Surveillance of vivax malaria vectors and civilian patients for malaria high-risk areas in northern Gyeonggi and Gangwon Provinces near the demilitarized zone,Republic of Korea, 2003–2006

After re-emergence of malaria in 1993, a continued increase in Plasmodium vivax cases was observed from 1993 to 2006 in northern Gyeonggi and Gangwon Provinces adjacent to the demilitarized zone separating North from South Korea. Annual parasite incidence per 1000 people ranged from 0.33 in 2004 to 0.89 in 2006. While malaria case rates declined (22.6%) in 2004, they increased 75.1% in 2005 and 51.7% in 2006 from the previous years. An initial incorrect diagnosis of 46.8% of malaria cases as common cold resulted in a mean delay of 1.3 days for the detection malarial parasites. Of the total cases, 10.2% from December to May were due to latent intrinsic incubation infections acquired the previous malaria season and the rest of the cases from June to November were either latent or short incubation infections. Overall, the peak anopheline population occurred from July to September, resulting in a similar peak in malaria cases. While malaria cases increased during 2005–2006, anopheline populations, based on trap indices, were not significantly different during 4 years of surveillance. To decrease the malaria patient infective period to mosquitoes, public health centers in Paju and Cheorwon in 2006 prescribed chloroquine + primaquine at days 0–3 after initial malaria diagnosis followed by an additional 11 days of primaquine (early primaquine treatment), rather than chloroquine on days 0–3 and primaquine on days 4–17 (delayed primaquine treatment). A reduction in the malaria parasite incidence during 2007 was recorded for the two locations offering the early primaquine treatment relative to other locations using the delayed primaquine treatment.     

Early evolution of metazoan serine/threonine and tyrosine kinases: identification of selected kinases in marine sponges

The phylum Porifera (sponges) was the first to diverge from the common ancestor of the Metazoa. In this study, six cDNAs coding for protein- serine/threonine kinases (PS/TKs) are presented; they have been isolated from libraries obtained from the demosponges Geodia cydonium and Suberites domuncula and from the calcareous sponge Sycon raphanus. Sequence alignments of the catalytic domains revealed that two major families of PS/TK, the "conventional" (Ca(2+)-dependent) protein kinase C (PKC), the cPKC subfamily, as well as the "novel" (Ca(2+)- independent) PKC (nPKC), form two separate clusters. In each cluster, the sequence from S. raphanus diverges first. To approach the question about the origin of protein-tyrosine kinases (PTK), which are found only in Metazoa, we analyzed two additional PS/TKs which have been cloned from S. domuncula: the stress-responsive protein kinase (KRSvSD) and the protein-kinase-C-related kinase (PRKvSD). The construction of the phylogenetic tree, comprising the eight PS/TKs and the PTK cloned previously from G. cydonium, revealed that the PTK derived from the branch including the KRSvSD kinase. These data facilitate the first molecular approach to elucidate the origin of metazoan PTK within the PS/TK superfamily.      

Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids

The cytochrome P450 arachidonic acid epoxygenase metabolites, the epoxyeicosatrienoic acids (EETs) are powerful, nonregioselective, stimulators of cell proliferation. In this study we compared the ability of the four EETs (5,6-, 8,9-, 11,12-, and 14,15-EETs) to regulate endothelial cell proliferation in vitro and angiogenesis in vivo and determined the molecular mechanism by which EETs control these events. Inhibition of the epoxygenase blocked serum-induced endothelial cell proliferation, and exogenously added EETs rescued cell proliferation from epoxygenase inhibition. Studies with selective ERK, p38 MAPK, or PI3K inhibitors revealed that whereas activation of p38 MAPK is required for the proliferative responses to 8,9- and 11,12-EET, activation of PI3K is necessary for the cell proliferation induced by 5,6- and 14,15-EET. Among the four EETs, only 5,6- and 8,9-EET are capable of promoting endothelial cell migration and the formation of capillary-like structures, events that are dependent on EET-mediated activation of ERK and PI3K. Using subcutaneous sponge models, we showed that 5,6- and 8,9-EET are pro-angiogenic in mice and that their neo-vascularization effects are enhanced by the co-administration of an inhibitor of EET enzymatic hydration, presumably because of reduced EET metabolism and inactivation. These studies identify 5,6- and 8,9-EET as powerful and selective angiogenic lipids, provide a functional link between the EET proliferative chemotactic properties and their angiogenic activity, and suggest a physiological role for them in angiogenesis and de novo vascularization.     

Unusual filamentous virus-like particles in symptomless blackberry associated with severe leaf curling in the virus indicator Rubus macraei, and anomalous data using a degenerate badnavirus primer in PCR of Rubus species

Electron microscopy of ultrathin sections of leaves of symptomless Himalaya Giant blackberry and of the virus indicator species, Rubus macraei, showing severe leaf curl symptoms following graft inoculation with scions from this blackberry, detected highly flexuous virus‐like particles with an unusual ‘beaded’ structure. Such particles were restricted to a few vascular cells and were distinct from P‐protein common in some such cells. This virus, provisionally named Hawaiian rubus leaf curl virus (HRLCV), symptomlessly infected a wide range of Rubus species and cultivars. Badnavirus‐like bacilliform particles were observed in some cells of a single R. macraei plant showing leaf curl symptoms following graft inoculation with the causal agent of this disease symptom from Himalaya Giant blackberry after passage through red raspberry, but not in any other material. PCR with primer sets for the badnaviruses Rubus yellow net virus and Gooseberry veinbanding associated virus, showed that no Rubus sources studied contained these viruses. However, using a sequence‐specific primer set designed from the sequence of the product generated with a badnavirus degenerate primer set, a specific product was amplified from healthy plants of all of 16 raspberry cultivars and two Rubus species, but not from 16 blackberry cultivars (including cv. Himalaya Giant). All of these sources were free from viruses known to occur in Rubus. Sequence analysis of this product showed no homology with any known badnavirus, or with any other published sequences. It seems most likely therefore that a region of the raspberry genome has been amplified using the degenerate badnavirus primer set and that it is absent from the blackberry genome.     

Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses

Introduction  

Stressful events are thought to contribute to the aetiology, maintenance and exacerbation of rheumatic diseases. Given the growing interest in acute stress responses and disease, this review investigates the impact of real-life experimental psychosocial, cognitive, exercise and sensory stressors on autonomic, neuroendocrine and immune function in patients with inflammatory rheumatic diseases.     

Mouse EP3 alpha, beta, and gamma receptor variants reduce tumor cell proliferation and tumorigenesis in vivo

Prostaglandin E(2), which exerts its functions by binding to four G protein-coupled receptors (EP1-4), is implicated in tumorigenesis. Among the four E-prostanoid (EP) receptors, EP3 is unique in that it exists as alternatively spliced variants, characterized by differences in the cytoplasmic C-terminal tail. Although three EP3 variants, alpha, beta, and gamma, have been described in mice, their functional significance in regulating tumorigenesis is unknown. In this study we provide evidence that expressing murine EP3 alpha, beta, and gamma receptor variants in tumor cells reduces to the same degree their tumorigenic potential in vivo. In addition, activation of each of the three mEP3 variants induces enhanced cell-cell contact and reduces cell proliferation in vitro in a Rho-dependent manner. Finally, we demonstrate that EP3-mediated RhoA activation requires the engagement of the heterotrimeric G protein G(12). Thus, our study provides strong evidence that selective activation of each of the three variants of the EP3 receptor suppresses tumor cell function by activating a G(12)-RhoA pathway.     

Male and female brain evolution is subject to contrasting selection pressures in primates

The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social brain" hypothesis) is now widely accepted. Some of the evidence to support this comes from the fact that species that live in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20) add significantly to our appreciation of this process by showing that there are striking differences between the two sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative) is related most closely to neocortex volume, but male sociality (which is more competitive and combative) is more closely related to subcortical units (notably those associated with emotional responses). Thus different brain units have responded to different selection pressures.     

Effect of sex and bright coloration on survival and predator‐induced wing damage in an aposematic lantern fly with startle display

1. Aposematic coloration in prey promotes its survival by conspicuously advertising unpalatability to predators. Although classical examples of aposematic signals involve constant presentation of a signal at a distance, some animals suddenly display warning colours only when they are attacked. 2. Characteristics of body parts suddenly displayed, such as conspicuous coloration or eyespot pattern, may increase the survival of the prey by startling the predator, and/or by signalling unpalatability to the predators at the moment of attack. 3. The adaptive value of such colour patterns suddenly displayed by unpalatable prey has not been studied. We experimentally blackened the red patch in the conspicuous red–white–black hindwing pattern displayed by an unpalatable insect Lycorma delicatula White (Hemiptera: Fulgoridae) in response to predator's attack. 4. There was no evidence that the presence of the red patch increased prey survival over several weeks. We hypothesise that predators generalised from the red–white–black patches on the hindwings of unpalatable L. delicatula to any similar wing display as a signal of unpalatability. Because a higher proportion of males than females stay put at their resting sites, displaying their wings in response to repeated attacks by predators, wing damage was more frequent in males than in females. 5. To our knowledge, this is the first experimental test of an adaptive role of aposematic signals presented by unpalatable prey during sudden displays triggered by direct predatory attack.     

Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation

Cyclooxygenase (COX) and its prostanoid metabolites have been implicated in the control of cell survival; however, their role as mitogens remains undefined. To better understand the role of prostanoids on cell growth, we used mouse colon adenocarcinoma (CT26) cells to investigate the role of prostaglandin E(2) (PGE(2)) in cell proliferation. CT26 cells express both COX1 and COX2 and metabolize arachidonic acid to PGE(2.) Treatment with indomethacin, or COX-selective inhibitors, prevents PGE(2) biosynthesis and CT26 cell proliferation. The anti-proliferative effects of COX inhibition are rescued specifically by treatment with PGE(2) or the EP4 receptor-selective agonist PGE(1)-OH via phosphatidylinositol 3-kinase/extracellular signal-regulated kinase (ERK) activation, thus providing a functional link between PGE(2)-induced cell proliferation and EP4-mediated ERK signaling. Indomethacin or COX2 inhibitors, but not COX1 inhibitors, reduced the size and number of CT26-derived tumors in vivo. These inhibitory effects are paralleled by marked declines in the levels of tumor PGE(2), suggesting that their anti-tumor effects are directly associated with the inhibition of COX2 enzymatic activity. The described anti-tumor effects of indomethacin are evident whether it is administered at the time of, or 7 days after, tumor cell injection, suggesting that it has tumor preventive and therapeutic actions. Furthermore, the observation that indomethacin increases the survival rates of tumor-bearing mice, even after withdrawal of the drug, indicates that its effects are long lasting and that it may be potentially useful for the prevention and the clinical management of human cancers.     

Rapid ex vivo expansion of highly enriched human invariant natural killer T cells via single antigenic stimulation for cell therapy to prevent graft-versus-host disease

Background aims

CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT.