Effect of Ionizing Radiation on Human Myeloperoxidase: Reaction With Hydrated Electrons

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Myeloperoxidase (MPO) is a myeloid-lineage restricted enzyme largely expressed in the azurophilic granules of neutrophils. It catalyses the formation of reactive oxygen species, mainly hypochlorous acid, contributing to anti-pathogenic defense. Disorders in the production or regulation of MPO may lead to a variety of health conditions, mainly of inflammatory origin, including autoimmune inflammation. We have studied the effect of ionizing radiation on the activity of MPO, as measured by the capacity retained by the enzyme to produce hypochlorous acid as reactive oxygen species after exposure to successive doses of solvated electrons, the strongest possible one-e− reducing agent in water. Chlorination activity was still present after a very high irradiation dose, indicating that radiation damage does not take place at the active site, hindered in the core of MPO structure. Decay kinetics show a dependence on the wavelength, supporting that the process must occur at peripheral functional groups situated on external and readily accessible locations of the enzyme. These results are relevant to understand the mechanism of resistance of our innate anti-pathogenic defense system and also to get insight into potential strategies to regulate MPO levels as a therapeutic target in autoimmune diseases.This work was supported by: the Spanish Ministerio de Ciencia y Tecnología (CTQ2004-00534/BQU), the European Commission through the Access to Large-Scale Scientific Facilities Program (ref 41365), and the regional government of the Xunta de Galicia (Project GPC ED431B 2020/52)Xunta de Galicia; ED431B 2020/5

The Conlara metamorphic complex: Lithology, provenance, metamorphic constraints on the metabasic rocks, and chime monazite dating

The Conlara Metamorphic Complex, the easternmost complex of the Sierra de San Luis, is a key unit to understand the relationship between the late Proterozoic-Early Cambrian Pampean and the Upper Cambrian-Middle Ordovician Famatinian orogenies of the Eastern Sierras Pampeanas. The Conlara Metamorphic Complex extends to the east to the foothills of the Sierra de Comechingones and to the west up the Río Guzmán shear zone. The main rock types of the CMC are metaclastic and metaigneous rocks that are intruded by Ordovician and Devonian granitoids. The metaclastic units comprise fine to medium-grained metagreywackes and scarce metapelites with lesser amounts of tourmaline schists and tourmalinites whereas the metaigneous rocks encompass basic and granitoids rocks. The former occur as rare amphibolite interlayered within the metasedimentary rocks. The granitic component corresponds to a series of orthogneisses and migmatites (stromatite and diatexite). The CMC is divided in four groups based on the dominant lithological associations: San Martin and La Cocha correspond mainly to schists and some gneisses and Santa Rosa and San Felipe encompass mainly paragneisses, migmatites and orthogneisses. The Conlara Metamoprphic Complex underwent a polyphase metamorphic evolution. The penetrative D2-S2 foliation was affected by upright, generally isoclinal, N-NE trending D3 folds that control the NNE outcrop patterns of the different groups. An earlier, relic S1 is preserved in microlithons. Discontinuous high-T shear zones within the schists and migmatites are related with D4 whereas some fine-grained discontinuous shear bands attest for a D5 deformation phase. Geochemistry of both non-migmatitic metaclastic units and amphibolites suggest that the Conlara Metamorphic Complex represents an arc related basin. Maximun depositional ages indicate a pre- 570 Ma deposition of the sediments. An ample interval between sedimentation and granite emplacement in the already metamorphic complex is indicated by the 497 ± 8 Ma age of El Peñon granite. D1-D2 history took place at 564 ± 21 Ma as indicated by one PbSL age calculated for the M2 garnet of La Cocha Group. D3 is constrained by the pervasively solid-state deformed Early Ordovician granitoids which exhibits folded xenoliths of the D1-D2 deformed metaclastic rocks. Pressure-temperature pseudosections were calculated for one amphibolite using the geologically realistic system MnNCKFMASHTO (MnO–Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–Fe2O3). Peak metamophic conditions (M2) indicate 6 kbar and 620 °C. Late chlorite on the rims and in cracks of garnet, along with titanite rims on ilmenite and matrix plagioclase breaking down to albite suggests that the P-T path moved back down. Monazite analyses yield isochron Th–U–Pb ages ranging from 446 to 418 Ma. The oldest age of 446 ± 5 Ma correspond to a migmatite from the Santa Rosa Group. Monazites in samples from the La Cocha and the San Martin group crystallized at decreasing temperatures, followed by the 418 ± 10 Ma low-Y2O3 monazites in one sample of the la Cocha Group that was also obtained from a migmatite, and would likely mark a later stage of a retrograde metamorphism New CHIME monazite ages presented here likely represent post-peak fluid assisted recrystallization that are similar to amphibole and muscovite cooling ages. Therefore the monazite ages may represent a re-equilibration of the monazite on the cooling path of the basement complex.Fil: López de Luchi, Mónica G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Martínez Dopico, Carmen Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Cutts, Kathryn Ann. Universidade do Estado de Rio do Janeiro; BrasilFil: Schulz, Bernhard. Institute of Mineralogy; AlemaniaFil: Siegesmund, Siegfried. Universität Göttingen; AlemaniaFil: Wemmer, Klaus. Universität Göttingen; AlemaniaFil: Montenegro, Teresita Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentin

Geochronology of quarz-monzodioritic to tonalitic Stock Musters, an Ordovician intrusive from Valcheta, Northpatagonian Massif

Esta contribución informa la primera edad de cristalización U-Pb en circón de un stock monzodiorítico cuarzoso a tonalítico, aquí denominado formalmente como Diorita Musters, y perteneciente al conjunto de granitoides asociados al plutón leucogranitíco Valchetaque forma parte del conjunto de granitoides de edad ordovícica temprana aflorantes en el sector nororiental del Macizo Norpatagónico(Complejo plutónico Punta Sierra, Busteros et al. 1998). Los resultados de los análisis U-Pb en circones revelan una edad de cristalización ordovícica inferior (470 ± 2 Ma; MSWD =0.99) para este pulso magmático, confirmando la extensión de este magmatismoordovícico por más de 200 km2 y afirmando su importancia regional y conexión con la orogenia Famatiniana.This contribution reports the first U-Pb age in zircons of a quartz-monzodioritic to tonalitic stock, here formally denominated as Musters Diorite and belonging to the group of Early Ordovician granitoids outcropping in the northeastern sector of the Northern Patagonian Massif (Punta Sierra Plutonic Complex, Busteros et al. 1998). Our results of U-Pb analyses in zircons reveal an Early Ordovician crystallization age (470 ± 2 Ma; MSWD =0.99; N=70/89) for this magmatic pulse, confirming the extension of this magmatism for more than 200 km2 and showing its regional importance and connection with the Famatinian OrogenyFil: Grillo Vidal, Carolina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; Argentina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Ciencias Geológicas. Area de Petrologia; ArgentinaFil: Martínez Dopico, Carmen Irene. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Ciencias Geológicas. Area de Petrologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: López de Luchi, Mónica G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; Argentin

Geochronology of quarz-monzodioritic to tonalitic Stock Musters, an Ordovician intrusive from Valcheta, Northpatagonian Massif

Esta contribución informa la primera edad de cristalización U-Pb en circón de un stock monzodiorítico cuarzoso a tonalítico, aquí denominado formalmente como Diorita Musters, y perteneciente al conjunto de granitoides asociados al plutón leucogranitíco Valchetaque forma parte del conjunto de granitoides de edad ordovícica temprana aflorantes en el sector nororiental del Macizo Norpatagónico(Complejo plutónico Punta Sierra, Busteros et al. 1998). Los resultados de los análisis U-Pb en circones revelan una edad de cristalización ordovícica inferior (470 ± 2 Ma; MSWD =0.99) para este pulso magmático, confirmando la extensión de este magmatismoordovícico por más de 200 km2 y afirmando su importancia regional y conexión con la orogenia Famatiniana.This contribution reports the first U-Pb age in zircons of a quartz-monzodioritic to tonalitic stock, here formally denominated as Musters Diorite and belonging to the group of Early Ordovician granitoids outcropping in the northeastern sector of the Northern Patagonian Massif (Punta Sierra Plutonic Complex, Busteros et al. 1998). Our results of U-Pb analyses in zircons reveal an Early Ordovician crystallization age (470 ± 2 Ma; MSWD =0.99; N=70/89) for this magmatic pulse, confirming the extension of this magmatism for more than 200 km2 and showing its regional importance and connection with the Famatinian OrogenyFil: Grillo Vidal, Carolina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; Argentina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Ciencias Geológicas. Area de Petrologia; ArgentinaFil: Martínez Dopico, Carmen Irene. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Ciencias Geológicas. Area de Petrologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: López de Luchi, Mónica G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; Argentin

Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms

Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables

Widespread seasonal gene expression reveals annual differences in human immunity and physiology.

Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease.The Gambian study providing data for analysis was supported by core funding MC-A760-5QX00 to the International Nutrition Group by the UK Medical Research Council (MRC) and the UK Department for the International Development (DFID) under the MRC/DFID Concordat agreement. This work was supported by the JDRF UK Centre for Diabetes-Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003), the JDRF (9-2011-253), the Wellcome Trust (WT061858/091157), the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC) and the Medical Research Council (MRC) Cusrow Wadia Fund. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007–2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (WT100140). X.C.D. was a University of Cambridge/Wellcome Trust Infection and Immunity PhD student. R.C.F. is funded by a JDRF post-doctoral fellowship (3-2011-374). C.W. and H.G are funded by the Wellcome Trust (WT089989). The BABYDIET study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG ZI-310/14-1 to-4), the JDRF (JDRF 17-2012-16 and 1-2006-665) and the German Center for Diabetes Research (DZD e.V.). E.B. is supported by the DFG Research Center and Cluster of Excellence—Center for Regenerative Therapies Dresden (FZ 111).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150512/ncomms8000/full/ncomms8000.html

Jurassic cooling ages in Paleozoic to early Mesozoic granitoids of northeastern Patagonia : 40Ar/39Ar, 40K–40Ar mica and U–Pb zircon evidence

University of Buenos Aires (PICTUBACYT X183), CONICET and ANPCYT (PICT20131162) financial support is acknowledged.U–Pb SHRIMP zircon crystallization ages and Ar–Ar and K–Ar mica cooling ages for basement rocks of the Yaminué and Nahuel Niyeu areas in northeastern Patagonia are presented. Granitoids that cover the time span from Ordovician to Early Triassic constitute the main outcrops of the western sector of the Yaminué block. The southern Yaminué Metaigneous Complex comprises highly deformed Ordovician and Permian granitoids crosscut by undeformed leucogranite dikes (U–Pb SHRIMP zircon age of 254 ± 2 Ma). Mica separates from highly deformed granitoids from the southern sector yielded an Ar–Ar muscovite age of 182 ± 3 Ma and a K–Ar biotite age of 186 ± 2 Ma. Moderately to highly deformed Permian to Early Triassic granitoids made up the northern Yaminué Complex. The Late Permian to Early Triassic (U–Pb SHRIMP zircon age of 252 ± 6 Ma) Cabeza de Vaca Granite of the Yaminué block yielded Jurassic mica K–Ar cooling ages (198 ± 2, 191 ± 1, and 190 ± 2 Ma). At the boundary between the Yaminué and Nahuel Niyeu blocks, K–Ar muscovite ages of 188 ± 3 and 193 ± 5 Ma were calculated for the Flores Granite, whereas the Early Permian Navarrete granodiorite, located in the Nahuel Niyeu block, yielded a K–Ar biotite age of 274 ± 4 Ma. The Jurassic thermal history is not regionally uniform. In the supracrustal exposures of the Nahuel Niyeu block, the Early Permian granitoids of its western sector as well as other Permian plutons and Ordovician leucogranites located further east show no evidence of cooling age reset since mica ages suggest cooling in the wake of crystallization of these intrusive rocks. In contrast, deeper crustal levels are inferred for Permian–Early Triassic granitoids in the Yaminué block since cooling ages for these rocks are of Jurassic age (198–182 Ma). Jurassic resetting is contemporaneous with the massive Lower Jurassic Flores Granite, and the Marifil and Chon Aike volcanic provinces. This intraplate deformational pulse that affected northeastern Patagonia during the Early Jurassic (Sinemurian–Pliensbachian) was responsible for the partial (re)exhumation of the mid-crustal Paleozoic basement along reactivated discrete NE–SW to ENE–WSW lineaments and the resetting of isotopic systems. These new thermochronological data indicate that Early Permian magmatic rocks of the Nahuel Niyeu block were below 300 °C for ca. 20 Ma prior to the onset of the main magmatic episode of the Late Permian to Triassic igneous and metaigneous rocks of the Yaminué block.PostprintPeer reviewe

Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease.

Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a vital role in this process. Genetic regulation of both inflammatory responses and anti-inflammatory protective mechanisms likely underlies the heritability of COPD observed in family studies. In alpha-1 protease inhibitor deficiency, the only genetic disorder known to cause COPD, lack of inhibition of elastase activity, results in the parenchymal destruction of emphysema. Other genetic polymorphisms have been hypothesized to alter the risk of COPD but have not been established as causes of this condition. It is likely that multiple genetic factors interacting with each other and with a number of environmental agents will be found to result in the development of COPD

A class of quasi-sparse companion pencils

In this paper, we introduce a general class of quasi-sparse potential companion pencils for arbitrary square matrix polynomials over an arbitrary field, which extends the class introduced in [B. Eastman, I.-J. Kim, B. L. Shader, K.N. Vander Meulen, Companion matrix patterns. Linear Algebra Appl. 436 (2014) 255-272] for monic scalar polynomials. We provide a canonical form, up to permutation, for companion pencils in this class. We also relate these companion pencils with other relevant families of companion linearizations known so far. Finally, we determine the number of different sparse companion pencils in the class, up to permutation.This work has been partially supported by theMinisterio de Economía y Competitividad of Spain through grants MTM2015-68805-REDT and MTM2015-65798-P

Ninety-Degree Chevron Osteotomy for Correction of Hallux Valgus Deformity: Clinical Data and Finite Element Analysis

Hallux valgus is a very common foot disorder, with its prevalence estimated at 33% in adult shoe-wearing populations. Conservative management is the initial treatment of choice for this condition, but surgery is sometimes needed. The 600 angle Chevron osteotomy is an accepted method for correction of mild to moderate hallux valgus in adults less than 60 years old. A modified 900 angle Chevron osteotomy has also been described; this modified technique can confer some advantages compared to the 600 angle method, and reported results are good. In the current work we present clinical data from a cohort of fifty-one female patients who had surgery for sixty-two hallux valgus deformities. In addition, in order to get a better physical insight and study the mechanical stresses along the two osteotomies, Finite Element Analysis (FEA) was also conducted. FEA indicated enhanced mechanical bonding with the modified 900 Chevron osteotomy, because the compressive stresses that keep the two bone parts together are stronger, and the shearing stresses that tend to slide the two bone parts apart are weaker, compared to the typical 600 technique. Follow-up data on our patient cohort show good or excellent long-term clinical results with the modified 900 angle technique. These results are consistent with the FEA-based hypothesis that a 900 Chevron osteotomy confers certain mechanical advantages compared to the typical 600 procedure