45 results on '"Schwaiger, T"'
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2. Force balance in numerical geodynamo simulations: a systematic study
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Schwaiger, T., Gastine, T., and Aubert, J.
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Physics - Geophysics - Abstract
Dynamo action in the Earth's outer core is expected to be controlled by a balance between pressure, Coriolis, buoyancy and Lorentz forces, with marginal contributions from inertia and viscous forces. Current numerical simulations of the geodynamo, however, operate at much larger inertia and viscosity because of computational limitations. This casts some doubt on the physical relevance of these models. Our work aims at finding dynamo models in a moderate computational regime which reproduce the leading-order force balance of the Earth. By performing a systematic parameter space survey with Ekman numbers in the range $10^{-6} \leq E \leq 10^{-4}$, we study the variations of the force balance when changing the forcing (Rayleigh number, $Ra$) and the ratio between viscous and magnetic diffusivities (magnetic Prandtl number, $Pm$). For dipole-dominated dynamos, we observe that the force balance is structurally robust throughout the investigated parameter space, exhibiting a quasi-geostrophic (QG) balance (balance between Coriolis and pressure forces) at zeroth order, followed by a first-order MAC balance between the ageostrophic Coriolis, buoyancy and Lorentz forces. At second order this balance is disturbed by contributions from inertia and viscous forces. Dynamos with a different sequence of the forces, where inertia and/or viscosity replace the Lorentz force in the first-order force balance, can only be found close to the onset of dynamo action and in the multipolar regime. Our study illustrates that most classical numerical dynamos are controlled by a QG-MAC balance, while cases where viscosity and inertia play a dominant role are the exception rather than the norm.
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- 2019
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3. The role of self-disgust in non-suicidal self-injury among individuals with personality disorder
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Schwaiger, T. and Feigenbaum, J. F.
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616.85 - Abstract
AIMS: There is growing evidence of a strong association between self-disgust and non- suicidal self-injury (NSSI). The aim of the current study was to investigate the role of self-disgust, alongside possible overlapping affect-states (shame, anger), in predicting lifetime NSSI among individuals with Personality Disorder (PD) features. This research also aimed to examine the psychometric structure of an existing self-disgust scale in this sample. METHOD: A cross-sectional online survey was conducted incorporating self-report questionnaires to screen for PD and to assess self-disgust, anger, shame, sexual abuse, lifetime NSSI and functions of NSSI. One hundred and eighty-eight individuals who screened positive for PD were recruited as well as 133 subjects who screened negative for PD. RESULT: Logistic regression analysis highlighted self-disgust as the single independent predictor of lifetime NSSI. Multiple regression analyses identified self-disgust as a predictor of the ‘self-punishment’, ‘anti-suicide’ and ‘communicating distress’ functions of NSSI. A principal component analysis of the self-disgust scale suggested that physical self-disgust explained over 50% of the variance out of the overall variability in the sample that screened positive for PD. CONCLUSIONS: The findings suggest that self-disgust may be a significant risk factor for NSSI among individuals who screen positive for PD and indicate that self-disgust may specifically be connected with the impulse to attack and punish the self through self-injury. The effectiveness of interventions for NSSI among individuals with PD symptoms may be enhanced by examining whether self-disgust contributes to and/or maintains self-injurious behaviour. Treatment may also benefit from taking into consideration the strong visceral experiences related to self-disgust.
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- 2016
4. Wave-like motions and torques in Earth's core as inferred from geomagnetic data: A synthetic study
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Schwaiger, T., primary, Gillet, N., additional, Jault, D., additional, Istas, M., additional, and Mandea, M., additional
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- 2023
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5. Local estimation of quasi-geostrophic flows in Earth’s core
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Schwaiger, T, primary, Jault, D, additional, Gillet, N, additional, Schaeffer, N, additional, and Mandea, M, additional
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- 2023
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6. Length-of-day, geostrophic motions in the core, and the conductance of the mantle
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Gillet, N., Jault, D., Aubert, J., and Schwaiger, T.
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Numerical simulations of the geodynamo are used to investigate the transfer of angular momentum between the core and the mantle, in the presence of both an electro-magnetic torque and a gravitational torque between the inner core and the mantle. Over a broad range of periods, angular momentum changes are accurately explained when deriving geostrophic motions (organized as cylinders co-axial with the Earth’s rotation vector) from core surface motions. Inverted core surface flows can thus be used to infer the core angular momentum budget. In the dynamo, the largest part of the EM torque variations is associated with the evolution of the solid body rotation, with little contribution from electrical currents originating deep inside the core (the "leakage torque”, formerly associated with the westward drift of the geomagnetic field). A 1D model of geostrophic motions is furthermore used to estimate the efficiency of torsional eigenmodes to couple with the solid Earth. From this we revisit the estimate of the mantle conductance from 1D simulations of geostrophic motions stochastically forced in the volume. We then discuss the ability of torsional waves to trigger the interannual oscillations observed in the length-of-day series, and the relative importance of forcing versus resonances in angular momentum changes at various time-scales., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)
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- 2023
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7. Satellite geomagnetic data reveal interannual magneto-Coriolis waves inside Earth’s core
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Gillet, N., Gerick, F., Jault, D., Schwaiger, T., Istas, M., and Aubert, J.
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We now benefit of more than two decades of global geomagnetic surveys from low-Earth orbiting satellites. They have revealed repeated interannual changes, more intense towards the equator. In order to reconstruct the dynamics at the surface of the core, these observational constraints are introduced in the “pygeodyn” data assimilation tool. This algorithm incorporates spatio-temporal constraints derived from geodynamo numerical simulations approaching Earth’s conditions. We discovered recurrent non-axisymmetric flow patterns presenting a period of about 7 yr. They propagate equatorward throughout the fluid core, and present their strongest amplitude (~3 km/yr) at the equator, where they show a coherent westward drift at phase speeds of about 1,500 km/yr. We interpret and model these flows as the signature of Magneto-Coriolis waves. Using synthetic data from dynamo simulations, we show that the recovery of such transient motions depends mostly on the data coverage and on their magnitude. The identification of Magneto-Coriolis waves offers a way to probe the cylindrical radial component of the dynamo field inside Earth’s core, and possibly to sample lateral variations in the electrical conductivity of the lower mantle. It follows from our work that there is no need for a stratified layer at the top of the core to account for these geomagnetic field changes. Such waves most likely also exist on longer time-scales, calling for long-lived magnetic records from space., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)
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- 2023
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8. P09.15 Patient-derived head and neck tumor slice cultures – a versatile tool to study oncolytic virus action
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Mayr, M, primary, Runge, A, additional, Schwaiger, T, additional, Sprung, S, additional, Chetta, P, additional, Gottfried, T, additional, Dudas, J, additional, Greier, M, additional, Glatz, M, additional, Haybaeck, J, additional, Elbers, K, additional, Riechelmann, H, additional, Erlmann, P, additional, and Petersson, M, additional
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- 2022
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9. Simplifying sampling for African swine fever surveillance: Assessment of antibody and pathogen detection from blood swabs
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Carlson, J., Zani, L., Schwaiger, T., Nurmoja, I., Viltrop, A., Vilem, A., Beer, M., and Blome, S.
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- 2018
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10. Relating force balances and flow length scales in geodynamo simulations
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Schwaiger, T, primary, Gastine, T, additional, and Aubert, J, additional
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- 2020
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11. Force balance in numerical geodynamo simulations: a systematic study
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Schwaiger, T, primary, Gastine, T, additional, and Aubert, J, additional
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- 2019
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12. Relating force balances and flow length scales in geodynamo simulations.
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Schwaiger, T, Gastine, T, and Aubert, J
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FLUID dynamics , *AXIAL flow , *LORENTZ force , *KINETIC energy , *ELECTRIC generators , *CORIOLIS force , *FORCED convection , *DYNAMO theory (Physics) - Abstract
In fluid dynamics, the scaling behaviour of flow length scales is commonly used to infer the governing force balance of a system. The key to a successful approach is to measure length scales that are simultaneously representative of the energy contained in the solution (energetically relevant) and also indicative of the established force balance (dynamically relevant). In the case of numerical simulations of rotating convection and magnetohydrodynamic dynamos in spherical shells, it has remained difficult to measure length scales that are both energetically and dynamically relevant, a situation that has led to conflicting interpretations, and sometimes misrepresentations of the underlying force balance. By analysing an extensive set of magnetic and non-magnetic models, we focus on two length scales that achieve both energetic and dynamical relevance. The first one is the peak of the poloidal kinetic energy spectrum, which we successfully compare to crossover points on spectral representations of the force balance. In most dynamo models, this result confirms that the dominant length scale of the system is controlled by a previously proposed quasi-geostrophic (QG-) MAC (Magneto-Archimedean-Coriolis) balance. In non-magnetic convection models, the analysis generally favours a QG-CIA (Coriolis-Inertia-Archimedean) balance. Viscosity, which is typically a minor contributor to the force balance, does not control the dominant length scale at high convective supercriticalities in the non-magnetic case, and in the dynamo case, once the generated magnetic energy largely exceeds the kinetic energy. In dynamo models, we introduce a second energetically relevant length scale associated with the loss of axial invariance in the flow. We again relate this length scale to another crossover point in scale-dependent force balance diagrams, which marks the transition between large-scale geostrophy (the equilibrium of Coriolis and pressure forces) and small-scale magnetostrophy, where the Lorentz force overtakes the Coriolis force. Scaling analysis of these two energetically and dynamically relevant length scales suggests that the Earth's dynamo is controlled by a QG-MAC balance at a dominant scale of about |$200 \, \mathrm{km}$| , while magnetostrophic effects are deferred to scales smaller than |$50 \, \mathrm{km}$|. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Simplifying sampling for African swine fever surveillance: Assessment of antibody and pathogen detection from blood swabs
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Carlson, J., primary, Zani, L., additional, Schwaiger, T., additional, Nurmoja, I., additional, Viltrop, A., additional, Vilem, A., additional, Beer, M., additional, and Blome, S., additional
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- 2017
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14. Cathepsin D expression in pancreatic ductal adenocarcinoma (PDAC) cells increases proliferation and reduces survival of pancreatic cancer patients
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Mahajan, U, primary, Langhoff, E, additional, Costello, E, additional, Greenhalf, W, additional, Halloran, C, additional, Schwaiger, T, additional, Beyer, G, additional, Weiss, F, additional, Neoptolemos, J, additional, Kohlmann, T, additional, Maron, M, additional, Büchler, M, additional, Lerch, M, additional, and Mayerle, J, additional
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- 2015
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15. Cathepsin B and D drive the fibrogenic potential of pancreatic stellate cells and modulate the stromal compartment in pancreatic ductal adenocarcinoma (PDAC)
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Mahajan, UM, primary, Schwaiger, T, additional, Weiss, FU, additional, Löhr, M, additional, Halangk, W, additional, Lerch, MM, additional, and Mayerle, J, additional
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- 2014
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16. The duration of time that beef cattle are fed a high-grain diet affects feed sorting behavior both before and after acute ruminal acidosis1,2
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DeVries, T. J., primary, Schwaiger, T., additional, Beauchemin, K. A., additional, and Penner, G. B., additional
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- 2014
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17. Impact of severity of ruminal acidosis on feed-sorting behaviour of beef cattle
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DeVries, T. J., primary, Schwaiger, T., additional, Beauchemin, K. A., additional, and Penner, G. B., additional
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- 2014
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18. Duration of time that beef cattle are fed a high-grain diet affects the recovery from a bout of ruminal acidosis: Short-chain fatty acid and lactate absorption, saliva production, and blood metabolites1
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Schwaiger, T., primary, Beauchemin, K. A., additional, and Penner, G. B., additional
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- 2013
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19. The duration of time that beef cattle are fed a high-grain diet affects the recovery from a bout of ruminal acidosis: Dry matter intake and ruminal fermentation1
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Schwaiger, T., primary, Beauchemin, K. A., additional, and Penner, G. B., additional
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- 2013
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20. In vivo imaging and targeted siRNA delivery using superparamagnetic nanoparticles (MNPs) in pancreatic ductal adenocarcinoma
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Mahajan, UM, primary, Teller, S, additional, Sendler, M, additional, Schwaiger, T, additional, Partecke, LI, additional, Gloeckl, G, additional, Aurich, K, additional, Hadlich, S, additional, Weiß, FU, additional, Kühn, JP, additional, Lerch, MM, additional, and Mayerle, J, additional
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- 2013
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21. Changes in the Rumen Epimural Bacterial Diversity of Beef Cattle as Affected by Diet and Induced Ruminal Acidosis
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Petri, R. M., primary, Schwaiger, T., additional, Penner, G. B., additional, Beauchemin, K. A., additional, Forster, R. J., additional, McKinnon, J. J., additional, and McAllister, T. A., additional
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- 2013
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22. Blockage of CTLA-4 suggests that autoimmune pancreatitis is a T-cell mediated disease responsive to ciclosporin A and rapamycin treatment
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Mayerle, J., primary, van den Brandt, C., additional, Schwaiger, T., additional, Kraatz, F., additional, Zaatreh, S., additional, Emmrich, J., additional, Fitzner, B., additional, Dummer, A., additional, Nizze, H., additional, Evert, M., additional, Salem, T., additional, Lerch, M.M., additional, and Jaster, R., additional
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- 2012
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23. The Reflective Fostering Programme-Adapting a group parenting programme for online delivery in response to the COVID-19 pandemic in the United Kingdom.
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Redfern S, Pursch B, Katangwe-Chigamba T, Sopp R, Irvine K, Sprecher EA, Schwaiger T, and Midgley N
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Objective: In the context of the Covid-19 pandemic and subsequent lockdown restrictions, service providers faced significant challenges in delivering programmes to support their vulnerable service users. Foster carers-an already often isolated group of caregivers - were offered an adapted remote-delivery model of the Reflective Fostering Programme (Redfern et al., Adopt. Foster., 42, 2018, 234) from March 2020., Method: This paper outlines the adaptation process of the original programme to online-remote delivery and describes the feedback from participants in the programme., Results: The adaptation of the Reflective Fostering programme to online, remote delivery had both strengths and weaknesses - including wider access to foster carers who might struggle to attend in person and challenge a to maintaining a Mentalizing space online and ensuring confidentiality within a therapeutic space. The programme was overwhelmingly well received by foster carers in this format., Conclusions: There are opportunities and challenges in the delivery of online therapeutic services, particularly those with a group format. This paper contributes initial reflections to what we hope will be a rapidly developing literature on best practice of supporting group services in an online format., (© 2023 The British Psychological Society.)
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- 2023
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24. Archaeome structure and function of the intestinal tract in healthy and H1N1 infected swine.
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Meene A, Gierse L, Schwaiger T, Karte C, Schröder C, Höper D, Wang H, Groß V, Wünsche C, Mücke P, Kreikemeyer B, Beer M, Becher D, Mettenleiter TC, Riedel K, and Urich T
- Abstract
Background: Methanogenic archaea represent a less investigated and likely underestimated part of the intestinal tract microbiome in swine., Aims/methods: This study aims to elucidate the archaeome structure and function in the porcine intestinal tract of healthy and H1N1 infected swine. We performed multi-omics analysis consisting of 16S rRNA gene profiling, metatranscriptomics and metaproteomics., Results and Discussion: We observed a significant increase from 0.48 to 4.50% of archaea in the intestinal tract microbiome along the ileum and colon, dominated by genera Methanobrevibacter and Methanosphaera . Furthermore, in feces of naïve and H1N1 infected swine, we observed significant but minor differences in the occurrence of archaeal phylotypes over the course of an infection experiment. Metatranscriptomic analysis of archaeal mRNAs revealed the major methanogenesis pathways of Methanobrevibacter and Methanosphaera to be hydrogenotrophic and methyl-reducing, respectively. Metaproteomics of archaeal peptides indicated some effects of the H1N1 infection on central metabolism of the gut archaea., Conclusions/take Home Message: Finally, this study provides the first multi-omics analysis and high-resolution insights into the structure and function of the porcine intestinal tract archaeome during a non-lethal Influenza A virus infection of the respiratory tract, demonstrating significant alterations in archaeal community composition and central metabolic functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meene, Gierse, Schwaiger, Karte, Schröder, Höper, Wang, Groß, Wünsche, Mücke, Kreikemeyer, Beer, Becher, Mettenleiter, Riedel and Urich.)
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- 2023
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25. Application of a maximal-clique based community detection algorithm to gut microbiome data reveals driver microbes during influenza A virus infection.
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Bhar A, Gierse LC, Meene A, Wang H, Karte C, Schwaiger T, Schröder C, Mettenleiter TC, Urich T, Riedel K, and Kaderali L
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Influenza A Virus (IAV) infection followed by bacterial pneumonia often leads to hospitalization and death in individuals from high risk groups. Following infection, IAV triggers the process of viral RNA replication which in turn disrupts healthy gut microbial community, while the gut microbiota plays an instrumental role in protecting the host by evolving colonization resistance. Although the underlying mechanisms of IAV infection have been unraveled, the underlying complex mechanisms evolved by gut microbiota in order to induce host immune response following IAV infection remain evasive. In this work, we developed a novel Maximal-Clique based Community Detection algorithm for Weighted undirected Networks (MCCD-WN) and compared its performance with other existing algorithms using three sets of benchmark networks. Moreover, we applied our algorithm to gut microbiome data derived from fecal samples of both healthy and IAV-infected pigs over a sequence of time-points. The results we obtained from the real-life IAV dataset unveil the role of the microbial families Ruminococcaceae, Lachnospiraceae, Spirochaetaceae and Prevotellaceae in the gut microbiome of the IAV-infected cohort. Furthermore, the additional integration of metaproteomic data enabled not only the identification of microbial biomarkers, but also the elucidation of their functional roles in protecting the host following IAV infection. Our network analysis reveals a fast recovery of the infected cohort after the second IAV infection and provides insights into crucial roles of Desulfovibrionaceae and Lactobacillaceae families in combating Influenza A Virus infection. Source code of the community detection algorithm can be downloaded from https://github.com/AniBhar84/MCCD-WN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhar, Gierse, Meene, Wang, Karte, Schwaiger, Schröder, Mettenleiter, Urich, Riedel and Kaderali.)
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- 2022
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26. Patient-derived head and neck tumor slice cultures: a versatile tool to study oncolytic virus action.
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Runge A, Mayr M, Schwaiger T, Sprung S, Chetta P, Gottfried T, Dudas J, Greier MC, Glatz MC, Haybaeck J, Elbers K, Riechelmann H, Erlmann P, and Petersson M
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- Animals, Ecosystem, Humans, Immunotherapy, Mice, Squamous Cell Carcinoma of Head and Neck therapy, Head and Neck Neoplasms therapy, Oncolytic Viruses physiology
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Head and neck cancer etiology and architecture is quite diverse and complex, impeding the prediction whether a patient could respond to a particular cancer immunotherapy or combination treatment. A concomitantly arising caveat is obviously the translation from pre-clinical, cell based in vitro systems as well as syngeneic murine tumor models towards the heterogeneous architecture of the human tumor ecosystems. To bridge this gap, we have established and employed a patient-derived HNSCC (head and neck squamous cell carcinoma) slice culturing system to assess immunomodulatory effects as well as permissivity and oncolytic virus (OV) action. The heterogeneous contexture of the human tumor ecosystem including tumor cells, cancer-associated fibroblasts and immune cells was preserved in our HNSCC slice culturing approach. Importantly, the immune cell compartment remained to be functional and cytotoxic T-cells could be activated by immunostimulatory antibodies. In addition, we uncovered that a high proportion of the patient-derived HNSCC slice cultures were susceptible to the OV VSV-GP. More specifically, VSV-GP infects a broad spectrum of tumor-associated lineages including epithelial and stromal cells and can induce apoptosis. In sum, this human tumor ex vivo platform might complement pre-clinical studies to eventually propel cancer immune-related drug discovery and ease the translation to the clinics., (© 2022. The Author(s).)
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- 2022
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27. Clinical, neuropathological, and immunological short- and long-term feature of a mouse model mimicking human herpes virus encephalitis.
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Sehl-Ewert J, Schwaiger T, Schäfer A, Hölper JE, Klupp BG, Teifke JP, Blohm U, and Mettenleiter TC
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- Animals, Central Nervous System pathology, Cytokines, Disease Models, Animal, Female, Humans, Mice, Neuropathology, Encephalitis, Herpes Simplex diagnosis, Encephalitis, Herpes Simplex pathology, Meningoencephalitis
- Abstract
Herpes simplex encephalitis (HSE) is one of the most serious diseases of the nervous system in humans. However, its pathogenesis is still only poorly understood. Although several mouse models of predominantly herpes simplex virus 1 (HSV-1) infections mimic different crucial aspects of HSE, central questions remain unanswered. They comprise the specific temporofrontal tropism, viral spread within the central nervous system (CNS), as well as potential molecular and immunological barriers that drive virus into latency while only rarely resulting in severe HSE. We have recently proposed an alternative mouse model by using a pseudorabies virus (PrV) mutant that more faithfully represents the striking features of human HSE: temporofrontal meningoencephalitis with few severely, but generally only moderately to subclinically affected mice as well as characteristic behavioral abnormalities. Here, we characterized this animal model using 6- to 8-week-old female CD-1 mice in more detail. Long-term investigation over 6 months consistently revealed a biphasic course of infection accompanied by recurring clinical signs including behavioral alterations and mainly mild meningoencephalitis restricted to the temporal and frontal lobes. By histopathological and immunological analyses, we followed the kinetics and spatial distribution of inflammatory lesions as well as the underlying cytokine expression in the CNS over 21 days within the acute phase of infection. Affecting the temporal lobes, the inflammatory infiltrate was composed of lymphocytes and macrophages showing a predominantly lymphocytic shift 15 days after infection. A strong increase was observed in cytokines CXCL10, CCL2, CCL5, and CXCL1 recruiting inflammatory cells to the CNS. Unlike the majority of infected mice, strongly affected animals demonstrated extensive temporal lobe edema, which is typically present in severe human HSE cases. In summary, these results support the validity of our animal model for in-depth investigation of HSE pathogenesis., (© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
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- 2022
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28. Satellite magnetic data reveal interannual waves in Earth's core.
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Gillet N, Gerick F, Jault D, Schwaiger T, Aubert J, and Istas M
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SignificanceThe physics responsible for most of the interannual geomagnetic field changes, continually recorded by satellites for 20 years, is a long-standing open issue. By analyzing magnetic data, we detect Magneto-Coriolis waves in the Earth's outer core that account for a significant part of this signal. We further propose theoretical advances in the physical characterization of these waves, enabling a deeper understanding of the dynamics behind the geomagnetic signal. It should allow one to better sketch the heterogeneous magnetic field deep within the core, shedding further light on the mechanisms that sustain the geodynamo. Our interpretation does not require the presence of a stratified layer at the top of the core, with potent consequences regarding the Earth's thermal history.
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- 2022
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29. Influenza A H1N1 Induced Disturbance of the Respiratory and Fecal Microbiome of German Landrace Pigs - a Multi-Omics Characterization.
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Gierse LC, Meene A, Schultz D, Schwaiger T, Schröder C, Mücke P, Zühlke D, Hinzke T, Wang H, Methling K, Kreikemeyer B, Bernhardt J, Becher D, Mettenleiter TC, Lalk M, Urich T, and Riedel K
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- Animals, Bacteria genetics, Disease Models, Animal, Fatty Acids, Volatile biosynthesis, Feces microbiology, Female, Gene Expression Profiling, Influenza A Virus, H1N1 Subtype pathogenicity, Male, Proteomics, RNA, Ribosomal, 16S genetics, Swine, Bacteria classification, Bacteria isolation & purification, Gastrointestinal Microbiome physiology, Orthomyxoviridae Infections pathology, Respiratory System microbiology
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Seasonal influenza outbreaks represent a large burden for the health care system as well as the economy. While the role of the microbiome has been elucidated in the context of various diseases, the impact of respiratory viral infections on the human microbiome is largely unknown. In this study, swine was used as an animal model to characterize the temporal dynamics of the respiratory and gastrointestinal microbiome in response to an influenza A virus (IAV) infection. A multi-omics approach was applied on fecal samples to identify alterations in microbiome composition and function during IAV infection. We observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, increased abundances of Prevotellaceae were detected, while Clostridiaceae and Lachnospiraceae decreased. Moreover, our metaproteomics data indicated that the functional composition of the microbiome was heavily affected by the influenza infection. For instance, we identified decreased amounts of flagellin, correlating with reduced abundances of Lachnospiraceae and Clostridiaceae , possibly indicating involvement of a direct immune response toward flagellated Clostridia during IAV infection. Furthermore, enzymes involved in short-chain fatty acid (SCFA) synthesis were identified in higher abundances, while metabolome analyses revealed rather stable concentrations of SCFAs. In addition, 16S rRNA gene sequencing was used to characterize effects on the composition and natural development of the upper respiratory tract microbiome. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae in the upper respiratory tract. Surprisingly, temporal development of the respiratory microbiome structure was not affected. IMPORTANCE Here, we used swine as a biomedical model to elucidate the impact of influenza A H1N1 infection on structure and function of the respiratory and gastrointestinal tract microbiome by employing a multi-omics analytical approach. To our knowledge, this is the first study to investigate the temporal development of the porcine microbiome and to provide insights into the functional capacity of the gastrointestinal microbiome during influenza A virus infection.
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- 2021
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30. A Multi-Omics Protocol for Swine Feces to Elucidate Longitudinal Dynamics in Microbiome Structure and Function.
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Gierse LC, Meene A, Schultz D, Schwaiger T, Karte C, Schröder C, Wang H, Wünsche C, Methling K, Kreikemeyer B, Fuchs S, Bernhardt J, Becher D, Lalk M, KoInfekt Study Group, Urich T, and Riedel K
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Swine are regarded as promising biomedical models, but the dynamics of their gastrointestinal microbiome have been much less investigated than that of humans or mice. The aim of this study was to establish an integrated multi-omics protocol to investigate the fecal microbiome of healthy swine. To this end, a preparation and analysis protocol including integrated sample preparation for meta-omics analyses of deep-frozen feces was developed. Subsequent data integration linked microbiome composition with function, and metabolic activity with protein inventories, i.e., 16S rRNA data and expressed proteins, and identified proteins with corresponding metabolites. 16S rRNA gene amplicon and metaproteomics analyses revealed a fecal microbiome dominated by Prevotellaceae, Lactobacillaceae , Lachnospiraceae , Ruminococcaceae and Clostridiaceae. Similar microbiome compositions in feces and colon, but not ileum samples, were observed, showing that feces can serve as minimal-invasive proxy for porcine colon microbiomes. Longitudinal dynamics in composition, e.g., temporal decreased abundance of Lactobacillaceae and Streptococcaceae during the experiment, were not reflected in microbiome function. Instead, metaproteomics and metabolomics showed a rather stable functional state, as evident from short-chain fatty acids (SCFA) profiles and associated metaproteome functions, pointing towards functional redundancy among microbiome constituents. In conclusion, our pipeline generates congruent data from different omics approaches on the taxonomy and functionality of the intestinal microbiome of swine., Competing Interests: The authors declare no conflict of interest.
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- 2020
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31. Impaired T-cell responses in domestic pigs and wild boar upon infection with a highly virulent African swine fever virus strain.
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Hühr J, Schäfer A, Schwaiger T, Zani L, Sehl J, Mettenleiter TC, Blome S, and Blohm U
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- Animals, Female, Male, Sus scrofa, Swine, Virulence, African Swine Fever immunology, African Swine Fever Virus pathogenicity, African Swine Fever Virus physiology, T-Lymphocytes immunology
- Abstract
Since African swine fever (ASF) first appeared in the Caucasus region in 2007, it has spread rapidly and is now present in numerous European and Asian countries. In Europe, mainly wild boar populations are affected and pose a risk for domestic pigs. In Asia, domestic pigs are almost exclusively affected. An effective and safe vaccine is not available, and correlates of protection are far from being understood. Therefore, research on immune responses, immune dysfunction and pathogenesis is mandatory. It is acknowledged that T cells play a pivotal role. Thus, we investigated T-cell responses of domestic pigs and wild boar upon infection with the highly virulent ASF virus (ASFV) strain 'Armenia08'. For this purpose, we used a flow cytometry-based multicolour analysis to identify T-cell subtypes (cytotoxic T cells, T-helper cells, γδ T cells) and their functional impairment in ASFV-infected pigs. Domestic pigs showed lymphopaenia, and neither in the blood nor in the lymphoid organs was a proliferation of CD8
+ effector cells observed. Furthermore, a T-bet-dependent activation of the remaining CD8 T cells did not occur. In contrast, a T-cell response could be observed in wild boar at 5 days post-inoculation in the blood and in tendency also in some organs. However, this cytotoxic response was not beneficial as all wild boars showed a severe acute lethal disease and a higher proportion died spontaneously or was euthanized at the humane endpoint., (© 2020 The Authors. Transboundary and Emerging Diseases published by Blackwell Verlag GmbH.)- Published
- 2020
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32. Janus-faced course of COVID-19 infection in patients with hematological malignancies.
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Bellmann-Weiler R, Burkert F, Schwaiger T, Schmidt S, Ludescher C, Oexle H, Wolf D, and Weiss G
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, COVID-19 immunology, Colonic Neoplasms, Comorbidity, Cytokine Release Syndrome etiology, Cytokine Release Syndrome prevention & control, Humans, Hypoxia therapy, Immunocompromised Host, Leukemia, Hairy Cell drug therapy, Leukemia, Hairy Cell immunology, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute immunology, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell immunology, Lymphoma, Follicular drug therapy, Lymphoma, Follicular immunology, Male, Neoplasms, Second Primary complications, Oxygen Inhalation Therapy, Pandemics, Recurrence, Respiration, Artificial, SARS-CoV-2, COVID-19 complications, Hypoxia etiology, Immunosuppression Therapy, Leukemia, Hairy Cell complications, Leukemia, Myeloid, Acute complications, Lymphoma, B-Cell complications, Lymphoma, Follicular complications
- Published
- 2020
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33. Henipavirus-like particles induce a CD8 T cell response in C57BL/6 mice.
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Stroh E, Fischer K, Schwaiger T, Sauerhering L, Franzke K, Maisner A, Groschup MH, Blohm U, and Diederich S
- Subjects
- Animals, Antibodies, Neutralizing, Chlorocebus aethiops, Cytokines, Gene Expression Regulation immunology, HEK293 Cells, Humans, Interferon-gamma genetics, Interferon-gamma metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Plasmids, Spleen cytology, Th1 Cells, Th2 Cells, Vero Cells, Viral Proteins genetics, Antigens, Viral immunology, CD8-Positive T-Lymphocytes physiology, Cell Proliferation physiology, Henipavirus immunology, Viral Proteins immunology
- Abstract
Nipah virus (NiV), a BSL-4 pathogen, belongs to the genus Henipavirus within the family Paramyxoviridae. To date, no effective vaccine is available. Although most of the current vaccine studies aim to induce a neutralizing antibody response, it has become evident that a promising vaccine should target both, humoral and cell-mediated immune response. Virus-like particles (VLPs) have been shown to activate both arms of the adaptive immune response. In our study, VLPs composed of the NiV surface glycoproteins G and F and the matrix protein of the closely related Hendra virus (HeV M) induced both, a neutralizing antibody response and an antigen-specific CD8 T cell response with proliferation, IFN-γ expression and Th1 cytokine secretion in C57BL/6 mice. In contrast, in BALB/c mice only a neutralizing antibody response was observed. All three viral proteins included in the VLPs were shown to harbor CD8 T cell epitopes; however, the combination of all three proteins enhanced the magnitude of the CD8 T cell response. To conclude, VLPs represent a promising vaccine candidate, as they induce humoral as well as CD8 T cell-mediated immune responses., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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34. Experimental H1N1pdm09 infection in pigs mimics human seasonal influenza infections.
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Schwaiger T, Sehl J, Karte C, Schäfer A, Hühr J, Mettenleiter TC, Schröder C, Köllner B, Ulrich R, and Blohm U
- Subjects
- Animals, Disease Models, Animal, Humans, Influenza A Virus, H1N1 Subtype physiology, Influenza, Human virology, Lung immunology, Lung virology, Orthomyxoviridae Infections veterinary, Orthomyxoviridae Infections virology, Swine, Swine Diseases virology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic virology, Influenza A Virus, H1N1 Subtype immunology, Influenza, Human immunology, Orthomyxoviridae Infections immunology, Seasons, Swine Diseases immunology
- Abstract
Pigs are anatomically, genetically and physiologically comparable to humans and represent a natural host for influenza A virus (IAV) infections. Thus, pigs may represent a relevant biomedical model for human IAV infections. We set out to investigate the systemic as well as the local immune response in pigs upon two subsequent intranasal infections with IAV H1N1pdm09. We detected decreasing numbers of peripheral blood lymphocytes after the first infection. The simultaneous increase in the frequencies of proliferating cells correlated with an increase in infiltrating leukocytes in the lung. Enhanced perforin expression in αβ and γδ T cells in the respiratory tract indicated a cytotoxic T cell response restricted to the route of virus entry such as the nose, the lung and the bronchoalveolar lavage. Simultaneously, increasing frequencies of CD8αα expressing αβ T cells were observed rapidly after the first infection, which may have inhibited uncontrolled inflammation in the respiratory tract. Taking together, the results of this study demonstrate that experimental IAV infection in pigs mimics major characteristics of human seasonal IAV infections., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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35. Porcine Invariant Natural Killer T Cells: Functional Profiling and Dynamics in Steady State and Viral Infections.
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Schäfer A, Hühr J, Schwaiger T, Dorhoi A, Mettenleiter TC, Blome S, Schröder C, and Blohm U
- Subjects
- Animals, Animals, Newborn, Antigens, CD metabolism, Antigens, CD1d metabolism, Cell Differentiation immunology, Cell Proliferation, Cells, Cultured, Flow Cytometry methods, Galactosylceramides immunology, Humans, Immunophenotyping, Interferon-gamma immunology, Interferon-gamma metabolism, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Models, Animal, Natural Killer T-Cells metabolism, Promyelocytic Leukemia Zinc Finger Protein immunology, Promyelocytic Leukemia Zinc Finger Protein metabolism, Swine, Virus Diseases metabolism, Virus Diseases virology, Antigens, CD immunology, Antigens, CD1d immunology, Natural Killer T-Cells immunology, Virus Diseases immunology
- Abstract
Pigs are important livestock and comprehensive understanding of their immune responses in infections is critical to improve vaccines and therapies. Moreover, similarities between human and swine physiology suggest that pigs are a superior animal model for immunological studies. However, paucity of experimental tools for a systematic analysis of the immune responses in pigs represent a major disadvantage. To evaluate the pig as a biomedical model and additionally expand the knowledge of rare immune cell populations in swine, we established a multicolor flow cytometry analysis platform of surface marker expression and cellular responses for porcine invariant Natural Killer T cells (iNKT). In humans, iNKT cells are among the first line defenders in various tissues, respond to CD1d-restricted antigens and become rapidly activated. Naïve porcine iNKT cells were CD3
+ /CD4- /CD8+ or CD3+ /CD4- /CD8- and displayed an effector- or memory-like phenotype (CD25+ /ICOS+ /CD5hi /CD45RA- /CCR7± /CD27+ ). Based on their expression of the transcription factors T bet and the iNKT cell-specific promyelocytic leukemia zinc finger protein (PLZF), porcine iNKT cells were differentiated into functional subsets. Analogous to human iNKT cells, in vitro stimulation of porcine leukocytes with the CD1d ligand α-galactosylceramide resulted in rapid iNKT cell proliferation, evidenced by an increase in frequency and Ki-67 expression. Moreover, this approach revealed CD25, CD5, ICOS, and the major histocompatibility complex class II (MHC II) as activation markers on porcine iNKT cells. Activated iNKT cells also expressed interferon-γ, upregulated perforin expression, and displayed degranulation. In steady state, iNKT cell frequency was highest in newborn piglets and decreased with age. Upon infection with two viruses of high relevance to swine and humans, iNKT cells expanded. Animals infected with African swine fever virus displayed an increase of iNKT cell frequency in peripheral blood, regional lymph nodes, and lungs. During Influenza A virus infection, iNKT cell percentage increased in blood, lung lymph nodes, and broncho-alveolar lavage. Our in-depth characterization of porcine iNKT cells contributes to a better understanding of porcine immune responses, thereby facilitating the design of innovative interventions against infectious diseases. Moreover, we provide new evidence that endorses the suitability of the pig as a biomedical model for iNKT cell research.- Published
- 2019
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36. Double-attenuated influenza virus elicits broad protection against challenge viruses with different serotypes in swine.
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Mamerow S, Scheffter R, Röhrs S, Stech O, Blohm U, Schwaiger T, Schröder C, Ulrich R, Schinköthe J, Beer M, Mettenleiter TC, and Stech J
- Subjects
- Animals, Antibodies, Viral, Female, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza Vaccines administration & dosage, Mice, Mice, Inbred BALB C, Mutation, Orthomyxoviridae Infections prevention & control, Reverse Genetics, Serogroup, Swine, Swine Diseases immunology, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated immunology, Virus Shedding, Cross Protection, Influenza Vaccines immunology, Orthomyxoviridae Infections veterinary, Swine Diseases prevention & control
- Abstract
Influenza A viruses (IAV) have caused seasonal epidemics and severe pandemics in humans. Novel pandemic strains as in 2009 may emerge from pigs, serving as perpetual virus reservoir. However, reliably effective vaccination has remained a key issue for humans and swine. Here, we generated a novel double-attenuated influenza live vaccine by reverse genetics and subjected immunized mice and pigs to infection with the homologous wild-type, another homosubtypic H1N1, or a heterosubtypic H3N2 virus to address realistic challenge constellations. This attenuated mutant contains an artificial, strictly elastase-dependent hemagglutinin cleavage site and a C-terminally truncated NS1 protein from the IAV A/Bayern/74/2009 (H1N1
pdm09 ). Prior to challenge, we immunized mice once and pigs twice intranasally. In vitro, the double-attenuated mutant replicated strictly elastase-dependently. Immunized mice and pigs developed neither clinical symptoms nor detectable virus replication after homologous challenge. In pigs, we observed considerably reduced clinical signs and no nasal virus shedding after homosubtypic and reduced viral loads in respiratory tracts after heterosubtypic infection. Protection against homosubtypic challenge suggests that an optimized backbone strain may require less frequent updates with recent HA and NA genes and still induce robust protection in relevant IAV hosts against drifted viruses., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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37. VOC breath profile in spontaneously breathing awake swine during Influenza A infection.
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Traxler S, Bischoff AC, Saß R, Trefz P, Gierschner P, Brock B, Schwaiger T, Karte C, Blohm U, Schröder C, Miekisch W, and Schubert JK
- Subjects
- Animals, Equipment Design, Orthomyxoviridae Infections diagnosis, Respiration, Swine Diseases virology, Breath Tests instrumentation, Influenza A virus isolation & purification, Orthomyxoviridae Infections veterinary, Swine virology, Swine Diseases diagnosis, Volatile Organic Compounds analysis
- Abstract
Influenza is one of the most common causes of virus diseases worldwide. Virus detection requires determination of Influenza RNA in the upper respiratory tract. Efficient screening is not possible in this way. Analysis of volatile organic compounds (VOCs) in breath holds promise for non-invasive and fast monitoring of disease progression. Breath VOC profiles of 14 (3 controls and 11 infected animals) swine were repeatedly analyzed during a complete infection cycle of Influenza A under high safety conditions. Breath VOCs were pre-concentrated by means of needle trap micro-extraction and analysed by gas chromatography mass spectrometry before infection, during virus presence in the nasal cavity, and after recovery. Six VOCs could be related to disease progression: acetaldehyde, propanal, n-propyl acetate, methyl methacrylate, styrene and 1,1-dipropoxypropane. As early as on day four after inoculation, when animals were tested positive for Influenza A, differentiation between control and infected animals was possible. VOC based information on virus infection could enable early detection of Influenza A. As VOC analysis is completely non-invasive it has potential for large scale screening purposes. In a perspective, breath analysis may offer a novel tool for Influenza monitoring in human medicine, animal health control or border protection.
- Published
- 2018
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38. Protection against transplacental transmission of moderately virulent classical swine fever virus using live marker vaccine "CP7_E2alf".
- Author
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Henke J, Carlson J, Zani L, Leidenberger S, Schwaiger T, Schlottau K, Teifke JP, Schröder C, Beer M, and Blome S
- Subjects
- Animals, Antibodies, Viral blood, Blood virology, Classical Swine Fever pathology, Female, Injections, Intramuscular, Pregnancy, Pregnancy Complications, Infectious pathology, Swine, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated immunology, Vaccines, Marker administration & dosage, Vaccines, Marker immunology, Classical Swine Fever prevention & control, Classical Swine Fever Virus immunology, Infectious Disease Transmission, Vertical prevention & control, Pregnancy Complications, Infectious prevention & control, Viral Vaccines administration & dosage, Viral Vaccines immunology
- Abstract
Classical swine fever (CSF) remains as one of the most important infectious diseases of swine. While prophylactic vaccination is usually prohibited in free countries with industrialized pig production, emergency vaccination is still foreseen. In this context, marker vaccines are preferred as they can reduce the impact on trade. The live-attenuated Suvaxyn® CSF Marker vaccine by Zoetis (based on pestivirus chimera "CP7_E2alf"), was recently licensed by the European Medicines Agency. Its efficacy for the individual animal had been shown in prior studies, but questions remained regarding protection against transplacental transmission. To answer this question, a trial with eight pregnant sows and their offspring was performed as prescribed by the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Six of the sows were intramuscularly vaccinated on day 44 of gestation, while the other two remained as unvaccinated controls. All sows were challenged with the moderately virulent CSFV strain "Roesrath" and euthanized shortly before the calculated farrowing date. Sows and piglets were grossly examined and necropsied. Organs (spleen, tonsil, lymph node, and kidney), EDTA-blood and serum were collected from all animals. All samples were tested for antibodies against CSFV glycoproteins E2 and E
rns as well as CSFV (virus, antigen and genome). It could be demonstrated that the vaccine complies with all requirements, i.e. no virus was found in the blood of vaccinated sows and their fetuses, and no antibodies were found in the serum of the fetuses from the vaccinated sows. All controls were valid. Thus, it was demonstrated that a single dose vaccination in the sows efficiently protected the offspring against transplacental infection with a moderately virulent CSFV strain., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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39. Newcastle disease virus mediates pancreatic tumor rejection via NK cell activation and prevents cancer relapse by prompting adaptive immunity.
- Author
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Schwaiger T, Knittler MR, Grund C, Roemer-Oberdoerfer A, Kapp JF, Lerch MM, Mettenleiter TC, Mayerle J, and Blohm U
- Subjects
- Animals, Cell Line, Tumor, Humans, Killer Cells, Natural metabolism, Lymphocyte Activation, Mice, Oncolytic Virotherapy, Pancreatic Neoplasms pathology, T-Lymphocytes, Helper-Inducer metabolism, Xenograft Model Antitumor Assays, Adaptive Immunity, Neoplasm Recurrence, Local prevention & control, Newcastle disease virus immunology, Oncolytic Viruses immunology, Pancreatic Neoplasms immunology
- Abstract
Pancreatic cancer is the 8th most common cause of cancer-related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957, it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngeneic orthotopic tumor model using two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed. A single treatment with NDV inhibited DT6606PDA tumor growth in mice and prevented recurrence for a period of three months. Tumor infiltration and systemic activation of NK cells, cytotoxic and helper T-cells was enhanced. NDV-induced melting of Panc02 tumors until d7 pi, but they recurred displaying unrestricted tumor growth, low immunogenicity and inhibition of tumor-specific immune response. Arrest of DT6606PDA tumor growth and rejection was mediated by activation of NK cells and a specific antitumor immune response via T-cells. Panc02 tumors rapidly decreased until d7 pi, but henceforth tumors characterized by the ability to perform immune-regulatory functions reappeared. Our results demonstrated that NDV-activated immune cells are able to reject tumors provided that an adaptive antitumor immune response can be initiated. However, activated NK cells that are abundant in Panc02 tumors lead to outgrowth of nonimmunogenic tumor cells with inhibitory properties. Our study emphasizes the importance of an adaptive immune response, which is initiated by NDV to mediate long-term tumor surveillance in addition to direct oncolysis., (© 2017 UICC.)
- Published
- 2017
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40. Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer.
- Author
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Mahajan UM, Teller S, Sendler M, Palankar R, van den Brandt C, Schwaiger T, Kühn JP, Ribback S, Glöckl G, Evert M, Weitschies W, Hosten N, Dombrowski F, Delcea M, Weiss FU, Lerch MM, and Mayerle J
- Subjects
- Animals, Apoptosis drug effects, Cell Proliferation drug effects, Disease Models, Animal, Drug Delivery Systems methods, Drug Monitoring methods, Gene Silencing, Mice, Polo-Like Kinase 1, Antineoplastic Agents pharmacology, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal pathology, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Magnetite Nanoparticles therapeutic use, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, RNA, Small Interfering metabolism, RNA, Small Interfering pharmacology
- Abstract
Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is projected to be the second leading cause of cancer-related death by 2030. Despite extensive knowledge and insights into biological properties and genetic aberrations of PDAC, therapeutic options remain temporary and ineffective. One plausible explanation for the futile response to therapy is an insufficient and non-specific delivery of anticancer drugs to the tumour site., Design: Superparamagnetic iron oxide nanoparticles (SPIONs) coupled with siRNA directed against the cell cycle-specific serine-threonine-kinase, Polo-like kinase-1 (siPLK1-StAv-SPIONs), could serve a dual purpose for delivery of siPLK1 to the tumour and for non-invasive assessment of efficiency of delivery in vivo by imaging the tumour response. siPLK1-StAv-SPIONs were designed and synthesised as theranostics to function via a membrane translocation peptide with added advantage of driving endosomal escape for mediating transportation to the cytoplasm (myristoylated polyarginine peptides) as well as a tumour-selective peptide (EPPT1) to increase intracellular delivery and tumour specificity, respectively., Results: A syngeneic orthotopic as well as an endogenous cancer model was treated biweekly with siPLK1-StAv-SPIONs and tumour growth was monitored by small animal MRI. In vitro and in vivo experiments using a syngeneic orthotopic PDAC model as well as the endogenous LSL-Kras
G12D , LSL-Trp53R172H , Pdx-1-Cre model revealed significant accumulation of siPLK1-StAv-SPIONs in PDAC, resulting in efficient PLK1 silencing. Tumour-specific silencing of PLK1 halted tumour growth, marked by a decrease in tumour cell proliferation and an increase in apoptosis., Conclusions: Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)- Published
- 2016
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41. Effect of magnesium supplementation and depletion on the onset and course of acute experimental pancreatitis.
- Author
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Schick V, Scheiber JA, Mooren FC, Turi S, Ceyhan GO, Schnekenburger J, Sendler M, Schwaiger T, Omercevic A, Brandt Cv, Fluhr G, Domschke W, Krüger B, Mayerle J, and Lerch MM
- Subjects
- Acute Disease, Animals, Biomarkers metabolism, Calcium metabolism, Ceruletide, Disease Progression, Hydrolases metabolism, Magnesium metabolism, Male, Mice, Pancreatitis etiology, Pancreatitis immunology, Pancreatitis metabolism, Peptide Hydrolases metabolism, Rats, Rats, Wistar, Severity of Illness Index, Treatment Outcome, Dietary Supplements, Magnesium therapeutic use, Magnesium Deficiency complications, Pancreatitis prevention & control
- Abstract
Background and Objective: High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis., Methods: Pancreatic acini were incubated with up to 10 mM magnesium; [Ca(2+)](i) (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (<300 ppm to 30 000 ppm) over two weeks before pancreatitis induction (intravenous caerulein 10 µg/kg/h/4 h); controls received 1 µg/kg/h caerulein or saline. C57BL6/J mice received four intraperitoneal doses of magnesium (NaCl, Mg(2+) 55 192 or 384 mg/kg bodyweight) over 72 h, then pancreatitis was induced by up to eight hourly supramaximal caerulein applications. Pancreatic enzyme activities, protease activation, morphological changes and the immune response were investigated., Results: Increasing extracellular Mg(2+) concentration significantly reduced [Ca(2+)](i) peaks and frequency of [Ca(2+)](i) oscillations as well as intracellular trypsin and elastase activity. Magnesium administration reduced pancreatic enzyme activities, oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T-cells during experimental pancreatitis. Protease activation was found in animals fed magnesium-deficient chow-even with low caerulein concentrations that normally cause no damage., Conclusions: Magnesium supplementation significantly reduces premature protease activation and the severity of pancreatitis, and antagonises pathological [Ca(2+)](i) signals. Nutritional magnesium deficiency increases the susceptibility of the pancreas towards pathological stimuli. These data have prompted two clinical trials on the use of magnesium in patients at risk for pancreatitis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2014
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42. IgG4-related disease: a new kid on the block or an old aquaintance?
- Author
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Beyer G, Schwaiger T, Lerch MM, and Mayerle J
- Abstract
IgG4-related systemic disease is a recently recognized systemic condition characterized by unique pathological features that can affect a variety of organs. It includes a growing number of medical conditions which have the following features in common: diffuse organ swelling or focal mass formation, sclerosing storiforme (whirl-shaped) fibrosis with a lymphoplasmacytic infiltrate rich in IgG4-bearing plasma cells, as well as elevated levels of serum IgG4. It invariably responds to steroid treatment and is mostly diagnosed in elderly men. Well-known syndromes like Mikulicz's disease of the salivary or lacrimal gland, Küttner's tumour of the submandibular gland, Riedel's thyroiditis, or retroperitoneal fibrosis, as well as novel entities such as autoimmune pancreatitis type 1, are now regarded to be manifestations of this systemic disease. This article provides an overview of the epidemiology, concepts of pathogenesis, clinical presentation, proposed diagnostic approaches, treatment options, and differential diagnosis of IgG4-related disease.
- Published
- 2014
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43. Autoimmune pancreatitis in MRL/Mp mice is a T cell-mediated disease responsive to cyclosporine A and rapamycin treatment.
- Author
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Schwaiger T, van den Brandt C, Fitzner B, Zaatreh S, Kraatz F, Dummer A, Nizze H, Evert M, Bröker BM, Brunner-Weinzierl MC, Wartmann T, Salem T, Lerch MM, Jaster R, and Mayerle J
- Subjects
- Animals, Autoimmune Diseases chemically induced, Autoimmune Diseases immunology, Autoimmune Diseases pathology, Azathioprine therapeutic use, Biomarkers metabolism, CTLA-4 Antigen antagonists & inhibitors, Cell Proliferation drug effects, Cyclosporine pharmacology, Dexamethasone therapeutic use, Drug Administration Schedule, Female, Flow Cytometry, Immunosuppressive Agents pharmacology, Lymphocyte Activation drug effects, Mice, Mice, Inbred Strains, Pancreas drug effects, Pancreas pathology, Pancreatitis, Chronic chemically induced, Pancreatitis, Chronic immunology, Pancreatitis, Chronic pathology, Poly I-C, Random Allocation, Sirolimus pharmacology, T-Lymphocyte Subsets drug effects, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory metabolism, Treatment Outcome, Autoimmune Diseases drug therapy, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Pancreas immunology, Pancreatitis, Chronic drug therapy, Sirolimus therapeutic use, T-Lymphocyte Subsets metabolism
- Abstract
Background: Autoimmune pancreatitis (AIP) in humans invariably responds to steroid treatment, but little is known about the underlying pathogenesis and the benefits of alternative treatments., Objective: To study the pathogenesis, and the efficacy of alternative immunosuppressant agents in the MRL/Mp mouse model of AIP., Design: MRL/Mp mice were pretreated for 4 weeks with polyinosinic:polycytidylic acid to induce AIP. Pancreatic sections of mice genetically deleted for CTLA-4 were analysed. Blockage of CTLA-4 was achieved by intraperitoneal antibody treatment with 2 μg/g anti-mouse-CD152. Subsequent therapeutic studies were performed for a period of 4 weeks using cyclosporine A (40 μg/g), rapamycin (1 μg/g) or azathioprine (15 μg/g)., Results: Blockage of CTLA-4 in MRL/Mp mice suppressed regulatory T cell (Treg) function and raised the effector T cell (Teff) response with subsequent histomorphological organ destruction, indicating that AIP is a T cell-driven disease. Using an established histopathological score, we found that dexamethasone, cyclosporine A and rapamycin, but less so azathioprine, reduced pancreatic damage. However, the beneficial effects of cyclosporine A and rapamycin were achieved via different mechanisms: cyclosporine A inhibited Teff activation and proliferation whereas rapamycin led to selective expansion of Tregs which subsequently suppressed the Teff response., Conclusions: The calcineurin inhibitor cyclosporine A and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, improve the course of AIP in MRL/Mp mice via different mechanisms. These findings further support the concept of autoreactive T cells as key players in the pathogenesis of AIP and suggest that cyclosporine A and rapamycin should be considered for treatment of AIP in humans.
- Published
- 2014
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44. Characterization of the core rumen microbiome in cattle during transition from forage to concentrate as well as during and after an acidotic challenge.
- Author
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Petri RM, Schwaiger T, Penner GB, Beauchemin KA, Forster RJ, McKinnon JJ, and McAllister TA
- Subjects
- Acidosis microbiology, Acidosis veterinary, Animals, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Bacteroidetes genetics, Bacteroidetes isolation & purification, Cattle Diseases microbiology, Female, Fermentation, Genes, Bacterial, Genes, rRNA, Hydrogen-Ion Concentration, Phylogeny, Proteobacteria genetics, Proteobacteria isolation & purification, RNA, Bacterial genetics, RNA, Ribosomal, 16S genetics, Animal Feed adverse effects, Animal Feed analysis, Cattle microbiology, Microbiota genetics, Rumen microbiology
- Abstract
This study investigated the effect of diet and host on the rumen bacterial microbiome and the impact of an acidotic challenge on its composition. Using parallel pyrosequencing of the V3 hypervariable region of 16S rRNA gene, solid and liquid associated bacterial communities of 8 heifers were profiled. Heifers were exclusively fed forage, before being transitioned to a concentrate diet, subjected to an acidotic challenge and allowed to recover. Samples of rumen digesta were collected when heifers were fed forage, mixed forage, high grain, during challenge (4 h and 12 h) and recovery. A total of 560,994 high-quality bacterial sequences were obtained from the solid and liquid digesta. Using cluster analysis, prominent bacterial populations differed (P≤0.10) in solid and liquid fractions between forage and grain diets. Differences among hosts and diets were not revealed by DGGE, but real time qPCR showed that several bacteria taxon were impacted by changes in diet, with the exception of Streptococcus bovis. Analysis of the core rumen microbiome identified 32 OTU's representing 10 distinct bacterial taxa including Bacteroidetes (32.8%), Firmicutes (43.2%) and Proteobacteria (14.3%). Diversity of OTUs was highest with forage with 38 unique OTUs identified as compared to only 11 with the high grain diet. Comparison of the microbial profiles of clincial vs. subclinical acidotic heifers found a increases in the relative abundances of Acetitomaculum, Lactobacillus, Prevotella, and Streptococcus. Increases in Streptococcus and Lactobacillus likely reflect the tolerance of these species to low pH and their ability to proliferate on surplus fermentable carbohydrate. The acetogen, Acetitomaculum may thereforeplay a role in the conversion of lactate to acetate in acidotic animals. Further profiling of the bacterial populations associated with subclinical and clinical acidosis could establish a microbial fingerprint for these disorders and provide insight into whether there are causative microbial populations that could potentially be therapeutically manipulated.
- Published
- 2013
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45. The consequences of reversible gill remodelling on ammonia excretion in goldfish (Carassius auratus).
- Author
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Perry SF, Schwaiger T, Kumai Y, Tzaneva V, and Braun MH
- Subjects
- Acclimatization drug effects, Ammonium Chloride pharmacology, Animals, Blotting, Western, Fish Proteins metabolism, Fluorescent Antibody Technique, Gills cytology, Gills drug effects, Hypoxia metabolism, Injections, Intraperitoneal, Nutritional Status drug effects, Physical Conditioning, Animal, Sodium Chloride pharmacology, Temperature, Ammonia metabolism, Gills metabolism, Goldfish metabolism
- Abstract
Goldfish acclimated to cold water (e.g. 7°C) experience a marked reduction in functional lamellar surface area owing to the proliferation of an interlamellar cell mass (ILCM), a phenomenon termed gill remodelling. The goal of the present study was to assess the consequences of the reduced functional surface area on the capacity of goldfish to excrete ammonia. Despite the expected impact of ambient temperature on functional surface area, fish acclimated to 7°C and 25°C exhibited similar rates of ammonia excretion (J(net,amm)); the Q₁₀ values for fed and starved fish were 1.07 and 1.20, respectively. To control for possible temperature-related differences in rates of endogenous ammonia production, J(net,amm) was determined at the two acclimation temperatures after loading fish with 1.12 μmol g₋₁ of NH₄Cl. In the 3 h post-injection period, J(net,amm) was elevated to a greater extent in the 25°C fish. To estimate the potential contribution of increased ventilation and cardiac output to ammonia clearance in the warmer fish, the ammonia loading experiment was repeated on the 7°C fish immediately after they were exercised to exhaustion. The rate of excretion of ammonia was significantly increased in the exercised 7°C fish (presumably experiencing increased ventilation and cardiac output for at least some of the measurement period) suggesting that differences in external and internal convection may at least partially explain the enhanced capacity of the 25°C fish to clear the ammonia load. To more specifically assess the contribution of the different functional surface areas on the differing rates of ammonia clearance at the two acclimation temperatures, the 7°C fish were exposed for 7 days to hypoxia (P(O₂)=10 mmHg=1.33 kPa), a treatment known to cause the disappearance of the ILCM. The results demonstrated that the hypoxia-associated loss of the ILCM was accompanied by a significant increase in the rate of ammonia clearance in the 7°C fish when returned to normoxic conditions. To determine whether compensatory changes in the ammonia transporting proteins might be contributing to sustaining J(net,amm) under conditions of reduced functional lamellar surface area, the relative expression and branchial distribution of four Rh proteins were assessed by western blotting and immunocytochemistry. Although the relative expression of the Rh proteins was unaffected by acclimation temperature, there did appear to be a change in the spatial distribution of Rhag, Rhbg and Rhcg1. Specifically, these three Rh proteins (and to a lesser extent Rhcg2) appeared to localize in cells on the outer edge of the ILCM that were enriched with Na(+)/K(+)-ATPase. Thus, we suggest that despite the impediment to ammonia excretion imposed by the ILCM, goldfish acclimated to 7°C are able to sustain normal rates of excretion owing to the redistribution of ammonia transporting cells.
- Published
- 2010
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