University of Freiburg
  • Freiburg, Baden-Württemberg, Germany
Recent publications
Studies on cultural ecosystem services (CES) in urban forests using Public Participation GIS mapping are a well-established field of research. However, far fewer studies do exist that also illuminate perceived disservices, thus omitting an important part of human-forest relation- ships. Advancing knowledge on unpleasant places can promote outdoor recreation and help forest managers focus on disservices that matter. This study aims at spatially identifying people’s perceptions in urban forests with focus on unpleasant experiences. We elicited perceived disservices and CES spatially by collecting Public Participation GIS data (PPGIS) from city dwellers in three urban forests in Germany’s Southwest (755 respondents mapped 1552 places of disservices). We investigated relationships between sociodemographic char- acteristics and the number of mapped places using Spearman’s rank. We also explored the spatial concurrence between disservices and CES using Spearman’s rank. We identified a hierarchy of importance of forest visitors’ perceived dislikes. We revealed that negative perceptions of urban forest visitors originated broadly from people and their traces and rarely from the ecosystem according to existing ecosystem disservices typologies (EDS). We found a significant relationship between age and the number of mapped services. We found clusters of disliked places and correlations between disservices and CES, indicating that hotspots of CES in turn are also hotspots of disservices. We conclude that city foresters may best address disservices by advancing guidance-concepts for spatial movements of urban forest visitors within the forest to avoid conflicting clusters of various stakeholders. Our results may help city foresters to better manage both the forest and visitors’ various interests.
There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.
The ability to precisely alter the genome holds immense potential for molecular biology, medicine and biotechnology. The development of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) into a genomic editing tool has vastly simplified genome engineering. Here, we explored the use of chemically synthesized chimeric oligonucleotides encoding a target-specific crRNA (CRISPR RNA) fused to a single-stranded DNA repair template for RNP-mediated precision genome editing. By generating three clinically relevant oncogenic driver mutations, two non-stop extension mutations, an FGFRi resistance mutation and a single nucleotide change, we demonstrate the ability of chimeric oligos to form RNPs and direct Cas9 to effectively induce genome editing. Further, we demonstrate that the polarity of the chimeric oligos is crucial: only chimeric oligos with the single-stranded DNA repair template fused to the 3'-end of the crRNA are functional for accurate editing, while templates fused to the 5'-end are ineffective. We also find that chimeras can perform editing with both symmetric and asymmetric single-stranded DNA repair templates. Depending on the target locus, the editing efficiency using chimeric RNPs is similar to or less than the efficiency of editing using the bipartite standard RNPs. Our results indicate that chimeric RNPs comprising RNA-DNA oligos formed from fusing the crRNA and DNA repair templates can successfully induce precise edits. While chimeric RNPs do not display an advantage over standard RNPs, they nonetheless represent a viable approach for one-molecule precision genome editing.
As the only oxygenic phototrophs among prokaryotes, cyanobacteria employ intricate mechanisms to regulate common metabolic pathways. These mechanisms include small protein inhibitors exerting their function by protein-protein interaction with key metabolic enzymes and regulatory small RNAs (sRNAs). Here we show that the sRNA NsiR4, which is highly expressed under nitrogen limiting conditions, interacts with the mRNA of the recently described small protein PirA in the model strain Synechocystis sp. PCC 6803. In particular, NsiR4 targets the pirA 5'UTR close to the ribosome binding site. Heterologous reporter assays confirmed that this interaction interferes with pirA translation. PirA negatively impacts arginine synthesis under ammonium excess by competing with the central carbon/nitrogen regulator PII that binds to and thereby activates the key enzyme of arginine synthesis, N-acetyl-L-glutamate-kinase (NAGK). Consistently, ectopic nsiR4 expression in Synechocystis resulted in lowered PirA accumulation in response to ammonium upshifts, which also affected intracellular arginine pools. As NsiR4 and PirA are inversely regulated by the global nitrogen transcriptional regulator NtcA, this regulatory axis enables fine tuning of arginine synthesis and conveys additional metabolic flexibility under highly fluctuating nitrogen regimes. Pairs of small protein inhibitors and of sRNAs that control the abundance of these enzyme effectors at the post-transcriptional level appear as fundamental building blocks in the regulation of primary metabolism in cyanobacteria.
Purpose: Tumor perfusion is considered to be the principal factor determining the build-up of therapeutically effective thermal fields. This assumes that malignancies have lower perfusions than their homologous tissues. This assumption, however, ignores the fact that several tumor types have higher perfusions than their healthy counterparts. Additionally, flow changes upon hyperthermia (39-43 °C) are non-predictable and extremely heterogeneous. Therefore, modeling temperature distribution further requires a more robust parameter, different in malignancies and healthy tissues, i.e., water content (Cw), which highly determines thermal properties upon electromagnetic irradiation. Method: Systematic literature reviews of Cw and specific heat capacities (cp) were conducted up to 28 February 2022, providing an updated, comprehensive data overview based on original manuscripts, reviews and databases. Results: Cw- and cp-values of cancers and their corresponding healthy tissues are presented. Strong correlations between these two parameters are described. In general, malignant tumors have distinctly higher Cw values than their homologous tissues. With increasing Cw in low-water-content normal tissues (<70 wt.%), cp rises exponentially from 1.5 to 3.3 J·g-1·K-1. In high-water-content normal tissues (≥70 wt.%), cp increases linearly from 3.5 to 3.8 J·g-1·K-1. In malignant tumors (>80 wt.%), cp rises linearly from 3.6 to 3.9 J·g-1·K-1. Cancers contain up to 27% more water than their tissues of origin and must be considered as 'high-capacitance-tissues'. Conclusions: Hyperhydration of cancers result in higher cp-values, causing cancers to be better heat reservoirs than corresponding normal tissues upon electromagnetic irradiation. Reliable, tissue-/cancer-specific cp values must be considered when modeling temperature distributions in hyperthermic treatment.
Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of “autoimmune OCD” is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for “autoimmune OCD” could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.
The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of sampling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are presampled, independent of the hard scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such presampled event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.
Hydrogeological properties of fluid reservoirs in the brittle continental crust at 5 km have been deduced from hydraulic and chemical data provided by the Deep Heat Mining well Basel-1 in the south of the Upper Rhine rift valley (central Europe, Switzerland). The investigation was challenging because no direct temperature logs or fluid samples from the undisturbed reservoir exist. However, the properties of the undisturbed reservoir have been reliably reconstructed from short time hydraulic tests and the evolution of outflow water composition. The rock of the open hole sections (4629–5000 m) is predominantly coarse-grained undeformed poorly fractured quartz-monzodiorite. The permeability k = 5.8 × 10 –18 m ² is characteristic for plutonic basement at 5 km depth. Fluid flow is restricted to few steeply dipping fracture zones in this section. Outflow water triggered by massive injection of river water contains predominantly NaCl. The total of dissolved solids (TDS) in the pristine reservoir at depth is about 45 g kg ⁻¹ . The origin of the high salinity is probably fossil seawater. The water has been modified in the reservoir by desiccation reactions related to the partial and local hydration of the igneous reservoir rock. The estimated reservoir temperature of 185 °C using three different calibrations of standard fluid geothermometers is in excellent agreement with measured and extrapolated temperatures in the borehole. The consistent application of different fluid geothermometers confirms the rock control of the fluid composition.
Background Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). PGRN is comprised of 7.5 granulin repeats and is processed into individual granulin peptides in the lysosome. However, very little is known about the levels and regulations of individual granulin peptides due to the lack of specific antibodies. Results Here we report the generation and characterization of antibodies specific to each granulin peptide. We found that the levels of granulins C, E and F are regulated differently compared to granulins A and B in various tissues. The levels of PGRN and granulin peptides vary in different brain regions and the ratio between granulins and PGRN is highest in the cortical region in the adult male mouse brain. Granulin-A is localized in the lysosome in both neurons and microglia and its levels in microglia increase under pathological conditions. Interestingly, the levels of granulin A in microglia change correspondingly with PGRN in response to stroke but not demyelination. Furthermore, deficiency of lysosomal proteases and the PGRN binding partner prosaposin leads to alterations in the ratios between individual granulin peptides. Granulins B, C and E are heavily glycosylated and the glycosylation patterns can be regulated under. Conclusion Our results support that the levels of individual granulin peptides are differentially regulated under physiological and pathological conditions and provide novel insights into how granulin peptides function in the lysosome.
Background Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelic COL9A3 variants reported to date. Results Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants in COL9A3 . Further, we have collected COL9A3 genotype–phenotype associations from the literature. Conclusion Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders.
Background: Beyond the degree of adiposity, the pattern of fat distribution has a profound influence on cardiometabolic risk. It is unclear if sex differences in body fat distribution can potentially explain any sex differences in the prevalence of the metabolic syndrome (MetS) and in individual cardiometabolic risk factors among obese men and women. Methods: In this cross-sectional analysis, 432 persons from the ongoing Obesity Weight Reduction Study (n = 356 obese, ØBMI 41 ± 8 kg/m2, and 76 non-obese, ØBMI 25 ± 3 kg/m2), were included. The relations of sex to MetS prevalence and selected cardiometabolic risk factors were assessed using univariate and multivariate adjusted regression models. Results: In crude analyses, %fat mass and the fat mass/lean mass ratio were significantly higher in women than in men, regardless of increasing obesity categories, from normal weight to grade-3-obesity. In contrast, markers of abdominal obesity, such as waist circumference and waist-to-hip ratio were higher in men than in women, despite similar BMI. The prevalence of the MetS was higher in obese men than in women (67.6 vs. 45.0%, p < 0.0001), particularly in younger individuals < 40 years (72.5 vs. 36.8%, p < 0.0001), but "metabolically healthy obesity" (BMI ≥ 30, no other NCEP ATPIII MetS component) was more common in women than in men (15.6 vs. 4.1%, p < 0.0001). After adjusting for age, %body fat and height, sex differences were observed for HDL-cholesterol (p < 0.001), triglycerides (p < 0.001), fasting glucose (p = 0.002), insulin and HOMA-IR levels (p < 0.001), ALAT (p < 0.001), adiponectin (p < 0.001), and sE-selectin (p = 0.005). In contrast, crude sex differences in other variables, such as leptin levels (68 ± 4 in obese women vs. 33 ± 2 µg/L in men, p < 0.0001), disappeared after accounting for differences in %body fat (least-squares means of leptin: 52 ± 4 vs. 55 ± 6 µg /L, p = 0.740). A logistic regression model adjusting for age and lifestyle factors revealed a lower risk of having MetS for women as compared to men (OR = 0.38[0.22-0.60]). That risk estimate did not materially alter after adding BMI to the model. In contrast, no statistically significant association between sex and MetS prevalence was observed after adding waist circumference and adiponectin to the model (OR = 1.41[0.59-3.36]). Conclusions: Different body fat distribution patterns, particularly abdominal adiposity, adiponectin, and related biomarkers, may contribute to sex differences in cardiometabolic risk factors and to the prevalence of the MetS.
Background In pediatric hereditary cystic kidney diseases, epithelial cell defects mostly result from rare, autosomal recessively inherited pathogenic variants in genes encoding proteins of the cilia-centrosome complex. Consequences of individual gene variants on epithelial function are often difficult to predict and can furthermore depend on the patient’s genetic background. Here, we studied urine-derived renal tubular epithelial cells (URECs) from genetically determined, pediatric cohorts of different hereditary cystic kidney diseases, comprising autosomal recessive polycystic kidney disease, nephronophthisis (NPH) and the Bardet Biedl syndrome (BBS). UREC characteristics and behavior in epithelial function-related 3D cell culture were compared in order to identify gene and variant-specific properties and to determine aspects of epithelial (cell) dysfunction. Results UREC preparations from patients (19) and healthy controls (39) were studied in a qualitative and quantitative manner using primary cells cultured for up-to 21 days. In patients with biallelic pathogenic variants in PKHD1 or NPHP genes, we were able to receive satisfactory amounts of URECs of reproducible quality. In BBS patients, UREC yield was lower and more dependent on the individual genotype. In contrast, in UREC preparations derived from healthy controls, no predictable and satisfactory outcome could be established. Considering cell proliferation, tubular origin and epithelial properties in 2D/3D culture conditions, we observed distinct and reproducible epithelial properties of URECs. In particular, the cells from patients carrying PKHD1 variants were characterized by a high incidence of defective morphogenesis of monolayered spheroids—a property proposed to be suitable for corrective intervention. Furthermore, we explored different ways to generate reference cell lines for both—patients and healthy controls—in order to eliminate restrictions in cell number and availability of primary URECs. Conclusions Ex vivo 3D cell culture of primary URECs represents a valuable, non-invasive source to evaluate epithelial cell function in kidney diseases and as such helps to elucidate the functional consequences of rare genetic disorders. In combination with genetically defined control cell lines to be generated in the future, the cultivation of primary URECs could become a relevant tool for testing personalized treatment of epithelial dysfunction in patients with hereditary cystic kidney disease.
The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with Geant4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.
Augmenting the body with artificial limbs controlled concurrently to one’s natural limbs has long appeared in science fiction, but recent technological and neuroscientific advances have begun to make this possible. By allowing individuals to achieve otherwise impossible actions, movement augmentation could revolutionize medical and industrial applications and profoundly change the way humans interact with the environment. Here, we construct a movement augmentation taxonomy through what is augmented and how it is achieved. With this framework, we analyze augmentation that extends the number of degrees-of-freedom, discuss critical features of effective augmentation such as physiological control signals, sensory feedback and learning as well as application scenarios, and propose a vision for the field.
Drilling of the Gotthard Rail Base Tunnel through the Central Alps from 2005 to 2010 opened up fractured basement units and frequent water inflows provided access to the major fluid-rock interactions processes in orogenic crystalline upper crust. Construction of the 57 km long tunnel was divided into five different sections. Here we report data and observations from the 10 km long central Sedrun section 211 water samples were collected at inflow points 900 to 2350 m below the surface. The exceptional samples and data provide a comprehension of the hydrochemical evolution and solute acquisition of deep groundwater in basement units. The investigated tunnel section drilled through steeply dipping rock units and vertical fracture systems at high angle. It cuts across granite, gneiss and schist of the pre-Alpine basement and across two narrow zones of meta-sediments. Rock temperature along the Sedrun section varies from 30 to 45 °C depending on the thickness of the overburden. The fracture water is of meteoric origin and acquires its composition exclusively by chemical interaction with the surrounding rocks along the flow path. Water from inflow points in the basement of the Gotthard Massif has typically a high pH of about 10 and total dissolved solids in the range of 100 to 300 mg L ⁻¹ . Sodium is the prime cation of most waters. Although plentiful in the rocks, calcium, potassium and magnesium are low to very low in water. The anions associated with Na are carbonate/bicarbonate, sulfate, fluoride and chloride in widely varying proportions. High fluoride concentrations of up to 15.4 mg L ⁻¹ are characteristic for most waters. As a result of the high pH dissolved silica (SiO 2 ) reached concentrations of up to 58 mg L ⁻¹ and represents 25—30 wt% of the solutes. The meteoric recharge provides dissolved O 2 and CO 2 to the fluid-rock interaction processes. The solutes derive from the dissolution of feldspar (Na ⁺ , SiO 2aq ), oxidation of sulfides to sulfate (SO 4 ²⁻ ), alteration of biotite (F ⁻ ), and fluid inclusions opened by brittle deformation (Cl ⁻ ). The solids formed during fluid-rock interaction, mainly zeolites, chlorite (and other clay minerals) and secondary Fe-minerals, remove Mg, Fe, and K almost quantitatively from the water. The high pH results from hydrolysis of silicates. The data distinctly show that within the depth interval of 1.0–2.5 km below surface deep water in continental basement evolves to a low TDS, high pH, sodium carbonate and silica solution by interaction of gneiss and granite with infiltrating pristine meteoric water, snow and rain.
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8,901 members
Christopher Schlett
  • Department of Diagnostic and Interventional Radiology
Knut Holtsträter
  • Zentrum für Populäre Kultur und Musik (ZPKM)
Felix Engel
  • Department of Biological Anthropology
Sonja-Verena Albers
  • Molecular Biology of Archaea
Fahnenbergplatz, 79098, Freiburg, Baden-Württemberg, Germany
Head of institution
Prof. Dr. Kerstin Krieglstein
+49 761 203-0
+49 761 203-4369