Modulation of Molecular Chaperones in Huntington's Disease and Other Polyglutamine Disorders

Polyglutamine expansion mutations in specific proteins underlie the pathogenesis of a group of progressive neurodegenerative disorders, including Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and several spinocerebellar ataxias. The different mutant proteins share ubiquitous expression and abnormal proteostasis, with misfolding and aggregation, but nevertheless evoke distinct patterns of neurodegeneration. This highlights the relevance of the full protein context where the polyglutamine expansion occurs and suggests different interactions with the cellular proteostasis machinery. Molecular chaperones are key elements of the proteostasis machinery and therapeutic targets for neurodegeneration. Here, we provide a focused review on Hsp90, Hsp70, and their co-chaperones, and how their genetic or pharmacological modulation affects the proteostasis and disease phenotypes in cellular and animal models of polyglutamine disorders. The emerging picture is that, in principle, Hsp70 modulation may be more amenable for long-term treatment by promoting a more selective clearance of mutant proteins than Hsp90 modulation, which may further decrease the necessary wild-type counterparts. It seems, nevertheless, unlikely that a single Hsp70 modulator will benefit all polyglutamine diseases. Indeed, available data, together with insights from effects on tau and alpha-synuclein in models of Alzheimer's and Parkinson's diseases, indicates that Hsp70 modulators may lead to different effects on the proteostasis of different mutant and wild-type client proteins. Future studies should include the further development of isoform selective inhibitors, namely to avoid off-target effects on Hsp in the mitochondria, and their characterization in distinct polyglutamine disease models to account for client protein-specific differences

Furanylfentanyl. ANNEX 1. Technical report on N-phenyl-N- [1-(2-phenylethyl)piperidin-4-yl]furan- 2-carboxamide (furanylfentanyl).

This publication presents the data and findings of the risk assessment on furanylfentanyl (N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide), carried out by the extended Scientific Committee of the EMCDDA on 23 May 2017. The Risk Assessment Report, which was submitted to the European Commission and the Council of the European Union on 23 May 2017, examines the health and social risks of the drug, information on international trafficking and the involvement of organised crime, as well as a consideration of the potential implications of subjecting the drug to control measures. Furanylfentanyl is the fourteenth new psychoactive substance to be risk assessed under the terms of Council Decision 2005/387/JHA. On the basis of the Risk Assessment Report - and on the initiative of the European Commission - on 15 November 2017, the Council decided that furanylfentanyl should be subject to control measures across the Member States. This decision was adopted in the final stage of the three-step process - early warning, risk assessment and control of new psychoactive substances - established by the Council Decision 2005/387/JHA. This legal framework allows the EU institutions and Member States to act on all new and potentially threatening narcotic and psychotropic drugs which appear on the European drug scene, with the EMCDDA and Europol, in collaboration with their respective networks playing a central role in the early detection of such substances as well as the harms caused by their use - information that underpins risk assessment, and, ultimately, decision-making

Technical report on N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyrylfentanyl; 4F-iBF). Annex 1 to the Risk Assessment Report on N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyrylfentanyl; 4F-iBF)

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances

Current Approaches to the Treatment of Early Hepatocellular Carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139902/1/onco0034.pd

Technical report on N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]oxolane-2-carboxamide (tetrahydrofuranylfentanyl; THF-F). Annex 1 to the Risk Assessment Report on N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]oxolane-2- carboxamide (tetrahydrofuranylfentanyl).

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances

Restrictive ID policies: implications for health equity

We wish to thank Synod Community Services for their critical work to develop, support, and implement a local government-issued ID in Washtenaw County, MI. We also thank Yousef Rabhi of the Michigan House of Representatives and Janelle Fa'aola of the Washtenaw ID Task Force, Lawrence Kestenbaum of the Washtenaw County Clerk's Office, Sherriff Jerry Clayton of the Washtenaw County Sherriff's Office, and the Washtenaw ID Task Force for their tireless commitment to developing and supporting the successful implementation of the Washtenaw ID. Additionally, we thank Vicenta Vargas and Skye Hillier for their contributions to the Washtenaw ID evaluation. We thank the Curtis Center for Research and Evaluation at the University of Michigan School of Social Work, the National Center for Institutional Diversity at the University of Michigan, and the University of California-Irvine Department of Chicano/Latino Studies and Program in Public Health for their support of the Washtenaw ID community-academic research partnership. Finally, we thank the reviewers for their helpful comments on earlier drafts of this manuscript. (Curtis Center for Research and Evaluation at the University of Michigan School of Social Work; National Center for Institutional Diversity at the University of Michigan; University of California-Irvine Department of Chicano/Latino Studies; Program in Public Health)https://link.springer.com/content/pdf/10.1007/s10903-017-0579-3.pdfPublished versio

Technical report on N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3- carboxamide (ADB-CHMINACA). Annex 1 to the Risk Assessment Report on N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1- (cyclohexylmethyl)-1H-indazole-3-carboxamide (ADB-CHMINACA).

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances

Technical report on 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide (CUMYL-4CN-BINACA). Annex 1 to the Risk Assessment Report on 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3- carboxamide (CUMYL-4CN-BINACA).

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances

Evidence from neurolinguistic methodologies: can it actually inform linguistic/ language acquisition theories and translate to evidence-based applications?

This special issue is a testament to the recent burgeoning interest by theoretical linguists, language acquisitionists and teaching practitioners in the neuroscience of language. It offers a highly valuable, state-of-the-art overview of the neurophysiological methods that are currently being applied to questions in the field of second language (L2) acquisition, teaching and processing. Research in the area of neurolinguistics has developed dramatically in the past twenty years, providing a wealth of exciting findings, many of which are discussed in the papers in this volume. The goal of this commentary is twofold. The first is to critically assess the current state of neurolinguistic data from the point of view of language acquisition and processing—informed by the papers that comprise this special issue and the literature as a whole—pondering how the neuroscience of language/processing might inform us with respect to linguistic and language acquisition theories. The second goal is to offer some links from implications of exploring the first goal towards informing language teachers and the creation of linguistically and neurolinguistically-informed evidence-based pedagogies for non-native language teaching

Manipulating the Optical Properties of Carbon Dots by Fine-Tuning their Structural Features

Contains fulltext : 207736.pdf (publisher's version ) (Closed access)11 p