421 research outputs found
Needs-based family support â Perception, structures and challenges in practical implementation
such as low-threshold access to services. Beside structural framework conditions in context of family
support, the question arises as to what extent the subjective perception of preventive family support
is one more aspect of utilisation and to what extent preventive family support actually matches the
needs of families. This Study asks as well what connotations and attitudes do families have regarding
family support services? How important do families consider these offers and what are their needs?
Based on a mixed-methods design, the Citizensâ Survey on Family Support was conducted by means
of a standardised questionnaire in combination with interviews of family support users and non-users in
order to elaborate deeper meaning structures through the qualitative analysis method of grounded theory.
Summary survey results point out that family support in Germany includes a wide range of offers, which
can promote a broad array of familial interests and competences, but not all families, diverse as they are,
feel consciously addressed â or else they see obstacles to using family services. Our qualitative results
point out that âfamily supportâ as a term is neither clearly identified nor properly understood by many
citizens â or else it has different connotations. However, those families who do use the services â within
the framework of transitioning to parenthood â feel supported in their psychosocial adaptations and
regulatory processes. In relation to results and as compared to other EU countries, practical implications
for further developments in family support approaches are discussed
Tracing back to Sources of MAIC Using Farm records and Lab Techniques
For the implementation of tracing back systems (particular agents, unwanted observation and other), detection techniques should be available. For MAIC, a step-by-step approach was established, combining visual observation, lab based PCR-identification, tracing back to the farm of origin and finally the search for potential ports of entry
Design considerations for a superconducting linac as an option for the ESS
An approach for a superconducting high-current proton linac for the ESS has been discussed as an option in the "Proposal for a Next Generation Neutron Source for Europe-the European Spallation Source (ESS)". The following work studies the technical and economic conditions for a superconducting linac at the high-energy end of the proposed accelerator system. The use of superconducting elliptical cavities for the acceleration of high-energetic particles beta =v/c-1 is certainly state of the art. This is documented by many activities (TJNAF, TESLA, LEP, LHC, and KEK). A design study for the cavities is described in another paper on this conference. For low energy particles ( beta <<1) quarter wave type cavities and spoke-type cavities have been discussed. The main motivation for this study is the expectation of significant cost reduction in terms of operational and possibly investment cost. (5 refs)
Comprehensive transcriptome analysis of the highly complex Pisum sativum genome using next generation sequencing
<p>Abstract</p> <p>Background</p> <p>The garden pea, <it>Pisum sativum</it>, is among the best-investigated legume plants and of significant agro-commercial relevance. <it>Pisum sativum </it>has a large and complex genome and accordingly few comprehensive genomic resources exist.</p> <p>Results</p> <p>We analyzed the pea transcriptome at the highest possible amount of accuracy by current technology. We used next generation sequencing with the Roche/454 platform and evaluated and compared a variety of approaches, including diverse tissue libraries, normalization, alternative sequencing technologies, saturation estimation and diverse assembly strategies. We generated libraries from flowers, leaves, cotyledons, epi- and hypocotyl, and etiolated and light treated etiolated seedlings, comprising a total of 450 megabases. Libraries were assembled into 324,428 unigenes in a first pass assembly.</p> <p>A second pass assembly reduced the amount to 81,449 unigenes but caused a significant number of chimeras. Analyses of the assemblies identified the assembly step as a major possibility for improvement. By recording frequencies of Arabidopsis orthologs hit by randomly drawn reads and fitting parameters of the saturation curve we concluded that sequencing was exhaustive. For leaf libraries we found normalization allows partial recovery of expression strength aside the desired effect of increased coverage. Based on theoretical and biological considerations we concluded that the sequence reads in the database tagged the vast majority of transcripts in the aerial tissues. A pathway representation analysis showed the merits of sampling multiple aerial tissues to increase the number of tagged genes. All results have been made available as a fully annotated database in fasta format.</p> <p>Conclusions</p> <p>We conclude that the approach taken resulted in a high quality - dataset which serves well as a first comprehensive reference set for the model legume pea. We suggest future deep sequencing transcriptome projects of species lacking a genomics backbone will need to concentrate mainly on resolving the issues of redundancy and paralogy during transcriptome assembly.</p
Glioblastoma and glioblastoma stem cells are dependent on functional MTH1
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target. We found MTH1 expression levels elevated and correlated with GBM aggressiveness and discovered that siRNA knock-down or inhibition of MTH1 with small molecules efficiently reduced viability of patient-derived GBM cultures. The effect of MTH1 loss on GBM viability was likely mediated through incorporation of oxidized nucleotides and subsequent DNA damage. We revealed that MTH1 inhibition targets GBM independent of aggressiveness as well as potently kills putative GBM stem cells in vitro. We used an orthotopic zebrafish model to confirm our results in vivo and light-sheet microscopy to follow the effect of MTH1 inhibition in GBM in real time.
In conclusion, MTH1 represents a promising target for GBM therapy and MTH1 inhibitors may also be effective in patients that suffer from recurring disease
The role of alanine and aspartate aminotransferases in C<sub>4</sub> photosynthesis
SchlĂŒter U, BrĂ€utigam A, Droz JâM, Schwender J, Weber APM. The role of alanine and aspartate aminotransferases in C<sub>4</sub> photosynthesis. Plant Biology. 2019;21(S1):64-76.âą Alanine and aspartate are essential transfer metabolites for C4 species of the NADmalic enzyme and phosphoenolpyruvate carboxykinase subtype. To some degree both amino acids are also part of the metabolite shuttle in NADP-malic enzyme plants. In comparison with C3 species, the majority of C4 species are therefore characterised by enhanced expression and activity of alanine and aspartate aminotransferases (AT) in the photosynthetically active tissue. Both enzymes exist in multiple copies and have been found in different subcellular compartments. We tested whether different C4 species show preferential recruitment of enzymes from speciïŹc lineages and subcellular compartments.
âą Phylogenetic analysis of alanine and aspartate ATs from a variety of monocot and eudicot C4 species and their C3 relatives was combined with subcellular prediction tools and analysis of the subsequent transcript amounts in mature leaves.
âą Recruitment of aspartate AT from a speciïŹc subcellular compartment was strongly connected to the biochemical subtype. Deviation from the main model was however observed in Gynandropsis gynandra. The conïŹguration of alanine AT generally differed in monocot and eudicot species. C4 monocots recruited an alanine AT from a speciïŹc cytosolic branch, but eudicots use alanine AT copies from a mitochondrial branch.
âą Generally, plants display high plasticity in the setup of the C4 pathway. Beside the common models for the different C4 subtypes, individual solutions were found for plant groups or lineages
MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool
MutT homologue 1 (MTH1) removes oxidized nucleotides from the nucleotide pool and thereby prevents their incorporation into the genome and thereby reduces genotoxicity. We previously reported that MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize the nucleotide pool from other methylated nucleotides. We here show that MTH1 efficiently catalyzes the hydrolysis of N6-methyl-dATP to N6-methyl-dAMP and further report that N6-methylation of dATP drastically increases the MTH1 activity. We also observed MTH1 activity with N6-methyl-ATP, albeit at a lower level. We show that N6-methyl-dATP is incorporated into DNA in vivo, as indicated by increased N6-methyl-dA DNA levels in embryos developed from MTH1 knock-out zebrafish eggs microinjected with N6-methyl-dATP compared with noninjected embryos. N6-methyl-dATP activity is present in MTH1 homologues from distantly related vertebrates, suggesting evolutionary conservation and indicating that this activity is important. Of note, N6-methyl-dATP activity is unique to MTH1 among related NUDIX hydrolases. Moreover, we present the structure of N6-methyl-dAMPâbound human MTH1, revealing that the N6-methyl group is accommodated within a hydrophobic active-site sub-pocket explaining why N6-methyl-dATP is a good MTH1 substrate. N6-methylation of DNA and RNA has been reported to have epigenetic roles and to affect mRNA metabolism. We propose that MTH1 acts in concert with adenosine deaminaseâlike protein isoform 1 (ADAL1) to prevent incorporation of N6-methyl-(d)ATP into DNA and RNA. This would hinder potential dysregulation of epigenetic control and RNA metabolism via conversion of N6-methyl-(d)ATP to N6-methyl-(d)AMP, followed by ADAL1 catalyzed deamination producing (d)IMP that can enter the nucleotide salvage pathway
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