How is the hazard landscape changing in Swiss cities and how do they adapt: The case of Basel

Compared to preindustrial times, global surface temperature has increased, in Switzerland more pronounced than in other countries with the strongest increase since the 1980s. Previous research showed that as a result of climate change, both individual natural hazards and compound risks will increase in Central Europe, especially in relation to water bodies. Swiss waters will be subject to changes in the quantity and pattern of runoff that can lead to either hydrological droughts or floods, thus an increase of frequency and persistence of related hazards has to be expected. Simultaneously, urban population is growing but also changing, for example towards higher life expectancy, which results in an increasing exposure and vulnerability. While this means a greater overall future risk for the urban population and infrastructure, adaptation measures are all the more important. As these must be tailored to local conditions and risks, within this thesis past and future hazards, impacts and adaptations are examined on the basis of the Basel case study. This is achieved by using multiple methods, which subsequently lead to a more complete picture of the complex urban interdependencies using the triangulation approach. The methods include a literature review, surveying the situation especially in Central European cities and an examination of the SFLDD (WSL) and reported impacts of the two focus events in 2018 and 2021 in newspapers. Furthermore, measured (FOEN, MeteoSwiss) and modelled (Hydro-CH2018) hydrological and meteorological data are statistically examined, especially with regard to long-lasting extreme events. Lastly, semi-structured interviews with experts from relevant fields contribute to an even more holistic view. The results showed that extreme high flow events on the Rhine in Basel have moderately increased since 1900, but their number will remain stable at a slightly higher level in future. Resulting impacts of the focus event 2021 as well as adaptation measures mainly refer to the direct watercourse area. Extreme low flow events used to occur mainly in winter and show a clear decreasing trend since 1900. Hydro-CH2018 indicates a reversal of this development towards an increase, the extent of which depends on the scenario, and at the same time a seasonal shift of these events to summer and autumn. The impacts occurring during the focus event 2018, a year hit by severe hydrological drought, were already under the simultaneous influence of heat and therefore not limited to the watercourse area but present in the entire city. An intensification, interconnection and larger spatial spread of the impacts of drought due to the simultaneously occurring hazard of extreme heat can be assumed for the city of Basel in the future. As a result of the opposing, not mutually exclusive but alternating risks of flood and drought, adaptations are necessary in particular those covering several risks. The canton of Basel-Stadt is already implementing or planning numerous adaptation measures, including some addressing multiple risks, but focusing on the areas of physical infrastructure and nature-based solutions. Therefore, for the future development of adaptation in the city of Basel, there is a potential in the inclusion of social measures, such as communication strategies or the promotion of adaptation at the individual level. As policy in Basel has been more responsive to flood focus events, it is important to continue to raise awareness of the alternating and increasing occurrence of droughts. This could be supported with a similar database on drought impacts and damages as it already exists on floods and mass movements (SFLDD, WSL)

Lessons learned: rearing the crown-boring weevil, Ceutorhynchus scrobicollis (Coleoptera: Curculionidae), in containment for biological control of garlic mustard (Alliaria petiolata)

In this paper, we describe lessons learned and protocols developed after a decade of rearing Ceutorhynchus scrobicollis Nerenscheimer and Wagner in a Biosafety Level 2 containment facility. We have developed these protocols in anticipation of approval to release C. scrobicollis in North America for the biocontrol of garlic mustard. The rearing protocol tried to minimize the potential of attack by the adult parasitoid, Perilitus conseutor, which may be present in field collected C. scrobicollis from Europe to prevent inadvertent introduction of parasitoids into North America. All C. scrobicollis used for our quarantine rearing were field collected near Berlin, Germany. We have successfully reared C. scrobicollis on caged garlic mustard plants in a growth chamber by alternating temperatures and photoperiods to simulate those in its native range. In Germany, C. scrobicollis produces one generation per year and F1 adults emerge in late May. In containment, a new generation of adults emerged an average of 108 days after adults were placed on plants. We found the optimal time spent to collect F1 adults was four weeks after the appearance of the first F1 adult, with 95% of potential adults collected. Simulating a three-month summer aestivation period, followed by a week of fall, and three weeks of winter conditions resulted in optimum levels of oviposition in F1 females. Larvae first hatched 8- to-10 days after adults were placed on plants at 15/14 C day/night temperatures with a 9.5 hour photoperiod. We therefore recommend that C. scrobicollis adults are removed from garlic mustard rosettes after 8 days. This will maximize the period of female oviposition while minimizing the time when larvae are available for attack from P. conseutor

Two Shoot-Miners, Ceutorhynchus alliariae and Ceutorhynchus roberti, Sharing the Same Fundamental Niche on Garlic Mustard

A combination of observational and experimental methods, in both the laboratory and field, were used to assess niche partitioning between Ceutorhynchus alliariae Brisout and C. roberti Gyllenhal (Coleoptera: Curculionidae), two coexisting shoot-boring weevils on garlic mustard, Alliaria petiolata (M. Bieb.) Cavara and Grande (Brassicaceae). We compared their morphology, oviposition behavior, larval development, distribution, abundance, and attack rates in their sympatric range, and of C. alliariae when found alone and in sympatry with C. roberti. Results indicate only very small differences in the fundamental niches of the two species. Comparison of C. alliariae in the range it occurs alone with the range where it co-occurs with C. roberti revealed some evidence for competition between the two species, i.e., attack levels of C. alliariae were reduced in areas where it co-occurred with C. roberti. However, the study showed no character displacement in regard to adult size or shoot choice of C. alliariae and we found no indication for superiority of either of the two species. Clearly, manipulative experiments would be necessary to unambiguously test for competition between the two species. Our results, based on a subset of niche dimensions known to be important in other systems, suggest that C. alliariae and C. roberti may present one of the rare cases, in which niche differentiation is not the main mechanism underlying coexistenc

Cellular adaptive immune response against porcine circovirus type 2 in subclinically infected pigs

<p>Abstract</p> <p>Background</p> <p>Porcine circovirus type 2 (PCV2) is a dominant causative agent of postweaning multisystemic wasting syndrome (PMWS), a multifactorial disease complex with putative immunosuppressive characteristics. Little is known about adaptive PCV2-specific immune responses in infected pigs. Therefore, the T and B cell responses following PCV2 infection in 3-week old SPF piglets infected with PCV2 or PCV2 plus porcine parvovirus (PPV) were studied.</p> <p>Results</p> <p>All animals were asymptomatically infected. At 7 days post infection (d p.i.), B lymphocyte and T lymphocyte numbers decreased in the dual infected, but not in the single infected piglets. At this time point a transient PCV2 viraemia was noted in the PCV2 infected groups. Antibodies against the infecting virus were detectable at day 24-28 p.i. for anti-PCV2 antibodies and at day 10 p.i. for anti-PPV antibodies, with no apparent influence of PCV2 on the early PPV antibody development. In the animals infected with PPV alone, IFN-γ secreting cells (SC) that were not specific for PCV2 were detected by ELISPOT assay at day 7 p.i. Interestingly, this response was absent in the PCV2/PPV dual infected animals. PCV2-specific IFN-γ SC were observed in the PCV2/PPV infected group at 7 d p.i. and in the PCV2 single infected group at 21 d p.i. A reduction in the numbers of IFN-γ SC was observed following anti-CD4 and anti-CD8 antibody treatment, suggesting roles for both CD4⁺and CD8⁺T cells in the response against PCV2 infection. This was supported by an observed increase in the percentage of IFN-γ positive CD8^hicytotoxic T cells as well as IFN-γ positive CD8^-/lowhelper T cells after PCV2 <it>in vitro </it>re-stimulation.</p> <p>Conclusions</p> <p>Infection of weaned SPF piglets with PCV2 alone or combined with PPV does not induce disease and in both cases a relatively slow anti-PCV2 antibody response and weak T lymphocyte responses were found. Knowledge on such immunological characteristics is important for both PCV2 pathogenesis and vaccination.</p

Lessons learned: rearing the crown-boring weevil, Ceutorhynchus scrobicollis (Coleoptera: Curculionidae), in containment for biological control of garlic mustard (Alliaria petiolata)

In this paper, we describe lessons learned and protocols developed after a decade of rearing Ceutorhynchus scrobicollis Nerenscheimer and Wagner in a Biosafety Level 2 containment facility. We have developed these protocols in anticipation of approval to release C. scrobicollis in North America for the biocontrol of garlic mustard. The rearing protocol tried to minimize the potential of attack by the adult parasitoid, Perilitus conseutor, which may be present in field collected C. scrobicollis from Europe to prevent inadvertent introduction of parasitoids into North America. All C. scrobicollis used for our quarantine rearing were field collected near Berlin, Germany. We have successfully reared C. scrobicollis on caged garlic mustard plants in a growth chamber by alternating temperatures and photoperiods to simulate those in its native range. In Germany, C. scrobicollis produces one generation per year and F1 adults emerge in late May. In containment, a new generation of adults emerged an average of 108 days after adults were placed on plants. We found the optimal time spent to collect F1 adults was four weeks after the appearance of the first F1 adult, with 95% of potential adults collected. Simulating a three-month summer aestivation period, followed by a week of fall, and three weeks of winter conditions resulted in optimum levels of oviposition in F1 females. Larvae first hatched 8- to-10 days after adults were placed on plants at 15/14 C day/night temperatures with a 9.5 hour photoperiod. We therefore recommend that C. scrobicollis adults are removed from garlic mustard rosettes after 8 days. This will maximize the period of female oviposition while minimizing the time when larvae are available for attack from P. conseutor

DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo.

Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of &lt; 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age &lt; 3 or &gt; 10 years (11% v 3% and 33% v 23%, respectively; P &lt; .001) and with longer symptom duration ( P &lt; .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Accurate MS-based Rab10 phosphorylation stoichiometry determination as readout for LRRK2 activity in Parkinson's disease

Pathogenic mutations in the Leucine-rich repeat kinase 2 (LRRK2) increase its activity leading to increased phosphorylation of Rab proteins. Here we introduce a sensitive and accurate assay to measure increased phospho Rab levels using synthetic stable isotope-labeled analogues for both phosphorylated and non-phosphorylated tryptic peptides surrounding Rab10-Thr73. Compared to healthy controls, carriers of mutated LRRK2 had 1.9-fold and those with VPS35 mutation 3.7-fold increased pRab10 levels in their neutrophils. Our generic MS-based assay helps to stratify PD patient and determine LRRK2 inhibitor efficiency in clinical trials. Pathogenic mutations in the Leucine-rich repeat kinase 2 (LRRK2) are the predominant genetic cause of Parkinson's disease (PD). They increase its activity, resulting in augmented Rab10-Thr73 phosphorylation and conversely, LRRK2 inhibition decreases pRab10 levels. Currently, there is no assay to quantify pRab10 levels for drug target engagement or patient stratification. To meet this challenge, we developed an high accuracy and sensitivity targeted mass spectrometry (MS)-based assay for determining Rab10-Thr73 phosphorylation stoichiometry in human samples. It uses synthetic stable isotope-labeled (SIL) analogues for both phosphorylated and nonphosphorylated tryptic peptides surrounding Rab10-Thr73 to directly derive the percentage of Rab10 phosphorylation from attomole amounts of the endogenous phosphopeptide. The SIL and the endogenous phosphopeptides are separately admitted into an Orbitrap analyzer with the appropriate injection times. We test the reproducibility of our assay by determining Rab10-Thr73 phosphorylation stoichiometry in neutrophils of LRRK2 mutation carriers before and after LRRK2 inhibition. Compared with healthy controls, the PD predisposing mutation carriers LRRK2 G2019S and VPS35 D620N display 1.9-fold and 3.7-fold increased pRab10 levels, respectively. Our generic MS-based assay further establishes the relevance of pRab10 as a prognostic PD marker and is a powerful tool for determining LRRK2 inhibitor efficacy and for stratifying PD patients for LRRK2 inhibitor treatment.Acknowledgments: We thank Sabine Suppmann, Leopold Urich, Stephan Uebel, Stefan Pettera, Martin Spitaler, Nagarjuna Nagaraj, Victoria Sanchez and Antonio Piras from the MPIB Biochemistry Core Facility