935 research outputs found

    Does Congress Find Facts or Construct Them - The Ascendance of Politics over Reliability, Perfected in Gonzales v. Carhart

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    The disparity between the rules of courts and the rules of Congress gives rise to this question: is the rigor-or lack of it-with which Congress evaluates the reliability of evidence an appropriate factor for courts to consider in deciding whether to defer to a congressional finding? In this Article, I consider whether Congress should adopt rules to fill the void. In Part I, I give a brief summary of the development and use of Congressional Committees. In Part II, I analyze several modern-day congressional hearings in an effort to examine the degree to which Congress and its committees require that the evidence on which they base their findings be reliable. I focus primarily, though not exclusively, on the modern-day impeachment trials and other high-profile proceedings such as the Clarence Thomas confirmation hearings. The usefulness of these more famous-sometimes infamous-proceedings arises from the fact that they place legislators and their evidentiary rulings in the limelight of public attention, thus heightening the visibility of Congress\u27s decisions to value trustworthiness or to sacrifice it to partisanship. I suggest that political considerations have infected fact-finding to an increasing extent, to the point that almost all fact-finding in modern hearings is deliberately shaped so as to accomplish a political goal. In Part III, I employ the United States Supreme Court\u27s decision in Gonzales v. Carhart, along with the legislative findings which were significant to that decision, as a lens through which to view the relationship between the reliability of Congress\u27s evidence and the propriety of judicial deference to the findings based on that evidence. In Part IV, I narrow the focus to examine the Court\u27s rationale for the decision in Gonzales v. Carhart, and I suggest that the rationale offered in the decision does not fully explain the ruling and that the subtext must be taken into account in order for the decision to be understood. In Part V, I recommend that Congress either employ neutral fact-finding bodies or adopt rules of evidence to promote reliability in its hearings, and I suggest that deference to legislative findings should depend on the presence of such limits to check unbridled discretion in fact-finding

    Activation of spleen tyrosine kinase (Syk) at fertilization in Rhinella arenarum eggs

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    Recently, we have provided evidence for the involvement of a cytosolic tyrosine–phosphorylatable 70 kDa oocyte protein in Rhinella arenarum (Anura: Bufonidae) fertilization. The aim of the present work was to characterize its phosphorylation, determine the identity of this protein and establish its biological role during the fertilization process. Tyrosine phosphorylation of the 70 kDa protein was not observed in eggs activated with the calcium ionophore A23187. Pretreatment of oocytes with the tyrosine kinase inhibitor genistein effectively blocked the fertilization-dependent phosphorylation of the 70 kDa protein. In order to identify this protein, we examined the presence in amphibian oocytes of non-receptor 70 kDa tyrosine kinase members of the Syk/Zap70 and Tec families by RT-PCR using degenerate primers. We found that R. arenarum oocytes contain the transcripts coding for Syk and Tec kinases. Western blot analysis confirmed the presence of Syk protein in unfertilized oocytes and eggs. Studies using phospho-Syk specific antibodies showed that fertilization rapidly (less than 10 minutes) induces phosphorylation on Syk tyrosine residues (352 and 525/526) that are necessary for the activation of the enzyme. Finally, specific inhibition of Syk with the R406 compound provoked a diminished fertilization score, thereby confirming a functional role of the Syk protein during R. arenarum fertilization. To our knowledge this is the first time that Syk is described as a player in the signaling cascade activated after fertilization.Fil: Mouguelar, Valeria Soraya. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Coux, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

    Insights into vertebrate head development: From cranial neural crest to the modelling of neurocristopathies

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    Although the vertebrate head has evolved to a wide collection of adaptive shapes, the fundamental signalling pathways and cellular events that outline the head skeleton have proven to be highly conserved. This conservation suggests that major morphological differences are due to changes in differentiation and morphogenetic programs downstream of a well-maintained developmental prepattern. Here we provide a brief examination of the mechanisms and pathways responsible for vertebrate head development, as well as an overview of the animal models suitable for studying face development. In addition, we describe the criteria for neurocristopathy classifica-tion, highlighting the contribution of zebrafish to the modelling of Treacher Collins/Franceschetti Syndrome, an emblematic neurocristopathy. The contributions from our laboratory reveal that proper zebrafish head development depends on the fine-tuning of developmental-gene expression mediated by nucleic acid binding proteins able to regulate DNA conformation and / or the neuroepithelium redox state.Fil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Coux, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

    Intégration de films épitaxiés de CoFe2O4 ferrimagnétiques sur silicium

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    L'intégration de couches minces de CoFe2O4, ferromagnétique et isolant électrique à température ambiante, sur silicium pourrait être utilisée en tant que barrière tunnel dans un dispositif de filtre à spin, comme alternative à l'injection utilisant des électrodes ferromagnétiques et des barrières tunnel passives. L'instabilité thermodynamique entre CoFe2O4 et Si impose l'utilisation d'une couche tampon pour son intégration. L'exigeant défi est donc de fabriquer des bicouches épitaxiées et ultrafines afin de préserver le ferromagnétisme et le transport par effet tunnel. Nous avons adopté une stratégie de recherche en parallèle considérant différents candidats pour la couche tampon pour déposer des couches de CoFe2O4 par dépôt par laser pulsé (PLD). Nous avons utilisé des couches tampon de SrTiO3 épitaxiées sur Si(001) fabriquées par des collaborateurs de l'INL-Lyon. Une diffusion de Ti dans CoFe2O4, et une possible instabilité de l'interface SrTiO3/Si(001) ont été décelés. L'étude des mécanismes de croissance épitaxiale de l'yttrium stabilisé avec de la zircone (YSZ) sur Si(001) a permis de déterminer les limites de réduction d'épaisseur d'YSZ et de la couche interfaciale de SiOx par PLD monitorisé par RHEED. L'épaisseur de CFO/YSZ/SiOx résultante est excessive pour un dispositif de filtre à spin. Les buffers de Sc2O3 et Y2O3 sur Si(111), fournis par des collaborateurs de l'IHP-Frankfurt Oder présentent un grand désaccord paramétrique avec CoFe2O4, mais permettent sa croissance épitaxiale par domaines avec une magnétisation proche de celle du matériau massif. Y2O3 étant stable avec Si est très prometteurs pour la structure de filtre à spin.The integration of ferromagnetic and electrically insulating at room temperature CoFe2O4 thin films with silicon could be used as tunnel barrier in a spin filter device as an alternative to the injection using ferromagnetic electrodes and passive tunnel barriers. The thermodynamical instability between CoFe2O4 and Si imposes the use of a buffer layer for its epitaxial integration. The challenging goal is therefore fabricating ultrathin epitaxial CoFe2O4/buffer bilayers on silicon in order to preserve ferromagnetism and allow the tunnel transport. The followed strategy was based on investigating in parallel several buffer candidates to grow CoFe2O4 by pulsed laser deposition (PLD). We have used thick SrTiO3 buffers fabricated by collaborators at INL-Lyon, which is epitaxial and ferromagnetic. However, there is diffusion of Ti into CoFe2O4 and the SrTiO3/Si(001) interface could be unstable. The epitaxial growth mechanism of yttria-stabilized-zirconia (YSZ) was investigated to determine the limits reducing the YSZ thickness and the interfacial layer by reflection high energy electron diffraction (RHEED) assisted PLD. The total thickness of CFO/YSZ/SiOx is excessive for a tunnel device. Sc2O3 and Y2O3 buffers on Si(111), provided by collaborators at IHP-Frankfurt Oder presents a huge lattice mismatch with CoFe2O4, but allows it epitaxial growth by domain matching epitaxy with a magnetization close to the bulk value. The absence of interfacial SiOx layer in the CoFe2O4/Y2O3/Si(111) sample indicates that Y2O3 is a very promising buffer layer and maybe convenient for the nanometric structure required in a spin filter

    What's new about CNBP? Divergent functions and activities for a conserved nucleic acid binding protein

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    Background: Cellular nucleic acid binding protein (CNBP) is a conserved single-stranded nucleic acid binding protein present in most eukaryotes, but not in plants. Expansions in the CNBP gene cause myotonic dystrophy type 2. Initially reported as a transcriptional regulator, CNBP was then also identified acting as a translational regulator. Scope of review: The focus of this review was to link the CNBP structural features and newly reported biochemical activities with the recently described biological functions, in the context of its pathological significance. Major conclusions: Several post-translational modifications affect CNBP subcellular localization and activity. CNBP participates in the transcriptional and translational regulation of a wide range of genes by remodeling single-stranded nucleic acid secondary structures and/or by modulating the activity of trans-acting factors. CNBP is required for proper neural crest and heart development, and plays a role in cell proliferation control. Besides, CNBP has been linked with neurodegenerative, inflammatory, and congenital diseases, as well as with tumor processes. General significance: This review provides an insight into the growing functions of CNBP in cell biology. A unique and robust mechanistic or biochemical connection among these roles has yet not been elucidated. However, the ability of CNBP to dynamically integrate signaling pathways and to act as nucleic acid chaperone may explain most of the roles and functions identified so far.Fil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Coux, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

    piRNA-mediated regulation of transposon alternative splicing in the soma and germ line

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    Transposable elements can drive genome evolution, but their enhanced activity is detrimental to the host and therefore must be tightly regulated1. The Piwi-interacting small RNA (piRNA) pathway is vital for the regulation of transposable elements, by inducing transcriptional silencing or post-transcriptional decay of mRNAs2. Here we show that piRNAs and piRNA biogenesis components regulate precursor mRNA splicing of P-transposable element transcripts in vivo, leading to the production of the non-transposase-encoding mature mRNA isoform in Drosophila germ cells. Unexpectedly, we show that the piRNA pathway components do not act to reduce transcript levels of the P-element transposon during P–M hybrid dysgenesis, a syndrome that affects germline development in Drosophila3,4. Instead, splicing regulation is mechanistically achieved together with piRNA-mediated changes to repressive chromatin states, and relies on the function of the Piwi–piRNA complex proteins Asterix (also known as Gtsf1)5,6,7 and Panoramix (Silencio)8,9, as well as Heterochromatin protein 1a (HP1a; encoded by Su(var)205). Furthermore, we show that this machinery, together with the piRNA Flamenco cluster10, not only controls the accumulation of Gypsy retrotransposon transcripts11 but also regulates the splicing of Gypsy mRNAs in cultured ovarian somatic cells, a process required for the production of infectious particles that can lead to heritable transposition events12,13. Our findings identify splicing regulation as a new role and essential function for the Piwi pathway in protecting the genome against transposon mobility, and provide a model system for studying the role of chromatin structure in modulating alternative splicing during development

    Antigen processing of a short viral antigen by proteasomes

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    Mass spectrometry (MS)-based methods coupled to reverse phase chromatography separation are a useful technology to analyze complex peptide pools that are comprised of different peptides with unrelated sequences. In antigen presentation, proteasomes generate a set of short peptides that are closely related and overlapping and in some instances may even have identical retention times and identical masses. In these situations, micro-liquid chromatography-MS/MS focused on each theoretical parent ion followed by manual interpretation optimizes the identification of generated peptides. The results suggest that the degradation of short antigens by the proteasome occurs by sequential cleavage.This work was supported by grants from the Programa Ramón y Cajal, Comunidad de Madrid, Instituto de Salud Carlos III, Fundación FIPSE, and Fondo de Investigaciones Sanitarias de la SS (to D. L.) and from the Ministerio de Educación y Ciencia, Comunidad de Madrid, and Instituto de Salud Carlos III (to M. D. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.S
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