37 research outputs found

    X-ray lensless microscopy from undersampled diffraction intensities

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    International audienceX-ray coherent diffraction imaging including ptychography provides the nanoscale resolved three-dimensional description of matter. The combination of these approaches to the Bragg geometry case arouses a strong interest for its capability to provide information about strain state in crystals. Among the existing approaches, ptychography is particularly appealing because it allows the investigation of extended or weakly scattering samples. Coherent diffraction imaging approaches, based on redundancy in the collected diffraction intensity data set, are highly time consuming and rely on state-of-the-art mechanical setups, both being strong limitations for a general application. We show here that these can be overcome by regularization-based inversion algorithms introducing a priori structural knowledge. This method, which can be generalized to other wavelengths or beam sources, opens new possibilities for the imaging of radiation-sensitive specimens or very large samples

    Apolipoprotein D synthesis progressively increases in frontal cortex during human lifespan

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    Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. In the other way, apo D expression has been correlated, in some brain regions, with normal aging and neurodegenerative diseases. To elucidate the regional and cellular expression of apo D in normal human brain during aging, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot blot techniques, for protein and mRNA, as well as immunohistochemistry and hybridohistochemistry methods were used. A positive correlation for apo D expression with aging was found; furthermore, mRNA levels, as well as the protein ones, were higher in the white than in the grey matter. Immunohistochemistry and non-isotopic HIS showed that apo D is synthesized in both neurons and glial cells. Apo D expression is notorious in oligodendrocytes but with aging the number of neurons that synthesize apo D is increased. Our results indicate that apo D could play a fundamental role in central nervous system aging and in the reduction of products derivated from lipid peroxidation. The increment in the expression of apo D with aging can be included in a global mechanism of cellular protection to prevent the deleterious effects caused by aging

    Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

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    The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

    Human plasma protein N-glycosylation

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    Soins palliatifs

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    Differential expression of LMO4 protein in Alzheimer's disease.

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    The molecular bases of late-onset and sporadic Alzheimer's disease (AD) still have to be unraveled. Among putative candidates for molecular variations in AD, we propose LMO4 protein, a transcription regulator, involved in multiple protein complexes. We investigated changes in LMO4 immunoreactivity in vulnerable brain regions of AD cases and controls of comparable age. Immunocytochemical analysis revealed a high level of LMO4 expression in the entorhinal cortex (EC) and in the CA1 hippocampal region of the control brains and a consistent decrease in the AD brains, correlated with the amount of neurofibrillary tangles (NFT) degenerating neurones and the severity of senile plaques deposition. The decrease in LMO4 immunoreactivity resulted both from weaker immunoreactive signals and from a loss of immunoreactive neurones. LMO4 immunocytochemical staining appeared not to be colocalized with NFT in a majority of neurones. Its expression was weak in the dentate gyrus and stronger in CA3-4, two regions with no or low numbers of NFT, but there was no decrease in AD compared to control cases. In the frontal cortex, the ventro-infero-median region (area 12) showed a greater LMO4 expression than the polar one (area 9), but no decrease in AD was observed. As LMO4 has been proposed to inhibit cellular differentiation, it can be hypothesized that a reduced expression is associated in EC and CA1 with attempts of diseased neurones to differentiate (e.g. compensatory neuritogenesis). Taken together, these data indicate that LMO4 protein is involved in the complexity of the disease phenotype, at least as a secondary factor

    Structural stigma and alcohol use among sexual and gender minority adults: A systematic review

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    Background: Sexual and gender minority (SGM) people are more likely than their cisgender, heterosexual counterparts to report negative alcohol-related outcomes. Although the association between individual- and interpersonal-level minority stressors and negative alcohol-related outcomes among SGM people is well-established, structural-level minority stressors are understudied. This systematic review examined structural-level stigma and alcohol-related outcomes among SGM people to inform future research, interventions, and policy. Methods: We used five electronic databases to search for studies published between January 2010 and May 2022 that examined associations between structural stigma and alcohol use among SGM adults in the United States. Peer-reviewed, quantitative studies available in English were included. We conducted quality appraisal using the Joanna Briggs Institute checklist. Results: The final sample included 11 studies. Overall, there was moderate to strong support for a positive association between structural stigma and negative alcohol-related outcomes among SGM people, with differences by gender, sexual identity, race, and ethnicity. All studies used cross-sectional designs, and nearly half utilized non-probability samples. Transgender and nonbinary people, SGM people of color, and sexual identity subgroups beyond gay, lesbian, and heterosexual were underrepresented. Structural stigma was most commonly measured as a state-level index. Alcohol measures were heterogeneous. Multilevel stigma and resiliency factors were understudied. Conclusions: Addressing structural stigma is critical in reducing negative alcohol-related outcomes and inequities among SGM people. Research is needed that includes probability samples, longitudinal designs, and samples that reflect the diversity of SGM people. Future studies should examine the influence of multilevel stigma and resiliency factors on alcohol-related outcomes
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