Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1

Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. Neurologic manifestations identified to date relate to enhanced atherosclerosis and cerebrovascular disease. Based on a clinical survey, we determined that half of Schimke immuno-osseous dysplasia patients have a small head circumference, and 15% have social, language, motor, or cognitive abnormalities. Postmortem examination of 2 Schimke immuno-osseous dysplasia patients showed low brain weights and subtle brain histologic abnormalities suggestive of perturbed neuron-glial migration such as heterotopia, irregular cortical thickness, incomplete gyral formation, and poor definition of cortical layers. We found that SMARCAL1 is highly expressed in the developing and adult mouse and human brain, including neural precursors and neuronal lineage cells. These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation

In-situ early age hydration of cement-based materials by synchrotron X-ray powder diffraction

Cement based binders are building materials of worldwide importance. Since these samples are very complex, the knowledge/control of their mineralogical composition are essential to design and predict materials with specific/improved performance. Rietveld quantitative phase analysis (RQPA) allows the quantification of crystalline phases and, when combined with specific methodologies, as the addition of an internal standard or the external standard approach (G-factor), amorphous and non-crystalline phases can also be quantified. However, to carry out a proper RQPA in hydrated cementitious-materials, a good powder diffraction pattern is necessary. In this work, synchrotron X-ray powder diffraction (SXRPD) has been used, allowing in-situ measurements during the early-age hydration process. This work deals with the early hydration study of cement-based materials. The studied samples were: a laboratory-prepared belite calcium sulphoaluminate (BCSAF) clinker (non-active) mixed with 10wt% gypsum, labelled G10B0; two active laboratory-prepared BCSAF clinkers (activated with 2wt% borax), one mixed with 10wt% gypsum and the other one with 10wt% monoclinic-bassanite, hereafter named G10B2 and B10B2, respectively; and an environmentally-friendly cement sample from Henkel, composed of bassanite mixed with 15wt% Portland cement and 10wt% Metakaolin, labelled H1. Anhydrous G10B0 contains beta-belite and orthorhombic-ye'elimite as main phases, while alpha'H-belite and pseudo-cubic-ye'elimite are stabilized in G10B2 and B10B2, with the corresponding sulphate source. Anhydrous H1 contains monoclinic and hexagonal bassanite and alite as main phases. Ye'elimite, in the non-active BCSAF cement pastes, dissolves at a higher pace than in the active one (degree of reaction is α~25% and α~10% at 1 h, respectively) (both prepared with gypsum), with the corresponding differences in ettringite crystallisation (degree of precipitation is α~30% and α~5%, respectively). Moreover, the type of sulphate source has important consequences on the hydration of the active BCSAF cement pastes. Bassanite is quickly dissolved and it precipitates as gypsum within the first hour of hydration (in B10B2). At that time, ettringite starts to crystallize, and after 12 hours is almost fully crystallized, similar to G10B2. In H1, bassanite transforms into gypsum within the first hour, being the principal hydration product; ettringite starts to be formed just after few hydration minutes. These results are crucial in the understanding and development of improved cement materials.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Creation and validation of a new tool for the monitoring efficacy of neurogenic bowel dysfunction treatment on response: the MENTOR tool

STUDY DESIGN: Prospective observational study. OBJECTIVES: A tool to help decision-making tool for Neurogenic Bowel Dysfunction (NBD) in individuals with SCI is needed. We present a project to create and validate a new tool, the Monitoring Efficacy of NBD Treatment On Response (MENTOR), and to determine its level of concordance with decisions made by experienced clinicians in the field. SETTING: UK, Denmark, USA, Italy, The Netherlands, Germany. METHODS: The first phase was creation of the tool through a modified Delphi process. The second phase was the validation, wherein individuals with spinal cord injury with NBD were asked to complete the MENTOR tool immediately prior to clinic consultation. From the responses to the questionnaire of the tool, each participant was allocated into one of three categories reflecting the possible therapeutic recommendations ("recommend change", "further discussion" and "monitoring"). An expert clinician then assessed the participant, blinded to MENTOR results, and made an independent treatment decision. RESULTS: A total of 248 MENTOR forms were completed. Strong agreement was found when the MENTOR tool recommended monitoring (92%) or treatment change (83%); the lowest concordance when the decision was for the "further discussion" option (59%). Patient acceptability was reported by 97% of individuals. CONCLUSIONS: MENTOR is an easy to use tool to monitor the treatment of NBD and determinate progression through the clinical pathway. This validation study shows good correspondence between expert clinician opinion and MENTOR result. The tool has potential to be used in other patient groups, following further studies

An AFM Approach of RBC Micro and Nanoscale Topographic Features During Storage

Blood gamma irradiation is the only available method to prevent transfusion-associated graft versus host disease (TA-GVHD). However, when blood is irradiated, determine blood shelf time is crucial. Non-irradiated blood has a self-time from 21 to 35 days when is preserved with an anticoagulated solution and stored at 4°C. During their storage, red blood cells (RBC) undergo a series of biochemical, biomechanical and molecular changes involving what is known as storage lesion (SL). SL include loss of structural integrity of RBC, a decrease of 2,3-diphosphatidylglyceric acid levels, and an increase of both ion potassium concentration and hemoglobin (Hb). On the other hand, Atomic force Microscopy (AFM) represents a versatile tool for a nano-scale high-resolution topographic analysis in biological systems. In order to evaluate SL in irradiated and non-irradiated blood, RBC topography and morphometric parameters were obtained from an AFM XE-BIO system. Cell viability was followed using flow cytometry. Our results showed that early markers as nanoscale roughness, allow us to evaluate blood quality since another perspective

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Influence of fly ash blending on hydration and physical behavior of Belite-Alite-Ye'elimite cements

A cement powder, composed of belite, alite and ye’elimite, was blended with 0, 15 and 30 wt% of fly ash and the resulting lended cements were further characterized. During hydration, the presence of fly ash caused the partial inhibition of both AFt degradation and belite reactivity, even after 180 days. The compressive strength of the corresponding mortars increased by increasing the fly ash content (68, 73 and 82 MPa for mortars with 0, 15 and 30 wt% of fly ash, respectively, at 180 curing days), mainly due to the diminishing porosity and pore size values. Although pozzolanic reaction has not been directly proved there are indirect evidences.This work is part of the Ph.D. of D. Londono-Zuluaga funded by Beca Colciencias 646—Doctorado en el exterior and Enlaza Mundos 2013 program grant. Cement and Building materials group (CEMATCO) from National University of Colombia is acknowledged for providing the calorimetric measurements. Funding from Spanish MINECO BIA2017-82391-R and I3 (IEDI-2016-0079) grants, co-funded by FEDER, are acknowledged

Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss: Links With Metabolic and Low-Grade Inflammation Markers

International audienceOBJECTIVE Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure. RESEARCH DESIGN AND METHODS Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB. RESULTS Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at MO and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lacto-bacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at MO and throughout the follow-up after surgery independently of changes in food intake. CONCLUSIONS These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake. Diabetes 59:3049-3057, 201