Meeting report: "Nachhaltig Wirken - Reallabore in der Transformation"; Conference, 2022, Karlsruhe

Der Reallaboransatz hat seit seinem Aufkommen 2012 einen richtiggehenden Boom erfahren. Reallabore sind in ihrem originären Ansatz als Experimentierräume, Forschungsmodus und methodologisches Werkzeug konzipiert, um zu nachhaltiger Entwicklung und gesellschaftlicher Transformation beizutragen und diese zu beschleunigen. Wesentlicher Ansatzpunkt ist dabei, Wissenschaft und Praxis in transdisziplinären Settings und transformativen Prozessen eng miteinander zu verknüpfen. Die Wissenschaft bzw. die Forschenden, begeben sich dabei selbst in Wandlungsprozesse: Sie initiieren, experimentieren und beforschen zugleich. Praxisakteure setzen dabei Themen und forschen aktiv mit, so dass im Idealfall sowohl wissenschaftliche Theorie als auch gesellschaftliche Praxis von den Ergebnissen profitieren. Die Ausgestaltung von Reallaborprojekten hat in den letzten zehn Jahren eine Vielzahl von Differenzierungen in Inhalten, Settings, Methodik und Ausrichtung erfahren. Die Konferenz "Nachhaltig wirken: Reallabore in der Transformation", die am 2. und 3. Juni 2022 in Karlsruhe stattfand, griff diese Entwicklungen auf, um gemeinsam mit der wachsenden Reallabor-Community den aktuellen Entwicklungsstand des Reallaboransatzes abzubilden. Organisiert vom Karlsruher Transformationszentrum für Nachhaltigkeit und Kulturwandel (KAT) in Zusammenarbeit mit den Gründungsinstitutionen des Netzwerkes Reallabore der Nachhaltigkeit, wurden auf der Tagung aktuelle methodische, konzeptionelle, praktische wie auch strategische Fragen aufgeworfen und diskutiert. Mit über 300 Teilnehmenden und 115 Beiträgen stellt sie die bislang größte und umfassendste Veranstaltung im Bereich der deutschsprachigen Reallaborforschung dar

A Profile of Working Memory Ability in Poor Readers

Objective: This study aimed to provide a comprehensive working memory profile of a group of children with established poor reading ability. Methods: Participants included a group of established “poor readers” and a group of age- and gender-matched controls with typically developing reading ability. The participants completed a comprehensive battery of assessments examining four components of working memory—the central executive, phonological loop, visuospatial sketchpad, and episodic buffer. Results: As predicted, the poor reading group scored significantly lower than the typically developing reading group on measures of the phonological loop and central executive. There were no significant differences between the two groups on measures of the visuospatial sketchpad or episodic buffer. Contrary to predictions, a subgroup of poor readers with poor visuospatial working memory was not found, further highlighting the inconsistent findings in this area of working memory. Conclusions: The results provide support for past research findings of deficits in the phonological loop and central executive of poor readers. The finding of typical episodic buffer functioning demonstrates the potential to draw on this relative strength in implementing interventions with poor readers. This implicates the importance of increasing awareness of specific working memory deficits in poor readers, and may guide future research into more effective teaching strategies and interventions for this population

OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

Mitochondria are essential organelles with multiple functions, especially in energy metabolism. Recently, an increasing number of data has highlighted the role of mitochondria for cellular differentiation processes. Metabolic differences between stem cells and mature derivatives require an adaptation of mitochondrial function during differentiation. In this study we investigated alterations of the mitochondrial phenotype of human mesenchymal stem cells undergoing adipogenic differentiation. Maturation of adipocytes is accompanied by mitochondrial biogenesis and an increase of oxidative metabolism. Adaptation of the mt phenotype during differentiation is reflected by changes in the distribution of the mitochondrial network as well as marked alterations of gene expression and organization of the oxidative phosphorylation system (OXPHOS). Distinct differences in the supramolecular organization forms of cytochrome c oxidase (COX) were detected using 2D blue native (BN)-PAGE analysis. Most remarkably we observed a significant increase in the abundance of OXPHOS supercomplexes in mitochondria, emphasizing the change of the mitochondrial phenotype during adipogenic differentiation

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

Late‐stage colorectal cancer (CRC) is still a clinically challenging problem. The activity of the tumor suppressor p53 is regulated via post‐translational modifications (PTMs). While the relevance of p53 C‐terminal acetylation for transcriptional regulation is well defined, it is unknown whether this PTM controls mitochondrially mediated apoptosis directly. We used wild‐type p53 or p53‐negative human CRC cells, cells with acetylation‐defective p53, transformation assays, CRC organoids, and xenograft mouse models to assess how p53 acetylation determines cellular stress responses. The topoisomerase‐1 inhibitor irinotecan induces acetylation of several lysine residues within p53. Inhibition of histone deacetylases (HDACs) with the class I HDAC inhibitor entinostat synergistically triggers mitochondrial damage and apoptosis in irinotecan‐treated p53‐positive CRC cells. This specifically relies on the C‐terminal acetylation of p53 by CREB‐binding protein/p300 and the presence of C‐terminally acetylated p53 in complex with the proapoptotic BCL2 antagonist/killer protein. This control of C‐terminal acetylation by HDACs can mechanistically explain why combinations of irinotecan and entinostat represent clinically tractable agents for the therapy of p53‐proficient CRC

Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa

West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.status: publishe

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes