An autoimmune disease prevented by anti-retroviral drugs

<p>Abstract</p> <p>Background</p> <p>Both Aicardi-Goutières syndrome, a Mendelian mimic of congenital infection, and the autoimmune disease systemic lupus erythematosus can result from mutations in the gene encoding the enzyme Trex1. In mice, the absence of Trex1 causes severe myocarditis. The enzyme is thought to degrade endogenous retroelements, thus linking them to autoimmune disease. However, inhibition of reverse transcription by the inhibitor zidovudine (AZT) did not ameliorate the disease, weakening the link to retroelements.</p> <p>Findings</p> <p>Here, we show that two other FDA-approved drugs that inhibit reverse transcriptase can ameliorate the myocarditis in Trex1-null mouse.</p> <p>Conclusions</p> <p>The result suggests that retroelements contribute to this hereditary form of autoimmunity, and that treatment with retroelement inhibitors might ameliorate Aicardi-Goutières syndrome in humans.</p

Experimental Evidence for Efimov Quantum States

Three interacting particles form a system which is well known for its complex physical behavior. A landmark theoretical result in few-body quantum physics is Efimov's prediction of a universal set of weakly bound trimer states appearing for three identical bosons with a resonant two-body interaction. Surprisingly, these states even exist in the absence of a corresponding two-body bound state and their precise nature is largely independent of the particular type of the two-body interaction potential. Efimov's scenario has attracted great interest in many areas of physics; an experimental test however has not been achieved. We report the observation of an Efimov resonance in an ultracold thermal gas of cesium atoms. The resonance occurs in the range of large negative two-body scattering lengths and arises from the coupling of three free atoms to an Efimov trimer. We observe its signature as a giant three-body recombination loss when the strength of the two-body interaction is varied near a Feshbach resonance. This resonance develops into a continuum resonance at non-zero collision energies, and we observe a shift of the resonance position as a function of temperature. We also report on a minimum in the recombination loss for positive scattering lengths, indicating destructive interference of decay pathways. Our results confirm central theoretical predictions of Efimov physics and represent a starting point from which to explore the universal properties of resonantly interacting few-body systems.Comment: 8 pages, 4 figures, Proceedings of ICAP-2006 (Innsbruck

Pvt1-encoded microRNAs in oncogenesis

<p>Abstract</p> <p>Background</p> <p>The functional significance of the <it>Pvt1 </it>locus in the oncogenesis of Burkitt's lymphoma and plasmacytomas has remained a puzzle. In these tumors, <it>Pvt1 </it>is the site of reciprocal translocations to immunoglobulin loci. Although the locus encodes a number of alternative transcripts, no protein or regulatory RNA products were found. The recent identification of non-coding microRNAs encoded within the <it>PVT1 </it>region has suggested a regulatory role for this locus.</p> <p>Results</p> <p>The mouse <it>Pvt1 </it>locus encodes several microRNAs. In mouse T cell lymphomas induced by retroviral insertions into the locus, the <it>Pvt1 </it>transcripts, and at least one of their microRNA products, mmu-miR-1204 are overexpressed. Whereas up to seven co-mutations can be found in a single tumor, in over 2,000 tumors none had insertions into both the <it>Myc </it>and <it>Pvt1 </it>loci.</p> <p>Conclusion</p> <p>Judging from the large number of integrations into the <it>Pvt1 </it>locus – more than in the nearby <it>Myc </it>locus – <it>Pvt1 </it>and the microRNAs encoded by it are as important as <it>Myc </it>in T lymphomagenesis, and, presumably, in T cell activation. An analysis of the co-mutations in the lymphomas likely place <it>Pvt1 </it>and <it>Myc </it>into the same pathway.</p

Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer

<p>Abstract</p> <p>Background</p> <p>GPR110 is an orphan G protein-coupled receptor--a receptor without a known ligand, a known signaling pathway, or a known function. Despite the lack of information, one can assume that orphan receptors have important biological roles. In a retroviral insertion mutagenesis screen in the mouse, we identified GPR110 as an oncogene. This prompted us to study the potential isoforms that can be gleaned from known GPR110 transcripts, and the expression of these isoforms in normal and transformed human tissues.</p> <p>Methods</p> <p>Various epitope-tagged isoforms of GPR110 were expressed in cell lines and assayed by western blotting to determine cleavage, surface localization, and secretion patterns. GPR110 transcript and protein levels were measured in lung and prostate cancer cell lines and clinical samples, respectively, by quantitative PCR and immunohistochemistry.</p> <p>Results</p> <p>We found four potential splice variants of GPR110. Of these variants, we confirmed three as being expressed as proteins on the cell surface. Isoform 1 is the canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are truncated products of isoform 1, and are 25 and 23 kD, respectively. These truncated isoforms lack the seven-span transmembrane domain characteristic of GPR proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can be secreted. Compared with the median gene expression of ~200 selected genes, GPR110 expression was low in most tissues. However, it had higher than average gene expression in normal kidney tissue and in prostate tissues originating from older donors. Although identified as an oncogene in murine T lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue cores. Additionally, staining with a GPR110 antibody enabled us to differentiate between benign prostate hyperplasia and potential incipient malignancy.</p> <p>Conclusion</p> <p>Our work suggests a role for GPR110 in tumor physiology and supports it as a potential therapeutic candidate and disease marker for both lung and prostate cancer.</p

Determination of atomic scattering lengths from measurements of molecular binding energies near Feshbach resonances

We present an analytic model to calculate the atomic scattering length near a Feshbach resonance from data on the molecular binding energy. Our approach considers finite-range square-well potentials and can be applied near broad, narrow, or even overlapping Feshbach resonances. We test our model on Cs$_2$ Feshbach molecules. We measure the binding energy using magnetic-field modulation spectroscopy in a range where one broad and two narrow Feshbach resonances overlap. From the data we accurately determine the Cs atomic scattering length and the positions and widths of two particular resonances.Comment: 6 pages, 4 figure

Evidence for Efimov quantum states in an ultracold gas of cesium atoms

Systems of three interacting particles are notorious for their complex physical behavior. A landmark theoretical result in few-body quantum physics is Efimov's prediction of a universal set of bound trimer states appearing for three identical bosons with a resonant two-body interaction. Counterintuitively, these states even exist in the absence of a corresponding two-body bound state. Since the formulation of Efimov's problem in the context of nuclear physics 35 years ago, it has attracted great interest in many areas of physics. However, the observation of Efimov quantum states has remained an elusive goal. Here we report the observation of an Efimov resonance in an ultracold gas of cesium atoms. The resonance occurs in the range of large negative two-body scattering lengths, arising from the coupling of three free atoms to an Efimov trimer. Experimentally, we observe its signature as a giant three-body recombination loss when the strength of the two-body interaction is varied. We also detect a minimum in the recombination loss for positive scattering lengths, indicating destructive interference of decay pathways. Our results confirm central theoretical predictions of Efimov physics and represent a starting point with which to explore the universal properties of resonantly interacting few-body systems. While Feshbach resonances have provided the key to control quantum-mechanical interactions on the two-body level, Efimov resonances connect ultracold matter to the world of few-body quantum phenomena.Comment: 18 pages, 3 figure

The Origin and Initial Rise of Pelagic Cephalopods in the Ordovician

BACKGROUND: During the Ordovician the global diversity increased dramatically at family, genus and species levels. Partially the diversification is explained by an increased nutrient, and phytoplankton availability in the open water. Cephalopods are among the top predators of today's open oceans. Their Ordovician occurrences, diversity evolution and abundance pattern potentially provides information on the evolution of the pelagic food chain. METHODOLOGY/PRINCIPAL FINDINGS: We reconstructed the cephalopod departure from originally exclusively neritic habitats into the pelagic zone by the compilation of occurrence data in offshore paleoenvironments from the Paleobiology Database, and from own data, by evidence of the functional morphology, and the taphonomy of selected cephalopod faunas. The occurrence data show, that cephalopod associations in offshore depositional settings and black shales are characterized by a specific composition, often dominated by orthocerids and lituitids. The siphuncle and conch form of these cephalopods indicate a dominant lifestyle as pelagic, vertical migrants. The frequency distribution of conch sizes and the pattern of epibionts indicate an autochthonous origin of the majority of orthocerid and lituitid shells. The consistent concentration of these cephalopods in deep subtidal sediments, starting from the middle Tremadocian indicates the occupation of the pelagic zone early in the Early Ordovician and a subsequent diversification which peaked during the Darriwilian. CONCLUSIONS/SIGNIFICANCE: The exploitation of the pelagic realm started synchronously in several independent invertebrate clades during the latest Cambrian to Middle Ordovician. The initial rise and diversification of pelagic cephalopods during the Early and Middle Ordovician indicates the establishment of a pelagic food chain sustainable enough for the development of a diverse fauna of large predators. The earliest pelagic cephalopods were slowly swimming vertical migrants. The appearance and early diversification of pelagic cephalopods is interpreted as a consequence of the increased food availability in the open water since the latest Cambrian