Dibutyryl Cyclic Amp-Induced Differentiation Of Epidermal Cells In Tissue Culture

Histochemical and biochemical techniques have been used to compare the effects of dibutyryl cyclic AMP on epidermal cells and dermal cells in primary tissue culture. Rhodamin B staining showed only scattered positive cells in nontreated epidermal cells and a few contaminating keratinizing cell foci in both nontreated and treated dermal cell cultures. In contrast, treated epidermal cells stained strongly and had many keratinizing cell foci. A significant increase in histidine, cystine, and arginine incorporation was noted in epidermal cells treated with dibutyryl cyclic AMP as compared to untreated epidermal cells and no dermal cell cultures both treated and untreated. Dibutyryl cyclic AMP had no significant effect on leucine and phenylalanine incorporation. These results seem to suggest that the intracellular level of cyclic AMP not only controls the synthesis of DNA by epidermal cells in culture but also induces the process of differentiation toward keratinization

A 31T split-pair pulsed magnet for single crystal x-ray diffraction at low temperature

We have developed a pulsed magnet system with panoramic access for synchrotron x-ray diffraction in magnetic fields up to 31T and at low temperature down to 1.5 K. The apparatus consists of a split-pair magnet, a liquid nitrogen bath to cool the pulsed coil, and a helium cryostat allowing sample temperatures from 1.5 up to 250 K. Using a 1.15MJ mobile generator, magnetic field pulses of 60 ms length were generated in the magnet, with a rise time of 16.5 ms and a repetition rate of 2 pulses/hour at 31 T. The setup was validated for single crystal diffraction on the ESRF beamline ID06

Pervasive deformation of an oceanic plate and relationship to large >Mw 8 intraplate earthquakes: The northern Wharton Basin, Indian Ocean

Large-magnitude intraplate earthquakes within the ocean basins are not well understood. The Mw 8.6 and Mw 8.2 strike-slip intraplate earthquakes on 11 April 2012, while clearly occurring in the equatorial Indian Ocean diffuse plate boundary zone, are a case in point, with disagreement on the nature of the focal mechanisms and the faults that ruptured. We use bathymetric and seismic reflection data from the rupture area of the earthquakes in the northern Wharton Basin to demonstrate pervasive brittle deformation between the Ninetyeast Ridge and the Sunda subduction zone. In addition to evidence of recent strike-slip deformation along approximately north-south–trending fossil fracture zones, we identify a new type of deformation structure in the Indian Ocean: conjugate Riedel shears limited to the sediment section and oriented oblique to the north-south fracture zones. The Riedel shears developed in the Miocene, at a similar time to the onset of diffuse deformation in the central Indian Ocean. However, left-lateral strike-slip reactivation of existing fracture zones started earlier, in the Paleocene to early Eocene, and compartmentalizes the Wharton Basin. Modeled rupture during the 11 April 2012 intraplate earthquakes is consistent with the location of two reactivated, closely spaced, approximately north-south–trending fracture zones. However, we find no evidence for WNW-ESE–trending faults in the shallow crust, which is at variance with most of the earthquake fault models

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

In-situ evidence for dextral active motion at the Arabia-India plate boundary

International audienceThe Arabia-India plate boundary--also called theOwen fracture zone--is perhaps the least-known boundary among large tectonic plates1-6. Although it was identified early on as an example of a transform fault converting the divergent motion along the Carlsberg Ridge to convergent motion in the Himalayas7, its structure and rate of motion remains poorly constrained. Here we present the first direct evidence for active dextral strike-slip motion along this fault, based on seafloor multibeam mapping of the Arabia-India-Somalia triple junction in the northwest Indian Ocean. There is evidence for 12km of apparent strike-slip motion along the mapped segment of the Owen fracture zone, which is terminated to the south by a 50-km-wide pull-apart basin bounded by active faults. By evaluating these new constraints within the context of geodetic models of global plate motions, we determine a robust angular velocity for the Arabian plate relative to the Indian plate that predicts 2-4mmyr−1 dextral motion along the Owen fracture zone. This transformfault was probably initiated around 8 million years ago in response to a regional reorganization of plate velocities and directions8-11, which induced a change in configuration of the triple junction. Infrequent earthquakes of magnitude 7 and greater may occur along the Arabia-India plate boundary, unless deformation is in the formof aseismic creep

An online spike detection and spike classification algorithm capable of instantaneous resolution of overlapping spikes

For the analysis of neuronal cooperativity, simultaneously recorded extracellular signals from neighboring neurons need to be sorted reliably by a spike sorting method. Many algorithms have been developed to this end, however, to date, none of them manages to fulfill a set of demanding requirements. In particular, it is desirable to have an algorithm that operates online, detects and classifies overlapping spikes in real time, and that adapts to non-stationary data. Here, we present a combined spike detection and classification algorithm, which explicitly addresses these issues. Our approach makes use of linear filters to find a new representation of the data and to optimally enhance the signal-to-noise ratio. We introduce a method called “Deconfusion” which de-correlates the filter outputs and provides source separation. Finally, a set of well-defined thresholds is applied and leads to simultaneous spike detection and spike classification. By incorporating a direct feedback, the algorithm adapts to non-stationary data and is, therefore, well suited for acute recordings. We evaluate our method on simulated and experimental data, including simultaneous intra/extra-cellular recordings made in slices of a rat cortex and recordings from the prefrontal cortex of awake behaving macaques. We compare the results to existing spike detection as well as spike sorting methods. We conclude that our algorithm meets all of the mentioned requirements and outperforms other methods under realistic signal-to-noise ratios and in the presence of overlapping spikes

Effects of dietary carotenoids on mouse lung genomic profiles and their modulatory effects on short-term cigarette smoke exposures

Male C57BL/6 mice were fed diets supplemented with either β-carotene (BC) or lycopene (LY) that were formulated for human consumption. Four weeks of dietary supplementations results in plasma and lung carotenoid (CAR) concentrations that approximated the levels detected in humans. Bioactivity of the CARs was determined by assaying their effects on the activity of the lung transcriptome (~8,500 mRNAs). Both CARs activated the cytochrome P450 1A1 gene but only BC induced the retinol dehydrogenase gene. The contrasting effects of the two CARs on the lung transcriptome were further uncovered in mice exposed to cigarette smoke (CS) for 3 days; only LY activated ~50 genes detected in the lungs of CS-exposed mice. These genes encoded inflammatory-immune proteins. Our data suggest that mice offer a viable in vivo model for studying bioactivities of dietary CARs and their modulatory effects on lung genomic expression in both health and after exposure to CS toxicants

Novel Retinoic Acid Receptor Alpha Agonists for Treatment of Kidney Disease

Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN