687 research outputs found

    POZ-, AT-hook-, and Zinc Finger-containing Protein (PATZ) Interacts with Human Oncogene B Cell Lymphoma 6 (BCL6) and Is Required for Its Negative Autoregulation.

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    The PATZ1 gene encoding a POZ/AT-hook/Kruppel zinc finger (PATZ) transcription factor, is considered a cancer-related gene because of its loss or misexpression in human neoplasias. As for other POZ/domain and Kruppel zinc finger (POK) family members, the transcriptional activity of PATZ is due to the POZ-mediated oligomer formation, suggesting that it might be not a typical transactivator but an architectural transcription factor, thus functioning either as activator or as repressor depending on the presence of proteins able to interact with it. Therefore, to better elucidate PATZ function, we searched for its molecular partners. By yeast two-hybrid screenings, we found a specific interaction between PATZ and BCL6, a human oncogene that plays a key role in germinal center (GC) derived neoplasias. We demonstrate that PATZ and BCL6 interact in germinal center-derived B lymphoma cells, through the POZ domain of PATZ. Moreover, we show that PATZ is able to bind the BCL6 regulatory region, where BCL6 itself acts as a negative regulator, and to contribute to negatively modulate its activity. Consistently, disruption of one or both Patz1 alleles in mice causes focal expansion of thymus B cells, in which BCL6 is up-regulated. This phenotype was almost completely rescued by crossing Patz1(+/-) with Bcl6(+/-) mice, indicating a key role for Bcl6 expression in its development. Finally, a significant number of Patz1 knock-out mice (both heterozygous and homozygous) also develop BCL6-expressing lymphomas. Therefore, the disruption of one or both Patz1 alleles may favor lymphomagenesis by activating the BCL6 pathway

    First-year ion-acoustic wave observations in the solar wind by the RPW/TDS instrument on board Solar Orbiter

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    Context. Electric field measurements of the Time Domain Sampler (TDS) receiver, part of the Radio and Plasma Waves (RPW) instrument on board Solar Orbiter, often exhibit very intense broadband wave emissions at frequencies below 20 kHz in the spacecraft frame. During the first year of the mission, the RPW/TDS instrument was operating from the first perihelion in mid-June 2020 and through the first flyby of Venus in late December 2020. Aims. In this paper, we present a year-long study of electrostatic fluctuations observed in the solar wind at an interval of heliocentric distances from 0.5 to 1 AU. The RPW/TDS observations provide a nearly continuous data set for a statistical study of intense waves below the local plasma frequency. Methods. The on-board and continuously collected and processed properties of waveform snapshots allow for the mapping plasma waves at frequencies between 200 Hz and 20 kHz. We used the triggered waveform snapshots and a Doppler-shifted solution of the dispersion relation for wave mode identification in order to carry out a detailed spectral and polarization analysis. Results. Electrostatic ion-acoustic waves are the most common wave emissions observed between the local electron and proton plasma frequency by the TDS receiver during the first year of the mission. The occurrence rate of ion-acoustic waves peaks around perihelion at distances of 0.5 AU and decreases with increasing distances, with only a few waves detected per day at 0.9 AU. Waves are more likely to be observed when the local proton moments and magnetic field are highly variable. A more detailed analysis of more than 10000 triggered waveform snapshots shows the mean wave frequency at about 3 kHz and wave amplitude about 2.5 mV/m. The wave amplitude varies as R−1.38 with the heliocentric distance. The relative phase distribution between two components of the E-field projected in the Y-Z Spacecraft Reference Frame (SRF) plane shows a mostly linear wave polarization. Electric field fluctuations are closely aligned with the directions of the ambient field lines. Only a small number (3%) of ion-acoustic waves are observed at larger magnetic discontinuities

    First observations and performance of the RPW instrument onboard the Solar Orbiter mission

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    The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument’s Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work

    The angular-momentum flux in the solar wind observed during Solar Orbiter's first orbit

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    Aims: We present the first measurements of the angular-momentum flux in the solar wind recorded by the Solar Orbiter spacecraft. Our aim is to validate these measurements to support future studies of the Sun’s angular-momentum loss. Methods: We combined 60-min averages of the proton bulk moments and the magnetic field measured by the Solar Wind Analyser (SWA) and the magnetometer (MAG) onboard Solar Orbiter. We calculated the angular-momentum flux per solid-angle element using data from the first orbit of the mission’s cruise phase in 2020. We separated the contributions from protons and from magnetic stresses to the total angular-momentum flux. Results: The angular-momentum flux varies significantly over time. The particle contribution typically dominates over the magneticfield contribution during our measurement interval. The total angular-momentum flux shows the largest variation and is typically anticorrelated with the radial solar-wind speed. We identify a compression region, potentially associated with a co-rotating interaction region or a coronal mass ejection, which leads to a significant localised increase in the angular-momentum flux, albeit without a significant increase in the angular momentum per unit mass. We repeated our analysis using the density estimate from the Radio and Plasma Waves (RPW) instrument. Using this independent method, we find a decrease in the peaks of positive angular-momentum flux, but otherwise, our results remain consistent. Conclusions: Our results largely agree with previous measurements of the solar wind’s angular-momentum flux in terms of amplitude, variability, and dependence on radial solar-wind bulk speed. Our analysis highlights the potential for more detailed future studies of the solar wind’s angular momentum and its other large-scale properties with data from Solar Orbiter. We emphasise the need for studying the radial evolution and latitudinal dependence of the angular-momentum flux in combination with data from Parker Solar Probe and other assets at heliocentric distances of 1 au and beyond

    Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

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    OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Concentration-Dependent, Size-Independent Toxicity of Citrate Capped AuNPs in Drosophila melanogaster

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    The expected potential benefits promised by nanotechnology in various fields have led to a rapid increase of the presence of engineered nanomaterials in a high number of commercial goods. This is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of the physical/chemical factors responsible for their toxic effects. In this work, we evaluated the toxicity of monodisperse citrate-capped gold nanoparticles (AuNPs) of different sizes (5, 15, 40, and 80 nm) in the model organism Drosophila melanogaster, upon ingestion. To properly evaluate and distinguish the possible dose- and/or size-dependent toxicity of the AuNPs, we performed a thorough assessment of their biological effects, using two different dose-metrics. In the first approach, we kept constant the total surface area of the differently sized AuNPs (Total Exposed Surface area approach, TES), while, in the second approach, we used the same number concentration of the four different sizes of AuNPs (Total Number of Nanoparticles approach, TNN). We observed a significant AuNPs-induced toxicity in vivo, namely a strong reduction of Drosophila lifespan and fertility performance, presence of DNA fragmentation, as well as a significant modification in the expression levels of genes involved in stress responses, DNA damage recognition and apoptosis pathway. Interestingly, we found that, within the investigated experimental conditions, the toxic effects in the exposed organisms were directly related to the concentration of the AuNPs administered, irrespective of their size

    Guideline for diagnosis and treatment of subacromial pain syndrome

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    Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-operatively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears
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