Genetic and Epigenetic Control of Soybean Agronomic Traits

Greater soybean productivity depends on the genetic improvement of yield components, epigenetic effects and the interactions with surrounding environment. We explored the possibility of soybean improvement by conventional biparental crossing of soybean lines, differing by seed quality, yield, and resistance to a range of pathogens, including soybean cyst nematode (SCN). We investigated the role of Resistance to Heterodera glycines (Rhg) 1 and 4 loci in soybean resistance to SCN, race 2 and 3. Further, we evaluated the adaptability of temperate-origin soybean lines in tropical environments of Rwanda. Lastly, we examined gene expression, RNA splicing, DNA methylation and their interactions in three distinct developmental stages of soybean nodules. Briefly, compared to the parental lines, the recombinant inbred lines (RILs) generated from the biparental cross, represented varying phenotypes for seed yield, protein and oil contents, with high broad-sense heritability scores. This suggests a possibility of selection of best individuals with potentially high genetic gain for each trait. Analysis of gene expression, nucleotide sequences, and copy number variation of Rhg1 and Rhg4 in a set of RILs revealed that resistance to race 2 is mediated independently of Rhg1 and Rhg4. Importantly, a QTL on chromosome 17, associated with resistance to SCN race 2 was identified, a finding that provides the foundation for cloning the underlying SCN resistance gene. Our data suggested a possibility to stack favorable SCN resistance alleles in high yielding cultivars as the yield of RILs harboring SCN resistance alleles to race 2, compared to the susceptible RILs, was not negatively impacted. Some US-developed soybean lines could adapt and double the current local yield potential. However, our data revealed a significant GXE interaction, implying their fitness in specific micro-climates of Rwanda. Amino acid profile and consequently seed storage protein can be improved through the manipulation of soybean nodulation. Our results revealed dynamic changes in gene expression, alternative splicing events and extensive DNA methylation reprogramming in the developing nodules. The results also revealed novel insights to the associations between the transcriptome, spliceome, and methylome of the developing soybean nodules and improved our understanding of the genetic and epigenetic mechanisms controlling soybean nodulation

Active and Participative Pedagogy at University Level: A Contribution to Higher Education in Rwanda

In dieser Arbeit geht es um aktivierende Hochschuldidaktik in Ruanda, die in Ruanda Pédagogie Active et Participative (PAP) genannt wird. Hintergrund der Arbeit ist der hohe Bedarf an Hochschuldidaktik in diesem Land (vgl. Kapitel 1 der vorliegenden Arbeit). Der Bedarf ist durch zwei Faktoren bedingt. Zum einen ist die Hochschuldidaktik bisher noch stark einem kolonialen Vermittlungsstil verbunden. Studierende erreichen durch diese Methoden die Kompetenzen nicht, die sie erreichen sollten (vgl. Kapitel 1). Lehramtsabsolvierende übernehmen diese Methoden aus ihrem Universitätsstudium und implementieren diese in ihrem Unterricht. Dies führt unter anderem dann zu einem zu geringen Kompetenzerwerb von Schülerinnen und Schülern (Kapitel 1) Vor diesem Hintergrund ist die Reflexion hochschuldidaktischer Methoden eine absolute Notwendigkeit. Zum zweiten hat der Hochschulmarkt in Ruanda zweistellige Zuwachsraten. Von daher steigt im Moment die Anzahl der Lehrenden an Universitäten und Hochschulen, ohne dass das Personal auf diese Aufgabe hinreichend vorbereitet wäre. Grund also auch, über Fragen der didaktischen Qualifizierung für Lehrende nachzudenken. Dies legen auch die Ausführungen zum Forschungsstand nahe (vgl. Kapitel 2 und 4.2 der vorliegenden Arbeit), in der zwar eine deutliche normative Forderung nach der Einführung und Verbreitung einer aktivierenden Hochschuldidaktik erhoben wird, die Erfahrungen mit einer solchen in Subsahara Afrika jedoch bisher kaum gegeben ist. Drittens werden mit dieser Studie die Wahrnehmungen von Hochschullehrkräften und Studierenden gegenüber einer aktivierenden Hochschuldidaktik erhoben. Beide Zugänge werden als Grundlage für den Beginn einer hochschuldidaktischen Debatte in Ruanda bzw. dem frankophonen Afrika diskutiert. Entsprechend werden mit dieser Arbeit zwei große Zugänge verfolgt. Zum einen werden die Grundlagen einer partizipativen und aktivierenden Didaktik für den afrikanischen Raum erarbeitet und damit Bausteine erziehungswissenschaftlicher Theoriedebatten für die Hochschuldidaktik in Ruanda erarbeitet (vgl. Kapitel 3). Zum andern werden mit dieser Arbeit die Wahrnehmungen unterschiedlicher Stakeholder in der Hochschullandschaft Ruandas erhoben und so die Bedingungen für eine hochschuldidaktische Arbeit zumindest ansatzweise geklärt (vgl. Kapitel 4). Die Grundlagen der Hochschuldidaktik kommen aus vier unterschiedlichen Quellen: aus historischen Zugängen zur Rolle des Lernenden im Bildungsprozess, aus systematischen Überlegungen zur Natur des Lernprozesses, aus der empirischen Forschung sowie wie aus konzeptionellem Wissen zu lerneraktivierenden Methoden (vgl. Kapitel 3). Diese unterschiedlichen Zugänge werden jeweils exemplarisch entfaltet. Hinsichtlich der historischen Zugänge wird auf die lernerorientierten Ansätze bei Pestalozzi, Dewey, Freinet und Freire eingegangen (vgl. Kap. 3.1). Die Auswahl dieser Schriften orientiert sich an den in der Ausbildung in Ruanda dominierenden Klassikern. Wichtig ist es, hier Lesarten zu generieren, die die Rolle des Lernenden reflektieren und damit bei Studierenden und Hochschullehrkräften den Boden bereitet für jenen „conceptual change“, der für die individuelle Veränderung von Lehrhaltungen von Bedeutung ist. Hinsichtlich der systematischen Zugänge zum Lehr-Lernprozess werden die Überlegungen, die aus der Debatte des Konstruktivismus und dem Verständnis von Lernen als autopoietischem Prozess resultieren, dargelegt (vgl. Kapitel 3.2). Beide Zugänge sind für ein lernerzentriertes Verständnis von Bildung zentral und können damit als bedeutsame systematische Grundlegung für eine partizipative und aktivierende Pädagogik in Lehrerbildung und Universität dienen. Mit Blick auf eine empirische Grundlegung dieses Zugangs ist spätestens mit der Metaanalyse von John Hattie deutlich geworden, dass didaktische Maßnahmen hinsichtlich ihrer Effizienz differieren und damit unterschiedlichen Einfluss auf die Qualität des Bildungsprozesses bzw. dessen Erträge haben (vgl. Kapitel 3.3). Aus den Arbeiten von Hattie lassen sich Schlussfolgerungen für eine evidenzbasierte Didaktik ziehen. Vor diesem Hintergrund wird die Effizienz einer partizipativen und aktivierenden Pädagogik ersichtlich. Empirische Forschung bietet damit diesem Unterrichtsansatz ein zusätzliches Gewicht und eine zusätzliche Legitimation. Aus der Praxis des lernerzentierten Unterrichts resultieren didaktische Zugänge wie der des problemlösenden Denkens, einer kooperativen Pädagogik, der Projektmethode, dem Portfolio-Ansatz (vgl. Kapitel 3.4). Diese werden als konzeptionelle Beiträge einer partizipativen Pädagogik abschließend dargestellt. Neben dieser literaturbasierten Darstellung wurde – wie oben dargestellt – mit dieser Arbeit zudem ein empirischer Zugang gewählt. Dazu wurden über drei Wochen Beobachtungen eines Trainings für Lehrkräfte an Sekundarschulen durchgeführt, sowie einundzwanzig Leitfadengestützte Interviews mit Studierenden, Dozierenden und Verantwortlichen im Hochschulwesen sowie mit Experten für die Einführung lernerzentrierter Didaktik an Schulen geführt (vgl. Kapitel 4). Interviews und Beobachtungen der Arbeit von Experten und Trainern in Lehrerfortbildungen für die Einführung von PAP in Schulen haben mir Eindrücklich vor Augen geführt, dass in diesem pädagogischen Feld die Einheit des Lehrinhalts mit der Lehrmethode gerade hinsichtlich der Fortbildung von Lehrkräften eine besondere Rolle spielt (vgl. Kapitel4.2.). Gerade deshalb dürfte es von so großer Bedeutung sein, Dozierende an Hochschulen entsprechend fortzubilden. Die Befragung der Hochschuldozenten ließ deren Vorbehalte, Hoffnungen und Ängste gegenüber einer lernerzentrierten Didaktik deutlich zu Wort kommen (vgl. Kap. 4.2.). Insgesamt wurde der erhebliche Fortbildungsbedarf in dieser Domäne sichtbar. Die Ergebnisse dieser Studie werden im fünften Kapitel diskutiert und im sechsten Kapitel abschließend zusammengefasst. Hier werden unter anderem Vorschläge für die Organisation der Ausbildung von Hochschullehrern, die Anforderung eines Zertifikats in Hochschuldidaktik und den erweiterten Austausch von Erfahrungen zwischen den Hochschullehrern der Bildungswissenschaften unterbreitet

Motivators and Barriers for Using E-learning During the COVID-19 Pandemic among Students at the College of Medicine and Health Sciences, University of Rwanda

BackgroundTo continue delivering the courses despite school closure during the covid-19 pandemic, the University of Rwanda abruptly shifted its teaching from traditional physical to online teaching. This was the compulsory medium of teaching during the lockdown period. This sudden change did not allow for adequate preparation for students. ObjectivesTo assess the preparation of learners to use the e-learning platform, and to explore the factors that enabled or inhibited learners’ use of the e-learning platform. MethodThis was a cross-sectional quantitative research design study done between June and July 2020. An online questionnaire was sent to all students registered in the College of Medicine and Health Sciences for the academic year 2019-2020. ResultsA total of 446 students completed the questionnaire. Students reported not being adequately oriented and unprepared to effectively use e-learning. Students were motivated to use e-learning when the learning objectives were clear, interactive, with engaging materials. Inadequate e-learning infrastructure, limited access to internet connectivity and inadequate devices were identified as the strongest barriers of using e-learning. ConclusionThe covid-19 pandemic has brought a transformational opportunity to embrace a blended learning approach. To sustain such a transformation, proper and timely planning and strategies need to be invested. Rwanda J Med Health Sci 2022;5(1):99-11

Teaching and Learning during COVID-19 Crisis: Faculty Preparedness and Factors Influencing the Use of E-learning Platform at the College of Medicine and Health Sciences, University of Rwanda

BackgroundTowards the beginning of 2020, the COVID-19 pandemic spread worldwide and caused many schools to close. Many educational institutions transitioned from traditional face-to-face or blended to a total e-learning approach. The University of Rwanda rapidly shifted from a blended teaching and learning approach to a total e-learning approach. Thus,this study assessed the faculty preparedness and the factors influencing the use of e-learningplatforms at the College of Medicine and Health Sciences.MethodsThe study used a cross-sectional design. A web self-administered questionnaire was used to collect data from 450 CMHS faculty from June to July 2020, with a response rate of 34.4% (n=155). SPSS was used to describe nominal variables with frequencies and percentages. Similarly, continuous variables were analyzed by calculating median and interquartile ranges. The Chi-Square and Man-Whitney tests were also computed using SPSS.ResultsThe majority of participants (93.7%) started using the e-learning approach, and 92.4% attended e-learning training. The top motivator for e-learning use was a personal interest in technology use (93.3%) and the leading barrier to using e-learning was the concern about access to students (77.1%).ConclusionThis study found that faculty preparedness was significantly associated with e-learning use. The leading motivator and barriers were a personal interest in technology use and concern about access to students, respectively.Rwanda J Med Health Sci 2022;5(2):189-20

A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB12) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0–2, and adequate organ function. Pemetrexed from 300 to 1200 mg m−2 was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB12. Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m−2, and infection and skin rash at 1200 mg m−2. The MTD/RD were determined to be 1200/1000 mg m−2, respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1200/1000 mg m−2, respectively, that is, a higher RD than without FA/VB12 (500 mg m−2). Pemetrexed with FA/VB12 showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study

Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.co

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients

Pemetrexed pharmacokinetics and pharmacodynamics in a phase I/II study of doublet chemotherapy with vinorelbine: implications for further optimisation of pemetrexed schedules

The purpose of this study was to investigate the utility of plasma pharmacokinetic and pharmacodynamic measures including plasma deoxynucleosides, homocysteine and methylmalonic acid concentrations in understanding the time course and extent of the inhibition of thymidylate synthase (TS) by pemetrexed in the context of a phase I/II combination study with vinorelbine. Eighteen patients received supplementation with folic acid and Vitamin B12 1 week before beginning treatment with pemetrexed and vinorelbine administered in a dose-escalating manner on a 21-day cycle. Heparinised blood samples were collected from consenting patients in the first cycle for pharmacokinetic analyses and in the first two cycles for determination of plasma thymidine, deoxyuridine, homocysteine and methylmalonic acid concentrations. These values were correlated with response and toxicity. Plasma deoxyuridine was used as a measure of TS inhibition, and concentrations of deoxyuridine were significantly elevated relative to baseline on days 1 (P<0.01), 2 (P<0.001) and 3 (P<0.05) after treatment at all pemetrexed dose levels (400–700 mg m−2). The magnitude of deoxyuridine elevation correlated with pemetrexed area under the plasma concentration–time curve (AUC) (r2=0.23, P<0.05). However, deoxyuridine concentrations returned to baseline between 8 and 15 days after treatment with pemetrexed, suggesting that inhibition of TS was not durable. Pemetrexed AUC correlated with the percentage decline (relative to baseline) in both platelets (r2=0.58, P<0.001) and leucocytes (r2=0.26, P<0.05) at day 8. Baseline homocysteine was also significantly correlated with these measures of haematological toxicity (r2=0.37, P<0.01 and r2=0.39, P<0.01, respectively). In addition, there was a significant reduction of plasma homocysteine on days 8 (P<0.005) and 15 (P<0.05) in cycle 1 compared to baseline values. The results suggest that the TS inhibitory effects of pemetrexed are short-lived and make the case for a more frequent schedule of administration such as every 2 weeks. The lack of protracted TS inhibition may be due to concomitant vitamin administration, and this may be the mechanism by which vitamins prevent life-threatening toxicity from pemetrexed. Baseline homocysteine concentration remains a predictive marker for haematological toxicity even following folate supplementation