In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress,and Inflammation in Protective and Adaptive Responses

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.     

Feasibility of fishmeal replacement by shrimp head silage protein hydrolysate in Nile tilapia (Oreochromis niloticus L) diets

This study provides information on the use of shrimp head silage protein hydrolysate (SPH) as an alternative protein source for tilapia feeding. Six diets (28% protein, 12% lipid) were prepared where fishmeal protein was replaced at levels of 0 (control), 10, 15, 20, 25 and 30% with the hydrolysate. The diets were supplied to Nile tilapia fry (338 mg initial weight) stocked in plastic recirculating 20 l tanks (10 animals per tank), with three replicates per treatment. After an 8 week experimental period, fish fed the diets containing 10 and 15% SPH showed significantly better performance in terms of final body weight, weight gain (%), mean daily weight gain (mg day^?1), specific growth ratio and feed conversion ratio than those fed the control diet (fishmeal as protein source) and higher‐SPH diets. It is concluded that shrimp head hydrolysate is a promising alternative protein source for tilapia feeding, improving growth ratio at dietary inclusion levels as high as 15%. In addition, the diets with added shrimp silage protein were well accepted by the fish, which avidly consumed the feed during the experiment. © 2002 Society of Chemical Industry     

Numerical analysis of two-dimensional steady-state and transient heat transfer in a parallel duct filled with pressurized He II

Analysis on steady-state and transient heat transfer on a flat plate at the middle of a parallel duct immersed in He II was performed for bath temperatures from 1.8 to 2.1 K at 101.3 kPa. Two-dimensional computer code named SUPER-2D developed by the authors based on the two-fluid model and the theory of mutual friction was used. Steady-state critical heat flux (CHF) and the time lag from the application of a step heat input to λ transition, that is called a lifetime, were obtained numerically for various step heat fluxes and for the channel gaps from 2 to 20 mm. Effect of the gap restriction on the CHF and the lifetime were clarified. The solutions were compared with the experimental data for the ducts with the same structures and the corresponding conditions. They agreed well with the experimental data. The heat transport mechanism in the parallel duct was clarified.     

Immunohistochemical demonstration of 3,2''-dimethyl-4-aminobiphenyl DNA adduct formation in various organs of Syrian golden hamsters

We attempted to purify endogenous growth factors of chick embryonal retinal pigment epithelial cells from bovine neural retina. Ammonium sulfate precipitation, gel filtration, and anion exchange column chromatography were used. Though only partially purification, bovine retinal extract had two effects, growth and transformation, on chick embryonal pigment epithelial cells. We think that these purified factors may be novel from the estimation of their molecular weight by gel filtration.     

A light-transmitting two-dimensional photodetector array using a-Sipin photodiodes and poly-Si TFT's integrated on a transparent substrate

A light-transmitting two-dimensional photodetector array (32×32 cells) using amorphous silicon (a-Si) pin photodiodes and polysilicon (poly-Si) thin film transistors (TFT's) integrated on a transparent substrate has been developed for use in a free-space optical switching network. The fabrication and the characteristics of the photodetector array are discussed. With driving circuits and sensing amplifiers, this photodetector array shows a minimum detectable power of -25 dBm and an insertion loss of 0.4 dB for an incident optical beam with a diameter of 550 μm. By monitoring the positions and the states of input optical beams, this photodetector array can be used to control the optical paths in photonic switching systems, such as a 1024-input-port optical concentrator