Le magmatisme de la région de Kwyjibo, Province\ud du Grenville (Canada) : intérêt pour les\ud minéralisations de type fer-oxydes associées

The granitic plutons located north of the Kwyjibo property in Quebec’s Grenville Province are of\ud Mesoproterozoic age and belong to the granitic Canatiche Complex . The rocks in these plutons are calc-alkalic, K-rich,\ud and meta- to peraluminous. They belong to the magnetite series and their trace element characteristics link them to\ud intraplate granites. They were emplaced in an anorogenic, subvolcanic environment, but they subsequently underwent\ud significant ductile deformation. The magnetite, copper, and fluorite showings on the Kwyjibo property are polyphased\ud and premetamorphic; their formation began with the emplacement of hydraulic, magnetite-bearing breccias, followed by\ud impregnations and veins of chalcopyrite, pyrite, and fluorite, and ended with a late phase of mineralization, during\ud which uraninite, rare earths, and hematite were emplaced along brittle structures. The plutons belong to two families:\ud biotite-amphibole granites and leucogranites. The biotite-amphibole granites are rich in iron and represent a potential\ud heat and metal source for the first, iron oxide phase of mineralization. The leucogranites show a primary enrichment in\ud REE (rare-earth elements), F, and U, carried mainly in Y-, U-, and REE-bearing niobotitanates. They are metamict and\ud underwent a postmagmatic alteration that remobilized the uranium and the rare earths. The leucogranites could also be\ud a source of rare earths and uranium for the latest mineralizing events

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challeng- ing. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments—huprine and rhein— that individually are endowed with very low activity against BACE-1. Examination of crystal structures reveals no appropriate binding site large enough to accommodate 1. Therefore we have examined the conformational flexibility of BACE-1 through extended molecular dynamics simulations, paying attention to the highly flexible region shaped by loops 8–14, 154–169 and 307–318. The analysis of the protein dynamics, together with studies of pocket druggability, has allowed us to detect the transient formation of a secondary binding site, which contains Arg307 as a key residue for the interaction with small molecules, at the edge of the catalytic cleft. The formation of this druggable “floppy” pocket would enable the bind- ing of multisite inhibitors targeting both catalytic and secondary sites. Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds support the feasibility of this hypothesis. The results provide a basis to explain the high inhibitory potency of the two enantiomeric forms of 1, together with the large dependence on the length of the oligo- methylenic linker. Furthermore, the multisite hypothesis has allowed us to rationalize the inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically regarding the apparent lack of sensitivity of the inhibition constant to the chemical modifications intro- duced in the chromene unit. Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors

The Swedish National Airway Register (SNAR) : development, design and utility to date

Background: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. Aim: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. Methods: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. Results: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children <12 yr, 6545 adolescents 12–17 yr, and 57,344 adults >17 yr) and 38,117 with COPD. Depending on age and disease group, 43–77% had performed spirometry, 36–65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. Conclusion: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide

Stratigraphy and tectonic setting of the host rocks to the Tjårrojåkka Fe-oxide Cu-Au deposits, Kiruna area, northern Sweden

The Tjårrojåkka area is located about 50 km WSW of Kiruna, northern Sweden, and hosts one of the best examples of spatially and possibly genetically related Fe-oxide and Cu-Au occurrences in the area. The bedrock is dominated by intermediate and basic extrusive and intrusive rocks. An andesite constrains the ages of these rocks with a U–Pb LA-ICPMS age of 1878±7 Ma. They are cut by dolerites, which acted as feeder dykes for the overlying basalts. Based on geochemistry and the obtained age the andesites and basaltic andesites can be correlated with the 1.9 Ga intermediate volcanic rocks of the Svecofennian Porphyrite Group in northern Sweden. They formed during subduction-related magmatism in a volcanic arc environment on the Archaean continental margin above the Kiruna Greenstone Group. Chemically the basalts and associated dolerites have the same signature, but cannot directly be related to any known basaltic unit in northern Sweden. The basalts show only minor contamination of continental crust and may represent a local extensional event in a subaquatic back arc setting with extrusion of mantle derived magma. The intrusive rocks range from gabbro to quartz-monzodiorite in composition. The area is metamorphosed at epidote-amphibolite facies and has been affected by scapolite, K-feldspar, epidote, and albite alteration that is more intense in the vicinity of deformation zones and mineral deposits. Three events of deformation have been distinguished in the area. D1 brittle–ductile deformation created NE–SW-striking steep foliation corresponding with the strike of the Tjårrojåkka-Fe and Cu deposits and was followed by the development of an E–W deformation zone (D2). A compressional event (D3), possible involving thrusting from the SW, produced folds in the central part of the area and a NNW–SSE striking deformation zone in NE