HMGB1 Stimulates Activity of Polymerase β on Nucleosome Substrates

The process of base excision repair (BER) recognizes and repairs small lesions or inappropriate bases on DNA through either a short-patch or long-patch pathway. The enzymes involved in BER have been well-characterized on DNA substrates, and, somewhat surprisingly, many of these enzymes, including several DNA glycosylases, AP endonuclease (APE), FEN1 endonuclease, and DNA ligases, have been shown to have activity on DNA substrates within nucleosomes. DNA polymerase β (Pol β), however, exhibits drastically reduced or no activity on nucleosomal DNA. Interestingly, acetylation of Pol β, by the acetyltransferase p300, inhibits its 5′ dRP-lyase activity and presumably pushes repair of DNA substrates through the long-patch base excision repair (LP-BER) pathway. In addition to the major enzymes involved in BER, a chromatin architectural factor, HMGB1, was found to directly interact with and enhance the activity of APE1 and FEN1, and thus may aid in altering the structure of the nucleosome to be more accessible to BER factors. In this work, we investigated whether acetylation of Pol β, either alone or in conjunction with HMGB1, facilitates its activity on nucleosome substrates. We find acetylated Pol β exhibits enhanced strand displacement synthesis activity on DNA substrates, but, similar to the unmodified enzyme, has little or no activity on nucleosomes. Preincubation of DNA templates with HMGB1 has little or no stimulatory effect on Pol β and even is inhibitory at higher concentrations. In contrast, preincubation of nucleosomes with HMGB1 rescues Pol β gap-filling activity in nucleosomes, suggesting that this factor may help overcome the repressive effects of chromatin

Revisiting a flux recovery systematic error arising from common deconvolution methods used in aperture-synthesis imaging

The point-spread function (PSF) is a fundamental property of any astronomical instrument. In interferometers, differing array configurations combined with their $uv$ coverage, and various weighting schemes can produce an irregular but deterministic PSF. As a result, the PSF is often deconvolved using CLEAN-style algorithms to improve image fidelity. In this paper, we revisit a significant effect that causes the flux densities measured with any interferometer to be systematically offset from the true values. Using a suite of carefully controlled simulations, we show that the systematic offset originates from a mismatch in the units of the image produced by these CLEAN-style algorithms. We illustrate that this systematic error can be significant, ranging from a few to tens of per cent. Accounting for this effect is important for current and future interferometric arrays, such as MeerKAT, LOFAR and the SKA, whose core-dominated configuration naturally causes an irregular PSF. We show that this offset is independent of other systematics, and can worsen due to some factors such as the goodness of the fit to the PSF, the deconvolution depth, and the signal-to-noise of the source. Finally, we present several methods that can reduce this effect to just a few per cent.Comment: 7 pages, 5 figures. Accepted for publication in MNRA

Conflict Analysis of Liberia, and Analysis of Issues and Implications for Future Swedish Development Co-operation

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Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection.

BACKGROUND: Lymphatic filariasis is a debilitating neglected tropical disease that affects impoverished communities. Rapid diagnostic tests of antigenaemia are a practical alternative to parasitological tests of microfilaraemia for mapping and surveillance. However the relationship between these two methods of measuring burden has previously been difficult to interpret. METHODS: A statistical model of the distribution of worm burden and microfilariae (mf) and resulting antigenaemic and mf prevalence was developed and fitted to surveys of two contrasting sentinel sites undergoing interventions. The fitted model was then used to explore the relationship in various pre- and post-intervention scenarios. RESULTS: The model had good quantitative agreement with the data and provided estimates of the reduction in mf output due to treatment. When extrapolating the results to a range of prevalences there was good qualitative agreement with published data. CONCLUSIONS: The observed relationship between antigenamic and mf prevalence is a natural consequence of the relationship between prevalence and intensity of adult worms and mf production. The method described here allows the estimation of key epidemiological parameters and consequently gives insight into the efficacy of an intervention programme

Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection

Background: Lymphatic filariasis is a debilitating neglected tropical disease that affects impoverished communities. Rapid diagnostic tests of antigenaemia are a practical alternative to parasitological tests of microfilaraemia for mapping and surveillance. However the relationship between these two methods of measuring burden has previously been difficult to interpret. Methods: A statistical model of the distribution of worm burden and microfilariae (mf) and resulting antigenaemic and mf prevalence was developed and fitted to surveys of two contrasting sentinel sites undergoing interventions. The fitted model was then used to explore the relationship in various pre- and post-intervention scenarios. Results: The model had good quantitative agreement with the data and provided estimates of the reduction in mf output due to treatment. When extrapolating the results to a range of prevalences there was good qualitative agreement with published data. Conclusions: The observed relationship between antigenamic and mf prevalence is a natural consequence of the relationship between prevalence and intensity of adult worms and mf production. The method described here allows the estimation of key epidemiological parameters and consequently gives insight into the efficacy of an intervention programme

Representation of Africa online: sourcing practice and frames of reference

The dominant perspective on the representation of Africa in the western media claims that western media coverage is bias and crisis orientated and the liberal perspective claims that the coverage of Africa is not as negative as is often assumed. However, there is a paucity of literature on the representation of Africa online. This research enquiry is relevant because literature claims that the Internet has the potential to resolve the journalistic predicament of representing other culture through political participation and deliberation. But this requires a re-orientation of the sourcing practice of news organization to embrace sensitivity to and knowledge of African cultures. Moreover, the journalistic predicament can be resolved or not depending on the news gathering approach adopted by the news organization. Literature has identified two approaches, that is, ‘gatekeeping’ used mainly by dominant traditional media and ‘gatewatching’ used by alternative media in their quest to counter mainstream ideology. This study examines the impacts of the ‘gatewatching’ approach adopted by Africa Have Your Say (AHYS) website on its representation and frames of reference of Africa. It uses on-site observation, in-depth interviews and textual analysis to gather data. The study found that although the sourcing practice at the AHYS is elaborate and complex, the ‘gatewatching’ approach makes its susceptible to second level agenda setting. Hence, its frame repeats the attributes and tone used by the mainstream traditional media. However, a minority of users did not use repeat this frame in their comments

Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted. RESULTS: Ten sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9-1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1-9.7%), whereas sites in Kilifi and Kwale counties had prevalences?<?1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night. CONCLUSIONS: Prevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA

Improved Land Management in the Lake Victoria Basin: Annual Technical Report, July 2000 to June 2001

ICRAF and the Kenyan Ministry of Agriculture and Rural Development (MOARD) are implementing a project on “Improved Land Management in the Lake Victoria Basin.” The project began in 1999 – 2000 with a one-year startup year of activities under the Sida-sponsored National Soil and Water Conservation Programme (NSWCP). The collaborative project of ICRAF and MOARD has now been continued for another three years under the National Agriculture and Livestock Extension Programme (NALEP). This paper summarizes achievements and findings for the project for the year 2000 / 2001. The Swedish International Development Agency (SIDA) supports “Improved Land Management in the Lake Victoria Basin” through NALEP. Additional financial support for the activities reported herein was also provided by the Rockefeller Foundation, ICRAF core funds, Danida, the University of Florida and the USAID. Research conducted during 2000 / 2001 addressed a range of issues across a large tract of Western Kenya. A coarse resolution assessment of soil erosion risk conducted for the entire Lake Victoria Basin identified the Nzoia / Yala and Kagera river basins as those with the greatest percentage of land at risk. Biophysical research on land management problem domains has quantified the widespread spatial extent of soil physical and chemical degradation in the Nyando river basin and illustrated four contrasting biophysical problem domains within the basin. District-level data on population density, poverty and agricultural production available from secondary sources have been complemented with baseline household and community survey data collected in 9 villages around the Nyando river basin. The overall picture that is emerging is that while much of the Nyando river basin has experienced some physical and chemical land degradation, there are pockets of severe poverty, severe environmental degradation and extremely low agricultural production. Different approaches to extension, investment and policy may be needed to address poverty – environment – agricultural problems in different parts of the river basin. Reversing trends in environmental deterioration will require interventions on farmers fields and in the many areas between farms that publicly-used, although usually privately-owned. Farmers have demonstrated their willingness to adopt recommended conservation practices on their individual family fields, but the intensity of adoption depends upon the potential returns to investments, their cultural grouping, and the approach that extension providers take to the provision of information and mobilization of community participation. Adoption of improved practices and investments on publicly-used areas between farms requires the mobilization of collective action among small, medium and large groups. Collective action in the Nyando River basin is most likely to be effective where it harnesses local institutional arrangements (e.g. sub-clan affiliations among the Luo) and advances common interests in the provision of high quality water and the generation of additional cash income. Among other opportunities, there appears to be good prospects for market-oriented agroforestry for production of fruit, fuelwood and timber. Changes in local and national policies would help to ensure good returns for smallholder farmers. This report begins with a presentation of a number of major findings, implications of those findings for extension and investment and implications for policy. A summary of progress by activity is then presented, followed by lists of personnel involved, presentations and publications. An annex presents detailed accomplishments by activity

International Coercion, Emulation and Policy Diffusion: Market-Oriented Infrastructure Reforms, 1977-1999

Why do some countries adopt market-oriented reforms such as deregulation, privatization and liberalization of competition in their infrastructure industries while others do not? Why did the pace of adoption accelerate in the 1990s? Building on neo-institutional theory in sociology, we argue that the domestic adoption of market-oriented reforms is strongly influenced by international pressures of coercion and emulation. We find robust support for these arguments with an event-history analysis of the determinants of reform in the telecommunications and electricity sectors of as many as 205 countries and territories between 1977 and 1999. Our results also suggest that the coercive effect of multilateral lending from the IMF, the World Bank or Regional Development Banks is increasing over time, a finding that is consistent with anecdotal evidence that multilateral organizations have broadened the scope of the “conditionality” terms specifying market-oriented reforms imposed on borrowing countries. We discuss the possibility that, by pressuring countries into policy reform, cross-national coercion and emulation may not produce ideal outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/40099/3/wp713.pd