Refine
Year of publication
Document Type
- Article (12)
- Monograph/Edited Volume (2)
- Part of a Book (1)
- Doctoral Thesis (1)
- Postprint (1)
- Report (1)
Is part of the Bibliography
- yes (18)
Keywords
- machine learning (2)
- Antisense agents (1)
- Argonaute 2 protein (1)
- Auftaktworkshop (1)
- Bedarfsanalyse (1)
- Cloud Computing (1)
- Drug design (1)
- Drug discovery (1)
- Forschungsprojekte (1)
- Future SOC Lab (1)
Institute
- Department Sport- und Gesundheitswissenschaften (7)
- Institut für Biochemie und Biologie (4)
- Hasso-Plattner-Institut für Digital Engineering GmbH (2)
- Department Psychologie (1)
- Extern (1)
- Hasso-Plattner-Institut für Digital Engineering gGmbH (1)
- Institut für Chemie (1)
- Mathematisch-Naturwissenschaftliche Fakultät (1)
- Universitätsbibliothek (1)
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
microRNAs (miRNAs) have been identified as high-value drug targets. A widely applied strategy in miRNA inhibition is the use of antisense agents. However, it has been shown that oligonucleotides are poorly cell permeable because of their complex chemical structure and due to their negatively charged backbone. Consequently, the general application of oligonucleotides in therapy is limited. Since miRNAs’ functions are executed exclusively by the Argonaute 2 protein, we therefore describe a protocol for the design of a novel miRNA inhibitor class: antagonists of the miRNA-Argonaute 2 protein complex, so-called anti-miR-AGOs, that not only block the crucial binding site of the target miRNA but also bind to the protein’s active site. Due to their lower molecular weight and, thus, more drug-like chemical structure, the novel inhibitor class may show better pharmacokinetic properties than reported oligonucleotide inhibitors, enabling them for potential therapeutic use.
miRNA Targeting Drugs
(2017)
Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. Addressing miRNAs as drug targets may enable the cure, or at least the treatment of diseases, which presently seems impossible. However, due to miRNAs’ chemical structure, generation of potential drug molecules with necessary pharmacokinetic properties is still challenging and requires a re-thinking of the drug discovery process. Therefore, this chapter highlights the potential of miRNAs as drug targets, discusses the challenges, and tries to give a complete overview of recent strategies in miRNA drug discovery.
Preface
(2017)
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Over the past ~40 years, several attempts were made to reintroduce Eurasian lynx to suitable habitat within their former distribution range in Western Europe. In general, limited numbers of individuals have been released to establish new populations. To evaluate the effects of reintroductions on the genetic status of lynx populations we used 12 microsatellite loci to study lynx populations in the Bohemian–Bavarian and Vosges–Palatinian forests. Compared with autochthonous lynx populations, these two reintroduced populations displayed reduced genetic diversity, particularly the Vosges–Palatinian population. Our genetic data provide further evidence to support the status of ‘endangered’ and ‘critically endangered’ for the Bohemian–Bavarian and Vosges–Palatinian populations, respectively. Regarding conservation management, we highlight the need to limit poaching, and advocate additional translocations to bolster genetic variability.
Das Forschungsprojekt „Workflow-Management-Systeme für Open-Access-Hochschulverlage (OA-WFMS)” ist eine Kooperation zwischen der HTWK Leipzig und der Universität Potsdam. Ziel ist es, die Bedarfe von Universitäts- und Hochschulverlagen und Anforderungen an ein Workflow-Management-Systeme (WFMS) zu analysieren, um daraus ein generisches Lastenheft zu erstellen. Das WFMS soll den Publikationsprozess in OA-Verlagen erleichtern, beschleunigen sowie die Verbreitung von Open Access und das nachhaltige, digitale wissenschaftliche Publizieren fördern.
Das Projekt baut auf den Ergebnissen der Projekte „Open-Access-Hochschulverlag (OA-HVerlag)“ und „Open-Access-Strukturierte-Kommunikation (OA-STRUKTKOMM)“ auf. Der diesem Bericht zugrunde liegende Auftaktworkshop fand 2024 in Leipzig mit Vertreter:innen von zehn Institutionen statt. Der Workshop diente dazu, Herausforderungen und Anforderungen an ein WFMS zu ermitteln sowie bestehende Lösungsansätze und Tools zu diskutieren.
Im Workshop wurden folgende Fragen behandelt:
a. Wie kann die Organisation und Überwachung von Publikationsprozessen in wissenschaftlichen Verlagen durch ein WFMS effizient gestaltet werden?
b. Welche Anforderungen muss ein WFMS erfüllen, um Publikationsprozesse optimal zu unterstützen?
c. Welche Schnittstellen müssen berücksichtigt werden, um die Interoperabilität der Systeme zu garantieren?
d. Welche bestehenden Lösungsansätze und Tools sind bereits im Einsatz und welche Vor- und Nachteile haben diese?
Der Workshop gliederte sich in zwei Teile : Teil 1 behandelte Herausforderungen und Anforderungen (Fragen a. bis c.), Teil 2 bestehende Lösungen und Tools (Frage d.). Die Ergebnisse des Workshops fließen in die Bedarfsanalyse des Forschungsprojekts ein.
Die im Bericht dokumentierten Ergebnisse zeigen die Vielzahl der Herausforderungen der bestehenden Ansätze bezüglich des OA-Publikationsmanagements . Die Herausforderungen zeigen sich insbesondere bei der Systemheterogenität, den individuellen Anpassungsbedarfen und der Notwendigkeit der systematischen Dokumentation. Die eingesetzten Unterstützungssysteme und Tools wie Dateiablagen, Projektmanagement- und Kommunikationstools können insgesamt den Anforderungen nicht genügen, für Teillösungen sind sie jedoch nutzbar. Deshalb muss die Integration bestehender Systeme in ein zu entwickelndes OA-WFMS in Betracht gezogen und die Interoperabilität der miteinander interagierenden Systeme gewährleistet werden. Die Beteiligten des Workshops waren sich einig, dass das OA-WFMS flexibel und modular aufgebaut werden soll. Einer konsortialen Softwareentwicklung und einem gemeinsamen Betrieb im Verbund wurde der Vorrang gegeben.
Der Workshop lieferte wertvolle Einblicke in die Arbeit der Hochschulverlage und bildet somit eine solide Grundlage für die in Folge zu erarbeitende weitere Bedarfsanalyse und die Erstellung des generischen Lastenheftes.
Moving in the Anthropocene
(2018)
Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.