A First Look at the Interim Merits Award in S.D. Myers, Inc. v. Canada: It Is Possible to Balance Legitimate Environmental Concerns with Investment Protection

This Article is a response to Joseph de Pencier\u27s paper Investment, Environment and Dispute Settlement: Arbitration Under NAFTA Chapter Eleven in issue 23:3-4 of this journal. This reply is based upon the author\u27s experience as counsel for the investor in S.D. Myers, Inc. v. Canada (Myers) and similar cases. This Article provides a critical commentary on various elements of Mr. de Pencier\u27s paper that deal with the Myers claim. It provides some tentative suggestions on how the substantive provisions of NAFTA Chapter 11 might be interpreted in future cases where investment protection and environmental protection appear to be at odds

Balancing Human Rights and Investor Protection: A New Approach for a Different Legal Order

Recognizing the political need to show that transnational investors should shoulder responsibilities in addition to the international rights to which they are granted access under investment protection treaties, this Article proposes a sort of counterclaim mechanism for use in future treaties. The mechanism would permit individuals who live in countries receiving foreign investment to bring claims against foreign investors for the violation of serious international rules by their agents or employees operating in the host country. Such rules would include safeguards for international human rights that might be violated in the operation of an investment, as has been documented recently before U.S. courts operating under the Alien Tort Claims Act. The Article concludes by providing an appendix with draft text that could be adopted by the negotiators of future bilateral investment treaties

Просвещение как форма популяризации культурно- художественных достижений этнических меньшинств Украины: тенденции 1990-2000-х годов

У статті розглянуто місце і роль просвітництва у популяризації культурно- мистецьких надбань етноменшин. На основі специфічного методологічного інструментарію проаналізовано відповідність популяризації культурно-мистецьких надбань – стратегічними цілями – визнання поліетнічного характеру українського суспільства, розбудові соціокультурного середовища і духовному розвитку етносів. Підкреслено, що в Україні діяла розгалужена мережа музеїв, де діяли спеціальні підрозділи – відділи, центри, експозиції тощо. Проаналізовані напрямки науково – дослідної роботи музеїв та виокремлена її просвітницької складової.В статье рассмотрены место и роль просвещения в популяризации культурно - художественных достижений этнических меньшинств. На основе специфического методологического инструментария проанализированы соответствие популяризации культурно - художественных достижений - стратегическими целями - признание полеэтнического характера украинского общества, развитии социокультурной среды и духовном развитии этносов. Подчеркнуто, что в Украине действовала разветвленная сеть музеев, в которых действовали специальные подразделения - отделы, центры, экспозиции и т.д. Проанализованы направления научно - исследовательской работы музеев с выделением ее просветительской составляющей.On the basis of archival, statistical materials, analytical inputs predecessors considered the place and role of education in promoting cultural - artistic achievements of ethnic minorities. Nonfiction includes the problems of cultural heritage of the Ukrainian people is partly considered problem areas, shapes, nature education. Importance designated problem is primarily due to the need to have a clear understanding of the mechanism solutions independent state problems of interethnic relations. Found that in Ukraine there and operated an extensive network of structures that were engaged in the popularization of cultural - artistic achievements of Ukraine’s ethnic groups: governments, national - cultural societies, cultural institutions. We considered the prospect of continuity and the protection and conservation of heritage. Considerable attention is given to finding areas of education: conducting scientific - practical conferences, advocacy through the museums, the publication of the relevant literature. First in the historiography on the basis of specific methodological tools to analyze the relevant promotion of cultural - artistic achievements - the strategic objectives - recognition of the field of an ethnic nature of Ukrainian society, the development of social and cultural environment and spiritual development of ethnic groups. Particular attention is given to explaining participation in the process of popularizing the achievements of local history museums in Ukraine. Stress that Ukraine had an extensive network of museums that had special units - departments, centers, exposure, etc.. Directions of scientific - research museums and highlighted its educational component. Significant place in the article devoted to subjects found clarification of the regional museum

Limbic Epileptogenesis in a Mouse Model of Fragile X Syndrome

Fragile X syndrome (FXS), caused by silencing of the Fmr1 gene, is the most common form of inherited mental retardation. Epilepsy is reported to occur in 20–25% of individuals with FXS. However, no overall increased excitability has been reported in Fmr1 knockout (KO) mice, except for increased sensitivity to auditory stimulation. Here, we report that kindling increased the expressions of Fmr1 mRNA and protein in the forebrain of wild-type (WT) mice. Kindling development was dramatically accelerated in Fmr1 KO mice, and Fmr1 KO mice also displayed prolonged electrographic seizures during kindling and more severe mossy fiber sprouting after kindling. The accelerated rate of kindling was partially repressed by inhibiting N-methyl-D-aspartic acid receptor (NMDAR) with MK-801 or mGluR5 receptor with 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The rate of kindling development in WT was not effected by MPEP, however, suggesting that FMRP normally suppresses epileptogenic signaling downstream of metabolic glutamate receptors. Our findings reveal that FMRP plays a critical role in suppressing limbic epileptogenesis and predict that the enhanced susceptibility of patients with FXS to epilepsy is a direct consequence of the loss of an important homeostatic factor that mitigates vulnerability to excessive neuronal excitation

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

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