Arsenic induces metabolome remodeling in mature human adipocytes.

Human lifetime exposure to arsenic through drinking water, food supply or industrial pollution leads to its accumulation in many organs such as liver, kidneys, lungs or pancreas but also adipose tissue. Recently, population-based studies revealed the association between arsenic exposure and the development of metabolic diseases such as obesity and type 2 diabetes. To shed light on the molecular bases of such association, we determined the concentration that inhibited 17% of cell viability and investigated the effects of arsenic acute exposure on adipose-derived human mesenchymal stem cells differentiated in vitro into mature adipocytes and treated with sodium arsenite (NaAsO <sub>2</sub> , 10 nM to 10 µM). Untargeted metabolomics and gene expression analyses revealed a strong dose-dependent inhibition of lipogenesis and lipolysis induction, reducing the cellular ability to store lipids. These dysregulations were emphasized by the inhibition of the cellular response to insulin, as shown by the perturbation of several genes and metabolites involved in the mentioned biological pathways. Our study highlighted the activation of an adaptive oxidative stress response with the strong induction of metallothioneins and increased glutathione levels in response to arsenic accumulation that could exacerbate the decreased insulin sensitivity of the adipocytes. Arsenic exposure strongly affected the expression of arsenic transporters, responsible for arsenic influx and efflux, and induced a pro-inflammatory state in adipocytes by enhancing the expression of the inflammatory interleukin 6 (IL6). Collectively, our data showed that an acute exposure to low levels of arsenic concentrations alters key adipocyte functions, highlighting its contribution to the development of insulin resistance and the pathogenesis of metabolic disorders

Brain connectivity using geodesics in HARDI

International audienceWe develop an algorithm for brain connectivity assessment using geodesics in HARDI (high angular resolution diffusion imaging). We propose to recast the problem of finding fibers bundles and connectivity maps to the calculation of shortest paths on a Riemannian manifold defined from fiber ODFs computed from HARDI measurements. Several experiments on real data show that out method is able to segment fibers bundles that are not easily recovered by other existing methods

Assessment of the reliability of the motor unit size index (MUSIX) in single subject “round-robin” and multi-centre settings

Objective The motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject “round robin” and multi-centre settings. Methods Data were obtained from i). a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and ii). a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intra/inter-rater data were provided by 5 centres, 1 centre provided only intra-rater data. Intra/inter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement. Results In the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle. Conclusions The MUSIX is a reliable neurophysiological biomarker of reinnervation. Significance MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation

New range limits of the sun-tailed monkey, Cercopithecus solatus, in Central Gabon

Cercopithecus solatus is a recently discovered monkey endemic to Gabon, present in parts of the Lopé National Park and the Forêt des Abeilles in the center of the country. It is listed as Vulnerable on the IUCN Red List (2010) due to its restricted extent of occurrence and continuing decline in population caused by high hunting pressure. All known field observations of this species are compiled here. Data collected since 1999 show that C. solatus occurs further to the south, east, and west than was previously known, and that its extent of occurrence almost certainly includes three national parks, rather than one

Impact of flu on hospital admissions during 4 flu seasons in Spain, 2000–2004

<p>Abstract</p> <p>Background</p> <p>Seasonal flu epidemics in the European region cause high numbers of cases and deaths. Flu-associated mortality has been estimated but morbidity studies are necessary to understand the burden of disease in the population. Our objective was to estimate the excess hospital admissions in Spain of diseases associated with influenza during four epidemic influenza periods (2000 – 2004).</p> <p>Methods</p> <p>Hospital discharge registers containing pneumonia, chronic bronchitis, heart failure and flu from all public hospitals in Spain were reviewed for the years 2000 to 2004. Epidemic periods were defined by data from the Sentinel Surveillance System. Excess hospitalisations were calculated as the difference between the average number of weekly hospitalisations/100,000 in epidemic and non-epidemic periods. Flu epidemics were defined for seasons 2001/2002, 2002/2003, 2003/2004.</p> <p>Results</p> <p>A(H3N2) was the dominant circulating serotype in 2001/2002 and 2003/2004. Negligible excess hospitalisations were observed during the 2002/2003 epidemic where A(H1N1) was circulating. During 2000/2001, flu activity remained below threshold levels and therefore no epidemic period was defined. In two epidemic periods studied a delay between the peak of the influenza epidemic and the peak of hospitalisations was observed. During flu epidemics with A(H3N2), excess hospitalisations were higher in men and in persons <5 and >64 years higher than 10 per 100,000. Pneumonia accounted for 70% of all flu associated hospitalisations followed by chronic bronchitis. No excess flu-specific hospitalisations were recorded during all seasons.</p> <p>Conclusion</p> <p>Flu epidemics have an impact on hospital morbidity in Spain. Further studies that include other variables, such as temperature and humidity, are necessary and will deepen our understanding of the role of each factor during flu epidemics and their relation with morbidity.</p

Fusion in diffusion MRI for improved fibre orientation estimation: an application to the 3T and 7T data of the Human Connectome Project

Determining the acquisition parameters in diffusion magnetic resonance imaging (dMRI) is governed by a series of trade-offs. Images of lower resolution have less spatial specificity but higher signal to noise ratio (SNR). At the same time higher angular contrast, important for resolving complex fibre patterns, also yields lower SNR. Considering these trade-offs, the Human Connectome Project (HCP) acquires high quality dMRI data for the same subjects at different field strengths (3T and 7T), which are publically released. Due to differences in the signal behavior and in the underlying scanner hardware, the HCP 3T and 7T data have complementary features in k- and q-space. The 3T dMRI has higher angular contrast and resolution, while the 7T dMRI has higher spatial resolution. Given the availability of these datasets, we explore the idea of fusing them together with the aim of combining their benefits. We extend a previously proposed data-fusion framework and apply it to integrate both datasets from the same subject into a single joint analysis. We use a generative model for performing parametric spherical deconvolution and estimate fibre orientations by simultaneously using data acquired under different protocols. We illustrate unique features from each dataset and how they are retained after fusion. We further show that this allows us to complement benefits and improve brain connectivity analysis compared to analyzing each of the datasets individually

Proteomic Analysis of Chikungunya Virus Infected Microgial Cells

Chikungunya virus (CHIKV) is a recently re-emerged public health problem in many countries bordering the Indian Ocean and elsewhere. Chikungunya fever is a relatively self limiting febrile disease, but the consequences of chikungunya fever can include a long lasting, debilitating arthralgia, and occasional neurological involvement has been reported. Macrophages have been implicated as an important cell target of CHIKV with regards to both their role as an immune mediator, as well evidence pointing to long term viral persistence in these cells. Microglial cells are the resident brain macrophages, and so this study sought to define the proteomic changes in a human microglial cell line (CHME-5) in response to CHIKV infection. GeLC-MS/MS analysis of CHIKV infected and mock infected cells identified some 1455 individual proteins, of which 90 proteins, belonging to diverse cellular pathways, were significantly down regulated at a significance level of p<0.01. Analysis of the protein profile in response to infection did not support a global inhibition of either normal or IRES-mediated translation, but was consistent with the targeting of specific cellular pathways including those regulating innate antiviral mechanisms

Statistical Computing on Non-Linear Spaces for Computational Anatomy

International audienceComputational anatomy is an emerging discipline that aims at analyzing and modeling the individual anatomy of organs and their biological variability across a population. However, understanding and modeling the shape of organs is made difficult by the absence of physical models for comparing different subjects, the complexity of shapes, and the high number of degrees of freedom implied. Moreover, the geometric nature of the anatomical features usually extracted raises the need for statistics on objects like curves, surfaces and deformations that do not belong to standard Euclidean spaces. We explain in this chapter how the Riemannian structure can provide a powerful framework to build generic statistical computing tools. We show that few computational tools derive for each Riemannian metric can be used in practice as the basic atoms to build more complex generic algorithms such as interpolation, filtering and anisotropic diffusion on fields of geometric features. This computational framework is illustrated with the analysis of the shape of the scoliotic spine and the modeling of the brain variability from sulcal lines where the results suggest new anatomical findings

Segmentation of corpus callosum using diffusion tensor imaging: validation in patients with glioblastoma

Abstract Background This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma. Methods Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the proposed segmentation method in such cases. Results Dice coefficients, estimated to compare automatic and manual segmentation results for Witelson subdivisions, ranged from 94% to 98% for control subjects and from 81% to 95% for tumor patients, illustrating closeness of automatic and manual segmentations. Studying the effect of corpus callosum rotation by different Euler angles showed that although segmentation results were more sensitive to azimuth and elevation than skew, rotations caused by brain tumors do not have major effects on the segmentation results. Conclusions The proposed method and similarity measure segment corpus callosum by propagating a hyper-surface inside the structure (resulting in high sensitivity), without penetrating into neighboring fiber bundles (resulting in high specificity)

Brain Structure and Degeneration Staging in Friedreich Ataxia: Magnetic Resonance Imaging Volumetrics from the ENIGMA-Ataxia Working Group

open48siThe method harmonization and multisite data analysis elements of this work were supported by the NIH BD2K (Big Data to Knowledge) program (grant U54 EB020403) and the Australian National Health and Medical Research Council (fellowship 1106533, grant 1184403).Objective: Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA. Methods: A coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole-brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls. Results: The brainstem, dentate nucleus region, and superior and inferior cerebellar peduncles showed the greatest reductions in volume relative to controls (Cohen d&nbsp;= 1.5–2.6). Cerebellar gray matter alterations were most pronounced in lobules I–VI (d&nbsp;= 0.8), whereas cerebral differences occurred most prominently in precentral gyri (d&nbsp;= 0.6) and corticospinal tracts (d&nbsp;= 1.4). Earlier onset age predicted less volume in the motor cerebellum (rmax&nbsp;= 0.35) and peduncles (rmax&nbsp;= 0.36). Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior/inferior cerebellar peduncles (rmax&nbsp;= −0.49); subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation. Cerebral white matter abnormalities, particularly in corticospinal pathways, emerge as intermediate disease features. Cerebellar and cerebral gray matter loss, principally targeting motor and sensory systems, preferentially manifests later in the disease course. Interpretation: FRDA is defined by an evolving spatial profile of neuroanatomical changes beyond primary pathology in the cerebellum and spinal cord, in line with its progressive clinical course. The design, interpretation, and generalization of research studies and clinical trials must consider neuroanatomical staging and associated interindividual variability in brain measures. ANN NEUROL 2021;90:570–583.openHarding I.H.; Chopra S.; Arrigoni F.; Boesch S.; Brunetti A.; Cocozza S.; Corben L.A.; Deistung A.; Delatycki M.; Diciotti S.; Dogan I.; Evangelisti S.; Franca M.C.; Goricke S.L.; Georgiou-Karistianis N.; Gramegna L.L.; Henry P.-G.; Hernandez-Castillo C.R.; Hutter D.; Jahanshad N.; Joers J.M.; Lenglet C.; Lodi R.; Manners D.N.; Martinez A.R.M.; Martinuzzi A.; Marzi C.; Mascalchi M.; Nachbauer W.; Pane C.; Peruzzo D.; Pisharady P.K.; Pontillo G.; Reetz K.; Rezende T.J.R.; Romanzetti S.; Sacca F.; Scherfler C.; Schulz J.B.; Stefani A.; Testa C.; Thomopoulos S.I.; Timmann D.; Tirelli S.; Tonon C.; Vavla M.; Egan G.F.; Thompson P.M.Harding I.H.; Chopra S.; Arrigoni F.; Boesch S.; Brunetti A.; Cocozza S.; Corben L.A.; Deistung A.; Delatycki M.; Diciotti S.; Dogan I.; Evangelisti S.; Franca M.C.; Goricke S.L.; Georgiou-Karistianis N.; Gramegna L.L.; Henry P.-G.; Hernandez-Castillo C.R.; Hutter D.; Jahanshad N.; Joers J.M.; Lenglet C.; Lodi R.; Manners D.N.; Martinez A.R.M.; Martinuzzi A.; Marzi C.; Mascalchi M.; Nachbauer W.; Pane C.; Peruzzo D.; Pisharady P.K.; Pontillo G.; Reetz K.; Rezende T.J.R.; Romanzetti S.; Sacca F.; Scherfler C.; Schulz J.B.; Stefani A.; Testa C.; Thomopoulos S.I.; Timmann D.; Tirelli S.; Tonon C.; Vavla M.; Egan G.F.; Thompson P.M