Insulin-like growth factor 1 signaling in motor neuron and polyglutamine diseases: From molecular pathogenesis to therapeutic perspectives

The pleiotropic peptide insulin-like growth factor 1 (IGF-I) regulates human body homeostasis and cell growth. IGF-I activates two major signaling pathways, namely phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB/Akt) and Ras/extracellular signal-regulated kinase (ERK), which contribute to brain development, metabolism and function as well as to neuronal maintenance and survival. In this review, we discuss the general and tissue-specific effects of the IGF-I pathways. In addition, we present a comprehensive overview examining the role of IGF-I in neurodegenerative diseases, such as spinal and muscular atrophy, amyotrophic lateral sclerosis, and polyglutamine diseases. In each disease, we analyze the disturbances of the IGF-I pathway, the modification of the disease protein by IGF-I signaling, and the therapeutic strategies based on the use of IGF-I developed to date. Lastly, we highlight present and future considerations in the use of IGF-I for the treatment of these disorders

Comparative clinical profile of patients of Benign Prostatic Hyperplasia (BPH) with and without Metabolic Syndrome: a prospective observational study

Background: Benign Prostatic Hyperplasia (BPH) is one of common disorder in men of old age group. The pathogenesis of BPH is multi-factorial and still not been fully elucidated. There are numerous reports which suggest possible link between several metabolic alterations known as Metabolic Syndrome. In the present study, the aim was to establish relation between Benign Prostatic Hyperplasia and Metabolic Syndrome and to find out effects of therapeutic intervention of Metabolic Syndrome on prostatic parameters.Methods: 93 patients of Benign Prostatic Hyperplasia enrolled who met qualifying criteria for inclusion in study and divided into three groups on the basis of Metabolic Syndrome and its treatment administered. Administration of alpha adrenergic blocker was common to all patients of all groups. Metabolic parameters including Fasting blood glucose, High-density lipoprotein (HDL), Triglycerides (TGs), waist circumference and prostatic parameters that is prostate volume, prostate specific antigen (PSA), uroflometry, International prostate symptom score (IPSS) were assessed at baseline, after 3 and 6 months follow-up. Further appropriate statistical tests were applied for comparison of parameters among groups.Results: Patients receiving no treatment for Metabolic Syndrome were having most deranged prostatic parameters as compared to patients without Metabolic Syndrome or patients with Metabolic Syndrome receiving treatment for same. Further patients receiving treatment for Metabolic Syndrome and alpha adrenergic blocker were having better clinical profile than patients of alpha adrenergic blocker alone.Conclusions: These findings show probable link between Metabolic Syndrome and worse prostatic profile. Metabolic Syndrome must be looked for and treated in patients of Benign Prostatic Hyperplasia. Metabolic derangements must not be overlooked and must be treated accordingly

The spectral form factor is not self-averaging

The spectral form factor, k(t), is the Fourier transform of the two level correlation function C(x), which is the averaged probability for finding two energy levels spaced x mean level spacings apart. The average is over a piece of the spectrum of width W in the neighborhood of energy E0. An additional ensemble average is traditionally carried out, as in random matrix theory. Recently a theoretical calculation of k(t) for a single system, with an energy average only, found interesting nonuniversal semiclassical effects at times t approximately unity in units of {Planck's constant) /(mean level spacing). This is of great interest if k(t) is self-averaging, i.e, if the properties of a typical member of the ensemble are the same as the ensemble average properties. We here argue that this is not always the case, and that for many important systems an ensemble average is essential to see detailed properties of k(t). In other systems, notably the Riemann zeta function, it is likely possible to see the properties by an analysis of the spectrum.Comment: 4 pages, RevTex, no figures, submitted to Phys. Rev. Lett., permanent e-mail address, [email protected]

The initial stellar mass function from random sampling in hierarchical clouds II: statistical fluctuations and a mass dependence for starbirth positions and times

Observed variations in the slope of the initial stellar mass function are shown to be consistent with a model in which the protostellar gas is randomly sampled from hierarchical clouds at a rate proportional to the square root of the local density. RMS variations in the IMF slope around the Salpeter value are +/- 0.4 when only 100 stars are observed, and +/- 0.1 when 1000 stars are observed. The hierarchical-sampling model also reproduces the tendency for massive stars to form closer to the center of a cloud, at a time somewhat later than the formation time of the lower mass stars. The assumed density dependence for the star formation rate is shown to be appropriate for turbulence compression, magnetic diffusion, gravitational collapse, and clump or wavepacket coalescence. The low mass flattening in the IMF comes from the inability of gas to form stars below the thermal Jeans mass at typical temperatures and pressures. Consideration of heating and cooling processes indicate why the thermal Jeans mass should be nearly constant in normal environments, and why it might increase in some starburst regions. The steep IMF in the extreme field is not explained by the model, but other origins are suggested.Comment: 21 pages, 8 figures, scheduled for ApJ vol. 515, April 10, 199

Magic Numbers of Silicon Clusters

A structural model for intermediate sized silicon clusters is proposed that is able to generate unique structures without any dangling bonds. This structural model consists of bulk-like core of five atoms surrounded by fullerene-like surface. Reconstruction of the ideal fullerene geometry results in the formation of crown atoms surrounded by $\pi$-bonded dimer pairs. This model yields unique structures for \Si{33}, \Si{39}, and \Si{45} clusters without any dangling bonds and hence explains why these clusters are least reactive towards chemisorption of ammonia, methanol, ethylene, and water. This model is also consistent with the experimental finding that silicon clusters undergo a transition from prolate to spherical shapes at \Si{27}. Finally, reagent specific chemisorption reactivities observed experimentally is explained based on the electronic structures of the reagents.Comment: 4 pages + 3 figures (postscript files after \end{document}

Early prediction of onset of South West monsoon from ERS-1 scatterometer winds

Detailed analysis of the surface winds over the Indian Ocean derived from ERS-1 scatterometer data during the years 1993 and 1994 has been used to understand and unambiguously identify the onset phase of south-west monsoon. Five day (pentad) averaged wind vectors for the period April to June during both years have been examined to study the exact reversal of wind direction as well as the increase in wind speed over the Arabian Sea in relation to the onset of monsoon over the Indian west coast (Kerala). The related upper level humidity available from other satellites has also been analysed. The results of our analysis clearly show a consistent dramatic reversal in wind direction over the western Arabian Sea three weeks in advance of the onset of monsoon. The wind speed shows a large increase coinciding with the onset of monsoon. These findings together show the dominant role of sea surface winds in establishing the monsoon circulation. The study confirms that the cross equatorial current phenomenon becomes more important after the onset of monsoon