Rassenkeuze biologische frambozenteelt - de zoektocht naar kwalitatief plantgoed

Door gebrek aan biologisch rassenonderzoek grijpt de biologische kleinfruitteler momenteel naar gangbaar rassenonderzoek voor zijn plantgoedkeuze. Het telen van framboos onder biologische omstandigheden is echter moeilijk te vergelijken. De groei en ziektegevoeligheid zijn verschillend onder organische bemesting en biologische bestrijding. In dit onderzoek werden interessante beschikbare rassen met elkaar vergeleken en beoordeeld op kenmerken die door kleinfruittelers als belangrijk worden beschouwd. Als algemene kanttekening bij dit onderzoek blijkt dat werken met gangbare naakte wortel long canes in het algemeen niet zo een goede zaak is voor de biologische frambozen sector. Het is de enige vorm van plantgoed die momenteel in beperkte hoeveelheden op de markt te koop is en in een biologisch teeltsysteem kan gebruikt worden, na aanvraag van ontheffing. In 2015 werden er op Proefcentrum Pamel proeven met Tulameen uitgevoerd. In deze periode mochten er nog gangbare potten worden gebruikt. De opbrengst lag met 0.47kg per plant 88% hoger dan de nieuw aangeplante naakte wortel long canes in 2017 (0.25 kg per plant) en 123% hoger dan dezelfde naakte wortel long canes een jaar later in 2018 (0.21 kg/plant). Deze cijfers tonen aan dat gedurende de eerste twee jaar na aanplant van een gangbare naakte wortel long canes, de opbrengsten erg kunnen tegenvallen. Dit benadrukt nog eens de noodzaak aan kwaliteitsvol biologische long canes. De sector heeft dus nood aan kwalitatieve biologische long canes waar geen ontheffing voor moet worden aangevraagd. Dit plantgoed zou meer moeten opbrengen en minder ziekte gevoelig zijn dan de huidige naakte wortel long canes. Om deze hypothese uit te testen werd een nieuw CCBT-projectvoorstel ingediend rond de opkweek van biologische long canes frambozen. In dit nieuwe project willen we onderzoeken of het mogelijk is om hoogwaardige biologische long canes op te kweken

4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma brucei

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.</jats:p

Experimental Selection of Paromomycin Resistance in Leishmania donovani Amastigotes Induces Variable Genomic Polymorphisms

The relatively high post-treatment relapse rates of paromomycin (PMM) in visceral leishmaniasis treatment and the swift emergence of experimental drug resistance challenge its broad application and urge for rational use and monitoring of resistance. However, no causal molecular mechanisms to Leishmania PMM resistance have been identified so far. To gain insights into potential resistance mechanisms, twelve experimentally selected Leishmania donovani clonal lines and the non-cloned preselection population, with variable degrees of PMM resistance, were subjected to whole genome sequencing. To identify genomic variations potentially associated with resistance, SNPs, Indels, chromosomal somy and gene copy number variations were compared between the different parasite lines. A total of 11 short nucleotide variations and the copy number alterations in 39 genes were correlated to PMM resistance. Some of the identified genes are involved in transcription, translation and protein turn-over (transcription elongation factor-like protein, RNA-binding protein, ribosomal protein L1a, 60S ribosomal protein L6, eukaryotic translation initiation factor 4E-1, proteasome regulatory non-ATP-ase subunit 3), virulence (major surface protease gp63, protein-tyrosine phosphatase 1-like protein), mitochondrial function (ADP/ATP mitochondrial carrier-like protein), signaling (phosphatidylinositol 3-related kinase, protein kinase putative and protein-tyrosine phosphatase 1-like protein) and vesicular trafficking (ras-related protein RAB1). These results indicate that, in Leishmania, the aminoglycoside PMM affects protein translational processes and underlines the complex and probably multifactorial origin of resistance

Epidemiology of Taenia saginata taeniosis/cysticercosis: a systematic review of the distribution in West and Central Africa

Background: The zoonotic tapeworm Taenia saginata, although causing only minor discomfort in humans, is responsible for considerable economic losses in the livestock sector due to condemnation or downgrading of infected beef carcasses. An overview of current knowledge on the distribution and prevalence of this parasite in West and Central Africa is lacking. Methods: We conducted a systematic review, collecting information on published and grey literature about T. saginata taeniosis and bovine cysticercosis from 27 countries/territories in West and Central Africa, published between January 1st, 1990 and December 31st, 2017. Results: The literature search retrieved 1672 records, of which 51 and 45 were retained for a qualitative and quantitative synthesis, respectively. Non-specified human taeniosis cases were described for Nigeria, Cameroon, Senegal, Burkina Faso, Democratic Republic Congo, Guinea, and Ivory Coast (seven out of 27 countries/territories), while T. saginata taeniosis specifically was only reported for Cameroon. Most prevalence estimates for taeniosis ranged between 0-11%, while three studies from Nigeria reported prevalence estimates ranging between 23-50%. None of the studies included molecular confirmation of the causative species. The presence of bovine cysticercosis was reported for Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Democratic Republic Congo, Ghana, Guinea, Ivory Coast, Mali, Niger, Nigeria, Senegal, and Tristan da Cunha (14 out of 27 countries/territories). Prevalence estimates ranged between 0-29%. Conclusions: Our systematic review has revealed that human taeniosis and bovine cysticercosis are seriously understudied in West and Central Africa. The high prevalence estimates of both conditions suggest an active dissemination of this parasite in the region, calling for a concerted One Health action from public health, veterinary health and food surveillance sectors

Identification of resistance determinants for a promising antileishmanial oxaborole series

Current treatment options for visceral leishmaniasis have several drawbacks, and clinicians are confronted with an increasing number of treatment failures. To overcome this, the Drugs for Neglected Diseases initiative (DNDi) has invested in the development of novel antileishmanial leads, including a very promising class of oxaboroles. The mode of action/resistance of this series to Leishmania is still unknown and may be important for its further development and implementation. Repeated in vivo drug exposure and an in vitro selection procedure on both extracellular promastigote and intracellular amastigote stages were both unable to select for resistance. The use of specific inhibitors for ABC-transporters could not demonstrate the putative involvement of efflux pumps. Selection experiments and inhibitor studies, therefore, suggest that resistance to oxaboroles may not emerge readily in the field. The selection of a genome-wide cosmid library coupled to next-generation sequencing (Cos-seq) was used to identify resistance determinants and putative targets. This resulted in the identification of a highly enriched cosmid, harboring genes of chromosome 2 that confer a subtly increased resistance to the oxaboroles tested. Moderately enriched cosmids encompassing a region of chromosome 34 contained the cleavage and polyadenylation specificity factor (cpsf) gene, encoding the molecular target of several related benzoxaboroles in other organisms

Effects of dietary supplementation with the green tea polyphenol epigallocatechin3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely healthpromoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre-and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo 20·058 (SE 0·75) mmHg; EGCG 2 2·68 (SE 0·72) mmHg; P¼0·014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29·11 (SE 0·44); placebo, 27·84 (SE 0·46); P¼0·048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis

Nucleoside analogues for the treatment of animal trypanosomiasis

Animal trypanosomiasis (AT) is a parasitic disease with high socio-economic impact. Given the limited therapeutic options and problems of toxicity and drug resistance, this study assessed redirecting our previously identified antitrypanosomal nucleosides for the treatment of AT. Promising hits were identified with excellent in vitro activity across all important animal trypanosome species. Compound 7, an inosine analogue, and our previously described lead compound, 3′-deoxytubercidin (8), showed broad spectrum anti-AT activity, metabolic stability in the target host species and absence of toxicity, but with variable efficacy ranging from limited activity to full cure in mouse models of Trypanosoma congolense and T. vivax infection. Several compounds show promise against T. evansi (surra) and T. equiperdum (dourine). Given the preferred target product profile for a broad-spectrum compound against AT, this study emphasizes the need to include T. vivax in the screening cascade given its divergent susceptibility profile and provides a basis for lead optimization toward such broad spectrum anti-AT compound

Experimental Induction of Paromomycin Resistance in Antimony-Resistant Strains of L. donovani: Outcome Dependent on In Vitro Selection Protocol

Paromomycin (PMM) has recently been introduced for treatment of visceral leishmaniasis in India. Although no clinical resistance has yet been reported, proactive vigilance should be warranted. The present in vitro study compared the outcome and stability of experimental PMM-resistance induction on promastigotes and intracellular amastigotes. Cloned antimony-resistant L. donovani field isolates from India and Nepal were exposed to stepwise increasing concentrations of PMM (up to 500 µM), either as promastigotes or intracellular amastigotes. One resulting resistant strain was cloned and checked for stability of resistance by drug-free in vitro passage as promastigotes for 20 weeks or a single in vivo passage in the golden hamster. Resistance selection in promastigotes took about 25 weeks to reach the maximal 97 µM inclusion level that did not affect normal growth. Comparison of the IC50 values between the parent and the selected strains revealed a 9 to 11-fold resistance for the Indian and 3 to 5-fold for the Nepalese strains whereby the resistant phenotype was also maintained at the level of the amastigote. Applying PMM pressure to intracellular amastigotes produced resistance after just two selection cycles (IC50 = 199 µM) compared to the parent strain (IC50 = 45 µM). In the amastigote-induced strains/clones, lower PMM susceptibilities were seen only in amastigotes and not at all in promastigotes. This resistance phenotype remained stable after serial in vitro passage as promastigote for 20 weeks and after a single in vivo passage in the hamster. This study clearly demonstrates that a different PMM-resistance phenotype is obtained whether drug selection is applied to promastigotes or intracellular amastigotes. These findings may have important relevance to resistance mechanism investigations and the likelihood of resistance development and detection in the field