On the effective conductivity and the apparent viscosity of a thin rough polymer interface using PGD‐based separated representations

Composite manufacturing processes usually proceed from preimpregnated preforms that are consolidated by simultaneously applying heat and pressure, so as to ensure a perfect contact compulsory for making molecular diffusion possible. However, in practice, the contact is rarely perfect. This results in a rough interface where air could remain entrapped, thus affecting the effective thermal conductivity. Moreover, the interfacial melted polymer is squeezed flowing in the rough gap created by the fibers located on the prepreg surfaces. Because of the typical dimensions of a composite prepreg, with thickness orders of magnitude smaller than its other in-plane dimensions, and its surface roughness having a characteristic size orders of magnitude smaller than the prepreg thickness, high-fidelity numerical simulations for elucidating the impact of surface and interface roughness remain today, despite the impressive advances in computational availabilities, unattainable. This work aims at elucidating roughness impact on heat conduction and the effective viscosity of the interfacial polymer squeeze flow by using an advanced numerical strategy able to reach resolutions never attained until now, a sort of numerical microscope able to attain the scale of the smallest geometrical detail

Specific Pathogen Recognition by Multiple Innate Immune Sensors in an Invertebrate

Detection of pathogens by all living organisms is the primary step needed to implement a coherent and efficient immune response. This implies a mediation by different soluble and/or membrane-anchored proteins related to innate immune receptors called PRRs (pattern-recognition receptors) to trigger immune signaling pathways. In most invertebrates, their roles have been inferred by analogy to those already characterized in vertebrate homologs. Despite the induction of their gene expression upon challenge and the presence of structural domains associated with the detection of pathogen-associated molecular patterns in their sequence, their exact role in the induction of immune response and their binding capacity still remain to be demonstrated. To this purpose, we developed a fast interactome approach, usable on any host-pathogen couple, to identify soluble proteins capable of directly or indirectly detecting the presence of pathogens. To investigate the molecular basis of immune recognition specificity, different pathogens (Gram-positive bacterium, Micrococcus luteus; Gram-negative, Escherichia coli; yeast, Saccharomyces cerevisiae; and metazoan parasites, Echinostoma caproni or Schistosoma mansoni) were exposed to hemocyte-free hemolymph from the gastropod Biomphalaria glabrata. Twenty-three different proteins bound to pathogens were identified and grouped into three different categories based on their primary function. Each pathogen was recognized by a specific but overlapping set of circulating proteins in mollusk's hemolymph. While known PRRs such as C-type lectins were identified, other proteins not known to be primarily involved in pathogen recognition were found, including actin, tubulin, collagen, and hemoglobin. Confocal microscopy and specific fluorescent labeling revealed that extracellular actin present in snail hemolymph was able to bind to yeasts and induce their clotting, a preliminary step for their elimination by the snail immune system. Aerolysin-like proteins (named biomphalysins) were the only ones involved in the recognition of all the five pathogens tested, suggesting a sentinel role of these horizontally acquired toxins. These findings highlight the diversity and complexity of a highly specific innate immune sensing system. It paves the way for the use of such approach on a wide range of host-pathogen systems to provide new insights into the specificity and diversity of immune recognition by innate immune systems

BgTEP: An Antiprotease Involved in Innate Immune Sensing in Biomphalaria glabrata

Insect thioester-containing protein (iTEP) is the most recently defined group among the thioester-containing protein (TEP) superfamily. TEPs are key components of the immune system, and iTEPs from flies and mosquitoes were shown to be major immune weapons. Initially characterized from insects, TEP genes homologous to iTEP were further described from several other invertebrates including arthropods, cniderians, and mollusks albeit with few functional characterizations. In the freshwater snail Biomphalaria glabrata, a vector of the schistosomiasis disease, the presence of a TEP protein (BgTEP) was previously described in a well-defined immune complex involving snail lectins (fibrinogen-related proteins) and schistosome parasite mucins (SmPoMuc). To investigate the potential role of BgTEP in the immune response of the snail, we first characterized its genomic organization and its predicted protein structure. A phylogenetic analysis clustered BgTEP in a well-conserved subgroup of mollusk TEP. We then investigated the BgTEP expression profile in different snail tissues and followed immune challenges using different kinds of intruders during infection kinetics. Results revealed that BgTEP is particularly expressed in hemocytes, the immune-specialized cells in invertebrates, and is secreted into the hemolymph. Transcriptomic results further evidenced an intruder-dependent differential expression pattern of BgTEP, while interactome experiments showed that BgTEP is capable of binding to the surface of different microbes and parasite either in its full length form or in processed forms. An immunolocalization approach during snail infection by the Schistosoma mansoni parasite revealed that BgTEP is solely expressed by a subtype of hemocytes, the blast-like cells. This hemocyte subtype is present in the hemocytic capsule surrounding the parasite, suggesting a potential role in the parasite clearance by encapsulation. Through this work, we report the first characterization of a snail TEP. Our study also reveals that BgTEP may display an unexpected functional dual role. In addition to its previously characterized anti-protease activity, we demonstrate that BgTEP can bind to the intruder surface membrane, which supports a likely opsonin role

Vitamin D and Subjective Memory Complaint in Community-Dwelling Older Adults

International audienceBACKGROUND: Older adults with hypovitaminosis D report more often subjective cognitive complaints, especially with regards to memory. This raises prospects that vitamin D may improve older adults' subjective experience of memory disorders.OBJECTIVE: To determine among older community-dwellers whether higher serum 25- hydroxyvitamin D (25OHD) concentrations were associated with fewer memory complaints, while considering different subtypes of memory complaints.METHOD: One hundred eighty Caucasian community-dwellers with memory complaint and no dementia (mean±standard deviation, 71.1±3.4years; 33.3%female) from the French 'EVATEM study' were included in this analysis. Subjective memory complaints regarding memory lapses, problems learning new information, problems finding words, problems calculating and problems concentrating were assessed using a standardized questionnaire. Participants were categorized according to the highest tertile of serum 25OHD (i.e., ≥68nmol/L). Age, gender, body mass index, morbidities burden, use of vitamin D supplements, cognitive performance, mood, serum concentrations of calcium, parathyroid hormone and vitamin B12, creatinine clearance, and season of evaluation were used as potential confounders.RESULTS: Compared to participants with 25OHD&lt;68nmol/L (n=121), those with 25OHD≥68nmol/L had less often problems learning new information (P=0.027). There were no between-group differences for the other memory complaints. The highest 25OHD tertile was cross-sectionally associated with fewer problems learning new information (odds ratio (OR)=0.48, P=0.029), even after adjustment for potential confounders (OR=0.32, P=0.039).CONCLUSION: Higher vitamin D status was associated with reduced problems memorizing new information in older community-dwellers. This novel finding provides a scientific base for vitamin D replacement trials attempting to improve older patients' subjective experience of cognitive decline.</p

Sympatric versus allopatric evolutionary contexts shape differential immune response in Biomphalaria / Schistosoma interaction

Selective pressures between hosts and their parasites can result in reciprocal evolution or adaptation of specific life history traits. Local adaptation of resident hosts and parasites should lead to increase parasite infectivity/virulence (higher compatibility) when infecting hosts from the same location (in sympatry) than from a foreign location (in allopatry). Analysis of geographic variations in compatibility phenotypes is the most common proxy used to infer local adaptation. However, in some cases, allopatric host-parasite systems demonstrate similar or greater compatibility than in sympatry. In such cases, the potential for local adaptation remains unclear. Here, we study the interaction between Schistosoma and its vector snail Biomphalaria in which such discrepancy in local versus foreign compatibility phenotype has been reported. Herein, we aim at bridging this gap of knowledge by comparing life history traits (immune cellular response, host mortality, and parasite growth) and molecular responses in highly compatible sympatric and allopatric Schistosoma/Biomphalaria interactions originating from different geographic localities (Brazil, Venezuela and Burundi). We found that despite displaying similar prevalence phenotypes, sympatric schistosomes triggered a rapid immune suppression (dual-RNAseq analyses) in the snails within 24h post infection, whereas infection by allopatric schistosomes (regardless of the species) was associated with immune cell proliferation and triggered a non-specific generalized immune response after 96h. We observed that, sympatric schistosomes grow more rapidly. Finally, we identify miRNAs differentially expressed by Schistosoma mansoni that target host immune genes and could be responsible for hijacking the host immune response during the sympatric interaction. We show that despite having similar prevalence phenotypes, sympatric and allopatric snail-Schistosoma interactions displayed strong differences in their immunobiological molecular dialogue. Understanding the mechanisms allowing parasites to adapt rapidly and efficiently to new hosts is critical to control disease emergence and risks of Schistosomiasis outbreaks. Author summary Schistosomiasis, the second most widespread human parasitic disease after malaria, is caused by helminth parasites of the genus Schistosoma. More than 200 million people in 74 countries suffer from the pathological, and societal consequences of this disease. To complete its life cycle, the parasite requires an intermediate host, a freshwater snail of the genus Biomphalaria for its transmission. Given the limited options for treating Schistosoma mansoni infections in humans, much research has focused on developing methods to control transmission by its intermediate snail host. Biomphalaria glabrata. Comparative studies have shown that infection of the snail triggers complex cellular and humoral immune responses resulting in significant variations in parasite infectivity and snail susceptibility, known as the so-called polymorphism of compatibility. However, studies have mostly focused on characterizing the immunobiological mechanisms in sympatric interactions. Herein we used a combination of molecular and phenotypic approaches to compare the effect of infection in various sympatric and allopatric evolutionary contexts, allowing us to better understand the mechanisms of host-parasite local adaptation. Learning more about the immunobiological interactions between B. glabrata and S. mansoni could have important socioeconomic and public health impacts by changing the way we attempt to eradicate parasitic diseases and prevent or control schistosomiasis in the field

Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33

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Novel phylogenetic clade of avian Haemoproteus parasites (Haemosporida, Haemoproteidae) from Accipitridae raptors, with description of a new Haemoproteus species

Harl J, Fauchois A, Puech M-P, et al. Novel phylogenetic clade of avian Haemoproteus parasites (Haemosporida, Haemoproteidae) from Accipitridae raptors, with description of a new Haemoproteus species. Parasite : Journal de la Société Française de Parasitologie . 2024;31: 5.Avian haemosporidian parasites (order Haemosporida, phylum Apicomplexa) are blood and tissue parasites transmitted by blood-sucking dipteran insects. Three genera (Plasmodium, Haemoproteus and Leucocytozoon) have been most often found in birds, with over 270 species described and named in avian hosts based mainly on the morphological characters of blood stages. A broad diversity of Haemoproteus parasites remains to be identified and characterized morphologically and molecularly, especially those infecting birds of prey, an underrepresented bird group in haemosporidian parasite studies. The aim of this study was to investigate and identify Haemoproteus parasites from a large sample comprising accipitriform raptors of 16 species combining morphological and new molecular protocols targeting the cytb genes of this parasite group. This study provides morphological descriptions and molecular characterizations of two Haemoproteus species, H. multivacuolatus n. sp. and H. nisi Peirce and Marquiss, 1983. Haemoproteus parasites of this group were so far found in accipitriform raptors only and might be classified into a separate subgenus or even genus. Cytb sequences of these parasites diverge by more than 15% from those of all others known avian haemosporidian genera and form a unique phylogenetic clade. This study underlines the importance of developing new diagnostic tools to detect molecularly highly divergent parasites that might be undetectable by commonly used conventional tools. © J. Harl et al., published by EDP Sciences, 2024

Artemisinin and its derivatives target mitochondrial c-type cytochromes in yeast and human cells

[email protected]@i2bc.paris-saclay.frInternational audienceArtemisinin and its derivatives kill malaria parasites and inhibit the proliferation of cancer cells. In both processes, heme was shown to play a key role in artemisinin bioactivation. We found that artemisinin and clinical artemisinin derivatives are able to compensate for a mutation in the yeast Bcs1 protein, a key chaperon involved in biogenesis of the mitochondrial respiratory complex III. The equivalent Bcs1 variant causes an encephalopathy in human by affecting complex III assembly. We show that artemisinin derivatives decrease the content of mitochondrial cytochromes and disturb the maturation of the complex III cytochrome c1. This last effect is likely responsible for the compensation by decreasing the detrimental over-accumulation of the inactive pre-complex III observed in the bcs1 mutant. We further show that a fluorescent dihydroartemisinin probe rapidly accumulates in the mitochondrial network and targets cytochromes c and c1 in yeast, human cells and isolated mitochondria. In vitro this probe interacts with purified cytochrome c only under reducing conditions and we detected cytochrome c-dihydroartemisinin covalent adducts by mass spectrometry analyses. We propose that reduced mitochondrial c-type cytochromes act as both targets and mediators of artemisinin bioactivation in yeast and human cells

A multistrain approach to studying the mechanisms underlying compatibility in the interaction between Biomphalaria glabrata and Schistosoma mansoni

In recent decades, numerous studies have sought to better understand the mechanisms underlying the compatibility between Biomphalaria glabrata and Schistosoma mansoni. The developments of comparative transcriptomics, comparative genomics, interactomics and more targeted approaches have enabled researchers to identify a series of candidate genes. However, no molecular comparative work has yet been performed on multiple populations displaying different levels of compatibility. Here, we seek to fill this gap in the literature. We focused on B. glabrata FREPs and S. mansoni SmPoMucs, which were previously demonstrated to be involved in snail/schistosome compatibility. We studied the expression and polymorphisms of these factors in combinations of snail and schistosome isolates that display different levels of compatibility. We found that the polymorphism and expression levels of FREPs and SmPoMucs could be linked to the compatibility level of S. mansoni. These data and our complementary results obtained by RNA-seq of samples from various snail strains indicate that the mechanism of compatibility is much more complex than previously thought, and that it is likely to be highly variable within and between populations. This complexity must be taken into account if we hope to identify the molecular pathways that are most likely to be good targets for strategies aimed at blocking transmission of the parasite through the snail intermediate host

IFN-γ induces MHCII expression on IECs.

<p>(A) Frequency of CD45.2⁻ EpCAM⁺ MHCII⁺ intestinal epithelial cells (IEC) isolated from Rag1−/− or Rag1−/− IFN-γ−/− mice that were adoptively transferred with CD4⁺ CD45RB^hi T cells from WT or IFN-γ−/− mice shown as means and SEM in representative histograms (<i>n</i> = 3 mice per group). (B–C) Frequency of CD45.2⁻ EpCAM⁺ MHCII⁺ IECs (B) and CD4⁺ T cells from the colonic intestinal epithelium (C) isolated from <i>H. hepaticus</i>-infected, anti-IL-10R mAb-administered pIV−/− K14 CIITA Tg, pIV+/− K14 CIITA Tg or pIV+/− K14 CIITA Tg that were treated with neutralizing anti-IFN-γ mAb. Shown are representative FACS plots, means and SEM from two pooled experiments (<i>n</i> = 4–7 mice per group). αIFN-y, anti-interferon-γ monoclonal antibodies; FSC, forward scatter; IFN, interferon; Rag, recombination activating gene; WT, wild type;</p