Riboswitch regulation of methionine metabolism and vitamin B12 uptake in mycobacteria – implications for drug susceptibility and pathogenesis

Alterations in the genetic capacity for cobamide biosynthesis have been identified as potentially critical in the evolution of Mycobacterium tuberculosis from a putative environmental ancestor. Moreover, recent studies have implicated cobamide biosynthesis pathway genes in the adaptation of the bacillus to intracellular pathogenesis. Although mycobacteria retain essential biochemical reactions that require cobamides, the specific role of these co-factors during tuberculosis (TB) disease remains unresolved. This thesis aimed to examine the production, uptake, and utilization of cobamides in mycobacteria using M. smegmatis as a model. To this end, the genetic capacity for de novo production and uptake of cobamide in host-associated and environmental mycobacteria was assessed, followed by direct validation in M. smegmatis. A combination of genetics, gene expression analysis, live-cell time-lapse microscopy and targeted metabolite and protein analysis via mass spectrometry (MS) was then employed to investigate cobamide riboswitch-dependent regulation of methionine biosynthesis in M. smegmatis. Results indicated that, in wild-type M. smegmatis, de novo cobamide biosynthesis ensured constitutive repression of metE, the gene encoding the mycobacterial cobalamin-independent methionine synthase. Owing to this repression, metH, a gene encoding the cobalamin-dependent methionine synthase, was found to be conditionally essential for bacillary replication in vitro. Drug susceptibility testing to investigate the link between cobamides and the intrinsic resistance to anti-folate antibiotics confirmed novel mycobacterial vulnerabilities in cobamide-related methionine metabolism, indicating that the outcomes of cobamidedependent regulation may have relevance to mycobacterial pathogenesis and drug discovery. In contrast to M. tuberculosis, which was previously shown to transport exogenous CNCbl readily, M. smegmatis poorly assimilated exogenous co-factor despite the presence of multiple putative cobamide transporters. However, uptake was enhanced in a mutant requiring CNCbl for growth. Elucidating the factors which regulate cobamide biosynthesis and co-factor utilization in M. smegmatis, an environmental mycobacterium, might provide a lens through which to consider the differential regulation and utilization of cobamides in M. tuberculosis, an obligate pathogen with a limited host range

Agricultural Trade Liberalization in Kenya and Implications for Kenya China Trade Relations

In developing economies such as Kenya, agriculture is a ‘special’ sector and a fundamental engine for economic growth. Kenya has actively pursued agricultural trade liberalization though the existing studies have not clearly delineated its implications on Kenya-China trade relations. What is evident though is that the trade deficit between Kenya and China had widened to the tune US$3.5 billion as of 2018. This is notwithstanding the fact that the trade relations have been beneficial to Kenya in terms of affording a market to major Kenyan exports. Nevertheless, there is flimsy research on the implications of agricultural trade liberalization on Kenya-China trade relations. It is in this regard that the study sought to give direction on how Kenya can capitalize on agricultural trade liberalization to address the widening trade deficit with China. Emphasis was on how tariffs in agriculture and foreign direct investment impact on Kenya-China trade relations. The study was guided by the theory of firm heterogeneity. The study utilized secondary data with United Nations Conference on Trade and Investment (UNCTAD), UN Comtrade database and the World Trade Organization as the sources of the data. The study established that there is limited FDI inflows in the agricultural sector. It is therefore important for the government to ensure that there is conducive environment for investment in agriculture so as to diversify the share of Kenya’s agricultural exports to China. Also, there is need for the adoption of policies that stimulate the diffusion of new technology in agriculture that would facilitate the transition to climate smart crops that would increase investment opportunities as well as contribute to Kenya’s exports. Moreover, since agricultural products face tariff barriers in China, Kenya needs to renegotiate its terms of trade with China in attempts to narrow down its trade deficit. Keywords: Agricultural trade liberalization, trade deficit, tariffs, foreign direct investment DOI: 10.7176/DCS/10-1-07 Publication date: January 31st 2020

Ionic Liquids and GUMBOS for Biomedical and Sensing Applications

This dissertation is a synopsis of advancements in the field of ionic liquids and a group of uniform materials based on organic salts (GUMBOS) in biomedical applications, especially with regard to cancer research. The toxicity of chemotherapeutic agents to normal tissues and drug resistance are a major concern in cancer treatment. In this dissertation, GUMBOS and nanoGUMBOS as well as ionic liquids and nanodroplets are explored as possible chemotherapeutic agents with minimal toxicity to normal cells. In the first part of my dissertation, exploitation of ionic liquid chemistry to modulate toxicity of rhodamine 6G is reported. Rhodamine 6G-based GUMBOS with varying counter-anions that are stable under physiological conditions, display excellent fluorescence photostability, and more importantly have tunable chemotherapeutic properties were synthesized. In vitro studies indicate that the hydrophobic compounds of this series allow production of nanoGUMBOS which are non-toxic to normal cells and toxic to cancer cells. Furthermore, the anions, in combination with cations such as sodium, were observed to be non-toxic to both normal and cancer cells. Thus, we demonstrate that both the cation and anion play an extremely important and cooperative role in the anticancer properties of these compounds. In the second part, the concept of multifunctional nanoparticles is introduced and exploited for theranostic applications. Nanoparticles possessing multiple properties such as luminescence, magnetism, and cancer targeting, were synthesized and explored for use in cancer therapy. In this regard, it is demonstrated that these nanoparticles can not only be used in diagnostics and as drug delivery agents, but also as active pharmacophores. Finally, the third part of this dissertation is a report of novel ionic liquid based pH sensitive colorimetric nanosensors based on phosphonium and fluorescein. The pH dependent size changes in the nanodroplets are demonstrated and potential applications in detecting acidic environment and anticancer activity are investigated

Determinants of Efficiency in Cargo Logistics: A Case Study of Bollore Transport and Logistics Kenya Limited.

This study sought to examine the determinants of efficiency in cargo logistics of Bollore Transport and Logistics Kenya limited. The specific objectives of the study were; to establish the effects of customs processes on efficiency of Bollore Transport and Logistics Limited; to establish the effects of logistics infrastructure on efficiency of Bollore Transport and Logistics Kenya Limited; to determine the effects of information technology on efficiency of Bollore Transport and Logistics Kenya Limited and to assess the effects of government clearing procedures on efficiency of Bollore Transport and Logistics Kenya Limited. To strengthen the conceptual framework the researcher used theories such as resource base theory, the theory of constraints and system’s theory.  The study was primary data which was collected through the use of questionnaires with respondents at the Bollore Transport and Logistics Company. The sample size was 93. A modified Likert scale questionnaire was developed and divided into three parts. A pilot study was carried out to refine the instrument. The quality and consistency of the study were further assessed using Cronbach's alpha. Data analysis was performed using Statistical Package for Social Science (SPSS Version 23) for Windows. The analysis was done using frequency counts, percentages, means and standard deviation, regression, correlation and the information generated will be presented in the form of graphs, charts and tables. From the research findings, the study concluded all the independent variables studied have a significant effect on the efficiency of cargo logistics as indicated by the strong coefficient of correlation and a p-value which is less than 0.05. The overall effect of the analysed factors was very high as indicated by the coefficient of determination. The overall P-value of 0.00 which is less than 0.05 (5%) is an indication of the relevance of the studied variables, significant at the calculated 95% level of significance. Keywords: Determinants, Efficiency, Cargo Logistics, Bolomore Transport Keny

Institutional Factors Inuencing Churches to Sponsor Public Schools in Turbo Division, Uasin Gishu County

The purpose of the study was to investigate institutional factors influencing churches to sponsor public schools in Turbo Division, Uasin Gishu County. The specific objective of the study was to establish institutional roles influencing churches to sponsor public schools. In the study, the literature review was guided by the objective of the study. The study adopted descriptive survey research design. The target population was 97 public schools. The study involved 41 church sponsored schools that comprised 23 primary schools and 18 public secondary schools. The respondents were drawn from school management committee members, Head Teachers and Board of Management members. Data was collected using questionnaires, oral interviews and observations schedules. The data was analyzed using both qualitative and quantitative techniques and presented using tables and figures. The results indicated that the institutional factors that influence churches to sponsor public schools include the religion of the teachers employed in their schools, the politics of the area, the school management representations and workshop career choices. On the hand, the church sponsors fail to admit students from different faith equally. The findings indicated that gaining influence of the school management raises faith of the sponsors and hence increase in sponsorship. It was recommended that the school sponsor should come up with neutral professional service scheme in the areas like guidance and counseling, teaching of religious syllabus and chaplaincy so as to help raise their level of influence. It was also recommended that the sponsors should also keep off politics within the schools they sponsor if their level of influence has to rise

Community Participation in Surface Water Harvesting in Marigat Division, Kenya

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Effects of Client-Oriented Marketing Strategies on Perception of Enrolment: Evidence from Moi University, Kenya

Self Sponsored students are increasingly demanding client-oriented institutions, and universities and colleges are working to meet their demands. This study investigated on the effects of Client-Oriented Marketing Strategies (COMS) on Perception of Enrolment (PE) by students under Privately Sponsored Students Programmes (PSSP). Many marketing specialists are now seeing the 4Ps (Product, Place, Pricing and Promotion) as too product-oriented and have adopted the COMS’s 4Cs (Customer Value, Customer Cost, Customer Convenience and Customer Communication) marketing mix. The study adopted survey design and cluster sampling was used to select the five academic schools/ faculties of Moi University. Simple random sampling was used to identify the targeted 284 individual students of the study. Questionaries was used to collect data. The results of the study showed that 4Cs affects Perception of Enrolment. Multiple Linear Regression showed that 4Cs accounted for a total variation of 55% of the changes in PE (R2=.550), while other Marketing strategies account for 45%. The model of 4Ps to 4Cs adopted by Elliott de Sáez was used to demonstrate how Client-Oriented Marketing Strategies impacts on Perception of Enrolment. The study recommends that Moi University and other universities should pay serious attention Clint-Oriented Marketing Strategies in the marketing of their programmes since they affect the Perception of Enrolment. Keywords: Customer Value, Customer Cost, Customer Convenience, Customer Communication, Perception of Enrolmen

Correlation between Class Size and Pupils’ Acquisition of Early Mathematics Competencies: A Case of Kericho County, Kenya

Mathematics is one of the core subjects in the Basic Education Curriculum in Kenya. It means that all pupils are required to have a strong grounding in the subject which depends on the level of their early mathematics competencies. The purpose of the study was therefore to establish the level of pupils’ acquisition of early mathematics competencies. The study was also to determine how class size was related to pupils’ acquisition of early mathematics competencies. The study was guided by Social Development Theory by Lev Vygotsky. The study adopted a correlation research design and a mixed research method approach. The dependent variable was pupils’ acquisition of early mathematics competencies while the independent variable was class size. The results from data analysis revealed that majority of the pupils had acquired early mathematics competencies and there was a difference in pupils’ acquisition of early mathematics competencies between grade three pupils in public and those in private primary schools. The relationship between class size and pupils’ acquisition of early mathematics competencies was significant at p<0.05 level of significance. Keywords: Class Size; Pupils; Acquisition of Early Mathematics Competencies; Kericho County; Kenya DOI: 10.7176/JEP/11-21-23 Publication date:July 31st 202

Guidance and Counselling: What is the level of Human and Physical Resource Preparedness in providing effective Services in Secondary Schools in Bureti Sub County, Kericho County, Kenya?

The gist of this study was to examine the human and resource preparedness to provide effective guidance and counselling (G&C) services   in secondary schools in Bureti Sub County, Kericho County, Kenya. The study used combinations of descriptive survey and correlation research designs.  Stratified sampling technique was employed to select 20 principals and 20 heads of G&C department while simple random sampling technique was used to select 400 students yielding a sample size of 440. Questionnaire, interview schedule and document analysis guide were used to collect data for the study. The study established that approximately two thirds of the practicing school guidance and counseling personnel did not have the required qualifications of diploma and above. Guidance and Counseling facilities were too inadequate to facilitate effective implementation of G&C services in most schools within the study locale. Based on the findings, it was recommended that regular workshops on G&C for public secondary school teachers and other service providers be intensified to enable them improve significantly in pedagogy and effectiveness. The importance of professional self-development and upgrading for teacher effectiveness through self-sponsored workshop attendance should be encouraged. These findings are significant to teacher counselors, Principals and the Ministry of Education Science and Technology as it will enable them to enhance G&C services in schools and achieve the set objectives of school guidance and counseling program in schools.[224  words] Keywords: Guidance and Counselling, Human and Physical Resources, Preparedness , effective Services ,  Secondary Schools,   Bureti Sub County, Kericho County, Kenya

Assessing influenza vaccine coverage among the elderly receiving long-term care services, and nurses' knowledge and attitudes towards influenza vaccination

Influenza occurs annually and has been found to be a major cause for morbidity and mortality among the elderly who are among the risk groups. The elderly residing in long-term care facilities (LTCFs) are at an even higher risk due to the confined nature of the environment and the possibility of a rapid spread in case of an outbreak. Nurses working in LTCFs often have direct contact with their patients. This puts them at greater risk of contracting influenza and also transmitting it to their patients. It is for this reason that influenza vaccination is recommended to both nurses and the elderly among other risk groups. Unfortunately, the coverage remains low for these groups. Therefore, understanding the relationship between these two groups and the factors influencing the uptake is crucial. The aim of this study was to determine trends in influenza vaccine uptake among the elderly within the LTCFs participating in the RAI-evaluation project in Finland. Additionally, the study explored the nurses' knowledge and attitudes towards influenza vaccination by means of a survey. Aggregate data on RAI-HC were obtained from the Finnish National Institute for Health and Welfare. The data contained information on different service types, the year, vaccination coverage, poor cognition, poor functioning in activities of daily living (ADL) as well as age (≥80). A survey on the nurses' knowledge and attitudes was also conducted among 89 nurses with different professional designations. Data were analyzed using SPSS and STATA. There were annual variations in influenza vaccination coverage among the 3 different service types during the years 2008-2015: 62% (57-68%) in homecare, 73% (69-76%) in residential care and 65% (54-77%) in service housing. Different patient characteristics including the service types and year of data collection were associated with vaccination coverage. Among the nurses, better knowledge and attitudes were positively associated with their vaccination status, other background factors such as professional designation and gender also affected but were not statistically significant. Even though the data used are not directly related, it supports the notion that there might be a relationship between nurses' vaccination status, knowledge and attitudes and the coverage among the elderly. This relationship can be seen by how the nurses' vaccination status affect their ability to recommend vaccination to their patients. As this relationship is being further explored, targeted vaccination programs should be developed towards meeting the needs of both nurses and their residents within respective service types. Based on the results, the coverage remains lower among both nurses and patients. With the knowledge that influenza vaccination still remains the most important preventive measure against influenza, focus on achieving a higher uptake among nurses and patients should be the goal. For patient safety, nurses should remember that it is their obligation and duty to get vaccinated and to advocate the same for their patients. Achieving the recommended coverage will lead to a reduction in morbidity and mortality leading to improved patient outcomes and a healthy workforce