77 research outputs found
RÀume erzÀhlen - erzÀhlende RÀume. Raumdarstellung als Poetik. Mit einer exemplarischen Analyse des Nibelungenliedes
Die Dissertation setzt sich mit literarischer Raumdarstellung auseinander. Im theoretischen und methodischen Abschnitt wird die Entwicklung des Raumbegriffs in seinen semantischen Facetten nachverfolgt, um die terminologische Grundlage fĂŒr ein eigenes methodisches Verfahren zu legen. Im textanalytischen Abschnitt wird der Interpretationsansatz des Raumes in seiner ProduktivitĂ€t und Reichweite am Beispiel des Nibelungenliedes ĂŒberprĂŒft.Die Dissertation ist im UniversitĂ€tsverlag Winter Heidelberg erschienen und steht in der Unibibliothek TĂŒbingen unter der Signatur 59 A 786:1 bzw. 59 A 786:2 zur VerfĂŒgung
Quantitative Bildgebung der Niere im ApoE-/-/LDL-/--Doppel-Knockout Maus-Modell mittels Mikro- und Nano-Computertomographie
Die ApoE-/-/LDL-/--Doppel-Knockout MĂ€use weisen bedeutende strukturelle Ăhnlichkeiten zur humanen Atherosklerose auf. Ziel der Studie war es, die renalen GefĂ€Ăe mittels hochauflösendem Mikro- und Nano-CT im Tiermodell der ApoE-/-/LDL-/--Doppel-Knockout Maus zu quantifizieren.
Die Nieren der 80 Wochen alten ApoE-/-/LDL-/--Doppel-Knockout MĂ€use und der Kontrolltiere wurden mittels Microfil perfundiert und anschlieĂend im Mikro- und Nano-CT (12 μm3 . 900 nm3 VoxelgröĂe) untersucht. Anhand der Mikro-CT DatensĂ€tze wurde das intrarenale GefĂ€Ăvolumen bestimmt. Nach histologischer Aufarbeitung der Proben wurden zudem Anzahl, Durchmesser und FlĂ€che der Glomeruli ermittelt.
Die Quantifizierung des renalen GefĂ€Ăbaums ergab eine signifikante Verminderung des GefĂ€Ăvolumens (p < 0.001). Die A. renalis wies fortgeschrittene atherosklerotische Plaques mit adventitieller Neovaskularisation auf. Zudem zeigten die ApoE-/-/LDL-/--Doppel-Knockout MĂ€use eine perivaskulĂ€re Inflammation. Die Gesamtanzahl der Glomeruli pro SchnittflĂ€che nahm deutlich zu mit einem Anteil von 41% pathologisch verĂ€nderten Glomeruli. Durchmesser und FlĂ€che der Glomeruli waren vergröĂert. Nach immunhistochemischer FĂ€rbung zeigten sich auĂerdem kapillĂ€re Aneurysmen gefĂŒllt mit Faktor VIII enthaltenden Lipoprotein-Emboli in den Glomeruli.
Die vorliegende Arbeit zeigt, dass die systemische Atherosklerose der ApoE-/-/LDL-/--Doppel-Knockout MĂ€use mit strukturellen VerĂ€nderungen der Glomeruli und einer Verminderung des intrarenalen GefĂ€Ăvolumens einhergeht, was mittels hochauflösendem Mikro- und Nano-CT quantifiziert werden kann.The apoE-/-/LDL-/--double-knockout mice are bearing considerable structural homology to human atherosclerosis. We hypothesized, that advanced atherosclerotic lesions in the renal artery are associated with kidney alterations in this animal model. The present study was designed to test the potential for quantitative imaging the renal vasculature as a marker of kidney function using high-resolution micro- and nano-CT.
Kidneys from apoE-/-/LDL-/--double-knockout mice at the age of 80 weeks and control animals were infused with Microfil, harvested and scanned with micro- and nano-CT (12 μm3 and 900 nm3 voxel size). The total vascular volume was quantitated using micro-CT. After histological work-up of the samples number, diameter and cross-sectional area were measured.
The quantification of the renal vasculature revealed a significant decrease of the total vascular volume (p < 0.001). The renal artery showed advanced atherosclerotic plaques with adventitial neovascularization. Moreover, a perivascular inflammation was present in kidneys of apoE-/-/LDL-/--double-knockout mice. The total number of glomeruli per cross-section strikingly increased, whereas 41% of them showed pathological alterations. Glomeruli cross-sectional area and diameter were enlarged. Furthermore, immunohistochemistry demonstrated capillary aneurysms of the glomeruli filled with factor 8 containing emboli.
Our study shows that systemic atherosclerosis in apoE-/-/LDL-/--double-knockout mice is associated with glomeruli alterations and reduced intra-renal total vascular volume, which can be quantitated by using high-resolution micro- and nano-CT
Intravital imaging reveals angiotensin IIâinduced transcytosis of albumin by podocytes
Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P”mÂł (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang IIâinfused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function
Water-content related alterations in macro and micro scale tendon biomechanics
Though it is known that the water content of biological soft tissues alters mechanical properties, little attempt has been made to adjust the tissue water content prior to biomechanical testing as part of standardization procedures. The objective of this study was to examine the effects of altered water content on the macro and micro scale mechanical tissues properties. Human iliotibial band samples were obtained during autopsies to osmotically adapt their water content. Macro mechanical tensile testing of the samples was conducted with digital image correlation, and micro mechanical tests using atomic force microscopy. Analyses were conducted for elastic moduli, tensile strength, and strain at maximum force, and correlations for water content, anthropometric data, and post-mortem interval. Different mechanical properties exist at different water concentrations. Correlations to anthropometric data are more likely to be found at water concentrations close to the native state. These data underline the need for adapting the water content of soft tissues for macro and micro biomechanical experiments to optimize their validity. The osmotic stress protocol provides a feasible and reliable standardization approach to adjust for water content-related differences induced by age at death, post-mortem interval and tissue processing time with known impact on the stress-strain properties
Comparison of mRNA Vaccinations with BNT162b2 or mRNA-1273 in Anti-CD20-Treated Multiple Sclerosis Patients
Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of â„100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A MannâWhitney test and Fisherâs exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4â49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (â„100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19
Palaeoenvironmental variability and carbon cycle perturbations during the Smithian-Spathian (Early Triassic) in Central Spitsbergen
The Early Triassic Smithian and Spathian time intervals are characterized by perturbations in the global carbon cycle, fluctuations in sea surface temperature, high turnover rates of marine nekton, and a change in terrestrial vegetation. Despite the importance of this time interval, comprehensive multiproxy investigations from Early Triassic high and middle latitude regions remain scarce due to the difficulty in accessing sections. The
objective of this study is to increase our understanding of regional and local palaeoenvironmental and carbon cycle perturbations from a middle Smithian to late Spathian middle latitude section from Central Spitsbergen. Geochemical analyses show an increase in phosphorus and nitrogen just at and above the SmithianâSpathian boundary (SSB). High primary productivity led to increasingly anoxic conditions in bottom waters
during the middle and late Spathian, enhancing the preservation of organic matter in the sediments. Anoxic conditions restrain phosphorus remineralization, allowing it to be recycled within the water column. This increase in anoxia is consistent with observations in other Arctic basins, demonstrating larger regional similarities in palaeoenvironmental conditions. The fluctuations in isostatic and eustatic sea levels affected organic
carbon sequestration by regulating organic matter mineral interactions via the control of grain size within the sediment. This study demonstrates that local organic carbon sequestration in the Barents Sea shelf during the Spathian was influenced by a multitude of factors, including sedimentology, redox conditions, nutrient availability, and primary productivity.
⥠VikinghĂžgda Formation, bulk rock geochemistry, particulate organic matter, extinction recovery, carbon isotopes, Stensiöfjellet Franziska R. Blattmann â [[email protected]], Zoneibe A.S. Luz [[email protected]] and Torsten W. Vennemann [[email protected]], Institute
of Earth Surface Dynamics, University of Lausanne, Quartier UNIL-Mouline, 1015 Lausanne, Switzerland; Elke Schneebeli-Hermann [[email protected]] and Hugo F.R. Bucher [[email protected]], Department of Palaeontology, University of
ZĂŒrich, Karl-Schmid-Strasse 4, 8006 ZĂŒrich, Switzerland; Thierry Adatte [[email protected]], Institute of Earth Sciences, University of Lausanne, Quartier UNIL-Mouline, CH-1015 Lausanne, Switzerland; Christian VĂ©rard [[email protected]], Section of Earth and Environmental Sciences, University of Geneva, Rue des MaraĂźchers 13, CH-1205 Geneva, Switzerland; Ăyvind Hammer [[email protected]], Natural History Museum, University of Oslo, Pb. 1172 Blindern, 0318 Oslo, Norway; manuscript received on 08/08/2023; manuscript accepted on 02/02/2024; manuscript published on 20/06/2024 in Lethaia 57(2)
Evergreen broadleaf greenness and its relationship with leaf flushing, aging, and water fluxes
13 PĂĄg.
Departamento de Medio Ambiente y AgronomĂaâ (INIA)Remote sensing capabilities to monitor evergreen broadleaved vegetation are limited by the low temporal variability in the greenness signal. With canopy greenness computed from digital repeat photography (PhenoCam), we investigated how canopy greenness related to seasonal changes in leaf age and traits as well as variation of treesâ water fluxes (characterized by sap flow and canopy conductance). The results showed that sprouting leaves are mainly responsible for the rapid increase in canopy green chromatic coordinate (GCC) in spring. We found statistically significantly differences in leaf traits and spectral properties among leaves of different leaf ages. Specifically, mean GCC of young leaves was 0.385 ± 0.010 (mean ± SD), while for mature and old leaves was 0.369 ± 0.003, and 0.376 ± 0.004, respectively. Thus, the temporal dynamics of canopy GCC can be explained by changes in leaf spectral properties and leaf age. Sap flow and canopy conductance are both well explained by a combination of environmental drivers and greenness (96% and 87% of the variance explained, respectively). In particular, air temperature and vapor pressure deficit (VPD) explained most of sap flow and canopy conductance variance, respectively. Besides, GCC is an important explanatory variable for variation of canopy conductance may because GCC can represent the leaf ontogeny information. We conclude that PhenoCam GCC can be used to identify the leaf flushing for evergreen broadleaved trees, which carries important information about leaf ontogeny and traits. Thus, it can be helpful for better estimating canopy conductance which constraints water fluxes.The authors acknowledge the Alexander von Humboldt Foundation for supporting this research with the Max Planck Prize to Markus Reichstein. Yunpeng Luo and Mirco Migliavacca gratefully acknowledge the financial support from the China Scholarship Council. ADR acknowledges support for the PhenoCam network from the National Science Foundation ( DEB- 1702697 ). Javier Pacheco-Labrador and Mirco Migliavacca acknowledge the German Aerospace Center (DLR) project OBEF-Accross2 âThe Potential of Earth Observations to Capture Patterns of Biodiversityâ (Contract No. 50EE1912). The research also received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 721995 and Ministerio de EconomĂay Competitividad through FLUXPEC CGL2012-34383 and SynerTGE CGL2015-G9095-R (MINECO/FEDER, UE) projects.Peer reviewe
No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study
It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (ÎČ = 16.1, CI(ÎČ) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (ÎČ = 4.86,CI(ÎČ) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest
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