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11.
Tanya L. Russell Paul F. Horwood Humpress Harrington Allan Apairamo Nathan J. Kama Albino Bobogare David MacLaren Thomas R. Burkot 《PLoS neglected tropical diseases》2022,16(2)
Across the Pacific, and including in the Solomon Islands, outbreaks of arboviruses such as dengue, chikungunya, and Zika are increasing in frequency, scale and impact. Outbreaks of mosquito-borne disease have the potential to overwhelm the health systems of small island nations. This study mapped the seroprevalence of dengue, Zika, chikungunya and Ross River viruses in 5 study sites in the Solomon Islands. Serum samples from 1,021 participants were analysed by ELISA. Overall, 56% of participants were flavivirus-seropositive for dengue (28%), Zika (1%) or both flaviviruses (27%); and 53% of participants were alphavirus-seropositive for chikungunya (3%), Ross River virus (31%) or both alphaviruses (18%). Seroprevalence for both flaviviruses and alphaviruses varied by village and age of the participant. The most prevalent arboviruses in the Solomon Islands were dengue and Ross River virus. The high seroprevalence of dengue suggests that herd immunity may be a driver of dengue outbreak dynamics in the Solomon Islands. Despite being undetected prior to this survey, serology results suggest that Ross River virus transmission is endemic. There is a real need to increase the diagnostic capacities for each of the arboviruses to support effective case management and to provide timely information to inform vector control efforts and other outbreak mitigation interventions. 相似文献
12.
Myra Hardy Josaia Samuela Mike Kama Meciusela Tuicakau Lucia Romani Margot J. Whitfeld Christopher L. King Gary J. Weil Tibor Schuster Anneke C. Grobler Daniel Engelman Leanne J. Robinson John M. Kaldor Andrew C. Steer 《PLoS medicine》2021,18(11)
BackgroundScabies is a neglected tropical disease hyperendemic to many low- and middle-income countries. Scabies can be successfully controlled using mass drug administration (MDA) using 2 doses of ivermectin-based treatment. If effective, a strategy of 1-dose ivermectin-based MDA would have substantial advantages for implementing MDA for scabies at large scale.Methods and findingsWe did a cluster randomised, noninferiority, open-label, 3-group unblinded study comparing the effectiveness of control strategies on community prevalence of scabies at 12 months. All residents from 35 villages on 2 Fijian islands were eligible to participate. Villages were randomised 1:1:1 to 2-dose ivermectin-based MDA (IVM-2), 1-dose ivermectin-based MDA (IVM-1), or screen and treat with topical permethrin 5% for individuals with scabies and their household contacts (SAT). All groups also received diethylcarbamazine and albendazole for lymphatic filariasis control. For IVM-2 and IVM-1, oral ivermectin was dosed at 200 μg/kg and when contraindicated substituted with permethrin. We designated a noninferiority margin of 5%.We enrolled 3,812 participants at baseline (July to November 2017) from the 35 villages with median village size of 108 (range 18 to 298). Age and sex of participants were representative of the population with 51.6% male and median age of 25 years (interquartile range 10 to 47). We enrolled 3,898 at 12 months (July to November 2018). At baseline, scabies prevalence was similar in all groups: IVM-2: 11.7% (95% confidence interval (CI) 8.5 to 16.0); IVM-1: 15.2% (95% CI 9.4 to 23.8); SAT: 13.6% (95% CI 7.9 to 22.4). At 12 months, scabies decreased substantially in all groups: IVM-2: 1.3% (95% CI 0.6 to 2.5); IVM-1: 2.7% (95% CI 1.1 to 6.5); SAT: 1.1% (95% CI 0.6 to 2.0). The risk difference in scabies prevalence at 12 months between the IVM-1 and IVM-2 groups was 1.2% (95% CI −0.2 to 2.7, p = 0.10). Limitations of the study included the method of scabies diagnosis by nonexperts, a lower baseline prevalence than anticipated, and the addition of diethylcarbamazine and albendazole to scabies treatment.ConclusionsAll 3 strategies substantially reduced prevalence. One-dose was noninferior to 2-dose ivermectin-based MDA, as was a screen and treat approach, for community control of scabies. Further trials comparing these approaches in varied settings are warranted to inform global scabies control strategies.Trial registrationClinitrials.gov and NCT03177993ANZCTR N12617000738325.In a cluster randomized trial, Myra Hardy and colleagues, compare mass drug administration of one-dose and two-dose ivermectin-based treatment for community control of scabies. 相似文献
13.
The human Batten disease gene CLN3 and yeast orthologue BTN1 encode proteins of unclear function. We show that the loss of BTN1 phenocopies that of BTN2, which encodes a retromer accessory protein involved in the retrieval of specific cargo from late endosomes (LEs) to the Golgi. However, Btn1 localizes to Golgi and regulates soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) function to control retrograde transport. Specifically, BTN1 overexpression and deletion have opposing effects on phosphorylation of the Sed5 target membrane SNARE, on Golgi SNARE assembly, and on Golgi integrity. Although Btn1 does not interact physically with SNAREs, it regulates Sed5 phosphorylation by modulating Yck3, a palmitoylated endosomal kinase. This may involve modification of the Yck3 lipid anchor, as substitution with a transmembrane domain suppresses the deletion of BTN1 and restores trafficking. Correspondingly, deletion of YCK3 mimics that of BTN1 or BTN2 with respect to LE-Golgi retrieval. Thus, Btn1 controls retrograde sorting by regulating SNARE phosphorylation and assembly, a process that may be adversely affected in Batten Disease patients. 相似文献
14.
Fox JH Connor T Stiles M Kama J Lu Z Dorsey K Lieberman G Liebermann G Sapp E Cherny RA Banks M Volitakis I DiFiglia M Berezovska O Bush AI Hersch SM 《The Journal of biological chemistry》2011,286(20):18320-18330
Huntington disease (HD) is a progressive neurodegenerative disorder caused by expression of polyglutamine-expanded mutant huntingtin protein (mhtt). Most evidence indicates that soluble mhtt species, rather than insoluble aggregates, are the important mediators of HD pathogenesis. However, the differential roles of soluble monomeric and oligomeric mhtt species in HD and the mechanisms of oligomer formation are not yet understood. We have shown previously that copper interacts with and oxidizes the polyglutamine-containing N171 fragment of huntingtin. In this study we report that oxidation-dependent oligomers of huntingtin form spontaneously in cell and mouse HD models. Levels of these species are modulated by copper, hydrogen peroxide, and glutathione. Mutagenesis of all cysteine residues within N171 blocks the formation of these oligomers. In cells, levels of oligomerization-blocked mutant N171 were decreased compared with native N171. We further show that a subset of the oligomerization-blocked form of glutamine-expanded N171 huntingtin is rapidly depleted from the soluble pool compared with "native " mutant N171. Taken together, our data indicate that huntingtin is subject to specific oxidations that are involved in the formation of stable oligomers and that also delay removal from the soluble pool. These findings show that inhibiting formation of oxidation-dependent huntingtin oligomers, or promoting their dissolution, may have protective effects in HD by decreasing the burden of soluble mutant huntingtin. 相似文献
15.
Yanping Zhou Wiktor Lisowski Yan Zhou Ng Wun Jern Kama Huang Eileen Fong 《Biotechnology letters》2017,39(10):1509-1514
Objectives
To improve its phosphate accumulating abilities for phosphate recycling from wastewater, a magnetotactic bacterium, Magnetospirillum gryphiswaldense, was genetically modified to over-express polyphosphate kinase.Results
Polyphosphate kinase was over-expressed in the bacterium. The recombinant strain accumulated ninefold more polyphosphate from synthetic wastewater compared to original wild type. The magnetic property of the recombinant M. gryphiswaldense strain was retained.Conclusions
The recombinant M. gryphiswaldense can be used for phosphate removal and recovery in bioremediation.16.
17.
Jonathan H Fox Teal Connor Vanita Chopra Kate Dorsey Jibrin A Kama Dorothee Bleckmann Claudia Betschart Daniel Hoyer Stefan Frentzel Marian DiFiglia Paolo Paganetti Steven M Hersch 《Molecular neurodegeneration》2010,5(1):26
Background
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD). In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD.Results
Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels.Conclusions
Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.18.
Li Jun Thean Adam Jenney Daniel Engelman Lucia Romani Handan Wand Jyotishna Mudaliar Jessica Paka Tuliana Cua Sera Taole Aalisha Sahukhan Mike Kama Meciusela Tuicakau Joseph Kado Natalie Carvalho Margot Whitfeld John Kaldor Andrew C. Steer 《PLoS neglected tropical diseases》2020,14(12)
Scabies is an important predisposing factor for impetigo but its role in more serious skin and soft tissue infections (SSTIs) is not well understood. Information is limited on incidence of SSTIs in the presence of endemic scabies. We conducted a prospective study of hospital admissions for SSTIs in the Northern Division of Fiji (population: 131,914). Prospective surveillance for admissions with impetigo, abscess, cellulitis, wound infection, pyomyositis, necrotizing fasciitis, infected scabies, and crusted scabies was conducted at the Division’s referral hospital between 2018 to 2019. Information was collected on demographic characteristics, clinical features, microbiology, treatment and outcomes. Over the study period, 788 SSTI admissions were recorded corresponding to a population incidence 647 per 100,000 person-years (95%CI 571–660). Incidence was highest at the extremes of age with peak incidence in children aged <5 years (908 per 100,000) and those aged ≥65 years (1127 per 100,000). Incidence was 1.7 times higher among the Indigenous Fijian population (753 per 100,000) compared to other ethnicities (442 per 100,000). Overall case fatality rate was 3.3%, and 10.8% for those aged ≥65 years. Scabies was diagnosed concurrently in 7.6% of all patients and in 24.6% of admitted children <5 years. There is a very high burden of hospital admissions for SSTIs in Fiji compared to high-income settings especially among the youngest, oldest and indigenous population which is concordant with scabies and impetigo distribution in this population. Our findings highlight the need for strategies to reduce the burden of SSTIs in Fiji and similar settings. 相似文献
19.
A Non-native Perennial Invades a Native Forest 总被引:5,自引:0,他引:5
Kama N. Almasi 《Biological invasions》2000,2(3):219-230
Disturbance is frequently a requirement for non-indigenous plant invasions, but plants that invade in the absence of significant disturbance pose special problems for conservationists and land stewards, as the invasion rates and effects are difficult to predict. Knowledge of the invader's population ecology is essential for the preservation of native plant communities. A sub-shrub native to South America, Tibouchina herbacea (Melastomataceae) is invading intact, wet forests and open, disturbed sites on the islands of Hawaii and Maui. Experimental tests of the importance of disturbance for reproductive rates showed that absence of canopy cover produced the highest rates of germination, survival and seed dispersal distance. Ground cover was less important, but had a positive effect on germination and a negative effect on survival. Results of these experiments suggest that T. herbacea will probably spread more quickly in open, disturbed areas, but is very capable of establishment in natural forests. If spread is arrested in the early stages, manual control may be effective, otherwise landscape-level control efforts, such as biological control, will be needed. Prevention of dispersal and control of T. herbacea in forested areas should be a priority for land managers in Hawaii. 相似文献
20.
Sujan Timilsina Mustafa O. Jibrin Neha Potnis Gerald V. Minsavage Misrak Kebede Allison Schwartz Rebecca Bart Brian Staskawicz Claudine Boyer Gary E. Vallad Olivier Pruvost Jeffrey B. Jones Erica M. Goss 《Applied and environmental microbiology》2015,81(4):1520-1529
Four Xanthomonas species are known to cause bacterial spot of tomato and pepper, but the global distribution and genetic diversity of these species are not well understood. A collection of bacterial spot-causing strains from the Americas, Africa, Southeast Asia, and New Zealand were characterized for genetic diversity and phylogenetic relationships using multilocus sequence analysis of six housekeeping genes. By examining strains from different continents, we found unexpected phylogeographic patterns, including the global distribution of a single multilocus haplotype of X. gardneri, possible regional differentiation in X. vesicatoria, and high species diversity on tomato in Africa. In addition, we found evidence of multiple recombination events between X. euvesicatoria and X. perforans. Our results indicate that there have been shifts in the species composition of bacterial spot pathogen populations due to the global spread of dominant genotypes and that recombination between species has generated genetic diversity in these populations. 相似文献