Measurement of H₂O₂ within living drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix

Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due to the difficulty of measuring mitochondrial H<sub>2</sub>O<sub>2</sub> in vivo. Here we report a ratiometric mass spectrometry probe approach to assess mitochondrial matrix H<sub>2</sub>O<sub>2</sub> levels in vivo. The probe, MitoB, comprises a triphenylphosphonium (TPP) cation driving its accumulation within mitochondria, conjugated to an arylboronic acid that reacts with H<sub>2</sub>O<sub>2</sub> to form a phenol, MitoP. Quantifying the MitoP/MitoB ratio by liquid chromatography-tandem mass spectrometry enabled measurement of a weighted average of mitochondrial H<sub>2</sub>O<sub>2</sub> that predominantly reports on thoracic muscle mitochondria within living flies. There was an increase in mitochondrial H<sub>2</sub>O<sub>2</sub> with age in flies, which was not coordinately altered by interventions that modulated life span. Our findings provide approaches to investigate mitochondrial ROS in vivo and suggest that while an increase in overall mitochondrial H<sub>2</sub>O<sub>2</sub> correlates with aging, it may not be causative

Efficacy of MSC for steroid-refractory acute GVHD associates with MSC donor age and a defined molecular profile

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Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MR arthrography

To assess the variability in accuracy of contrast media introduction, leakage, required time and patient discomfort in four different centres, each using a different image-guided glenohumeral injection technique. Each centre included 25 consecutive patients. The ultrasound-guided anterior (USa) and posterior approach (USp), fluoroscopic-guided anterior (FLa) and posterior (FLp) approach were used. Number of injection attempts, effect of contrast leakage on diagnostic quality, and total room, radiologist and procedure times were measured. Pain was documented with a visual analogue scale (VAS) pain score. Access to the joint was achieved in all patients. A successful first attempt significantly occurred more often with US (94%) than with fluoroscopic guidance (72%). Leakage of contrast medium did not cause interpretative difficulties. With US guidance mean room, procedure and radiologist times were significantly shorter (p < 0.001). The USa approach was rated with the lowest pre- and post-injection VAS scores. The four image-guided injection techniques are successful in injection of contrast material into the glenohumeral joint. US-guided injections and especially the anterior approach are significantly less time consuming, more successful on the first attempt, cause less patient discomfort and obviate the need for radiation and iodine contrast

The additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress cardiac MRI for the detection of myocardial ischemia

Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 μg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6–20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation

Coordinated X-Ray, Ultraviolet, Optical, and Radio Observations of the PSR J1023+0038 System in a Low-mass X-Ray Binary State

The PSR J1023+0038 binary system hosts a neutron star and a low-mass, main-sequence-like star. It switches on year timescales between states as an eclipsing radio millisecond pulsar and a low-mass X-ray binary (LMXB). We present a multi-wavelength observational campaign of PSR J1023+0038 in its most recent LMXB state. Two long XMM-Newton observations reveal that the system spends ~70% of the time in a ≈3 × 10^(33) erg s^(−1) X-ray luminosity mode, which, as shown in Archibald et al., exhibits coherent X-ray pulsations. This emission is interspersed with frequent lower flux mode intervals with ≈5 x 10^(32) erg s^(−1) and sporadic flares reaching up to ≈10^(34) erg s^(−1), with neither mode showing significant X-ray pulsations. The switches between the three flux modes occur on timescales of order 10 s. In the UV and optical, we observe occasional intense flares coincident with those observed in X-rays. Our radio timing observations reveal no pulsations at the pulsar period during any of the three X-ray modes, presumably due to complete quenching of the radio emission mechanism by the accretion flow. Radio imaging detects highly variable, flat-spectrum continuum radiation from PSR J1023+0038, consistent with an origin in a weak jet-like outflow. Our concurrent X-ray and radio continuum data sets do not exhibit any correlated behavior. The observational evidence we present bears qualitative resemblance to the behavior predicted by some existing "propeller" and "trapped" disk accretion models although none can account for key aspects of the rich phenomenology of this system

Proteomic analysis of nitrate-dependent acetone degradation by Alicycliphilus denitrificans strain BC

Alicycliphilus denitrificans strain BC grows anaerobically on acetone with nitrate as electron acceptor. Comparative proteomics of cultures of A. denitrificans strain BC grown on either acetone or acetate with nitrate was performed to study the enzymes involved in the acetone degradation pathway. In the proposed acetone degradation pathway, an acetone carboxylase converts acetone to acetoacetate, an AMP-dependent synthetase/ligase converts acetoacetate to acetoacetyl-CoA, and an acetyl-CoA acetyltransferase cleaves acetoacetyl-CoA to two acetyl-CoA. We also found a putative aldehyde dehydrogenase associated with acetone degradation. This enzyme functioned as a -hydroxybutyrate dehydrogenase catalyzing the conversion of surplus acetoacetate to -hydroxybutyrate that may be converted to the energy and carbon storage compound, poly--hydroxybutyrate. Accordingly, we confirmed the formation of poly-?-hydroxybutyrate in acetone-grown cells of strain BC. Our findings provide insight in nitrate-dependent acetone degradation that is activated by carboxylation of acetone. This will aid studies of similar pathways found in other microorganisms degrading acetone with nitrate or sulfate as electron acceptor.This work was supported by the Technology Foundation, the Applied Science Division (STW) of the Netherlands Organization for Scientific Research (NWO) [project 08053]. Additional funding was provided by BE-BASIC [grant F08.004.01 to SA], an ERC grant [project 323009 to AJMS] and the Gravitation grant [project 024.002.002 to AJMS] of the Netherlands Ministry of Education, Culture and Science and NWO

FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fcγ receptors. Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis

Accretion-powered Pulsations in an Apparently Quiescent Neutron Star Binary

Accreting millisecond X-ray pulsars (AMXPs) are an important subset of low-mass X-ray binaries (LMXBs) in which coherent X-ray pulsations can be observed during occasional, bright outbursts (X-ray luminosity ). These pulsations show that matter is being channeled onto the neutron star's magnetic poles. However, such sources spend most of their time in a low-luminosity, quiescent state (L_X ≲ 10^(34) erg s^(-1)), where the nature of the accretion flow onto the neutron star (if any) is not well understood. Here we report that the millisecond pulsar/LMXB transition object PSR J1023+0038 intermittently shows coherent X-ray pulsations at luminosities nearly 100 times fainter than observed in any other AMXP. We conclude that in spite of its low luminosity, PSR J1023+0038 experiences episodes of channeled accretion, a discovery that challenges existing models for accretion onto magnetized neutron stars

Religious socialisation and fertility: transition to third birth in the Netherlands

Although previous studies have demonstrated that religious people in Europe have larger families, the role played by religious socialisation in the context of contemporary fertility behaviour has not yet been analysed in detail. This contribution specifically looks at the interrelation between religious socialisation and current religiosity and their impact on the transition to the third child for Dutch women. It is based on data of the first wave of the Netherlands Kinship Panel Study (2002–2004) and uses event history analysis. The transitions to first, second and third birth are modelled jointly with a control for unobserved heterogeneity. The findings provide evidence for an impact of women’s current church attendance as well as religious socialisation measured by their fathers’ religious affiliation, when they were teenagers. A religious family background remains influential even when a woman has stopped attending church. The effects of religious indicators strengthen over cohorts. Moreover, the combined religious make-up of the respondent’s parents also significantly determines the progression to the third child.S’il est bien établi que les croyants en Europe ont plus d’enfants que les autres, le rôle de la socialisation religieuse dans le contexte de la fécondité contemporaine n’a pas encore été analysé à ce jour. Cette étude s’intéresse au lien entre la socialisation religieuse et la religiosité actuelle, et à leur impact sur la probabilité d’agrandissement de deux à trois enfants de la descendance des femmes néerlandaises. Les données exploitées sont celles de la première vague du Panel Néerlandais d’Etude de la Parenté (the Netherlands Kinship Panel Study, 2002–2004). A l’aide des techniques de l’analyse des biographies, les probabilités d’agrandissement de rang 1, rang 2 et rang 3 ont été modélisées de façon conjointe, en contrôlant l’hétérogénéité non observée. Les résultats mettent en évidence l’impact de la fréquentation actuelle de l’église par les femmes et de leur socialisation religieuse, mesurée par l’appartenance religieuse de leur père quand elles étaient adolescentes. Il apparaît que la religiosité du contexte familial exerce une influence, même quand la femme ne fréquente plus l’église, et que les effets des indicateurs de pratique religieuse se renforcent d’une génération à l’autre. Enfin, l’appartenance religieuse conjointe des parents de la femme détermine significativement la probabilité d’avoir un troisième enfant