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Article ; Online: Factors influencing olfactory function in an adult general population sample: the CHRIS study.

Gögele, Martin / Emmert, David / Fuchsberger, Christian / Frasnelli, Johannes

2024 Volume 49

Abstract: The sense of smell allows for the assessment of the chemical composition of volatiles in our environment. Different factors are associated with reduced olfactory function, including age, sex, as well as health and lifestyle conditions. However, most ... ...

Abstract	The sense of smell allows for the assessment of the chemical composition of volatiles in our environment. Different factors are associated with reduced olfactory function, including age, sex, as well as health and lifestyle conditions. However, most studies that aimed at identifying the variables that drive olfactory function in the population suffered from methodological weaknesses in study designs and participant selection, such as the inclusion of convenience sample or only of certain age groups, or recruitment biases. We aimed to overcome these issues by investigating the Cooperative Health Research in South Tyrol (CHRIS) cohort, a population-based cohort, by using a validated odor identification test. Specifically, we hypothesized that a series of medical, demographic and lifestyle variables is associated with odor identification abilities. In addition, our goal was to provide clinicians and researchers with normative values for the Sniffin' Sticks identification set, after exclusion of individuals with impaired nasal patency. We included 6,944 participants without acute nasal obstruction and assessed several biological, social, and medical parameters. A basic model determined that age, sex, years of education, and smoking status together explained roughly 13% of the total variance in the data. We further observed that variables related to medical (positive screening for cognitive impairment and for Parkinson's disease, history of skull fracture, stage 2 hypertension) and lifestyle (alcohol abstinence) conditions had a negative effect on odor identification scores. Finally, we provide clinicians with normative values for both versions of the Sniffin' Sticks odor identification test, i.e. with 16 items and with 12 items.
MeSH term(s)	Adult ; Humans ; Olfaction Disorders/diagnosis ; Olfaction Disorders/epidemiology ; Smell ; Odorants ; Parkinson Disease ; Cognitive Dysfunction ; Sensory Thresholds
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	754122-3
ISSN	1464-3553 ; 0379-864X
ISSN (online)	1464-3553
ISSN	0379-864X
DOI	10.1093/chemse/bjae011
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Article ; Online: Quantification of Empty, Partially Filled and Full Adeno-Associated Virus Vectors Using Mass Photometry.

Wagner, Christina / Fuchsberger, Felix F / Innthaler, Bernd / Lemmerer, Martin / Birner-Gruenberger, Ruth

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Adeno-associated viruses (AAV) are one of the most commonly used vehicles in gene therapies for the treatment of rare diseases. During the AAV manufacturing process, particles with little or no genetic material are co-produced alongside the desired AAV ... ...

Abstract	Adeno-associated viruses (AAV) are one of the most commonly used vehicles in gene therapies for the treatment of rare diseases. During the AAV manufacturing process, particles with little or no genetic material are co-produced alongside the desired AAV capsid containing the transgene of interest. Because of the potential adverse health effects of these byproducts, they are considered impurities and need to be monitored carefully. To date, analytical ultracentrifugation (AUC), transmission electron microscopy (TEM) and charge-detection mass spectrometry (CDMS) are used to quantify these subspecies. However, they are associated with long turnaround times, low sample throughput and complex data analysis. Mass photometry (MP) is a fast and label-free orthogonal technique which is applicable to multiple serotypes without the adaption of method parameters. Furthermore, it can be operated with capsid titers as low as 8 × 10
MeSH term(s)	Dependovirus/genetics ; Dependovirus/chemistry ; Genetic Vectors/genetics ; Capsid/chemistry ; Capsid Proteins/genetics ; Microscopy, Electron, Transmission
Chemical Substances	Capsid Proteins
Language	English
Publishing date	2023-07-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241311033
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Article ; Online: Automated Mass Photometry of Adeno-Associated Virus Vectors from Crude Cell Extracts.

Wagner, Christina / Fuchsberger, Felix F / Innthaler, Bernd / Pachlinger, Robert / Schrenk, Irene / Lemmerer, Martin / Birner-Gruenberger, Ruth

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Mass photometry (MP) is a fast and simple analysis method for the determination of the proportions of subpopulations in an AAV sample. It is label-free and requires minimal sample volumes between 5-10 µL, which makes it a promising candidate over ... ...

Abstract	Mass photometry (MP) is a fast and simple analysis method for the determination of the proportions of subpopulations in an AAV sample. It is label-free and requires minimal sample volumes between 5-10 µL, which makes it a promising candidate over orthogonal techniques such as analytical ultracentrifugation (AUC), cryo-transmission electron microscopy (Cryo-TEM) or charge-detection mass spectrometry (CDMS). However, these methods are limited in their application to purified samples only. Here we developed a purification step based on single-domain monospecific antibody fragments immobilised on either a poly(styrene-divinylbenzene) resin or on magnetic beads prior to MP analysis that allows the quantification of empty, partially filled, full and overfull AAV vectors in crude cell extracts. This is aimed at identifying potentially promising harvest conditions that yield large numbers of filled AAV vectors during the early stages of the viral vector development platform, e.g., the type of transfection reagent used. Furthermore, we provide a direct comparison of the automated and manual handling of the mass photometer with respect to the quantities of AAV subspecies, molar mass of the capsid and payload, and highlight the differences between the "buffer-free" sample measurement and the "buffer-dilution" mode. In addition, we provide information on which candidates to use for calibration and demonstrate the limitations of the mass photometer with respect to the estimation of the capsid titer.
MeSH term(s)	Cell Extracts ; Dependovirus/genetics ; Biotechnology ; Calibration ; Capsid Proteins ; Photometry ; Single-Domain Antibodies
Chemical Substances	Cell Extracts ; Capsid Proteins ; Single-Domain Antibodies
Language	English
Publishing date	2024-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25020838
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Article ; Online: Alteration of early dendritic cell activation by cancer cell lines predisposes immunosuppression, which cannot be reversed by TLR4 stimulation.

Kong, Ying Ying / Fuchsberger, Martina / Plebanski, Magdalena / Apostolopoulos, Vasso

Acta biochimica et biophysica Sinica

2016 Volume 48, Issue 12, Page(s) 1101–1111

Abstract: Dendritic cells (DCs) have shown promise for use in cancer vaccine and cancer immunotherapy studies. However, we demonstrate that cancer cell lines can negatively interfere with DC generation in granulocyte-macrophage colony-stimulating factor (GM-CSF)- ... ...

Abstract	Dendritic cells (DCs) have shown promise for use in cancer vaccine and cancer immunotherapy studies. However, we demonstrate that cancer cell lines can negatively interfere with DC generation in granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived cultures, although cancer cells are able to enhance CD80 cell surface activation marker and cytokine secretion. Furthermore, in the presence of cancer cells, GM-CSF-derived DCs are unable to stimulate T-cells. Additional stimulation with toll-like receptor 4 cannot fully reverse the suppressive effect of cancer cells or supernatant. Hence, it is imperative to understand the immunosuppressive effects of cancer on DCs in order for DC-based cancer immunotherapy to be successful.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cell Proliferation ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Immune Tolerance ; Immunotherapy ; Lipopolysaccharides/administration & dosage ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Toll-Like Receptor 4/agonists
Chemical Substances	Lipopolysaccharides ; Tlr4 protein, mouse ; Toll-Like Receptor 4 ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2016-12
Publishing country	China
Document type	Journal Article
ZDB-ID	2175256-4
ISSN	1745-7270 ; 0582-9879 ; 1672-9145
ISSN (online)	1745-7270
ISSN	0582-9879 ; 1672-9145
DOI	10.1093/abbs/gmw102
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Article ; Online: Quantification of Empty, Partially Filled and Full Adeno-Associated Virus Vectors Using Mass Photometry

Christina Wagner / Felix F. Fuchsberger / Bernd Innthaler / Martin Lemmerer / Ruth Birner-Gruenberger

International Journal of Molecular Sciences, Vol 24, Iss 11033, p

2023 Volume 11033

Abstract	Adeno-associated viruses (AAV) are one of the most commonly used vehicles in gene therapies for the treatment of rare diseases. During the AAV manufacturing process, particles with little or no genetic material are co-produced alongside the desired AAV capsid containing the transgene of interest. Because of the potential adverse health effects of these byproducts, they are considered impurities and need to be monitored carefully. To date, analytical ultracentrifugation (AUC), transmission electron microscopy (TEM) and charge-detection mass spectrometry (CDMS) are used to quantify these subspecies. However, they are associated with long turnaround times, low sample throughput and complex data analysis. Mass photometry (MP) is a fast and label-free orthogonal technique which is applicable to multiple serotypes without the adaption of method parameters. Furthermore, it can be operated with capsid titers as low as 8 × 10 10 cp mL −1 with a CV < 5% using just 10 µL total sample volume. Here we demonstrate that mass photometry can be used as an orthogonal method to AUC to accurately quantify the proportions of empty, partially filled, full and overfull particles in AAV samples, especially in cases where ion-exchange chromatography yields no separation of the populations. In addition, it can be used to confirm the molar mass of the packaged genomic material in filled AAV particles.
Keywords	adeno-associated virus vectors ; partially filled particles ; single-molecule mass photometry ; genomic cargo ; analytical ultracentrifugation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	621 ; 333
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Algorithms for railway traffic management in complex central station areas

Fuchsberger, Martin

2012

Abstract: Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 20398, ... ...

Abstract	Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 20398, 2012
Keywords	EISENBAHNVERKEHR (VERKEHR UND TRANSPORT) ; TRANSPORTTHEORIE + VERKEHRSFLUSSTHEORIE (OPERATIONS RESEARCH) ; EISENBAHNBETRIEB + BAHNHÖFE (EISENBAHNVERKEHR) ; VERKEHRSMODELLE + VERKEHRSSIMULATION (VERKEHR UND TRANSPORT) ; VERKEHRSMANAGEMENT (VERKEHR UND TRANSPORT) ; BERN ; STADT (KANTON BERN) ; FALLSTUDIEN (DOKUMENTENTYP)
Language	English
Publisher	Zürich, ETH
Publishing country	ch
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Thesis ; Online: Algorithms for railway traffic management in complex central station areas

Fuchsberger, Martin

2012

Keywords	VERKEHRSMODELLE + VERKEHRSSIMULATION (VERKEHR UND TRANSPORT) ; FALLSTUDIEN (DOKUMENTENTYP) ; CASE STUDIES (DOCUMENT TYPE) ; EISENBAHNBETRIEB + BAHNHÖFE (EISENBAHNVERKEHR) ; TRANSPORT MODELS + TRAFFIC SIMULATION (TRANSPORTATION AND TRAFFIC) ; RAILWAY TRANSPORT (TRANSPORTATION AND TRAFFIC) ; TRAFFIC MANAGEMENT (TRANSPORTATION AND TRAFFIC) ; RAILWAY OPERATION + RAILWAY STATIONS (RAILWAY TRANSPORT) ; TRANSPORTTHEORIE + VERKEHRSFLUSSTHEORIE (OPERATIONS RESEARCH) ; VERKEHRSMANAGEMENT (VERKEHR UND TRANSPORT) ; BERN ; STADT (KANTON BERN) ; BERNE ; CITY (CANTON OF BERNE) ; TRANSPORT THEORY + TRAFFIC FLOW THEORY (OPERATIONS RESEARCH) ; EISENBAHNVERKEHR (VERKEHR UND TRANSPORT) ; info:eu-repo/classification/ddc/380 ; Commerce ; communications ; transport
Language	English
Publisher	ETH
Publishing country	ch
Document type	Thesis ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: On-Chip Neo-Glycopeptide Synthesis for Multivalent Glycan Presentation.

Mende, Marco / Tsouka, Alexandra / Heidepriem, Jasmin / Paris, Grigori / Mattes, Daniela S / Eickelmann, Stephan / Bordoni, Vittorio / Wawrzinek, Robert / Fuchsberger, Felix F / Seeberger, Peter H / Rademacher, Christoph / Delbianco, Martina / Mallagaray, Alvaro / Loeffler, Felix F

Chemistry (Weinheim an der Bergstrasse, Germany)

2020 Volume 26, Issue 44, Page(s) 9954–9963

Abstract: Single glycan-protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent ... ...

Abstract	Single glycan-protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent display. Laser-based array synthesis technology allows for flexible and rapid on-surface synthesis of different peptides. By combining this technique with click chemistry, neo-glycopeptides were produced directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well-defined glycan structures for multivalent display. The two lectins concanavalin A and langerin were probed with different glycans on multivalent scaffolds, revealing strong spacing-, density-, and ligand-dependent binding. In addition, we could also measure the surface dissociation constant. This approach allows for a rapid generation, screening, and optimization of a multitude of multivalent scaffolds for glycan binding.
MeSH term(s)	Binding Sites ; Glycopeptides/analysis ; Glycopeptides/chemical synthesis ; Humans ; Microarray Analysis ; Polysaccharides/analysis ; Polysaccharides/chemical synthesis
Chemical Substances	Glycopeptides ; Polysaccharides
Language	English
Publishing date	2020-06-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202001291
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Article ; Online: Nanoparticles modify dendritic cell homeostasis and induce non-specific effects on immunity to malaria.

Xiang, Sue D / Kong, Ying Y / Hanley, Jennifer / Fuchsberger, Martina / Crimeen-Irwin, Blessing / Plebanski, Magdalena

Transactions of the Royal Society of Tropical Medicine and Hygiene

2015 Volume 109, Issue 1, Page(s) 70–76

Abstract: Background: Many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. We propose that their particulate nature contributes to non-specific effects. Herein, we demonstrate polystyrene ... ...

Abstract	Background: Many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. We propose that their particulate nature contributes to non-specific effects. Herein, we demonstrate polystyrene nanoparticles modulate dendritic cell (DC) homeostasis, thereby promoting a persistent enhanced state of immune readiness to a subsequent infectious challenge. Methods: Particles (approximately 40 nm and 500 nm carboxylated polystyrene nanoparticles; PSNPs) alone or conjugated to a model antigen were injected in mice, and DCs in draining lymph nodes (dLNs) and bone-marrow (BM) quantified by flow cytometry. BM cells were tested for capacity to generate DCs upon culture with granulocyte and macrophage colony stimulating factor. Mice were challenged with Plasmodium yoelli. Blood parasitaemias were monitored by GIEMSA. Sera was analyzed for antibodies by ELISA. Results: Intradermal administration of 40 nm PSNPs induced anti-inflammatory cytokines, chemokines and growth factors, increased numbers and proportions of DCs in the dLN, and increased the capacity of BM to generate DCs. Consistent with these unexpected changes, 40 nm PSNPs pre-injected mice had enhanced ability to generate immunity to a subsequent malarial infection. Conclusions: Intradermal administration of 40 nm PSNPs modifies DC homeostasis, which may at least in part explain the observed beneficial heterologous effects of current particulate vaccines. Further nanotechnological developments may exploit such strategies to promote beneficial non-specific effects.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Animals ; Cytokines/drug effects ; Cytokines/immunology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Disease Models, Animal ; Homeostasis ; Immunoconjugates/pharmacology ; Malaria/immunology ; Malaria/prevention & control ; Malaria Vaccines/pharmacology ; Mice ; Mice, Inbred C57BL ; Nanoparticles/chemistry ; Particle Size ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Vaccines, Synthetic/pharmacology
Chemical Substances	Adjuvants, Immunologic ; Cytokines ; Immunoconjugates ; Malaria Vaccines ; Vaccines, Synthetic
Language	English
Publishing date	2015-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	441375-1
ISSN	1878-3503 ; 0035-9203
ISSN (online)	1878-3503
ISSN	0035-9203
DOI	10.1093/trstmh/tru182
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Article ; Online: Smoking and salivary microbiota: a cross-sectional analysis of an Italian alpine population.

Antonello, Giacomo / Blostein, Freida / Bhaumik, Deesha / Davis, Elyse / Gögele, Martin / Melotti, Roberto / Pramstaller, Peter / Pattaro, Cristian / Segata, Nicola / Foxman, Betsy / Fuchsberger, Christian

Scientific reports

2023 Volume 13, Issue 1, Page(s) 18904

Abstract: The oral microbiota plays an important role in the exogenous nitrate reduction pathway and is associated with heart and periodontal disease and cigarette smoking. We describe smoking-related changes in oral microbiota composition and resulting potential ... ...

Abstract	The oral microbiota plays an important role in the exogenous nitrate reduction pathway and is associated with heart and periodontal disease and cigarette smoking. We describe smoking-related changes in oral microbiota composition and resulting potential metabolic pathway changes that may explain smoking-related changes in disease risk. We analyzed health information and salivary microbiota composition among 1601 Cooperative Health Research in South Tyrol participants collected 2017-2018. Salivary microbiota taxa were assigned from amplicon sequences of the 16S-V4 rRNA and used to describe microbiota composition and predict metabolic pathways. Aerobic taxa relative abundance decreased with daily smoking intensity and increased with years since cessation, as did inferred nitrate reduction. Former smokers tended to be more similar to Never smokers than to Current smokers, especially those who had quit for longer than 5 years. Cigarette smoking has a consistent, generalizable association on oral microbiota composition and predicted metabolic pathways, some of which associate in a dose-dependent fashion. Smokers who quit for longer than 5 years tend to have salivary microbiota profiles comparable to never smokers.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Nitrates ; Cigarette Smoking ; Microbiota/genetics ; Smokers ; RNA, Ribosomal, 16S/genetics
Chemical Substances	Nitrates ; RNA, Ribosomal, 16S
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-42474-7
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