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"Wittwer, Samuel"
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Neues Palais in Sanssouci
A hundred years ago, the baroque Neues Palais in Sanssouci Gardens became a museum. Today's visitors are scarcely aware that its room sequences continue beyond the palatial interiors, and served for a long time as workshops, offices, or depots. Due to a comprehensive restoration of the castle, these functions have now been moved elsewhere, which marks a major turning point for the Neues Palais. For Samuel Wittwer, Director of the Department of Castles and Collections, it seemed important to preserve the unique atmosphere of the castle during the transition period, taking an artistic rather than objectively documentary look at the character of the building. Berlin based photographer Friederike von Rauch succeeded in doing so convincingly on her countless forays through the castle: she has captured the special features in detail as well as in wider pictorial gestures. With insightful observations, texts by Rudolf Prinz zur Lippe provide accomplished counterpoints to the visual highlights. The result is a book that goes beyond conventional notions Prussia's castles have never presented themselvesso poetically before.
Book
Cooperative partner choice in multi-level male dolphin alliances
Investigations into cooperative partner choice should consider both potential and realised partners, allowing for the comparison of traits across all those available. Male bottlenose dolphins form persisting multi-level alliances. Second-order alliances of 4–14 males are the core social unit, within which 2–3 males form first-order alliances to sequester females during consortships. We compared social bond strength, relatedness and age similarity of potential and realised partners of individual males in two age periods: (i) adolescence, when second-order alliances are formed from all available associates, and (ii) adulthood, when first-order allies are selected from within second-order alliances. Social bond strength during adolescence predicted second-order alliance membership in adulthood. Moreover, males preferred same-aged or older males as second-order allies. Within second-order alliances, non-mating season social bond strength predicted first-order partner preferences during mating season consortships. Relatedness did not influence partner choice on either alliance level. There is thus a striking resemblance between male dolphins, chimpanzees and humans, where closely bonded non-relatives engage in higher-level, polyadic cooperative acts. To that end, our study extends the scope of taxa in which social bonds rather than kinship explain cooperation, providing the first evidence that such traits might have evolved independently in marine and terrestrial realms.
Journal Article
Inter-group alliance dynamics in Indo-Pacific bottlenose dolphins (Tursiops aduncus)
The social intelligence hypothesis holds that complex social relationships are the major selective force underlying the evolution of large brain size and intelligence. Complex social relationships are exemplified by coalitions and alliances that are mediated by affiliative behavior, resulting in differentiated but shifting relationships. Male Indo-Pacific bottlenose dolphins in Shark Bay, Australia, form three alliance levels or ‘orders’, primarily among non-relatives. Strategic alliance formation has been documented within both first- and second-order alliances and between second-order alliances (‘third-order alliances’), revealing that the formation of strategic inter-group alliances is not limited to humans. Here we conducted a fine-scale study on 22 adult males over a 6-year period to determine if third-order alliance relationships are differentiated, and mediated by affiliative interactions. We found third-order alliance relationships were strongly differentiated, with key individuals playing a disproportionate role in maintaining alliances. Nonetheless, affiliative interactions occurred broadly between third-order allies, indicating males maintain bonds with third-order allies of varying strength. We also documented a shift in relationships and formation of a new third-order alliance. These findings further our understanding of dolphin alliance dynamics and provide evidence that strategic alliance formation is found in all three alliance levels, a phenomenon with no peer among non-human animals.
Journal Article
The Prevalence of Potential Drug-Drug-Gene Interactions: A Descriptive Study Using Swiss Claims Data
We aimed to determine the prevalence of interactions between PGx drugs metabolized by CYP2C9, CYP2C19, and CYP2D6 and drugs that act as inhibitors or inducers of those enzymes in the Swiss population.
We defined concomitant use of PGx drugs and inhibitors/inducers as instances where a claim of a PGx drug and a claim of an inducer or inhibitor concerning the same enzyme were made within a specified temporal window, either ± 5 days or ± 30 days. We assessed concomitant drug use between 2017 and 2021, using claims data from a Swiss insurance company (Helsana).
Out of 894,748 individuals continuously insured, between 17.4% (± 5-days window) and 24.8% (± 30-days window) were exposed to potentially interacting drug pairs, with 1.5% to 2.2% being exposed to potentially strong interacting drug pairs. Individuals exposed to potentially interacting drugs were more frequently female, older and took a greater number of drugs than the general population. The majority of potential interactions were associated with CYP2D6 or CYP2C19.
In light of the high prevalence of the simultaneous use of PGx drugs with inhibitor and inducer drugs, it is imperative to consider non-genetic factors, such as drug-induced phenoconversions, when interpreting PGx test results.
Journal Article
Comprehensive Description of an Automated Drug Dispensing System Database
Medifilm is a company that blisters drug therapies recorded by pharmacists in the Medifilm software. The Medifilm dataset collates this information and provides details on drug substances, dosages, pharmacotherapy duration, the sequence of therapies, as well as demographic data on the patients. This article aims to provide an overview of the database, to describe the contents, and to demonstrate possibilities for researchers. The database and the recorded information were described. Furthermore, the data coverage was characterized in terms of the number of available pharmacies, patients, and their drug regimens. The database has been recording data since 2013 and has registered 470,801 blistered therapies for 45,594 patients ordered by 441 pharmacies so far. The longitudinal nature of the database allows researchers to study drug utilization, including medication changes, initiations, and discontinuations over time.
Journal Article
A “Culture” Shift: Broad Bacterial Detection, Identification, and Antimicrobial Susceptibility Testing Directly from Whole Blood
The time required for bloodstream pathogen detection, identification (ID), and antimicrobial susceptibility testing (AST) does not satisfy the acute needs of disease management. Conventional methods take up to 3 days for ID and AST. Molecular diagnostics have reduced times for ID, but their promise to supplant culture is unmet because AST times remain slow. We developed a combined quantitative PCR (qPCR)-based ID+AST assay with sequential detection, ID, and AST of leading nosocomial bacterial pathogens.
ID+AST was performed on whole blood samples by (
) removing blood cells, (
) brief bacterial enrichment, (
) bacterial detection and ID, and (
) species-specific antimicrobial treatment. Broad-spectrum qPCR of the internal transcribed spacer between the 16S and 23S was amplified for detection. High-resolution melting identified the species with a curve classifier. AST was enabled by Ct differences between treated and untreated samples.
A detection limit of 1 CFU/mL was achieved for
,
,
, and
. All species were accurately identified by unique melting curves. Antimicrobial minimum inhibitory concentrations were identified with Ct differences of ≥1 cycle. Using an RNA target allowed reduction of AST incubation time from 60 min to 5 min. Rapid-cycle amplification reduced qPCR times by 83% to 30 min.
Combined, sequential ID+AST protocols allow rapid and reliable detection, ID, and AST for the diagnosis of bloodstream infections, enabling conversion of empiric to targeted therapy by the second dose of antimicrobials.
Journal Article
Utilization of Drugs with Pharmacogenetic Dosing Recommendations in Switzerland: A Descriptive Study Using the Helsana Database
Purpose: In Switzerland 167 drugs on the market contain information about pharmacogenetics in their drug label (PGx drug). Preemptive pharmacogenetic testing is reimbursed by health care insurance for only seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fuorouracil, capecitabine, and irinotecan) although, it is proposed to be a cost-effective approach to personalized medicine. The aim of this study was to describe the use of PGx drugs and their corresponding genes in Switzerland. Methods: We identified 90 drugs with dosing recommendations from the Pharmacogenetic Knowledgebase involving 24 genes. We assessed the utilization of those drugs between 2016 and 2020, using claims data from a large Swiss insurance company (Helsana). Results: Of 841 491 persons with drug claims during the whole study period, 78.7% were exposed to PGx drugs. Ibuprofen, pantoprazole, and tramadol had the highest number of users. Seven genes (CYP2C19, CYP2C9, CYP2D6, SLCO1B1, HLA-B, MTRNR1, and VKORC1) were responsible for over 95% of all potential drug-gene interactions. Conclusion: The prevalence of PGx drug prescriptions is high in the Swiss population. Therefore, intensified preemptive testing may be a useful option as a substantial amount of the Swiss population might benefit. Keywords: PGx, drug use, claims data, pharmacoepidemiology
Journal Article
Draft Genome Sequence of Chromatium okenii Isolated from the Stratified Alpine Lake Cadagno
Blooms of purple sulfur bacteria (PSB) are important drivers of the global sulfur cycling oxidizing reduced sulfur in intertidal flats and stagnant water bodies. Since the discovery of PSB
Chromatium okenii
in 1838, it has been found that this species is characteristic of for stratified, sulfidic environments worldwide and its autotrophic metabolism has been studied in depth since. We describe here the first high-quality draft genome of a large-celled, phototrophic,
γ
-proteobacteria of the genus
Chromatium
isolated from the stratified alpine Lake Cadagno,
C
.
okenii
strain LaCa. Long read technology was used to assemble the 3.78 Mb genome that encodes 3,016 protein-coding genes and 67 RNA genes. Our findings are discussed from an ecological perspective related to Lake Cadagno. Moreover, findings of previous studies on the phototrophic and the proposed chemoautotrophic metabolism of
C
.
okenii
were confirmed on a genomic level. We additionally compared the
C
.
okenii
genome with other genomes of sequenced, phototrophic sulfur bacteria from the same environment. We found that biological functions involved in chemotaxis, movement and S-layer-proteins were enriched in strain LaCa. We describe these features as possible adaptions of strain LaCa to rapidly changing environmental conditions within the chemocline and the protection against phage infection during blooms. The high quality draft genome of
C
.
okenii
strain LaCa thereby provides a basis for future functional research on bioconvection and phage infection dynamics of blooming PSB.
Journal Article
Anoxygenic Photosynthesis and Dark Carbon Metabolism under micro-oxic conditions in the Purple Sulfur Bacterium \Thiodictyon syntrophicum\ nov. strain Cad16T
The microbial ecosystem of the meromictic Lake Cadagno (Ticino, Swiss Alps) has been studied intensively to understand metabolic functions driven by the highly abundant anoxygenic phototrophic sulfur bacteria of the families Chromatiaceae and Chlorobiaceae. It was found that the sequenced isolate \"Thiodictyon syntrophicum\" nov. sp. str. Cad16T, belonging to the Chromatiaceae, may fix 26% of all bulk inorganic carbon in the chemocline at day and night. With this study, we elucidated the mode of dark carbon fixation of str. Cad16T with a combination of long-term monitoring of key physicochemical parameters with CTD, 14C-incorporation experiments and quantitative proteomics of in situ dialysis bag incubations of pure cultures. Regular vertical CTD profiling during the study period in summer 2017 revealed that the chemocline sank from 12 to 14 m which was accompanied by a bloom of cyanobacteria and the subsequent oxygenation of the deeper water column. Sampling was performed both day and night in September. While CO2 assimilation rates were higher during the light period, the relative change in the proteome (663 quantified proteins) was only 1% of all CDS encoded in str. Cad16T. Oxidative respiration was thereby upregulated at light, whereas stress-related mechanisms prevailed during the night. These results indicate that the low light availability due to high cell concentrations and the oxygenation of the chemocline induced a mixotrophic growth in str. Cad16T. The complete proteome data have been deposited to the ProteomeXchange with identifier PXD010641.
Paper