Toxoplasma gondii CDPK1 (TgCDPK1) was found to be the target of the toxoplasmocidal compound, 1NM-PP1. When TgCDPK1 was mutated at position 128 from glycine to methionine, resistance was gained. Inhibition of gliding motility without inhibition of micronemal secretion by 1NM-PP1 suggests a function for TgCDPK1 in gliding motility.

We investigated the changes of matrix metalloproteinase (MMP)-9 in the peripheral blood samples of patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs), and the effect of azelnidipine on plasma MMP-9 levels in those patients. Levels of MMP-9 were measured in 22 patients who underwent EVAR for AAAs, and results were compared between a group receiving 16 mg azelnidipine daily (n=12) and a control group without azelnidipine (n=10). Measurements were taken preoperatively, and at 1 month and 3 months, postoperatively. Patients without endoleaks after EVAR showed a significant decrease in mean plasma MMP-9 levels (preoperative value: 39.5+/-14.3 ng/mL, after 1 month: 25.0+/-12.6, after 3 months: 28.2+/-10.2 ng/mL; P=0.004). In contrast, no significant decreases in mean plasma MMP-9 levels were observed in the patients with endoleaks after EVAR (preoperative value: 37.5+/-9.0 ng/mL, after 1 month: 26.8+/-8.4, after 3 months: 38.5+/-15.7 ng/mL; P=0.219). Moreover, among patients without endoleaks, those receiving azelnidipine showed a significantly greater decrease in the mean plasma MMP-9 levels for 3 months postoperatively (preoperative value: 47.7+/-13.2 ng/mL, after 1 month: 26.6+/-12.8, after 3 months: 26.1+/-11.4 ng/mL; P0.001) compared with the control group without endoleaks (preoperative value: 31.3+/-10.5 ng/mL, after 1 month: 33.4+/-12.1, after 3 months: 30.3+/-9.1 ng/mL; P=0.792). These results showed that azelnidipine treatment in patients without endoleak after EVAR was associated with a significant decrease in mean plasma MMP-9 levels for 3 months postoperatively.

The implementation of decentralization policies in the health sector of many developing countries has been a major issue in international health. The objectives were to focus on health sector reform, health financing system, and human resource development. However, less attention has been paid to the institutional capacity development of health systems. In this paper, institutional capacity refers to the abilities of organizations to make effective management in order to build local capacity and to achieve goals with local ownership. The aims of this paper were to explore the developmental process of districts institutional capacity by assistance of an NGO in Cambodia, and to identify the key factors influencing this development. We chose five operational districts (ODs) and two of them were contracted to NGO for management assistance. We conducted semi-structured in-depth interview to 17 managers and 16 key informant interviews. For analysis, we used qualitative analysis based on a grounded theory approach to clarify a conceptual framework for understanding management practices at district health institutions. There is a 4-stage capacity developmental process at the district-level institution. Supportive supervision and widening of decision-making authority were identified as key factors for sustainable institutional capacity development. They have complementary function each other. External agencies such as NGOs can use these key factors to develop local management capacities, and also this capacity development can be done internally within institutions such as OD health offices and by upper authorities such as the PHD.

Bats are now known as the source of several diseases in humans, but few studies regarding immune responses and factors associated with bats have so far been reported. In this study, we focused on STAT1, one of the critical components in interferon (IFN)-signaling and antiviral activity, which is often targeted by viral proteins to reduce antiviral activity and increase viral replication. We found that Rousettus aegyptiacus STAT1 (bat STAT1) is phosphorylatable and translocates to the nucleus when stimulated with human IFN-alpha (hIFN-alpha). Furthermore, phosphorylation of bat STAT1 and inhibition of nuclear translocation was observed in IFN-stimulated cells infected with the HEP-Flury strain of rabies virus, in the same manner as in other mammals. Additionally, quantitative real-time RT-PCR revealed that bat STAT1 mRNA was highly expressed in the liver, while low in muscle and spleen.

This is the first report on the cDNA sequences of bat interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 p40, and tumor necrosis factor (TNF)-alpha. The cDNAs of bat IL-2, IL-4, IL-6, IL-10, IL-12 p40, and TNF-alpha comprise 459, 405, 624, 537, 990, and 699 base pairs respectively. Moreover, each of the cDNAs of bat IL-2, IL-4, IL-6, IL-10, IL-12 p40, and TNF-alpha contain a single open reading frames encoding 152, 134, 207, 178, 329, and 232 amino acids, respectively. The comparison of bat cytokines with Perrissodactyla (horse), Carnivora (dog and cat), and Cetartiodactyla (cattle and pig) orthologs revealed a high degree of homology. Although the N-terminal amino acids and cysteine residues are highly conserved in each mature cytokine, the deduced N-linked glycosylation sites vary across species.

A new water-insoluble Fe(3+)-TCAS[4]/TMPyP complex linked tetraanionic Fe(III)-thiacalix[4]arenetetrasulfonate (Fe(3+)-TCAS[4]) with tetracationic tetrakis(1-methylpyridinium-4-yl)porphine (TMPyP) via ionic interaction was prepared. The peroxidase-like catalytic activity of the Fe(3+)-TCAS[4]/TMPyP complex was investigated based on the dye formation reaction by oxidation of 4-aminoantipyrine and phenol with H(2)O(2) catalyzed by peroxidase. This Fe(3+)-TCAS[4]/TMPyP complex showed the highest activity in pH 5.5 acetate buffer solutions, and it was applied to the photometric determination of trace amounts of H(2)O(2). The calibration curve was linear over the range from 1.0 to 35 mug of H(2)O(2) in a 1.0 ml sample solution. Moreover, the method using glucoseoxidase and the Fe(3+)-TCAS[4]/TMPyP complex was applied to the determination of glucose, and the results were satisfactory even in control sera. The Fe(3+)-TCAS[4]/TMPyP complex can be applied to a practical sample, such as blood or urine, as an analytical reagent for the photometric determination of H(2)O(2) in place of peroxidase.

In this study, cDNA of Toll-like receptor (TLR) 3, 7, and 9 were synthesized and completely sequenced. The coding regions of cDNA for bat TLR3, 7, and 9 were 2,718, 3,150, and 3,090 bp in length, respectively. Open reading frames encoded 905, 1,049, and 1,029 amino acids for TLR3, 7, and 9, respectively. Nucleotide sequences, predicted amino acid sequences and predicted domain structures of the three bat TLRs had high homology with those of other mammals. In addition, the expression profile of each TLR in main organs was analyzed. Expression of TLR3 was highest in liver, whereas TLR7 and TLR9 expression was highest in spleen.

Erythrocyte invasion is critical to the pathogenesis and survival of the malarial parasite, Plasmodium falciparum. This process is partly mediated by proteins that belong to the Duffy binding-like family, which are expressed on the merozoite surface. One of these proteins, BAEBL (also known as EBA-140), is thought to bind to glycophorin C in a sialic acid-dependent manner. In this report, by the binding assay between recombinant BAEBL protein and enzyme-treated erythrocytes, we show that the binding of BAEBL to erythrocytes is mediated primarily by sialic acid and partially through heparan sulfate (HS). Because BAEBL binds to several kinds of HS proteoglycans (HSPGs) or purified HS, the BAEBL-HS binding was found to be independent of the HSPG peptide backbone and the presence of sialic acid moieties. Furthermore, both the sialic acid- and HS-dependent binding were disrupted by the addition of soluble heparin. This inhibition may be the result of binding between BAEBL and heparin. Invasion assays demonstrated that HS-dependent binding was related to the efficiency of merozoite invasion. These results suggest that HS functions as a factor that promotes the binding of BAEBL and merozoite invasion. Moreover, these findings may explain the invasion inhibition mechanisms observed following the addition of heparin and other sulfated glycoconjugates.

Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79DeltaTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied by means of a plaque reduction assay. GCV proved to be more potent and showed a superior anti-EHV-4 activity. On the other hand, ACV showed very poor ability to inhibit EHV-4 replication. As predicted, WA79DeltaTK was insensitive to GCV. Although EHV-4 is normally insensitive to ACV, it showed >20-fold increase in sensitivity when the equine herpesvirus-1 (EHV-1) TK was supplied in trans. Furthermore, both ACV and GCV resulted in a significant reduction of plaque size induced by EHV-4 and 1. Taken together, these data provided direct evidence that GCV is a potent selective inhibitor of EHV-4 and that the virus-encoded TK is an important determinant of the virus susceptibility to nucleoside analogues.

Bovine viral diarrhea virus (BVDV) field isolates show genetic and antigenic diversity. At least 14 subgenotypes of BVDV-1 and 4 of BVDV-2 have been identified in Artiodactyla worldwide. Of these, 6 subgenotypes of BVDV-1 and 1 of BVDV-2 have been isolated in Japan. Previously, we reported that each subgenotype virus expresses different antigenic characteristics. Here we investigated the reactivity of neutralizing antibodies against representative strains of Japanese BVDV subgenotypes using sera from 266 beef cattle to estimate the prevalence of this epidemic virus among cattle in Japan. Antibody titers at concentrations at least 4-fold higher than antibodies against other subgenotype viruses were considered subgenotype specific. Subgenotype-specific antibodies were detected from 117 (80.7%) of 145 sera samples (69.7% against BVDV-1a, 1.4% against BVDV-1b, 8.3% against BVDV-1c, and 1.4% against BVDV-2a). The results suggest that neutralization tests are useful in estimating currently epidemic subgenotypes of BVDV in the field.