Mechanisms of action of Methylthioadenosine: pathways implicated in neuroprotection in models of Multiple Sclerosis and other neurological diseases

From 5th European Workshop on Immune-Mediated Inflammatory Diseases (Sitges-Barcelona, Spain. 1-3 December 2010)Background Methylthioadenosine (MTA) has anti-oxidant and anti-proliferative properties and was shown to induce cell protection in hepatic cells. We previously demonstrated that exert immunomodulatory and neuroprotective effects in the animal model of Multiple Sclerosis (MS) and other neurological diseases like Parkinson disease, stroke and Epilepsy. Objective To study the mechanisms of action and different pathways implicated in the neuroprotective effect of MTA in neurological diseases. Methods RN22 (Schwnoma cell line) and PC12 (Pheochromocytoma cell line) were used to test the neuroprotective activity of MTA against stress in RN22 and to differentiate neurites in PC12. BV2 cells were used to test the effect of MTA in microglia. Organotypic cerebellum cultures were used to determine MTA effect in demyelination/remyelination. Luminex technology, western blot and ELISA were used in order to study the phosphorylated state of different pathways (AkT/PKB, ERK/MAPK, P38/SAPK or STAT3) and to determine the amount of different cytokines (IL-1β and TNF-α). Ros determination was also done by fluorescence determination. Results In vitro studies revealed that MTA protection against different stresses and its capacity to differentiate neurites implies pathways like ERK/MAPK, P38/SAPK or STAT3. MTA neuroprotective capacity is also related with its ability to reduce ROS production and oxidative stress. MTA was shown to protect against demyelination in cerebellum organotypic cultures treated with LPS or Lysolecithin. Conclusions MTA is neuroprotective in models of MS, Parkinson disease, stroke or Epilepsy. This neuroprotective effect depends on its capacity to protect against demyelination, its anti-oxidant effect and the activation of pathways related with protection against stress and production of neurite differentiation

BSSRDF estimation from single images

We present a novel method to estimate an approximation of the reflectance characteristics of optically thick, homogeneous translucent materials using only a single photograph as input. First, we approximate the diffusion profile as a linear combination of piecewise constant functions, an approach that enables a linear system minimization and maximizes robustness in the presence of suboptimal input data inferred from the image. We then fit to a smoother monotonically decreasing model, ensuring continuity on its first derivative. We show the feasibility of our approach and validate it in controlled environments, comparing well against physical measurements from previous works. Next, we explore the performance of our method in uncontrolled scenarios, where neither lighting nor geometry are known. We show that these can be roughly approximated from the corresponding image by making two simple assumptions: that the object is lit by a distant light source and that it is globally convex, allowing us to capture the visual appearance of the photographed material. Compared with previous works, our technique offers an attractive balance between visual accuracy and ease of use, allowing its use in a wide range of scenarios including off-the-shelf, single images, thus extending the current repertoire of real-world data acquisition techniques

Aging, Transition, and Estimating the Global Burden of Disease

The World Health Organization's Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries.Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08).These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered

Characterization of Structures of Equivalent Tissue With a Pixel Detector

Research using hybrid pixel detectors in medical physics is on the rise. Timepix detectors have arrays of 256 × 256 pixels with a resolution of 55 μm. Here, and by using Timepix counts instead of Hounsfield units, we present a calibration curve of a Timepix detector analog to those used for CT calibration. Experimentation consisted of the characterization of electron density in 10 different kinds of tissue equivalent samples from a CIRS 062M phantom (lung, 3 kinds of bones, fat, breast, muscle, water and air). Radiation of the detector was performed using an orthodontic X-ray machine at 70 KeV and .06 second of tube current with a purpose-built aluminum collimator. Data acquisition was performed at 1 frame per second and taking 3 frames per phantom. We were able to find a curve whose behavior was similar to others already published. This will lead to the verification of the usage of Timepix for identification of different tissues in an organ

Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death

The brains of patients with Alzheimer’s disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1M146LxAPP751sl) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells

A Survey of key methods, traits, parameters, and conditions for measuring texture in cranberry (Vaccinium macrocarpon Ait.)

In the cranberry (Vaccinium macrocarpon Ait.) industry, the textural properties and firmness of the fruit are priority traits for producing processed products, such as sweetened dried cranberry (SDC), which have gained popularity in recent years. However, there is currently no reliable methodology for screening these traits in breeding programs. In this study, we examine the key methodologies, textural traits, parameters, and conditions that are necessary to accurately and efficiently measure the texture of cranberry fruit. Double compression, single compression, puncture, shearing and Kramer shear cell methodologies were successfully implemented in cranberry, resulting in a total of 47 textural features. These features allowed the evaluation of the texture of the cranberry fruit based on key factors such as flesh, structure, and skin. This study also examined factors than can affect the performance of texture measurements, including the optimal sample size, storage time, fruit texture-size correlation, fruit temperature and orientation, optimal speed/strain combinations, and the effect of probe diameter. The results of the study suggests that certain texture traits of the compression and puncture methodologies could potentially be used to test varieties and aid in breeding program

Versatile Graphene-Based Platform for Robust Nanobiohybrid Interfaces

Technologically useful and robust graphene-based interfaces for devices require the introduction of highly selective, stable, and covalently bonded functionalities on the graphene surface, whilst essentially retaining the electronic properties of the pristine layer. This work demonstrates that highly controlled, ultrahigh vacuum covalent chemical functionalization of graphene sheets with a thiol-terminated molecule provides a robust and tunable platform for the development of hybrid nanostructures in different environments. We employ this facile strategy to covalently couple two representative systems of broad interest: metal nanoparticles, via S-metal bonds, and thiol-modified DNA aptamers, via disulfide bridges. Both systems, which have been characterized by a multi-technique approach, remain firmly anchored to the graphene surface even after several washing cycles. Atomic force microscopy images demonstrate that the conjugated aptamer retains the functionality required to recognize a target protein. This methodology opens a new route to the integration of high-quality graphene layers into diverse technological platforms, including plasmonics, optoelectronics, or biosensing. With respect to the latter, the viability of a thiol-functionalized chemical vapor deposition graphene-based solution-gated field-effect transistor array was assessed

Surface plasmon polaritons on narrow-ridged short-pitch metal gratings

Ian R. Hooper and J. Roy Sambles, Physical Review B, Vol. 66, article 205408 (2002). "Copyright © 2002 by the American Physical Society."The reflectivity of short pitch metal gratings consisting of a series of narrow Gaussian ridges in the classical mount has been modeled as a function of frequency and in-plane wave vector (the plane of incidence containing the grating vector) for various ridge heights. Surface plasmon polaritons (SPP’s) are found to be excited even in the zero-order region of the spectrum. These may result in strong absorption of radiation polarized with its electric field in the plane of incidence (transverse magnetic). For zero in-plane wave vector the SPP modes consist of a symmetric charge distribution on either side of the grating ridges, a family of these modes existing with different numbers of field maxima per grating period. Because of the charge symmetry these modes may only be coupled to at angles away from normal incidence where strong resonant absorption may then occur. The dispersion of these SPP modes as a function of the in-plane wave vector is found to be complex arising from the formation of very large band gaps due to the harmonic content of the grating profile, the creation of a pseudo high-energy mode, and through strong interactions between different SPP bands