Late Quaternary foraminifera and paleoceanography off eastern Gaspe Peninsula, Gulf of St. Lawrence.

Changes in the temperature and salinity of the waters off eastern Gaspe Peninsula following the Late Quaternary deglaciation are recognized on the basis of benthonic foraminiferal zones in box, trigger weight and piston cores from depths of 373 and 109 m in the Laurentian Channel and Chaleur Trough respectively. The deglacial stage in the Laurentian Channel was characterized by oscillating low- ({\u3c}25\perthous) and high- (ca. 35\perthous) salinity bottom water. This was followed by bottom water with salinity between 34 and 35\perthous, and then a salinity minimum (30-34\perthous). Radiocarbon ages for foraminifera and pelecypods indicate that the deglacial stage began before 14 ka BP and ended approximately 13.5 ka BP; the salinity minimum began about 12.1 ka BP in the Laurentian Channel. Benthonic foraminiferal zones show that the temperature of the bottom water in Chaleur Trough has remained close to 0\sp\circC since deglaciation. However, the salinity of the bottom water has increased from between 28 and 30\perthous during the deglacial stage to about 33\perthous at present. (Abstract shortened by UMI.)Dept. of Geology and Geological Engineering. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1992 .C453. Source: Masters Abstracts International, Volume: 31-04, page: 1706. Thesis (M.Sc.)--University of Windsor (Canada), 1992

Event Identification as a Decision Process with Non-linear Representation of Text

We propose scale-free Identifier Network(sfIN), a novel model for event identification in documents. In general, sfIN first encodes a document into multi-scale memory stacks, then extracts special events via conducting multi-scale actions, which can be considered as a special type of sequence labelling. The design of large scale actions makes it more efficient processing a long document. The whole model is trained with both supervised learning and reinforcement learning.Comment: 8 pages, 8 figure

The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer

The fragile X mental retardation protein (FMRP) is a RNA-binding protein proposed to post-transcriptionally regulate the expression of genes important for neuronal development and synaptic plasticity. We previously demonstrated that FMRP binds to its own FMR1 mRNA via a guanine-quartet (G-quartet) RNA motif. However, the functional effect of this binding on FMR1 expression was not established. In this work, we characterized the FMRP binding site (FBS) within the FMR1 mRNA by a site directed mutagenesis approach and we investigated its importance for FMR1 expression. We show that the FBS in the FMR1 mRNA adopts two alternative G-quartet structures to which FMRP can equally bind. While FMRP binding to mRNAs is generally proposed to induce translational regulation, we found that mutations in the FMR1 mRNA suppressing binding to FMRP do not affect its translation in cellular models. We show instead that the FBS is a potent exonic splicing enhancer in a minigene system. Furthermore, FMR1 alternative splicing is affected by the intracellular level of FMRP. These data suggest that the G-quartet motif present in the FMR1 mRNA can act as a control element of its alternative splicing in a negative autoregulatory loop

Diklofenak Sodyum ve Montelukast Sodyumun Travmatik Omurilik Yaralanmalarında Akut Enflamasyon Üzerindeki Koruyucu Etkileri: Sıçanlarda Deneysel Bir Çalışma

Amaç: Bu çalışmanın amacı travmatik omurilik yaralanmasında (T-SCI) diklofenak sodyum (DF) ve montelukast sodyumun (ML) akut enflamasyon üzerindeki koruyucu etkilerini araştırmaktır. Gereç ve Yöntem: Kırk Sprague-Dawley sıçanı rastgele beş gruba ayrıldı. Kontrol grubuna herhangi bir müdahale yapılmazken, travma grubuna SCI uygulandı. Kalan üç gruba travma sonrası diklofenak sodyum (tDF), ML (tML) ve tDF+ML intraperitoneal yolla uygulandı. Sıçanlar sakrifiye edildikten sonra hem omurilik hem de dura içeren doku örnekleri histopatolojik incelemeye tabi tutuldu ve ödem, nekroz, enflamatuvar hücreler, apoptoz, nöron hasarı ve kanama açısından skorlandı. Bulgular: Kontrol ve travma grupları arasındaki histopatolojik değişikliklerde gruplar arasında anlamlı fark bulundu (p0,05). Kontrol grubu ile gruplar arasında ödem farkı olmayan grubun tDF grubu olduğu görüldü (p=0,059). Enflamatuvar hücreler incelendiğinde hücre miktarının en az tDF grubunda olduğu izlendi (p=0,068). Nekroz (p=0,1), apoptoz (p=0,061) ve nöral hasar durumunun (p=0,139) tDF+ML kombine grubunda en az olduğu görüldü. Kanama miktarı açısından gruplar arasında anlamlı bir fark yoktu (p>0,05). Sonuç: DF’nin tek başına kullanımı ödem ve enflamatuvar hücre sayısını azaltırken, DF+ML’nin birlikte kullanımının T-SCI’da nekroz, apoptoz ve nöral hasar gelişimini azalttığı saptandı

FMRP Mediates mGluR(5)-Dependent Translation of Amyloid Precursor Protein

Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Aβ) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission. Fragile X mental retardation protein (FMRP) is a cytoplasmic mRNA binding protein whose expression is lost in fragile X syndrome. Here we show that FMRP binds to the coding region of APP mRNA at a guanine-rich, G-quartet–like sequence. Stimulation of cortical synaptoneurosomes or primary neuronal cells with the metabotropic glutamate receptor agonist DHPG increased APP translation in wild-type but not fmr-1 knockout samples. APP mRNA coimmunoprecipitated with FMRP in resting synaptoneurosomes, but the interaction was lost shortly after DHPG treatment. Soluble Aβ(40) or Aβ(42) levels were significantly higher in multiple strains of fmr-1 knockout mice compared to wild-type controls. Our data indicate that postsynaptic FMRP binds to and regulates the translation of APP mRNA through metabotropic glutamate receptor activation and suggests a possible link between Alzheimer disease and fragile X syndrome

Fragile Mental Retardation Protein Interacts with the RNA-Binding Protein Caprin1 in Neuronal RiboNucleoProtein Complexes

Fragile X syndrome is caused by the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein. FMRP is associated with messenger RiboNucleoParticles (mRNPs) present in polyribosomes and its absence in neurons leads to alteration in synaptic plasticity as a result of translation regulation defects. The molecular mechanisms by which FMRP plays a role in translation regulation remain elusive. Using immunoprecipitation approaches with monoclonal Ab7G1-1 and a new generation of chicken antibodies, we identified Caprin1 as a novel FMRP-cellular partner. In vivo and in vitro evidence show that Caprin1 interacts with FMRP at the level of the translation machinery as well as in trafficking neuronal granules. As an RNA-binding protein, Caprin1 has in common with FMRP at least two RNA targets that have been identified as CaMKIIα and Map1b mRNAs. In view of the new concept that FMRP species bind to RNA regardless of known structural motifs, we propose that protein interactors might modulate FMRP functions

A study of the ultrastructure of Fragile-X-related proteins

Fragile-X-related proteins form a family implicated in RNA metabolism. Their sequence is composed of conserved N-terminal and central regions which contain Tudor and KH domains and of a divergent C-terminus with motifs rich in arginine and glycine residues. The most widely studied member of the family is probably FMRP (fragile X mental retardation protein), since absence or mutation of this protein in humans causes fragile X syndrome, the most common cause of inherited mental retardation. Understanding the structural properties of FMRP is essential for correlating it with its functions. The structures of isolated domains of FMRP have been reported, but nothing is yet known with regard to the spatial arrangement of the different modules, partly because of difficulties in producing both the full-length protein and its multidomain fragments in quantities, purities and monodispersity amenable for structural studies. In the present study, we describe how we have produced overlapping recombinant fragments of human FMRP and its paralogues which encompass the evolutionary conserved region. We have studied their behaviour in solution by complementary biochemical and biophysical techniques, identified the regions which promote self-association and determined their overall three-dimensional shape. The present study paves the way to further studies and rationalizes the existing knowledge on the self-association properties of these proteins

Degradation of Mouse Invariant Chain: Roles of Cathepsins S and D and the Influence of Major Histocompatibility Complex Polymorphism

Antigen-presenting cells (APC) degrade endocytosed antigens into peptides that are bound and presented to T cells by major histocompatibility complex (MHC) class II molecules. Class II molecules are delivered to endocytic compartments by the class II accessory molecule invariant chain (Ii), which itself must be eliminated to allow peptide binding. The cellular location of Ii degradation, as well as the enzymology of this event, are important in determining the sets of antigenic peptides that will bind to class II molecules. Here, we show that the cysteine protease cathepsin S acts in a concerted fashion with other cysteine and noncysteine proteases to degrade mouse Ii in a stepwise fashion. Inactivation of cysteine proteases results in incomplete degradation of Ii, but the extent to which peptide loading is blocked by such treatment varies widely among MHC class II allelic products. These observations suggest that, first, class II molecules associated with larger Ii remnants can be converted efficiently to class II–peptide complexes and, second, that most class II–associated peptides can still be generated in cells treated with inhibitors of cysteine proteases. Surprisingly, maturation of MHC class II in mice deficient in cathepsin D is unaffected, showing that this major aspartyl protease is not involved in degradation of Ii or in generation of the bulk of antigenic peptides

Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis