Sonic boom simulation by means of low-pressure sources

Sonic boom simulation by low pressure source

Evaluating grazing response strategies in winter annuals : A multi-trait approach

Plants minimize fitness losses through grazing by three fundamental strategies: tolerance, avoidance and escape. Annual species have been traditionally assumed to escape grazing through their short life cycle and seed dormancy; however, their grazing response strategies remain almost unexplored. How traits and their coordination affect species' grazing responses, and whether the generalized grazing model, which posits convergent filtering by grazing and drought, is applicable to this ecologically and economically important species group thus remain unclear. We used a trait-based approach to evaluate grazing response strategies of winter annuals from the Middle East. Across 23 species, we examined the coordination of 16 traits hypothesized to be relevant for grazing responses, and linked them to species' fecundity responses, as proxy for fitness responses, to simulated grazing in controlled conditions, to species' abundance responses to grazing in the field and to species' distribution along a large-scale rainfall gradient. Winter annuals exhibited both grazing escape and to a lesser extent tolerance indicated by (a) independent coordination of escape and tolerance traits, and (b) maintenance of higher fecundity in species with more pronounced escape or tolerance traits under simulated grazing. In the natural habitat, species with a more pronounced escape but not tolerance strategy maintained higher abundance under grazing in dry habitats, indicating convergent favouring of escape by both grazing and drought. However, this finding at the local scale was not mirrored by a strategy shift along a large-scale rainfall gradient. Synthesis. The convergent favouring of escape traits by grazing and drought in annuals is consistent with the generalized grazing model. This model, which has been developed for perennials based on the avoidance strategy, can thus be extended to annuals based on escape, a finding that should facilitate projecting consequences of global change in drylands dominated by annuals. © 2021 The Authors. Journal of Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Societ

Evaluating grazing response strategies in winter annuals : A multi-trait approach

Plants minimize fitness losses through grazing by three fundamental strategies: tolerance, avoidance and escape. Annual species have been traditionally assumed to escape grazing through their short life cycle and seed dormancy; however, their grazing response strategies remain almost unexplored. How traits and their coordination affect species' grazing responses, and whether the generalized grazing model, which posits convergent filtering by grazing and drought, is applicable to this ecologically and economically important species group thus remain unclear. We used a trait-based approach to evaluate grazing response strategies of winter annuals from the Middle East. Across 23 species, we examined the coordination of 16 traits hypothesized to be relevant for grazing responses, and linked them to species' fecundity responses, as proxy for fitness responses, to simulated grazing in controlled conditions, to species' abundance responses to grazing in the field and to species' distribution along a large-scale rainfall gradient. Winter annuals exhibited both grazing escape and to a lesser extent tolerance indicated by (a) independent coordination of escape and tolerance traits, and (b) maintenance of higher fecundity in species with more pronounced escape or tolerance traits under simulated grazing. In the natural habitat, species with a more pronounced escape but not tolerance strategy maintained higher abundance under grazing in dry habitats, indicating convergent favouring of escape by both grazing and drought. However, this finding at the local scale was not mirrored by a strategy shift along a large-scale rainfall gradient. Synthesis. The convergent favouring of escape traits by grazing and drought in annuals is consistent with the generalized grazing model. This model, which has been developed for perennials based on the avoidance strategy, can thus be extended to annuals based on escape, a finding that should facilitate projecting consequences of global change in drylands dominated by annuals. © 2021 The Authors. Journal of Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Societ

An open prospective study on the efficacy of Navina Smart, an electronic system for transanal irrigation, in neurogenic bowel dysfunction

Background: Transanal irrigation (TAI) has emerged as a key option when more conservative bowel management does not help spinal cord injured (SCI) individuals with neurogenic bowel dysfunction (NBD). Aim: To investigate the short-term efficacy and safety of an electronic TAI system (Navina Smart) in subjects with NBD. Design: We present an open, prospective efficacy study on Navina Smart, in individuals with NBD secondary to SCI, studied at three months. Population: Eighty-nine consecutive consenting established SCI individuals (61 male; mean age 48, range 18–77) naïve to TAI treatment were recruited from ten centres in seven countries. Subjects had confirmed NBD of at least moderate severity (NBD score ≥10). Methods: Subjects were taught how to use the device at baseline assisted by the Navina Smart app, and treatment was tailored during phone calls until optimal TAI regime was achieved. The NBD score was measured at baseline and at three months follow up (mean 98 days). Safety analysis was performed on the complete population while per protocol (PP) analysis was performed on 52 subjects. Results: PP analysis showed a significant decrease in mean NBD score (17.8 to 10, p<0.00001). In subjects with severe symptoms (defined as NBD score ≥14), mean NBD scores decreased (19.4 to 10.9, p<0.0001). The number of subjects with severe symptoms decreased from 41 (79%) subjects at baseline to 16 (31%) at three months follow-up. Device failure accounted for the commonest cause for loss of data. Side effects possibly related to the device developed in 11 subjects (12%). Discontinuation due to failure of therapy to relieve symptoms was reported by 5 subjects (6%). Conclusion: Navina Smart is effective for individuals with NBD, even those with severe symptoms; long-term data will follow. Whilst there were some device problems (addressed by the later stages of subject recruitment) the treatment was generally safe

An open prospective study on the efficacy of Navina Smart, an electronic system for transanal irrigation, in neurogenic bowel dysfunction

Background: Transanal irrigation (TAI) has emerged as a key option when more conservative bowel management does not help spinal cord injured (SCI) individuals with neurogenic bowel dysfunction (NBD). Aim: To investigate the short-term efficacy and safety of an electronic TAI system (Navina Smart) in subjects with NBD. Design: We present an open, prospective efficacy study on Navina Smart, in individuals with NBD secondary to SCI, studied at three months. Population: Eighty-nine consecutive consenting established SCI individuals (61 male; mean age 48, range 18–77) naïve to TAI treatment were recruited from ten centres in seven countries. Subjects had confirmed NBD of at least moderate severity (NBD score ≥10). Methods: Subjects were taught how to use the device at baseline assisted by the Navina Smart app, and treatment was tailored during phone calls until optimal TAI regime was achieved. The NBD score was measured at baseline and at three months follow up (mean 98 days). Safety analysis was performed on the complete population while per protocol (PP) analysis was performed on 52 subjects. Results: PP analysis showed a significant decrease in mean NBD score (17.8 to 10, p<0.00001). In subjects with severe symptoms (defined as NBD score ≥14), mean NBD scores decreased (19.4 to 10.9, p<0.0001). The number of subjects with severe symptoms decreased from 41 (79%) subjects at baseline to 16 (31%) at three months follow-up. Device failure accounted for the commonest cause for loss of data. Side effects possibly related to the device developed in 11 subjects (12%). Discontinuation due to failure of therapy to relieve symptoms was reported by 5 subjects (6%). Conclusion: Navina Smart is effective for individuals with NBD, even those with severe symptoms; long-term data will follow. Whilst there were some device problems (addressed by the later stages of subject recruitment) the treatment was generally safe

Disruption of the Autophagy-Lysosome Pathway Is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis

Variant late-infantile neuronal ceroid lipofuscinosis, a fatal lysosomal storage disorder accompanied by regional atrophy and pronounced neuron loss in the brain, is caused by mutations in the CLN6 gene. CLN6 is a non-glycosylated endoplasmic reticulum (ER)-resident membrane protein of unknown function. To investigate mechanisms contributing to neurodegeneration in CLN6 disease we examined the nclf mouse, a naturally occurring model of the human CLN6 disease. Prominent autofluorescent and electron-dense lysosomal storage material was found in cerebellar Purkinje cells, thalamus, hippocampus, olfactory bulb and in cortical layer II to V. Another prominent early feature of nclf pathogenesis was the localized astrocytosis that was evident in many brain regions and the more widespread microgliosis. Expression analysis of mutant Cln6 found in nclf mice demonstrated synthesis of a truncated protein with a reduced half-life. Whereas the rapid degradation of the mutant Cln6 protein can be inhibited by proteasomal inhibitors, there was no evidence for ER stress or activation of the unfolded protein response in various brain areas during postnatal development. Age-dependent increases in LC3-II, ubiquitinated proteins, and neuronal p62-positive aggregates were observed, indicating a disruption of the autophagy-lysosome degradation pathway of proteins in brains of nclf mice, most likely due to defective fusion between autophagosomes and lysosomes. These data suggest that proteasomal degradation of mutant Cln6 is sufficient to prevent the accumulation of misfolded Cln6 protein, whereas lysosomal dysfunction impairs constitutive autophagy promoting neurodegeneration

Characterization of Chromosomal Instability in Murine Colitis-Associated Colorectal Cancer

Patients suffering from ulcerative colitis (UC) bear an increased risk for colorectal cancer. Due to the sparsity of colitis-associated cancer (CAC) and the long duration between UC initiation and overt carcinoma, elucidating mechanisms of inflammation-associated carcinogenesis in the gut is particularly challenging. Adequate murine models are thus highly desirable. For human CACs a high frequency of chromosomal instability (CIN) reflected by aneuploidy could be shown, exceeding that of sporadic carcinomas. The aim of this study was to analyze mouse models of CAC with regard to CIN. Additionally, protein expression of p53, beta-catenin and Ki67 was measured to further characterize murine tumor development in comparison to UC-associated carcinogenesis in men.The AOM/DSS model (n = 23) and IL-10(-/-) mice (n = 8) were applied to monitor malignancy development via endoscopy and to analyze premalignant and malignant stages of CACs. CIN was assessed using DNA-image cytometry. Protein expression of p53, beta-catenin and Ki67 was evaluated by immunohistochemistry. The degree of inflammation was analyzed by histology and paralleled to local interferon-γ release.CIN was detected in 81.25% of all murine CACs induced by AOM/DSS, while all carcinomas that arose in IL-10(-/-) mice were chromosomally stable. Beta-catenin expression was strongly membranous in IL-10(-/-) mice, while 87.50% of AOM/DSS-induced tumors showed cytoplasmatic and/or nuclear translocation of beta-catenin. p53 expression was high in both models and Ki67 staining revealed higher proliferation of IL-10(-/-)-induced CACs.AOM/DSS-colitis, but not IL-10(-/-) mice, could provide a powerful murine model to mechanistically investigate CIN in colitis-associated carcinogenesis

Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens

This is the final version of the article. Available from the publisher via the DOI in this record.Background: Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses. Results: We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses. Conclusions: Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.This article is a joint effort of the working group TRANSBEE and an outcome of two workshops kindly supported by sDiv, the Synthesis Centre for Biodiversity Sciences within the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Science Foundation (FZT 118). New datasets were performed thanks to the Insect Pollinators Initiative (IPI grant BB/I000100/1 and BB/I000151/1), with participation of the UK-USA exchange funded by the BBSRC BB/I025220/1 (datasets #4, 11 and 14). The IPI is funded jointly by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government and the Wellcome Trust, under the Living with Environmental Change Partnershi

Distinct Early Molecular Responses to Mutations Causing vLINCL and JNCL Presage ATP Synthase Subunit C Accumulation in Cerebellar Cells

Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL), caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6nclf/nclf cerebellar cells and compared them to wild-type and CbCln3Δex7/8/Δex7/8 cerebellar cells. CbCln6nclf/nclf cells and CbCln3Δex7/8/Δex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6nclf/nclf cells, while fluid-phase endocytosis and LysoTracker® labeled vesicles were decreased in both CbCln6nclf/nclf and CbCln3Δex7/8/Δex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3Δex7/8 and Cln6nclf mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival