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For instance, now Washing Stations are able to negotiate between 4. For the Tea sector, the production of green leaves evolved from 67 MT to 87 MT, but the most significant change is the productivity increase in leaves per hectare, from 5.

For the bench Terraces, achievements are very good and with a very good quality. The programme enabled the building of terasses have on 1. District and sector agronomist have received technical training to follow up the activities. For the Diversification projects, a call for proposals was launched in and 16 proposals out of were awarded in the following sectors: Fish culture, Dairy goat, Ikambere Dairy, Potatoes, Honey Nyungwe, Soya, Mushrooms, Macadamia, Sericulture, Terraces, Essential oils.

As for the Decentralization component, the programme financed a pilot project called UBUDEHE that has generated important social impacts helping the cells in the formulation of their action plans and financing the realization of priority micro projects mainly targeted on agriculture and breeding. Some difficulties were quoted for UBUDEHE, however, the efficiency of the projects has finally been largely positive for the beneficiaries. In total persons were trained in districts of 6 provinces. In so far, the programme was considered as a great success.

Ubudehe can be sustainable on a long term basis, but it depends on the community organization and management capacity. Following the privatization process, institutions will have to redirect their role in favour of a more strategic way, including, policy design, planning, monitoring, impact studies. The lack of strategic planning, high management staff turnover and the weakness of monitoring of the implementing institutions made some actions more difficult to deliver.

With more strategic approaches and appropriate monitoring, the Programme could have gained an even higher degree of effectiveness. For export commodities the potential viability should be related to quality products, focussing on niche markets, instead of quantitative targets, as it is the case now for the tea production.

The pilot Ubudehe project in the Butare province provides guidance on how to best work in a participative way with the beneficiaries. In June , two evaluations provided positive feedback suggesting principally that funds spent at Cells level should essentially fund collective actions. Physical achievements for coffee, tea, diversification, and decentralization are substantial as aforementioned. In Rwanda, the major donors are currently designing their own support, in particular in the framework of budget support modalities, by taking into account the lessons learnt by EU in these fields agriculture and decentralization.

The views expressed are those of the consultant and do not necessarily represent any official view of the Commission or the Government of this country 1 This version, based on June final version, includes comments received in August from RADA team. Source : census Data source : Census March 31st, The bench terracing programme covers six districts, in which population amounts 1,, persons, the project area covers , hectares. The project aims to build around 1, hectares of bench terraces on cultivated lands high slopes to fight against erosion, to increase agricultural production and productivity, to improve population incomes by high labour intensity works and agricultural intensification, to improve food security.

The project is implemented according to the decentralisation policy, through district level cost estimates French: devis — programmes. RADA is in charge of the overall management. All procurements are managed by the districts, with respect of the national tendering procedures. Works are managed by the way of service contracts with specialized private operators [OSTR]. The labour force is recruited by the district, managed by the operators. As regards to the environment topics, a wider approach would be required, taking the whole catchment area in consideration.

A set of erosion mitigation corrective techniques has to be deployed, in conjunction with conservative agricultural practices. As regard to agricultural productivity, relying on chemical fertilisers will give a instant increase on the expense of soil quality deterioration but will have to be supported in the long run by accompanying measures, to manage soil fertility. Implementation procedures were evaluated very effective. Fertility and productivity management will require high recurrent costs normally balanced by high yields : this is a main change in farmers habits, change that has to be strengthen with suitable and intensive support from agricultural extension services.

This is clearly a challenge. Impact on agricultural production has to be monitored during the next seasons, the present evaluation takes place too early to assess this impact. Agricultural productivity will only be increased in the future if accompanying measures are effective in the coming months. In this analysis, the following different stages were done: 1. Explaining the links with the key elements of the Logframe 2.

Analysing the interests of the main Stakeholders. In those situations, two kinds of prices have been implemented in the models: maximum sales prices and minimum sales prices. The sharing in harvests, productions, average area of terraces per household 0, ha , Maximum average sales prices and Minimum average sales prices directly comes from the results of the adhoc survey initiated by the mission.

Private companies: an alternative situation in which OSTR and farmers are replaced by private companies was described. Progressive Terraces: another alternative situation was tested. In this situation, the use of progressive terraces instead of the use of radical terraces was modelled. The models stay quite the same.

Nevertheless, it was considered that yearly productions have a linear increase on five years instead of three years in the radical terraces model. Developing the Financial analysis The financial analysis measures the Net Present Values and the Internal Rates of Return for each Incremental situation and alternatives. For quite all of those situations, profitability criteria measured are very good.

It is evident that under productivity hypotheses, when the yearly productivity is higher. Elaborating the Economic Analysis The consolidated financial data have been translated economically. This process has been carried out. Total Investment Costs are broken down. Summing up conclusions, and Criteria for Decision According to the EcoFin analysis results, it is clear that the radical terraces project is financially and economically profitable. This project is also sustainable in terms of costs.

It takes into accounts and has positive environmental impacts in the rural areas of the country. Nevertheless, the models show that it would be more relevant for the government to strengthen the creation of progressive terraces because they are more profitable than radical terraces. Even very positive aspects, the cost per hectare is very high and can not be replicated on a large extend.

Fight against erosion should be conducted through a mix of techniques and agricultural practices, amongst them bench terracing. Progressive terracing is more profitable. The end of its operational phase has been set on the 31th of December , the various commitments are planned to end no later than the 31th of December The diverse budget allocations have increased the total amount of the COM to just under EUR 24 million.

Privatisation sub-programme Tea, coffee and pyrethrum sectors received financial support mainly intended to: — conduct studies and strengthen the training process in parallel of the privatization process of OCIR Tea and SOPYRWA; — contribute to public investment related to the privatization of the tea sector : maintenance of drainage systems; access road works, buildings rehabilitation, training of farmers, agronomists and agricultural extension officers, miscellaneous equipments, surveys of industrial plantations; — increase pyrethrum flowers drying capacity and availability of improved seeds.

The strategy of intervention was revised in and resulted in the successful dispatch of the unused funds of support of decentralization and diversification components. Raindrops create splash erosion that moves tiny particles of soil. Water collecting on the surface of the soil collects tiny rivulets and streams and creates sheet erosion as it moves towards. Erosion is a natural process. In general, the background erosion removes soil at roughly the same rate as soil is formed. Accelerated erosion leads to the loss of soil nutrients, reduced soil fertility and subsequent reduction in the growth of the plant, which conduct to: — reduced ground and canopy cover, reduced yields, — changed vegetation condition, — invasion of weed species, ferns soil acidity indicator , — etc.

Downstream sedimentation occurs and may fill the plains and river beds during floods. The left materials can damage the infrastructures. A comprehensive approach, on the catchment area has to be developed. On already completed sites, the very first crops have just been harvested. On another side, this evaluation comes as the next EDF fund is about to start, with a revised implementation procedure, a sectoral budget support, instead of the project's approach. District Burera Gasabo Karongi Nyabihu Nyaruguru Rulindo Area km2 ,42 ,14 ,43 ,47 ,82 ,02 Households 68, , 59, 57, 51, 54, Table 3: Project : areas and population by districts.

Source : census. The project is implemented according to the decentralization policy, through district level cost estimates French: devis — programmes. This option appears naturally in this case, as the population density is very high and under employment is still a topic in Rwanda. At least people benefiting directly from revenues related to terracing works revenues related to terracing works 4. RADA services strengthened in their capacity to implement the national agricultural policies 6. Elected people, districts and sectors' officers trained, supported and advised in bench terracing and erosion mitigation.

Elected people, districts and sectors' officers trained, supported and advised in bench terracing and erosion mitigation It was initially planned hectares of bench terraces, but with favourable exchange rate, this target was revised up to hectares. Related to result 3: — Support local communities in selecting candidates amongst target groups criteria of vulnerability. Elected people, districts and sectors' officers trained, Works completed according to supported and advised in bench terracing and erosion norms, mitigation Knowledge of maintenance requirements.

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Internal monitoring and reporting are very weak throughout the project. Dates of provisional acceptance were recorded in notes of meetings and notes of site visits, made available by EC delegation officer, but were not compiled by the project. One can also distinguish between those two goals and find out the mix of techniques with the best returns in terms of : — erosion mitigation and — agricultural production Vision puts also a target in potable water availability for which, as a positive side effect, bench terraces can contribute. The rainfall percolation increase may result in increased spring flows.

Managing soil acidity is compulsory as below pH 5. Agricultural production depends of : — seeds quality — good agricultural practises : ploughing, seed spacing and seeding date season , weeding, …. Production increase could also be achieved on progressive terraces. Data and research works on land productivity and limiting factors are still not enough documented in order to identify the specific benefit of bench terraces. Increase in agricultural production does not mean increase in farmers income, the link between production and income is far from being obvious. Sustainability in long term is questionable.

Results Quantified results are clear and do not require comments. Indicators Indicators are poorly related to logical framework terms. This indicator should be presented at the purpose level, not at the results level. Erosion is not monitored. This aspects is frequently reported by interviewees as a very positive impact.

In fact, in rural areas, cash scarcity is still common and every cash input is most welcome. Half of the total project amount, around RWF millions has been directly injected in salaries. Technically speaking, ploughing, weeding, The very first harvests were promising, but it's almost impossible to identify the effect of the terraces by itself and the effect of the lime and fertilizers. Joint Evaluation Unit. Volume 3. Every peasant met talked about erosion mitigation, no one did complain.

Some negative aspects are minimized by the technicians surrounding the peasant and should be monitored closely : — intensification implies labour force input peaks during specific periods 6, which are not seen in low productivity schemes. It is not obvious that every farmer can mobilize the labour force within its own family or can afford to pay for same when required. The monetization and access to financial services are still in early development stage. The operators' market is not known but there is a common understanding that : — the market depends on public orders solely, and more precisely to cooperation funds flows, — private operators and not really specialised in bench terraces but are active more widely in all rural works : they recruit personnel according to their contracts and are surviving meanwhile.

In this context, a near RWF millions volume of contracts is very relevant to keep them active. The Pillars of Vision 7 are: 1. The reconstruction of the nation and its social capital; 2. The development of a credible and efficient state governed by the rule of law; 2. Development of basic infrastructure, including urban planning; 4. Development of entrepreneurship and the private sector, and 5.

Modernization of agriculture and animal husbandry. Human pressure Input use fertilizers Intensification Water conservation Extracts of the Vision policy : i Land use management [ Productive high value and market oriented agriculture [ Agricultural policy orientation will have to be overhauled, promoting intensification so as to increase productivity and achieve growth rates of 4. There is a need to contain the fragmentation and degradation of further arable land as a result of high pressure and soil erosion.

The level of technology is low, infrastructure in rural areas is inadequate and human and physical capital is in short supply. As a result, agricultural productivity is low which generates poor returns on private investment. A set of erosion mitigation corrective techniques has to be deployed, in conjunction with conservative agricultural practices 4.

For results to be sustainable it is essential to promote a coherent and conducive policy environment on all levels. The Community will continue to work to improve food security at international, regional and national level. It will support strategic approaches in countries affected by chronic vulnerability.

Focus will be on prevention, safety nets, improving access to resources, the quality of nutrition and capacity development. Particular attention will be paid to transition situations and to the effectiveness of emergency aid. Objectives are on two domains : — Erosion mitigation, erosion tamed. A third domain can be added : increase of population income, either with direct income and long term improved revenues Are the bench terraces the best response to this two objectives?

In a certain extend, bench terraces are one of the best technical response to both objectives on slopes but diminishing margins theory applies in this domain as well and other techniques have to be introduced too. As regard to erosion control, the problem has to be dealt with at the whole watershed level, from erosion itself to solid material deposit and resulting flooding downstream.

Increase of agricultural productivity? The lands are being terraced and fertilised. The lack of accurate and reliable monitoring of the production and yields amongst other data hampers any sound evaluation; districts officers could be tempted to 11 Joel Le Turioner, Rukazambuga Ntirushwa Daniel. Evaluation report for Crop Intensification Program. The procedures give all the project management and responsibilities to the districts according to the national policy and also provide all kind of support to temporarily strengthen the district staff and capacities : — technical knowledge is provided through a service contract with a local company, bringing capacities in labour force management and technical issues; — districts officers are receiving extra payment for increase of work load : accounting works, procurements, reporting, Tendering lead to the selection of 15 OSTR, for 42 sites.

OSTR found the procedure fair. OSTR find that the service contract procedure is adequate to perform the works in due time : they find that being freed from paying labour force facilitates their works. One OSTR complains of 3 months delays for the payment of its invoices. Without investigation to see from where comes the problem invoicing could be wrongly made , this does not make an issue.

Apparently, no real control of works has been performed.

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In most cases, the sector agronomist was frequently on site, but with no technical competencies and no technical documents. Labour force management As regard to the labour force management, the implementation procedures gained from other HIMO projects which took place in the late years in Rwanda and in other countries.

One main constraints in HIMO works is the regularity of salaries payments : a few days delay can result in stopped works. Under works contracts, enterprise cash flow frequently shows bottlenecks, due to inadequate management but also delays in payments from the part of the project owner French : maitre d'ouvrage. With direct payment made by the project owner, the district, cascade delays are very limited and payment can be made available to workers in due time. Things did improve with time.

Delays of payments were not monitored. Labour force recruitment Recruitment has been made by the districts officers, amongst the beneficiaries and neighbours. The procedure is not clearly transparent, but no one did mention any problem in the recruitment process, without any social disturbance. Works completed according to norms, knowledge of No specific reporting.

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Table Results indicators 4. All other costs are similar, with or without tigistes. The prices paid by the project were the market prices at the time the procurement took place, subsidisation came later. Manure and composts purchased for a specific project are depleting soil fertility on other cultivated lands. DWHH personal communication. During the evaluation, the organic fertilizers seen seemed to be of very poor quality, not matured, this will result in temporary nitrogen depletion in the soil.

Activities of fertilization included the application of lime, manure and fertilizers, but the total quantities of the fertilizers have not been recorded by RADA. This figure indicates a rather good performance of the management team, considering the area of intervention, the pressure to complete the works during the time frame. Two officers are given extra payment for project specific work related to reports and funds management. This is a very positive efficiency criteria. This performance has been made possible with the right procedures but also the strong involvement of all the partners, including office of the National Authorising Officer [NAO].

Problems have been treated in an participatory approach, on the field. This is particularly the case of site identification and land owner participation , recourse of tigistes, All criteria are positive and their values are relevant in financial and economic terms. Figure should be revised after full completion. Research is very new on this issue in Rwanda. According to local technicians, from operators to local consultants office, cases should be very rare, up to now. Causal sequence of events can be found in the literature In 14 Crawford,T. Organic fertilizers will never be in excess, to maintain fertility and soil stability, but availability of same is a matter of concern.

The poor farmers are facing a challenge when their lands are transformed in bench terraces, the direct income gained during the works, if any, is very limited and will not be sufficient to allow them to sustain the changes. BEED sarl. Extension services at farmers' levels still have to be improved in order to achieve sustainability.

Districts have been strengthened to cope with works management. As regard to the works completed under the project, the issue is closed. Extension services at farmers levels still have to be improved in order to achieve sustainability. Illustration 4: work site panel The land owners are the final beneficiaries of the works and they should agree with the concepts and details of works performed on their lands. They are the real project owners.

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Administrative management is de facto delegated to the districts, conception, scope of works are delegated to RADA, some responsibilities are delegated to owners' contact committees. These committees are not considered as land owner associations, which are in charge of managing long term sustainability of the bench terraces, including soil fertility, production and profitability, …. OSTR mention that those committee were very helpful during the works. Formally, they had to countersign delivery bills, which is a very good procedure in order to reinforce appropriation and to seek quality.

For example, the payback period of the project is short around two years. The cash flow is positive and all costs are covered. The net present values measured in the three hypotheses are positive and become high when productivity increases. Impacts have been reviewed to comply with terms of reference.

But a comprehensive evaluation of all impacts can not be achieved in the time frame of the mission. More, even if donors are very interested to show the direct impact of the intervention, attributing all the modifications to the project is not relevant. Nonetheless when donors and recipients try to be accountable for achieving impact, they are severely limiting their potential for understanding how and why impact occurs.

The drive to claim credit interferes with the creation of knowledge. See bibliography. Data source : Census 4. This direct income is counterbalanced with a reduction of agricultural production on lands under terracing works. Although one billion Rwandan francs certainly have a local impact, the sum can be related to the active population of each district. Considering the figures of the census from Rwandan National Institute of Statistics, the overall population amounts 1.

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The active population is taken as the population aged between 15 and 50 years old. The number of man. Data are not available. The way workers are paid on a bank account has probably a good impact on the living conditions of workers. This was monitored in another project Community Based Reintegration — RDRC — KfW, personal communication and revealed that access, frequently for the first time, to a bank account, to credit facilities, was considered as a very high benefit of the job.

This is not monitored by the project. Impact on local financial institutions could be very high. Unfortunately, this is not monitored by the project and the financial institutions need lot of time to provide summaries or analysis on workers' behaviour related to their bank accounts bank account management at local branches is not yet computerised. Results of the survey were only partial with a low rate of answers.

Nevertheless, answers allowed drawing the following charts illustrating the uses of revenues generated by the project. For example, according to the survey results, the average number of days worked in radical terraces project was 89,22 days and the median was 60 days. The three next charts illustrate results of the survey concerning the uses of incomes obtained through to the implementation of the project.

Illustration 6: savings use As illustrated in the above chart, the choice to use savings for paying mutual health for family is a real success. On the other hand, savings has not been used a lot for investments. Having recourse to tigistes implies a smaller impact on districts' economies. Those organizations are very young or not yet in place.

This is clearly a weakness in the intervention. The whole procedures service contract, labour force payments, tenders for procurements, … proved to be efficient, allowing to achieve ha of bench terraces in the planned time. The analysis should refer to agricultural lands only, data are not available. On the contrary, Community Service elicits positive reactions in each group, even if opinions are divided and numerous fears persist, primarily due to the difficulty the survivors and the former genocide perpetrators have in imagining a life together again.

Are terracing works absolutely in the public interest? Complying with …. It is not clear at all that recourse or not to tigistes have a positive impact on reconciliation. The issue is still very sensitive in Rwanda amongst the population. This issue should be treated by a sociologist, considering all political aspects, history, gacaca process, … 4. Technical data are not recorded. The present evaluation had to work on budgets not on actual expenses. Community Service TIG. Areas of reflection. On the technical aspects, the experience remains in the private operators hands only. Scientific research should be conducted on the bench terraces, on all aspects before any further investments.

First raw results were made available on March 26th, Database is more precisely used for the EcoFin analysis. Here under some basic information is presented. The survey also indicates that family structure are still impacted by the past conflict with very young people and elders being over represented. Cultivation tasks are either made by men or women, or both. It is also very interesting to note that young people are not really involved in agriculture tasks.

This methodology is divided into seven key stages of analysis. Links with the key elements of the Logframe 2. Analysing the interests of the main Stakeholders 3. Economic Analysis 7. Summing up conclusions, and Criteria for Decision 6. It has been used to make project definition more precise and in particular the key elements of the Logframe.

Links between expected results of the EcoFin analysis and the Evaluation criteria mainly contribution to efficiency, impact and financial and economic sustainability will be measured has been underlined in the following sections of the EcoFin Analysis. Many data was collected on those households via a survey conducted by interviewers. Farmers were the labour force and the direct beneficiaries of the project.

Indirect beneficiaries would include the population who benefited from the creation of new jobs and a direct use of labour in the bench terraces. According to data available the financial models have been design with several variables. Both with and without situations are tested according to Maximum and Minimum prices of productions measured by speculation.

See table below to know the amount of revenue. The table below gives revenue according to the Min or Max sales prices. Year 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Total Yearly Productions by household with Max Prices Revenue: - The yearly production of beans, maize, sorghum, sweet potatoes, potatoes, colocase and fruits. It is considered that there is no production in year 1 time needed to start the process of yields in the project , then the productions begin to increase gradually to achieve the full production level in year 5.

It means that 3 complete years after the implementation of the project are necessary to become fully productive. The result of this is multiplied by the share of labour in the total investment costs Taxes: 23 See Table 2 to know revenue on productions of the without project situation. Those revenue are multiplied by 1,5 or 2 or 2,5 in the different hypothesis of the with-project situation. At this stage, it is quite impossible to isolate the effect of fertilizer, lime and manure to the effect "terraces" itself. A conservative assumption was made on the residual value.

It is considered null. In the end the project should generate more net benefits benefits minus costs than without the project. Cash flows projection of the three situations with, without and incremental On this basis, the Incremental situations are measured according to the three hypotheses. Table below presents the situation of incremental cash flows with maximum prices.

Year 1 2 3 4 5 6 7 8 9 GOP without project Results of this analysis are given in the next section. Comparison with variants Private companies An alternative situation in which OSTR and farmers are replaced by private companies was described. Nevertheless, it was considered that yearly productions have a linear increase on five years instead of three years in the radical terraces model source of this hypothesis: Fleskens Luuk.

Catalist project. The following tables give amounts of cash flows in the without and with project situations under the three different hypothesis explained earlier. Table below presents the situation of incremental cash flows in the alternative situation with maximum prices Year GOP without project 1 Year 1 2 3 4 5 6 7 8 9 10 11 GOP without project It is important to verify affordability.

If alternative projects require investments of different sizes, it is recommended to divide the NPV of each project by the discounted investment, so as to allow comparisons between these projects. In other words, the IRR should at least be above the opportunity cost of capital in the country where the project takes place. Those results are presented in the tables above. The first two tables show profitability criteria for the initial situation as described in section 1. In the financial analysis process, cash flows of individual farmers were designed.

Syntheses of these cash flows are presented in Tables 3 and 4. Then, individual cash flows were consolidated through the following stages: 1. Investments costs for the overall project are included in the model. Costs are spread evenly over the first three years of the project. Financial Operating Profits are measured at the level of the overall project instead of at the level of households. An Inflation rate is applied for the first 4 years year 4 is the baseline.

Firstly, tables 33 and 34 present criteria for the consolidated initial situation. Nevertheless, there is a clear sensitivity to agricultural prices. The alternative situation financial analysis In the tables below, profitability criteria for the alternative situation are given according to Maximum prices and Minimum prices situations.

Figures in these tables show that the alternative situation in which firms are contracted to a much lower profitability. This is due to the lack of quality of work provided by such companies.

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In this alternative situation, there is no revenue distributed to farmers to allow them achieving the investment in bench terraces in the contrary of other situations. In this situation, yearly productions have a linear increase during the first five years. This hypothesis is based on the theory developed in the "Fleskens Luuk.

Table of contents

In this document, it is explained that productions in radical and progressive terraces are quite the same but that the timing of those productions vary a little bit. Tables below give more details on the results of the financial analysis of this variant.

The Center has identified numerous human genes and has made the data available to the scientific community. Lander and his colleagues have also pioneered in the application of genomics to biomedical research, such as methods for analyzing complex genetic traits. Among diseases of special interest to his group are cancer, diabetes, hypertension and dwarfism.

Lander is a geneticist, mathematician and molecular biologist. Among many other distinctions, he was selected to deliver a special Millennium Lecture at the White House in One of the first graduate students of Sydney Brenner in Cambridge, he set up an independent laboratory that helped to establish the nematode worm c. Following a second visit to Cambridge to work with John Sulston in , his work increasingly concentrated on genomic mapping and sequencing.

Building on his experience, he led one of the teams that published the working draft of the human genome in Waterston was at Washington University, St. He has had close scientific collaborations with many prominent genome researchers on both sides of the Atlantic and had a pivotal role in the completion of the first rough draft of the human genome in Maynard Olson was one of the first to recognize the potential of genome analysis and to develop experimental techniques for analysis of complex genomes.

The YAC system has become routine for positional cloning of genes involved in human diseases and was the prototype for other large-fragment cloning systems that play a central role in genome analysis. Olson graduated from the California Institute of Technology and earned a Ph. His major interest changed to genetics during his faculty positions at Dartmouth College, the University of Washington, Seattle and Washington University, St.

Louis, where he became a Professor of Genetics. His many honors include the Genetics Society of America Medal. Craig Venter has played a vital role in the sequencing and analysis of the human genome. His accomplishments in the development of methods for decoding genetic sequences, notably expressed-sequence tags ESTs and in bioinformatics, have provided a foundation for understanding the relationships between species and the biology of microbes.

He is known for the so-called "shotgun sequencing" strategy, which accelerates sequencing and is now a central component of all whole genome-sequencing strategies. Michael Waterman is responsible for the introduction of some of the most important mathematical concepts, statistical models and computer algorithms used for genome analysis. He pioneered RNA secondary structure prediction, evolutionary tree comparison, gapped alignment, parametric alignment and other sequence analyses. He has recently released a new algorithm representing a remarkable improvement in the efficiency and accuracy of genome sequence assembly.

He has trained many prominent computational genomicists and has been a prime mover in the development of the field. Waterman graduated in mathematics from Oregon State University and obtained his Ph. Jean Weissenbach is recognized for his work in human molecular genetics, particularly his studies of the human sex chromosomes, linkage mapping and the mapping and cloning of disease genes.

His studies of linkage led to the construction of the first extensive map of the human genome and greatly accelerated this field, while his own research on disease genes and his extensive network of collaborations demonstrated the usefulness of unpublished data from the genetic linkage map. He is currently Director of Genoscope, the French National Sequencing Centre, which is actively contributing to the sequencing of genes on chromosome Francis Collins also received the Canada Gairdner International Award in for his outstanding leadership in the Human Genome Project and particularly for the international effort to map and sequence the human and other genomes.

Ralph Steinman was a cell biologist whose research focused on the immune system including the human immune system in the setting of several diseases. He and his collaborators discovered a previously unknown class of immune cells, called dendritic cells. Dendritic cells are important and unique accessories in the onset of several immune responses including graft rejection, resistance to tumors, autoimmune diseases, and infections such as AIDS.

After completing an internship and residency at Massachusetts General Hospital, he joined The Rockefeller University in as a postdoctoral fellow in the Laboratory Cellular Physiology and Immunology headed by Dr. Zanvil A. Cohn and the late James G. He was named Henry G. Ralph Steinman is editor of the Journal of Experimental Medicine and serves on numerous editorial and advisory boards.

Richard Axel's laboratory studies how sensory information is represented in the brain. Olfactory sensory neurons expressing a given receptor project to spatially invariant loci in the brain to create a topographic map of olfactory information. His studies suggest a mechanism by which this sensory map may be translated in higher brain centers to allow for the discrimination of odors and appropriate behavioral responses.

Linda Buck explores the mechanisms underlying smell, taste, and pheromone sensing in mammals. In the olfactory system, hundreds of different odorant receptors are used in a combinatorial fashion to encode the identities of thousands of odorous chemicals. Studies using receptor genes as molecular and genetic tools have revealed how these combinatorial codes are represented in the nose, olfactory bulb, and olfactory cortex to ultimately generate diverse odor perceptions.

She did postdoctoral research in neuroscience at Columbia University College of Physicians and Surgeon. Linda Buck's honors include the Lewis S. Wright Award in olfactory research, the Unilever Science Award. Wayne Hendrickson's pioneering studies of the anomalous dispersion effect have established this technique as the method of choice for determining protein crystal structures in as rapid and straightforward manner as possible and has made the concept of structural genomics an experimental reality.

In addition to his central role in the development of multi-wavelength anomalous diffraction MAD methods, he was also a pioneer in the development of computer programs that are used to build and refine atomic models for proteins on the basis of X-ray diffraction measurements. His contributions to methodology are complemented by his determination of the first structure of a tyrosine kinase and the structure of the HIV protein, gp, in complex with the CD4 receptor and a neutralizing human antibody. In , he joined the faculty of the Department of Biochemistry and Molecular Biophysics at Columbia.

He showed that this functional brain mapping depended on the oxygenation status of the blood feeding the active neurons. It is used in surgical planning to identify the motor cortex. He is the recipient of a number of awards in Magnetic Resonance, is a member of the Institute of Medicine of the National Academy of Sciences and this year was awarded the Japan International Prize.

John Ellis was a leader in the field of chloroplast biogenesis. He studied the biochemistry of the development of chloroplasts in higher plants. In Ellis discovered the first molecular chaperone. He found that in chloroplasts unassembled subunits of the rubisco complex were associated with another protein which turned out to be a chaperone. These seminal experiments foreshadowed the discoveries of Horwich and Hartl. Ellis subsequently made substantial contributions to the concept of molecular chaperones which are required to assist a variety of cellular processes in all types of cells.

Ellis earned his doctorate in from King's College, London for research on transamination reactions with Professor Davies. Postdoctoral studies were done at Oxford in the Biochemistry Department on sulfate reduction in bacteria with Professor Pasternak. In was awarded a Personal Chair in the department and in was elected to the Royal Society.

Ulrich Hartl's research is in mechanisms of cellular protein folding, specifically the structure and function of molecular chaperones. He delineated, resolved and reconstituted the complete pathway by which molecular chaperones cooperate to fold proteins in the living cell. In a series of elegant studies he established how the folding protein is recognized by one chaperone, thereby preventing premature misfolding, and then transferred to a molecular machine which promotes proper folding.

While initially highly controversial, this mechanism is now well accepted and confirmed by x-ray crystallography. When these protein folding pathways are saturated or non-functional, protein aggregates accumulate in the cell. Examples of diseases that are likely the result of such aggregates are Alzheimer's and Huntington's Diseases. Hartl earned his medical degree from the University of Heidelberg in He began his postdoctoral fellowship in organelle biogenesis at the Institute of Physiological Chemistry at the University of Munich and continued his studies in protein secretion at the University of California at Los Angeles.

In he was appointed to the William E. Arthur Horwich is a pioneer in the field of molecular chaperones. These are a special class of proteins that assist other proteins in folding into their final form, which determines their function. Horwich discovered an accessory protein that is required for folding of proteins imported into mitochondria. His discoveries have advanced the understanding of protein folding and have profound implications for diseases, such as Alzheimer's, that are thought to result from protein misfolding.

Horwich is a recipient of the Hans Neurath Award. He is a member of the National Academy of Sciences. George Sachs is an exemplary bench to bedside medical scientist. These agents have truly revolutionized the therapy for gastric acid disorders such as ulcers and gasttroesophageal reflux, which has benefited millions of patients, reduced greatly the need for surgery and simultaneously created a billion dollar industry.

Sachs continues his translational research in defining mechanisms for gastric disease and producing new agents to optimize treatment. Sachs, born in Austria, is a medical graduate of the University of Edinburgh in Sachs has had many professional and editorial responsibilities and his honours include the Beaumont Prize and the Hoffman LaRoche Award.

The incidence of obesity is reaching epidemic proportions in developed countries. Importantly, Douglas Coleman is a pioneer in the field of obesity. His innovative studies in mouse genetic models of obesity in the early s provided compelling evidence for the existence of a hormone system that participated in the control of fat cell homeostasis. His research was the first to hint that the "dumb" fat cell participates in regulating the integrative biology of metabolism and weight control. Using elegant parabiosis cross-circulation protocols he noted that deficiency of a circulating "satiety" factor, or resistance to a circulating "satiety" factor, explained the phenotype of the obese ob and diabetes db mice, respectively.

He concluded that the circulating factor would be fat cell-derived. The ob and db mice are now known to carry mutations in the leptin ligand and leptin receptor, respectively. These seminal findings, performed using integrative physiologic approaches, provided breakthrough insights into the causes of obesity. His full career has been spent at the Jackson Laboratory in Bar Harbour, Maine, where he performed his classic parabiosis studies. Douglas Coleman is a recipient of numerous prestigious awards and accolades including the Claude Bernard Medal and membership in the National Academy of Sciences For more than 50 years, the name of Professor Brenda Milner has been synonymous with memory.

In the early s, in collaboration with Dr. The origins of modern cognitive neuroscience of memory can be traced directly to her rigorous and imaginative studies. She continues to pursue her research activities using modern brain imaging to dissect even further key components and regions functionally involved in cognitive processes. Her research has paved the way to molecularly-oriented approaches aimed at deciphering key genomic and cellular steps leading to memory traces. Since her service at the Universite de Montreal as Professeur agrege at the Institut de psychologie , she has been associated with McGill University, where she first became Research Associate in the Psychology Department in Endel Tulving has clarified the nature of human memory at the behavioural level and made substantial additions to our knowledge of its neural correlates.

His theorizing is of unusual breadth and coherence, has dealt with the relations between memory and consciousness at the experimental level, with the measurement of memory organization at the behavioural level, with methods for distinguishing memory systems at the experimental level, and with the neuroanatomical correlates of memory systems and processes at the level of brain mechanisms.

In an incredibly productive career spanning nearly half a century, he has radically changed how scientists view human memory, and his theoretical frameworks now guide the whole field of memory research. Tulving was born in Estonia, moving to Canada as a young adult. He earned his doctorate from Harvard University in and accepted a position at the University of Toronto. He remained in Toronto except for a brief period at Yale University , serving as Chair of the Department of Psychology from to , and becoming University Professor in Jeffrey M.

Friedman is a leader in the biology of the mechanisms that control body weight. In he completed an investigative "tour de force" that spanned nearly a decade when he discovered the genetic defect in the murine "obese" ob mutant. Leptin was the first fat cell-derived hormone to be discovered. Building on the seminal early work of Douglas Coleman Gairdner International Award Winner he employed positional cloning approaches to characterize the defective gene well before the advent of today's repositories of gene sequence and sophisticated investigative genetic tools and informative DNA markers.

The isolation of the gene rapidly led to his integrative studies which helped define the biological effects of leptin at the whole animal level and the elucidation of a genetic defect in the leptin receptor in the "diabetes" db mouse model of obesity. Taken together his work provided the "spark" that has ignited an international frenzy of academic and industry-based research into the study of the causes and treatment options for obesity.

The discovery of leptin and newer studies defining the link between leptin released from fat cells and modulation of brain function by leptin have fundamentally advanced our understanding of the control of total body fat content. Most recently, he has been awarded many accolades and awards including membership in the National Academy of Sciences and the Bristol-Meyers Squibb Award for Distinguished Achievement in Metabolic.

Andrew Fire, with his studies on gene regulation in the nematode Caenorhabditis elegans, has made important contributions to describing and elucidating mechanisms of gene silencing by double stranded RNA. This paradigm of gene silencing contributed to by the work of Fire has been described as "one of the most exciting discoveries of recent times in molecular biology". Much effort has been focused on the efficacy of a system that can use just a few molecules of dsRNA to silence a large population of target molecules.

The underlying responses to these silencing triggers are present in many organisms, and in plants have clearly been shown to be involved in response to pathogenic challenges. These gene silencing processes in animal systems have a role in viral pathogenesis and in tumor progression in mammalian systems.

Sydney Brenner from Craig Mello is a pioneer in the field of regulation of gene expression by small RNA molecules, an area recently described as "arguably the most important advance in biology in decades". His studies, focused through elegant experiments with a very powerful model organism, the nematode Caenorhabditis elegans, were and continue to be instrumental in elucidating mechanisms of gene regulation through short double-stranded RNAs, short interfering siRNA.

RNAi has become an extremely powerful tool for basic studies on gene silencing and has led the way to important practical applications in biotechnology and medicine. He is known in both the developed world and in East Africa for his research as a clinical scientist and as a humanitarian who has given selflessly in nurturing others. He mentored 70 infectious diseases Fellows who have gone on to populate Canadian academic institutions.

He began a shared program with the University of Nairobi where over 80 Africans have received MSc or PhD degrees, and in collaboration with major universities over peer-reviewed papers have been published. Central to these have been studies on the epidemiology of HIV and other sexually transmitted diseases. Ronald was born in Manitoba and graduated in medicine from the University of Manitoba Ronald was head of the Department of Medical Microbiology , and H.

Sellers Professor and Head of Internal Medicine Starr Award CMA. Ralph Brinster is a pioneer in the development of techniques for manipulating the cellular and genetic composition of early mouse embryos. These techniques have made the mouse the major genetic model for understanding the basis of human biology and disease.

He began his work by showing how mouse embryos could be cultured in a Petri dish in a simple culture medium and then showing how cells could be added to such embryos to make animals of mixed cell origins or chimeras. This work was a key enabler of targeted mutagenesis in embryonic stem cells, which has revolutionized our ability to understand gene function in mammals. He is acknowledged as the founder of the field of mammalian transgenesis, with its applications to human disease models and biotechnology.

In recent years he has developed new models of germline manipulation using sperm progenitor cell transplants. In all these studies, Dr. Brinster has been an innovator, a perfectionist and a forward thinker, understanding clearly the need to develop enabling technologies to pursue novel biological questions.

His range of contributions is unmatched in the field.

Νικασ βασιλειοσ γυναικολογοσ καλαματα

Brinster grew up on a small farm in Cedar Grove, New Jersey, where some of his early experiences with animals included, as a teenager, running a small poultry business, which helped finance his studies in veterinary medicine. He is a member of the National Academy and the Institute of Medicine and has received many awards and honours including the Wolf Prize, and the first March of Dimes Prize in Developmental Biology in Ronald A.

Evans' scientific contributions in the field of nuclear receptors and their function have been seminal. His work is in an area that has wide medical application. In , his cloning and characterization of the first nuclear hormone receptor, the human glucocorticoid receptor, heralded a "molecular revolution" that transformed the field and, with it our understanding of how hormones, fat-soluble vitamins and dietary lipids elicit changes in gene expression in health and disease.

In the years that followed, he uncovered nearly 50 such receptors that, taken together, constitute the nuclear receptor superfamily and represent an important mechanistic link between diet, exercise and a myriad of human diseases, including cancers, diabetes and osteoporosis. Particularly noteworthy was the discovery of the peroxisome proliferator-activated receptor PPAR family of orphan receptors that provided "a molecular interface between dietary fats and the genome.

Ronald M. James Darnell. Alan Hall has been a pioneer in showing how external signals control the cellular cytoskeleton, composed of proteins such as actin, which in turn organizes the shape and movement of cells. His research revealed a series of crucial molecular switches called Rho GTPases , which acting together determine when and where the cell's outer membrane and actin cytoskeleton become rearranged to drive changes in cell migration.

These are crucial features of cellular function in normal tissues, and critical for the aberrant behaviour of cancer cells. Hall's work has therefore transformed our understanding of the biology of human cells. He obtained his PhD from Harvard University Following postdoctoral training in Edinburgh and Zurich, he became a group leader at the Chester Beatty Laboratories in London , where he was promoted to Professor Hall holds many prominent editorial and advisory positions.

Thomas Pollard pioneered the biochemical and biophysical analysis of the actin cytoskeleton, which is responsible for form and movement in all cells. His many contributions have defined the actin cytoskeleton field for nearly three decades, and include the basis for directional actin polymerization, the discovery of actin capping, severing and nucleation factors and the mechanisms of actin-based intracellular movement. The complex actin-based cytoskeletal network underlies cell shape and motility in virtually all biological contexts, including intracellular transport, polarized cell growth and division, tissue formation and developmental morphogenesis.

In addition, actin dynamics is essential for virulence of a number of human bacterial pathogens. He returned to Harvard in , and was promoted to Associate Professor Pollard has held innumerable prestigious advisory and editorial board positions, including the Presidency of the American Society for Cell Biology and the Biophysical Society. He has given many named lectures and won a number of prestigious awards including a Guggenheim Fellowship, the Rosensteil Award and the E.

Wilson Medal. He is also a renowned mentor, for which he has won numerous teaching awards. She has worked with many different biological systems, from bacterial viruses to unicellular eukaryotes, to other eukaryotic model organisms, to mammalian systems including human to address key questions about fundamental biological questions. Her enthusiasm for scientific research has been influential in the education, training, and mentoring of numerous students and postdoctoral fellows, particularly women, many who have gone on to exceptional careers and contributions of their own.

James Watson. Wilson Medal , the Rosalind E. David Allis is a leader in the field of chromatin biology. He has pioneered experimental and theoretical studies elucidating the mechanisms by which post-translational modifications of histones regulate the functions of chromatin. His studies demonstrating the identity between biochemically purified histone modifying enzymes and genetically defined transcription co-activators established a critical link between covalent histone modifications and gene activation and opened a new era in chromatin biology and our understanding of genome function.

He proposed and refined the current paradigm referred to as the 'histone code hypothesis' to explain how cell signaling cascades result in individual or combinatorial histone modifications, forming an epigenetic code that dictates specific functional outcomes through downstream interactions with distinct combinations of transcriptional regulatory factors. His research has been driven by his development of novel methods for studying protein modifications that are now mainstream in the field. His work has brought together the fields of chromatin biology and genome function and has had major impact on the basic fields of genetics, cell, developmental, and molecular biology with major impact for the understanding of abnormal development and cancer.

Byrd Jr. Professor of Biochemistry and Molecular Genetics. He has received numerous awards including the Syracuse University William J. He has presented many Distinguished Lectures, has published over scientific papers, and is co-editor of a recent ground breaking book on Epigenetics. Proper chromosome segregation during mitosis is essential for all life, and has been one of the outstanding problems in cell biology for over years. Nasmyth has dominated the field of mitotic regulation with a series of incisive discoveries, including characterization of the anaphase promoting complex that degrades mitotic cyclins, the cohesin complex that links sister chromatids together prior to mitosis, and most importantly, the novel proteolytic mechanism that rapidly breaks up sister chromatid cohesion at the onset of mitosis.

Nasmyth's work on fundamental aspects of cell divison has profound implications for our understanding of chromosome non-disjunction in human cancer and other genetic diseases. Harry F. Noller's work has led to fundamental changes in our thinking about the role of RNA in the many steps of protein synthesis. He has used the full range of techniques including traditional biochemical as well as high resolution structural analysis to elucidate mechanisms of protein synthesis.

His contributions to the sequencing and of genes encoding ribosomal RNAs and to phylogenetic and other analysis of these data led to insights into the secondary structure of these molecules and to functional inferences. Chemical probing and crosslinking experiments provided the key insights to appreciate the possibility that the peptidyl transferase activity of the large subunit of the ribosome may comprise RNA. His subsequent refined structural analysis building on results from biochemical analysis of stripping of proteins from the large ribosomal subunit and assaying for peptidyl transferase activity has provided a significant contribution to the full understanding of RNA catalysis of peptide bond synthesis and other aspects of ribosome structure and function and protein synthesis.

He has been Robert L. He has authored or co-authored approximately high impact publications and has trained many outstanding students and postdoctoral fellows. Thomas Steitz's scientific career has involved studies of biological structure using X-ray crystallography including developing and refining novel techniques to determine the structure of proteins and nucleic acids with the focus of addressing questions of biological function and mechanism of action. Much of his work has been directed to understanding the structural basis of enzyme mechanisms and on protein-nucleic acid interactions.

His earliest studies on protein structure and mechanism of enzyme action include work on yeast hexokinase demonstrating that substrate binding induces a large conformational change in the enzyme providing experimental support for the induced fit mechanism of enzyme specificity. Subsequently, his work has focused on providing a structural basis for understanding the mechanisms and specificity of gene expression including replication, genetic recombination, transcription, reverse transcription, and translation, the work cited for this award.

He provided the first structure of a DNA polymerase, a bacterial polymerase, followed by studies on mammalian polymerases and the HIV reverse transcriptase. These studies and elucidating structures of recombination enzymes, RNA polymerases, transcription factors, and aminoacyl tRNA synthetases have all provided important and in many cases unexpected insights into biological function in pathways involved in information transfer and genome stability and change.

His structural studies on the large ribosomal subunit provided the first atomic level insights into the structure and function of the ribosome, the site of protein synthesis in the cell. Further studies have refined insights into principles of RNA folding, stability, and RNA-protein interaction, and have also addressed questions of the mechanisms of peptide bond formation and other aspects of protein synthesis on the ribosome.

Structures of complexes between the large subunit and antibiotics make possible the structure-based design of new antibiotics potentially active against antibiotic resistant microorganisms. Tom Steitz is a co-founder and Chairperson of the Scientific Advisory Board of a company involved in the translation of the basic studies of the ribosome to be applied to the development of important health care products, effective antibiotics active against presently antibiotic resistant microorganisms.

Likely the most significant outcome of the studies on the ribosome from the Steitz lab is the elucidation of the chemical mechanism of RNA catalyzed peptide bond formation and the key role of RNA in ribosome structure and function; the ribosome is a ribozyme. Dennis Slamon's work exemplifies translational research of the highest order. His work has saved the lives of thousands of women. Herceptin has provided a paradigm shift in the field of cancer therapy by showing that drugs can be developed against defects present in specific cancers.

He received his PhD in cell biology the same year In he became Executive Vice-Chair for Research. After receiving further medical training, he was a research fellow first at the University of Dusseldorf , and then at the Children's Hospital of Philadelphia, , where he worked under Prof.

Werner Henle. In , he became an emeritus professor at the German Cancer Research Center. The earliest was the recognition that there are multiple HPV genotypes, particularly that the HPVs that caused non-genital warts and those that caused genital warts might be distinct 2,3. Prior to his studies, it was believed that there might be a single HPV, as it had been shown in the first part of the 20th century that cutaneous warts could be induced with filtrates from genital or laryngeal warts.

His most important finding was the identification and molecular cloning of the HPV16 and HPV18 genomes, and the associated demonstration that a majority of cervical cancers contained DNA that hybridized under stringent conditions to probes from HPV16 or HPV18 and that an even higher proportion of cervical cancers would hybridize to these probes under less stringent conditions.

These observations strongly implied: 1 papillomaviruses were etiologically involved in this cancer; 2 infection by more than one HPV type could result in cervical cancer; and 3 there were additional related HPV types that also caused cervical cancer. The third critical finding was that the HPV DNA was integrated into the host genome in cervical cancer cell lines and the associated demonstration that the viral E6 and E7 genes were preferentially retained and expressed in the tumors.

These observations provided a mechanism for the efficient transfer of viral DNA progeny cells, implied that viral gene expression might be required for maintenance of the tumorigenic phenotype, and that E6 and E7 probably represented key viral oncogenes. In addition to the role of HPV in cervical cancer, other evidence has led to the conclusion that a substantial proportion of several additional types of cancer are also caused by HPV infection.

These include various genital cancers such as vulvar and penile cancers , anal cancers, and head-and-neck cancers. Some of the more important findings made during this period include: 1 finding that most Buschke-Loewenstein tumors, which are large but low-grade malignant penile tumors, contain HPV6 or HPV11, which usually do not cause malignancy at other sites; determining that E6 and E7 expression in cervical cancer cell lines is required for maintaining the transformed phenotype; finding that HPV DNA in cervical tumors may be integrated near the c-Myc oncogene and be associated with its activation; the isolation of several new HPV types and their clinical importance; epidemiological studies delineating the prevalence of genital HPV infection and the risk of progression dysplasia or cancer; identification of cellular transcription factors that interact with the main HPV promoter; and the role of AP-1, Fos, and Fra-1 in regulating HPV transcription.

He has also been a highly sought after and effective spokesman for the papillomavirus research community and for the role of viruses in human cancer. Gary Ruvkun is a professor of genetics at Harvard Medical School. Ruvkun is a graduate of UC Berkeley and Harvard. Ruvkun began to work with C. The genetic analysis that Ambros and Horvitz had done suggested that the gene lin-4 negatively regulates lin but the molecular basis of that regulatory axis was not known.

In the Horvitz lab, Ruvkun and Ambros had to develop new technologies to allow such genetically defined loci to be analyzed molecularly, and they succeeded to isolate the lin gene. This work continued in their own labs at Harvard, starting in for Ambros and for Ruvkun. The first hint that the key regulatory element of the lin gene was in its 3' untranslated region came from the molecular analysis of lin gain-of-function mutations, showing that they are deletions of conserved elements in the lin 3' untranslated region that relieve the normal late stage-specific repression of LIN protein production, and showing that lin-4 is necessary for that repression.

The Ambros lab discovered in that lin-4 encodes a very small RNA product. When Ambros and Ruvkun compared the sequence of the lin-4 miRNA and the lin 3' untranslated region, they discovered that the lin-4 RNA base pairs with conserved bulges and loops to the 3' untranslated region of the lin target mRNA to downregulate its translation, and that deletions in the lin 3' UTR complementary sites, which are conserved in evolution, relieve the repression normally induced by base pairing to the lin-4 miRNA These papers revealed a world of RNA regulation at an unprecedented small size scale and the mechanism of that regulation.

In , the Ruvkun lab, again in collaboration with the Ambros and Horvitz labs, reported in Nature the identification of second microRNA, let-7, which like the first microRNA regulates translation of the target gene lin via imperfect base pairing to the 3' untranslated region of that mRNA. The microRNA field was shown to be general in biology with the publication from the Ruvkun lab of a second Nature paper in reporting that the sequence and regulation of the let-7 microRNA is conserved across animal phylogeny, including in humans. Presently thousands of miRNAs have been discovered, pointing to a world of gene regulation at this size regime.

In a Nature paper, the Ruvkun lab reported that mutations in the retinoblastoma ortholog of C. This revealed that small RNAs are likely to mediate the dysregulations of cell cycle during tumor formation, a previously unsuspected regulatory modality in tumor formation. In addition to revealing fundamental regulatory axes in biology, some of these components may be developed as drug targets to enhance RNAi in mammals, a technical improvement that may be necessary to elevate a laboratory tool to a therapeutic modality.

Ruvkun has also worked in other fields, such as control of longevity and fat storage, where his lab discovered for example that insulin signaling is key to longevity in C. Ruvkun has an active research program in microbiology, searching for deeply divergent microbial life, even on other planets. He did his graduate research with David Baltimore at MIT, studying poliovirus genome structure and replication.

He began to study the genetic pathways controlling developmental timing in the nematodeC. Robert Horvitz's lab at MIT, and continued those studies while on the faculty of Harvard Dartmouth , and the University of Massachusetts Medical School present. In , members of the Ambros lab identified the first microRNA, the product oflin-4, a heterochronic gene ofC.

Since then, the role of microRNAs in development has been a major focus of his research. Primarily a developmental biologist, Prof. Mycorrhiza 14, — Journal of Ecology 84, — Brundrett, M. C Mycorrhizas in natural ecosystems. Advances in Ecological Research 21, — Caravaca, F. Plant Science , — Carvalho, L. Cook, R. Cornwell, W. American Journal of Botany 88, — Davies Jr. San Luis with arbuscular mycorrhiza indigenous to Mexico. Scientia Horticulturae 92, — Escudero, V. Mycorrhiza 15, — Fougnies, L. Mycorrhiza 17, — Plant and Soil , — Journal of Experimental Botany 54, — Giri, B. Biology and Fertility of Soils 38, — Microbial Ecology 54, — Hartmond, U.

Plant and Soil , 37— Hetrick, B. Canadian Journal of Botany 74, 19— Ipsilantis, I. Applied Soil Ecology 35, — Jackson, M. Journal of Experimental Botany 53, — Jacobson, K. Journal of Arid Environments 35, 59— Juniper, S. Mycorrhiza 4, 45— Mycorrhiza 16, — Kaya, C. Koide, R. In: Advances in Plant Pathology Vol. Academic Press, London, pp. Lugo, M. Mycologia 94, — McMillen, B.

Soil Biology and Biochemistry 30, — Mendoza, R. Ecologia Austral 12, — Miller, S. Oecologia , — Functional Ecology 14, — Mullen, R. Oecologia 94, — Muthukumar, T. Acta Oecologica 23, — Neto, D. Plant and Soil , 51— Nielsen, K. Pfeiffer, C. New Phytologist , — Pringle, A.

American Journal of Botany 89, — Querejeta, J. Soil Biology and Biochemistry 39, — Ray, A. Aquatic Botany 84, — Redman, R. Rilling, M. Ecology Letters 7, — Ruiz-Lozano, J. Mycorrhiza 10, — Physiologia Plantarum 98, — Plant Science , 37— Sannazzaro, A. Schellenbaum, L. New Phytologist , 59— Smith, S. Subramanian, K. Mycorrhiza 9, 69— Scientia Horticulturae , — Taylor, T.

Mycologia 87, — Tian, C. Applied Soil Ecology 26, — Tobar, R. Mycorrhiza 4, — Tornbjerg, T. Convective throughflow pathways and ecological significance. Aquatic Botany 49, 91— Vandenkoornhuyse, P. Molecular Ecology 11, — Wu, Q-S. Journal of Plant Physiology , — Botanical Studies 48, — Yano-Melo, A. Pacovan plantlets to saline stress. Agriculture, Ecosystems and Environment 95, — Introduction Mycotoxins are a diverse group of fungal secondary metabolites, which are harmful to animals and humans.

Several fungi are able to produce mycotoxins. Most of the mycotoxin-producing species are filamentous ascomycetes, basidiomycetes or imperfect fungi, with Aspergillus, Fusarium, Penicillium and Alternaria usually being considered the most important mycotoxin-producing genera. Postharvest spoilage caused by these and other fungi is the most important source of mycotoxins in foods and feeds.

However, many fungi produce toxins while interacting with living plants as pathogens or as endophytes preharvest spoilage. Ochratoxin A OTA is a pentaketide mycotoxin that contaminates different plant products, including cereals, coffee beans, nuts, cocoa, pulses, beer, wine, spices and dried vine fruits see Fig. Ochratoxins are cyclic pentaketides, and are dihydroisocoumarin derivatives linked to an l-phenylalanine moiety. OTA was first discovered in in an isolate of Aspergillus ochraceus van der Merwe et al. OTA was shown to exhibit nephrotoxic, immunosuppressive, teratogenic and carcinogenic properties.

Several nephropathies affecting animals as well as humans have been attributed to OTA; and for example, it is the aetiological agent of Danish porcine nephropathy, and renal disorders observed in other animals Smith and Moss, In humans, OTA is frequently cited as the possible causative agent of Balkan endemic nephropathy, a syndrome characterized by contracted kidneys with tubular degeneration, interstitial fibrosis and hyalinization of glomeruli Krogh et al.

Recently, it has been suggested that OTA may have a role in chronic karyomegalic interstitial nephropathy and chronic interstitial nephropathy in Tunisia Maaroufi et al. Several reviews have recently been published on the chemistry, molecular biology and mode of action of ochratoxins Abarca et al. In this chapter we will give a general overview of recent progress in ochratoxin research, with emphasis on OTA-producing organisms, biosynthesis, molecular detection methods and control strategies.

Occurrence and Legislation of Ochratoxins in Agricultural Products Ochratoxins have been detected in several agricultural products including cereals, coffee beans, cocoa, spices, soybeans, peanut, rice, maize, figs and. Ochratoxin-producing organisms are usually considered as causing postharvest spoilage. However, Penicillium verrucosum is often isolated from surface-sterilized cereals examined at harvest, indicating that preharvest infestation by OTA-producing fungi is at least partly responsible for OTA contamination Miller, Indeed, OTA contamination of green coffee beans has recently been suggested to occur before storage Bucheli et al.

Mantle examined the uptake of radiolabelled OTA from the soil by coffee plants, and suggested that OTA contamination of coffee beans is partly due to fungal activity in soil rather than to fungi growing on coffee beans. Further studies are necessary to clarify the significance of these observations.

OTA-producing Penicillium spp. OTA contamination of cereals, green coffee beans and foods such as mouldy cheese, fish, milk powder, bread and spices is a serious health hazard throughout the world. Contamination of green coffee beans is especially important, as some studies have found that OTA is not completely degraded during roasting Tsubouchi et al. OTA has also been detected in beer Mateo et al.

aid-for-trade: case story

The potential danger presented by OTA to humans and animals has led many countries to take measures to restrict OTA contamination of foods and feedstuffs. In , about countries had in place some regulations regarding mycotoxins FAO, and, of these, 37 had regulations for OTA levels in agricultural products. Table 3. Fungal species responsible for ochratoxin contamination of different agricultural products after Frisvad et al. Agricultural products.

Cereals Penicillium verrucosum, Aspergillus ochraceus Fermented products meat, cheese P. The main contributors to OTA intake in the EU are cereals and cereal products and, to a lesser degree, wine see Chapter 9, this volume , coffee, beer, pork, pulses and spices EFSA, Ochratoxin-producing Organisms Ochratoxins are produced mostly by Penicillium spp. Two other species, A. The most important species regarding potential OTA production in coffee, rice, beverages and other foodstuffs are A.

The most important OTA-producing species in this section is A. While most A. Two other black Aspergillus species, A. Black aspergilli have been implicated in OTA contamination of coffee beans, grapes and spices see Table 3. A number of species in the genus Penicillium were described as OTA producers in the early s Ciegler et al.

Some of these, such as the OTA-producing P. Although Pitt suggested that P. Ochratoxin-producing Aspergillus species. Reference s Varga et al. The OTA-producing abilities of these species have not yet been confirmed by other laboratories. Recently, OTA production has also been claimed for some endophytes of coffee, including one isolate each of P. The isocoumarin ring of OTA is a pentaketide skeleton, to which a chlorine atom is introduced, and a C1 unit is added from methionine which is subsequently oxidized to carboxyl.

An intact l-phenylalanine is linked to the isocoumarin ring through this carboxyl group Moss, Wei et al. The isocoumarin group is a pentaketide skeleton formed from acetate and malonate via a polyketide pathway. A chlorine atom is incorporated most probably through the action of a chloroperoxidase to form the isocoumarin portion of OTA.

Phenylalanine that is derived from the shikimic acid pathway is linked to OTA through the additional carboxyl group. Precursor feeding experiments carried out by Harris and Mantle did not support an intermediary role for mellein in OTA biosynthesis, but could not rule out the role of 7-methyl-mellein. However, there was no evidence for the intermediate role of the ester ochratoxin C as proposed by Huff and Hamilton Various enzymes and genes are involved in OTA biosynthesis.

The latter enzyme is possibly a non-ribosomal peptide synthetase. Genes coding for some of these enzymes have been identified in some species, including P. Recently, two additional open reading frames have also been identified from P. Molecular Detection of Ochratoxin A-producing Fungi Several approaches have been used for the molecular detection of ochratoxinproducing fungi.

Schmidt et al. Fungaro et al. Perrone et al. Mule et al. Morello et al. A low-complexity oligonucleotide microarray OLISA has also been developed based on oligonucleotide probes obtained from sequences of the calmodulin gene for the detection of black aspergilli A. Atoui et al. The latter two groups have developed species-specific primer pairs designed from the acyltransferase domain of the polyketide synthase sequence. Part of the gene cluster responsible for OTA production in P. Specific primers have been developed for either P.

Recently, SchmidtHeydt and Geisen developed a microarray method for the detection of various mycotoxin-producing fungi based on sequences of genes involved in the aflatoxin, trichothecene, fumonisin, patulin and ochratoxin biosynthetic pathways. Controlling Ochratoxin Levels in Foods and Feeds Several strategies have been investigated for lowering mycotoxin contamination of feeds and foods.

The prevention of growth and mycotoxin production by fungi on plants and in feedstuffs is usually considered as the best approach to limit the harmful effects of mycotoxins on animal and human health. Knowledge of the key critical control points during harvesting, drying and storage stages in the cereal production chain is essential in developing effective pre- and postharvest prevention strategies. Ecological studies on the effects of environmental factors on growth and mycotoxin production have been identified for P. Plant breeding is traditionally used to improve the resistance of host plants to fungal infection.

Kernels of several varieties of wheat, rye and barley have been found to have varying levels of resistance to fungal attack and OTA accumulation, and so varieties with stronger resistance to fungal invasion during storage could be selected Chelkowski et al. However, to our knowledge, breeding has not been used to increase the resistance of host plants to OTA accumulation, and treating field crops with fungicides remains the traditional technique for lowering preharvest contamination. Several studies have examined the effects of fungicide treatments on the OTA content of wine.

Lo Curto et al. Greek studies have found pesticides such as Carbendazim and Chorus to be ineffective in controlling sour rot caused by aspergilli, while the application of another pesticide, Switch, led to a significant decrease in the incidence of aspergilli on grapes Tjamos et al. Although preventing mycotoxin contamination in the field is the main goal of the agricultural and food industries, the contamination of various commodities with Aspergillus or Penicillium isolates and their mycotoxins is unavoidable under certain environmental conditions.

For postharvest control, storage conditions should be improved to minimize the mycotoxin content of foods and feeds. Mycotoxin production is dependent on a number of factors, including the water activity of the stored product, temperature,. An integrated approach for controlling several of these factors could give much more effective control of deterioration, without requiring the extreme control of any one factor.

While certain treatments have been found to reduce levels of specific mycotoxins, no single method has been developed that is equally effective against the wide variety of mycotoxins that may co-occur in different commodities. Several strategies are available for the detoxification or decontamination of commodities containing mycotoxins. These can be classified as physical, physicochemical, chemical and micro biological approaches.

OTA is a moderately stable molecule which can survive most food processing such as roasting, brewing and baking to some extent Scott, Ensiling was found to reduce the OTA content of barley Rotter et al. These methods have, however, achieved only varying degrees of success, and none of them have been recommended for practical detoxification of OTA-contaminated grains and feeds Scott, Alternatively, microbes or their enzymes could also be applied for mycotoxin detoxification, and such biological approaches have been widely studied Sweeney and Dobson, There are several reports of OTAdegrading activities in the microbial flora of the mammalian gastrointestinal tract, including ruminal microbes in cows and sheep Hult et al.

The species responsible for OTA detoxification have not yet been identified, although protozoa were suggested as taking part in the biotransformation process in ruminants Ozpinar et al. Numerous bacteria, protozoa and fungi have been found that are able to degrade OTA see Table 3. Some enzymes, such as carboxypeptidase A Pitout, , a lipase from A. Bacteria such as Lactobacillus plantarum and Oenococcus oeni, and application of absorbents such as charcoal, liquid gelatine, yeast cell wall preparations or conidia of aspergilli have all been found to reduce the OTA content of wine Bejaoui et al.

Prevention of the Toxic Effects of Ochratoxins In some instances it is possible to prevent the toxic effects of OTA after it has been ingested. Sodium bicarbonate can be effective in preventing absorption from the stomach Creppy et al. The phenylalanine analogue. Bacteria Ruminal microbes Hult et al. Skrinjar et al. Lactobacillus spp. Fungi Aspergillus niger, A. Adsorbents have also been tested as potential binding agents for lowering OTA levels in body fluids. Cholestyramine, a resin used for pharmaceutical purposes in decreasing total and LDL cholesterol, can adsorb zearalenone, aflatoxins, OTA and fumonisins in in vivo experiments Kerkadi et al.

However, it is too expensive to be used on farms efficiently. Activated carbons have been shown to have high in vitro affinity to OTA Galvano et al. However, although several adsorbents have been developed for lowering the toxic effects of mycotoxins as feed additives, most of them have been found to be ineffective against OTA-induced toxicity in in vivo experiments Garcia et al.

Future Prospects Ochratoxins are among the most economically important mycotoxins. However, our knowledge of the occurrence, biosynthesis, mode of action and control of OTA is still fragmentary. Understanding the biosynthesis and effects of ochratoxins could facilitate the safeguarding of human and animal health. To achieve this goal, further research is needed to clarify the biosynthetic pathway of ochratoxins, to identify the significance of preharvest contamination of agricultural products and to determine the role of ochratoxins in animal and human pathogenesis. Further efforts are needed in order to reduce OTA contamination of foods.

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