Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research

Strain driven fast osseointegration of implants

BACKGROUND: Although the bone's capability of dental implant osseointegration has clinically been utilised as early as in the Gallo-Roman population, the specific mechanisms for the emergence and maintenance of peri-implant bone under functional load have not been identified. Here we show that under immediate loading of specially designed dental implants with masticatory loads, osseointegration is rapidly achieved. METHODS: We examined the bone reaction around non- and immediately loaded dental implants inserted in the mandible of mature minipigs during the presently assumed time for osseointegration. We used threaded conical titanium implants containing a titanium2+ oxide surface, allowing direct bone contact after insertion. The external geometry was designed according to finite element analysis: the calculation showed that physiological amplitudes of strain (500–3,000 ustrain) generated through mastication were homogenously distributed in peri-implant bone. The strain-energy density (SED) rate under assessment of a 1 Hz loading cycle was 150 Jm-3 s-1, peak dislocations were lower then nm. RESULTS: Bone was in direct contact to the implant surface (bone/implant contact rate 90%) from day one of implant insertion, as quantified by undecalcified histological sections. This effect was substantiated by ultrastructural analysis of intimate osteoblast attachment and mature collagen mineralisation at the titanium surface. We detected no loss in the intimate bone/implant bond during the experimental period of either control or experimental animals, indicating that immediate load had no adverse effect on bone structure in peri-implant bone. CONCLUSION: In terms of clinical relevance, the load related bone reaction at the implant interface may in combination with substrate effects be responsible for an immediate osseointegration state

C. elegans VANG-1 Modulates Life Span via Insulin/IGF-1-Like Signaling

The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans

Interventions to control myopia progression in children: protocol for an overview of systematic reviews and meta-analyses.

Background Myopia is a common visual disorder with increasing prevalence among developed countries of the world. Myopia constitutes a substantial risk factor for several ocular conditions that can lead to blindness. The purpose of this study is to conduct an overview of systematic reviews and meta-analyses in order to identify and appraise robust research evidence regarding the management of myopia progression in children and adolescents. Methods A literature search will be conducted in MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessment (HTA) Database via Centre for Reviews and Dissemination (CRD). We will search for systematic reviews or meta-analyses that examine optical or pharmaceutical modalities for myopia control. Two independent overview authors will screen the titles and abstracts against the eligibility criteria. Individual study’s methodological quality and quality of evidence for each outcome of interest will be assessed by two independent authors using the ROBIS tool and GRADE rating, respectively. In cases of disagreement, consensus will be reached with the help of a third author. Our primary outcomes will be the mean change in refractive error, mean axial length change, and adverse events. A citation matrix will be generated, and the corrected covered area (CCA) will be estimated, in order to identify overlapping primary studies. Possible meta-biases and measures of heterogeneity will be described, and cases of dual co-authorship will be identified and discussed. If any recently published randomized controlled trials (RCTs) are detected, these will be appraised and their findings will be presented. An overall summary of outcomes will be provided using descriptive statistics and will be supplemented by narrative synthesis. Discussion This overview will examine the high level of existing evidence for treatment of myopia progression. Efficient interventions will be identified, and side effects will be reported. The expected benefit is that all robust recent research evidence will be compiled in a single study. The results may inform future research in this area, which should provide insight into the appropriate regimes for the administration of these modalities and contribute to future guideline development

WMS-Tutorial Tl. 2: Optimierung in der Lagerverwaltung

Lagerverwaltungssysteme müssen heutzutage eine Vielzahl an Optimierungsaufgaben übernehmen. Dieser Beitrag kategorisiert die unteschiedlichen Optimierungsaufgaben in einem Ebenenmodell und gibt eine Übersicht über einige gängige (z.B. Branch & Bound) und innovative Lösungsmöglichkeiten ("Ameisen"-Algorithmen ) dieser Optimierungsprobleme. Zudem wird das Plug-In Konzept von myWMS vorgestellt, über das sich unterschiedliche Optimierungsalgorithmen in ein Lagerverwaltungssystem, das auf myWMS basiert, integrieren lassen