affects predator–prey interaction outcomes. Early‐hatched predators can easily consume prey when they first interact because they encounter smaller prey. However, this process by itself may be insufficient to explain all predator–prey interaction outcomes over the whole interaction period because the predator–prey size balance changes dynamically throughout their ontogeny. We hypothesized that hatching phenology influences predator–prey interactions via a feedback mechanism between the predator–prey size balance and prey consumption by predators. We experimentally tested this hypothesis in an amphibian predator–prey model system. Frog tadpoles Rana pirica were exposed to a predatory salamander larva Hynobius retardatus that had hatched 5, 12, 19 or 26 days after the frog tadpoles hatched. We investigated how the salamander hatch timing affected the dynamics of prey mortality, size changes of both predator and prey, and their subsequent life history (larval period and size at metamorphosis). The predator–prey size balance favoured earlier hatched salamanders, which just after hatching could successfully consume more frog tadpoles than later hatched salamanders. The early‐hatched salamanders grew rapidly and their accelerated growth enabled them to maintain the predator‐superior size balance; thus, they continued to exert strong predation pressure on the frog tadpoles in the subsequent period. Furthermore, frog tadpoles exposed to the early‐hatched salamanders were larger at metamorphosis and had a longer larval period than other frog tadpoles. These results suggest that feedback between the predator‐superior size balance and prey consumption is a critical mechanism that strongly affects the impacts of early hatching of predators in the short‐term population dynamics and life history of the prey. Because consumption of large nutrient‐rich prey items supports the growth of predators, a similar feedback mechanism may be common and have strong impacts on phenological shifts in size‐dependent trophic relationships.     

Rapamycin induces binding activity to the terminal oligopyrimidine tract of ribosomal protein mRNA in rats

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen. The relative order of potency in releasing angiotensin II by the three proteinases at equivalent concentrations is cathepsin G > elastase > proteinase 3. When all three proteinases are used together, the release of angiotensin II is greater than the sum of the release when each proteinase is used individually. Cathepsin G and elastase can also degrade angiotensin II, reactions which might be important in regulating the activity of angiotensin II. The release and degradation of angiotensin II by the neutrophil proteinases are reactions which could play a role in the local inflammatory response and wound healing.