| 1. |
- Loibl, S., et al.
(författare)
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ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC)
- 2023
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Ingår i: Annals of Oncology. - 0923-7534. ; 34:10, s. 849-866
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Tidskriftsartikel (refereegranskat)abstract
- The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: 1. PrBC: incidence, epidemiology, biology and pathology, diagnostic work-up, staging and risk assessment, prognosis (Chairs: Vincent Vandecaveye, Fedro Peccatori). 2. Clinical pharmacology of systemic agents during pregnancy: management of localized disease and (neo) adjuvant therapies, management of systemic disease (Chairs: Giuseppe Curigliano, Peter Schmid). 3. Obstetric care and fetal/newborn follow-up and outcomes: metastases to fetus, management of pregnancy during anticancer therapy, lactation, psychological support (Chairs: Elyce Cardonick, Mathilde van Gerwen). Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.
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| 4. |
- Alcalde, J., et al.
(författare)
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3-D reflection seismic imaging of the Hontomin structure in the Basque-Cantabrian Basin (Spain)
- 2013
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Ingår i: Solid Earth. - : Copernicus GmbH. - 1869-9510 .- 1869-9529. ; 4:2, s. 481-496
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Tidskriftsartikel (refereegranskat)abstract
- The Basque-Cantabrian Basin of the northern Iberia Peninsula constitutes a unique example of a major deformation system, featuring a dome structure developed by extensional tectonics followed by compressional reactivation. The occurrence of natural resources in the area and the possibility of establishing a geological storage site for carbon dioxide motivated the acquisition of a 3-D seismic reflection survey in 2010, centered on the Jurassic Hontomin dome. The objectives of this survey were to obtain a geological model of the overall structure and to establish a baseline model for a possible geological CO2 storage site. The 36 km(2) survey included approximately 5000 mixed (Vibroseis and explosives) source points recorded with a 25 m inline source and receiver spacing. The target reservoir is a saline aquifer, at approximately 1450 m depth, encased and sealed by carbonate formations. Acquisition and processing parameters were influenced by the rough topography and relatively complex geology. A strong near-surface velocity inversion is evident in the data, affecting the quality of the data. The resulting 3-D image provides constraints on the key features of the geologic model. The Hontom n structure is interpreted to consist of an approximately 10(7) m(2) large elongated dome with two major (W-E and NW-SE) striking faults bounding it. Preliminary capacity estimates indicate that about 1.2 Gt of CO2 can be stored in the target reservoir.
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| 5. |
- Butlin, Roger, 1955, et al.
(författare)
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PARALLEL EVOLUTION OF LOCAL ADAPTATION AND REPRODUCTIVE ISOLATION IN THE FACE OF GENE FLOW
- 2014
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Ingår i: Evolution. - : Wiley. - 0014-3820. ; 68:4, s. 935-949
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Tidskriftsartikel (refereegranskat)abstract
- Parallel evolution of similar phenotypes provides strong evidence for the operation of natural selection. Where these phenotypes contribute to reproductive isolation, they further support a role for divergent, habitat-associated selection in speciation. However, the observation of pairs of divergent ecotypes currently occupying contrasting habitats in distinct geographical regions is not sufficient to infer parallel origins. Here we show striking parallel phenotypic divergence between populations of the rocky-shore gastropod, Littorina saxatilis, occupying contrasting habitats exposed to either wave action or crab predation. This divergence is associated with barriers to gene exchange but, nevertheless, genetic variation is more strongly structured by geography than by ecotype. Using approximate Bayesian analysis of sequence data and amplified fragment length polymorphism markers, we show that the ecotypes are likely to have arisen in the face of continuous gene flow and that the demographic separation of ecotypes has occurred in parallel at both regional and local scales. Parameter estimates suggest a long delay between colonization of a locality and ecotype formation, perhaps because the postglacial spread of crab populations was slower than the spread of snails. Adaptive differentiation may not be fully genetically independent despite being demographically parallel. These results provide new insight into a major model of ecologically driven speciation.
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| 6. |
- Drotz, Marcus K., et al.
(författare)
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Ecotype Differentiation in the Face of Gene Flow within the Diving Beetle Agabus bipustulatus (Linnaeus, 1767) in Northern Scandinavia
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2, s. e31381-
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Tidskriftsartikel (refereegranskat)abstract
- The repeated occurrence of habitat-specific polyphyletic evolved ecotypes throughout the ranges of widely distributed species implies that multiple, independent and parallel selection events have taken place. Ecological transitions across altitudinal gradients over short geographical distances are often associated with variation in habitat-related fitness, these patterns suggest the action of strong selective forces. Genetic markers will therefore contribute differently to differences between ecotypes in local hybrid zones. Here we have studied the adaptive divergence between ecotypes of the water beetle Agabus bipustulatus along several parallel altitudinal gradients in northern Scandinavia. This water beetle is well known for its remarkable morphological variation associated with mountain regions throughout the western Palaearctic. Two morphological ecotypes are recognised: a montane type with reduced flight muscles and a lowland type with fully developed muscles. Using a multilocus survey of allozyme variation and a morphological analysis with landmark-based morphometrics, across thirty-three populations and seven altitudinal gradients, we studied the local adaptive process of gene flow and selection in detail. Populations were sampled at three different elevations: below, at and above the tree line. The results indicate that the levels of divergence observed between ecotypes in morphology and allele frequencies at alpha-Glycerophosphate dehydrogenase relative to those shown by neutral molecular markers reflects local diversifying selection in situ. Four main lines of evidence are shown here: (1) A repeated morphological pattern of differentiation is observed across all altitudinal transects, with high reclassification probabilities. (2) Allele and genotype frequencies at the alpha-Gpdh locus are strongly correlated with altitude, in sharp contrast to the presumable neutral markers. (3) Genetic differentiation is two to three times higher among populations across the tree line than among populations at or below. (4) Genetic differentiation between ecotypes within independent mountain areas is reflected by different sets of allozymes.
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| 8. |
- Mühlbauer, Max E., et al.
(författare)
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Water-Gated Proton Transfer Dynamics in Respiratory Complex I
- 2020
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 142:32, s. 13718-13728
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory complex I transduces redox energy into an electrochemical proton gradient in aerobic respiratory chains, powering energy-requiring processes in the cell. However, despite recently resolved molecular structures, the mechanism of this gigantic enzyme remains poorly understood. By combining large-scale quantum and classical simulations with site-directed mutagenesis and biophysical experiments, we show here how the conformational state of buried ion-pairs and water molecules control the protonation dynamics in the membrane domain of complex I and establish evolutionary conserved long-range coupling elements. We suggest that an electrostatic wave propagates in forward and reverse directions across the 200 angstrom long membrane domain during enzyme turnover, without significant dissipation of energy. Our findings demonstrate molecular principles that enable efficient long-range proton-electron coupling (PCET) and how perturbation of this PCET machinery may lead to development of mitochondrial disease.
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| 12. |
- Rivas, M. J., et al.
(författare)
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Population genomics of parallel evolution in gene expression and gene sequence during ecological adaptation
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Natural selection often produces parallel phenotypic changes in response to a similar adaptive challenge. However, the extent to which parallel gene expression differences and genomic divergence underlie parallel phenotypic traits and whether they are decoupled or not remains largely unexplored. We performed a population genomic study of parallel ecological adaptation among replicate ecotype pairs of the rough periwinkle (Littorina saxatilis) at a regional geographical scale (NW Spain). We show that genomic changes underlying parallel phenotypic divergence followed a complex pattern of both repeatable differences and of differences unique to specific ecotype pairs, in which parallel changes in expression or sequence are restricted to a limited set of genes. Yet, the majority of divergent genes were divergent either for gene expression or coding sequence, but not for both simultaneously. Overall, our findings suggest that divergent selection significantly contributed to the process of parallel molecular differentiation among ecotype pairs, and that changes in expression and gene sequence underlying phenotypic divergence could, at least to a certain extent, be considered decoupled processes. © 2018, The Author(s).
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| 13. |
- Röpke, Michael, et al.
(författare)
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Deactivation blocks proton pathways in the mitochondrial complex I
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:29
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Tidskriftsartikel (refereegranskat)abstract
- Cellular respiration is powered by membrane-bound redox enzymes that convert chemical energy into an electrochemical proton gradient and drive the energy metabolism. By combining large-scale classical and quantum mechanical simulations with cryo-electron microscopy data, we resolve here molecular details of conformational changes linked to proton pumping in the mammalian complex I. Our data suggest that complex I deactivation blocks water-mediated proton transfer between a membrane bound quinone site and proton-pumping modules, decoupling the energy-transduction machinery. We identify a putative gating region at the interface between membrane domain subunits ND1 and ND3/ND4L/ND6 that modulates the proton transfer by conformational changes in transmembrane helices and bulky residues. The region is perturbed by mutations linked to human mitochondrial disorders and is suggested to also undergo conformational changes during catalysis of simpler complex I variants that lack the "active"-to-"deactive" transition. Our findings suggest that conformational changes in transmembrane helices modulate the proton transfer dynamics by wetting/dewetting transitions and provide important functional insight into the mammalian respiratory complex I.
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