Wound healing and Cadmium detoxification in the earthworm Lumbricus terrestris – a potential case for coelomocytes?

Earthworms are affected by physical stress, like injury, and by exposure to xenobiotics, such as the toxic metal cadmium (Cd), which enters the environment mainly through industry and agriculture. The stress response to the single and the combination of both stressors was examined in regenerative and unharmed tissue of Lumbricus terrestris to reveal if the stress response to a natural insult like injury (amputation) interferes with Cd detoxification mechanisms. We characterized the roles of metallothionein 1 (MT1) and MT2 isoforms, heat shock protein 70 as well as immune biomarkers such as the toll-like receptors (TLR) single cysteine cluster TLR and multiple cysteine cluster TLR. The role of the activated transcription factors (ATFs) ATF2, ATF7, and the cAMP responsive element binding protein as putative regulatory intersection as well as a stress-dependent change of the essential trace elements zinc and calcium was analyzed. Phosphorylated AMP activated protein kinase, the cellular energy sensor, was measured to explore the energy demand, while the energy status was determined by detecting carbohydrate and protein levels. Taken together, we were able to show that injury rather than Cd is the driving force that separates the four treatment groups – Control, Cd exposure, Injury, Cd exposure and injury. Interestingly, we found that gene expression differed regarding the tissue section that was analyzed and we hypothesize that this is due to the migration of coelomocytes, earthworm immune cells, that take over a key role in protecting the organism from a variety of environmental challenges. Surprisingly, we discovered a role for MT1 in the response to multiple stressors and an isoform-specific function for the two newly characterized TLRs. In conclusion, we gathered novel information on the relation of innate immunity, wound healing, and Cd detoxification mechanisms in earthworms

Modeling and Bioinformatics Identify Responders to G-CSF in Patients With Amyotrophic Lateral Sclerosis

Objective: Developing an integrative approach to early treatment response classification using survival modeling and bioinformatics with various biomarkers for early assessment of filgrastim (granulocyte colony stimulating factor) treatment effects in amyotrophic lateral sclerosis (ALS) patients. Filgrastim, a hematopoietic growth factor with excellent safety, routinely applied in oncology and stem cell mobilization, had shown preliminary efficacy in ALS. Methods: We conducted individualized long-term filgrastim treatment in 36 ALS patients. The PRO-ACT database, with outcome data from 23 international clinical ALS trials, served as historical control and mathematical reference for survival modeling. Imaging data as well as cytokine and cellular data from stem cell analysis were processed as biomarkers in a non-linear principal component analysis (NLPCA) to identify individual response. Results: Cox proportional hazard and matched-pair analyses revealed a significant survival benefit for filgrastim-treated patients over PRO-ACT comparators. We generated a model for survival estimation based on patients in the PRO-ACT database and then applied the model to filgrastim-treated patients. Model-identified filgrastim responders displayed less functional decline and impressively longer survival than non-responders. Multimodal biomarkers were then analyzed by PCA in the context of model-defined treatment response, allowing identification of subsequent treatment response as early as within 3 months of therapy. Strong treatment response with a median survival of 3.8 years after start of therapy was associated with younger age, increased hematopoietic stem cell mobilization, less aggressive inflammatory cytokine plasma profiles, and preserved pattern of fractional anisotropy as determined by magnetic resonance diffusion tensor imaging (DTI-MRI). Conclusion: Long-term filgrastim is safe, is well-tolerated, and has significant positive effects on disease progression and survival in a small cohort of ALS patients. Developing and applying a model-based biomarker response classification allows use of multimodal biomarker patterns in full potential. This can identify strong individual treatment responders (here: filgrastim) at a very early stage of therapy and may pave the way to an effective individualized treatment option

Biomarkers of Nutrition for Development (BOND)—Iron Review

This is the fifth in the series of reviews developed as part of the Biomarkers of Nutrition for Development (BOND) program. The BOND Iron Expert Panel (I-EP) reviewed the extant knowledge regarding iron biology, public health implications, and the relative usefulness of currently available biomarkers of iron status from deficiency to overload. Approaches to assessing intake, including bioavailability, are also covered. The report also covers technical and laboratory considerations for the use of available biomarkers of iron status, and concludes with a description of research priorities along with a brief discussion of new biomarkers with potential for use across the spectrum of activities related to the study of iron in human health. The I-EP concluded that current iron biomarkers are reliable for accurately assessing many aspects of iron nutrition. However, a clear distinction is made between the relative strengths of biomarkers to assess hematological consequences of iron deficiency versus other putative functional outcomes, particularly the relationship between maternal and fetal iron status during pregnancy, birth outcomes, and infant cognitive, motor and emotional development. The I-EP also highlighted the importance of considering the confounding effects of inflammation and infection on the interpretation of iron biomarker results, as well as the impact of life stage. Finally, alternative approaches to the evaluation of the risk for nutritional iron overload at the population level are presented, because the currently designated upper limits for the biomarker generally employed (serum ferritin) may not differentiate between true iron overload and the effects of subclinical inflammation

Self-nonself recognition and aggression in Tetramorium alpestre populations

Ants are eusocial insects with complex social structures and behavior patterns that vary strongly across species. In the myrmicine mountain ant Tetramorium alpestre, social structure and behavior vary also intraspecifically, as monodomous-monogynous colonies act peacefully in North Tyrol (Austria) but aggressively in South Tyrol (Italy), and polydomous-polygynous colonies act peacefully in Carinthia (Austria). This social and behavioral polymorphism makes T. alpestre an ideal study organism to identify the factors leading to these differences. In this thesis, we investigated the behavior of T. alpestre from the three populations mentioned by performing worker aggression assays between populations, calculated five different behavior indices, and tested if geographic distance, temporal factors, and/or relatedness influenced the observed behavior. To detect if workers are able to discriminate between nestmates and non-nestmates, we performed bioassays using cuticular hydrocarbon (CHC) extracts of workers. To further detect if peaceful workers can discriminate between nestmates and non-nestmates, we calculated the time of workers at different peaceful behavior levels and compared these results between internest and intranest encounters. We revealed that the between-population behavior was aggressive in most cases. The observed behavior was not influenced by geographic distance among colonies, internest relatedness, intranest relatedness, time of the day, nor the number of days after sampling. The only significant influence we found was that colonies of the South Tyrolean population were influenced by the time that had passed since the start of the experiment, leading to more aggression the later the behavior videos were filmed. We hypothesise that increased vibrations while filming the behavior movies may have caused this effect. The bioassay revealed that the South Tyrolean population was able to discriminate between nestmates and non-nestmates, whereas no evidence was found that populations of North Tyrol and Carinthia were able to do so. Among the peaceful internest encounters, only the workers of the North Tyrolean population could be demonstrated to discriminate between self and nonself, as the amount of time spent at the behavior level “being next to each other” differed significantly between internest and intranest encounters. To explain the observed differences in behavior patterns and nestmate discrimination across the different populations, we suggest to further search for differences in the amount and structure of CHCs of the different workers, as CHCs are known to influence nestmate discrimination and thus the behavior between workers of different colonies.by Gerhard P. Aigner, BSc.University of Innsbruck, Masterarbeit, 2019(VLID)368081