Genetic and molecular analysis reveals that two major loci and their interaction confer clubroot resistance in canola introgressed from rutabaga.

Clubroot disease caused by Plasmodiophora brassicae is one of the serious threats to canola (Brassica napus L. subsp. napus) production. The evolution of new pathotypes rendering available resistances ineffective compel the introgression of new resistance into canola and extend our understanding of the genetic and molecular basis of the resistance. In this paper, we report the genetic and molecular basis of clubroot resistance in canola, introgressed from a rutabaga (B. napus L. subsp. rapifera Metzg. 'Polycross'), by using a doubled-haploid (DH) mapping population. Whole-genome resequencing (WGRS)-based bulked segregant analysis followed by genetic mapping and expression analysis of the genes in resistant and susceptible DH lines at 7 and 14 d after inoculation were carried out. Following this approach, two major quantitative trait loci (QTL) located at 14.41-15.44 Mb of A03 and at 9.96-11.09 Mb of A08 chromosomes and their interaction was observed to confer resistance to pathotypes 3H, 3A, and 3D. Analysis of the genes from the two QTL regions suggested that decreased expression of sugar transporter genes (BnaA03g29290D and BnaA03g29310D) may play an important role in resistance conferred by the A03 QTL, while increased expression of the toll/interleukin-1 receptor (TIR)-nucleotide binding (NB)-leucine rich repeat (LRR) (TNL) genes (BnaA08g10100D, BnaA08g09220D, and BnaA08g10540D) could be the major determinant of the resistance conferred by the A08 QTL. Single-nucleotide polymorphism (SNP) allele-specific polymerase chain reaction (PCR)-based markers, which could be detected by agarose gel electrophoresis, were also developed from the two QTL regions for use in breeding including pyramiding of multiple clubroot resistance genes.

Mining for natural product antileishmanials in a fungal extract library.

Leishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the World's poorest, however vaccines are absent and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leishmaniasis. Most of these collaborative efforts have relied upon the small molecule synthetic compound libraries held by industry, but the number of New Chemical Entities (NCE) identified and entering development as antileishmanials has been very low. In light of this, here we describe a public-private effort to identify natural products with activity against Leishmania mexicana, a causative agent of cutaneous leishmanaisis (CL). Utilising Hypha Discovery's fungal extract library which is rich in small molecule (<500 molecular weight) secondary metabolites, we undertook an iterative phenotypic screening and fractionation approach to identify potent and selective antileishmanial hits. This led to the identification of a novel oxidised bisabolane sesquiterpene which demonstrated activity in an infected cell model and was shown to disrupt multiple processes using a metabolomic approach. In addition, and importantly, this study also sets a precedent for new approaches for CL drug discovery.

Mortality and Disability-Adjusted Life-Years (Dalys) for Common Neglected Tropical Diseases in Ethiopia, 1990-2015: Evidence from the Global Burden of Disease Study 2015.

INTRODUCTION: Neglected tropical diseases (NTDs) are important public health problems in Ethiopia. In 2013, the Federal Ministry of Health (FMOH) has launched a national NTD master plan to eliminate major NTDs of public health importance by 2020. Benchmarking the current status of NTDs in the country is important to monitor and evaluate the progress in the implementation of interventions and their impacts. Therefore, this study aims to assess the trends of mortality and Disability-adjusted Life-Years (DALY) for the priority NTDs over the last 25 years. METHODS: We used the Global Burden of Disease (GBD) 2015 estimates for this study. The GBD 2015 data source for cause of death and DALY estimation included verbal autopsy (VA), Demographic and Health Surveys (DHS), and other disease specific surveys, Ministry of Health reports submitted to United Nations (UN) agencies and published scientific articles. Cause of Death Ensemble modeling (CODEm) and/or natural history models were used to estimate NTDs mortality rates. DALY were estimated as the sum of Years of Life Lost (YLL) due to premature mortality and Years Lived with Disability (YLD). RESULTS: All NTDs caused an estimated of 6,293 deaths (95% uncertainty interval (UI): 3699-10,080) in 1990 and 3,593 deaths (95% UI: 2051 - 6178) in 2015, a 43% reduction over the 25 years. Age-standardized mortality rates due to schistosomiasis, STH and leshmaniasis have declined by 91.3%, 73.5% and 21.6% respectively between 1990 to 2015. The number of DALYs due to all NTDs has declined from 814.4 thousand (95% UI: 548 thousand-1.2million) in 1990 to 579.5 thousand (95%UI: 309.4 thousand-1.3 million) in 2015. Age-standardized DALY rates due to all NTDs declined by 30.7%, from 17.6 per 1000(95%UI: 12.5-26.5) in 1990 to 12.2 per 1000(95%UI: 6.5 - 27.4) in 2015. Age-standardized DALY rate for trachoma declined from 92.7 per 100,000(95% UI: 63.2 - 128.4) in 1990 to 41.2 per 100,000(95%UI: 27.4-59.2) in 2015, a 55.6% reduction between 1990 and 2015. Age-standardized DALY rates for onchocerciasis, schistosomiasis and lymphiaticfilariasis decreased by 66.2%, 29.4% and 12.5% respectively between 1990 and 2015. DALY rate for ascariasis fell by 56.8% over the past 25 years. CONCLUSIONS: Ethiopia has made a remarkable progress in reducing the DALY rates for most of the NTDs over the last 25 years. The rapid scale of interventions and broader system strengthening may have a lasting impact on achieving the 2020 goal of elimination of most of NTDs. Ethiopia should strengthen the coverage of integrated interventions of NTD through proper coordination with other health programs and sectors and community participation to eliminate NTDs by 2020.

The Ethiopian initiative to build sustainable capacity for operational research: overview and lessons learned.

SETTING: Programme-based operational research is instrumental for the enhancement of tuberculosis (TB) control. In 2012, the Ethiopian Federal Ministry of Health launched an initiative for capacity building in operational research (OR). OBJECTIVE: To develop sustainable capacity for OR in Ethiopia in a multiyear initiative. DESIGN: The initiative was developed in collaboration with regional, national and international experts. Teams representing regions in Ethiopia conducted OR addressing national and regional priorities. To make use of local expertise and increase sustainability, a domestic mentor training programme was included. Existing capacity was enhanced through a competitive grant scheme providing TB researchers with financial and technical support. The Ethiopian Tuberculosis Research Advisory Committee was also supported in its functions. Regional ethics review bodies were strengthened or established where they did not exist. RESULTS: Fifty-two people were trained and conducted 13 OR projects, of which six have been published to date. In addition, eight protocols were supported through grants. Ethics review bodies were strengthened in all regions. CONCLUSION: The initiative trained participants from all regions and succeeded in the completion of all stages of the OR process. The success of the programme can be attributed to the team approach, 'learning while doing', integrated mentorship programme and strong national ownership.

Contexte : La recherche opérationnelle programmatique joue un rôle majeur dans la lutte contre la tuberculose (TB). En 2012, le ministère éthiopien de la santé a lancé une initiative de renforcement des capacités en recherche opérationnelle (OR).Objectif : Développer des capacités pérennes d'OR en Ethiopie dans le cadre d'une initiative s'étalant sur plusieurs années.Schéma : L'initiative a été élaborée en collaboration avec des experts régionaux, nationaux et internationaux. Des équipes représentant les régions d'Ethiopie ont réalisé une OR relative aux priorités nationales et régionales. Un programme de formation de mentors domestiques a été inclus afin d'exploiter l'expertise locale et d'accroitre la pérennité. La capacité existante a été renforcée grâce à un financement compétitif offrant aux chercheurs du domaine de la TB un soutien financier et technique. Le fonctionnement du comité de concertation éthiopien sur la recherche relative à la TB a également bénéficié d'un soutien. Les comités d'éthique régionaux ont été renforcés ou créés lorsqu'ils n'existaient pas.Résultats : Cinquante-deux personnes ont été formées et ont réalisé 13 projets d'OR, dont six ont été publiés à ce jour. De plus, huit protocoles ont été soutenus par des subventions. Les comités d'éthique ont été renforcés dans toutes les régions.Conclusion: L'initiative a formé des participants de toutes les régions et ceux-ci ont terminé avec succès toutes les étapes du processus d'OR. Le succès de ce programme peut être attribué à une approche sous forme de travail d'équipe, à un apprentissage sur le tas, au programme intégré de mentors et à une forte appropriation nationale.

Marco de referencia: La práctica de investigación operativa dentro del marco programático es importante en el fortalecimiento del control de la tuberculosis (TB). En el 2012, el Ministerio Federal de Salud de Etiopía puso en marcha una iniciativa encaminada a crear capacidad de investigación operativa (OR).Objetivo: Desarrollar capacidad sostenible de OR en el país mediante una iniciativa plurianual.Método: La iniciativa se formuló en cooperación con expertos regionales, nacionales e internacionales. Varios equipos, en representación de las regiones de Etiopía, llevaron a cabo proyectos de OR que respondían a las prioridades nacionales y regionales. Con el propósito de aprovechar las competencias locales y mejorar la sostenibilidad se incorporó al proyecto un programa interno de capacitación de tutores. Se reforzó la capacidad existente mediante un plan de subvenciones otorgadas por concurso y destinado a suministrar ayuda económica y técnica a los investigadores en el campo de la TB. Asimismo, se prestó apoyo al funcionamiento del Comité Asesor de la Investigación sobre TB en Etiopía. Se reforzaron los comités de ética existentes y donde no existían se crearon nuevos comités.Resultados: Se capacitó a 52 personas y se llevaron a cabo 13 proyectos de OR, de los cuales seis han publicado sus resultados hasta la fecha. Se financiaron además ocho protocolos por conducto de las subvenciones. Se reforzaron los comités de ética en todas las regiones.Conclusión: Gracias a esta iniciativa se capacitó a los participantes provenientes de todas las regiones y se logró la compleción de todas las etapas del proceso de OR. El éxito del programa se puede atribuir a la estrategia de equipo, el aprendizaje en la acción, la integración del programa de tutoría y a una decidida apropiación nacional de la iniciativa.

Aggressive angiomyxoma of the pelvis and perineum: case study.

Aggressive angiomyxoma (AAM) is a rare locally aggressive tumor affecting the pelvis and perineum of young females. Histopathologically, it is characterized by fibreoblasts in a myxoid background with vascular proliferation, scanty mitotic figure and no real capsule. AAM needs to be considered in the differential diagnosis of vulval mass in a reproductive age woman. We describe the first Ethiopian case of huge, recurrent, AAM of the pelvis and perineum in a 35 year old para II lady and stress that early diagnosis offers a better option for treatment by wide local excision and low recurrence rate.

Urinary phenolic glycolipid 1 in the diagnosis and management of leprosy.

A simplified assay to measure the phenolic glycolipid 1 (PGL-1) of Mycobacterium leprae in the urine was applied to the diagnosis of leprosy and the monitoring of antileprosy chemotherapy. One hundred seventy-nine previously untreated patients and 25 normal controls were tested. The specificity of the assay was 100%. There were no false-positive results. The sensitivity of the assay varied with the type of leprosy from 92% for lepromatous leprosy to 56% for borderline lepromatous and 18% for borderline tuberculoid patients. After the onset of chemotherapy in lepromatous leprosy patients, there was often a transient increase of urinary PGL-1, followed by a steady decline. Within 3 months of multiple drug therapy, urinary PGL-1 levels were reduced by 90%-99% and were often undetectable. This assay appears to have considerable potential for monitoring chemotherapy and detecting treatment failure and relapse in patients with Hansen's disease.