Spatial and temporal distribution of reported dengue cases and hot spot identification in Quezon City, Philippines, 2010-2017.

BACKGROUND: Dengue remains a major public health problem in the Philippines, particularly in urban areas of the National Capital Region. Thematic mapping using geographic information systems complemented by spatial analysis such as cluster analysis and hot spot detection can provide useful information to guide preventive measures and control strategies against dengue. Hence, this study was aimed to describe the spatiotemporal distribution of dengue incidence and identify dengue hot spots by barangay using reported cases from Quezon City, the Philippines from 2010 to 2017. METHODS: Reported dengue case data at barangay level from January 1, 2010 to December 31, 2017 were obtained from the Quezon City Epidemiology and Surveillance Unit. The annual incidence rate of dengue from 2010 to 2017, expressed as the total number of dengue cases per 10,000 population in each year, was calculated for each barangay. Thematic mapping, global cluster analysis, and hot spot analysis were performed using ArcGIS 10.3.1. RESULTS: The number of reported dengue cases and their spatial distribution varied highly between years. Local clusters were evident during the study period. Eighteen barangays were identified as hot spots. CONCLUSIONS: Considering the spatial heterogeneity and instability of hot spots in Quezon City across years, efforts towards the containment of dengue can be made more targeted, and efficient with the application of hot spot analysis in routine surveillance. This may be useful not only for the control of dengue but also for other diseases, and for public health planning, monitoring, and evaluation.

Hyperthermia inhibits homologous recombination repair and sensitizes cells to ionizing radiation in a time- and temperature-dependent manner.

Hyperthermia has long been known as a radio-sensitizing agent that displays anti-tumor effects, and has been developed as a therapeutic application. The mechanisms of hyperthermia-induced radio-sensitization are highly associated with inhibition of DNA repair. Our investigations aimed to show how hyperthermia inactivate homologous recombination repair in the process of sensitizing cells to ionizing radiation by using a series of DNA repair deficient Chinese Hamster cells. Significant differences in cellular toxicity attributable to hyperthermia at and above 42.5°C were observed. In wild-type and non-homologous end joining repair mutants, cells in late S phase showed double the amount heat-induced radio-sensitization effects of G1-phase cells. Both radiation-induced DNA double strand breaks and chromatin damage resulting from hyperthermia exposure was measured to be approximately two times higher in G2-phase cells than G0/G1 cells. Additionally, G2-phase cells took approximately two times as long to repair DNA damage over time than G0/G1-phase cells. To supplement these findings, radiation-induced Rad51 foci formations at DNA double strand break sites were observed to gradually dissociate in response to the temperature and time of hyperthermia exposure. Dissociated Rad51 proteins subsequently re-formed foci at damage sites with time, and occurred in a trend also related to temperature and time of hyperthermia exposure. These findings suggest Rad51's dissociation and subsequent reformation at DNA double strand break sites in response to varying hyperthermia conditions plays an important role in hyperthermia-induced radio-sensitization.

Genomic instability and telomere fusion of canine osteosarcoma cells.

Canine osteosarcoma (OSA) is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH) using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of γ-H2AX and telomere signals in interphase cells was observed. Each cell line was characterized by a combination of data representing cellular doubling time, DNA content, chromosome number, metacentric chromosome frequency, telomere signal level, cellular radiosensitivity, and DNA-PKcs protein expression level. We have also studied primary cultures from 10 spontaneous canine OSAs. Based on the observation of telomere aberrations in those primary cell cultures, we are reasonably certain that our observations in cell lines are not an artifact of prolonged culture. A correlation between telomere fusions and the other characteristics analyzed in our study could not be identified. However, it is important to note that all of the canine OSA samples exhibiting telomere fusion utilized in our study were telomerase positive. Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA.

Invasion of dwarf bamboo into alpine snow-meadows in northern Japan: pattern of expansion and impact on species diversity.

Recently, a dwarf bamboo species,Sasa kurilensis; Poaceae, has invaded into alpine snow-meadows in the wilderness area of the Taisetsu Mountains, northern Japan. This dwarf bamboo species has a wide distribution range from lowland to alpine sites of snowy regions. Because of the formation of dense evergreen culms and an extensive rhizome system, other plants are excluded following invasion by this dwarf bamboo, resulting in low species diversity. Dwarf bamboo originally inhabited the leeward slopes of alpine dwarf pine (Pinus pumila) clumps in alpine regions. During the last 32 years, however, dwarf bamboo has expanded its distribution area by up to 47% toward snow-meadows, especially on southeastern facing slopes. This rapid change may be related to the decrease in soil moisture and expansion of the annual growing period caused by the recent acceleration of snowmelt time. A multiyear census revealed that the density of bamboo culms increased 30-150% during 2 years, and the annual expansion of bamboo rhizomes was 39 cm on average. In addition to the expansion of bamboo clumps by vegetative growth, the possibility of migration by seed dispersal was also suggested by a genet analysis. With the increase in culm density, the species richness of snow-meadow vegetation decreased to less than one-quarter of the original level due to intense shading by dwarf bamboo. The rapid vegetation change in these almost pristine alpine environments isolated from the human activity implies that global climate change already influences the alpine ecosystem.

Monitoring of environmental contamination by Echinococcus multilocularis in an urban fringe forest park in Hokkaido, Japan.

OBJECTIVES: The aim of this study was to determine the prevalence of Echinococcus multilocularis environmental contamination in an urban fringe-the Nopporo forest park of Sapporo city, Hokkaido, Japan. A secondary aim was to determine possible transmission risks areas by associating percentage occurrence of E. multilocularis-positive faeces with the different land-use classes. METHODS: Wild fox faeces collected from the environment were examined by intravital methods, such as the taeniid egg sucrose floatation technique, E. multilocularis coproantigen enzyme-linked immunosorbent analysis and DNA test of taeniid eggs by PCR. Geospatial maps produced by the Global Positioning System and Landsat data were analysed using geographic information system software to determine the association between percentage occurrences of E. multilocularis-positive fox faeces and land-use classes. RESULTS: Our findings showed high prevalence rates in both E. multilocularis egg and coproantigen-positive faeces (16 and 49%, respectively) in the investigated urban fringe forest park. Data revealed that percentage occurrence of E. multilocularis-positive fox faeces was associated with land-use classes, such as forest and open field (P < 0.05). CONCLUSIONS: We conclude that Nopporo forest park in the urban fringe of Sapporo city, Hokkaido is a reservoir with a high prevalence of zoonotic infective agents for alveolar echinococcosis. Our findings suggest that interface habitats between forests or woodlands and open fields are indispensable for continued maintenance of the life-cycle of E. multilocularis and, as such, constitute high risk areas for echinococcosis transmission.

Conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin, for Hsp90 inhibitory activity.

Hsp90 is an attractive chemotherapeutic target because it is essential to maturation of multiple oncogenes. We describe the conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin isolated from Streptomyces sp. Their native free structures are similar to the active form of geldanamycin bound to Hsp90 protein. Their conformational character is a probable reason for their high-affinity binding. Lack of toxic benzoquinone in EH21A1-A4 also adds to their potential as lead compounds for anti-tumor drugs.

Mixed lineage kinase activity of indolocarbazole analogues.

The MLK1-3 activity for a series of analogues of the indolocarbazole K-252a is reported. Addition of 3,9-bis-alkylthiomethyl groups to K-252a results in potent and selective MLK inhibitors. The in vitro and in vivo survival promoting activity of bis-isopropylthiomethyl-K-252a (16, CEP-11004/KT-8138) is reported.