Identifying permethrin resistance loci in malaria vectors by genetic mapping

Identification of the major loci responsible for insecticide resistance in malaria vectors would aid the development andimplementation of effective resistance management strategies, which are urgently needed to tackle the growing threat posedby resistance to the limited insecticides available for malaria control. Genome-wide association studies in the major malariavector, Anopheles gambiae, have been hindered by the high degree of within-population structuring and very low levels oflinkage disequilibrium hence we revisited the use of quantitative trait loci (QTL) mapping to study resistance phenotypesin this vector species. Earlier work, identified two major QTL associated with pyrethroid resistance in A. gambiae s.s. fromEast Africa using genetic crossing of laboratory-colonized resistant and susceptible strains. In this study, we report theresults from genetic mapping of pyrethroid resistance in three isofemale pedigrees established from wild-caught femaleA. gambiae s.s. mosquitoes from Benin. We identified two QTL on chromosomes 2L and 3R in these field populations, insimilar genomic locations to theQTLidentified in laboratory strains. The relative merits of two alternative study designs arediscussed and suggestions made for future genetic mapping studies of insecticide resistance in mosquitoes

Malaria reemergence in the Peruvian Amazon region.

Epidemic malaria has rapidly emerged in Loreto Department, in the Peruvian Amazon region. Peru reports the second highest number of malaria cases in South America (after Brazil), most from Loreto. From 1992 to 1997, malaria increased 50-fold in Loreto but only fourfold in Peru. Plasmodium falciparum infection, which has increased at a faster rate than P. vivax infection in the last 3 years, became the dominant Plasmodium infection in the highest transmission areas in the 1997 rainy season. The vector Anopheles darlingi has also increased during this epidemic in Loreto. Moreover, chloroquine and pyrimethamine-sulfadoxine drug-resistant P. falciparum strains have emerged, which require development of efficacious focal drug treatment schemes

Nitrate reducing commensal bacterium stimulates germination through nitric oxide production-a hypothesis [abstract]

Abstract only availableThe pink-pigmented (PPFM) commensal bacterium bacterium, Methylobacterium extorquens AM1, stimulates germination of soybean and other plants. I am testing the hypothesis that germination is stimulated by bacterial-produced nitric oxide (NO). A potential source of NO is nitrate reductase (NR) action on nitrite. Our goal was to identify NR gene(s), disrupt it(them) and examine germination stimulation of the mutants. Two nitrate reductase (NR) sequences were identified in the M. extorquens genome. Primers were designed and used to amplify both full-length and internal fragments of each NR gene. The internal fragments were cloned into a suicide vector (pAYC61) which encodes PPFM-expressed resistance gene to tetracycline (tetR). Tri-parental mating was then used to introduce pAYC61, carrying the internal NR sequences, into the PPFM strain, and tet-resistant PPFM colonies were selected. Methanol was used as the sole carbon source, thus selecting against the E. coli partners in the mating. A screen was devised to test among the tet-resistant progeny "exconjugates" for those with homologous integration of the internal NR sequence integrated into the respective host PPFM NR gene. Such integration will create two non-functional incomplete copies of the host NR gene. The screen will be based on PCR whereby primers will match vector sequence with NR sequence that is NOT part of the internal fragment. Once each NR gene is confirmed to be interrupted, the mutants will be tested for their ability to reduce nitrate to an utilizable nitrogen source. Germination stimulation and seedling root development will be examined by imbibing seed with progenitor and NR- PPFMs. The experiment will confirm or refute our observations of increased germination and lateral root formation in plants with PPFMs. Further, it will indicate whether such effects are due to nitric oxide produced by bacterial NR action on nitrate. Controls will be bacterium grown with without nitrate and seedlings grown with external NO sources and with an NO trap.MU Monsanto Undergraduate Research Fellowshi

What do pink pigs and soybeans have in common? Selecting for mutants in the ureide pathway

Abstract only availablePink Pigmented Facultative Methylotrophic bacteria (PPFMs) have been found to be the most abundant microorganisms among phylloplane microflora, and have been recovered from all plants examined. PPFMs are seed-transmitted and have been shown to enhance germination. PPFMs may contribute nitrogen, which is an essential nutrient, to the plant. In an attempt to determine this and gain a better understanding of the genes involved in ureide (allantoin, allantoate, etc,) utilization in PPFMs, we tried to ellicit mutants along the pathway. We performed a bi-parental mating between the PPFM soybean isolate (wild-type) and an E. coli strain containing a plasmid for a kanamycin resistance. This antibiotic resistance plasmid was randomly inserted into the PPFM's genome. The goal is to select mutants that lose the ability to break down ureides. Selection on different media is used to isolate the different mutants along the pathway. Seed surface sterilization does not remove PPFMs since they are found below the seed coat. We have devised a method to eliminate the bacteria by heating the seeds at 50°C for 48 hours. This treatment does not damage the seed. Heat-treated and un-heated soybean seeds were inoculated with a kanamycin resistant soybean isolate strain of PPFM (B140). These plants were grown to maturity in the greenhouse and seeds were collected. We germinated this second generation of seed and are looking to recover kanamycin resistant PPFM bacteria both from the seed as well as the first unifoliate leaves of the soybean. We were able to isolate several putative PPFM ureide utilization mutants. This research will give insight into the interactions between PPFMs and soybean that may be applied to many other plants. Experiments to recover kanamycin resistant bacteria from the seed and from the first unifoliate leaves of the plants are in progress.MU Monsanto Undergraduate Research Fellowshi

Atroposelective synthesis of tetra-ortho-substituted biaryls by catalyst-controlled non-canonical polyketide cyclizations

The cyclization of poly-β-carbonyl-substrates controlled by polyketide synthases intricately governs the biosynthesis of a wide range of aromatic polyketides. Analogous small-molecule-catalysed processes would conceivably induce selective cyclizations of non-canonical polycarbonyl substrates to provide products distinct from natural polyketides. Here, we report a secondary amine-catalysed twofold cyclization of non-canonical hexacarbonyl substrates, furnishing enantioenriched tetra-ortho-substituted binaphthalenes. The substrates were prepared by a fourfold ozonolysis of dicinnamyl biindenes and converted under catalyst control with high atroposelectivity. Privileged catalysts, helicenes and ligands are readily accessible from the binaphthalene products stemming from the non-canonical polyketide cyclizations

New fathers, old mothers? Parenthood between equality and difference

Im vorliegenden Artikel werden die aktuellen Diskussionen um die Revision des Sorgerechts und des Kindesunterhalts in der Schweiz diskurspsychologisch untersucht. Konkret lassen sich in den untersuchten Dokumenten vier interpretative Repertoires identifizieren: Egalität, Kindeswohl, Ungleichheit von Mutter und Vater und individuelle familiäre Lösungen. Zwischen diesen Repertoires lassen sich deutlich ideologische Dilemmata erkennen: Egalität der Eltern und Ungleichheit zwischen Vater und Mutter widersprechen sich, und die Nichteinmischung des Staates in die familiale Privatsphäre wird durch die hohe Gewichtung des Kindeswohls tangiert. Die Diskursanalyse zeigt, dass sich die ausführlich diskutierte Vorstellung von der Egalität der Eltern nicht durchsetzen kann gegen den verborgenen, nie thematisierten Subtext des Unterschieds zwischen Mutter und Vater. Gelöst wird das Dilemma, indem die diskutierten Ideale und Leitbilder als individuell zu realisierende erklärt werden. Mutter und Kind werden hier in essentialistischer Weise miteinander verknüpft und Veränderungen höchstens in marginaler Weise am Vaterbild zugelassen.This article presents a discourse analysis of recent legislative changes in the fields of child custody and child support in Switzerland. We identified four interpretative repertoires in these documents: Equality of women and men, child’s welfare, inequality of mothers and fathers and individual familial solutions. Between these repertoires, we identified several ideological dilemmas: Equality of women and men directly contradicts the inequality of mothers and fathers, while the principle of governmental non-intervention into the private sphere of the family is being questioned by the high importance attributed to the child’s welfare. This discourse analysis shows that the widely discussed ideal of the equality of women and men does not hold up against the hidden subtext of the inequality of mothers and fathers. The dilemma is solved by declaring the implementation of the ideal of equality as an individual problem. In this reading, mother and child are still connected in an essentialist way, while the image of the father undergoes marginal changes only

Exzellenz, Diversität oder Effizienz? „Implicit bias“ in Berufungsverfahren als Zielkonflikte sozialer Praktiken

Gendergerechtes Diversitätsmanagement soll den Einfluss von implicit bias auf die Entscheidungsfindung in Berufungsverfahren reduzieren. Konventionelle Schulungsformate vermitteln jedoch wenig anwendbares Praxiswissen für typische kommunikative Situationen in den Sitzungen einer Berufungskommission. Wird implicit bias als soziale Praktik konzeptualisiert, lassen sich typische Zielkonflikte zwischen Diversität, Exzellenz und Effizienz in solchen Verfahren jedoch operationalisieren und mit überprüfbaren Lernzielen versehen. Dazu wurden fachübergreifend aggregierte Daten aus Berufungsprozessen an einer Schweizer Hochschule narrativ strukturiert und in die Form idealtypischer Vignetten gebracht. Ein webbasierter Videokurs (serious game) simuliert die szenische Umsetzung der sozialen Praktiken von implicit bias sowohl für die Vermittlung von Reflexionswissen als auch das Trainieren von Handlungswissen

Catalytic Arene-forming Aldol Condensation: Stereoselective Synthesis of Rotationally Restricted Aromatic Compounds

By taking inspiration from the fascinating biosynthetic machinery that creates aromatic polyketides, our group investigates analogous reactions catalyzed by small molecules. We are particularly captivated by the prospects of intramolecular aldol condensation reactions to generate different rotationally restricted aromatic compounds. In a first project of our independent research group, a highly stereoselective amine catalyzed synthesis of axially chiral biaryls, tertiary aromatic amides and oligo-1,2-naphthylenes has been developed. In this article, we outline the twists and turns for our escape from the aromatic flatland to structurally intriguing chiral arene scaffolds relevant for various fields of application

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma

Abstract Background Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL). Methods Patients received oral lenalidomide 25 mg on days 1–21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR). Results Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months [95% confidence interval (CI) 2.7–5.1]. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0–NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively. Conclusion Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma