46 research outputs found
Inelastic neutron scattering study of binding of para-hydrogen in an ultra-microporous metal-organic framework
Metal-organic framework (MOF) materials show promise for H2 storage and it is widely predicted by computational modelling that MOFs incorporating ultra-micropores are optimal for H2 binding due to enhanced overlapping potentials. We report the investigation using inelastic neutron scattering of the interaction of H2 in an ultra-microporous MOF material showing low H2 uptake capacity. The study has revealed that adsorbed H2 at 5 K has a liquid recoil motion along the channel with very little interaction with the MOF host, consistent with the observed low uptake. The low H2 uptake is not due to incomplete activation or decomposition as the desolvated MOF shows CO2 uptake with a measured pore volume close to that of the single crystal pore volume. This study represents a unique example of surprisingly low H2 uptake within a MOF material, and complements the wide range of studies on systems showing higher uptake capacities and binding interactions
Leadership and Strategic Management: keys to institutional priorities and planning *
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75630/1/j.1465-3435.2008.00363.x.pd
Molecular decoding using luminescence from an entangled porous framework
Chemosensors detect a single target molecule from among several molecules, but cannot differentiate targets from one another. In this study, we report a molecular decoding strategy in which a single host domain accommodates a class of molecules and distinguishes between them with a corresponding readout. We synthesized the decoding host by embedding naphthalenediimide into the scaffold of an entangled porous framework that exhibited structural dynamics due to the dislocation of two chemically non-interconnected frameworks. An intense turn-on emission was observed on incorporation of a class of aromatic compounds, and the resulting luminescent colour was dependent on the chemical substituent of the aromatic guest. This unprecedented chemoresponsive, multicolour luminescence originates from an enhanced naphthalenediimideâaromatic guest interaction because of the induced-fit structural transformation of the entangled framework. We demonstrate that the cooperative structural transition in mesoscopic crystal domains results in a nonlinear sensor response to the guest concentration
Mécanismes du dysfonctionnement cérébral dans la dystrophie myotonique de type 1 : impacte des expansions CTG sur la physiologie neuronale et astrogliale
Myotonic dystrophy type 1 (DM1) is a severe disorder that affects many tissues, including the central nervous system (CNS). The degree of brain impairment ranges from executive dysfunction, attention deficits, low processing speed, behavioural changes and hypersomnia in the adult form, to pronounced intellectual disability in the congenital cases. The neurological manifestations have a tremendous impact on the academic, professional, social and emotional aspects of daily life. Today there is no cure for this devastating condition. DM1 is caused by the abnormal expansion of a CTG trinucleotide repeat in the 3âUTR of the DMPK gene. Expanded DMPK transcripts accumulate in RNA aggregates (or foci) in the nucleus of DM1 cells, disrupting the activity of important RNA-binding proteins, like the MBNL and CELF families, and leading to abnormalities in alternative splicing, gene expression, RNA polyadenylation, localisation and translation. In spite of recent progress, fundamental gaps in our understanding of the molecular and cellular mechanisms behind the neurological manifestations still exist: we do not know the contribution of each cell type of the CNS to brain dysfunction, or the molecular pathways specifically deregulated in response to the CTG expansion. The aim of my PhD project has been to gain insight into these two important questions using a relevant transgenic mouse model of DM1 and cell cultures derived thereof. In my studies I used the DMSXL mice, previously generated in my host laboratory. The DMSXL mice express expanded DMPK mRNA with more than 1,000 CTG repeats. They recreate relevant DM1 features, such as RNA foci and missplicing in multiple tissues. The functional impact of expanded DMPK transcripts in the CNS of DMSXL mice translates into behavioural and cognitive abnormalities and defective synaptic plasticity. To identify the molecular mechanisms behind these abnormalities, a global proteomics analysis revealed changes in both neuron-specific and glial-specific proteins in DMSXL brain. We also investigated RNA foci in DMSXL and human DM1 brains and found non-homogenous distribution between cell types, with a higher foci content in astrocytes relative to neurons. Together these results suggest that both neuronal and glial defects contribute to DM1 neuropathogenesis. The global proteomics analysis of DMSXL brains also identified abnormalities in neuronal synaptic proteins that we have validated in human brain samples. SYN1 is hyperphosphorilated in a CELF-dependent manner while RAB3A is upregulated in association with MBNL1 depletion. CELF and MBNL proteins regulate the alternative splicing of a subset of transcripts throughout development, and their deregulation in DM1 leads to abnormal expression of fetal splicing isoforms in adult DM1 brains. In this context, I have studied if RAB3A and SYN1 deregulations observed in adult brains are associated with splicing abnormalities or if they recreated embryonic expression and phosphorylation events. My results indicate that the synaptic proteins abnormalities observed in adult DMSXL brains are not caused by defective alternative splicing and do not recreate embryonic events. Thus, DM1 neuropathogenesis goes beyond missplicing and other molecular pathways must be explored in DM1 brains. To better understand the cellular sub-populations susceptible of accumulating toxic RNA foci we have studied foci distribution in different brain regions. We identified pronounced accumulation of toxic RNAs in Bergman astrocytes of DMSXL mice cerebellum and DM1 patients, associated with neuronal hyperactivity of Purkinje cells. A quantitative proteomics analysis revealed a significant downregulation of GLT1 â a glial glutamate transporter expressed by the Bergmann cell in the cerebellum. I have confirmed the GLT1 downregulation in other brain regions of mouse and human brain. (...)La dystrophie myotonique de type 1 (DM1), ou maladie de Steinert, est une maladie qui touche plusieurs tissus, dont le systĂšme nerveux central (SNC). Lâatteinte neurologique est variable et inclut des troubles de la fonction exĂ©cutive, des changements de comportement et une hypersomnolence dans la forme adulte, ainsi quâune dĂ©ficience intellectuelle marquĂ©e dans la forme congĂ©nitale. Dans leur ensemble, les symptĂŽmes neurologiques ont un fort impact sur le parcours acadĂ©mique, professionnel et les interactions sociales. Aujourdâhui aucune thĂ©rapie nâexiste pour cette maladie. La DM1 est due Ă une expansion anormale dâun triplet CTG non-codant dans le gĂšne DMPK. Les ARN messagers DMPK, porteurs de lâexpansion, sâaccumulent dans le noyau des cellules (sous forme de foci) et perturbent la localisation et la fonction de protĂ©ines de liaison Ă lâARN, notamment des familles MBNL et CELF, ce qui entraĂźne des dĂ©fauts dâĂ©pissage alternatif, dâexpression, de polyadenylation et de localisation dâautres ARN cibles. MalgrĂ© le progrĂšs rĂ©cent dans la comprĂ©hension des mĂ©canismes de la maladie, les aspects cellulaires et molĂ©culaires de lâatteinte neurologique restent mĂ©connus: nous ne connaissons ni la contribution de chaque type cellulaire du cerveau, ni les voies molĂ©culaires spĂ©cifiquement dĂ©rĂ©gulĂ©es dans chaque type cellulaire. Lâobjectif de ma thĂšse a Ă©tĂ© de rĂ©pondre Ă ces deux questions importantes en utilisant un modĂšle de souris transgĂ©niques et des cellules primaires dĂ©rivĂ©es de celui-ci. Pour mon projet, jâai utilisĂ© les souris DMSXL gĂ©nĂ©rĂ©es par mon laboratoire. Ces souris reproduisent des caractĂ©ristiques importantes de la DM1, notamment lâaccumulation des ARN toxiques et la dĂ©rĂ©gulation de lâĂ©pissage alternatif dans plusieurs tissus. Lâimpacte fonctionnel des transcrits DMPK toxiques dans le SNC des souris DMSXL se traduit par des problĂšmes comportementaux et cognitifs et par des dĂ©fauts de la plasticitĂ© synaptique. Afin dâidentifier les mĂ©canismes molĂ©culaires associĂ©s Ă ces anomalies, une Ă©tude protĂ©omique globale a montrĂ© une dĂ©rĂ©gulation de protĂ©ines neuronales et astrocytaires dans le cerveau des souris DMSXL. De plus, lâĂ©tude de la distribution des foci dâARN dans les cerveaux des souris et des patients a montrĂ© un contenu plus Ă©levĂ© dans les astrocytes par rapport aux neurones. Ensemble, ces rĂ©sultats suggĂšrent une contribution Ă la fois neuronale et gliale dans la neuropathogenĂšse de la DM1. LâĂ©tude protĂ©omique globale des cerveaux des souris DMSXL, a aussi montrĂ© des dĂ©fauts de protĂ©ines synaptiques spĂ©cifiques des neurones, que nous avons par la suite validĂ©s dans le cerveau des patients. SYN1 est hyperphosphorylĂ©e dâune façon CELF-dĂ©pendante et RAB3A est surexprimĂ© en rĂ©ponse Ă lâinactivation de MBNL1. Les protĂ©ines MBNL et CELF rĂ©gulent lâĂ©pissage alternatif dâun groupe de transcrits au cours du dĂ©veloppement, et leur dĂ©rĂ©gulation dans la DM1 entraĂźne lâexpression anormale dâisoformes dâĂ©pissage embryonnaires dans le tissu adulte. Dans ce contexte, jâai Ă©tudiĂ© si les dĂ©fauts des protĂ©ines RAB3A et SYN1 sont associĂ©s Ă une dĂ©rĂ©gulation dâĂ©pissage, et si les anomalies des protĂ©ines synaptiques identifiĂ©es dans la DM1 reproduisent des Ă©vĂšnements embryonnaires de la rĂ©gulation de RAB3A et SYN1. Mes rĂ©sultats indiquent que les dĂ©fauts de ces protĂ©ines dans les cerveaux adultes ne sont pas dus Ă une altĂ©ration de lâĂ©pissage alternatif des transcrits et ne recrĂ©ent pas des Ă©vĂšnements embryonnaires. La neuropathogenĂšse de la DM1 va, donc, au delĂ de la dĂ©rĂ©gulation de lâĂ©pissage et dâautres voies molĂ©culaires restent Ă explorer dans les cerveaux DM1. Afin dâidentifier des sous-populations cellulaires susceptibles Ă lâaccumulation des ARN toxiques, nous avons Ă©tudiĂ© la distribution des foci dans plusieurs rĂ©gions cĂ©rĂ©brales. (...
Paleobotanical contributions to the knowledge of economical and spiritual life of the GumelniĆŁaâs communities
CĂąrciumaru Marin, DincĂŁ Rodica. Paleobotanical contributions to the knowledge of economical and spiritual life of the GumelniĆŁaâs communities. In: Annales d'UniversitĂ© "Valahia" TĂąrgoviĆte. Section d'ArchĂ©ologie et d'Histoire, Tome 2-3, 2000. pp. 114-116
Spectrographic analysis of neo-eneolithic obsidian samples and several considerations about the obsidian supply sources
CĂąrciumaru Marin, Popovici Dragomir, Cosac Marian, DincĂŁ Rodica. Spectrographic analysis of neo-eneolithic obsidian samples and several considerations about the obsidian supply sources. In: Annales d'UniversitĂ© "Valahia" TĂąrgoviĆte. Section d'ArchĂ©ologie et d'Histoire, Tome 2-3, 2000. pp. 117-127
Toxic RNA impairs synaptic function and vesicle transport in myotonic dystrophy type 1.
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