Nonlinear excitation of low-n harmonics in reduced magnetohydrodynamic simulations of edge-localized modes

Nonlinear simulations of the early ELM phase based on a typical type-I ELMy ASDEX Upgrade discharge have been carried out using the reduced MHD code JOREK. The analysis is focused on the evolution of the toroidal Fourier spectrum. It is found that during the nonlinear evolution, linearly subdominant low-n Fourier components, in particular the n = 1, grow to energies comparable with linearly dominant harmonics. A simple model is developed, based on the idea that energy is transferred among the toroidal harmonics via second order nonlinear interaction. The simple model reproduces and explains very well the early nonlinear evolution of the toroidal spectrum in the JOREK simulations. Furthermore, it is shown for the n = 1 harmonic, that its spatial structure changes significantly during the transition from linear to nonlinearly driven growth. The rigidly growing structure of the linearly barely unstable n = 1 reaches far into the plasma core. In contrast, the nonlinearly driven n = 1 has a rigidly growing structure localized at the plasma edge, where the dominant toroidal harmonics driving the n = 1 are maximal and in phase. The presented quadratic coupling model might explain the recent experimental observation of strong low-n components in magnetic measurements [Wenninger et al., Non-linear magnetic perturbations during edge localized modes in TCV dominated by low n mode components, submitted to Nuclear Fusion]

Clonal in vitro propagation of peat mosses (Sphagnum L.) as novel green resources for basic and applied research

As builders and major components of peatlands, Sphagnopsida (peat mosses) are very important organisms for ecosystems and world’s climate. Nowadays many Sphagnum species as well as their habitats are largely protected, while their scientific and economic relevance remains considerable. Advanced methods of in vitro cultivation provide the potential to work in a sustainable way with peat mosses and address aspects of basic research as well as biotechnological and economical topics like biomonitoring or the production of renewable substrates for horticulture (Sphagnum farming). Here, we describe the establishment of axenic in vitro cultures of the five peat moss species Sphagnum fimbriatum Wils. and Hook., Sphagnum magellanicum Brid., Sphagnum palustre L., Sphagnum rubellum Wils. and Sphagnum subnitens Russ. and Warnst. with specific focus on large-scale cultivation of S. palustre in bioreactors. Axenic, clonal cultures were established to produce high quantities of biomass under standardized laboratory conditions. For advanced production of S. palustre we tested different cultivation techniques, growth media and inocula, and analyzed the effects of tissue disruption. While cultivation on solid medium is suitable for long term storage, submerse cultivation in liquid medium yielded highest amounts of biomass. By addition of sucrose and ammonium nitrate we were able to increase the biomass by around 10- to 30-fold within 4 weeks. The morphology of in vitro-cultivated gametophores showed similar phenotypic characteristics compared to material from the field. Thus the tested culture techniques are suitable to produce S. palustre material for basic and applied researchThis work was funded by FP7-ENV.2011.3.1.9-1 (MOSSCLONE)S

Clonal in vitro propagation of peat mosses (Sphagnum L.) as novel green resources for basic and applied research

As builders and major components of peatlands, Sphagnopsida (peat mosses) are very important organisms for ecosystems and world’s climate. Nowadays many Sphagnum species as well as their habitats are largely protected, while their scientific and economic relevance remains considerable. Advanced methods of in vitro cultivation provide the potential to work in a sustainable way with peat mosses and address aspects of basic research as well as biotechnological and economical topics like biomonitoring or the production of renewable substrates for horticulture (Sphagnum farming). Here, we describe the establishment of axenic in vitro cultures of the five peat moss species Sphagnum fimbriatum Wils. and Hook., Sphagnum magellanicum Brid., Sphagnum palustre L., Sphagnum rubellum Wils. and Sphagnum subnitens Russ. and Warnst. with specific focus on large-scale cultivation of S. palustre in bioreactors. Axenic, clonal cultures were established to produce high quantities of biomass under standardized laboratory conditions. For advanced production of S. palustre we tested different cultivation techniques, growth media and inocula, and analyzed the effects of tissue disruption. While cultivation on solid medium is suitable for long term storage, submerse cultivation in liquid medium yielded highest amounts of biomass. By addition of sucrose and ammonium nitrate we were able to increase the biomass by around 10- to 30-fold within 4 weeks. The morphology of in vitro-cultivated gametophores showed similar phenotypic characteristics compared to material from the field. Thus the tested culture techniques are suitable to produce S. palustre material for basic and applied researchThis work was funded by FP7-ENV.2011.3.1.9-1 (MOSSCLONE)S

Recruitment and Baseline Characteristics of Participants in the AgeWell.de Study: A Pragmatic Cluster-Randomized Controlled Lifestyle Trial against Cognitive Decline

Targeting dementia prevention, first trials addressing multiple modifiable risk factors showed promising results in at-risk populations. In Germany, AgeWell.de is the first large-scale initiative investigating the effectiveness of a multi-component lifestyle intervention against cognitive decline. We aimed to investigate the recruitment process and baseline characteristics of the AgeWell.de participants to gain an understanding of the at-risk population and who engages in the intervention. General practitioners across five study sites recruited participants (aged 60-77 years, Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE dementia risk score ≥ 9). Structured face-to-face interviews were conducted with eligible participants, including neuropsychological assessments. We analyzed group differences between (1) eligible vs. non-eligible participants, (2) participants vs. non-participants, and (3) between intervention groups. Of 1176 eligible participants, 146 (12.5%) dropped out before baseline; the study population was thus 1030 individuals. Non-participants did not differ from participants in key sociodemographic factors and dementia risk. Study participants were M = 69.0 (SD = 4.9) years old, and 52.1% were women. The average Montreal Cognitive Assessment/MoCA score was 24.5 (SD = 3.1), indicating a rather mildly cognitively impaired study population; however, 39.4% scored ≥ 26, thus being cognitively unimpaired. The bandwidth of cognitive states bears the interesting potential for differential trial outcome analyses. However, trial conduction is impacted by the COVID-19 pandemic, requiring adjustments to the study protocol with yet unclear methodological consequences

Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from C-14-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from C-14-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from C-14-acid lactic, while STC1-A increased gluconeogenesis from C-14-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil; Foundation for Science and Technology of Portugal [PTDC/MAR/121279/2010]; bilateral programme CAPES (Brazil)/GRICES (Portugal) CAPES/GRICES [215/08]info:eu-repo/semantics/publishedVersio

DNA sequence and chromatin modifiers cooperate to confer epigenetic bistability at imprinting control regions

Genomic imprinting is regulated by parental-specific DNA methylation of imprinting control regions (ICRs). Despite an identical DNA sequence, ICRs can exist in two distinct epigenetic states that are memorized throughout unlimited cell divisions and reset during germline formation. Here, we systematically study the genetic and epigenetic determinants of this epigenetic bistability. By iterative integration of ICRs and related DNA sequences to an ectopic location in the mouse genome, we first identify the DNA sequence features required for maintenance of epigenetic states in embryonic stem cells. The autonomous regulatory properties of ICRs further enabled us to create DNA-methylation-sensitive reporters and to screen for key components involved in regulating their epigenetic memory. Besides DNMT1, UHRF1 and ZFP57, we identify factors that prevent switching from methylated to unmethylated states and show that two of these candidates, ATF7IP and ZMYM2, are important for the stability of DNA and H3K9 methylation at ICRs in embryonic stem cells

Patterns of Spatial Variation of Assemblages Associated with Intertidal Rocky Shores: A Global Perspective

Assemblages associated with intertidal rocky shores were examined for large scale distribution patterns with specific emphasis on identifying latitudinal trends of species richness and taxonomic distinctiveness. Seventy-two sites distributed around the globe were evaluated following the standardized sampling protocol of the Census of Marine Life NaGISA project (www.nagisa.coml.org). There were no clear patterns of standardized estimators of species richness along latitudinal gradients or among Large Marine Ecosystems (LMEs); however, a strong latitudinal gradient in taxonomic composition (i.e., proportion of different taxonomic groups in a given sample) was observed. Environmental variables related to natural influences were strongly related to the distribution patterns of the assemblages on the LME scale, particularly photoperiod, sea surface temperature (SST) and rainfall. In contrast, no environmental variables directly associated with human influences (with the exception of the inorganic pollution index) were related to assemblage patterns among LMEs. Correlations of the natural assemblages with either latitudinal gradients or environmental variables were equally strong suggesting that neither neutral models nor models based solely on environmental variables sufficiently explain spatial variation of these assemblages at a global scale. Despite the data shortcomings in this study (e.g., unbalanced sample distribution), we show the importance of generating biological global databases for the use in large-scale diversity comparisons of rocky intertidal assemblages to stimulate continued sampling and analyses

Rise and Fall of an Anti-MUC1 Specific Antibody

So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10) M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology