An orchestrated intron retention program in meiosis controls timely usage of transcripts during germ cell differentiation

Global transcriptome reprogramming during sper-matogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Sper-matocytes and spermatids require particularly exten-sive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete func-tion. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differ-ently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis

A Rigorous Approach to the Feynman-Vernon Influence Functional and its Applications. I

A rigorous representation of the Feynman-Vernon influence functional used to describe open quantum systems is given, based on the theory of infinite dimensional oscillatory integrals. An application to the case of the density matrices describing the Caldeira-Leggett model of two quantum systems with a quadratic interaction is treated

CXCR3 and α_Eβ₇ integrin identify a subset of CD8+ mature thymocytes that share phenotypic and functional properties with CD8+ gut intraepithelial lymphocytes

Background: We previously demonstrated the existence of two distinct subsets of T cell receptor (TCR)αβ+CD8αβ+ single positive (SP) cells in human postnatal thymus which express the chemokine receptor CCR7 or CXCR3 and migrate in vitro in response to their specific ligands. Aim: To investigate whether these two CD8+ thymocyte subsets had distinct peripheral colonisation. Methods: TCRαβ+CD8+ SP cells were obtained from normal postnatal thymus, mesenteric lymph node (LNs), small bowel, and peripheral blood (PB) specimens. Cells were then evaluated for expression of surface molecules, cytolytic potential, telomere length, and profile of cytokine production. Results: CD8+CCR7+CXCR3− thymocytes exhibited CD62L, in common with those which localise to LNs. In contrast, CD8+CCR7−CXCR3+ thymocytes lacked CD62L but exhibited CD103, similar to intraepithelial lymphocytes (IELs) present in the gut mucosa where the CXCR3 ligand, CXCL10, and the CD103 ligand, E-cadherin, are highly and consistently expressed. In addition, thymocytes and gut CD8+CXCR3+CD103+ cells showed comparable telomere length, which was higher than that of PB CXCR3+CD8+ T cells. However, both of these populations contained perforin and granzyme A, and displayed the ability to produce interferon γ and interleukin 2. Of note, CXCR3 deficient, in comparison with wild-type C57Black/6, mice showed decreased proportions of CD3+CD8αβ+ and increased proportions of CD3+CD8αα+ lymphocytes at gut level. Moreover, adoptive transfer of CD3+CD8αβ+ thymocytes from wild-type into CXCR3 deficient mice resulted in a significant increase in CD3+CD8αβ+ T cells in the gut mucosa but not in other tissues. Conclusions: The results of this study demonstrate the existence of a previously unrecognised subset of TCRαβ+CD8αβ+ SP CXCR3+CD103+ thymocytes which share phenotypic and functional features with CD8+ IELs, thus suggesting the possibility of their direct colonisation of the gut mucosa

Progress on the development of the Stellar X-ray Polarimeter on board of the Spectrum-X-Gamma Satellite

We present the status of the Stellar X-ray Polarimeter at November’94 devoted to measure linear polarisation from cosmic X-ray sources between 2 keV and 15 keV which will be flown on the Spectrum-X-Gamma Satellite. In particular, we focus on the performances of the engineering model after the calibrations at Lawrence Livermore Laboratories and on the improvements which have been introduced on the four flight model imaging proportional counters which are key parts of the experiment

Discovery of extreme particle acceleration in the microquasar Cygnus X-3

The study of relativistic particle acceleration is a major topic of high-energy astrophysics. It is well known that massive black holes in active galaxies can release a substantial fraction of their accretion power into energetic particles, producing gamma-rays and relativistic jets. Galactic microquasars (hosting a compact star of 1-10 solar masses which accretes matter from a binary companion) also produce relativistic jets. However, no direct evidence of particle acceleration above GeV energies has ever been obtained in microquasar ejections, leaving open the issue of the occurrence and timing of extreme matter energization during jet formation. Here we report the detection of transient gamma-ray emission above 100 MeV from the microquasar Cygnus X-3, an exceptional X-ray binary which sporadically produces powerful radio jets. Four gamma-ray flares (each lasting 1-2 days) were detected by the AGILE satellite simultaneously with special spectral states of Cygnus X-3 during the period mid-2007/mid-2009. Our observations show that very efficient particle acceleration and gamma-ray propagation out of the inner disk of a microquasar usually occur a few days before major relativistic jet ejections. Flaring particle energies can be thousands of times larger than previously detected maximum values (with Lorentz factors of 105 and 102 for electrons and protons, respectively). We show that the transitional nature of gamma-ray flares and particle acceleration above GeV energies in Cygnus X-3 is clearly linked to special radio/X-ray states preceding strong radio flares. Thus gamma-rays provide unique insight into the nature of physical processes in microquasars.Comment: 29 pages (including Supplementary Information), 8 figures, 2 tables version submitted to Nature on August 7, 2009 (accepted version available at http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature08578.pdf

Detection of Gamma-Ray Emission from the Vela Pulsar Wind Nebula with AGILE

Pulsars are known to power winds of relativistic particles that can produce bright nebulae by interacting with the surrounding medium. These pulsar wind nebulae (PWNe) are observed in the radio, optical, x-rays and, in some cases, also at TeV energies, but the lack of information in the gamma-ray band prevents from drawing a comprehensive multiwavelength picture of their phenomenology and emission mechanisms. Using data from the AGILE satellite, we detected the Vela pulsar wind nebula in the energy range from 100 MeV to 3 GeV. This result constrains the particle population responsible for the GeV emission, probing multivavelength PWN models, and establishes a class of gamma-ray emitters that could account for a fraction of the unidentified Galactic gamma-ray sources.Comment: Accepted by Science; first published online on December 31, 2009 in Science Express. Science article and Supporting Online Material are available at http://www.sciencemag.or

XIPE: the X-ray Imaging Polarimetry Explorer

X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068