Genetic analysis for drought tolerance and yield stability in interspecific and oryza sativa L. rice germplasm.

Doctor of Philosophy in Agriculture (Plant Breeding)Rice is currently an important staple food crop in Kenya. However, consumption continues to outstrip production. In spite of this, the country is endowed with untapped virgin land for rice production under rainfed upland and lowland ecologies. Nonetheless, drought, lack of modern improved farmer preferred cultivars, poor agronomic practices, and continued cultivation of low yielding late maturing landraces, are among the major challenges to rice production and expansion in the country. The objectives of this study were to: 1) document farmers’ desired traits in rice cultivars and perceptions of rice production constraints in coastal region of Kenya, 2) identify drought tolerant rice genotypes at reproductive growth stage among the popular landraces, local cultivars, and exotic interspecific and Oryza sativa L. lines, 3) determine the inheritance of earliness and combining ability effects for phenological and morphological traits in rice under drought and no drought stress conditions, 4) determine the combining ability effects for grain yield and related traits in rice under drought and no drought stress conditions, 5) assess the heritability, correlation and the direct and indirect effect of phenological, morphological and yield component characters on grain yield and 6) estimate the magnitude of genotype x environment interaction (GEI) for grain yield in rice. The study period was between January 2013 and March 2015. Farmers’ desired traits in rice cultivars and perceptions of rice production constraints in coastal region of Kenya were assessed using formal household survey and participatory rural appraisal (PRA) methodology during 2013 and 2014. Data were collected from Msambweni Sub-county of Kwale County and Kaloleni sub-County of Kilifi County of coastal region of Kenya from a total of 326 respondents. The results established that farmers preferred high yielding, short duration and drought tolerant cultivars of medium height with white, long and bold grains. Preference for cultivars with good baking qualities was one of the unique traits that featured in this study. Important traits for a variety with good baking qualities were; white milled rice flour with low fat content, dough easy to work on, porous and does not stick on the baking tin while baking. Drought was ranked as the most important constraint and drought stress occurring at reproductive and grain filling stage was the most prevalent. These findings reveal that an opportunity exists in the coastal region to breed for high yielding, early maturing drought tolerant cultivars with white, long, bold, tasty and aromatic grains, good for confectionery purposes. Genetic variability for drought tolerance at reproductive stage was assessed among 21 rice genotypes comprising of 6 interspecific and 15 Oryza sativa genotypes. These were evaluated at KALRO-Mtwapa in pot experiments under two conditions of no drought and drought between April 2013 and March 2014. For each treatment, the experimental design was randomized complete block design with four replications and the plot size made up of 10 pots. Data collection included canopy temperature, relative leaf water content, leaf rolling and drying, days to 50% flowering, spikelet fertility and grain yield per plant. Considerable genetic variability for drought tolerance at reproductive stage existed among the interspecific and Oryza sativa L. rice lines. Two local Oryza sativa cultivars, Shingo la Mjakazi and Kitumbo were moderately drought tolerant. The interspecific genotype CT16323-CA-25-M was highly drought tolerant while NERICA 2 was moderately tolerant. These genotypes were identified as potential donors for drought tolerance at reproductive stage and may be used in breeding programmes aimed at developing drought tolerant cultivars for the rainfed lowland and upland ecologies in sub-Saharan Africa. Inheritance and combining ability effects for earliness, grain yield and its contributing traits were studied using 10 x 10 half diallel mating design. The 10 parents included five interspecific and five O. sativa L. lines. The resulting F1 progenies were advanced to F3 generation. The 45 F3 populations, 10 parents and one check were evaluated in 7 x 8 alpha lattice design with two replications under three no drought and one random managed drought stress conditions at three sites in coastal region of Kenya. Inheritance of earliness was found to be conditioned by non-additive gene action under random drought conditions and additive gene action under no drought conditions. One interspecific line CT16323-CA-25-M and one O. sativa line, Vandana, consistently exhibited desirable general combining ability for earliness under drought and no drought conditions. In addition, Vandana, was a good general combiner for grain yield and spikelet fertility under no drought conditions. Across environments, the line Dourado precoce had the best general combining ability effect for a thousand grain weight. The interspecific line, NERICA 2, was the best for number of grains per panicle while NERICA 1 had the best general combining ability effects for heavy panicle weight and weight of grains per panicle, and good grain phenotypic acceptability. Therefore these parents (CT16323-CA-25-M, Vandana, Dourado precoce, NERICA 2 and NERICA 1) may be hybridized with the intent of selecting promising genotypes within the segregating generations. The best F3 populations with desirable specific combining ability effects were CT16323-CA-25-M x Vandana and Duorado x Vandana combining short duration with increased plant height and higher tiller number and NERICA 1 x NERICA 2 combining moderate drought tolerance index with desirable alleles for high yields, high thousand grain weight, heavy panicle weight, heavy grains per panicle and a good grain phenotypic acceptability. Early generation testing in these crosses was recommended to identify plants with desirable characters that may be advanced to homozygosity followed by selection of best pure lines for release in the region. The narrow sense heritability estimates for earliness based on days to heading was high (67%), indicating predominance of additive gene action while that for grain yield was low (0.1%) implying predominance of non-additive gene action. Direct effects on grain yield were significant and positive for number of productive tillers per plant (P = 0.71), panicle weight (P = 0.66) and spikelet fertility (P = 0.49). However, the heritability estimates for number of productive tillers per plant (29%) were moderate, and low for panicle weight (0.7%) and spikelet fertility (4%) limiting their use in early generation selections. A thousand grain weight had a high narrow sense heritability (82%) and positive indirect effect (P =0.44) on grain yield via panicle weight indicating that improvement of grain yield may begin in early generations by indirectly selecting for high thousand grain weight via heavy panicle weight. The stability analysis of the 45 F3 populations and their parents over four environments using the AMMI and GGE biplot models showed that ranking of the genotypes changed across environments. This revealed a crossover type of genotype by environment interaction. Both AMMI and GGE biplot analyses showed that the four environments fell into three mega environments and identified G37 (Luyin 46 x IR55423-01) as the most high yielding genotype. However they differed on the most stable and high yielding genotype across the test environments. The AMMI analysis showed that G41 (NERICA-L-25 x Vandana) followed by G1 (NERICA 1 x NERICA 2) and G34 (CT16323-CA-25-M x Vandana) were the most stable and high yielding genotypes. In contrast, the GGE biplot showed that G39 (Luyin 46 x IR74371-54-1-1) followed by G40 (NERICA-L-25 x IR55423-01) were the most stable and high yielding genotypes. Overall, this study provided valuable information that will help in setting and prioritization of breeding goals and objectives aimed at breeding for early maturing, farmer preferred cultivars, tolerant to drought stress at rice reproductive stage

Building partnerships and networks among science granting councils and other science system actors in Sub-Saharan Africa : final technical report

This project, part of the Science Granting Councils Initiative (SGCI), sought to support the Councils to improve their performance by utilizing innovative platforms for building networks among science system actors in Sub-Saharan Africa. The report summarizes major activities, outputs and impacts over the project period (2017 - 2020). The Annual Regional Meeting (ARM) and Annual Forums (AFs) which bring together Heads of Councils are of strategic importance to participating Councils. They contribute to the implementation of the African Union Commission’s (AUC) Science, Technology and Innovation Strategy for Africa 2024, and to key STI policy debates at regional and continental levels.UK's Department for International Developmen

Rainfed Rice Farming Production Constrains and Prospects, the Kenyan Situation

Kenya experiences huge production-consumption deficit in relation to rice. This is due to changing eating habits that has adopted more rice in the menu and rapidly rising population. Rice production has remained low being unable to meet consumption. Rice ecosystems in Kenya include irrigated, rainfed lowland and rainfed upland. Irrigated ecosystem has over the years been given more emphasis despite rainfed rice farming having double the potential over irrigation system. Ecologically rice grows well in abundant water supply, warm to high temperatures and in Clay sandy to loamy soils with slightly acidic to neutral pH. Rice varieties grown in Kenya are mainly traditional, introduced improved, hybrids and landraces. Rainfed rice farming faces constraint’s key among them being; drought and erratic rainfall, weeds, pest and diseases, cheap imports, land ownership and poor infrastructure. Mitigating against drought and erratic rainfall, improving farm inputs and equipment, increasing germplasm production and distribution, credit support and marketing to farmers, improving farmers skills through technological transfers and infrastructural development are prospects that if adopted could increase rainfed rice productivity. More attention towards improvement of rainfed rice farming could greatly contribute to bridging the production-consumption deficit that is bridged through imports. It is with this, that this review updates our understanding of rain fed rice farming in Kenya in terms of ecological conditions, ecological systems, varieties, constraints and prospects

The importance of market signals in crop varietal development: Lessons from Komboka rice variety

Growing high-yielding varieties is crucial for successful crop production and maximizing farmers’ net returns. One such example is IR05N221, locally referred to as Komboka rice variety, which was released in Kenya in 2013. On the one hand, Komboka can bridge the gap in rice imports since yields of existing rice varieties do not meet the increasing rice consumption levels of the Kenyan population. On the other hand, it has taken about seven years for Komboka to be appreciated by farmers, necessitating the need to understand farmer preferences when it comes to adopting a new improved variety. We used a mixed-method study approach by combining quantitative and qualitative data collected regionally and locally in both rainfed and irrigated ecologies. When compared to most of the other rice varieties under evaluation, Komboka was high-yielding, early-maturing, and had moderate tolerance to diseases in both rainfed and irrigated ecologies. However, farmers at the regional level ranked Komboka either at the same or lower rank in terms of sensory attributes. At the local level, farmers predominantly grew older and more aromatic Basmati 370 rice variety for sale, as it fetched them more money, with preferences for both men and women rice farmers being the same. Despite Komboka being a high-yielding variety, Mwea rice farmers’ perceptions and preferences for this improved variety were low. While Komboka was equally aromatic, the lack of a ready market dissuaded these farmers from widely preferring the new Komboka variety. We provide prerequisite information that can support the commercialization and promotion of the Komboka variety. We also show that widespread favourable perception of new varieties hinges on matching preferences between breeders’ efforts for improved rice productivity with farmers’ needs for market competitiveness in these new varieties

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Membrane active polymer anticancer conjugates

HPMA copolymer-drug anticancer conjugates have been successfully transferred into clinical evaluation. Such macromolecular constructs selectively accumulate within solid tumours by the enhanced permeability and retention (EPR) effect. However, lysosomotropically activated compounds such as HPMA copolymer- doxorubicin (PK1) present limitations in that they require enzymatic activation within lysosomes in order to release the active moiety which in turn exerts its cytotoxic effect. Hence this study looked at the development of a second generation, membrane active polymeric anticancer conjugates. Using melittin (MLT) as a model peptide, HPMA copolymer-MLT conjugates were synthesised and characterised using standard biochemical techniques (SDS PAGE, BCA protein assay and FPLC). The effect of MLT content using conjugates with high (38.9 ± 2.5 % w/w), medium (25.8 ± 6.2 % w/w) and low (12.1 ± 8.6 % w/w) MLT loading and the effect of peptidyl linker (-Gly- Gly- (GG) and -Gly-Phe-Leu-Gly- (GFLG)) were investigated in vitro. The MLT conjugate with medium loading and GG spacer showed reduced haemolytic activity (Hb50 19.9 ± 6.2 μg/ml (p < 0.05)) in a rat red blood cell lysis model, and maintained cytotoxic activity against a B16F10 murine melanoma cell line (IC50 7.3 ± 1.5 μg/ml; p = 0.46 (NS)) relative to free MLT. This conjugate was chosen to proceed with preliminary in vivo studies. The MTD of HPMA copolymer-MLT was found to be 4- fold greater than that of free MLT (10 mg/kg MLT-equivalent) and body distribution of MLT conjugate 3 mg/kg (MLT-equivalent) (i.p.) showed 3 - 4-fold increased circulation time. However, no improved tumour targeting by the EPR effect was established 4 h after i.p. administration. Disappointingly, no antitumour activity was observed in vivo following i.p. or i.v. administration. Nevertheless, improved synthetic procedures to prepare more compounds of this new class of anticancer agents is warranted

Synthesis and preliminary evaluation of poly(amidoamine)-melittin conjugates as endosomolytic polymers and/or potential anticancer therapeutics

The pH-responsive poly(amidoamine)s (PAAs) have been previously described. Whereas ISA23 enhances transfection in vitro and ISA1 promotes the cytosolic delivery of the non-permeant toxins this process shows poor efficiency. The aim of this study was to prepare and evaluate PAA conjugates containing the membrane disrupting peptide melittin (MLT). It was hypothesised that PAA conjugation would reduce the haemolytic activity of MLT at pH 7.4, however, upon delivery to tumours by the EPR effect, the polymer would uncoil in an acidic environment exposing MLT and allowing it to interact with membranes. PAA-MLT conjugates were prepared using MLT as a comonomer together with bis-acryloylpiperazine, 2-methylpiperazine and bis-hydroxyethylethylenediamine (ISA1-like), or bis-acrylamidoacetic acid and 2-methylpiperazine (ISA23-like). The melittin content of the conjugates was 6-19% (w/w). Although ISA1-MLT improved gelonin delivery compared to the parent polymer ISA1 (alpha 13-fold increase) and showed pH-dependent haemolytic activity at a polymer concentration of 0.05 mg/ml, this conjugate also displayed high haemolytic activity at pH 7.4. In contrast, ISA23-MLT like the parent compound ISA23 did not deliver gelonin. However, this conjugate could have potential as a novel polymeric anticancer conjugate due to its lack of haemolytic activity at pH 7.4 and retention of cytotoxicity. (c) 2005 Elsevier B.V. All rights reserved

Sharing knowledge for policy action in low- and middle-income countries: A literature review of managed entry agreements

Managed entry agreements (MEAs)—a type of formal institutional arrangement between pharmaceutical companies and payers for sharing the risk with respect to the introduction of new pharmaceutical technologies—may expand access to new pharmaceutical technologies for non-communicable diseases (NCDs). Although common in highincome countries (HICs), there is limited evidence of their use in low- and middle-income countries (LMICs). This article aims to document international experiences of countries implementing MEAs and potential barriers and facilitators for their use in LMICs. We reviewed published literature sources on MEAs over the past 10 years considering peer-reviewed publications and gray literature data. We took into consideration the MEAs taxonomy presented by Kanavos and Ferrario et al. to categorize our findings, and extract information on factors for their implementation. We retrieved 285 MEAs documented in the literature, mostly from HICs and for a broad spectrum of NCDs. Financial schemes were slightly more prominent than performance-based agreements. Identified factors that could potentially facilitate or hinder the implementation of MEAs included the presence of quality administrative and information systems to track their implementation; availability of quality data and evidence of positive outcomes; uncertainty of drug efficacy/effectiveness, safety, and financial impact; and cultural factors, namely country’s preference for certain type of agreement and trust among payers and manufacturers. The increased availability of publications in recent years suggests a growing interest among policy-makers and researchers in the implementation of MEAs. While the use of MEAs in LMICs is very limited, this could be the result of limited empirical evidence on its use and possibly due to the use of a different taxonomy for describing MEAs in these settings. As any other policy option, the implementation and use of MEAs come with advantages and challenges. Since there is limited evidence on their use in LMICs, the identified cases of implementation in HICs may serve to inform the interest on MEAs in resource limited settings. Therefore, further research in this field especially in the context of LMICs may be of value for the global community as all countries are embarking into fairer and sustainable Universal Health Coverage (UHC)

Contribution of genes related to grain number (Gn1a and WFP) introgressed into NERICA 1 to grain yield under tropical highland conditions in central Kenya

ABSTRACTIn Kenya and many other African countries, improving rice productivity is vital for future food security. To improve rice productivity in Kenya, near-isogenic lines (NIL) were developed by introducing Gn1a and WFP, genes that function to increase grain number per panicle by increasing secondary and primary rachis-branches, into NERICA 1, a registered variety in Kenya. The aim of this study was to determine whether the introduction of these genes has the potential to improve rice productivity under tropical highland conditions in central Kenya. Field experiments were conducted in 2016 and 2017 at a lowland rice field in Mwea, Kenya, under different nitrogen fertilization conditions using three lines of NERICA 1 introgressed with Gn1a and/or WFP (NIL-Gn1a, NIL-WFP, and NIL-Gn1a+WFP) and their recurrent parents, NERICA 1. Two years of field experiments revealed that the introgression lines enhanced grain yield by increasing the number of primary and secondary rachis-branches and the number of grains per panicle. Gn1a and WFP showed additive effects and the introgression of both genes alleviated the negative effects on yield components observed in the introgressed lines, resulting in higher grain yield. Sufficient nitrogen fertilization was required to increase yield in the single-gene introgression lines. However, the line with both Gn1a and WFP achieved reasonable yields even under low fertilizer conditions in Mwea, Kenya. As these introgression lines have similar growing characteristics to their parent variety, they are expected to contribute to increased rice production in Kenya and similar environments in sub-Saharan Africa