Identifiers in e-Science platforms for the ecological sciences

In the emerging Web of Data, publishing stable and unique identifiers promises great potential in using the web as common platform to discover and enrich data in the ecologic sciences. With our collaborative e-Science platform “BEFdata”, we generated and published unique identifiers for the data repository of the Biodiversity – Ecosystem Functioning Research Unit of the German Research Foundation (BEF-China; DFG: FOR 891). We linked part of the identifiers to two external data providers, thus creating a virtual common platform including several ecological repositories. We used the Global Biodiversity Facility (GBIF) as well the International Plant Name Index (IPNI) to enrich the data from our own field observations. We conclude in discussing other potential providers for identifiers for the ecological research domain. We demonstrate the ease of making use of existing decentralized and unsupervised identifiers for a data repository, which opens new avenues to collaborative data discovery for learning, teaching, and research in ecology

The influence of human interaction on guinea pigs: behavioral and thermographic changes during animal-assisted therapy

Guinea pigs are often involved in animal-assisted therapy (AAT) but there is little knowledge about the effects of human contact on guinea pigs involved in AAT. The aim of this study was to investigate effects of availability of a retreat, presence of conspecifics, prior experience with AAT, and human interaction on indicators of welfare in guinea pigs involved in AAT. Guinea pigs of both sexes and different ages (n=20) were assigned to a randomized, controlled within-subject trial with repeated measurements. Each guinea pig was tested in four settings: (I) therapy with retreat possibility with conspecifics, (II) therapy with retreat possibility without conspecifics, (III) therapy without retreat possibility, and (IV) setting without human interaction. We measured changes in eye temperature, as a proxy to infer stress levels, at 5-s intervals with a thermographic camera. All sessions were video recorded and the guinea pigs' behavior was coded using continuous recording and focal animal sampling. For the statistical analysis we used generalized linear mixed models, with therapy setting as a fixed effect and individual guinea pig as a random effect. We observed a temperature increase relative to baseline in settings (I) therapy with retreat with conspecifics present and (III) therapy without retreat. The percentage of time a guinea pig was petted was positively correlated with a rise in the eye temperature independent of the setting. Time spent eating was reduced in all therapy settings (I-III) compared to the setting without HAI (human animal interaction) (IV). In the setting with retreat (I), guinea pigs showed more active behaviors such as locomotive behavior or startling compared to the setting without retreat (III) and the setting without HAI (IV). When no retreat was available (III), they showed more passive behaviors, such as standing still or freezing compared to therapy with retreat (I). Based on our results we identified the behaviors "reduced eating", "increased startle" and "increased freezing" as indicators of an increased stress level. Petting the guinea pigs was correlated with a rise in the eye temperature and might be a factor which can cause stress. Our results support the suggestion that guinea pigs involved in AAT should have a retreat possibility, should have access to conspecifics, and should be given time to adapt to a new setting. In this way, stress might be reduced

Tree species traits but not diversity mitigate stem breakage in a subtropical forest following a rare and extreme ice storm

Peer reviewedPublisher PD

Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression

Separase is a protease whose liberation from its inhibitory chaperone Securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesin's kleisin subunit. We have created conditional knockout alleles of the mouse Separase and Securin genes. Deletion of both copies of Separase but not Securin causes embryonic lethality. Loss of Securin reduces Separase activity because deletion of just one copy of the Separase gene is lethal to embryos lacking Securin. In embryonic fibroblasts, Separase depletion blocks sister chromatid separation but does not prevent other aspects of mitosis, cytokinesis, or chromosome replication. Thus, fibroblasts lacking Separase become highly polyploid. Hepatocytes stimulated to proliferate in vivo by hepatectomy also become unusually large and polyploid in the absence of Separase but are able to regenerate functional livers. Separase depletion in bone marrow causes aplasia and the presumed death of hematopoietic cells other than erythrocytes. Destruction of sister chromatid cohesion by Separase may be a universal feature of mitosis in eukaryotic cells

Designing forest biodiversity experiments : general considerations illustrated by a new large experiment in subtropical China

Funded by German Research Foundation. Grant Number: DFG FOR 891/1 and 2 National Natural Science Foundation of China. Grant Numbers: NSFC 30710103907, 30930005, 31170457 , 31210103910 Swiss National Science Foundation (SNSF) Sino-German Centre for Research Promotion in BeijingPeer reviewedPublisher PD

A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models

In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes

Protein modification with ISG15 blocks coxsackievirus pathology by antiviral and metabolic reprogramming

Protein modification with ISG15 (ISGylation) represents a major type I IFN–induced antimicrobial system. Common mechanisms of action and species-specific aspects of ISGylation, however, are still ill defined and controversial. We used a multiphasic coxsackievirus B3 (CV) infection model with a first wave resulting in hepatic injury of the liver, followed by a second wave culminating in cardiac damage. This study shows that ISGylation sets nonhematopoietic cells into a resistant state, being indispensable for CV control, which is accomplished by synergistic activity of ISG15 on antiviral IFIT1/3 proteins. Concurrent with altered energy demands, ISG15 also adapts liver metabolism during infection. Shotgun proteomics, in combination with metabolic network modeling, revealed that ISG15 increases the oxidative capacity and promotes gluconeogenesis in liver cells. Cells lacking the activity of the ISG15-specific protease USP18 exhibit increased resistance to clinically relevant CV strains, therefore suggesting that stabilizing ISGylation by inhibiting USP18 could be exploited for CV-associated human pathologies

Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects

International audienceInterference with immune cell proliferation represents a successful treatment strategy in T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS). One prominent example is pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), which mediates de novo pyrimidine synthesis in actively proliferating T and B lymphocytes. Within the TERIDYNAMIC clinical study, we observed that the DHODH inhibitor teriflunomide caused selective changes in T cell subset composition and T cell receptor repertoire diversity in patients with relapsing-remitting MS (RRMS). In a preclinical antigen-specific setup, DHODH inhibition preferentially suppressed the proliferation of high-affinity T cells. Mechanistically, DHODH inhibition interferes with oxidative phosphorylation (OXPHOS) and aerobic glycolysis in activated T cells via functional inhibition of complex III of the respiratory chain. The affinity-dependent effects of DHODH inhibition were closely linked to differences in T cell metabolism. High-affinity T cells preferentially use OXPHOS during early activation, which explains their increased susceptibility toward DHODH inhibition. In a mouse model of MS, DHODH inhibitory treatment resulted in preferential inhibition of high-affinity autoreactive T cell clones. Compared to T cells from healthy controls, T cells from patients with RRMS exhibited increased OXPHOS and glycolysis, which were reduced with teriflunomide treatment. Together, these data point to a mechanism of action where DHODH inhibition corrects metabolic disturbances in T cells, which primarily affects profoundly metabolically active high-affinity T cell clones. Hence, DHODH inhibition may promote recovery of an altered T cell receptor repertoire in autoimmunity