Dr. Ulrike Ewe & TÄin Ines Kussmann. Dr. Mirja Fenske. Kleintiere. Osterrade 36a Hamburg Bezirk: Bergedorf Stadtteil: Lohbrügge. Tel: 10 40 Tierärztin Ines Kussmann staunt nicht schlecht, als sie plötzlich sechs Yorkshire-Terrier im Behandlungszimmer empfängt. Doch wer von der Rasselbande ist. Gutartig oder böse – das ist die alles entscheidende Frage. Die Tierärztinnen Dr. Melanie Langer und Ines Kussmann sollen den Patienten operieren. Bange.
Ines Kussmann Gemeinschaftspraxis "Die Tierärzte am Grandweg 68 GmbH"
Als neue Mitinhaberin ist Frau Ines Kussmann seit Oktober in unser Team der Kleintierpraxis gekommen. Um uns fachlich noch breiter aufzustellen, haben. Ines Kussmann ist bei Facebook. Tritt Facebook bei, um dich mit Ines Kussmann und anderen Nutzern, die du kennst, zu vernetzen. Facebook gibt Menschen. Ines Kussmann is on Facebook. Join Facebook to connect with Ines Kussmann and others you may know. Facebook gives people the power to share and. Ines Kussmann (Tierärztin) in Brookdeich 14, Hamburg ✓ Das sagen Nutzer über Frau Kussmann ✓ Finden Sie mehr zu Frau. Kleintierspezialisten, Bergedorf, Dr. Ulrike Ewe und Ines Kussmann in Hamburg ➤ Gemeinschaftspraxis ✓ Erfahrungsberichte echter. Ines Kussmann (Heimtiere, Zahnheilkunde, Chirurgie); Dr. Melanie Langer (Zahnheilkunde, Ambulanz); Uta Rönneburg; Dr. Friedrich Müller (Klinikleiter. Impressum – Kleintierspezialisten Bergedorf – Praxis Dr. Ulrike Ewe und Ines Kussmann. Dr. med. vet. Ulrike Ewe und Frau Ines Kussmann Brookdeich
ines kussmann partner. Kleintierspezialisten, Bergedorf, Dr. Ulrike Ewe und Ines Kussmann in Hamburg ➤ Gemeinschaftspraxis ✓ Erfahrungsberichte echter. Die Besitzer haben große Angst "Nola" zu verlieren und hoffen Tierärztin Ines Kussmann kann helfen. In der Untersuchung fällt der Tierärztin auf, dass die junge.
Ines Kussmann Treffer aus Sozialen NetzenDa er nicht mehr der Jüngste ist, wundert sich Tierärztin Kabel1 Classics Schröder nicht gerade über ChefS Table Stream Deutsch beschriebenen Probleme. Im Rahmen der Weiterentwicklung unseres Praxisangebotes haben wir viele neue Leistungen in unseren Katalog aufgenommen. Der Kleine pinkelt und trinkt extrem viel und der Verdacht auf eine Blasenentzündung liegt nahe. Mo: - Di: - Mi: - Do: - Fr: - Sa: - Das Ziel: Die Tiere sollen nicht aufgrund von Geldsorgen oder Krankheit abgegeben werden oder auf eine gute medizinische Versorgung verzichten müssen. Die Familie der Katze ist sehr besorgt und hofft auf Hilfe in der Tierklinik.
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Proteome analysis of the leukocytes from the American alligator Alligator mississippiensis using mass spectrometry. Efficient S-alkylation of cysteine in the presence of 1,1,3,3-tetramethylguanidine.
Tetrahedron Letters , 51 46 , Crop Science , 50 6 , Claesen, M. Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides.
Proceedings of the National Academy of Sciences , 37 , Impact of the storage temperature on human plasma proteomic analysis: Implications for the use of human plasma collections in research.
Bruins, Hjalmar P. Oxidative protein labeling in mass-spectrometry-based proteomics. Identification and characterization of cysteinyl exposure in proteins by selective mercury labeling and nano-electrospray ionization quadrupole time-of-flight mass spectrometry.
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European Journal of Mass Spectrometry , 16 3 , Identification of Neospora caninum proteins regulated during the differentiation process from tachyzoite to bradyzoite stage by DIGE.
Gel and gel-free proteomics to identify Saccharomyces cerevisiae cell surface proteins. Journal of Proteomics , 73 6 , Evaluation of plasma carcinogenic markers in rat hepatic tumors models induced by rat hepatoma N1-S1 cells and benzo[a]pyrene.
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Adsorbed protein detection by scanning electrochemical microscopy. Journal of Electroanalytical Chemistry , 2 , Proteomics of RAW Characterisation and tissue distribution of polyphenol oxidase of deepwater pink shrimp Parapenaeus longirostris.
Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues. Molecular BioSystems , 5 9 , Proteomic approach for the analysis of acrylamide—hemoglobin adducts.
Electrospray ionization mass spectroscopic analysis of peptides modified with N-ethylmaleimide or iodoacetanilide. Meyer, Klaus Gerwert, Carsten Kötting.
Systematic approach to group-specific isotopic labeling of proteins for vibrational spectroscopy. Vibrational Spectroscopy , 48 1 , Immunoproteomic analysis of the protective response obtained from vaccination with Candida albicans ecm33 cell wall mutant in mice.
Presence of hemocyanin with diphenoloxidase activity in deepwater pink shrimp Parapenaeus longirostris post mortem.
Food Chemistry , 4 , Experimental and computational approaches to quantitative proteomics: Status quo and outlook.
Journal of Proteomics , 71 1 , The origin and control of ex vivo oxidative peptide modifications prior to mass spectrometry analysis.
Girault, Baohong Liu. Angewandte Chemie , 14 , Angewandte Chemie International Edition , 47 14 , Proteomic analysis of human osteoarthritic chondrocytes reveals protein changes in stress and glycolysis.
Larsen, Phillip J. Chapter 12 Phosphoproteomics. Proteomic analysis reveals metabolic changes during yeast to hypha transition inYarrowia lipolytica.
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Analytical and Bioanalytical Chemistry , 4 , Diagonal chromatographic selection of cysteinyl peptides modified with benzoquinones.
Analytical and Bioanalytical Chemistry , 3 , Experimental Parasitology , 1 , Identification of a 7S globulin as a novel coconut allergen.
Russell, Robert T. Sarisky, M. Lamine Mbow, C. Cheng Kao. Journal of Biological Chemistry , 10 , Standardisation of rapid in-gel digestion by mass spectrometry.
Turko, Salvatore Sechi. Multitrack electrospray chips. Journal of Mass Spectrometry , 41 11 , Serrano, Elisa J.
Structure and interaction with lipid interfaces. FEBS Journal , 19 , LeFebvre, Nadejda L. Duzan, Christopher A. Bradley, John W.
Hershey, Robert E. Journal of Biological Chemistry , 32 , M C. Ruiz-Romero, M. Mitochondrial proteomic characterization of human normal articular chondrocytes.
Osteoarthritis and Cartilage , 14 6 , Proteomic analysis of quorum sensing inRhizobium leguminosarum biovarviciae UPM Proteomic analysis of detergent-resistant membranes fromCandida albicans.
Differential protein expression of murine macrophages upon interaction with Candida albicans. Williams, Christian Schöneich. Biochemical Journal , 3 , Reduction of proteins during sample preparation and two-dimensional gel electrophoresis of woody plant samples.
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Mass spectrometry—based proteomics turns quantitative. Nature Chemical Biology , 1 5 , Rapid Communications in Mass Spectrometry , 19 17 , Hedberg, Erik J.
A simplified 2-D electrophoresis protocol with the aid of an organic disulfide. Proteomic characterization of human normal articular chondrocytes: A novel tool for the study of osteoarthritis and other rheumatic diseases.
Choudhury, Hong Xu, Ami P. Journal of Biological Chemistry , 26 , Detection of peroxidase activity in two-dimensional gel electrophoresis. European Food Research and Technology , , Isolation and identification of an 11S globulin as a new major allergen in mustard seeds.
On-line counting of cysteine residues in peptides during electrospray ionization by electrogenerated tags and their application to protein identification.
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Physical Chemistry Chemical Physics , 7 24 , Journal of Food Science , 70 1 , SS Isotope-coded N-terminal sulfonation of peptides allows quantitative proteomic analysis with increasedde novo peptide sequencing capability.
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The abc's and xyz's of peptide sequencing. Nature Reviews Molecular Cell Biology , 5 9 , Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a.
Protein Science , 13 9 , Roorda, Tobias M. Journal of Neurophysiology , 92 1 , Information for proteomics: ESI-MS titration by sodium ions gives the number of carboxylate groups in peptides.
Boja, Tanya Hoodbhoy, Henry M. Fales, Jurrien Dean. Journal of Biological Chemistry , 36 , Essential cysteine-alkylation strategies to monitor structurally altered estrogen receptor as found in oxidant-stressed breast cancers.
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Location of Disulfide bonds in mature? Journal of Peptide Science , 7 6 , Codina, I. Giralt, I. The Journal of Peptide Research , 57 6 , Jolly, T.
William Jordan. Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome. Nature Biotechnology , 19 4 , European Journal of Mass Spectrometry , 7 2 , Thiol Alkylation below Neutral pH.
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Journal of Mass Spectrometry , 35 8 , Future Medicinal Chemistry, 10 19 : Caddeo, C. Stability, biocompatibility and antioxidant activity of PEG-modified liposomes containing resveratrol.
International Journal of Pharmaceutics, 1 : Tocopherolloaded transfersomes: In vitro antioxidant activity and efficacy in skin regeneration. International Journal of Molecular Sciences, 19 5 : Polyamidoamine nanoparticles for the oral administration of antimalarial drugs Pharmaceutics 10, 4 , Nanoscale bioelectrical characterization Gabriel Gomila The main goal of the Nanoscale bioelectrical characterization group is to develop new experimental setups based on atomic force microscopy, and new theoretical frameworks enabling the quantification of the electrical properties of biological systems at the nanoscale including biomembranes, single viruses, single bacteria cells and eukaryotic cells.
Our main objective is to contribute to develop new labelfree biological nanoscale characterization methods and new electronic biosensors.
During the group has been involved in the investigation of the dielectric properties of water confined in nanostructures.
This result can have a strong impact in the understanding of the electrostatic interactions in liquid media, where such confined water can be present in most surfaces in the form of adsorbed water, including the surfaces of biological molecules.
We have also completed on the dielectric properties of small-scale filamentous protein structures and applied them to the dielectric characterization of bacterial polar flagella.
This result points towards a rather universal value of the dielectric constant of protein structures. We have also carried theoretical and experimental studies on the subsurface capabilities of Electrostatic Force Microscopy and the potential development of a nanotomographic technique based on it.
On the other side, we continued in advancing the theoretical understanding of electrostatic force microscopy in liquid media and on its application to a variety of biological systems ranging from self-assembled monolayers and lipid bilayers to cells.
During this year, we also completed our study on the electrogenic properties of Shewanella Oneidensis and identified some of the key proteins involved in the extracellular electron exchange with solid materials.
We also worked on the use of organic field effect transistors for the extracellular recording of cell membrane action potentials in cardiomyocytes, obtaining results for practical applications.
Voltage distribution numerically calculated for a nanochannel-electrostatic force microscope tip structure. The numerical calculations have been used to quantify the electrostatic force acting on the tip as a function of the thickness of the nanochannels containing water.
These calculations allowed demonstrating an anomalously low dielectric constant of water confined in nanochannels. The height of the channels varied from 1 nm to nm and they are buried below a layer 50 nm thick.
Left Scanning Electron Microscopy image of Shewanella Oneidensis bacterial cells on a carbon substrate of an electrochemical cell.
The body of the bacterial cell is known to be able to exchange electrons extracellularly with solid surfaces. We have investigated this property from macroscale electrochemical cyclic voltammetry experiments.
The bacterial extensions are believed to posses also the property of exchanging electrons with solid supports and transporting electrons over long distances.
We are currently investigating these properties with the use of electric scanning probe microscopy techniques samples prepared by the group of Eduard Torrents, IBEC.
This example shows the sub-surface imaging capabilities of Electrostatic Force Microscopy as compared to conventional Atomic Force Microscopy.
A theoretical nanotomographic algorithm to retrieve the structural and physical properties of the buried structure has been developed. Fumagalli, L.
Anomalously low dielectric constant of confined water. Science, : Lozano, H. Dielectric constant of flagellin proteins measured by scanning dielectric microscopy.
Nanoscale, 10 Dols-Perez, A. Interdigitation in spin-coated lipid layers in air. Colloids and Surfaces B: Biointerfaces, These tools include instrumentation based on proximity probes, such as electrochemical tunnelling microscopy and spectroscopy, that we apply to investigate electron transfer in metal oxides and individual redox proteins.
These studies are relevant to the development of biosensors and molecular electronics devices. Another set of nanotools that we are developing is based on molecular actuators that can be switched with light, such as azobenzene, which can be chemically attached to biomolecules in order to optically control their activity.
We have demonstrated for the first time two-photon stimulation of neurons and astrocytes with azobenzene-based photoswitches.
We have also developed several bioactive compounds that have been engineered to be regulated by light. Electrochemical tunneling spectroscopy and molecular dynamics simulations indicate that a reduced ionic density at the volume confined between redox protein partners hCc left, orange and pCc1 right, green causes an extended electric field equipotential lines shown in the background that allows long distance charge transport between them.
Heme groups are highlighted in each protein Lagunas et al. Image credit: Alba Nin-Hill. Rational structural modifications of the chemotherapy agent methotrexate enabled control of cytotoxic efficacy with light.
In vitro and in vivo experiments showed that the new compound, named phototrexate, behaves as a potent antifolate in its photoactivated configuration, and that it is nearly inactive in its thermodynamically stable state.
The insights provided by this work open up new possibilities for developing innovative agents for light-controlled precision chemotherapy. Matera et al.
Matera, C. A photoswitchable antimetabolite for targeted photoactivated chemotherapy. Journal of the American Chemical Society, 46 : Lagunas, A.
Long distance electron transfer through the aqueous solution between redox partner proteins. Nature Communications, 9 1 : Insights into the structure and nanomechanics of a quatsome membrane by force spectroscopy measurements and molecular simulations.
Nanoscale, 10 48 : Gumi-Audenis, B. In-plane molecular organization of hydrated single lipid bilayers: DPPC:cholesterol.
Mireia Oliva, Dept. Artur Llobet, Dept. Crespo-Villanueva, A. Casein interaction with lipid. Burkhard König, Univ Regensburg Prof.
Michael Decker, Univ Würzburg. Influence of texture on the electrical properties of Al-doped ZnO films prepared by ultrasonic spray pyrolysis.
Journal of Materials Science: Materials in Electronics, 29 3 : Casanellas, I. Dendrimer-based uneven nanopatterns to locally control surface adhesiveness: A method to direct chondrogenic differentiation.
Journal of Visualized Experiments, Bioengineering : e Sebastian, P. Surface sensitive nickel electrodeposition in.
Lightinduced regulation of ligand-gated channel activity British Journal of Pharmacology, , 11 , Our main objective is to improve diagnosis capability through the characterization of physiological phenomena and to enhance early detection of major cardiac and respiratory diseases and sleep disorders.
We propose and design new signal processing algorithms and develop new biosignal databases, with the collaboration of our hospital partners.
The group focuses its research in a translational way to promote the transfer of our scientific and technological contributions.
Currently, our prototypes are used in hospitals for research purposes and for future industrial developments. Characterization of the microvascular cerebral blood flow response to obstructive apneic events Neurophotonics , 5: with the ICFO and the Hospital de Sant Pau.
Cardiac and cardiorespiratory diseases Novel eingvalue-based method for time delay estimation of respiratory signals in patients with chronic heart failure Digital Signal Processing , , with Lund University, Sweden, and University of Zaragoza.
Novel method for differentiating normal from adventitious respiratory sounds RS to improve the diagnosis of pulmonary diseases. Particularly, continuous adventitious sounds CAS are of clinical interest because they reflect the severity of certain diseases.
The new method is based on the multi-scale analysis of instantaneous frequency IF and envelope IE calculated after ensemble empirical mode decomposition EEMD of respiratory sounds.
Lozano et al. Peyman, Z. Characterization of the microvascular cerebral blood flow response to obstructive apneic events during night sleep.
Neurophotonics, 5 4 : Surface mechanomyography and electromyography provide non-invasive indices of inspiratory muscle force and activation in healthy subjects.
Scientific Reports, 8 1 : Estrada, L. Onset and offset estimation of the neural inspiratory time in surface diaphragm electromyography: A pilot study in healthy subjects.
Laguna, P. Eigenvalue-based time delay estimation of repetitive biomedical signals. Digital Signal Processing, 75 EMG activity during reaching and grasping.
Pisa, Italy Honolulu, USA Rafols-De-Urquia, M. Assessment of respiratory muscle activity with surface.
Lozano-Garcia, M. Assessment of inspiratory muscle activation using surface diaphragm. Winfried J. KG, Karlsruhe, Germany Prof. Giraldo, B.
Respiratory sinus arrhythmia quantified with linear and non-linear techniques to classify dilated and ischemic cardiomyopathy.
A novel artifact reconstruction method applied to blood pressure signals. Cardiorespiratory phase synchronization increases during certain mental stimuli in healthy subjects.
In this context, we are interested in intelligent chemical instruments for the detection of volatile compounds and smells.
These systems can be based on an array of nonspecific chemical sensors with a pattern recognition engine, taking inspiration from the olfactory system.
Some spectrometries, e. Ion Mobility Spectrometry, are capable of very fast analysis with good detection limits but poor selectivity.
These technologies have been proposed for the fast determination of the volatolome volatile fraction of the metabolome , instead of the reference technique of gas chromatography — mass spectrometry.
Our Research in included 1. We have studied the impact of low power operation modes in the performance of Metal Oxide Sensors 4.
We are developing algorithms for the analysis of mass spectrometry images for the study of heterogeneity in colorectal cancer tissues 5.
We are developing analytical methods for the study of the majoritary compounds in human flatus in collaboration with Dr. We have proposed methods to estimate the limit of detection in non-linear chemical sensors using univariate and multivariate calibration models 7.
We have proposed methods to find universal calibration models for chemical sensor arrays 8. We have studied the impact of cross-validation methods in the overoptimism of PLS-DA models applied to omics data 9.
We have proposed methods to evaluate and correct the impact of instrumental shifts in GC-MS data for breath metabolomics.
Multiunit calibration rejects inherent device variability of chemical sensor arrays. Sensors and Actuators B: Chemical, Contreras, M. Thermal desorption-ion mobility spectrometry: A rapid sensor for the detection of cannabinoids and discrimination of Cannabis sativa L.
Sensors and Actuators B:. Chemical, Multivariate estimation of the limit of detection by orthogonal partial least squares in temperature-modulated MOX sensors.
Analytica Chimica Acta, Estimation of the limit of detection in semiconductor gas sensors through linearized calibration models.
Fernandez, L. A practical method to estimate the resolving power of a chemical sensor array: Application to feature selection. Frontiers in Chemistry, 6 Article Oller-Moreno, S.
The differential plasma proteome of obese and overweight individuals undergoing a nutritional weight loss and maintenance intervention. Gardner, Microsensors and Bioelectronics Lab, Dept.
Ivan Montoliu and Dra. Journal of Breath Research, 12 3 : Overoptimism in crossvalidation when using partial least squares-discriminant analysis for omics data: a systematic study.
Analytical and Bioanalytical Chemistry, 23 : Taghadomi-Saberi, S. Classification of bitter orange essential oils according to fruit ripening stage by untargeted chemical profiling and machine learning.
Sensors, 18 6 : Fonollosa, J. Chemical sensor systems and associated algorithms for fire detection: A review. Sensors, 18 2 : Low power operation of temperature-modulated metal oxide semiconductor gas sensors.
Graz, Austria The need of external validation for metabolomics predictive models. Cumeras, R. The main conceptual problem of the standard in vitro cell-based assays is that they rely on two dimensional monolayer cellular cultures, which fail to replicate the complexity of living systems.
There is an urgent need to create technological platforms with complex cell culture systems that mimic better the tissue-like cellular microenvironment.
We propose to combine engineering microfabrication technologies, tissue engineering concepts and recent advances in stem cell research, exploiting stem cell unique properties, to create cell culture microenvironments that will go beyond current 3D in vitro models.
Resulting in vitro tissue equivalents aim at. The cell culture platforms proposed will provide physiologically relevant and highly reproducible data, and they will be compatible with conventional cell culture assays and high-throughput testing.
The new organotypic cell culture platforms will aim to advance the in vitro modelling of diseases, the preclinical screening for drug toxicity, the understanding of organ development and the regenerative medicine applications.
Current main projects are: i to engineer and validate a complex in vitro model of small intestinal epithelium and ii to engineer and validate a novel in vitro model of engineered cardiac tissue.
Mimicking small intestinal tissue by culturing intestinal-organoid derived cells on poly ethylene glycol diacrylate PEGDA microstructures.
Cell nuclei are stained in green and actin cytoskeleton in red. The role of mucus as an invisible cloak to transepithelial drug delivery by nanoparticles.
Hortigüela, V. Nanopatterns of surface-bound ephrinB1 produce multivalent ligand-receptor interactions that tune EphB2 receptor clustering.
Nano Letters, 18 1 : Macedo, M. Derived enterocyte-like cells for drug absorption and metabolism studies. Trends in Molecular Medicine, 24 8 : Torras, N.
Mimicking epithelial tissues in threedimensional cell culture models. Javier Santos, Dra. Conference Papers de Goede, M. High quality factor Al2O3 microring resonators for on-chip sensing applications.
California, USA Al2O3 Mmicroresonators for passive and active sensing applications. Optical Sensors. Zurich, Switzerland Al2O3 Microresonator based passive and active biosensors.
Bucharest, Romania Successful replacement, or augmentation, of the function of damaged cells by patient derived differentiated stem cells would provide a novel cell-based therapy for diseases.
Since iPSCs resemble human embryonic stem cells hESCs in their ability to generate cells of three germ layers, patient-specific iPSCs offer definitive solutions for the ethical and histo-incompatibility issues related to hESCs.
One of our aims is to generate and correct diseasespecific hiPSCs for disease modelling and drug screening.
The combination of gene-editing based methodologies together with the development of novel. In this regard we are particularly interested in generation of transgene-free and disease free patient derived hiPSCs for disease modelling and the discovery of novel therapeutic targets.
We believe that the recovery of tissue function should not be restricted to the development of cell replacement therapies. In this regard, in our laboratory we take advantage of organisms that possess the ability to regenerate such as zebrafish, in order to understand which molecular and cellular pathways lead to organ regeneration.
Surprisingly, studies in neonatal mice have demonstrated that soon after birth this organism posses the capability to regenerate its heart.
Taking advantage of such preliminary observations we are translating such analysis in order to understand if the mammalian neonatal kidney still posses the capability to regenerate, and more importantly, if we are able to dissect the epigenetic and cellular mechanisms leading to those responses.
Lastly, and in an effort to fully develop in vitro and ex vivo platforms for organ regeneration, in our lab we are focused in the development of reporter cell lines for different transcription factors essential for tissue-specific commitment and differentiation i.
The possibility to combine pluripotent stem cell lines together with decellularized matrices, functionalized biomaterials and ex vivo organoids offers and unprecedented opportunity for the immediate generation of patient-specific in vitro and ex vivo platforms for disease modelling and organ regeneration Figure 2.
Latorre, E. Active superelasticity in threedimensional epithelia of controlled shape. Nature, : Hernandez-Benitez, R.
Martinez, M. At the heart of genome editing and cardiovascular diseases. Circulation Research, 2 : Niederberger, C.
Swain, J. Laufer, N. Forty years of IVF. Fertility and Sterility, 2 : Hurtado del Pozo, C. Modeling epigenetic modifications in renal development and disease with organoids and genome editing.
Garreta, E. Studying kidney disease using tissue and genome engineering in human pluripotent stem cells.
Nephron, Roadblocks in the path of iPSC to the vlinic. Current Transplantation Reports, 5 1 : Kidney organoids for disease modeling. Oncotarget, 9 16 : However, despite such a great advance and promise, our ability to treat diseases such as neurological maladies, genetic syndromes and cancer, remains a major challenge.
One of the prime obstacles is. A plethora of promising tools are becoming available to tackle health problems, such as new drug carriers or delivery systems, macromolecular assemblies within the nanoscale-size range which can be loaded with diagnostic and therapeutic agents to improve their solubility,.
Pictures are reproduced or adapted from the following sources Copyrights reside on the respective publishers and associated professional societies :  Mane et al.
Our lab generates knowledge and tools aimed to improve our ability to deliver therapeutic agents to specific disease sites.
Focusing on endothelial cell adhesion molecules as examples of accessible targets and on genetic conditions which serve as models for metabolic, neurodegenerative and cardiovascular syndromes, our ultimate goal is to enable effective treatment for these life-threatening disorders and other maladies characterized by similar pathological traits.
Some of our main programmatic efforts are described below. Biologically-Controlled Transport of Drug Carriers How drug delivery systems are sensed, transported, and disposed of within the body, which is greatly dependent upon biological properties and processes, is far from being understood and much less controlled.
Most targeted strategies are designed to achieve specific binding of drug delivery systems to cellsurface receptors, but then they simply depend on the signaling and transport processes the bound receptor regulates in nature.
Instead, by deciphering the biological bases of these events, we impart the drug carrier control over biological signaling events independently from the receptor being bound, bypassing.
J Control Release. This provides a new and complementary avenue at the interface between the use of novel technological tools to decipher the biological mechanisms that regulate health and fail in disease, and the use of biological knowledge to optimize nanotechnology tools aimed to diagnose and treat human pathologies.
For instance, we have shown how even using the same targeting or receptor, the kinetics, mechanism, and destination of a drug carrier can be modulated by: a varying its size, shape, and targeting valency; b varying the receptor epitope to which the carrier binds; c using auxiliary drugs to modulate the endocytic machinery; d coupling carriers to signaling molecules that can tune the uptake route independently from the receptor being used Figure 2 ; e combining targeting to several receptors; or f coupling targeting moieties with anti-phagocytic moieties on the surface of drug carriers.
Transport of Drug Carriers Across Physiological Barriers Crossing the linings that separate body and cellular compartments is paramount for efficient drug delivery.
For instance, an epithelial barrier separates the gastrointestinal tract from the bloodstream, controlling uptake of orally ingested substances. While certain chemical entities are able to cross this barrier, many therapies do not and their successful utilization needs of means to bypass this obstacle.
As for neurodegenerative conditions, they remain largely untreatable because. Muro S. Another example is that of novel biological therapeutics, which have demonstrated potential to manipulate disease targets far more precisely than their small chemical counterparts.
However, these large and fragile therapeutics fail to traverse the membranes that separate the extracellular environment from the intracellular milieu and those of intracellular.
We demonstrated that the ICAM-1 pathway described in the next section enables transcytosis across epithelial and endothelial linings, which we explore for oral delivery and delivery across the bloodbrain barrier.
We were also able to target DNA-built dendrimers to cells specifically, whereby these DNA dendrimers enabled endosomal escape and cytosol delivery of a variety of cargoes, including small toxins, carbohydrates Figure 3 , proteins, and nucleic acids.
ICAMtargeted nano- and micro-carriers are both internalized by cells due to natural sphingomyelinase SMase -dependent generation of ceramide at ICAMbinding sites.
Ceramide improves carrier engulfment and membrane invagination, and acts as a second messenger toward actin re-organization, helping endocytic uptake left panel.
In contrast, targeting drug carriers to receptors associated with more size-restrictive pathways, e. Surface-functionalization of M6PR-targeted carriers with elements mimicking the ICAM-1 pathway, namely exogenous SMases such as NSM , supplies the necessary ceramide and actin re-organization, improving endocytosis of nano- and micro-carriers even when targeted to receptors different from ICAM-1 right panel.
Reproduced from Ansar et al. This new transport route is different from most others classically utilized for drug delivery, including clathrin-, caveolar-, macropinocytosis-, or phagocytosis-mediated pathways.
My independent laboratory continues to unravel the regulation of this route, particularly focusing on ICAM-1 Figure 4 , and its implications in patho-physiology and drug delivery.
The relevance of this new pathway is illustrated by the fact that ICAM-1 mediates extravasation of leukocytes during inflammation, signaling at the immune synapsis, and invasion by some pathogens e.
The understanding of this fundamental route and its properties is also advancing diverse drug delivery applications by our group and many others.
Improving Treatment of Lysosomal Disorders Monogenic pathologies due to genetic deficiency, such as the case of lysosomal disorders, are valuable models to study disease progression and therapeutic.
Also, their unequivocal diagnosis enables the tracing of their progression from early to late stages. Since these diseases present with either acute or long-term effects depending on genetic severity, and associate with neurodegeneration, cardiovascular, metabolic, and cancer-like syndromes, they represent excellent disease models.
The current lack of efficient therapies to treat these syndromes stems from problems similar to those described above, i.
Consequently, we are applying targeted nanotechnology concepts to the treatment of genetic lysosomal disorders. Current therapies by i.
Yet, delivery to other organs brain, lungs, etc. Using types A and B Niemann-Pick Figure 5 , Fabry, and Gaucher diseases as examples, we have shown improved delivery of therapeutic enzymes to all affected organs in animal models, holding considerable translational potential.
Left Illustrative cartoon and corresponding microscopy showing that fluorescent dextran delivered to cells via targeted polymer nanoparticles resides in vesicular compartments bright red spots around the cell nucleus blue.
DNA-built dendrimers. Adapted from Muro Adv Funct Mat, 24 19 Adapted from Serrano et al. Top Polymer nanocarriers NCs bearing therapeutic acid sphingomyelinase ASM and targeted to ICAM-1 were observed by fluorescent microscopy to abundantly reach the lungs, as observed 30 min after i.
Bottom Transmission electron microscopy of lungs collected 3 h after i. For instance, NCs can be seen being engulfed by cells black arrows , within cell endosomes white arrowheads and lysosomes black arrowheads , and transcytosed across the endothelium into subjacent epithelial cells white arrow.
Reproduced from Garnacho et al. Juan Marugan and Dr. Brigitte Städler, Aarhus University, Denmark.
Biosafety level 2 culture hoods CO2 incubators Liquid nitrogen storage tank Thermocycler Confocal-epifluorescence microscope Spectrofluorometer.
Cellular and respiratory biomechanics Daniel Navajas The goal of our research is to gain a deeper understanding of cellular and respiratory biomechanics to improve the diagnosis and treatment of respiratory diseases.
The work is organized in two interrelated areas, focused on respiratory mechanics at both the systemic and the cellular level. We use basic and translational approaches in a multidisciplinary framework involving close cooperation with clinical groups.
Our current research interest is focused on the study of cell-matrix mechanical cross-talk for tissue engineering and regenerative medicine. Cells sense and actively respond to the biophysical features of their microenvironment.
Mechanical properties of the extracellular matrix regulate critical cell processes such as contraction, migration, proliferation, gene expression and differentiation.
We use atomic force microscopy and other cutting-edge biophysical techniques to study the mechanical properties of the extracellular matrix and their impact in cell behavior.
We have implemented protocols to decellularize different soft tissues. This innovative. By seeding cells in these scaffolds we study the impact of the mechanical features of the microenvironment on stem cell engraftment and differentiation onto lung and heart phenotypes.
We produce lab-on-chip devices mimicking the native cell microenvironment to investigate mechanical signaling driving stem cell differentiation under precisely controlled conditions.
Using 3D bioprinters we integrate stem cells into synthetic and extracellular matrix hydrogels to fabricate tissue patches as an innovative approach to regenerate ventricular scars resulting from heart infarct.
Organ biofabrication reengineered from decellularized tissue scaffolds offers a promising alternative for transplantation.
We develop improved bioreactors mimicking breathing and blood perfusion to biofabricate lungs by seeding stem cells into acellular lung scaffolds.
Villanueva, J. A portable continuous positive airway pressure device that can perform optimally under strenuous conditions.
Torres, M. Aging reduces intermittent hypoxiainduced lung carcinoma growth in a mouse model of sleep apnea. Is telemedicine a key tool for improving continuous positive airway pressure adherence in patients with sleep apnea?
Notari, M. The local microenvironment limits the regenerative potential of the mouse neonatal heart. Science Advances, 4 5 : eaao Alcaraz, J.
Bidirectional mechanobiology between cells and their local extracellular matrix probed by atomic force microscopy. Seminars in Cell and Developmental Biology, Perea-Gil, I.
Head-to-head comparison of two engineered cardiac grafts for myocardial. Menal, M. Frontiers in Neurology, 9: Article 1 Intermittent hypoxia mimicking sleep apnea increases passive stiffness of myocardial extracellular matrix.
A multiscale study. Frontiers in Physiology, 9: Article Passive stiffness of left ventricular myocardial tissue is reduced by ovariectomy in a post-menopause mouse model.
Bioengineered lungs: A challenge and an opportunity. In the case of animal models we have not only some ethical problems but also the ability to extrapolate data to human conditions is limited and in vitro platforms often do not simulate the complex cell—cell and cell—matrix interactions crucial for regulating cell behaviour.
Biosensors for bioengineering group is focused in a new line of research that has become of extreme importance in the last years.
The idea is to integrate biosensor technology and nanotechnology with stem cell research and with tissue engineering. Engineered tissues are integrated with biosensing technology to obtain microdevices for detecting cellular responses to external stimuli, monitoring the quality of the microenvironment e.
This research on 3D-functional engineered tissues is expected to develop knowledge of tissue construction and their functions and relation with some human diseases.
These chips could be used in pharmaceutical assays and could be a step toward the ultimate goal of producing in vitro drug testing systems crucial to the medicine and pharmaceutical industry.
Pancreas islet stained in blue for nuclei and red for actin inside a microporous microfibrillated cellulose-gelatin scaffold stained with green.
Composite biomaterials as long-lasting scaffolds for 3D bioprinting of highly aligned muscle tissue. Macromolecular Bioscience, 18 10 : Conference Paper.
We believe that combining several different stimuli in the chip resembles a more realistic environment that nerve cells will encounter in the living animal in normal and disease conditions.
These experiments using Labon-a-Chip models in turn will make future studies on the role of neuronal cells in development and regeneration more accurate and complete.
Thus, we developed a new device able to reproduce the formation of the neuromuscular junction NMJ in lab on chip devices. In addition, a device designed to analyse axon lesions of cortical neurons was also developed.
Current experiments. For example: i on chip lab platform to monitor drug delivery modulating neuronal activity see figure ; ii cortico-spinal chips to develop axon regenerative studies of new drug formulation in collaboration with Imperial College; London ; iii devices to molecular gradient generation for migrating neurons in collaboration with i3A, Zaragoza and, iv in silico 3D modeling for neurodegenerative diseases Alzheimer and Parkinson chip.
Last experiments are focused to reproduce a lab on chip devices to analyse and to reproduce ALS models in collaboration with Biodonostia Hospital Figure 2.
However, the basis of the spreading process remains poorly understood although cell to cell transport via. Experimental evidence suggests that providing a permissive extracellular environment containing cellular or biomaterial bridges is not enough to increase axon regrow to obtain functional regeneration, supporting the importance of clarifying the complex transcriptional response below these signalling pathways.
As an alternative, activating or recapitulating the developmental program of the lesioned neuron to.
Hervera, A. Nature Cell Biology, 20 3 : Role of cellular prion protein in interneuronal amyloid transmission. Progress in Neurobiology, Urrea, L. Molecular Neurobiology, 55 3 : Optogenetics is currently the state-of-the-art method for activity-based nervous system research, allowing more specific cellular stimulations by light in a less invasive techniques compared to classical electrical stimulation, but leading to a more tailored physiological responses.
In our laboratory, we started to analyse whether optical stimulation of lesioned neurons is able to enhance axonal growth or sprouting.
These experiments were performed on lesioned cortical neurons and in vivo. Matamoros-Angles, A. Molecular Neurobiology, 55 4 : Llorens, F.
Vivancos, A. Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.
PLoS Pathogens, 14 1 : e Garcia-Esparcia, P. Brain Pathology, 28 1 : Ferrer, I. Brain Pathology, 28 6 : — Elisabeth Engel page 13 , Prof.
Josep Samitier, page 61 , Prof. Xavier Trepat, page 75 and Prof. Antonella Consiglio and Dr. Beth L. Mata, A. New functions of Semaphorin 3E and its receptor PlexinD1 during developing and adult hippocampal formation.
Franco, R. N-methyl-D-aspartate receptor link to the MAP kinase pathway. Frontiers in Molecular Neuroscience, 11 : Article Tomas-Roig, J. Effects of repeated.
Badiola-Mateos, M. Challenges and future prospects on 3D in-vitro modeling of the neuromuscular circuit. Frontiers in Bioengineering and Biotechnology, 6 Article Cellular and molecular mechanobiology Pere Roca-Cusachs Every time we blink, move a hand, draw a breath, or walk, cells in our body exert, transmit, withstand, and detect forces.
This mechanical interaction with the environment determines how cells proliferate, differentiate, and move, and regulates development, tumorigenesis or wound healing.
Just like biochemical stimuli initiate signaling cascades, mechanical forces affect the links and conformation of a network of molecules connecting cells to the extracellular matrix.
Our research aims precisely at unraveling the mechanisms that these molecules use to detect and respond to mechanical stimuli like forces or tissue rigidity, triggering downstream cell responses.
To this end, we combine biophysical techniques like magnetic tweezers, Atomic Force Microscopy, traction microscopy, and microfabricated force sensors with molecular biology, advanced optical microscopy, and theoretical modelling.
Sensing rigidity: Using this multi-disciplinary approach, we have recently unveiled a molecular mechanism that cells employ to detect and respond to the rigidity of their environment, which could be crucial in breast tissue.
Cell Biol. This affects force transmission from the environment to cells, and also within different cell components. Recently, we have begun to explore how force transmission to the nucleus affects the dynamics of transcriptional regulators, such as YAP Elosegui-Artola et al.
Sensing the environment: We are currently expanding on the idea of the molecular clutch, to explore how cell molecular engines sense not only mechanical rigidity, but other important parameters from their environment: for instance, the composition and distribution of ligands.
Artistic rendering of a cell attaching to a substrate coated with a gold nano-pattern array, used to study how cells detect spatial cues From Oria et al.
In this regard, we recently uncovered that this concept can explain how cells sense the spatial distribution of ligands in the extracellular matrix Oria et al.
We have also demonstrated that cell-cell force transmission, mediated by a molecular clutch, is essential for cells to sense gradients in stiffness Sunyer et al.
Ultimately, when we determine the molecular mechanisms that communicate cells with their environment, we will understand how forces determine development when things go right, and tumor formation when they go wrong.
The membrane as a mechanosensor: Due to its mechanical properties, the plasma membrane itself can respond to forces and act as a mechanosensor. Recently, we have shown that cell membranes can use purely physical principles to adapt their shape in response to mechanical forces Kosmalska et al.
We are currently studying how cells harness this physical membrane behavior to respond to signals from their environment.
Cartoon depicting how force transmission to the nucleus affects nuclear pores, leading to nuclear protein import from Elosegui-Artola et al.
Elosegui-Artola, A. Control of. Trends in Cell Biology, 28 5 : Thottacherry, J. Mechanochemical feedback and control of endocytosis and membrane tension.
Nature Communications, 9 Gauthier, N. Mechanosensing at integrin-mediated cell—matrix adhesions: from molecular to.
Current Opinion in Cell Biology, 50 Bennett, M. Molecular clutch drives cell response to surface viscosity. Roca-Cusachs, P. Cell scientist to watch - Pere Roca-Cusachs.
Journal of Cell Science, 16 : jcs Escribano, J. A hybrid computational model for collective cell durotaxis. Biomechanics and Modeling in Mechanobiology, 17 4 : Nanobioengineering Josep Samitier The Nanobioengineering group is a truly multidisciplinary team composed by researchers coming from very diverse backgrounds working together in applying nanotechnology for the development of new biomedical systems and devices, mainly for diagnostic purposes, and integrated microfluidic Organ-on-aChip devices for the study of organ physiology, disease etiology, or drug screening.
The main research activities of the group include the engineering and biochemical functionalization of biomaterials integrated with microfluidics systems.
The bioengineered microdevices are used to study cell responses to biomolecular compounds applied to Organon-Chip devices, or for the development of new Lab-on-aChip based biosensors.
The goal is to fabricate microsystems containing living cells that recapitulate tissue and organ level functions in vitro and new portable diagnosis devices that can be used as Point-of-Care systems.
The projects carried out by the group are focused on clinical and industrial problems and are related to three convergent research lines:.
Tumor Cancer on a chip in vitro development Microfluidic Vessel on-a-chip for screening drug delivery systems.
Katuri, J. Directed flow of micromotors through alignment interactions with micropatterned ratchets. ACS Nano, 12 7 : Gorostiza, P.
Molecular architecture for DNA wiring. Biosensors and Bioelectronics, Blood-based cancer biomarkers in liquid biopsy: A.
U nanoET-leukemia Nanoconductance of electron transfer proteins of the respiratory chain. International Journal of Molecular Sciences, 19 10 : Silva, N.
Nanomaterials, 8 12 : Cross-fertilization of Key Enabling Technologies: An empirical study of nanotechnology-related projects.
Dana-Farber Cancer Institute, Inc. Journal of Engineering and Technology Management, 49 Multi-disciplinarity breeds diversity: the influence of innovation project characteristics on diversity creation in nanotechnology.
Journal of Technology Transfer, 43 2 : Juan C. Producing 3D biomimetic nanomaterials for musculoskeletal system regeneration.
Sampietro, Politecnico di Milano, Italy Prof. Molly M. Miguel A. Industry partners: Biokit S. Werfen group ; Genomica S. Zeltia group ; Tallers Fiestas S.
We are interested in fundamental studies of active matter, the use of nanobots for future nanomedicine and environmental applications and the bioengineering of new devices based on hybrid systems.
Nano-Bio Team The use of enzyme catalysis is emerging as an attractive alternative to power micro- and nanomachines due to their unique features including biocompatibility, versatility and fuel bioavailability.
Our group has demonstrated the use of different enzymes, including urease and glucose oxidase, to generate active propulsion of nano- and microparticles, paving the way towards new applications of artificial active matter in biomedicine.
In particular, we take advantage of the 3D bioprinting technique to develop bio-robotic systems composed of skeletal muscle cells embedded.
Smart micro- and nanorobots are able to swim, monitor their own activity, sense their environment and deliver drugs to 3D bladder cancer spheroids using biocompatible and bioavailable fuels such as urea.
These materials can act as scaffolds, support, or flexible parts, as well as be responsive upon certain stimuli. By controlling the contractions of skeletal muscle cells via electric fields, we can measure the forces exerted by these bio-actuators against artificial 3D-printed posts.
Using this setup, we have performed studies on the adaptability of bio-actuators after applying different training protocols and we have observed how their force generation and gene expression can adapt to the frequency of stimulation and stiffness of the artificial posts.
Active matter in complex systems We study colloidal suspensions of Pt-coated silica particles as a model system of synthetic active matter.
These systems have mostly been studied in homogeneous environments until now. Our interest lies in observing these systems in more complex settings, such as near interfaces, complex media or with flow involved.
Since the self-propelled particles generate chemical and hydrodynamic fields around them, they interact in complex ways with flows and nearby surfaces that often leads to.
Upon electrical stimulation, the muscle can contract, bend the post and their force can be calculated. Fundamental aspects of enzyme-powered micro- and nanoswimmers.
Accounts of Chemical Research, 51 11 : — Influence of enzyme quantity and distribution on the self-propulsion of non-Janus urease-powered micromotors.
Journal of the American Chemical Society, 30 : Vilela, D. Medical imaging for the tracking of micromotors.
When flow is present, particles also behave different as they reorient perpendicular to the flow. Environmental applications of micro-nano motors Artificial micromotors, based on bubble self-propulsion have demonstrated to be able to mix solutions and.
These micromotors are mostly based on two main structures, tubular and spherical. On the other hand, electrodeposited microjets, which are smaller.
Catalytically active colloids generate chemical gradients and interact with their nearby surfaces while they swim. When they swim in capillaries where a flow is imposed, they present a cross stream migration deviating from straight trajectories, perpendicular to the flow lines.
This type of motion resembles, in some aspects, the motion of biological microswimmers. ACS Nano, 12 2 : Wang, X.
Fuel-free nanocap-like motors actuated under. Advanced Functional Materials, 28 25 : Enzyme-powered nanobots enhance anticancer drug delivery.
Advanced Functional Materials, 28 Xuan, M. Noncontinuous super-diffusive dynamics of a light-activated nanobottle motor.
Angewandte Chemie International Edition, 57 23 : Cross-stream migration of active particles. Science Advances, 4 1 : eaao In this case, the metal is adsorbed and removed from the contaminated water.
The metal can thereafter be desorbed and the microjets used again. In order to target other water pollution problems, such as microorganism contamination, we have developed spherical microbots that can kill bacteria while they swim.
These microbots have a Janus structure based on spherical magnesium microparticles, able to dissolve in water producing hydrogen bubbles, covered in one of their faces by Fe, Au and AgNPs which provide magnetic, bacteria attachment and bactericidal properties to the microjets.
Towards scaling-up of the micromotor synthesis for cleaning large volumes of water, we have fabricated micromotors using exclusively chemical methods such as, precipitation, reduction and sol-gel chemistry.
These micromotors are based on a silica microtubular structure which contains an inner-layer of a catalytic material PtNPs or MnO2 capable of removing pollutants efficiently from water while they swim in the presence of hydrogen peroxide.
The external decoration of these structures with magnetic nanoparticles provides for good magnetic control. Finally, magnetic and catalytic micromotors formed by the aggregation of cobalt ferrite nanoparticles were synthesized to remove antibiotics from water.
All these micromotors, due to their magnetic properties can be removed from the solution after finishing their targeting action by the application of an external magnetic field.
Villa, K. Metal-oxide-based microjets for the simultaneous removal of organic pollutants and heavy metals. Romeo, A. Inkjet printed flexible non-enzymatic glucose sensor for tear fluid analysis.
Applied Materials Today, 10 Core-shell microspheres for the ultrafast degradation of estrogen hormone at neutral pH. RSC Advances, 8 11 : Conference Papers Mestre, R.
Paris, France Point-of-care diagnostics allows decentralizing clinical diagnostic practices and monitoring health out of specialized hospital settings.
Advantages of such decentralization are improved quality of life of patients, enhanced therapeutic efficacy thanks to more frequent tests, and lower overall cost of the health system.
We develop flexible biochemical sensors for non-invasive and cost-effective monitoring of analytes in biological fluids alternative to blood, e.
We combine electrochemical electrochemical sensors with microfluidics and electronics to achieve fully integrated devices, that are well suited for low-cost, portable and user-friendly medical diagnostics.
Dietrich, Dr. Popescu, M. Tasinkevych, Dr. Analytes are quickly quantified by electrochemical techniques.
Gabriel and Prof. Bacterial Infections: Antimicrobial Therapies Eduard Torrents Infectious diseases constitute a tenacious and major public health problem all over the world.
The emergence and increasing prevalence of bacterial strains that are resistant to available antibiotics demand the discovery of new therapeutic approaches.
There is an urgent need for reliable and rapid detection of infecting bacteria and its pattern of resistance to antibiotics. Our lab aims to investigate new antimicrobial therapies and strategies to combat bacterial infections with different objectives:.
Model of ribonucleotide reductase activity and vitamin B12 availability during P. Antibacterial activity of two ribonucleotide reductase inhibitors on formed flow cell Pseudomonas aeruginosa biofilm.
Vladimir Arion, Department of Inorganic Chemistry. University of Vienna, Austria. Facultad de Ciencias, Universidad de Granada, Spain.
Basas, J. High-dose daptomycin is effective as an antibiotic-lock therapy in a rabbit model of Staphylococcus epidermidis catheterrelated infection.
Antimicrobial Agents and Chemotherapy, 62 2 : e Crespo, A. Aerobic vitamin B12 biosynthesis is essential for pseudomonas aeruginosa class II ribonucleotide reductase activity during planktonic and biofilm growth.
Frontiers in Microbiology, 9 : Article Pressure microinjection system Nikon Inverted fluorescent. Pujol, E. Pentafluorosulfanyl-containing triclocarban analogs with potent antimicrobial activity.
Molecules, 23 11 : Miret-Casals, L.Sieh dir an, was Ines Kussmann (ineskussmann) auf Pinterest entdeckt hat – die weltweit größte Ideensammlung. Ines-Kussmann«in Facebook - Finden Sie alle Informationen ✓ zur Person im sozialen Netzwerk. Aufnahmeort: Lüneburger Heide. Kamera: Lumix G6. Fotograf: Tierärzte Ines Kussmann Uwe Zimmermann Wittorf. Ines Kussmann/Dr. Uwe Zimmermann. Dr. Ulrike Ewe & TÄin Ines Kussmann. Dr. Mirja Fenske. Kleintiere. Osterrade 36a Hamburg Bezirk: Bergedorf Stadtteil: Lohbrügge. Tel: 10 40 Tierärztin Ines Kussmann staunt nicht schlecht, als sie plötzlich sechs Yorkshire-Terrier im Behandlungszimmer empfängt. Doch wer von der Rasselbande ist.