Optimalisatie en teeltversnelling in de teelt van stamrozen : de mogelijkheden van stenten

Uit eerder onderzoek was gebleken dat het stekken van stamrozen een goed alternatief is voor de traditionele teelt van stamrozen, waarbij een teler in de zomer oculeert op een getrokken onderstam (stammentrekker) en een leverbare stamroos heeft in het najaar van het daaropvolgende jaar. Het stekken moet in de winter in een kas gebeuren. Onder plastic folie bewortelen de ‘Pfänder’-stekken in de winter en in het voorjaar kunnen de stekken naar buiten, om vervolgens in de zomer geoculeerd te worden. Ruim een jaar later is er dan een leverbare stamroos. In vergelijking met de traditionele stamrozenteelt is dan een tijdwinst gerealiseerd van een jaar. Ook heeft een gestekte onderstam een mooier wortelstelsel. PPO en Cultus Agro Advies hebben samen met enkele bedrijven onderzocht of een verdere teeltversnelling en teeltoptimalisatie mogelijk is. Hiertoe zijn de mogelijkheden van enten direct na beworteling in de kas en van gelijktijdig stekken en enten (= stenten) onderzocht

Bestrijding Black Mold in geoculeerde rozenteelt 2008-2009

Black Mold (Chalaropsis thielavioides) is een schimmel die in 2007 veel schade heeft veroorzaakt in de struikrozen. De schimmel infecteert de oculatiewond met als gevolg dat het oculatieoog niet aanslaat. Op sommige percelen ging tot wel 70% van de enten verloren. In een tweejarig PT project is onderzocht wateen goede beheersingsstrategie voor Black Mold is. Er is gekeken naar de volgende punten: Bestrijding van Black Mold met chemische middelen. In het kader van het ontwikkelen van een bestrijdingsstrategie van Black Mold zijn verschillende middelen getest. Het druppelen van middel T in de T-snede bleek goed te werken tegen Black Mold. Het was echter niet mogelijk Black Mold te bestrijden via de traditionele manier zoals het bespuiten van de stam of de plant in zijn geheel. Ook het bespuiten van de T-snede werkte niet. Het bleek dat Black Mold alleen bestreden kon worden wanneer het bestrijdingsmiddel in de T-snede werd gedruppeld. Resistente onderstammen. In de literatuur waren aanwijzingen gevonden dat er rozenonderstam varianten zouden bestaan die resistent zijn tegen Black Mold. Smid’s Ideal en Multiflora zijn beide in een kas- en veldproef getest en bleken vatbaar voor Black Mold te zijn. Epidemiologie van Black Mold. Verschillende facetten van de epidemiologie van Black Mold zijn onderzocht. het was niet mogelijk een relatie tussen de weersomstandigheden in 2007 en de grootschalige uitbraak van Black Mold vast te stellen. Onder laboratorium condities is uitgezocht dat Black Mold verschillende optimum temperaturen heeft. Zo is de optimum temperatuur voor myceliumgroei 24°C, voor kieming 15°C en voor sporulatie 30°C. Het is echter nog niet duidelijk wat de optimale infectie temperatuur van Black Mold is. Verder is er gekeken of Black Mold in de grond een infectiebron kan zijn. Stukjes peen zijn gebruikt in een lokaastoets omdat Black Mold ook peen infecteert. Met behulp van deze toets kon echter niet worden vastgesteld dat percelen met grootschalige Black Mold uitbraken ook meer stukjes peen aantastten. . Klaarblijkelijk is de hoeveelheid van Black Mold in de grond niet van belang. Verder is gekeken of besmette grond Black Mold infecties kon veroorzaken door de grond op te laten spatten of aan te aarden. Dit bleek niet het geval. Plant materiaal en het oculatiemes zijn waarschijnlijk geen grote infectiebronnen van Black Mold. Het is echter wel gebleken dat Black Mold via het mes verspreid kan worden. Daarom is het effect van mesontsmetting ook onderzocht. Het is aan te raden het mes regelmatig te ontsmetten met spiritus of alcohol

Long-term use of Everolimus in patients with Tuberous Sclerosis Complex: final results from the EXIST-1 study

BACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828). Methods and FINDINGS: EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m 2 /day) titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point) was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years) who received ≥1 dose of everolimus (median duration, 47.1 months), 57.7% (95% confidence interval [CI], 47.9-67.0) achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2%) achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs) was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence) suspected to be treatment-related were stomatitis (43.2%) and mouth ulceration (32.4%). CONCLUSIONS: Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients. Trial Registration ClinicalTrials.gov NCT0078982

Endoplasmic reticulum stress and cell death in mTORC1-overactive cells is induced by nelfinavir and enhanced by chloroquine

Inappropriate activation of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is common in cancer and has many cellular consequences including elevated endoplasmic reticulum (ER) stress. Cells employ autophagy as a critical compensatory survival mechanism during ER stress. This study utilised drug-induced ER stress through nelfinavir in order to examine ER stress tolerance in cell lines with hyper-active mTORC1 signalling. Our initial findings in wild type cells showed nelfinavir inhibited mTORC1 signalling and upregulated autophagy, as determined by decreased rpS6 and S6K1 phosphorylation, and SQTSM1 protein expression, respectively. Contrastingly, cells with hyper-active mTORC1 displayed basally elevated levels of ER stress which was greatly exaggerated following nelfinavir treatment, seen through increased CHOP mRNA and XBP1 splicing. To further enhance the effects of nelfinavir, we introduced chloroquine as an autophagy inhibitor. Combination of nelfinavir and chloroquine significantly increased ER stress and caused selective cell death in multiple cell line models with hyper-active mTORC1, whilst control cells with normalised mTORC1 signalling tolerated treatment. By comparing chloroquine to other autophagy inhibitors, we uncovered that selective toxicity invoked by chloroquine was independent of autophagy inhibition yet entrapment of chloroquine to acidified lysosomal/endosomal compartments was necessary for cytotoxicity. Our research demonstrates that combination of nelfinavir and chloroquine has therapeutic potential for treatment of mTORC1-driven tumours

Allelic mutations of the sodium channel SCN8A reveal multiple cellular and physiological functions

Allelic mutations of Scn8a in the mouse have revealed the range of neurological disorders that can result from alternations of one neuronal sodium channel. Null mutations produce the most severe phenotype, with motor neuron failure leading to paralysis and juvenile lethality. Two less severe mutations cause ataxia, tremor, muscle weakness, and dystonia. The electrophysiological effects have been studied at the cellular level by recording from neurons from the mutant mice. The data demonstrate that Scn8a is required for the complex spiking of cerebellar Purkinje cells and for persistent sodium current in several classes of neurons, including some with pacemaker roles. The mouse mutations of Scn8a have also provided insight into the mode of inheritance of channelopathies, and led to the identification of a modifier gene that affects transcript splicing. These mutations demonstrate the value of mouse models to elucidate the pathophysiology of human disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42795/1/10709_2004_Article_5381441.pd

Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J

Membrane-bound phosphoinositides are signalling molecules that have a key role in vesicle trafficking in eukaryotic cells(1). Proteins that bind specific phosphoinositides mediate interactions between membrane-bounded compartments whose identity is partially encoded by cytoplasmic phospholipid tags. Little is known about the localization and regulation of mammalian phosphatidylinositol-3,5-bisphosphate ( PtdIns( 3,5)P-2), a phospholipid present in small quantities that regulates membrane trafficking in the endosome - lysosome axis in yeast(2). Here we describe a multi-organ disorder with neuronal degeneration in the central nervous system, peripheral neuronopathy and diluted pigmentation in the 'pale tremor' mouse. Positional cloning identified insertion of ETn2 beta ( early transposon 2 beta)(3) into intron 18 of Fig4 (A530089I17Rik), the homologue of a yeast SAC ( suppressor of actin) domain PtdIns(3,5) P-2 5-phosphatase located in the vacuolar membrane. The abnormal concentration of PtdIns( 3,5) P2 in cultured fibroblasts from pale tremor mice demonstrates the conserved biochemical function of mammalian Fig4. The cytoplasm of fibroblasts from pale tremor mice is filled with large vacuoles that are immunoreactive for LAMP-2 (lysosomal-associated membrane protein 2), consistent with dysfunction of the late endosome - lysosome axis. Neonatal neurodegeneration in sensory and autonomic ganglia is followed by loss of neurons from layers four and five of the cortex, deep cerebellar nuclei and other localized brain regions. The sciatic nerve exhibits reduced numbers of large-diameter myelinated axons, slowed nerve conduction velocity and reduced amplitude of compound muscle action potentials. We identified pathogenic mutations of human FIG4 (KIAA0274) on chromosome 6q21 in four unrelated patients with hereditary motor and sensory neuropathy. This novel form of autosomal recessive Charcot - Marie - Tooth disorder is designated CMT4J.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62835/1/nature05876.pd

Staphylococcal Enterotoxins

Staphylococcus aureus (S. aureus) is a Gram positive bacterium that is carried by about one third of the general population and is responsible for common and serious diseases. These diseases include food poisoning and toxic shock syndrome, which are caused by exotoxins produced by S. aureus. Of the more than 20 Staphylococcal enterotoxins, SEA and SEB are the best characterized and are also regarded as superantigens because of their ability to bind to class II MHC molecules on antigen presenting cells and stimulate large populations of T cells that share variable regions on the β chain of the T cell receptor. The result of this massive T cell activation is a cytokine bolus leading to an acute toxic shock. These proteins are highly resistant to denaturation, which allows them to remain intact in contaminated food and trigger disease outbreaks. A recognized problem is the emergence of multi-drug resistant strains of S. aureus and these are a concern in the clinical setting as they are a common cause of antibiotic-associated diarrhea in hospitalized patients. In this review, we provide an overview of the current understanding of these proteins

Genomics in neurodevelopmental disorders: an avenue to personalized medicine

Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in genomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered, the etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype- based diagnosis of individual patients has become a requisite. In this review we look at recent advancements in genomic analysis and their translation into clinical practice

Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms

This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this recordTrue physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes that we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution, without inducing undue stress on either. We combined lattice light-sheet microscopy with adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.Howard Hughes Medical Institute (HHMI)BiogenIonis PharmaceuticalsNational Institutes of Health (NIH)University of ExeterCarol M. Baldwin FoundationDamon Runyon Cancer Research FoundationNational Science Foundation (NSF)Pew Charitable Trust