Dynamics of antifolate transport via the reduced folate carrier and the membrane folate receptor in murine leukaemia cells in vitro and in vivo

Murine L1210 leukaemia cells expressing either the reduced folate carrier (RFC) or the membrane folate receptor (MFR) were studied in vitro and in vivo to assess the dynamics of membrane transport of two categories antifolates; folate-based inhibitors of dihydrofolate reductase (methotrexate, edatrexate, aminopterin, PT523, and PT644) and thymidylate synthase (TS) [CB3717, raltitrexed, plevitrexed (BGC9331), pemetrexed and GW1843]. The potency of in situ inhibition of TS was used as an endpoint to analyze the in vitro dynamics of RFC/ MFR-membrane transport of these antifolates. Both for L1210-RFC and L1210-MFR cells, the potency of in situ TS inhibition was closely correlated with increasing aYnities of these transporters for the antifolates (r = 0.64, P < 0.05 and r = ¡0.65, P < 0.05, respectively). Within the group of antifolates for which MFR had a low binding aYnity, those that had the ability to become polyglutamylated, were more potent inhibitors of TS in situ activity than non-polyglutamatable antifolates. In vivo activity of methotrexate, edatrexate, raltitrexed and pemetrexed was assessed in L1210-RFC and L1210-MFR bearing mice that were fed either a standard or a folate-deWcient chow. Dietary folate depletion signiWcantly reduced the MTD for methotrexate (sevenfold), edatrexate (sevenfold), raltitrexed (50-fold) and pemetrexed (150-fold). Based on increased life spans, antitumor eVects of methotrexate and edatrexate were markedly better in L1210-RFC bearing mice on the folate-deWcient chow (ILS: 455 and 544%, respectively) than on standard chow (ILS: 213 and 263%, respectively). No therapeutic eVects of methotrexate and edatrexate were observed for L1210-MFR bearing mice on either chow condition, which may be consistent with the low binding aYnity for MFR. Irrespective of the folate diet status, pemetrexed and raltitrexed were inactive against both L1210-RFC and L1210-MFR bearing mice, which may be due to high circulating plasma thymidine levels. Collectively, this study underscores that modulation of dietary folate status can provide a basis within which the therapeutic eVect of antifolates may be further improved

Dryland resources, livelihoods and institutions : diversity and dynamics in use and management of gum and resin trees in Ethiopia

Dry woodlands comprise the largest forest resources in Ethiopia. An important feature of these forests is their richness in Acacia, Boswellia and Commiphora (ABC) species that produce gum and resin. Gums/resins significantly contribute to rural livelihoods, the national economy, and ecosystem stability. Their contribution to local livelihoods is in terms of both cash income and subsistence value. In different parts of the country they contribute up to one-third of the annual household income. Currently, an estimated US2 million gum and resin are consumed locally, the rest is exported. During the 2007/08 fiscal year, Ethiopia earned a revenue of about US.7 million from this export. However, the woodlands and the ABC species are under intense pressure. Especially in the traditional production areas in north Ethiopia the pressure is high and the policies that were enacted to shape their use and management have not been very effective. The main objective of this study is to investigate how gum and resin utilization and management is carried out in the drylands of Ethiopia and what processes affect this. The following four questions were addressed: (i) What types of gum-resin woodland management and production systems are present in Ethiopia and how are they related to the land-use and socio-political conditions?, (ii) What dynamic processes in institutional arrangements and gum-resin production and management have occurred in various regions of Ethiopia?; (iii) How do multi-level formal and informal institutions interact and affect gum and resin production and management?, and (iv) How does gumresin utilization fits into the livelihoods strategies of households in the study areas? The study is based on a multi-theoretical approach giving attention to both diversity and dynamics in ABC woodlands production systems, institutional diversity and interaction regarding the governance of ABC resources, and the role of gum and resin in the livelihoods strategies of the households. The study design consisted of a comparative case study of three regions in north (Abergelle), northwest (Metema and Quara), and south Ethiopia (Borana). The three locations are characterized by ecological and socio-economic differences as well as a different history of gum and resin production. A two-phase research approach consisting of a base-line survey and a systematic household survey was used. The base-line survey served to assess the local socio-economic, institutional and land-use conditions; data were collected through open interviews with groups and key informants. The household survey served to obtain further detailed information on the ABC production conditions and the role of the products at household level. The survey included 327 respondents; it was follow-up by feedback meetings with groups of participants to check and validate the main issues that emerged from it. The qualitative data from key informant interviews and focus group discussion were transcribed, categorized, and interpreted. The data from household survey was analysed using descriptive statistics and mean comparisons in SPSS. Chapter 2 discusses the diversity in gum and resin management and production systems and how different exploitation arrangements are related to different phases of resource domestication and/or degradation. Seven presently existing production models are identified. In south Ethiopia pastoral people mainly collect the products in the form of ooze from natural vegetation. In north Ethiopia the production is part of mixed farming practices or is done by externally hired laborers. Production is done by tapping wild trees. Despite decades of production history in this region, the species is not cultivated and hardly domesticated in an ecological or biological sense. The production systems gradually evolved from openaccess extraction of wild trees to a controlled production in assigned forest plots. This institutionalisation of access rules concerns a process of domestication in a social sense. However, this process is not yet very effective; the ABC woodlands are often subject to serious degradation as a result of competing land-use practices and inappropriate social arrangements for production and trade of the gums/resins. These findings show that the nature of domestication in a social sense determines whether forests and/or specific forest resources can be further domesticated in an ecological and biological sense resulting in intensified management and resource enrichment, or whether they are subject to degradation. Chapter 3 and 4 elaborate how gum and resin production is shaped in the different parts of Ethiopia by the location-specific interaction between formal and informal institutions. Chapter 3 discusses how gum and resin production and marketing in Borana is related to the interplay between well-established traditional land-use institutions and external institutions. Both the traditional and external institutions do not explicitly control access to the gum and resin production system, but under traditional conditions gum and resin extraction was embedded in a strong customary system for controlled pastoral land use. The traditional institutions did not developed rules and norms regulating market access. The external institutions impacted gum and resin production mainly by creating access to markets, but this has not yet had much impact on the actual exploitation arrangements. The woodlands are experiencing increasing pressure due to the increase in non-traditional and non-gum and resin based livelihoods activities that negatively affect ABC woodlands. Also, the traditional natural resources management institutions are weakened due to modernization processes and contribute at present little to sustainable use and management of gum-resin resources. This situation calls for either revitalizing the traditional range land management system, or generating institutions specific to ABC species that integrate the customary and external institutions. Chapter 4 discusses the nature and interactions of formal and informal institutions concerning the AB resource use and management in the north and northwest Ethiopia. Existing government regulations recognize gum and resin production and marketing by both smallholders, cooperatives, and companies. However, in practice gum and resin production and marketing by smallholders is restricted. This is the result of informal bureaucratic institutions that act as rules-in-use regarding gum and resin production and marketing regardless of whether they contradict with the regulations of federal and regional states. Moreover, the customary rules and practices and the sectoral government policies often compete with the formal regulations for ABC species use and management. The interaction between government regulations and informal institutions is generally competing; this often results in indiscriminate tree cutting and woodland conversion. The situation requires harmonization of the formal and informal institutions and coordination of institutions across sectors. Chapter 5 discusses the relationship between gum and resin production and the livelihood systems of local producers. Both the livelihoods systems and the contribution of the multiple activities to cash and total income vary among the study areas. In Borana the use of gum and resin is part of a predominantly pastoral livelihood system with gum and resin acting as supplementary cash crops or safety nets in times of emergency. In Abergelle the production fits into a diversification strategy with gum and resin exploitation forming a component of a mixed farming system. In Metema local farmers were not involved in gum and resin exploitation; here production is a specialized activity of commercial enterprises using laborers from outside the region. The findings show that not only the value of the ABC resources, but also the degree of the embeddedness of the product in multi-livelihoods strategies of the households as well as the institutional arrangements that govern production system and market access are important regarding how these products fit into the livelihoods strategies of the households. Chapter 6 brings all the information together and further assesses the nature of the different institutional arrangements for gum and resin exploitation, and their dynamics and interaction. It also elaborates the relation between the status of ABC resource domestication and their exploitation arrangements. The process of organizing gum and resin utilization followed different pathways in north and south Ethiopia. In the south it started as the collection of products for chewing gum for subsistence use; later it was marketed as a coping mechanism during periods of livelihood stress. In contrast to these endogenous developments, in the north the production was introduced by external private and state companies. Only gradually also some informal systems of private exploitation evolved. After 1990 cooperatives took over many of the concession areas of the commercial companies. This cooperative movement also was introduced in the south. As a result of these location-specific dynamics in organizing the production, six exploitation arrangements evolved. These arrangements differ with respect to whether their organization is companybased, cooperative-based or privately based, and are characterized by different rules and regulations regarding access to resources and markets, and the type of labor used for production. In all study areas the exploitation arrangements co-exist with a growing importance of the cooperative arrangements. The institutional arrangements are not conducive to stimulate intensification of production, rather they may limit local participation and endogenous development of informal and location-specific institutions. Moreover, the effectiveness of the exploitation arrangements may be limited as a result from competing development policies and programmes aimed at other land-use sectors. These findings further illustrate that the limited progress in ABCs domestication greatly depends on the nature of institutional arrangements for access to resources and markets, the relation of formal and informal institutional arrangements, and development polices. In chapter 7 it is concluded that the use and management of the ABC species in Ethiopia is very divers both in terms of production systems, institutional arrangements for exploitation, and roles in local livelihoods. The nature of location-specific production systems is greatly affected by the local system for ABC governance. Such a system involves complex set of both formal and informal institutions at both government level and local level. The informal institutions do not only include customary institutions of local communities, but also informal rules-in-use of local bureaucrats. The historic process of institutionalisation of ABC governance differs between regions. Depending on local land-use conditions and government policies, different exploitation arrangements have been developed based on either company, cooperative or private control over the production, labor and marketing. But despite of this diversified stage of domestication in a social sense, the production systems are still in an early phase of domestication in ecological and technical sense and intensified production through tree cultivation or plantation establishment has hardly been developed. Several gum and resin production systems are even subject to serious degradation due to the inappropriate nature of, and sometimes even competition between, the exploitation arrangements, as well as the economic position of the ABC resources in relation to other forms of land-use. The complex pattern of institutions governing the production of gum and resin also impacts on the role that the resources play in local livelihoods. Both the role of gum and resin production in the prevailing land-use conditions and the degree of control on market and resource access determine how the gum and resin fit into the livelihoods strategies of the households. As the governance of gum and resin production involves a complex, diverse and dynamic web of formal and informal institutions, it will not be effective to stimulate production as a means for both sustainable forest use and livelihood improvement by a generic development policy. Rather a diversified and regional-specific approach is needed that builds upon the location specific characteristics of the gum and resin production systems and exploitation arrangements

Cross-Sectional Study on Prevalence, Risk Factors and Major Bacterial Causes of Bovine Mastitis in and Around Wolaita Soddo, Southern Ethiopia

A cross-sectional study was conducted from November 2014 to March 2015 on lactating dairy cows to determine the overall prevalence of bovine mastitis, assess concomitant risk factors and isolate the major bacterial agents involved in causing mastitis in and around Wolaita Soddo. A total of 320 lactating cows were examined for mastitis using clinical examination and California mastitis test (CMT). Bacteriological methods were also done to isolate the causative bacteria. An overall 26.25% prevalence of mastitis was recorded in the area of which 12/84 (3.75%) were clinical and 72/84 (22.50%) subclinical cases. About 125 bacterial isolates belong to 5 species were identified from mastitic milk samples. The isolates based on their relative frequency of occurrence were Staphylococcus aureus (39.85%), Coagulase Negative Staphylococcus (CNS) (20.30%), Streptococcus dysgalactiae (13.53%), Streptococcus agalactiae (12.03%), Escherichia coli (8.27%). In this study risk factors like parity, lactation stage, and body condition were shown association with mastitis. Animals with many parity Odds Ratio (OR: 3.55, 95% CI: 1.64 – 7.67, P value: 0.001), moderate (OR: 1.49, 95% CI: 0.76 – 2.91, P: 0.242) were at higher risk than animals with few parity. Animals with early lactation (OR: 3.93, 95% CI: 2.02 -7.66, P: 0.001), mid lactation (OR: 1.63, 95% CI: 0.75 – 0.54, P: 0.214) were at higher risk than animals with late lactation. Animals with poor body condition (OR: 3.53, 95% CI: 1.58 – 7.85, P: 0.002), medium body condition (OR: 1.51, 95% CI: 0.68 – 3.35, P: 0.308) were at risk than animals with good body condition. Generally, the study showed that mastitis was a serious problem for dairy production in the study area. Therefore, appropriate control measures targeting the specific causative agents should be in place to reduce the impact of the disease. The farmers should also be aware of the impact of the disease and practice hygienic milking, culling of chronic mastitis carriers and treating of clinically infected cows. Keywords: Dairy cattle, Mastitis, Milk, Risk factor, Wolaita Sodd

The informal features of micro and small enterprises and its incompatibility with the partnership law in Ethiopia

This paper aims to analyze unfitness of micro and small enterprises with the existing trade law particularly partnership rules in Ethiopia. Qualitative research methodology is utilized in order to capture and analyze accurate and in-depth insight of the fact that micro and small enterprises in Ethiopia are not compatible with the existing partnership law though partnership form of firms are suitable for small business. The available literatures related to the issue were professionally scrutinized and analyzed for the purpose of the research. The results of this research shows that micro and small enterprises in Ethiopia are formed as simply business organization which does not specify the kind of firm structure. Formation, management, liability and dissolution of micro and small enterprises deviate from the partnership requirements stipulated under the Ethiopian commercial code. Furthermore, micro and small enterprises are operating as informal sector business though the sectors‘ development strategy clearly states that they should be organized under trade law. Therefore, micro and small enterprises system should be reformed in order to make them to be compatible with the existing commercial law

Review on Recent Development and Application of Dispersive Liquid-Liquid Micro Extraction

Dispersive liquid-liquid micro extraction (DLLME) has become a very popular environmentally benign sample-preparation technique, due to its simplicity, rapidity of operation and low consumption of solvent and reagent. It has attracted much interest from scientist working in separation science and much improvement has been made since its introduction in 2006. It has been combined with different extraction techniques such as floating organic drop, solid-phase extraction, and supercritical fluid extraction. This seminar has focused on the review on development of dispersive liquid micro extraction (DLLME) and its application in different samples, such as water, soil, food and biological material with different analytical techniques.DOI: 10.7176/CMR/11-3-02Publication date:March 31st 201

Review on Utilization of Plants for the Phytoremidiation Purpose on Heavy Metal Contaminated Soil

Heavy metal pollution in the soil has been the main environmental problems in recent years all over the world. Heavy metals that are commonly contaminating soil include lead, chromium, arsenic, zinc, cadmium, copper, mercury and nickel. The main sources of these metals are dust produced by energy, transport, metallurgy, production of construction materials; sanitary sewage, chemical wastewater, industrial mining wastewater and urban mining mixed sewage; mining and industrial solid waste contamination, Fertilizers and pesticides are important agricultural inputs for agricultural production and there is a growing public concern over the potential accumulation of heavy metals in soil owing to rapid industrial development and also the heavy metals pollution is one of the problems that arise due to the increased uses of fertilizers and other chemicals to meet the higher demands of food production for human consumption. Heavy metals exhibit toxic effects towards soil biota by affecting key microbial processes and decrease the number and activity of soil microorganisms. Even low concentration of heavy metals may inhibit the physiological metabolism of plant. Plants growing on these soils show a reduction in growth, performance, and yield. Uptake of heavy metals by plants and subsequent accumulation along the food chain is a potential threat to animal and poses serious health risks to humans. To overcome the problem phytoremediation using of plants to reduce the concentrations or toxic effects of heavy metal contaminants in the environments and relatively recent technology which perceived as cost-effective, efficient remedy of soils by improving phisico-chemical of the soil with cheap and practically acceptable techniques. Keywords: Contaminants, Heavy metal, Phytoremediation, Soil, Toxic DOI: 10.7176/JNSR/9-6-0

Assessment of Major Livestock Feed Resources and Constraints in Guji Zone, Southern Oromia

The study was conducted with objective of assessing and rank the major livestock feed resources and its constraints in Guji Zone, Southern Oromia. Data was collected by group discussions and structured questionnaire in six districts. Data was collected from both secondary and primary data. A total of two hundred eighty eight (288) respondents were randomly selected and interviewed from districts based upon pre-tested structured questionnaire. Native pastures, crop residues, grazing of crop stubbles and browse trees were the major feed resources in the study area. Natural pasture and crop residues were produced in large amounts in the study area. The main cause of grazing land deterioration was drought 69.1% lowland, over grazing 58.2% highland and bush encroachment 21.9%. The major traditional range land management practice of the study area was conservation enclosure (kalo). The main source income of stakeholders depends upon sale of livestock and livestock product, and sale of crop. In the lowland area livestock cover long distance (&gt;6 km) to reach water compared to the mid and highland parts. Further research and development work should be encouraged to improve dry season feed scarcity through different options such as utilization of non-convention feeds, forages development program, use of alternative means of crop residue utilization and adaptation, demonstration of improved forage varieties. Keywords: Assessment; Communal; Enclosure; Feed; Native pasture; Stubbles DOI: 10.7176/JRDM/92-02 Publication date:October 31st 202