Interaction of glutathione transferase from horse erythrocytes with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole

7-Chloro-4-nitrobenzo-2-oxa-1,3-diazole reacts with two thiol groups of the dimeric horse erythrocyte glutathione transferase at pH 5.0, with strong inactivation reversible on dithiothreitol treatment. The inactivation kinetic follows a biphasic pattern, similar to that caused by other thiol reagents as recently reported. Both S-methylglutathione and 1-chloro-2,4-dinitrobenzene protect the enzyme from inactivation. Analysis of the reactive SH group-containing peptide gives the sequence Ala-Ser-Cys-Leu-Tyr, identical with that of the peptide that contains the reactive cysteine 47 of the human placental transferase. In the presence of glutathione, the enzyme is not inactivated by this reagent, but it catalyzes its conjugation to glutathione. At higher pH values, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole reacts with 2 tyrosines/dimer and lysines, as well as with cysteines. Reaction with lysine seems essentially without effect on activity; whether the reactive tyrosines are important for activity could not be determined using this reagent only. However, 2 tyrosines among the 4 that are nitrated by tetranitro-methane are important for activity

Relating Green-Schwarz and Extended Pure Spinor Formalisms by Similarity Transformation

In order to gain deeper understanding of pure-spinor-based formalisms of superstring, an explicit similarity transformation is constructed which provides operator mapping between the light-cone Green-Schwarz (LCGS) formalism and the extended pure spinor (EPS) formalism, a recently proposed generalization of the Berkovits' formalism in an enlarged space. By applying a systematic procedure developed in our previous work, we first construct an analogous mapping in the bosonic string relating the BRST and the light-cone formulations. This provides sufficient insights and allows us to construct the desired mapping in the more intricate case of superstring as well. The success of the construction owes much to the enlarged field space where pure spinor constraints are removed and to the existence of the ``B-ghost'' in the EPS formalism.Comment: 37pages, no figur

Rapid hemodilution induced by desmopressin after erythropoietin administration in humans

We have shown that treatment with desmopressin has a very effective hemodilution effect in healthy humans. These results led us to suggest the possible role of desmopressin to mask blood doping in sports. Based on our results, the World Anti-Doping Agency included the desmopressin in the 2011 List of Prohibited Substances and Methods. On this occasion, the aim of our study was to test the desmopressin-induced hemodilution after rHuEpo administration in humans. This was an intra-subject, crossover study in which five physically active males acted as their own controls. A basal blood sample was taken on their first visit to the laboratory. The next day, the subjects began the treatment. They received a subcutaneous rHuEpo injection three times/week for a two-week period. On the second visit to the laboratory, seventeen days later, a blood sample was taken. Thereafter, the subjects received an oral dose of 4.3 μg/kg of desmopressin and were instructed to ingest 1.5 liters of mineral water during the following fifteen minutes. Three hours after the water ingestion a second blood sample was obtained. The samples were analyzed for hematocrit (HCT), hemoglobin (Hb), reticulocytes (Ret%) and OFF Hr-Score. We found significantly higher HCT, Hb and Ret% levels after rHuEpo administration. Administration of desmopressin significantly decreased the HCT and Hb values but we did not find significant changes in Ret%. The values of the OFF Hr-Score also decreased after treatment with desmopressin. Desmopressin has a very effective hemodilution effect after rHuEpo administration and significantly modifies the hematological values measured by the anti-doping authorities to detect blood doping. We consider that these results reinforce the conclusions reported in our first study and confirm that desmopressin is a very effective masking agent for blood doping.This work was supported by grants SAF2008-00270; SAF2009-08334; BFU2007-65803/BFI; from the Spanish Ministry of Education and Science (MEC); PROMETEO/2010/074 from the Consellería de Educación de la Generalitat Valenciana. ISCIII2006-RED13-027 from the “Red Temática de investigación cooperativa en envejecimiento y fragilidad (RETICEF)”, EU Funded COSTB35 and DPS2008-06968 from Spanish Ministry of Innovation and Science. This study has been co-financed by FEDER funds from the European Union

Núcleo de microbiota en el cáncer de pulmón central con enriquecimiento estreptocócico como posible marcador de diagnóstico

Background: Dysbiosis in lung cancer has been underexplored. The aim of this study was to define the bacterial and fungal microbiota of the bronchi in central lung cancer and to compare it with that of the oral and intestinal compartments. Methods: Twenty-five patients with central lung cancer and sixteen controls without antimicrobial intake during the previous month were recruited. Bacterial and fungal distribution was determined by massive sequencing of bronchial biopsies and saliva and faecal samples. Complex computational analysis was performed to define the core lung microbiota. Results: Affected and contralateral bronchi of patients have almost identical microbiota dominated by Streptococcus, whereas Pseudomonas was the dominant genera in controls. Oral and pulmonary ecosystems were significantly more similar in patients, probably due to microaspirations. Streptococcal abundance in the bronchi differentiated patients from controls according to a ROC curve analysis (90.9% sensitivity, 83.3% specificity, AUC = 0.897). The saliva of patients characteristically showed a greater abundance of Streptococcus, Rothia, Gemella and Lactobacillus. The mycobiome of controls (Candida) was significantly different from that of patients (Malassezia). Cancer patients’ bronchial mycobiome was similar to their saliva, but different from their contralateral bronchi. Conclusions: The central lung cancer microbiome shows high levels of Streptococcus, and differs significantly in its composition from that of control subjects. Changes are not restricted to tumour tissue, and seem to be the consequence of microaspirations from the oral cavity. These findings could be useful in the screening and even diagnosis of this disease

Significant changes in the magma dynamics of Stromboli steady-state volcano recorded by clinopyroxene crystals.

&amp;lt;p&amp;gt;Steady-state volcanic activity implies equilibrium between the rate of magma replenishment and eruption of compositionally homogeneous magmas, lasting for tens to thousands of years in an open conduit system. The Present-day activity of Stromboli volcano (Aeolian Islands, Southern Italy) has long been recognised as typical of a steady-state volcano, with a shallow magmatic reservoir (highly porphyritic or hp-magma) continuously refilled by more mafic magma (with low phenocryst content or lp-magma) at a constant rate and accompanied by mixing, crystallisation and eruption. The lp-magma is erupted only during more violent explosive events (paroxysms), which usually occur at intervals of a few years. However, the two most recent paroxysms occurred at very short timescales on 3 July and 28 August 2019 offering the unique opportunity of obtaining crucial information on the current magma dynamics of Stromboli.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Albeit the plumbing system shows such uniformity, clinopyroxene phenocrysts exhibit marked chemical heterogeneities and complex textures caused by continuous lp-hp magma mixing as well as antecryst recycling from different mush portions. The compositional zoning in clinopyroxene provides essential information on pre-eruptive magma dynamics, indicating multi-stage crystallization across the lp-hp-reservoirs, where diopsidic compositions are markers of more primitive, high-T magmas injecting into shallow, low-T domains of the plumbing system. By comparing clinopyroxene texture, chemistry and residence times from the Present-day eruptions with the previous Post-Pizzo activity, we conclude that a distinct phase in the life of Stromboli volcano commenced after the violent 2003 paroxysm. Our observations suggest there are more efficient mechanisms of mush disruption and cannibalization, in which old diopsidic antecrysts are continuously remobilized and transported by the lp-magmas permeating the mush. The disappearance of diopsidic recharge bands within augitic overgrowths indicates that over time, magmatic injections feeding the persistent Present-day activity are more intensively mixed and homogenized prior to eruption.&amp;lt;/p&amp;gt; </jats:p

Host and Viral Genetic Correlates of Clinical Definitions of HIV-1 Disease Progression

BACKGROUND: Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP). METHODOLOGY AND PRINCIPAL FINDINGS: We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the "viral dating" (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals. CONCLUSIONS: A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research

The Imaging Magnetograph eXperiment (IMaX) for the Sunrise balloon-borne solar observatory

The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne telesocope in June 2009 for almost six days over the Arctic Circle. As a polarimeter IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mAA. IMaX uses the high Zeeman sensitive line of Fe I at 5250.2 AA and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15-0.18 arcsec range over a 50x50 arcsec FOV. Time cadences vary between ten and 33 seconds, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are four Gauss for longitudinal fields and 80 Gauss for transverse fields per wavelength sample. The LOS velocities are estimated with statistical errors of the order of 5-40 m/s. The design, calibration and integration phases of the instrument, together with the implemented data reduction scheme are described in some detail.Comment: 17 figure

Magma recharge and mush rejuvenation drive paroxysmal activity at Stromboli volcano

AbstractOpen-conduit basaltic volcanoes can be characterised by sudden large explosive events (paroxysms) that interrupt normal effusive and mild explosive activity. In June-August 2019, one major explosion and two paroxysms occurred at Stromboli volcano (Italy) within only 64 days. Here, via a multifaceted approach using clinopyroxene, we show arrival of mafic recharges up to a few days before the onset of these events and their effects on the eruption pattern at Stromboli, as a prime example of a persistently active, open-conduit basaltic volcano. Our data indicate a rejuvenated Stromboli plumbing system where the extant crystal mush is efficiently permeated by recharge magmas with minimum remobilisation promoting a direct linkage between the deeper and the shallow reservoirs that sustains the currently observed larger variability of eruptive behaviour. Our approach provides vital insights into magma dynamics and their effects on monitoring signals demonstrating the power of petrological studies in interpreting patterns of surficial activity.</jats:p