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Microclimatic gradients cause phenological variations within temperate tree canopies in autumn but not in spring
No full textTree crowns experience strong vertical microclimatic gradients, particularly in light availability. Surprisingly, little is known about whether these gradients cause within-crown variation in leaf phenology and whether such variations represent different light-use strategies of sun-and shade leaves.In a temperate mixed forest at the Swiss Canopy Crane II site in Switzerland, we measured over three years the annual leaf phenology in the upper and lower crowns of mature trees from six broadleaved and three conifer species. We further recorded the microclimate (temperature, humidity, light) continuously in various positions within the canopy.We found microclimatic canopy gradients to be strongest during summer, but negligible in winter and spring, indicating that any phenological gradients in autumn, but not in spring, might be driven by microclimatic dif-ferences. Budbreak timing did not differ within the crowns of any of the broadleaved trees. However, in the three species with deeper crowns, leaf unfolding was up to 10 days faster in the lower crown but showed no difference in the more shallow-crowned species. Surprisingly, only the evergreen conifers Abies alba and Picea abies showed earlier bud break in the lower crowns. In autumn, senescence in all broadleaved species progressed from the upper crown downwards, resulting in up to two weeks longer vegetation seasons in the lower crown.With this first broad assessment of within-tree phenology, we show how microclimatic gradients and different light-use strategies lead to a considerable variability of within-crown phenological gradients. We interpret the faster leaf unfolding in the lower crown of three broadleaved species as a shade avoidance strategy, allowing shade branches to improve their C balance early in the season. In contrast, longer retention of lower leaves in autumn is unlikely to significantly improve the C balance, and more likely caused by higher summer temperature and irradiance in the upper leaves
Association of long-term exposure to ambient air pollution with retinal neurodegeneration: the prospective alienor study
No full textChronic exposure to air pollution may have adverse effects on neurodegenerative diseases. Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve, characterized by progressive thinning of the retinal nerve fiber layer (RNFL). We investigated the relationship of air pollution exposure with longitudinal changes of RNFL thickness in the Alienor study, a population-based cohort of residents of Bordeaux, France, aged 75 years or more. Peripapillary RNFL thickness was measured using optical coherence tomography imaging every 2 years from 2009 to 2020. Measurements were acquired and reviewed by specially trained technicians to control quality. Air pollution exposure (particulate matter </=2.5 mum (PM(2.5)), black carbon (BC), nitrogen dioxide (NO(2))) was estimated at the participants' geocoded residential address using land-use regression models. For each pollutant, the 10-year average of past exposure at first RNFL thickness measurement was estimated. Associations of air pollution exposure with RNFL thickness longitudinal changes were assessed using linear mixed models adjusted for potential confounders, allowing for intra-eye and intra-individual correlation (repeated measurements). The study included 683 participants with at least one RNFL thickness measurement (62% female, mean age 82 years). The average RNFL was 90 mum (SD:14.4) at baseline. Exposure to higher levels of PM(2.5) and BC in the previous 10 years was significantly associated with a faster RNFL thinning during the 11-year follow-up (-0.28 mum/year (95% confidence interval (CI) [-0.44;-0.13]) and -0.26 mum/year (95% CI [-0.40;-0.12]) per interquartile range increment; p < 0.001 for both). The size of the effect was similar to one year of age in the fitted model (-0.36 mum/year). No statistically significant associations were found with NO(2) in the main models. This study evidenced a strong association of chronic exposure to fine particulate matter with retinal neurodegeneration, at air pollution levels below the current recommended thresholds in Europe
Factors associated with COVID-19 non-vaccination in Switzerland: a nationwide study
Get PDFObjectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness
Niche differentiation between some species of Ghanaian orb-web spiders (Araneae: Araneidae, Tetragnathidae)
No full textThe web placement and web structure of the nine most common species of orb-web spiders (Araneae: Araneidae, Tetragnathidae) coexisting in the park-like campus of the University of Ghana in Legon, Ghana, were investigated to analyse differences between their ecological niches. Various web parameters, such as: relation to habitat, height, light exposure, web size, mesh size, and web inclination, were measured. When comparing these parameters in all species pairs, the webs of each species were found to differ in at least two parameters from the web of every other species. Since the analysed web parameters are all likely to influence the number and kind of prey caught, this suggests a niche differentiation between all analysed species. Some observations were also made on the prey caught. While the prey analysis was not detailed enough to find differences between all species, there was a positive correlation between the web's mesh size and the size of the prey
Structural and functional analysis of the human chemokine receptor and HIV-1 co-receptor CCR5
Get PDFThis thesis describes the elucidation of the activation mechanism of the human CC chemokine receptor 5 (CCR5) by a chemokine analog, its signaling complexes with the heterotrimeric Gi protein, and subsequent interactions with arrestin2.
Chapter 1 presents a general introduction to G protein-coupled receptor (GPCR) biology and recent advances in the structure elucidation of GPCRs and their signaling complexes. Additionally, the chapter covers the biology of chemokine receptors, focusing on the role of CCR5 in the human immune system.
Chapter 2 describes the cryo-EM structure of wild-type human CCR5 in an active conformation bound to the super-agonist [6P4]CCL5 and the heterotrimeric Gi. The structure of the signaling complex allowed to describe the activation mechanism of CCR5 and to elucidate key elements of the variable pharmacology of CCL5 analogs. These results shed new light on the molecular pharmacology of chemokine receptors and show how a chemokine receptor can be activated by the ‘deep’ binding of the agonist N-terminus into the orthosteric receptor pocket.
Chapter 3 provides a detailed protocol for the biochemical preparation of the [6P4]CCL5•CCR5•Gi signaling complex and describes current advances in chemokine structure determination and associated challenges. An additional NMR characterization of the [5P14]CCL5 partial agonist and [5P12]CCL5 antagonist chemokines is given in the Appendix of this Chapter.
Chapter 4 focuses on the last step of the GPCR signaling cascade – the interaction of CCR5 with arrestin2. Two high-resolution X-ray structures of human arrestin2 in complex with two distinct CCR5 C-terminal phosphopeptides were solved. These structures, in combination with mass spectrometry, NMR, and biochemical and cellular assays, uncovered a key GPCR phosphomotif, which is recognized by arrestin2 and enables its tight association with a GPCR. A further analysis of available structural and functional data on GPCR•arrestin interactions suggests how a certain arrangement of phosphoresidues within the intracellular side of GPCRs define arrestin2 and arrestin3 isoforms specificities.
Chapter 5 describes the isolation of the full-length [6P4]CCL5•CCR5•arrestin2 complex, its biochemical and structural characterization. Furthermore, it discusses the challenges of the structural analysis of this complex
Artificial intelligence and the doctor-patient relationship expanding the paradigm of shared decision making
Get PDFArtificial intelligence (AI) based clinical decision support systems (CDSS) arebecoming ever more widespread in healthcare and could play an important role indiagnostic and treatment processes. For this reason, AI‐based CDSS has an impacton the doctor-patient relationship, shaping their decisions with its suggestions. Wemay be on the verge of a paradigm shift, where the doctor-patient relationship is nolonger a dual relationship, but a triad. This paper analyses the role of AI‐based CDSSfor shared decision‐making to better comprehend its promises and associated ethicalissues. Moreover, it investigates how certain AI implementations may instead fosterthe inappropriate paradigm of paternalism. Understanding how AI relates to doctorsand influences doctor-patient communication is essential to promote more ethicalmedical practice. Both doctors' and patients' autonomy need to be considered in thelight of AI
Modelling gene expression in terms of DNA sequence
Get PDFUnderstanding the gene regulatory networks that control gene expression remains one of the most of important questions in molecular biology. Much of gene expression is controlled through transcription initiation, whose regulation is ultimately encoded in the constellations of small sequence motifs in the DNA that are bound by transcription factors (TFs) in a sequence-specific manner. In this thesis, we addressed the task of understanding gene regulation on two levels. Firstly, we present a computational pipeline for inferring a set of gene regulatory elements in a given organism which includes identifying genes that encode DNA-binding domains (DBDs), mapping them to known binding motifs by leveraging similarity in DBDs between species, annotating promoter regions genome-wide, aligning promoters with orthologous regions from related genomes, and predicting genome-wide transcription factor binding sites (TFBSs). We demonstrated the use of our pipeline by applying it to zebrafish. Furthermore, we integrated these results into our previously developed Integrated System for Motif Activity Response Analysis (ISMARA) which models gene expression data in terms of predicted regulatory sites. Using ISMARA, we predicted known and novel key regulatory TFs in zebrafish using a number of RNA-seq datasets. Secondly, we zoom in at the scale of one single TF regulating a set of constitutive promoters in \textit{Escherichia coli}. We analyzed an artificially evolved set of synthetic promoter sequences which are selected for expression constitutive promoters regulated by transcription factor. We looked closely into promoter sequences and TF binding dynamics and investigated the predictive power of TF binding affinity on gene expression
Characterization of rostral brainstem nuclei controlling locomotion directionality
No full textRecent studies have uncovered specific functions for brainstem nuclei based on mouse genetics and viral tracing technologies. In this thesis, we characterize pre-motor nuclei of the rostral brainstem and interogate their role in specific full body locomotor functions