G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Involvement of microbial mats in early fossilization by decay delay and formation of impressions and replicas of vertebrates and invertebrates

Microbial mats have been hypothesized to improve the persistence and the preservation of organic remains during fossilization processes. We test this hypothesis with long-term experiments (up to 5.5 years) using invertebrate and vertebrate corpses.Once placed on mats,the microbial community coats the corpses and forms a three-dimensional sarcophagus composed of microbial cells and exopolymeric substances (EPS). This coverage provides a template for i) moulding superficial features, resulting in negative impressions, and ii) generating replicas.The impressions of fly setulae, fish scales and frog skin verrucae are shaped mainly by small cells in an EPS matrix. Microbes also replicate delicate structures such as the three successive layers that compose a fish eye.The sarcophagus protects the body integrity, allowing the persistence of inner organs such as the ovaries and digestive apparatus in flies,the swim bladder and muscles in fish, and the bone marrow in frog legs.This study brings strong experimental evidence to the idea that mats favour metazoan fossilization by moulding, replicating and delaying decay. Rapid burial has classically been invoked as a mechanism to explain exceptional preservation. However, mats may play a similar role during early fossilization as they can preserve complex features for a long timeThis work, which is part of the research projects CGL2013-42643P and the research grant supporting M. Iniesto were funded by the Spanish Ministry of Economy and Competitiveness. The SEM facility at IMPMC was supported by Region Ile de France grant SESAME 2006 I-07-593/R, INSU-CNRS, INP-CNRS, and University Pierre et Marie Curie, Paris. SEM analyses performed for this study were supported by a grant from the Foundation Simone et Cino Del Duca (PI: K. Benzerara). Some SEM observations were also conducted at SIdI UAM (Madrid). Environmental SEM observations were performed at the MNCN (Madrid

The Cambrian Explosion: The Appearance and Evolution of Calcification in the Geologic Record Including a Case Study of Modern Calcification in a Living Species of Ostracod, Triebelina coronata

Abstract Not Available

Fabrication and performance of a microfluidic traveling-wave electrophoresis system

A microfluidic traveling-wave electrophoresis (TWE) system is reported that uses a locally defined traveling electric field wave within a microfluidic channel to achieve band transport and separation. Low voltages, over a range of-0.5 to +0.5 V, are used to avoid electrolysis and other detrimental redox reactions while the short distance between electrodes, ∼25 μm, provides high electric fields of ∼200 V cm -1. It is expected that the low voltage requirements will simplify the future development of smaller portable devices. The TWE device uses four interdigitated electrode arrays: one interdigitated electrode array pair is on the top of the microchannel and the other interdigitated electrode array pair is on the microchannel bottom. The top and bottom substrates are joined by a PDMS spacer that has a nominal height of 15 μm. A pinched injection scheme is used to define a narrow sample band within an injection cross either electrokinetically or hydrodynamically. Separation of two dyes, fluorescein and FLCA, with baseline resolution is achieved in less than 3 min and separation of two proteins, insulin and casein is demonstrated. Investigation of band broadening with fluorescein reveals that sample band widths equivalent to the diffusion limit can be achieved within the microfluidic channel, yielding highly efficient separations. This low level of band broadening can be achieved with capillary electrophoresis, but is not routinely observed in microchannel electrophoresis. Sample enrichment can be achieved very easily with TWE using a device with converging electric field waves controlled by two sets of independently controlled interdigitated electrodes arrays positioned serially along the microchannel. Sample enrichment of 40-fold is achieved without heterogeneous buffer/solvent systems, sorptive, or permselective materials. While there is much room for improvement in device fabrication, and many capabilities are yet to be demonstrated, it is anticipated that the capabilities and performance demonstrated herein will enable new lab-on-a-chip processes and systems. © The Royal Society of Chemistry 2012

A unifying model for Neoproterozoic-Palaeozoic exceptional fossil preservation through pyritization and carbonaceous compression

© 2014 Macmillan Publishers Limited. All rights reserved. Soft-tissue fossils capture exquisite biological detail and provide our clearest views onto the rise of animals across the Ediacaran-Cambrian transition. The processes contributing to fossilization of soft tissues, however, have long been a subject of debate. The Ediacaran Gaojiashan biota displays soft-tissue preservational styles ranging from pervasive pyritization to carbonaceous compression, and thus provides an excellent opportunity to dissect the relationships between these taphonomic pathways. Here geochemical analyses of the Gaojiashan fossil Conotubus hemiannulatus show that pyrite precipitation was fuelled by the degradation of labile tissues through bacterial sulfate reduction (BSR). Pyritization initiated with nucleation on recalcitrant tube walls, proceeded centripetally, decelerated with exhaustion of labile tissues and possibly continued beneath the BSR zone. We propose that pyritization and kerogenization are regulated principally by placement and duration of the decaying organism in different microbial zones of the sediment column, which hinge on post-burial sedimentation rate and/or microbial zone thickness