Oxidative DNA damage modulates genome and epigenome integrity via base excision repair

Oxidative DNA damage is one of the leading causes of genome instability, cell death, and diseases. It is repaired by DNA base excision repair (BER), during which repair and translesion DNA polymerases may incorporate damaged nucleotides and mediate RNA-guided DNA repair induced by DNA replication and gene transcription leading to the modulation of genome stability. On the other hand, oxidative DNA damage may result in cellular epigenetic responses to regulate DNA repair, altering genome stability and integrity. In this dissertation, we revealed the molecular mechanisms underlying the misincorporation of oxidized nucleotides, 5′,8-cyclo-2-cyclodeoxyadenosine (cdA) and RNA-guided base lesion repair mediated by repair and translesion DNA polymerases. We then explored how oxidative DNA damage induced cellular epigenetic responses by disrupting microRNA expression to regulate BER. We found that DNA polymerase β (pol β) and DNA polymerase η (pol η) incorporated cdA that basepaired with dC, resulting in an A:C mismatch. We further demonstrated that cdA lesions were readily extended and ligated in duplex DNA. We showed that the polymerases incorporated cdAs independent of their hydrogen bonding with a template nucleotide using molecular docking. Our study reveals a unique mechanism underlying the accumulation of cyclodeoxypurine lesions in the genome. We then explored the mechanisms by which DNA polymerases can utilize RNA as a template to synthesize DNA and repair a DNA base lesion. We found that translesion DNA polymerases, pol η, θ, and ν and repair DNA polymerases, pol β, λ and κ exhibited DNA synthesis activity, i.e., reverse transcriptase activity to mediate RNA-guided DNA base lesion repair. We further demonstrated that the completion of base lesion repair was accomplished by the RNA-guided translocation of a nick into duplex DNA via the strand displacement synthesis of the polymerases. We then explored the cellular mechanisms by which oxidative DNA damage modulates microRNA expression to regulate DNA repair. Our study revealed that oxidative DNA damage upregulated the expression of microRNA-499-5p (miR-499-5p) that subsequently downregulated the expression of the key BER enzyme, pol β, in human cells. Further analysis showed that the inhibition of 8-oxoG DNA glycosylase 1 (OGG1) activity significantly suppressed the upregulation of miR-499-5p, suggesting the epigenetic role of OGG1 in mediating the expression of miR-449-5p as cellular DNA damage response. Our study provides new insights into the crosstalk among oxidative DNA damage and repair, miRNAs, RNA-guided base lesion repair in modulating genome stability and integrity

The Great Green Forest is here and expanding all on its own: A call for action

Prosopis juliflora is recognized as one of the most invasive tree species worldwide. Following widespread introductions throughout arid and semi-arid regions of Africa and throughout the world, it has spread rapidly, threatening natural ecosystems and livelihoods. Control through utilization as a resource is now accepted as the way forward in developing countries, but efforts have so far been uncoordinated, with only isolated impacts. This paper reports on the global state of knowledge and recent advances, but focuses on prosopis-related research and innovations from IGAD member countries; the successes, failures, challenges and opportunities. It underlines the need to build and apply scientific knowledge to scale up new, resilient, drought-proof livelihood options in the Greater Horn of Africa and elsewhere where introduced, from value-added prosopis wood and non wood products. The authors estimate that there are at least five million hectares of prosopis forest across the region of the perhaps ten million throughout Africa, and growing significantly in extent every year. Experiences from the native range such as in Peru are well documented, where community associations sustainably manage and make a living from fuel, fodder, food, honey and timber from their prosopis forests. Efforts in Ethiopia, Djibouti and Kenya have had mixed results, but milling the sweet protein-rich pods into animal feed is becoming increasingly popular with the introduction of appropriate small scale technologies. Its use as a human food ingredient has also been promoted, though with little uptake, but there is sharp rise in the use of prosopis charcoal in the region, and the possibility of electricity generation using wood chips (bioenergy), with the transfer of experiences from India where there are at least 15 power stations fueled entirely by prosopis. But much more can be done by applying scientific knowledge and innovation to enhance the role of prosopis in improving food security, climate change mitigation and adaptation, and building resilience for millions of the poorest rural and urban people in the Greater Horn of Africa, with great potential for exchange and scaling up in other arid areas in Africa, Asia and the Americas. This paper is a call to the African Union, national governments, IGAD, IFAD, FAO, the Arab League and other international, regional and bilateral donors, to come together and support a regional research and development programme to push the frontiers on prosopis management and utilization and develop a transnational strategy, as the impacts are potentially enormous and immediate. The initial objectives are to take stock of existing knowledge and practices, assess prosopis forest areas throughout the region, estimate wood and pod volumes and production rates, document prosopis management and utilization experiences, enhance South-South knowledge sharing, and rapidly and effectively scale up the successes

Volatile profile of green coffee beans from Coffea arabica L. plants grown at different altitudes in Ethiopia

ABSTRACT. This study was aimed to identify volatile compounds of 31 green coffee bean samples and evalute their correlation with altitude of the coffee plants grown in two zones (Gedeo and Jimma) in Ethiopia. A total of 81 different compounds were detected. The contents of dominant volatile compounds in green coffee beans were in the range: trans-linalooloxide (3.24⎯19.13%), linalool (1.56⎯21.76%), 2-methoxy-4-vinylphenol (2.34⎯15.08%) and cis-linalooloxide (1.03⎯13.27%). In addition, benzene acetaldehyde (0.45⎯10.97%), 2-heptanol (0.67⎯8.49%), ⍺-terpineol (0.64⎯6.52%), phenylethyl alcohol (0.44⎯4.98%) and furfural (0.92⎯5.3%) were the next dominant compounds. The volatile compounds identified in the green coffee beans are groups of alcohols, aldehydes, ketones, pyrazines, pyridines, and furans. The volatile compounds in green coffee beans showed either weak positive or weak negative correlation with the altitude of coffee plants indicating that variation in altitude of the coffee plants does not significantly influence the volative compounds of green coffee beans.               KEY WORDS: Coffea arabica L., Coffee plants, Green coffee beans, Volatile compounds, Effect of altitudes, Heterocyclic compounds Bull. Chem. Soc. Ethiop. 2019, 33(3), 401-413.   DOI: https://dx.doi.org/10.4314/bcse.v33i3.

Historical land degradation strongly influences soil geography : a case in Ethiopia’s mountains

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Water productivity improvement of cereals and foods legumes in the Atbara Basin of Eritrea

The project ‘Water Productivity Improvement of Cereals and Food Legumes in the Atbara Basin of Eritrea’ is an example of organization and implementation of farmers’ participatory research, conducted utilizing the available indigenous knowledge while empowering farming communities. Farmers have been partners in technology development with extension and research, with full decision-making power in planning, implementation, monitoring, and evaluation. The project produced, in partnership with farmers, new varieties of cereals and food legumes which have proven farmer acceptability; established seed systems which supply farmers with quality seed in a sustainable manner; enhanced farmers’ skills in participatory research and in community based seed production; strengthened the capacity of National Institutions to carry out participatory research and technology transfer, and strengthened linkages between research, seed, and extension departments by working together in cooperation with farmers and farmers’ communities. Working conditions, during the course of the project were not always easy and became challenging towards the end of the project, but to work with farmers and learn from them has been an extremely rewarding experience

Using qualitative methods to explore lay explanatory models, health-seeking behaviours and self-care practices of podoconiosis patients in north-west Ethiopia

Background: Podoconiosis (endemic non-filarial elephantiasis) is a chronic, non-infectious disease resulting from exposure of bare feet to red-clay soil in tropical highlands. This study examined lay beliefs about three under-researched aspects of podoconiosis patients’ care: explanatory models, health-seeking behaviours and self-care. Methods: In-depth interviews and focus group discussions were undertaken with 34 participants (19 male, 15 female) between April-May 2015 at podoconiosis treatment centres across East and West Gojjam regions in north-west Ethiopia. Results: Explanatory models for podoconiosis included contamination from blood, magic, soil or affected individuals. Belief in heredity or divine punishment often delayed clinic attendance. All participants had tried holy water treatment and some, holy soil. Herbal treatments were considered ineffectual, costly and appeared to promote fluid escape. Motivators for clinic attendance were failure of traditional treatments and severe or disabling symptoms. Patients did not report self-treatment with antibiotics. Self-care was hindered by water being unavailable or expensive and patient fatigue. Conclusion: A pluralistic approach to podoconiosis self-treatment was discovered. Holy water is widely valued, though some patients prefer holy soil. Priests and traditional healers could help promote self-care and “signpost” patients to clinics. Change in behaviour and improving water access is key to self-care