Armut in Österreich, Fallstudie Sozialmärkte als Institutionen der Armutslinderung

Im Zentrum dieser Arbeit steht die Analyse von Sozialmärkten als Institutionen zur Linderung von Armut, von denen es mittlerweile 68 in ganz Österreich gibt. Einerseits tragen sie zur Armutslinderung bei, andererseits sind sie aber auch funktionierende Werkzeuge der Armutsbekämpfung, da in vielen SOMAs ehemalige Arbeitslose Beschäftigung finden, und durch Qualifikationsmaßnahmen sowie sozialarbeiterische Unterstützung wieder auf die Integration in den ersten Arbeitsmarkt vorbereitet werden. Auch der ökologische Nutzen von Sozialmärkten darf nicht unterschätzt werden. Zu den wichtigsten Trägern der österreichischen Armutsbekämpfung zählen der öffentliche Sektor sowie die Organisationen des dritten Sektors. Von Institutionen, die sich der Armutsbekämpfung verschrieben haben, wird immer wieder die starke Ausrichtung des österreichischen Sozialsystems an der Erwerbsarbeit kritisiert. Demnach haben nur jene Personen, die einen bestimmten Zeitraum in die Sozialversicherung einbezahlt haben, Anspruch auf Leistungen aus dieser. Im Vergleich zu den Maßnahmen des öffentlichen Sektors zur Armutsbekämpfung bzw. -prävention gestaltet sich das Angebot der Nonprofit Organisationen heterogener und niederschwelliger. Es wird versucht, eine möglichst ganzheitliche Hilfestellung, abgestimmt auf die jeweilige Problemkonstellation, anzubieten. Methodisch beruht diese Diplomarbeit in erster Linie auf einer Analyse vorhandener Sekundärliteratur. Um ein umfassendes Bild über den Wirkungsbereich von Sozialmärkten zu erhalten, wurden Gespräche mit ExpertInnen geführt

The primary structure of a monoclonal λ-type immunoglobulin L-chain of subgroup II (Bence-Jones protein NEI): Evolutionary origin of antibody variability

ObjectiveThe objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5-year period. MethodsA case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013. ResultsOverall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n=110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p=0.001), and gestational age at or beyond 11weeks of gestation (p=0.024). ConclusionImproving detection of anencephaly in the first trimester requires ultrasound screening at or after 11weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies. (c) 2015 John Wiley & Sons, Ltd

Comprehensive annotation and evolutionary insights into the canine (Canis lupus familiaris) antigen receptor loci

Dogs are an excellent model for human disease. For example, the treatment of canine lymphoma has been predictive of the human response to that treatment. However, an incomplete picture of canine (Canis lupus familiaris) immunoglobulin (IG) and T cell receptor (TR) - or antigen receptor (AR) - gene loci has restricted their utility. This work advances the annotation of the canine AR loci and looks into breed-specific features of the loci. Bioinformatic analysis of unbiased RNA sequence data was used to complete the annotation of the canine AR genes. This annotation was used to query 107 whole genome sequences from 19 breeds and identified over 5,500 alleles across the 550 genes of the seven AR loci: the IG heavy, kappa, and lambda loci; and the TR alpha, beta, gamma, and delta loci. Of note was the discovery that half of the IGK variable (V) genes were located downstream of, and inverted with respect to, the rest of the locus. Analysis of the germline sequences of all the AR V genes identified greater conservation between dog and human than mouse with either. This work brings our understanding of the genetic diversity and expression of AR in dogs to the same completeness as that of mice and men, making it the third species to have all AR loci comprehensively and accurately annotated. The large number of germline sequences serves as a reference for future studies, and has allowed statistically powerful conclusions to be drawn on the pressures that have shaped these loci.This work was supported by funding from the BBSRC and the Wellcome Trust

Differential gene expression in cells with different p53 mutations identifies genome-wide p53 targets and shows distinct modulation of cellular pathways in response to DNA damage

© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/The fundamental transcription factor p53 regulates cellular processes and integrates signals of cellular stress, triggering a coordinated response to ensure survival of cells restored to healthy function and programmed death of those that couldn’t be repaired. Unsurprisingly, this is one of the most mutated genes in human cancers, with most changes occurring in the DNA-binding domain of the protein. In this work, we take a genome-wide approach and use available resources to identify high confidence p53-target genes, that we examine in three breast cancer cell lines with different p53 status, wild type (MCF-7) and different mutations in the DNA-binding domain (MDA-MB231, T47D). Comparison of p53-targets expression in response to DNA damage by RNAseq and cellular assays reveals that MDA-MB231 have a severely impaired p53-dependent pathway functionality while T47D are much less affected. MDA-MB231 are more resistant to DNA damage yet unable to repair and able to override cell cycle arrest leading to survival while T47D are sensitive only to high dose and exposure to genotoxic agents. This data shows the variability of effects of different p53 mutations and highlight the importance of understanding the mechanisms of p53 in the context of genotoxicity-based treatment

Relationship between the tissue-specificity of mouse gene expression and the evolutionary origin and function of the proteins

BACKGROUND: The combination of complete genome sequence information with expression data enables us to characterize the relationship between a protein's evolutionary origin or functional category and its expression pattern. In this study, mouse proteins were assigned into functional and phyletic groups and the gene expression patterns of the different protein groupings were examined by microarray analysis in various mouse tissues. RESULTS: Our results suggest that the proteins that are universally distributed in all tissues are predominantly enzymes and transporters. In contrast, the tissue-specific set is dominated by regulatory proteins (signal transduction and transcription factors). An increased tendency to tissue-specificity is observed for metazoan-specific proteins. As the composition of the phyletic groups highly correlates with that of the functional groups, the data were tested in order to determine which of the two factors - function or phyletic age - is dominant in shaping the expression profile of a protein. The observed differences in expression patterns of genes between functional groups were found mainly to reflect their different phyletic origin. The connection between tissue specificity and phyletic age cannot be explained by the recent rate of evolution. Finally, although metazoan-specific proteins tend to be tissue-specific compared with phyletically conserved proteins present in all domains of life, many such 'universal' proteins are also tissue-specific. CONCLUSION: The minimal cellular transcriptome of the metazoan cell differs from that of the ancestral unicellular eukaryote: new functions were added (metazoan-specific proteins), whilst other functions became specialized and no longer took place in all cells (tissue-specific pre-metazoan proteins)

The genetics and expression of canine antigen receptors analysed with a novel RNA-seq strategy.

INTRODUCTION Dogs are an excellent model for human disease, e.g. the treatment of canine lymphoma is often predictive of the human response to that treatment. However, an incomplete picture of their antigen-receptor (AR) gene loci and a limited set of available experimental tools has restricted their use. This work advances the annotation of the canine AR loci, develops methods to interrogate their expression patterns, and looks into breed-specific features of the loci. METHODS A bioinformatic approach alongside unbiased RNA-seq was used to complete the annotation of the canine AR genes, and these sequences were used to query 107 whole genome sequences from 19 breeds. A 5’RACE strategy was developed to selectively amplify ARs for next generation sequencing, and this was applied to RNA isolated from canine peripheral blood samples. RESULTS >5,500 novel alleles were identified across the ~550 gene segments (of which 326 were newly annotated) of the AR loci, yielding insight into AR evolution as well as confirming the greater conservation between dog and human than mouse with either. The 5’RACE strategy was validated with a pilot study that cast light onto the baseline expression and mutation patterns of healthy dogs, finding they closely mirrored their human counterparts. CONCLUSION This work brings our understanding of the genetics and expression of ARs in dogs to the same high standard as mice and men. The large number of genome sequences serves as a reference for future studies, and has allowed statistically powerful conclusions to be drawn on the pressures that have shaped these loci. Finally, it confirms the dog as a superior immunological model, particularly in the context of the high conservation seen in both sequence and expression features

Genome-Scale CRISPRa Screen Identifies Novel Factors for Cellular Reprogramming.

Primed epiblast stem cells (EpiSCs) can be reverted to a pluripotent embryonic stem cell (ESC)-like state by expression of single reprogramming factor. We used CRISPR activation to perform a genome-scale, reprogramming screen in EpiSCs and identified 142 candidate genes. Our screen validated a total of 50 genes, previously not known to contribute to reprogramming, of which we chose Sall1 for further investigation. We show that Sall1 augments reprogramming of mouse EpiSCs and embryonic fibroblasts and that these induced pluripotent stem cells are indeed fully pluripotent including formation of chimeric mice. We also demonstrate that Sall1 synergizes with Nanog in reprogramming and that overexpression in ESCs delays their conversion back to EpiSCs. Lastly, using RNA sequencing, we identify and validate Klf5 and Fam189a2 as new downstream targets of Sall1 and Nanog. In summary, our work demonstrates the power of using CRISPR technology in understanding molecular mechanisms that mediate complex cellular processes such as reprogramming

Novel stem cell technologies are powerful tools to understand the impact of human factors on Plasmodium falciparum malaria

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Plasmodium falciparum parasites have a complex life cycle, but the most clinically relevant stage of the disease is the invasion of erythrocytes and the proliferation of the parasite in the blood. The influence of human genetic traits on malaria has been known for a long time, however understanding the role of the proteins involved is hampered by the a nuclear nature of erythrocytes that makes them inaccessible to genetic tools. Here we overcome this limitation using stem cells to generate erythroid cells with an in-vitro differentiation protocol and assess parasite invasion with an adaptation of flow cytometry to detect parasite hemozoin. We combine this strategy with reprogramming of patient cells to Induced Pluripotent Stem Cells and genome editing to understand the role of key genes and human traits in malaria infection. We show that deletion of basigin ablates invasion while deletion of ATP2B4 has a minor effect and that erythroid cells from reprogrammed patient-derived HbBart α-thalassemia samples poorly support infection. The possibility to obtain patient-secific and genetically modifed erythoid cells offers an unparalleled opportunity to study the role of human genes and polymorphisms in malaria allowing preservation of the genomic background to demonstrate their function and understand their mechanisms.Peer reviewe

A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection.

A genome-scale CRISPR knockout library screen of THP-1 human macrophages was performed to identify loss-of-function mutations conferring resistance to Salmonella uptake. The screen identified 183 candidate genes, from which 14 representative genes involved in actin dynamics (ACTR3, ARPC4, CAPZB, TOR3A, CYFIP2, CTTN, and NHLRC2), glycosaminoglycan metabolism (B3GNT1), receptor signaling (PDGFB and CD27), lipid raft formation (CLTCL1), calcium transport (ATP2A2 and ITPR3), and cholesterol metabolism (HMGCR) were analyzed further. For some of these pathways, known chemical inhibitors could replicate the Salmonella resistance phenotype, indicating their potential as targets for host-directed therapy. The screen indicated a role for the relatively uncharacterized gene NHLRC2 in both Salmonella invasion and macrophage differentiation. Upon differentiation, NHLRC2 mutant macrophages were hyperinflammatory and did not exhibit characteristics typical of macrophages, including atypical morphology and inability to interact and phagocytose bacteria/particles. Immunoprecipitation confirmed an interaction of NHLRC2 with FRYL, EIF2AK2, and KLHL13.IMPORTANCESalmonella exploits macrophages to gain access to the lymphatic system and bloodstream to lead to local and potentially systemic infections. With an increasing number of antibiotic-resistant isolates identified in humans, Salmonella infections have become major threats to public health. Therefore, there is an urgent need to identify alternative approaches to anti-infective therapy, including host-directed therapies. In this study, we used a simple genome-wide screen to identify 183 candidate host factors in macrophages that can confer resistance to Salmonella infection. These factors may be potential therapeutic targets against Salmonella infections

ConPlex: a server for the evolutionary conservation analysis of protein complex structures

Evolutionary conservation analyses are important for the identification of protein–protein interactions. For protein complex structures, sequence conservation has been applied to determine protein oligomerization states, to characterize native interfaces from non-specific crystal contacts, and to discriminate near-native structures from docking artifacts. However, a user-friendly web-based service for evolutionary conservation analysis of protein complexes has not been available. Therefore, we developed ConPlex (http://sbi.postech.ac.kr/ConPlex/) a web application that enables evolutionary conservation analyses of protein interactions within protein quaternary structures. Users provide protein complex structures; ConPlex automatically identifies protein interfaces and carries out evolutionary conservation analyses for the interface regions. Moreover, ConPlex allows the results of the residue-specific conservation analysis to be displayed on the protein complex structure and provides several options to customize the display output to fit each user’s needs. We believe that ConPlex offers a convenient platform to analyze protein complex structures based on evolutionary conservation of protein–protein interface residues