Single-Molecule Studies Of Local And Global Nucleic-Acid Dynamics

Nucleic acids undergo both global and local conformational changes that are important for their function. Structural studies have over the decades been invaluable in elucidation of various biomolecular mechanisms, hence contributing significantly to the understanding of biological events. However, a clear understanding of how molecules function in the cellular context requires investigation of their interconversion between multiple conformations, including mapping the folding landscape and any coupled changes in conformation. Work in this thesis focuses on fluorescence experiments, mainly at a single-molecule level to investigate such processes. First, a novel single-molecule approach is described focusing on local dynamics within nucleic acids and taking advantage of the fluorescent properties of 2-aminopurine (2AP) and pyrrolo-cytosine (PC) to study local dynamics at single base resolution. A click chemistry-based, single-molecule immobilization methodology that enables sufficient minimization of background fluorescence to allow single-molecule detection was utilized. In the absence of stacking interactions, both PC and 2AP fluoresce steadily for several seconds hence demonstrating their sufficient photostability for single-molecule utilization. Local dynamics using 2AP across a DNA abasic-site mimic, SAM-1 riboswitch binding pocket reorganization, and tRNAPro 3\u27 end are reported. Additionally, RNA global motions in conditions with molecular crowding, which mimics the cellular environment, are reported using the cyclic-diguanylate monophosphate (c-di-GMP) riboswitch aptamer domain as a model. Riboswitches are examples of gene-regulating elements that normally act in cis to their host mRNAs and are hence located within their 5\u27 untranslated regions. in vivo, the intracellular physiology, which is highly crowded, dictates the folding landscape of RNAs. Macromolecular crowding influences, and hence alters, the riboswitch folding pathway, and subsequently may change their mode of ligand/substrate recognition in comparison to experiments in a non-crowded medium. Single-molecule and steady-state FRET studies show that the presence of molecular crowding enhances docking of the ubiquitous bacterial c-di-GMP riboswitch aptamer region even in the absence of it\u27s metabolite. The adoption of a structure reminiscent of the ligand-bound form implies that in vivo the riboswitch can fully fold, and hence, ligand binding may only require minimal rearrangements. This may further decrease the time between ligand-recognition, interaction, and transcription enhancement

Macroeconomics and Health: The Way Forward in the WHO African Region

The specific objectives of this paper were: (i) to estimate the effects of life expectancy and mortality rates on the per capita gross national income; and (ii) to propose to countries in the African region a set of generic steps for implementing the action agenda recommended by WHO Commission for Macroeconomics and Health (CMH), within the context of national development plans and poverty reduction strategies. Four simple double-log (log-linear or constant elasticity) regression equations were estimated with data from the World Health Statistics 2011. The dependent variable in all equations was the logarithm of per capita gross national income. The key findings were as follows: in equation 1 the coefficients for life expectancy and adult literacy had a positive sign and were statistically significant at 95% confidence level; in equation 2 the coefficient for under 5 mortality rate took a negative sign and was statistically significant; in equation 3 the coefficients for adult mortality rate and adult literacy were statistically significant and had expected signs; and in equation 4 the coefficient for maternal mortality was not statistically significant at 95% level of confidence but had a negative sign as expected. These results clearly show a significant correlation between per capita gross national income and life expectancy, under 5 mortality rate, and adult mortality rate. This implies that by working closely with health development partners, countries in the African region can better their economic prospects through greater investments in close-to-client health systems and increased use of proven cost-effective prevention and treatment interventions to curb mortality and increase life expectancy. Keywords: Macroeconomics, Health, African Region, Way Forwar

Republic of Sierra Leone National Health Accounts: Financial Year 2004, 2005 and 2006

Objectives: (i) To estimate the total health expenditure from various sources; (ii) to determine total health expenditure by various financing agents; (iii) to track the flow of health funds from financing agents to various providers; (iv) to examine the distribution of funds from providers to various public health functions. Data sources: Data were collected from both secondary and primary sources. The primary data were collected using seven specially NHA designed survey questionnaires for donors,  government ministries, local councils, private employers, health service providers, insurance companies, parastatals and NGOs. The household health expenditure data were obtained from the national population census of 2004. Study selections: The NHA questionnaires were administered to were administered to a total of 177 Agencies/Institutions, comprising: 16 Donors, 11 Ministries, 19 Local Councils, 36 Private Employers, 55 Providers, 1 Insurance Company, 20 Parastatals and 36 NGOs. No information was collected on Traditional Healers, drug stores and other clinics that are not legally registered with the Ministry of Health and Sanitation. Data synthesis: The total health expenditure (THE) was approximately Le 815,911,166,288 in 2004; Le 966,849,360,080 in 2005; and Le 968,441,819,608 in 2006. The per capita total health expenditure was Le163,941 in 2004, Le189,783 in 2005 and Le185,636 in 2006. The households, through direct out-of-pocket payments to health care providers, contributed 67.13% in 2004, 64.08% in 2005 and 69.25% in 2006 to the total health expenditure. During the three years between 17.76% (year 2004) and 10.97% (year 2006) of the total health funding came from donors (international health development partners). The Government of Sierra Leone contribution grew from 15% in 2004 to 19% of the total health expenditure in 2006. Conclusion: There is need to institutionalise NHA to ensure that it can be conducted on a regular and sustained basis. In the process of institutionalizing NHA, it will be necessary: (i) to reinforce the institutional and human capacities of the unit responsible for undertaking NHA; (ii) to explore the feasibility of integrating NHA data collection within the national health information management systems; (iii) to include questions on household out-pocket payments for health care in the national household survey data collection instruments routinely carried out by the Statistics Sierra Leone (SSL); and (iv) to continually involve SSL in NHA activities

Health challenges in Africa and the way forward

Africa is confronted by a heavy burden of communicable and non-communicable diseases. Cost-effective interventions that can prevent the disease burden exist but coverage is too low due to health systems weaknesses. This editorial reviews the challenges related to leadership and governance; health workforce; medical products, vaccines and technologies; information; financing; and services delivery. It also provides an overview of the orientations provided by the WHO Regional Committee for Africa for overcoming those challenges. It cautions that it might not be possible to adequately implement those orientations without a concerted fight against corruption, sustained domestic and external investment in social sectors, and enabling macroeconomic and political (i.e. internally secure) environment

The Benefits of Employee Volunteering

Employee Volunteering helps companies build partnerships with their community. Employees, community organizations and the public at large, all benefit from the give-and-take relationships.York's Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

The essence of governance in health development

<p>Abstract</p> <p>Background</p> <p>Governance and leadership in health development are critically important for the achievement of the health Millennium Development Goals (MDGs) and other national health goals. Those two factors might explain why many countries in Africa are not on track to attain the health MDGs by 2015. This paper debates the meaning of 'governance in health development', reviews briefly existing governance frameworks, proposes a modified framework on health development governance (HDG), and develops a HDG index.</p> <p>Discussion</p> <p>We argue that unlike 'leadership in health development', 'governance in health development' is the sole prerogative of the Government through the Ministry of Health, which can choose to delegate (but not abrogate) some of the governance tasks. The general governance domains of the UNDP and the World Bank are very pertinent but not sufficient for assessment of health development governance. The WHO six domains of governance do not include effective external partnerships for health, equity in health development, efficiency in resource allocation and use, ethical practises in health research and service provision, and macroeconomic and political stability. The framework for assessing health systems governance developed by Siddiqi <it>et al </it>also does not include macroeconomic and political stability as a separate principle. The Siddiqi <it>et al </it>framework does not propose a way of scoring the various governance domains to facilitate aggregation, inter-country comparisons and health development governance tracking over time.</p> <p>This paper argues for a broader health development governance framework because other sectors that assure human rights to education, employment, food, housing, political participation, and security combined have greater impact on health development than the health systems. It also suggests some amendments to Siddigi <it>et al</it>'s framework to make it more relevant to the broader concept of 'governance in health development' and to the WHO African Region context.</p> <p>Summary</p> <p>A strong case for broader health development governance framework has been made. A health development governance index with 10 functions and 42 sub-functions has been proposed to facilitate inter-country comparisons. Potential sources of data for estimating HDGI have been suggested. The Governance indices for individual sub-functions can aid policy-makers to establish the sources of weak health governance and subsequently develop appropriate interventions for ameliorating the situation.</p

Talking the Walk: The Deflation Response to Legitimacy Challenges

Organizations need legitimacy to be able to operate effectively. Consequently, and just like their participants, Multi-Stakeholder Initiatives (MSIs) need to respond when faced with legitimacy challenges from external parties. We build on current theory to identify three organizational elements that can be made the subject of legitimacy critique – i.e., statutory procedures, objectives, mechanisms – and use these elements to structure our analysis of a conflict-ridden case concerning the United Nations Global Compact (UNGC). Whereas prior work suggests that organizations can respond to such conflicts in a fashion consistent with either moral entrapment or decoupling, we show that organizations can also respond by deflating their statutory procedures and objectives. A deflationary response can help organizations maintain their validity by diminishing the ability of external parties to advance propriety legitimacy critiques against them. By examining this alternative response, we expand the scope and refine the analytic detail by which organizational legitimacy conflicts can be investigate

Dollar value of disability-adjusted life years in South Africa in 2019

Background To date, no study has estimated the dollar value of DALYs lost from a wide range of diseases and conditions in South Africa. The specific objectives of this study were: (a) to estimate the dollar value of disability-adjusted life-years (DALYs) lost in South Africa in 2019, and (b) to forecast the reductions in the dollar value of DALY losses assuming the United Nations Sustainable Development Goal 3 (SDG3) five disease-specific targets are attained by 2030. Methods The study employs the human capital approach to convert the DALYs lost from all causes into their International Dollar (Int$) equivalents. The DALYs data used in the analysis was from the Institute for Health Metrics and Evaluation (IHME) Database, per capita GDP data from the International Monetary Fund (IMF) Database, and current health expenditure per person from the Global Health Expenditure Database of the World Health Organization (WHO). Results South Africa lost 26.6 million DALYs in 2019 with a total value of Int$ 313.5 billion and an average value of Int$11,791.6 per DALY. Approximately Int$ 155.6 billion (50%) was attributed to communicable, maternal, neonatal, and nutritional diseases (CMNND); Int$120.4 billion (38$ 37.4 billion (12%) to injuries (INJ). The health conditions related to SDG3 targets 3.1 (maternal mortality), 3.2 (neonatal mortality), 3.3 (CMNND), 3.4 (NCD) and 3.6 (INJ) resulted in DALY losses with a value of 256.4 billion, i.e. 82% of the total monetary value of DALYs lost in 2019. Therefore, achieving the five SDG targets would potentially save South Africa Int$ 139.7 billion per year. Conclusions Health development policy-makers should employ this type of evidence when making a case for increased investments into the national health-related systems to bridge the extant gap in the universal health service coverage index for South Africa

Corporate community involvement in Bangladesh:an empirical study

This paper empirically examines a corporate community involvement (CCI) initiative in Bangladesh. Drawing on a conceptual framework of 'collaborative betterment' and 'collaborative empowerment' and by using focus group discussions and interviews, it assesses the initiative to examine the extent to which it meets expectations of the community where it operates. Some of the key findings of the paper include: (i) although the initiative provides vital healthcare services to some of the most vulnerable and desperately poor communities, the level of actual engagement of the local people - the main stakeholders - has been marginal; (ii) when the principles of collaborative betterment and empowerment are considered, it can be concluded that the initiative struggles even as a 'betterment' process; and (iii) notwithstanding the rhetoric and high-blown statements, corporate role in terms of practical efforts in the field has been mostly superficial and limited

SYMBIOTIC EFFECTIVENESS OF BRADYRHIZOBIUM JAPONICUM USDA 110 AND SINORHIZOBIUM FREDII USDA 191 ON TWO DIFFERENT SOYBEAN CULTIVARS

Green house experiments were conducted to investigate the symbioticeffectiveness of two bacteria that fix nitrogen to soybeans: Slow growingbacteria (Bradyrhizobium japonicum USDA 110) and fast growing bacteria(Sinorhizobium fredii USDA 191). Two varieties of soybeans were used:Gazelle (non promiscuous variety) and TGx 1740 (promiscuous variety). Theexperimental design was a randomized complete design arrangementreplicated four times. Nodulation, acetylene reduction activity and dry matteraccumulation by nodulated plants growing in a nitrogen-free culture systemwere used to compare the symbiotic effectiveness of the fast-growingSinorhizobium fredii USDA 191 with that of the slow-growingBradyrhizobium japonicum USDA 110 in symbiosis with two soybean(Glycine max (L.) Merr.) Cultivars. Measurement of the amount of nitrogenaccumulated 30 day period of vegetative growth showed that Sinorhizobiumfredii was more effective in nitrogen fixation in TGX variety than in Gazellevariety while Bradyrhizobium japonicum was more effective in Gazellevariety than in TGx. The superior N2 fixation capability of Sinorhizobiumfredii with TGx variety as host resulted primarily from higher Nitrogenaseactivity per unit nodule mass (specific acetylene reduction activity) andhigher nodule number per plant. The higher N2-fixation capabilities of Bradyrhizobium japonicum with unimproved Gazelle variety as host resultedprimarily from higher nodule mass per plant which was associated with wasassociated with higher nodule numbers