Introduction: Increasing resistance to beta-lactam antibiotics is an alarming development worldwide. Fecal carriership of TEM, SHV, CTX-M and CMY was studied in a community-dwelling population of... Show moreIntroduction: Increasing resistance to beta-lactam antibiotics is an alarming development worldwide. Fecal carriership of TEM, SHV, CTX-M and CMY was studied in a community-dwelling population of middle-aged and elderly individuals.Patients and methods: Feces was obtained from individuals of the Rotterdam Study. Carriership of the TEM, SHV, CTX-M and CMY genes was determined using real-time polymerase chain reaction (qPCR). Possible associations were investigated between carriership of these genes and several risk factors, such as the use of antimicrobial drugs, diabetes mellitus, protein pump inhibitor (PPI) use, travelling, the composition of the gut microbiota, and intake of certain foods.Results: The most prevalent gene was TEM (53.0%), followed by SHV (18.4%), CTX-M (5.4%) and CMY (3.6%). Use of penicillins with extended spectrum was associated with TEM carriership, whereas use of macrolides and lincosamides was associated with TEM and SHV carriership. Interestingly, use of PPIs was associated with a higher prevalence of carriership of TEM, SHV and CMY (TEM: odds ratio [OR] 1.34; 95% confidence interval [CI] 1.05-1.77; SHV: OR 2.17; 95%CI 1.55-2.87; CMY: OR 2.26; 95%CI 1.23-4.11). Furthermore, associations were found between the richness and composition of the gut microbiota and TEM and SHV carriership.Conclusions: The prevalence of carriership of TEM was substantial, but the prevalence of carriership of the extended-spectrum beta-lactamase gene, CTX-M and the AmpC beta-lactamase gene, CMY was relatively low in this community-dwelling, population-based cohort. The composition of the microbiota might play a role in the retention of resistance genes, but future studies are necessary to further elucidate this relationship. (C) 2021 Published by Elsevier Ltd. Show less
Photosynthesis is a highly cross linked process. However, we can distinguish a set of fundamental building blocks like chlorophylls, which interact to form photosystem, which performs the complex... Show morePhotosynthesis is a highly cross linked process. However, we can distinguish a set of fundamental building blocks like chlorophylls, which interact to form photosystem, which performs the complex function of water splitting. The key challenge in artificial photosynthesis is to learn how to design systems that can adapt and optimize their topologies in line with self-assembly of natural photosystem. In this thesis I combine different techniques of cross polarization Magic angle spinning Nuclear Magnetic Resonance and Transmission Electron Microscopy with simulation and modeling, to resolve the global packing of molecules which are potential candidates for efficient solar fuel cell devices. This thesis focuses on the packing analysis of three-dimensional structures, which are heterogeneous in nature. I demonstrate a new and general structure determination approach that, in combination with first-principles quantum chemical calculations, establishes the structures of molecularly ordered antenna complexes that lack long-range 3D atomic crystalline order. This is possible despite the absence of a priori information on the space group or atomic coordinates. Chapter 2 describes DATZnS(3ʹ-NMe) parallel stacking in an antiparallel framework with the P2/c space group. 13C CP/MAS NMR yields number of asymmetric sites in the structure and recognition motif. This in conjunction with unit cell parameters and diffraction spots from the Fourier transformation of a TEM image is used to resolve the structure. Supramolecular recognition motif is a characteristic of the packing of the DATZnS(3ʹ-NMe) molecule. The molecular recognition and molecular symmetry steer the packing into a racemic mixture with a c-glide plane and inversion symmetry to release the steric hindrance. Simulation of the LGCP build up curve between specific pairs and electron diffraction were used to validate the proposed packing. Chapter 3 describes the centerosymmetric dimer formation with NMI extending outwards to capture the solar energy. MAS NMR chemical shifts were used to generate a truncated 1,7-perylene-3,4,9,10-tetracarboxylic monoimide dibutylester motif. This motif is further optimized and used for molecular replacement approach to generate a partial 3D electron density approach. The P-1 symmetry obtained from Electron Nano Crystallography is used to graft the naphathelene monoimide substituents. The alkyl chains are modeled using the intermolecular correlation observed in HETCOR. Naphthalene monoimide antennas projecting out from the rows of dimers formed out of rod type D1A2 could capture the light energy and transfer to dimers through FRET. Finally, in chapter 4 C2 molecular symmetry obtained from MAS NMR and DFT modeling is used as the core motif to propose the packing of the DATZnS(4H). Intermolecular correlations obtained from the HETCOR shows the folding of the tails along the phenazine moiety. The analogous modeling showed how the packing could be steered by the NCH3 functional group between antiparallel and parallel dipoles. This understanding opens the way for the evidence based design of light harvesting antenna. In summary, a novel methodology to resolve the structure of chromophore antenna from a structural background with static and dynamic heterogeneity that strongly limits the diffraction response is shown. Furthermore, I anticipate that the insights into packing of the antenna are key to the design of the organic solar fuel cell device in the future. Show less
In the past decade, advances in structure determination with electron microscopy of organic, beam sensitive, materials have been significant. The newly developed techniques, triggered by new... Show moreIn the past decade, advances in structure determination with electron microscopy of organic, beam sensitive, materials have been significant. The newly developed techniques, triggered by new microscope systems and new cameras, made it possible to acquire 3D structural information from these samples to a resolution which was impossible to achieve before. Knowledge is required to improve structure solution and every aspect of the process involved, from treatment of radiation sensitive materials, sample preparation, TEM imaging and diffraction systems all the way to how data must be interpreted. In this thesis I explained multiple new techniques and methods developed by us, using both new microscopes as well as a new type of detector: Timepix. I describe how these tools can help to overcome (what were) the most important problems and bottlenecks in detection of very low dose electron diffraction. Show less
Buddendiek, A.; Schrabback, T.; Greer, C.H.; Hoekstra, H.; Sommer, M.; Eifler, T.; ... ; Linden, A. von der 2015
