Search

Abstract Background Loss of heterozygosity (LOH) at chromosome arm 16q is frequently observed in human breast cancer, suggesting that one or more target tumor suppressor genes (TSGs) are located there. However, detailed mapping of the smallest region of LOH has not yet resulted in the identification of a TSG at 16q. Therefore, the present study attempted to identify TSGs using an approach based on mRNA expression. Methods A cDNA microarray for the 16q region was constructed and analyzed using RNA samples from 39 breast tumors with known LOH status at 16q. Results Five genes were identified to show lower expression in tumors with LOH at 16q compared to tumors without LOH. The genes for NAD(P)H dehydrogenase quinone (NQO1) and AT-binding transcription factor 1 (ATBF1) were further investigated given their functions as potential TSGs. NQO1 has been implicated in carcinogenesis due to its role in quinone detoxification and in stabilization of p53. One inactive polymorphic variant of NQO1 encodes a product showing reduced enzymatic activity. However, we did not find preferential targeting of the active NQO1 allele in tumors with LOH at 16q. Immunohistochemical analysis of 354 invasive breast tumors revealed that NQO1 protein expression in a subset of breast tumors is higher than in normal epithelium, which contradicts its proposed role as a tumor suppressor gene. ATBF1 has been suggested as a target for LOH at 16q in prostate cancer. We analyzed the entire coding sequence in 48 breast tumors, but did not identify somatic sequence changes. We did find several in-frame insertions and deletions, two variants of which were reported to be somatic pathogenic mutations in prostate cancer. Here, we show that these variants are also present in the germline in 2.5% of 550 breast cancer patients and 2.9% of 175 healthy controls. This indicates that the frequency of these variants is not increased in breast cancer patients. Moreover, there is no preferential LOH of the wildtype allele in breast tumors. Conclusion Two likely candidate TSGs at 16q in breast cancer, NQO1 and ATBF1, were identified here as showing reduced expression in tumors with 16q LOH, but further analysis indicated that they are not target genes of LOH. Furthermore, our results call into question the validity of the previously reported pathogenic variants of the ATBF1 gene.

Background: The vector species in the Amazon River Basin are regionally and locally diverse, which makes it imperative to understand and compare their roles in malaria transmission to help select appropriate methods of intervention and evaluation. The major aim of this study was to measure the vectorial capacity of five Anopheles species in three neighbouring villages, for two Plasmodium parasite species affecting humans., Methods: From 32 consecutive months of sampling in three villages, 1.5-7.0 km apart, on the Matapi River, Amapá State, Brazil, vectorial capacities (C) were estimated as time series for An. darlingi, An. marajoara, An. nuneztovari, An. triannulatus, and An. intermedius. Monthly parity measurements for each vector species were used to estimate daily survivorship and compared to estimates of survivorship from mark-release-recapture experiments. Gonotrophic cycle lengths were estimated through a time-series analysis of parity data, and durations of sporogony at study site temperatures for the two malaria parasite species were estimated from previous literature., Results: The absolute abundances of five vector species were strongly tracked by the spatial variation in C among villages. Temporally, C varied between wet and dry seasons, with An. darlingi, An. marajoara and An. triannulatus exhibiting higher C in the dry season from August to December, and An. nuneztovari its highest C early in the rainy season in January and February. Anopheles intermedius exhibited higher C in the rainy season from April to June than in the dry season. Significant differences in overall survival for each independent variable, and a significant difference in C between wet and dry seasons, among villages, and among vector species for both Plasmodium falciparum and Plasmodium vivax. A generalized linear mixed model (GLMM) analysis by village showed significant effects of vector species on C in only one village, but significant effects of parasite species in all three. Although the GLMM analysis detected no significant parasite x vector species interaction effects on C, effects on C of spline regressions of C dynamics x vector species interactions were significant in all villages., Conclusions: These detailed analyses of entomological and parasitological variables revealed hidden complexities of malaria epidemiology at local scales in neighbouring riverine villages of the Amazon Region., (© 2022. The Author(s).)

Mosquito larvae were collected from the subalpine region of the eastern Sierra Nevada Mountains from 2011 to 2014. Two watersheds were sampled and sites selected were mainly vernal snow-melt pools and wet meadows. Seven Aedes species, Culiseta incidens (Thomson), and Culex tarsalis Coquillett were collected. The most abundant and widely distributed species were Ae. hexodontus Dyar and Ae. tahoensis Dyar. Aedes tahoensis was the predominate species in woodland snow-melt habitats. Some species were found at most elevations while others were found more often at specific elevations. The most restrictive species was Ae. ventrovittis Dyar which occurred almost exclusively between 3,219 m a.s.l. and 3,390 m a.s.l. Shannon and Simpson species diversity indices demonstrated that species diversity was greater in meadow habitats compared to woodland habitats. Mixed woodland/meadows, rock pools, and shallow grass pools were intermediate in species diversity. Abiotic factors such as snowpack and water temperature impacted species development times and when habitats dried. It was concluded that spatial and temporal patterns of habitats, along with elevation, influenced species presence and larval development. The results of the present study and previous work in the eastern Sierras will help guide future research that focuses on the potential change in the distribution and seasonality of subalpine mosquitoes and disease potential in the eastern Sierras as climatic conditions change., (© 2019 The Society for Vector Ecology.)

Background: The biting cycle of anopheline mosquitoes is an important component in the transmission of malaria. Inter- and intraspecific biting patterns of anophelines have been investigated using the number of mosquitoes caught over time to compare general tendencies in host-seeking activity and cumulative catch. In this study, all-night biting catch data from 32 consecutive months of collections in three riverine villages were used to compare biting cycles of the five most abundant vector species using common statistics to quantify variability and deviations of nightly catches from a normal distribution., Methods: Three communities were selected for study. All-night human landing catches of mosquitoes were made each month in the peridomestic environment of four houses (sites) for nine consecutive days from April 2003 to November 2005. Host-seeking activities of the five most abundant species that were previously captured infected with Plasmodium falciparum, Plasmodium malariae or Plasmodium vivax, were analysed and compared by measuring the amount of variation in numbers biting per unit time (co-efficient of variation, V), the degree to which the numbers of individuals per unit time were asymmetrical (skewness = g1) and the relative peakedness or flatness of the distribution (kurtosis = g2). To analyse variation in V, g1, and g2 within species and villages, we used mixed model nested ANOVAs (PROC GLM in SAS) with independent variables (sources of variation): year, month (year), night (year X month) and collection site (year X month)., Results: The biting cycles of the most abundant species, Anopheles darlingi, had the least pronounced biting peaks, the lowest mean V values, and typically non-significant departures from normality in g1 and g2. By contrast, the species with the most sharply defined crepuscular biting peaks, Anopheles marajoara, Anopheles nuneztovari and Anopheles triannulatus, showed high to moderate mean V values and, most commonly, significantly positive skewness (g1) and kurtosis (g2) moments. Anopheles intermedius was usually, but not always, crepuscular in host seeking, and showed moderate mean V values and typically positive skewness and kurtosis. Among sites within villages, significant differences in frequencies of departures from normality (g1 and g2) were detected for An. marajoara and An. darlingi, suggesting that local environments, such as host availability, may affect the shape of biting pattern curves of these two species., Conclusions: Analyses of co-efficients of variation, skewness and kurtosis facilitated quantitative comparisons of host-seeking activity patterns that differ among species, sites, villages, and dates. The variable and heterogeneous nightly host-seeking behaviours of the five exophilic vector species contribute to the maintenance of stable malaria transmission in these Amazonian villages. The abundances of An. darlingi and An. marajoara, their propensities to seek hosts throughout the night, and their ability to adapt host-seeking behaviour to local environments, contribute to their impact as the most important of these vector species.

Three communities separated by 1.5-7.0 km, along the Matapí River, Amapá State, Brazil, were sampled monthly from April 2003 to November 2005 to determine relationships between seasonal abundance of host-seeking anophelines, rainfall and malaria cases. Out of the 759 821 adult female anophelines collected, Anopheles darlingi Root (Diptera: Culicidae) was the most abundant (56.2%) followed by An. marajoara Galvão & Damasceno (24.6%), An. nuneztovari Gabaldón (12.4%), An. intermedius (Chagas) (4.4%) and An. triannulatus (Neiva and Pinto) (2.3%). Vector abundance, as measured by human landing catches, fluctuated during the course of the study and varied in species-specific ways with seasonal patterns of rainfall. Anopheles darlingi and An. triannulatus were more abundant during the wet-dry transition period in June to August, whereas An. marajoara began to increase in abundance in February in two villages, and during the wet-dry transition in the other village. Anopheles nuneztovari and An. intermedius increased in abundance shortly after the rains began in January to February. A generalized linear mixed model (GLMM) analysis of 32 consecutive months of collections showed significant differences in abundance for each species by village and date (P < 0.0001). Correlations between lagged rainfall and abundances also differed among species. A strong positive correlation of An. darlingi abundance with rainfall lagged by 4 and 5 months (Pearson's r = 0.472-0.676) was consistent among villages and suggests that rainfall may predict vector abundance. Significant correlations were detected between numbers of malaria cases and abundances of suspected vector species. The present study shows how long-term field research may connect entomological and climatological correlates with malaria incidence.

The aim of this study was to determine the prevalence of malaria infection and antibodies against the repetitive epitopes of the circumsporozoite (CS) proteins of Plasmodium falciparum, P. malariae, P. vivax VK210, P. vivax VK247, and P. vivax-like in individuals living in the states of Rondônia, Pará, Mato Grosso, Amazonas, and Acre. Active malaria transmission was occurring in all studied sites, except in Acre. P. falciparum was the predominant species in Pará and Rondônia and P. vivax in Mato Grosso. Infection by P. malariae was low but this Plasmodium species was detected in Rondônia (3.5%), Mato Grosso (2.5%), and Pará (0.8%). High prevalence and levels of serological reactivity against the CS repeat peptides of P. falciparum were detected in Rondônia (93%) and Pará (85%). Sera containing antibodies against the CS repeat of P. malariae occurred more frequently in Rondônia (79%), Pará (76%), and Amazonas (68%). Antibodies against the repeat epitope of the standard CS protein of P. vivax VK210, P. vivax VK247, and P. vivax-like were more frequent in Rondônia, Pará, and Mato Grosso. The high frequency of reactions to P. malariae in most of the areas suggests that the infection by this Plasmodium species has been underestimated in Brazil.

Vector incrimination studies were conducted from April 2003 to February 2005 at three riverine villages 1.5 km to 7.0 km apart, along the Matapi River, Amapa State, Brazil. A total of 113,117 mosquitoes were collected and placed in pools of

Hosts of blood-fed anophelines (Diptera: Culicidae) were determined in three riverine villages, 1.5-7.0 km apart, along the Matapí River, Amapá state, Brazil, by enzyme-linked immunosorbent assay midgut analysis for IgG of common vertebrates. Anopheles marajoara Galvão & Damsceno and Anopheles darlingi Root had higher human blood indices (HBI) than Anopheles nuneztovari Gabaldón, Anopheles triannulatus (Neiva and Pinto), and Anopheles intermedius (Chagas), which were relatively zoophilic. HBIs of An. darlingi varied significantly among villages, attributable to a low proportion of human-fed mosquitoes in Santo Antônio. Significantly higher incidence of An. marajoara and An. nuneztovari fed on pig blood at two villages, associated with a low number of pigs in Santo Antônio. The incidences of bovine blood varied significantly among villages for all three of the most common anopheline species. The incidence of mixed meals ranged from 7.1 to 27.6% among common species, and, for An. marajoara, varied significantly among villages. This study demonstrates differences in host selection patterns among villages only a few kilometers apart, which may be influenced by host availability and have important epidemiological consequences.

This paper examines problems of assessment and decision-making that result from poor or inadequate communication of indicators among the disciplines of public health, the physical sciences, and economics. The specific examples used are drawn from climate impacts in the Americas although the issues are more general to environmental health. In terms of physical processes, problems arise in confusion about indicators at different steps along the DPSEEA framework of environmental health indicators and general scientific uncertainty about the underlying physical processes. Communication between public health and economics is hindered by a lack of understanding of economic costs used in making decisions and the presence of implicit value judgments in economic analysis. Organizational structures may further inhibit the effective use of indicators. Finally, the paper discusses the Pan American Health Organization proposal to enhance the communication of indicators by using information technology networking to support communication among program managers and decision-makers at the national and local levels. The aim of this initiative is to establish a better environment for making decisions. The problem of cholera in Peru is shown as an example of the need for better communication.

There is a historical association between wetlands and infectious disease that has led to the modification of wetlands to prevent disease. At the same time there has been the development of water resources projects that increase the risk of disease. The demand for more water development projects and the increased pressure to make natural wetlands economically beneficial creates the need for an ecological approach to wetland management and health assessment. The environmental and health interactions are many. There is a need to take into account the landscape, spatial boundaries, and cross-boundary interactions in water development projects as well as alternative methods to provide water for human needs. The research challenges that need to be addressed are discussed.

The author reviews the malaria research program in Sucre State, Venezuela, taking an ecosystem approach. The goal was to determine which methods could have been introduced at the onset that would have made the study more ecological and interdisciplinary. Neither an ecosystem approach nor integrated disease control were in place at the time of the study. This study began to introduce an ecosystem approach when two contrasting ecosystems in Sucre State were selected for study and vector control methods were implemented based on research results. The need to have a health policy in place with an eco-health approach is crucial to the success of research and control. The review suggests that sustainability is low when not all the stakeholders are involved in the design and implementation of the research and control strategy development. The lack of community involvement makes sustainability doubtful. The author concludes that there were two interdependent challenges for malaria control: development of an ecosystem approach for malaria research and control, and the implementation of an integrated disease control strategy, with malaria as one of the important health issues.

An ecoregional approach to the classification of malaria in the neotropics region can give health personnel a new prespective on how to manage malaria control programs. We propose an ecoregional classification based on vector distribution and important environmental determinants, including vegetation type, rainfall patterns, mean temperatures, elevation, and geomorphology. The following 5 ecoregions are described: (1) coastal, (2) piedmont, (3) savanna, (4) interior lowland forest, and (5) high valley. Subregional differences are classified when appropriate. Because human activities and extensive changes in land use usually leads to increased human-vector contact and alter local vector distribution and abundance, it is important that these changes be considered in the classification of vector ecoregions. Using this approach, risk areas can be classified as to the presence and potential abundance of particular vectors. Then, in combination with other components of malaria transmission (e.g., migration, cultural practices, living conditions), areas for surveillance and intervention can be prioritized. It is hoped that this forum will be a catalyst for discussion, future research, and the development of ecologically orientated malaria control programs.

This article reviews the current status of the use of insecticide-impregnated mosquito nets and other impregnated materials in the Americas. Studies from Brazil, Colombia, Ecuador, Guatemala, Peru, Suriname, and Venezuela are examined. It is concluded that most studies have suffered from experimental design errors, short duration problems, and/or inadequate measurement of health indicators. The review brings out the great difficulty of conducting scientific studies that attempt to measure the impact of insecticide-treated materials on malaria incidence. In particular, the low incidence of malaria in the Americas, the high prevalences of P. vivax and relapsing cases, and the relationship between human activity patterns and the crepuscular biting patterns of certain malaria vectors stand in the way of easy experimental design and execution. The utilization of impregnated mosquito nets or other impregnated materials as a major component of an integrated malaria control program would be premature at this time. However, it is recommended that well-conceived large-scale trials and interventions be considered when they are based on a thorough understanding of the dynamics of malaria transmission in the area of study.

The resurgence of malaria in the Americas has renewed interest in Anopheles biology. Anopheles darlingi, An. albimanus, An. nuneztovai and An. aquasalis are reconfirmed as major malaria vectors and other species are playing important roles in regional malaria transmission. Adult biting activity and larval ecology are discussed in detail. Seasonal abundance and daily biting activity of Anophelines vary considerably among species and geographically for the same species. Anopheles albimanus has the least amount of variation in biting activity over its range and An. darlingi has the greatest. All species studied are more exophilic and exophagic than endophilic and endophagic. Anopheles darlingi is more anthropophilic, endophilic and endophagic than other Anophelines. Larval studies remain more descriptive than comprehensive. Research on Anophelines is becoming more integrated and biologists are using new biochemical techniques and ecological principles to answer critical questions. This "pluralization" will help us understand species complexes, population dynamics and malaria transmission. Integrated control programs will require more regional, in-depth ecological studies.

A project on management of lone star ticks, Amblyomma americanum (L.), at Land Between the Lakes, a Tennessee Valley Authority recreational area in Kentucky-Tennessee, during 1984-1988, demonstrated the effectiveness and economics of three control technologies. Acaricide applications (chlorpyrifos at 0.28 kg [AI]/ha), vegetative management (mowing and removal of 40% overstory and 90-100% of midstory, understory, and leaf litter), and host management (white-tailed deer exclusion from a 71-ha campground with a single-line fence) provided 75, 70, and 64% mean controls of all life stages of the lone star tick, respectively. Combinations of acaricide applications + vegetative management, acaricide applications + host management, and acaricide applications + vegetative management + host management produced 94, 89, and 96% mean control of all life stages, respectively. The costs of acaricide applications (two per year), vegetative management (two mowings per year), and white-tailed deer exclusion (single-line fence) were $45, $150, and $30/ha/yr, respectively. Results of this project are used to design management strategies that could be considered for use against lone star ticks in recreational areas.

Application of the ethoxy analog of rhizobitoxine (l-2-amino-4-[2'-aminoethoxy]-trans-3-butenoic acid), an inhibitor of ethylene biosynthesis, inhibited growth of apple, crabapple, and apricot buds released from dormancy by chilling or by treatment with benzyladenine. When tea crabapple (Malus hupehensis [Pamp.] Rehd.) buds were sprayed once with 8.8 x 10(-3)m benzyladenine, ethylene production by the buds increased significantly 24 to 48 hours after benzyladenine treatment. Application of the rhizobitoxine analog to the buds at the time of benzyladenine treatment reduced ethylene evolution to the level of the controls for up to 2 weeks after treatment. Increase in bud weight was inhibited also but to a lesser extent. These data suggest that growth of buds is accompanied by ethylene production and that the inhibition of ethylene biosynthesis also inhibits bud growth. Since additional metabolic effects result from the action of the rhizobitoxine analog, no firm conclusions on its role can be drawn at this time.

Taylor's power law (y = amb) was used to analyze the spatial pattern of Boophilus microplus (Canestrini) larvae in tropical pastures. The index of aggregation b was 2.75 and showed that larvae were highly aggregated. The b-values differed significantly among certain pastures (LSD, P less than 0.05), and pasture type and use could have contributed to differences in b. The use of Taylor's power law to adjust for sampling inconsistencies that occur in tropical pastures where regimented sampling cannot always be followed is discussed.

Utilization of glucose, uracil and valine by flower and leaf buds of seedling pear trees (Pyrus calleryana Decne.) from the time of flower bud initiation to flowering was investigated. A very high rate of glucose utilization through the pentose phosphate pathway was observed throughout the development of buds. There was no difference in the type of glucose metabolism between flower and leaf buds except immediately before flowering, when the metabolism in flower buds was shifted toward the glycolytic pathway. Such a shift did not occur in leaf buds. The incorporation of uracil and valine into the nucleic acid and protein fraction of buds, respectively, was high throughout bud development, perhaps indicating a high rate of turnover in the resting buds. Incorporation of both compounds decreased when buds started to expand prior to flowering.

Various tissues in flower buds of Pyrus calleryana Decne. differ in their metabolic activity. Brown outer scales utilized more exogenously supplied glucose, particularly through the pentose phosphate pathway, than did the central axes and the green inner scales. They also contained more endogenous reducing sugars, and glucose leaked out more readily from the brown scales than from the other tissues. In contrast, respiration of the central axes was nine times as great as that of the brown scales, and two to four times as much glucose was metabolized through glycolysis. Membranes of the central axes were less permeable to glucose. Because the brown scales are 75% of the dry weight of the bud, they dominate its pattern of glucose metabolism.

The lower alkyl esters of the C(8) to C(12) fatty acids and the C(8) to C(10) fatty alcohols selectively kill or inhibit the terminal meristem without damaging the axillary meristems, foliage, or stem tissue of a wide variety of plants. The axillary meristems develop at nearly the same time as those of plants whose terminal meristems have been removed manually. The concentration of the fatty acid esters and alcohols required to kill the terminal meristem range from 0.025 to 0.05M for herbaceous plants, 0.05 to 0.16M for semi-woody plants, and 0.16 to 0.27M for woody plants.