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Background: Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. Methods: This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. Results: We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. Conclusion: The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, an

Background: Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. Methods: This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. Results: We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. Conclusion: The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, an

The geometric relaxation following light absorption of the biliverdin, phycocyanobilin and phytochromobilin tetrapyrrole chromophores of bacterial, cyanobacterial and plant phytochromes has been investigated using density functional theory methods. Considering stereoisomers relevant for both red-absorbing Pr and far-red-absorbing Pfr forms of the photoreceptor, it is found that the initial excited-state evolution is dominated by torsional motion at the C10-C11 bond. This holds true for all three chromophores and irrespective of which configuration the chromophores adopt. This finding suggests that the photochromic cycling of phytochromes between their Pr and Pfr forms, which is known to be governed by Z/E photoisomerizations at the C15-C16 bond, relies on interactions between the chromophore and the protein to prevent photoisomerizations at C10-C11. Further, it is found that the uneven distribution of positive charge between the pyrrole rings is a major factor for the photochemical reactivity of the C10-C11 bond., Original Publication:Angela Strambi and Bo Durbeej, Initial excited-state relaxation of the bilin chromophores of phytochromes: a computational study, 2011, PHOTOCHEMICAL and PHOTOBIOLOGICAL SCIENCES, (10), 4, 569-579.http://dx.doi.org/10.1039/c0pp00307gCopyright: Royal Society of Chemistryhttp://www.rsc.org

The geometric relaxation following light absorption of the biliverdin, phycocyanobilin and phytochromobilin tetrapyrrole chromophores of bacterial, cyanobacterial and plant phytochromes has been investigated using density functional theory methods. Considering stereoisomers relevant for both red-absorbing Pr and far-red-absorbing Pfr forms of the photoreceptor, it is found that the initial excited-state evolution is dominated by torsional motion at the C10-C11 bond. This holds true for all three chromophores and irrespective of which configuration the chromophores adopt. This finding suggests that the photochromic cycling of phytochromes between their Pr and Pfr forms, which is known to be governed by Z/E photoisomerizations at the C15-C16 bond, relies on interactions between the chromophore and the protein to prevent photoisomerizations at C10-C11. Further, it is found that the uneven distribution of positive charge between the pyrrole rings is a major factor for the photochemical reactivity of the C10-C11 bond., Original Publication:Angela Strambi and Bo Durbeej, Initial excited-state relaxation of the bilin chromophores of phytochromes: a computational study, 2011, PHOTOCHEMICAL and PHOTOBIOLOGICAL SCIENCES, (10), 4, 569-579.http://dx.doi.org/10.1039/c0pp00307gCopyright: Royal Society of Chemistryhttp://www.rsc.org

The geometric relaxation following light absorption of the biliverdin, phycocyanobilin and phytochromobilin tetrapyrrole chromophores of bacterial, cyanobacterial and plant phytochromes has been investigated using density functional theory methods. Considering stereoisomers relevant for both red-absorbing Pr and far-red-absorbing Pfr forms of the photoreceptor, it is found that the initial excited-state evolution is dominated by torsional motion at the C10-C11 bond. This holds true for all three chromophores and irrespective of which configuration the chromophores adopt. This finding suggests that the photochromic cycling of phytochromes between their Pr and Pfr forms, which is known to be governed by Z/E photoisomerizations at the C15-C16 bond, relies on interactions between the chromophore and the protein to prevent photoisomerizations at C10-C11. Further, it is found that the uneven distribution of positive charge between the pyrrole rings is a major factor for the photochemical reactivity of the C10-C11 bond., Original Publication:Angela Strambi and Bo Durbeej, Initial excited-state relaxation of the bilin chromophores of phytochromes: a computational study, 2011, PHOTOCHEMICAL and PHOTOBIOLOGICAL SCIENCES, (10), 4, 569-579.http://dx.doi.org/10.1039/c0pp00307gCopyright: Royal Society of Chemistryhttp://www.rsc.org

The geometric relaxation following light absorption of the biliverdin, phycocyanobilin and phytochromobilin tetrapyrrole chromophores of bacterial, cyanobacterial and plant phytochromes has been investigated using density functional theory methods. Considering stereoisomers relevant for both red-absorbing Pr and far-red-absorbing Pfr forms of the photoreceptor, it is found that the initial excited-state evolution is dominated by torsional motion at the C10-C11 bond. This holds true for all three chromophores and irrespective of which configuration the chromophores adopt. This finding suggests that the photochromic cycling of phytochromes between their Pr and Pfr forms, which is known to be governed by Z/E photoisomerizations at the C15-C16 bond, relies on interactions between the chromophore and the protein to prevent photoisomerizations at C10-C11. Further, it is found that the uneven distribution of positive charge between the pyrrole rings is a major factor for the photochemical reactivity of the C10-C11 bond., Original Publication:Angela Strambi and Bo Durbeej, Initial excited-state relaxation of the bilin chromophores of phytochromes: a computational study, 2011, PHOTOCHEMICAL and PHOTOBIOLOGICAL SCIENCES, (10), 4, 569-579.http://dx.doi.org/10.1039/c0pp00307gCopyright: Royal Society of Chemistryhttp://www.rsc.org

The geometric relaxation following light absorption of the biliverdin, phycocyanobilin and phytochromobilin tetrapyrrole chromophores of bacterial, cyanobacterial and plant phytochromes has been investigated using density functional theory methods. Considering stereoisomers relevant for both red-absorbing Pr and far-red-absorbing Pfr forms of the photoreceptor, it is found that the initial excited-state evolution is dominated by torsional motion at the C10-C11 bond. This holds true for all three chromophores and irrespective of which configuration the chromophores adopt. This finding suggests that the photochromic cycling of phytochromes between their Pr and Pfr forms, which is known to be governed by Z/E photoisomerizations at the C15-C16 bond, relies on interactions between the chromophore and the protein to prevent photoisomerizations at C10-C11. Further, it is found that the uneven distribution of positive charge between the pyrrole rings is a major factor for the photochemical reactivity of the C10-C11 bond., Original Publication:Angela Strambi and Bo Durbeej, Initial excited-state relaxation of the bilin chromophores of phytochromes: a computational study, 2011, PHOTOCHEMICAL and PHOTOBIOLOGICAL SCIENCES, (10), 4, 569-579.http://dx.doi.org/10.1039/c0pp00307gCopyright: Royal Society of Chemistryhttp://www.rsc.org

The implementation of multiconfigurational quantum chemistry methods into a quantum-mechanics/molecular-mechanics protocol has allowed the construction of a realistic computer model for the sensory rhodopsin of the cyanobacterium Anabaena PCC 7120. The model, which reproduces the absorption spectra of both the all-trans and 13-cis forms of the protein and their associated K and L intermediates, is employed to investigate the light-driven steps of the photochromic cycle exhibited by the protein. It is found that the photoisomerizations of the all-trans and 13-cis retinal chromophores occur through unidirectional, counterclockwise 180 deg rotations of the =C14-C15= moiety with respect to the Lys210-linked end of the chromophore axis. Thus, the sequential interconversions of the all-trans and 13-cis forms during a single photochromic cycle yield a complete (360 deg) unidirectional rotation of the =C14-C15= moiety. This finding implies that Anabaena sensory rhodopsin is a biological realization of a light-driven molecular rotor., Original Publication:Angela Strambi, Bo Durbeej, Nicolas Ferre and Massimo Olivucci, Anabaena sensory rhodopsin is a light-driven unidirectional rotor, 2010, Proceedings of the National Academy of Sciences of the United States of America, (107), 50, 21322-21326.http://dx.doi.org/10.1073/pnas.1015085107Copyright: National Academy of Sciences; 1999http://www.nas.edu

The implementation of multiconfigurational quantum chemistry methods into a quantum-mechanics/molecular-mechanics protocol has allowed the construction of a realistic computer model for the sensory rhodopsin of the cyanobacterium Anabaena PCC 7120. The model, which reproduces the absorption spectra of both the all-trans and 13-cis forms of the protein and their associated K and L intermediates, is employed to investigate the light-driven steps of the photochromic cycle exhibited by the protein. It is found that the photoisomerizations of the all-trans and 13-cis retinal chromophores occur through unidirectional, counterclockwise 180 deg rotations of the =C14-C15= moiety with respect to the Lys210-linked end of the chromophore axis. Thus, the sequential interconversions of the all-trans and 13-cis forms during a single photochromic cycle yield a complete (360 deg) unidirectional rotation of the =C14-C15= moiety. This finding implies that Anabaena sensory rhodopsin is a biological realization of a light-driven molecular rotor., Original Publication:Angela Strambi, Bo Durbeej, Nicolas Ferre and Massimo Olivucci, Anabaena sensory rhodopsin is a light-driven unidirectional rotor, 2010, Proceedings of the National Academy of Sciences of the United States of America, (107), 50, 21322-21326.http://dx.doi.org/10.1073/pnas.1015085107Copyright: National Academy of Sciences; 1999http://www.nas.edu

The implementation of multiconfigurational quantum chemistry methods into a quantum-mechanics/molecular-mechanics protocol has allowed the construction of a realistic computer model for the sensory rhodopsin of the cyanobacterium Anabaena PCC 7120. The model, which reproduces the absorption spectra of both the all-trans and 13-cis forms of the protein and their associated K and L intermediates, is employed to investigate the light-driven steps of the photochromic cycle exhibited by the protein. It is found that the photoisomerizations of the all-trans and 13-cis retinal chromophores occur through unidirectional, counterclockwise 180 deg rotations of the =C14-C15= moiety with respect to the Lys210-linked end of the chromophore axis. Thus, the sequential interconversions of the all-trans and 13-cis forms during a single photochromic cycle yield a complete (360 deg) unidirectional rotation of the =C14-C15= moiety. This finding implies that Anabaena sensory rhodopsin is a biological realization of a light-driven molecular rotor., Original Publication:Angela Strambi, Bo Durbeej, Nicolas Ferre and Massimo Olivucci, Anabaena sensory rhodopsin is a light-driven unidirectional rotor, 2010, Proceedings of the National Academy of Sciences of the United States of America, (107), 50, 21322-21326.http://dx.doi.org/10.1073/pnas.1015085107Copyright: National Academy of Sciences; 1999http://www.nas.edu

The implementation of multiconfigurational quantum chemistry methods into a quantum-mechanics/molecular-mechanics protocol has allowed the construction of a realistic computer model for the sensory rhodopsin of the cyanobacterium Anabaena PCC 7120. The model, which reproduces the absorption spectra of both the all-trans and 13-cis forms of the protein and their associated K and L intermediates, is employed to investigate the light-driven steps of the photochromic cycle exhibited by the protein. It is found that the photoisomerizations of the all-trans and 13-cis retinal chromophores occur through unidirectional, counterclockwise 180 deg rotations of the =C14-C15= moiety with respect to the Lys210-linked end of the chromophore axis. Thus, the sequential interconversions of the all-trans and 13-cis forms during a single photochromic cycle yield a complete (360 deg) unidirectional rotation of the =C14-C15= moiety. This finding implies that Anabaena sensory rhodopsin is a biological realization of a light-driven molecular rotor., Original Publication:Angela Strambi, Bo Durbeej, Nicolas Ferre and Massimo Olivucci, Anabaena sensory rhodopsin is a light-driven unidirectional rotor, 2010, Proceedings of the National Academy of Sciences of the United States of America, (107), 50, 21322-21326.http://dx.doi.org/10.1073/pnas.1015085107Copyright: National Academy of Sciences; 1999http://www.nas.edu

The implementation of multiconfigurational quantum chemistry methods into a quantum-mechanics/molecular-mechanics protocol has allowed the construction of a realistic computer model for the sensory rhodopsin of the cyanobacterium Anabaena PCC 7120. The model, which reproduces the absorption spectra of both the all-trans and 13-cis forms of the protein and their associated K and L intermediates, is employed to investigate the light-driven steps of the photochromic cycle exhibited by the protein. It is found that the photoisomerizations of the all-trans and 13-cis retinal chromophores occur through unidirectional, counterclockwise 180 deg rotations of the =C14-C15= moiety with respect to the Lys210-linked end of the chromophore axis. Thus, the sequential interconversions of the all-trans and 13-cis forms during a single photochromic cycle yield a complete (360 deg) unidirectional rotation of the =C14-C15= moiety. This finding implies that Anabaena sensory rhodopsin is a biological realization of a light-driven molecular rotor., Original Publication:Angela Strambi, Bo Durbeej, Nicolas Ferre and Massimo Olivucci, Anabaena sensory rhodopsin is a light-driven unidirectional rotor, 2010, Proceedings of the National Academy of Sciences of the United States of America, (107), 50, 21322-21326.http://dx.doi.org/10.1073/pnas.1015085107Copyright: National Academy of Sciences; 1999http://www.nas.edu

The >0.50 eV bathochromic shift of the absorption by the carotenoid astaxanthin in crustacyanin, the carotenoprotein responsible for the coloration of lobster shell, is believed to result from ground-state polarization of the chromophore and/or exciton coupling between the two chromophores of each protein subunit. Here, the contribution of exciton coupling to the shift is quantified using quantum chemical calculations that do not rely on the dipole-dipole approximation but rather consider the full astaxanthin dimer in the geometry relevant for the protein-bound state. Employing a variety of methods, it is found that the exciton coupling amounts to 0.04 eV only. Furthermore, even when more closely aggregated dimers than the one in the protein are considered, the predicted couplings remain small (0.05-0.09 eV). These findings demonstrate that the bathochromic shift cannot be explained in terms of exciton coupling. It is therefore argued that polarization is likely to be the dominant mechanism, a notion supported by the fact that calculations carried out at the same levels of theory identify a scenario (hydrogen bonding with a histidine residue) whose contribution to the shift vastly exceeds that of exciton coupling.

We have developed automatic methods to calculate multipoles and anisotropic polarizabilities for all atoms and bond centers in a protein and to include such a model in the calculation of electronic properties at any level of quantum mechanical theory. This approach is applied for the calculation of the electronic spectra of retinal in rhodopsin at the CASPT2//CASSCF level (second-order multiconfigurational perturbation theory) for the wild-type protein, as well as two mutants and isorhodopsin in QM/MM structures based on two crystal structures. We also perform a detailed investigation of the importance and distance dependence of the multipoles and the polarizabilities for both the absolute and the relative absorption energies. It is shown that the model of the surrounding protein strongly influences the spectrum and that different models give widely different results. For example, the Amber 1994 and 2003 force fields give excitation energies that differ by up to 16 kJ/mol. For accurate excitation energies, multipoles up to quadrupoles and anisotropic polarizabilities are needed. However, interactions with residues more than 10 A from the chromophore can be treated with a standard polarizable force field without any dipoles or quadrupoles.

The >0.50 eV bathochromic shift of the absorption by the carotenoid astaxanthin in crustacyanin, the carotenoprotein responsible for the coloration of lobster shell, is believed to result from ground-state polarization of the chromophore and/or exciton coupling between the two chromophores of each protein subunit. Here, the contribution of exciton coupling to the shift is quantified using quantum chemical calculations that do not rely on the dipole-dipole approximation but rather consider the full astaxanthin dimer in the geometry relevant for the protein-bound state. Employing a variety of methods, it is found that the exciton coupling amounts to 0.04 eV only. Furthermore, even when more closely aggregated dimers than the one in the protein are considered, the predicted couplings remain small (0.05-0.09 eV). These findings demonstrate that the bathochromic shift cannot be explained in terms of exciton coupling. It is therefore argued that polarization is likely to be the dominant mechanism, a notion supported by the fact that calculations carried out at the same levels of theory identify a scenario (hydrogen bonding with a histidine residue) whose contribution to the shift vastly exceeds that of exciton coupling.