Geographical distribution of human Schistosoma japonicum infection in The Philippines: tools to support disease control and further elimination

Schistosoma japonicum infection is believed to be endemic in 28 of the 80 provinces of The Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small-scale spatial variation in S. japonicum prevalence across The Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geo-located at the barangay level and included in the analysis. The analysis was then stratified geographically for the regions of Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ?20 years had significantly higher prevalence of S. japonicum compared with females and children <5 years. The role of the environmental variables differed between regions of The Philippines. Schistosoma japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in the prevalence of S. japonicum infection in The Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritised for areas identified to be at high risk but which were under-represented in our dataset.     

Species of Mycosphaerellaceae and Teratosphaeriaceae on native Myrtaceae in Uruguay: evidence of fungal host jumps

Mycosphaerella species are well-known causal agents of leaf diseases on many economically and ecologically important plant species. In Uruguay, a relatively large number of Mycosphaerellaceae and Teratosphaeriaceae are found on Eucalyptus, but nothing is known of these fungi on native Myrtaceae. The aim of this study was to identify Mycosphaerellaceae and Teratosphaeriaceae species associated with leaf diseases on native Myrtaceae in Uruguay and to consider whether host jumps by the pathogen from introduced Eucalyptus to native Myrtaceae have occurred. Several native forests throughout the country were surveyed with special attention given to those located close to Eucalyptus plantations. Five species belonging to the Mycosphaerellaceae and Teratosphaeriaceae clades were found on native Myrtaceous trees and three of these had previously been reported on Eucalyptus in Uruguay. Those occurring both on Eucalyptus and native Myrtaceae included Pallidocercospora heimii, Pseudocercospora norchiensis, and Teratosphaeria aurantia. In addition, Mycosphaerella yunnanensis, a species known to occur on Eucalyptus but not previously recorded in Uruguay, was found on leaves of two native Myrtaceous hosts. Because most of these species occur on Eucalyptus in countries other than Uruguay, it appears that they were introduced in this country and have adapted to be able to infect native Myrtaceae. These apparent host jumps have the potential to result in serious disease problems and they should be carefully monitored.     

Antioxidant activities of polysaccharides from Lentinus edodes and their significance for disease prevention

The crude polysaccharide (LEP) was extracted by hot water from the fruiting bodies of Lentinus edodes, and further purified by DEAE-cellulose and Sepharose CL-6B chromatography, giving three polysaccharide fractions coded as LEPA1, LEPB1 and LEPC1. In this study, their chemical and physical characteristics of polysaccharide fractions and antioxidant capacities, including scavenging activity against hydroxyl radicals, superoxide radicals and Fe²⁺-chelating ability, were valuated. The results showed that LEPC1 exhibited significantly antioxidant activity at a concentration-dependent manner. Therefore these results indicated that the water-extractable polysaccharide fraction was a potent antioxidant and could be developed to be new health medicine for fighting against various human diseases.     

A scientific note on the detection of honeybee viruses using real-time PCR (TaqMan) in Varroa mites collected from a Thai honeybee (Apis mellifera) apiary

Bee parasitic mite syndrome is a disease complex of colonies simultaneously infested with Varroa destructor mites and infected with viruses and accompanied by high mortality. By using real-time PCR (TaqMan), five out of seven bee viruses were detected in mite samples (V. destructor) collected from Thailand. Moreover, the results of this study provide an evidence for the co-existence of several bee viruses in a single mite. This is also the first report of bee viruses in mites from Thailand.     

Inhibition of Metarhizium anisopliae in the alimentary tract of the eastern subterranean termite Reticulitermes flavipes

Reticulitermes flavipes workers were individually inoculated with 10,000 conidia of the entomopathogenic fungus Metarhizium anisopliae. After being kept in groups of 20 individuals for 1-6 d, histopathological approach showed that most of the inoculated conidia were groomed from the surface of the cuticle by nestmates within 24 h, and that a large number of conidia was subsequently found in different parts of the gut of the groomers. Our observations showed that, among thousands of conidia found in the termite’s gut, conidial germination never occurred in all inspected specimens, even when the conidia had the chance to bind to the surface of the cuticular lining of the gut. In addition, when termites were left for decomposition several days after death caused by an external infection of M. anisopliae, the hyphal growth was generalized in the body cavity of the cadaver, but was never observed in the lumen of the gut even 2 d post-mortem. Our observation suggests that the putative biochemicals involved in the termite’s gut defense against fungal pathogens are from multiple origins.     

Cellular encapsulation in the eastern subterranean termite, Reticulitermes flavipes (Isoptera), against infection by the entomopathogenic fungus Metarhizium anisopliae

Reticulitermes flavipes workers were topically inoculated with ≈10,000 conidia of the entomopathogenic fungus Metarhizium anisopliae. After being kept in groups of 20 individuals for 1-9 d, histopathological examination showed that termites had an individual immune reaction. The nodule formation at the point of entrance of the fungal hyphae was identified as a cellular encapsulation and the different steps in the nodule formation are described. The relative number of hemocytes per termite increased 24 h after fungal exposure and remained high in the hemolymph for at least 3 d before decreasing back to pre-exposure levels. The role of an individual immune cellular reaction in social insects is discussed.     

Ubiquitination Regulates the Neuroprotective Function of the Deubiquitinase Ataxin-3 in Vivo

Deubiquitinases (DUBs) are proteases that regulate various cellular processes by controlling protein ubiquitination. Cell-based studies indicate that the regulation of the activity of DUBs is important for homeostasis and is achieved by multiple mechanisms, including through their own ubiquitination. However, the physiological significance of the ubiquitination of DUBs to their functions in vivo is unclear. Here, we report that ubiquitination of the DUB ataxin-3 at lysine residue 117, which markedly enhances its protease activity in vitro, is critical for its ability to suppress toxic protein-dependent degeneration in Drosophila melanogaster. Compared with ataxin-3 with only Lys-117 present, ataxin-3 that does not become ubiquitinated performs significantly less efficiently in suppressing or delaying the onset of toxic protein-dependent degeneration in flies. According to further studies, the C terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase that ubiquitinates ataxin-3 in vitro, is dispensable for its ubiquitination in vivo and is not required for the neuroprotective function of this DUB in Drosophila. Our work also suggests that ataxin-3 suppresses degeneration by regulating toxic protein aggregation rather than stability.     

Human receptor for activated protein kinase C1 associates with polyglutamine aggregates and modulates polyglutamine toxicity

Formation of SDS-insoluble protein aggregates in affected neurons is a cellular pathological feature of polyglutamine (polyQ) disease. We identified a multi-WD-domain protein, receptor for activated protein kinase C1 (RACK1), as a novel polyQ aggregate component from a Drosophila transgenic polyQ disease model. We showed that WD domains were crucial determinants for the recruitment of RACK1 to polyQ aggregates. Over-expression of the human RACK1 protein suppressed polyQ-induced neurodegeneration in vivo. This is the first report to demonstrate the involvement of WD-domain proteins in polyQ pathogenesis, and the proteomic approach described here can be applied to the investigation of other protein aggregation disorders including Alzheimer’s and Parkinson’s diseases.     

Comparative genomics: from genotype to disease phenotype in the leishmaniases

Recent progress in sequencing the genomes of several Leishmania species, causative agents of cutaneous, mucocutaneous and visceral leishmaniasis, is revealing unusual features of potential relevance to parasite virulence and pathogenesis in the host. While the genomes of Leishmania major, Leishmania braziliensis and Leishmania infantum are highly similar in content and organisation, species-specific genes and mechanisms distinguish one from another. In particular, the presence of retrotransposons and the components of a putative RNA interference machinery in L. braziliensis suggest the potential for both greater diversity and more tractable experimentation in this Leishmania Viannia species.     

Antifungal activity of the termite alkaloid norharmane against the mycelial growth of Metarhizium anisopliae and Aspergillus nomius

Antifungal activity of norharmane, a β-carboline alkaloid found in termites (Isoptera, Rhinotermitidae) was tested against two entomopathogenic fungi, Metarhizium anisopliae and Aspergillus nomius. It was determined that, at physiological concentration (10 μg ml⁻¹), norharmane had no significant effect on A. nomius mycelial growth rate but reduced M. anisopliae growth rate by 11.9%. Contrary to previous findings, we suggest that norharmane has a limited role in disease resistance against fungal pathogens in individual subterranean termites, and we discuss the potential role of this chemical at a colony level.     

Within-colony variation in inducibility of coral disease resistance

The abiotic environment influences a variety of ecological processes, including the emergence, transmission, and distribution of disease. In the oceans, increased temperatures associated with climate change are hypothesized to decrease host resistance and/or increase pathogen growth, virulence, or infectivity. Colonial organisms, such as corals, could face a unique challenge with respect to temperature and disease stress: heterogeneous within-colony distribution of constitutive and temperature-induced resistance to infection. This could facilitate disease if warming temperatures promote pathogen growth while decreasing resistance of some areas of the coral colony. Here, an experiment was used to test the hypothesis that temperature-induced disease resistance is heterogeneous within colonies of the sea fan coral, Gorgonia ventalina. Resistance, measured as activity of antifungal metabolites, increased (approx. 30%) with temperature only in young edge tissue, not in older center tissue, consistent with patterns of infection in older, larger sea fan colonies on Caribbean reefs.     

Ascosphaera aggregata contamination on alfalfa leafcutting bees in a loose cell incubation system

The alfalfa leafcutting bee, a solitary bee used to pollinate alfalfa seed crops, is seriously affected by chalkbrood, a larval disease caused by the fungus Ascosphaera aggregata. One attempt to control the disease includes removing nests from the nesting boards (the “loose cell” system). We report here that adults emerging from the loose cells are heavily contaminated with A. aggregata spores. The contamination levels are not as high as previously reported for bees emerging directly from the boards, but they are still a likely focus for disease spread and may need to be targeted in chalkbrood control strategies.     

A Novel Inhibitor of Amyloid β (Aβ) Peptide Aggregation: FROM HIGH THROUGHPUT SCREENING TO EFFICACY IN AN ANIMAL MODEL OF ALZHEIMER DISEASE*

Compelling evidence indicates that aggregation of the amyloid β (Aβ) peptide is a major underlying molecular culprit in Alzheimer disease. Specifically, soluble oligomers of the 42-residue peptide (Aβ42) lead to a series of events that cause cellular dysfunction and neuronal death. Therefore, inhibiting Aβ42 aggregation may be an effective strategy for the prevention and/or treatment of disease. We describe the implementation of a high throughput screen for inhibitors of Aβ42 aggregation on a collection of 65,000 small molecules. Among several novel inhibitors isolated by the screen, compound D737 was most effective in inhibiting Aβ42 aggregation and reducing Aβ42-induced toxicity in cell culture. The protective activity of D737 was most significant in reducing the toxicity of high molecular weight oligomers of Aβ42. The ability of D737 to prevent Aβ42 aggregation protects against cellular dysfunction and reduces the production/accumulation of reactive oxygen species. Most importantly, treatment with D737 increases the life span and locomotive ability of flies in a Drosophila melanogaster model of Alzheimer disease.     

Diseases of Nephrops and Metanephrops: a review

Nephrops and Metanephrops are commercially exploited genera within the family Nephropidae (clawed lobsters). Commercial fisheries for each genus exist in the Northern and Southern Hemispheres and utilise trawling or trapping for capture. Despite a relative lack of dedicated disease surveys on lobsters from these fisheries, several important symbionts and pathogens have been described. The most significant known pathogen of Metanephrops (challengeri) is a microsporidian parasite (Myospora metanephrops) which causes destruction of the skeletal and heart muscles of infected lobsters while the most significant known pathogen of Nephrops (norvegicus) is a dinoflagellate parasite assigned to the genus Hematodinium. This parasite has been responsible for an ongoing epidemic in fished populations of N. norvegicus in Northern Europe since at least the early 1980s and since then extensive studies on its life history and pathogenesis have occurred. Despite these research efforts significant gaps exist in our knowledge of the effects of parasites such as Hematodinium on the fished and non-fished portions of Nephrops populations and on the effect of fishery practices on the spread of infection. Furthermore, little is known about the effect of this (and other) pathogens on cohort survivability and the likelihood that early life stages will be effectively recruited to the fishery. This review summarises the available literature on diseases of these two lobster genera and provides an assessment of future research needs in this discipline.     

Expression in drosophila of tandem amyloid β peptides provides insights into links between aggregation and neurotoxicity

The generation and subsequent aggregation of amyloid β (Aβ) peptides play a crucial initiating role in the pathogenesis of Alzheimer disease (AD). The two main isoforms of these peptides have 40 (Aβ(40)) or 42 residues (Aβ(42)), the latter having a higher propensity to aggregate in vitro and being the main component of the plaques observed in vivo in AD patients. We have designed a series of tandem dimeric constructs of these Aβ peptides to probe the manner in which changes in the aggregation kinetics of Aβ affect its deposition and toxicity in a Drosophila melanogaster model system. The levels of insoluble aggregates were found to be substantially elevated in flies expressing the tandem constructs of both Aβ(40) and Aβ(42) compared with the equivalent monomeric peptides, consistent with the higher effective concentration, and hence increased aggregation rate, of the peptides in the tandem repeat. A unique feature of the Aβ(42) constructs, however, is the appearance of high levels of soluble oligomeric aggregates and a corresponding dramatic increase in their in vivo toxicity. The toxic nature of the Aβ(42) peptide in vivo can therefore be attributed to the higher kinetic stability of the oligomeric intermediate states that it populates relative to those of Aβ(40) rather than simply to its higher rate of aggregation.     

兴国红鲤 MHC Ⅱ类 α 基因多态性、表达及其与鱼体抗病力关系的分析简

对41尾感病和22尾抗病兴国红鲤的308个有效克隆进行测序,获得171条不同的MHCⅡ类α基因编码序列,分属26个不同的等位基因,其中Cyca-DXA24—Cyca-DXA36为新发现的13个等位基因。MHCⅡ类α基因片段的长度为624 bp,包括第1—4个外显子,分别编码信号肽、α1和α2结构域及连接肽/跨膜区。α1结构域的变异明显大于α2结构域,表现在α1结构域中核苷酸和氨基酸变异位点比例(55.16%和79.76%)明显高于α2结构域的变异位点比例(45.96%和68.42%)。α1结构域的PBR区的非同义碱基替换率(dN)与同义碱基替换率(dS)的比值ω(ω=dN/dS)为5.742,远远高于非抗原结合位点(non-PBR)及α2结构域的0.755、0.592,揭示兴国红鲤MHCⅡ类α基因的α1结构域在进化过程中受到正向选择作用。等位基因Cyca-DXA24(P0.01)与兴国红鲤对嗜水气单胞菌的抗性相关,等位基因Cyca-DXA3(P0.05)、Cyca-DXA4(P0.01)、Cyca-DXA6(P0.05)、Cyca-DXA33(P0.05)与兴国红鲤对嗜水气单胞菌的易感性相关。荧光定量PCR结果表明,MHCⅡ类α基因在健康兴国红鲤的肾、肝、鳃等10个组织均能普遍表达。人工感染嗜水气单胞菌后,肾、肝、脾3个组织中的MHCⅡ类α基因的表达量均发生了不同程度的变化,表明MHCⅡ类α分子在兴国红鲤的免疫反应中起到重要作用。     

Infection and replication sites of Spiroplasma kunkelii (Class: Mollicutes) in midgut and Malpighian tubules of the leafhopper Dalbulus maidis

Spiroplasma kunkelii distribution and infection mechanisms in the intestines and Malpighian tubules of Dalbulus maidis were investigated by transmission electron microscopy. Spiroplasmas were found between microvilli and in endocytic vesicles of the midgut epithelium. At the basal part, cytoplasmic vesicles contained multiple spiroplasmas with tube-like extensions and spiroplasmas accumulated between the laminae rara and densa of the basal lamina. Tip structures of flask-shaped spiroplasmas pierced the lamina densa that was discontinuous in close proximity to spiroplasmas. Spiroplasmas were found in hemolymph, crossed the basal lamina of Malpighian tubule epithelium and accumulated at high numbers in muscle cells that had cytopathogenic changes. S. kunkelii had perithrochous approximately 8nm diameter structures determined to be fimbriae protruding from the cell surface, and similar structures were adhering to the basal lamina of midgut epithelium and to external lamina of muscle cells. Further, spiroplasmas had pili-like appendages at one or both cell poles and appeared to conjugate. This is the first time that fimbriae and pili have been observed in a mollicutes.