Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis

The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.

Prolapse-free relativistic Gaussian basis sets for the superheavy elements up to Uuo (Z=118) and Lr (Z=103)

Prolapse-free basis sets suitable for four-component relativistic quantum chemical calculations are presented for the superheavy elements UP to (118)Uuo ((104)Rf, (105)Db, (106)Sg, (107)Bh, (108)Hs, (109)Mt, (110)Ds, (111)Rg, (112)Uub, (113)Uut, (114)Uuq, (115)Uup, (116)Uuh, (117)Uus, (118)Uuo) and Lr-103. These basis sets were optimized by minimizing the absolute values of the energy difference between the Dirac-Fock-Roothaan total energy and the corresponding numerical value at a milli-Hartree order of magnitude, resulting in a good balance between cost and accuracy. Parameters for generating exponents and new numerical data for some superheavy elements are also presented. (c) 2007 Elsevier B.V. All rights reserved.

Scaling in few-body nuclear physics

The nuclear matter calculations with realistic nucleon-nucleon potentials present a general scaling between the nucleon-nucleus binding energy, the corresponding saturation density, and the triton binding energy. The Thomas-Efimov three-body effect implies in correlations among low-energy few-body and many-body observables. It is also well known that, by varying the short-range repulsion, keeping the two-nucleon information (deuteron and scattering) fixed, the four-nucleon and three-nucleon binding energies lie on a very narrow band known as a Tjon line. By looking for a universal scaling function connecting the proper scales of the few-body system with those of the many-body system, we suggest that the general nucleus-nucleon scaling mechanism is a manifestation of a universal few-body effect.

Long- and medium-range components of the nuclear force in quark-model based calculations

Quark-model descriptions of the nucleon-nucleon interaction contain two main ingredients, a quark-exchange mechanism for the short-range repulsion and meson exchanges for the medium- and long-range parts of the interaction. We point out the special role played by higher partial waves, and in particular the (1)F(3), as a very sensitive probe for the meson-exchange pan employed in these interaction models. In particular, we show that the presently available models fail to provide a reasonable description of higher partial waves and indicate the reasons for this shortcoming.

The plethysm technique applied to the classification of nuclear states

A short summary of the theory of symmetric group and symmetric functions needed to follow the theory of Schur functions and plethysms is presented. One then defines plethysm, gives its properties and presents a procedure for its calculation. Finally, some aplications in atomic physics and nuclear structure are given.

The STATFLUX code: a statistical method for calculation of flow and set of parameters, based on the Multiple-Compartment Biokinetical Model

The code STATFLUX, implementing a new and simple statistical procedure for the calculation of transfer coefficients in radionuclide transport to animals and plants, is proposed. The method is based on the general multiple-compartment model, which uses a system of linear equations involving geometrical volume considerations. Flow parameters were estimated by employing two different least-squares procedures: Derivative and Gauss-Marquardt methods, with the available experimental data of radionuclide concentrations as the input functions of time. The solution of the inverse problem, which relates a given set of flow parameter with the time evolution of concentration functions, is achieved via a Monte Carlo Simulation procedure.Program summaryTitle of program: STATFLUXCatalogue identifier: ADYS_v1_0Program summary URL: http://cpc.cs.qub.ac.uk/summaries/ADYS_v1_0Program obtainable from: CPC Program Library, Queen's University of Belfast, N. IrelandLicensing provisions: noneComputer for which the program is designed and others on which it has been tested: Micro-computer with Intel Pentium III, 3.0 GHzInstallation: Laboratory of Linear Accelerator, Department of Experimental Physics, University of São Paulo, BrazilOperating system: Windows 2000 and Windows XPProgramming language used: Fortran-77 as implemented in Microsoft Fortran 4.0. NOTE: Microsoft Fortran includes non-standard features which are used in this program. Standard Fortran compilers such as, g77, f77, ifort and NAG95, are not able to compile the code and therefore it has not been possible for the CPC Program Library to test the program.Memory, required to execute with typical data: 8 Mbytes of RAM memory and 100 MB of Hard disk memoryNo. of bits in a word: 16No. of lines in distributed program, including test data, etc.: 6912No. of bytes in distributed Program, including test data, etc.: 229 541Distribution format: tar.gzNature of the physical problem: the investigation of transport mechanisms for radioactive substances, through environmental pathways, is very important for radiological protection of populations. One such pathway, associated with the food chain, is the grass-animal-man sequence. The distribution of trace elements in humans and laboratory animals has been intensively studied over the past 60 years [R.C. Pendlenton, C.W. Mays, R.D. Lloyd, A.L. Brooks, Differential accumulation of iodine-131 from local fallout in people and milk, Health Phys. 9 (1963) 1253-1262]. In addition, investigations on the incidence of cancer in humans, and a possible causal relationship to radioactive fallout, have been undertaken [E.S. Weiss, M.L. Rallison, W.T. London, W.T. Carlyle Thompson, Thyroid nodularity in southwestern Utah school children exposed to fallout radiation, Amer. J. Public Health 61 (1971) 241-249; M.L. Rallison, B.M. Dobyns, F.R. Keating, J.E. Rall, F.H. Tyler, Thyroid diseases in children, Amer. J. Med. 56 (1974) 457-463; J.L. Lyon, M.R. Klauber, J.W. Gardner, K.S. Udall, Childhood leukemia associated with fallout from nuclear testing, N. Engl. J. Med. 300 (1979) 397-402]. From the pathways of entry of radionuclides in the human (or animal) body, ingestion is the most important because it is closely related to life-long alimentary (or dietary) habits. Those radionuclides which are able to enter the living cells by either metabolic or other processes give rise to localized doses which can be very high. The evaluation of these internally localized doses is of paramount importance for the assessment of radiobiological risks and radiological protection. The time behavior of trace concentration in organs is the principal input for prediction of internal doses after acute or chronic exposure. The General Multiple-Compartment Model (GMCM) is the powerful and more accepted method for biokinetical studies, which allows the calculation of concentration of trace elements in organs as a function of time, when the flow parameters of the model are known. However, few biokinetics data exist in the literature, and the determination of flow and transfer parameters by statistical fitting for each system is an open problem.Restriction on the complexity of the problem: This version of the code works with the constant volume approximation, which is valid for many situations where the biological half-live of a trace is lower than the volume rise time. Another restriction is related to the central flux model. The model considered in the code assumes that exist one central compartment (e.g., blood), that connect the flow with all compartments, and the flow between other compartments is not included.Typical running time: Depends on the choice for calculations. Using the Derivative Method the time is very short (a few minutes) for any number of compartments considered. When the Gauss-Marquardt iterative method is used the calculation time can be approximately 5-6 hours when similar to 15 compartments are considered. (C) 2006 Elsevier B.V. All rights reserved.

Genomic organization of the Neurospora crassa gsn gene: possible involvement of the STRE and HSE elements in the modulation of transcription during heat shock

Glycogen synthase, an enzyme involved in glycogen biosynthesis, is regulated by phosphorylation and by the allosteric ligand glucose-6-phosphate (G6P). In addition, enzyme levels can be regulated by changes in gene expression. We recently cloned a cDNA for glycogen synthase (gsn) from Neurospora crassa, and showed that gsn transcription decreased when cells were exposed to heat shock (shifted from 30degreesC to 45degreesC). In order to understand the mechanisms that control gsn expression, we isolated the gene, including its 5' and 3' flanking regions, from the genome of N. crassa. An ORF of approximately 2.4 kb was identified, which is interrupted by four small introns (II-V). Intron I (482 bp) is located in the 5'UTR region. Three putative Transcription Initiation Sites (TISs) were mapped, one of which lies downstream of a canonical TATA-box sequence (5'-TGTATAAA-3'). Analysis of the 5'-flanking region revealed the presence of putative transcription factor-binding sites, including Heat Shock Elements (HSEs) and STress Responsive Elements (STREs). The possible involvement of these motifs in the negative regulation of gsn transcription was investigated using Electrophoretic Mobility Shift Assays (EMSA) with nuclear extracts of N. crassa mycelium obtained before and after heat shock, and DNA fragments encompassing HSE and STRE elements from the 5'-flanking region. While elements within the promoter region are involved in transcription under heat shock, elements in the 5'UTR intron may participate in transcription during vegetative growth. The results thus suggest that N. crassa possesses trans-acting elements that interact with the 5'-flanking region to regulate gsn transcription during heat shock and vegetative growth.

The contribution of transposable elements to Bos taurus gene structure

In an effort to identify the contribution of TEs to bovine genome evolution, the abundance, distribution and insertional orientation of TEs were examined in all bovine nuclear genes identified in sequence build 2.1 (released October 11, 2005). Exons, introns and promoter segments (3 kb upstream the transcription initiation sites) were screened with the RepeatMasker program. Most of the genes analyzed contained TE insertions, with an average of 18 insertions/gene. The majority of TE insertions identified were classified as retrotransposons and the remainder classified as DNA transposons. TEs were inserted into exons and promoter segments infrequently, while insertion into intron sequences was strikingly more abundant. The contribution of TEs to exon sequence is of great interest because TE insertions can directly influence the phenotype by altering protein sequences. We report six cases where the entire exon sequences of bovine genes are apparently derived from TEs and one of them, the insertion of Charlie into a bovine transcript similar to the zinc finger 452 gene is analyzed in detail. The great similarity of the TE-cassette sequence to the ZNF452 protein and phylogenetic relationship strongly suggests the occurrence of Charlie 10 DNA exaptation in the mammalian zinc finger 452 gene. (c) 2006 Published by Elsevier B.V.

Short-range repulsion and isospin dependence in the kaon-nucleon (KN) system

The short-range properties of the kaon-nucleon (KN) interaction are studied within the meson-exchange model of the Jülich group. Specifically, dynamical explanations for the phenomenological short-range repulsion, required in this model for achieving agreement with the empirical KN data, are explored. Evidence is found that contributions from the exchange of a heavy scalar-isovector meson [a0(980)] as well as from genuine quark-gluon exchange processes are needed. Taking both mechanisms into account, a satisfactory description of the KN phase shifts can be obtained without resorting to phenomenological pieces.

Orphan nuclear receptor NGFI-B forms dimers with nonclassical interface

The orphan receptor nerve growth factor-induced B (NGFI-B) is a member of the nuclear receptor's subfamily 4A (Nr4a). NGFI-B was shown to be capable of binding both as a monomer to an extended half-site containing a single AAAGGTCA motif and also as a homodimer to a widely separated everted repeat, as opposed to a large number of nuclear receptors that recognize and bind specific DNA sequences predominantly as homo- and/or heterodimers. To unveil the structural organization of NGFI-B in solution, we determined the quaternary structure of the NGFI-B LBD by a combination of ab initio procedures from small-angle X-ray scattering (SAXS) data and hydrogen-deuterium exchange followed by mass spectrometry. Here we report that the protein forms dimers in solution with a radius of gyration of 2.9 nm and maximum dimension of 9.0 nm. We also show that the NGFI-B LBD dimer is V-shaped, with the opening angle significantly larger than that of classical dimer's exemplified by estrogen receptor (ER) or retinoid X receptor (RXR). Surprisingly, NGFI-B dimers formation does not occur via the classical nuclear receptor dimerization interface exemplified by ER and RXR, but instead, involves an extended surface area composed of the loop between helices 3 and 4 and C-terminal fraction of the helix 3. Remarkably, the NGFI-B dimer interface is similar to the dimerization interface earlier revealed for glucocorticoid nuclear receptor (GR), which might be relevant to the recognition of cognate DNA response elements by NGFI-B and to antagonism of NGFI-B-dependent transcription exercised by GR in cells. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society.

Intrinsic magnetic properties of BixCo2-xMnO 4 spinels obtained by short-time etching

We report the structural and magnetic properties of Co2MnO 4, partially substituted by Bi at the octahedral site. Bismuth enhances ferromagnetism due to a decrease of the Co2+-Co2+ antiferromagnetic interactions and an increase of the Mn3+-Mn 4+ exchanges. Spurious phases (magnetic and/or nonmagnetic oxides) can easily form because of the large differences between the ionic radii of Bi3+ and Co3+, hiding or altering the intrinsic physical properties of the main BixCo2-xMnO4 phase. An easy way to eliminate the secondary phases is using acid reagents. Short-time etching of Bi0.1Co1.9MnO4 using nitric acid was successfully used, keeping most of the properties of the initial compound, with no alteration of the crystallographic structure. Final stoichiometry was respected (∼Bi0.08Co1.82MnO4), meaning that the material after etching definitely contains bismuth elements in its structure and the observed properties are intrinsic to the oxide spinel. Additional experiments were performed as a function of the synthesis conditions, showing that an optimal pH value of 7 allowed the best magnetic response of the non-doped material. © 2013 Elsevier B.V. All rights reserved.

Ultrastructural Morphology and Nuclear Maturation Rates of Immature Equine Oocytes Vitrified with Different Solutions and Exposure Times

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Aplicação dos princípios de radioproteção em medicina nuclear

The Nuclear Medicine is a medical specialty which uses different radioisotopes for diagnostic and therapeutic purposes. The isotopes are radioactive elements which are administered in vivo and present distribution to specific organs or cell types. The knowledge of radioactivity and notions related to ionizing radiation allow to contextualize the radiological protection measures to be taken in Nuclear Medicine. So it is possible to minimize unnecessary exposure to patients, the public, and individuals occupationally exposed and the environmental. For this it is necessary to relate the physical and technological bases apply to this mode with the standards established by regulatory agencies, including the CNEN (National Nuclear Energy Commission) and ANVISA (National Agency for Sanitary Vigilance). In this scenario, it is important that the theoretical endorse the activities which are periodically audited for verification of compliance with the standards that aim to radioprotection. One role of the Medical Physicist in these services is, therefore, act as Radiation Protection Supervisor exerting numerous activities and ensuring compliance with these standards. In this context the stage in the area of Nuclear Medicine was developed in many customers of the enterprise Rad Dimenstein & Associados LTDA, among them the hospitals Israelita Albert Einstein (HIAE), Nossa Senhora de Lourdes (HNSL), Santa Paula (HSP), Cruz Azul (CRAZ), Grupo Fleury, among other clinics. Following the routine and then carrying out various activities pertaining to the Medical Physicist in the area, it was noted that the measures and actions are extremely effective and fundamental in terms of radiological protection

Contaminação radioativa: aspectos fundamentais associados à poluição nuclear

Since its discovery, radioactivity has brought numerous benefits to human societies. It has many applications in medicine, serving as a tool for non-invasive methods for diagnosis and therapies against diseases such as cancer. It also applies to technologies for energy in nuclear power plants with relatively low impacts on terms of perfect security. All applications, however, have risks, requiring maximum caution to drive processes and operations involving radioactive elements because, once released into the environment, they have extremely harmful effects on organisms affected. This paper presents fundamental concepts and principles of nuclear physics in order to understand the effects of radioactive elements released into the environment, culminating on the issue of radioactive contamination. Literature review allowed us to understand the radioactive contamination problem on living beings. Three major nuclear accidents have happened in the last thirty years, two of them in consecutive years. The nuclear accident at Chernobyl, Ukraine, in 1986, polluted large areas, condemning hundreds of thousands of people to live with consequences of the accident and effects of radiation, killing thousands of people throughout the years. In 1987, a major radiological accident occurred in Goiania (GO) when a source of radioactive cesium was violated, leading to the death of those who had direct or indirect contact with cesium. The most recent accident, in March, 2011, was located at the nuclear power plant in Fukushima Prefecture, Japan, after an earthquake and tsunami hit the region. There is no extensive and accurate knowledge about the consequences of the contamination entailed in that accident, although it is possible to verify signals on a global scale. An analysis of reports of contamination of large areas generated by nuclear plants with release of hazardous wastes suggests it is necessary to rethink the energy matrix of the various countries...

Loss of nuclear poly(A)-binding protein 1 (PABPN1) causes defects in myogenesis and mRNA biogenesis

The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.