Genome-wide patterns of polymorphism in an inbred line of the African malaria mosquito Anopheles gambiae.

Anopheles gambiae is a major mosquito vector of malaria in Africa. Although increased use of insecticide-based vector control tools has decreased malaria transmission, elimination is likely to require novel genetic control strategies. It can be argued that the absence of an A. gambiae inbred line has slowed progress toward genetic vector control. In order to empower genetic studies and enable precise and reproducible experimentation, we set out to create an inbred line of this species. We found that amenability to inbreeding varied between populations of A. gambiae. After full-sib inbreeding for ten generations, we genotyped 112 individuals--56 saved prior to inbreeding and 56 collected after inbreeding--at a genome-wide panel of single nucleotide polymorphisms (SNPs). Although inbreeding dramatically reduced diversity across much of the genome, we discovered numerous, discrete genomic blocks that maintained high heterozygosity. For one large genomic region, we were able to definitively show that high diversity is due to the persistent polymorphism of a chromosomal inversion. Inbred lines in other eukaryotes often exhibit a qualitatively similar retention of polymorphism when typed at a small number of markers. Our whole-genome SNP data provide the first strong, empirical evidence supporting associative overdominance as the mechanism maintaining higher than expected diversity in inbred lines. Although creation of A. gambiae lines devoid of nearly all polymorphism may not be feasible, our results provide critical insights into how more fully isogenic lines can be created

Incompatibility and Competitive Exclusion of Genomic Segments between Sibling Drosophila Species

The extent and nature of genetic incompatibilities between incipient races and sibling species is of fundamental importance to our view of speciation. However, with the exception of hybrid inviability and sterility factors, little is known about the extent of other, more subtle genetic incompatibilities between incipient species. Here we experimentally demonstrate the prevalence of such genetic incompatibilities between two young allopatric sibling species, Drosophila simulans and D. sechellia. Our experiments took advantage of 12 introgression lines that carried random introgressed D. sechellia segments in different parts of the D. simulans genome. First, we found that these introgression lines did not show any measurable sterility or inviability effects. To study if these sechellia introgressions in a simulans background contained other fitness consequences, we competed and genetically tracked the marked alleles within each introgression against the wild-type alleles for 20 generations. Strikingly, all marked D. sechellia introgression alleles rapidly decreased in frequency in only 6 to 7 generations. We then developed computer simulations to model our competition results. These simulations indicated that selection against D. sechellia introgression alleles was high (average s = 0.43) and that the marker alleles and the incompatible alleles did not separate in 78% of the introgressions. The latter result likely implies that most introgressions contain multiple genetic incompatibilities. Thus, this study reveals that, even at early stages of speciation, many parts of the genome diverge to a point where introducing foreign elements has detrimental fitness consequences, but which cannot be seen using standard sterility and inviability assays

Building Public Health System Capacity for Diabetes and Hypertension Care in Western Kenya

Background and Hypothesis: In western Kenya, estimates for prevalence of hypertension are 6-24% and diabetes are 3-5%. Complications of hypertension and diabetes are some of the fastest growing causes of morbidity and mortality in Kenya. There is limited knowledge and poor training pertaining to noncommunicable diseases (NCDs) making treatment difficult. With shortages of physicians and mid-level providers, protocol driven nursing care of hypertension and diabetes has shown to be effective. Through partnerships with counties, the NCD care program has screened 134,923 and treated 12,566 individuals for diabetes and screened 238,078 and treated 29,377 individuals for hypertension. My summer project was to utilize Academic Model Providing Access to Healthcare’s (AMPATH) partnership with the Kenyan Ministry of Health (MOH) to improve access and quality of hypertension and diabetes care delivery at county MOH facilities. These improvements can be achieved through increasing our joint mentorship program led by AMPATH and county MOH staff; introducing the AMPATH Medical Record System (AMRS) into county clinics to improve care; and quality improvement with the Home Glucose Monitoring team. Personal Role: I created Standard Operating Procedures (SOPs) for Integrative Screening, Clinical Mentorship, and Home Glucose Monitoring (HGM); designed a user manual for AMRS; helped develop a M&E plan for the HGM program; and assisted in the authorship of a grant to scale mentorship for diabetes and hypertension to 60 more clinical sites. Conclusion and Potential Impact: This project is a product of the partnership of AMPATH and the MOH to make accessible, high-quality care for hypertension and diabetes available across levels of care. By partnering with the Kenyan government and implementing care in the public sector, improvements in care are sustainable. My involvement will facilitate scaling the project to treat more patients through improving organizational capacity and helping apply for funds to implement in new areas. &nbsp

<i>Phytophthora betacei</i>, a new species within <i>Phytophthora</i> clade 1c causing late blight on <i>Solanum betaceum </i>in Colombia

Over the past few years, symptoms akin to late blight disease have been reported on a variety of crop plants in South America. Despite the economic importance of these crops, the causal agents of the diseases belonging to the genus Phytophthora have not been completely characterized. In this study, a new Phytophthora species was described in Colombia from tree tomato (Solanum betaceum), a semi-domesticated fruit grown in northern South America. Comprehensive phylogenetic, morphological, population genetic analyses, and infection assays to characterize this new species, were conducted. All data support the description of the new species, Phytophthora betacei sp. nov. Phylogenetic analyses suggest that this new species belongs to clade 1c of the genus Phytophthora and is a close relative of the potato late blight pathogen, P. infestans. Furthermore, it appeared as the sister group of the P. andina strains collected from wild Solanaceae (clonal lineage EC-2). Analyses of morphological and physiological characters as well as host specificity showed high support for the differentiation of these species. Based on these results, a complete description of the new species is provided and the species boundaries withinPhytophthora clade 1c in northern South America are discussed

Determination of variation with frequency of fatigue crack growth rates in aggresive environments

An analytical method is presented for separating the frequency dependent and frequency independent components of fatigue crack growth rate data. An expression is then developed which can be used to calculate the aggressive environment fatigue crack growth rate at an arbitrary frequency. By use of this fatigue data analysis method, aggressive environment fatigue crack growth rates are predicted for two material-environment combinations. For the same two material-environment combinations, fatigue crack growth rates are also calculated using a superposition technique frequently proposed in the literature, in which the environmental fatigue component is determined from sustained load stress corrosion data. Results calculated from the two methods are compared, and it is shown that the prediction of aggressive environment fatigue crack growth by fatigue data analysis is generally a superior approach.Includes bibliographical references (pages 52-53)California State University, Northridge. Department of Engineering

HIV-positive parents, HIV-positive children, and HIV-negative children’s perspectives on disclosure of a parent’s and child’s illness in Kenya

HIV disclosure from parent to child is complex and challenging to HIV-positive parents and healthcare professionals. The purpose of the study was to understand the lived experiences of HIV-positive parents and their children during the disclosure process in Kenya. Sixteen HIV-positive parents, seven HIV-positive children, and five HIV-negative children completed semistructured, in-depth interviews. Data were analyzed using the Van Kaam method; NVivo 8 software was used to assist data analysis. We present data on the process of disclosure based on how participants recommended full disclosure be approached to HIV-positive and negative children. Participants recommended disclosure as a process starting at five years with full disclosure delivered at 10 years when the child was capable of understanding the illness, or by 14 years when the child was mature enough to receive the news if full disclosure had not been conducted earlier. Important considerations at the time of full disclosure included the parent’s and/or child’s health statuses, number of infected family members’ illnesses to be disclosed to the child, child’s maturity and understanding level, and the person best suited to deliver full disclosure to the child. The results also revealed it was important to address important life events such as taking a national school examination during disclosure planning and delivery. Recommendations are made for inclusion into HIV disclosure guidelines, manuals, and programs in resource-poor nations with high HIV prevalence

Husisha: Training Peer-Counselors in Adolescent Problem-Solving Therapy in Eldoret, Kenya: Implementation, Adaptation, and Outcomes

Background and Objective: In Kenya, youth needing mental health (MH) treatment vastly outnumber licensed mental health professionals. Task-sharing MH treatment to non-professionals has potential to reduce the treatment gap. For youth, non-professional peer counselors have the benefit of increasing engagement and reducing stigma. Problem-solving therapy (PST) is one treatment shown to alleviate MH symptoms even when delivered by non-professionals. Here we (1) evaluate the implementation of a PST training and (2) codify adaptations for PST implementation at a youth drop-in center at Family Health Options Kenya.Experimental Design or Project Methods: A 2-week training for peer mentors was conducted. Curriculum included core counseling skills, overview of MH, and PST introduction and application. Peer Outcomes: Mean scores from pre- and post-written exams were compared using paired t-tests. Standard role plays were evaluated using the Working with children – Assessment of Competencies Tool (WeACT). Consensus WeACT scores from pre- and post-role plays were compared using paired t-tests. Adaptations: Feedback on cultural acceptability, language comprehensibility, and intervention flow was collected. Proposed intervention changes were coded within the Ecological Validity Model framework.Results: Based on a written exam, mentors’ knowledge of MH conditions and core counseling skills improved after training (Pre: 10.88±4.36; Post: 15.38±2.88; p=.026). Competence in application of counseling skills evaluated with WeACT improved after training (Pre: 20.63±6.61; Post: 28±1.69). Examples of adaptations to PST include changes to address stigma for MH treatment in Kenya and redistribution of content between sessions. Conclusion and Potential Impact: A 2-week PST training improved peers\u27 counseling skills and ability to deliver a manualized PST treatment. Training allowed contextual, conceptual, and methodological adaptations to PST for use in a Kenyan context.Implementing and improving lay-counselor trainings for MH interventions in Kenya has the potential to increase access to preliminary MH treatment

Metapopulation dominance and genomic-island acquisition of Bradyrhizobium with superior catabolic capabilities

Root nodule-forming rhizobia exhibit a bipartite lifestyle, replicating in soil and also within plant cells where they fix nitrogen for legume hosts. Host control models posit that legume hosts act as a predominant selective force on rhizobia, but few studies have examined rhizobial fitness in natural populations. Here, we genotyped and phenotyped Bradyrhizobium isolates across more than 800 km of the native Acmispon strigosus host range. We sequenced chromosomal genes expressed under free-living conditions and accessory symbiosis loci expressed in planta and encoded on an integrated ‘symbiosis island’ (SI). We uncovered a massive clonal expansion restricted to the Bradyrhizobium chromosome, with a single chromosomal haplotype dominating populations, ranging more than 700 km, and acquiring 42 divergent SI haplotypes, none of which were spatially widespread. For focal genotypes, we quantified utilization of 190 sole-carbon sources relevant to soil fitness. Chromosomal haplotypes that were both widespread and dominant exhibited superior growth on diverse carbon sources, whereas these patterns were not mirrored among SI haplotypes. Abundance, spatial range and catabolic superiority of chromosomal, but not symbiosis genotypes suggests that fitness in the soil environment, rather than symbiosis with hosts, might be the key driver of Bradyrhizobium dominance

Metapopulation dominance and genomic-island acquisition of Bradyrhizobium with superior catabolic capabilities

Root nodule-forming rhizobia exhibit a bipartite lifestyle, replicating in soil and also within plant cells where they fix nitrogen for legume hosts. Host control models posit that legume hosts act as a predominant selective force on rhizobia, but few studies have examined rhizobial fitness in natural populations. Here, we genotyped and phenotyped Bradyrhizobium isolates across more than 800 km of the native Acmispon strigosus host range. We sequenced chromosomal genes expressed under free-living conditions and accessory symbiosis loci expressed in planta and encoded on an integrated ‘symbiosis island’ (SI). We uncovered a massive clonal expansion restricted to the Bradyrhizobium chromosome, with a single chromosomal haplotype dominating populations, ranging more than 700 km, and acquiring 42 divergent SI haplotypes, none of which were spatially widespread. For focal genotypes, we quantified utilization of 190 sole-carbon sources relevant to soil fitness. Chromosomal haplotypes that were both widespread and dominant exhibited superior growth on diverse carbon sources, whereas these patterns were not mirrored among SI haplotypes. Abundance, spatial range and catabolic superiority of chromosomal, but not symbiosis genotypes suggests that fitness in the soil environment, rather than symbiosis with hosts, might be the key driver of Bradyrhizobium dominance

Husisha: Training Peer-Counselors in Adolescent Problem-Solving Therapy in Eldoret, Kenya: Implementation, Adaptation, and Outcomes

Background and Objective:In Kenya, youth needing mental health (MH) treatment vastly outnumber licensed mental health professionals. Task-sharing MH treatment to non-professionals has potential to reduce the treatment gap. For youth, non-professional peer counselors have the benefit of increasing engagement and reducing stigma. Problem-solving therapy (PST) is one treatment shown to alleviate MH symptoms even when delivered by non-professionals. Here we (1) evaluate the implementation of a PST training and (2) codify adaptations for PST implementation at a youth drop-in center at Family Health Options Kenya. Experimental Design or Project Methods:A 2-week training for peer mentors was conducted. Curriculum included core counseling skills, overview of MH, and PST introduction and application.Peer Outcomes: Mean scores from pre- and post-written exams were compared using paired t-tests. Standard role plays were evaluated using the Working with children – Assessment of Competencies Tool (WeACT). Consensus WeACT scores from pre- and post-role plays were compared using paired t-tests.Adaptations: Feedback on cultural acceptability, language comprehensibility, and intervention flow was collected. Proposed intervention changes were coded within the Ecological Validity Model framework. Results:Based on a written exam, mentors’ knowledge of MH conditions and core counseling skills improved after training (Pre: 10.88±4.36; Post: 15.38±2.88; p=.026). Competence in application of counseling skills evaluated with WeACT improved after training (Pre: 20.63±6.61; Post: 28±1.69). Examples of adaptations to PST include: changes to address stigma for MH treatment in Kenya and redistribution of content between sessions. Conclusion and Potential Impact:A 2-week PST training improved peers\u27 counseling skills and ability to deliver a manualized PST treatment. Training allowed contextual, conceptual, and methodological adaptations to PST for use in a Kenyan context. Implementing and improving lay-counselor trainings for MH interventions in Kenya has the potential to increase access to preliminary MH treatment