30 research outputs found

    Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life

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    Influenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life. Offspring born to influenza A virus infected mothers are stunted in growth and more vulnerable to heterologous infections (influenza B virus and MRSA) than those born to PBS- or poly(I:C)-treated mothers. Enhanced vulnerability to infection in neonates is associated with reduced haematopoetic development and immune responses. In particular, alveolar macrophages of offspring exposed to maternal influenza have reduced capacity to clear second hit pathogens. This impaired pathogen clearance is partially reversed by adoptive transfer of alveolar macrophages from healthy offspring born to uninfected dams. These findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring

    Comparative study of continuum damage mechanics and Mechanics of Porous Media based on multi-mechanism model on Polyamide 6 semi-crystalline polymer

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    International audienceThe biphasic character of semi-crystalline polymer was modeled by the multi-mechanism (MM) constitutive relationships. Here, a comparative study between continuum damage mechanics (CDM) theory and Mechanics of Porous Media (MPM) approach, both related to the MM model, is performed. This comparison is based upon creep tests conducted on notched round bars made of PA6 semi-crystalline polymer to enhance a multiaxial stress state. For CDM model, the damage is classically described by a unique overall variable whereas the average of the local porosity at each phase level was considered for the MPM model. For each model, the optimization of the set of material’s parameters was carried out by combining the overall behavior of notched specimens subjected to creep loading, as well as the local information such as the distribution of porosity. It is found that both CDM and MPM models, each coupled with MM model correctly describe the overall creep behavior of the notched specimen if two damage variables are used. Moreover the MM/MPM model is more relevant for predicting porosity distribution

    Multi-mechanism damage-plasticity model for semi-crystalline polymer: Creep damage of notched specimen of PA6

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    International audienceThe multi-mechanism model devoted to the semi-crystalline polymers proposed in the recent study (Regrain et al. [1]) is generalized in this work to account for mechanical damage behaviour. To assess model reliability, finite element simulations of notched specimens subjected to creep behaviour were performed and compared successfully to experiments in terms of creep notch opening displacement. The model is able to reproduce the location of the maximum damage in a structure. This is a key information for the lifetime prediction of engineering components made of semi-crystalline polymers such as pressure vessel or pipes subjected to creep loading

    Endolysosomal cation channels and lung disease.

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    Endolysosomal cation channels are emerging as key players of endolysosomal function such as endolysosomal trafficking, fusion/fission, lysosomal pH regulation, autophagy, lysosomal exocytosis, and endocytosis. Diseases comprise lysosomal storage disorders (LSDs) and neurode-generative diseases, metabolic diseases, pigmentation defects, cancer, immune disorders, autophagy related diseases, infectious diseases and many more. Involvement in lung diseases has not been a focus of attention so far but recent developments in the field suggest critical functions in lung physiology and pathophysiology. Thus, loss of TRPML3 was discovered to exacerbate emphysema formation and cigarette smoke induced COPD due to dysregulated matrix metalloproteinase 12 (MMP-12) levels in the extracellular matrix of the lung, a known risk factor for emphysema/COPD. While direct lung function measurements with the exception of TRPML3 are missing for other endolysosomal cation channels or channels expressed in lysosome related organelles (LRO) in the lung, links between those channels and important roles in lung physiology have been established such as the role of P2X4 in surfactant release from alveolar epithelial Type II cells. Other channels with demonstrated functions and disease relevance in the lung such as TRPM2, TRPV2, or TRPA1 may mediate their effects due to plasma membrane expression but evidence accumulates that these channels might also be expressed in endolysosomes, suggesting additional and/or dual roles of these channels in cell and intracellular membranes. We will discuss here the current knowledge on cation channels residing in endolysosomes or LROs with respect to their emerging roles in lung disease

    Phytochemicals as Antimicrobials: Prospecting Himalayan Medicinal Plants as Source of Alternate Medicine to Combat Antimicrobial Resistance

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    Among all available antimicrobials, antibiotics hold a prime position in the treatment of infectious diseases. However, the emergence of antimicrobial resistance (AMR) has posed a serious threat to the effectiveness of antibiotics, resulting in increased morbidity, mortality, and escalation in healthcare costs causing a global health crisis. The overuse and misuse of antibiotics in global healthcare setups have accelerated the development and spread of AMR, leading to the emergence of multidrug-resistant (MDR) pathogens, which further limits treatment options. This creates a critical need to explore alternative approaches to combat bacterial infections. Phytochemicals have gained attention as a potential source of alternative medicine to address the challenge of AMR. Phytochemicals are structurally and functionally diverse and have multitarget antimicrobial effects, disrupting essential cellular activities. Given the promising results of plant-based antimicrobials, coupled with the slow discovery of novel antibiotics, it has become highly imperative to explore the vast repository of phytocompounds to overcome the looming catastrophe of AMR. This review summarizes the emergence of AMR towards existing antibiotics and potent phytochemicals having antimicrobial activities, along with a comprehensive overview of 123 Himalayan medicinal plants reported to possess antimicrobial phytocompounds, thus compiling the existing information that will help researchers in the exploration of phytochemicals to combat AMR

    Synergistic partnerships of endophytic fungi for bioactive compound production and biotic stress management in medicinal plants

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    The fungal endophytes are an understudied area of research with great potential for new bioactive compounds’ discovery. These are the fungal strains that live within the inner compartments of the host plant without causing it any kind of harm. These fungal endophytes, in combination with the host organisms, synthesize many compounds with a range of pharmaceutical values. Most recently, the discovery of fungal endophyte genes which are linked with the biosynthesis of plant metabolites has opened a new field of research. These plant partners assist plants against biotic stress and protect them from pathogenic attacks or diseases with the presence of some important gene families like WRKY and MYB. The bioactive metabolites from this group are known for their anticancer, antimicrobial, antioxidant, antidiabetic, and anti-tubercular properties. Therefore, these bioactive compounds offer new routes for discovering novel drugs, which can boost the pharmaceutical industry in times of great demand for novel drugs. Extracellular enzymes are also produced within the members of this distinct group which are crucial for several industrial sectors, including the biofuel production industry. Furthermore, fungal endophytes are capable of synthesizing silver nanoparticles, which exhibit significant potential in fields like biomedical imaging and water purification. This article aims to document all the available data on this group of fungi living in medicinal plants and the major compounds produced by members of this distinct group that are in use for the therapy of various ailments
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