Matrix Metalloproteinases and Minocycline: Therapeutic Avenues for Fragile X Syndrome

Fragile X syndrome (FXS) is the most common known genetic form of intellectual disability and autism spectrum disorders. FXS patients suffer a broad range of other neurological symptoms, including hyperactivity, disrupted circadian activity cycles, obsessive-compulsive behavior, and childhood seizures. The high incidence and devastating effects of this disease state make finding effective pharmacological treatments imperative. Recently, reports in both mouse and Drosophila FXS disease models have indicated that the tetracycline derivative minocycline may hold great therapeutic promise for FXS patients. Both models strongly suggest that minocycline acts on the FXS disease state via inhibition of matrix metalloproteinases (MMPs), a class of zinc-dependent extracellular proteases important in tissue remodeling and cell-cell signaling. Recent FXS clinical trials indicate that minocycline may be effective in treating human patients. In this paper, we summarize the recent studies in Drosophila and mouse FXS disease models and human FXS patients, which indicate that minocycline may be an effective FXS therapeutic treatment, and discuss the data forming the basis for the proposed minocycline mechanism of action as an MMP inhibitor

Bessel bridges decomposition with varying dimension. Applications to finance

We consider a class of stochastic processes containing the classical and well-studied class of Squared Bessel processes. Our model, however, allows the dimension be a function of the time. We first give some classical results in a larger context where a time-varying drift term can be added. Then in the non-drifted case we extend many results already proven in the case of classical Bessel processes to our context. Our deepest result is a decomposition of the Bridge process associated to this generalized squared Bessel process, much similar to the much celebrated result of J. Pitman and M. Yor. On a more practical point of view, we give a methodology to compute the Laplace transform of additive functionals of our process and the associated bridge. This permits in particular to get directly access to the joint distribution of the value at t of the process and its integral. We finally give some financial applications to illustrate the panel of applications of our results

Connecting discrete and continuous path-dependent options

This paper develops methods for relating the prices of discrete- and continuous-time versions of path-dependent options sensitive to extremal values of the underlying asset, including lookback, barrier, and hindsight options. The relationships take the form of correction terms that can be interpreted as shifting a barrier, a strike, or an extremal price. These correction terms enable us to use closed-form solutions for continuous option prices to approximate their discrete counterparts. We also develop discrete-time discrete-state lattice methods for determining accurate prices of discrete and continuous path-dependent options. In several cases, the lattice methods use correction terms based on the connection between discrete- and continuous-time prices which dramatically improve convergence to the accurate price.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42332/1/780-3-1-55_90030055.pd

Science and Morality: Mind the Gap, Use Happiness as a Safe Bridge! Book review of ‘‘Exploring Happiness: from Aristotle to Brain Science’’ by Sissela Bok, Yale University Press, New Haven and London, 2010

Abstract In 2002 Sissela Bok re-published her book ‘‘Common Values’’, first published in 1995, about her search for a minimal set of values to be respected all over the world. In her view such a set of values is needed to facilitate international communication and cooperation. Values already recognized in every society can be included as a starting point. In her book ‘‘Exploring happiness’’, published in 2010, she explains why she finds happiness unfit to be included. She observes that there are discordant claims about what happiness is. Any particular vision can lead to practical choices that either adhere or violate the values she prefers. In my view subjective happiness should be included, because there are no discordant claims about the meaning of subjective happiness, and subjective happiness is simultaneously attractive as a moral value and as an object of scientific research. Subjective happiness can function as a bridge between science and morality. The only discordant claims are about ‘objective’ happiness, as a wider interpretation of well-being in the context of some specific morality or ideology

Characterization of voltage-gated ionic currents in a peripheral sensory neuron in larval Drosophila.

BACKGROUND: The development, morphology and genetics of sensory neurons have been extensively studied in Drosophila. Sensory neurons in the body wall of larval Drosophila in particular have been the subject of numerous anatomical studies, however, little is known about the intrinsic electrical properties of larval sensory cells. FINDINGS: We performed whole cell patch recordings from an identified peripheral sensory cell, the dorsal bipolar sensory neuron (dbd) and measured voltage-gated ionic currents in 1st instar larvae. Voltage clamp analysis revealed that dbds have a TEA sensitive, non-inactivating IK type potassium current as well as a 4-AP sensitive, inactivating IA type potassium current. dbds also show a voltage-gated calcium current (ICa) and a voltage-gated sodium current (INa). CONCLUSIONS: This work provides a first characterization of voltage-activated ionic currents in an identified body-wall sensory neuron in larval Drosophila. Overall, we establish baseline physiology data for future studies aimed at understanding the ionic and genetic basis of sensory neuron function in fruit flies and other model organisms.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Professionalism, Golf Coaching and a Master of Science Degree: A commentary

As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues

The institutional shaping of management: in the tracks of English individualism

Globalisation raises important questions about the shaping of economic action by cultural factors. This article explores the formation of what is seen by some as a prime influence on the formation of British management: individualism. Drawing on a range of historical sources, it argues for a comparative approach. In this case, the primary comparison drawn is between England and Scotland. The contention is that there is a systemic approach to authority in Scotland that can be contrasted to a personal approach in England. An examination of the careers of a number of Scottish pioneers of management suggests the roots of this systemic approach in practices of church governance. Ultimately this systemic approach was to take a secondary role to the personal approach engendered by institutions like the universities of Oxford and Cambridge, but it found more success in the different institutional context of the USA. The complexities of dealing with historical evidence are stressed, as is the value of taking a comparative approach. In this case this indicates a need to take religious practice as seriously as religious belief as a source of transferable practice. The article suggests that management should not be seen as a simple response to economic imperatives, but as shaped by the social and cultural context from which it emerges