Transformation of PbI2, PbBr2 and PbCl2 salts into MAPbBr3 perovskite by halide exchange as an effective method for recombination reduction

Halide perovskite derivatives present unprecedented physical phenomena among those materials which are suitable for photovoltaics, such as a fast ion diffusion coefficient. In this paper it is reported how the benefits of this property can be used during the growth of halide perovskites in order to control the morphological and optoelectronic properties of the final thin film. Using a large enough halide reservoir, the nature of the halides present in the final perovskite layer can be exchanged and this depends on the initial salt used in the two-step deposition method. In particular, the preparation of a methylammonium lead bromide (MAPbBr3) thin film is reported, using a two-step method based on the transformation of lead(II) iodide (PbI2), lead(II) bromide (PbBr2) and lead(II) chloride (PbCl2) salts into MAPbBr3 perovskite after dipping in a methylammonium bromide (MABr) solution. The films prepared from different salts present different properties in terms of morphology and optoelectronic properties, thus providing significantly different performance when they are used for the preparation of photovoltaic devices. Interestingly, the use of PbI2 and PbCl2 salts reduce the charge recombination and increase the open circuit potential obtained, especially in the former case. However, the highest photocurrent is obtained when PbBr2 is used. For PbI2 and PbCl2 salts no traces of the former salt are observed in the MAPbBr3 layer obtained after 10 minutes of dipping time, however, the presence of PbBr2 has still been detected (using X-ray diffraction) when this salt has been employed

Reading Inclusion – (Um-)Wege durch das Labyrinth des Inklusionsbegriffs

Die Autor*innen betrachten den Begriff der Inklusion aus verschiedenen (räumlichen) Perspektiven und laden mit ihren Überlegungen dazu ein, sich in das scheinbare Labyrinth aus Deutungen und Lesarten des Inklusionsbegriffs zu begeben, sich seiner Mehrdimensionalität zu nähern und darüber in den Austausch zu kommen. (DIPF/Orig.

Sociomateriality in medical practice and learning: Attuning to what matters

CONTEXT In current debates about professional practice, learning and education, increasing emphasis is being placed on understanding learning as ongoing participation rather than as acquiring knowledge and skills. Close attention is paid to the sociocultural context as well as to cognition. While this general sociocultural view is important and useful, issues have emerged in studies of practice-based learning that point to certain oversights. METHOD Three issues are described here: (1) the general lack of attention to the importance of materiality – objects, technologies, nature etc – in questions of learning; (2) the human-centric view of challenges and complexities in practice that fail to note the transformational entanglements among social and material forces; and (3) the conflicts between ideals of evidence-based standardized models and the sociomaterial contingencies of clinical practice.    DISCUSSION It is argued here that a sociomaterial approach to learning and practice offers important insights for medical education. This view joins a growing field of research in the materiality of practice and everyday life, which embraces wide-ranging theoretical families that can only be briefly mentioned in this short introduction. The main premise they share is that social and material forces, culture, nature and technology, are enmeshed in everyday practice. Objects and humans act upon one another in ways that mutually transform their characteristics and activity. Examples from research in medical practice show how materials actively influence clinical practice, how learning itself is a material matter, how protocols are in fact temporary sociomaterial achievements, and how practices form unique and sometimes conflicting sociomaterial worlds, with diverse diagnostic and treatment approaches for the same thing.   CONCLUSIONS The article concludes with implications for learning in practice. The shift is from sole emphasis on acquiring knowledge representations to learning how to participate more wisely in particular situations. Focus is on learning how to attune to minor material fluctuations and surprises, how to track one’s own and other’s effects on the ‘intra-actions’ and emerging effects, and how to improvise solutions

The Multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities

The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. We identify four distinct homodimerization interfaces on the GR-LBD surface, which can associate into 20 topologically different homodimers. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution, quantitative fluorescence microscopy in living cells, and transcriptomic analyses. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work illustrates the unique flexibility of GR's LBD and suggests different dimeric conformations within cells. In addition, we unveil pathophysiologically relevant quaternary assemblies of the receptor with important implications for glucocorticoid action and drug design

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions

The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities

20 páginas, 7 figurasThe glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. We identify four distinct homodimerization interfaces on the GR-LBD surface, which can associate into 20 topologically different homodimers. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution, quantitative fluorescence microscopy in living cells, and transcriptomic analyses. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work illustrates the unique flexibility of GR's LBD and suggests different dimeric conformations within cells. In addition, we unveil pathophysiologically relevant quaternary assemblies of the receptor with important implications for glucocorticoid action and drug designE.E.-P. thanks the generosity of the Gemma E. Carretero Fund; MINECO [BFU2017-86906-R, SAF2017-71878-REDT, SAF2015-71878-REDT to E.E.-P., RTI2018-101500-B-I00 to P.F.-P., RTI2018-096735-B-100 to A.R.M., PID2019-110167RB-I00 to J.F.-R., SAF2017-89510-R to A.V.F. and C.C.]; G.L.H thanks the NIH Intramural Research Program; D.M.P was supported by CONICET. Funding for open access charge: Spanish Ministry of Science (MINECO).Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms