ACTH: Differential effects on avoidance and discrimination

Zusammenfassung Andauernde ACTH-Behandlung beeinflusst sowohl Vermeidungs- als auch Fehlerkomponenten im Zweiwahl-Y-Labyrinthtest. Die Einwirkungen waren von der Intensität des Elektroschocks wie auch von der Reaktionsfähigkeit der Tiere abhängig.

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This work was supported by Medical Research Council Grant No. MA 1746. Some of the work was done while the first author held a pre-doctoral terminal year grant from the USPHS and while the second author held a Research Career Award from the Canadian Association for Retarded Children. We are indebted toSusanna Kertesz for help in running the subjects in these studies. Requests for reprints should be sent to Dr.J. A. Corson, Allan Memorial Institute, 1033 Pine Avenue West, Montreal 112 (P.Q., Canada).     

Self and non-self discrimination is needed for the existence rather than deletion of autoimmunity: the role of regulatory T cells in protective autoimmunity

Autoimmune T cells have been viewed for decades as an outcome of immune system malfunction, and specifically as a failure to distinguish between components of self and non-self. The need for discrimination between self and non-self as a way to avoid autoimmunity has been repeatedly debated over the years. Recent studies suggest that autoimmunity, at least in the nervous system, is the bodys defense mechanism against deviations from the normal. The ability to harness neuroprotective autoimmunity upon need is evidently allowed by naturally occurring CD4+CD25+ regulatory T cells, which are themselves controlled by brain-derived compounds. These findings challenge widely accepted concepts of the need for discrimination between self and non-self, as they suggest that while such discrimination is indeed required, it is needed not as a way to avoid an anti-self response but to ensure its proper regulation. Whereas a response to non-self can be self-limited by a decreased presence of the relevant antigen, the response to self needs a mechanism for strict control, such as that provided by the naturally occurring regulatory T cells.Received 8 June 2004; accepted 6 July 2004     

Modeling Realized Volatility Dynamics with a Genetic Algorithm

The heterogeneous autoregressive model of realized volatility (HAR‐RV) is inspired by the heterogeneous market hypothesis and characterizes realized volatility dynamics through a linear function of lagged daily, weekly and monthly realized volatilities with a (1, 5, 22) lag structure. Considering that different markets can have different heterogeneous structures and a market's heterogeneous structure can vary over time, we build an adaptive heterogeneous autoregressive model of realized volatility (AHAR‐RV), whose lag structure is optimized with a genetic algorithm. Using nine common loss functions and the superior predictive ability test, we find that our AHAR‐RV model and its extensions provide significantly better out‐of‐sample volatility forecasts for the CSI 300 index than the corresponding HAR models. Furthermore, the AHAR‐RV model significantly outperforms all the other models under most loss functions. Besides, we confirm that Chinese stock markets' heterogeneous structure varies over time and the (1, 5, 22) lag structure is not the optimal choice. Copyright © 2016 John Wiley & Sons, Ltd.     

Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis

Pelizaeus-Merzbacher disease (PMD) and the allelic spastic paraplegia type 2 (SPG2) arise from mutations in the X-linked gene encoding myelin proteolipid protein (PLP). Analysis of mutations affecting PLP, the major protein in central nervous system myelin, has revealed previously unsuspected roles for myelinating glia in maintaining the integrity of the nervous system. The disease spectrum for PMD and SPG2 is extraordinarily broad and can be best understood by accounting not only for the wide range of mutations that can occur but also for the effects of PLP1 mutations on both cell autonomous and non-cell autonomous processes in myelinating cells. Appreciating the wide range of genetic and cellular effects of PLP1 mutations is important for patient and family counseling, understanding disease pathogenesis, and, ultimately, for developing future disease-specific therapies. Received 24 April 2006; received after revision 3 July 2006; accepted 9 October 2006     

Genetic knockouts in mice: An update

Gene disruption technology in mammals, by homologous recombination in embryonic stem cells, is a powerful method to manipulate the mouse germ line. In the past decade it has produced a wealth of knowledge concerning neuronal development, neurodegenerative disorders and the roles of oncogenes, Hox genes and growth factors during development. A surprising variety of genes, however, have given unexpected and disappointing results. A gene/function redundancy theory proposed by many investigators to explain the unexpected results has been supported in certain cases by the generation of double knockout mice. Modification of the basic technology now allows the investigators to carry out a variety of manipulations including conditional or tissue-specific knockout. This may provide a better opportunity in the future for the gene therapy approach to correct the genetic disorder.     

Understanding is not simulating: a reply to Gibbs and Perlman

In this response, I do four things. First, I defend the claim that the action compatibility effect does not distinguish between embodied and traditional accounts of language comprehension. Second, I present neuroimaging and neuropsychological results that seem to support the traditional account. Third, I argue that metaphorical language poses no special challenge to the arguments I gave against embodied theories of comprehension. Fourth, I lay out the architecture of language I advocate and suggest the sorts of data that would decide between traditional and embodied accounts.     

What is a lefthander?

Summary Attributes of lefthanders and lefthandedness were examined and 3 etiologies of lefthandedness were proposed.     

Language understanding is grounded in experiential simulations: a response to Weiskopf

Several disciplines within the cognitive sciences have advanced the idea that people comprehend the actions of others, including the linguistic meanings they communicate, through embodied simulations where they imaginatively recreate the actions they observe or hear about. This claim has important consequences for theories of mind and meaning, such as that people’s use and interpretation of language emerges as a kind of bodily activity that is an essential part of ordinary cognition. Daniel Weiskopf presents several arguments against the idea that experiential simulations play a major role in immediate language use and meaning. We offer several rebuttals to Weiskopf, in which we critique his interpretation of simulation theory, present additional psycholinguistic evidence supportive of the simulation perspective, and suggest that a more traditional theory of linguistic meaning and processing has little psychological and empirical validity.     

Genetic polymorphism: from electrophoresis to DNA sequences

Summary Recent studies indicate that the amount of protein variation undetected by electrophoresis may be reasonably small. Nevertheless, at the protein level, a typical sexually-reproducing organism may be heterozygous at 20 or more percent of the gene loci. Although the evidence is limited, it appears that at the level of the DNA nucleotide sequence every individual is heterozygous at every locus — if introns as well as exons are taken into account. The evidence available does not support the hypothesis that, at least at the protein level, the variation is adaptively neutral.This work was supported by grant GM 22221 from the PHS (USA).     

Ceramide function in the brain: when a slight tilt is enough

Ceramide, the precursor of all complex sphingolipids, is a potent signaling molecule that mediates key events of cellular pathophysiology. In the nervous system, the sphingolipid metabolism has an important impact. Neurons are polarized cells and their normal functions, such as neuronal connectivity and synaptic transmission, rely on selective trafficking of molecules across plasma membrane. Sphingolipids are abundant on neural cellular membranes and represent potent regulators of brain homeostasis. Ceramide intracellular levels are fine-tuned and alteration of the sphingolipid–ceramide profile contributes to the development of age-related, neurological and neuroinflammatory diseases. The purpose of this review is to guide the reader towards a better understanding of the sphingolipid–ceramide pathway system. First, ceramide biology is presented including structure, physical properties and metabolism. Second, we describe the function of ceramide as a lipid second messenger in cell physiology. Finally, we highlight the relevance of sphingolipids and ceramide in the progression of different neurodegenerative diseases.     

CD100 is a leukocyte semaphorin

CD100 was originally described as an activation molecule on the surface of human T lymphocytes. Its triggering through distinct epitopes leads to different signals of costimulation with phorbol myristate acetate (PMA) or with CD3 and CD2. Interestingly, CD100 was shown to associate with different partner molecules in T cells. First, CD100 can associate with CD45, a key molecule with protein tyrosine phosphatase activity involved in T-cell transduction this association is physical and has functional consequences for both partners. Second, CD100 interacts in its cytoplasmic domain with a Ser/Thr kinase for which it represents a preferential substrate. Recently, CD100 was identified as a member of the semaphorin gene family. This family comprises approximately 20 structurally related proteins. The first semaphorins were identified in the developing nervous system. Function has been shown for only some of them and involves repulsion during growth cone guidance. Since CD100 was the first semaphorin identified in the immune system, this raises the possibility of the involvement of members of the semaphorin family in other physiological phenomena outside the nervous system. Received 1 March 1998; received after revision 8 June 1998; accepted 8 June 1998     

Piroxicam-induced analgesia: Evidence for a central component which is not opioid mediated

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p<0.05) and 50% (p<0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.