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481.
Parej Nath Nishant Ranjan Chauhan Kautilya Kumar Jena Ankita Datey Nilima Dinesh Kumar Subhash Mehto Saikat De Tapas Kumar Nayak Swatismita Priyadarsini Kshitish Rout Ramyasingh Bal Krushna C Murmu Manjula Kalia Srinivas Patnaik Punit Prasad Fulvio Reggiori Soma Chattopadhyay Santosh Chauhan 《EMBO reports》2021,22(11)
The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs, APOBECs, SAMHD1, tetherin, viperin, and HERC5/6. Additionally, antiviral processes such as MHC‐I antigen presentation and stress granule signaling are enhanced in IRGM‐deficient cells, indicating a robust cell‐intrinsic antiviral immune state. Consistently, IRGM‐depleted cells are resistant to the infection with seven viruses from five different families, including Togaviridae, Herpesviridae, Flaviviverdae, Rhabdoviridae, and Coronaviridae. Moreover, we show that Irgm1 knockout mice are highly resistant to chikungunya virus (CHIKV) infection. Altogether, our work highlights IRGM as a broad therapeutic target to promote defense against a large number of human viruses, including SARS‐CoV‐2, CHIKV, and Zika virus. 相似文献
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483.
The cytoskeleton is an essential component of the cell and it is involved in multiple physiological functions, including intracellular organization and transport. It is composed of three main families of proteinaceous filaments; microtubules, actin filaments and intermediate filaments and their accessory proteins. Motor proteins, which comprise the dynein, kinesin and myosin superfamilies, are a remarkable group of accessory proteins that mainly mediate the intracellular transport of cargoes along with the cytoskeleton. Like other cellular structures and pathways, viruses can exploit the cytoskeleton to promote different steps of their life cycle through associations with motor proteins. The complexity of the cytoskeleton and the differences among viruses, however, has led to a wide diversity of interactions, which in most cases remain poorly understood. Unveiling the details of these interactions is necessary not only for a better comprehension of specific infections, but may also reveal new potential drug targets to fight dreadful diseases such as rabies disease and acquired immunodeficiency syndrome (AIDS). In this review, we describe a few examples of the mechanisms that some human viruses, that is, rabies virus, adenovirus, herpes simplex virus, human immunodeficiency virus, influenza A virus and papillomavirus, have developed to hijack dyneins, kinesins and myosins. 相似文献
484.
Mariarosaria Boccellino Raffaele La Porta Mario Coppola Pasquale Petronella Fulvio Freda Vincenzo Calderaro Lucio Quagliuolo 《Apoptosis : an international journal on programmed cell death》2013,18(1):43-56
A larger diffusion of peritoneal dialysis (PD) is limited by the progressive deterioration of the dialysis membrane structure and function, characterized in vitro and in vivo by mesothelial cell loss and closely related to the use of bioincompatible dialysis solutions. The apoptosis rate of rat and human mesothelial cells incubated in commercial PD fluid (PDF, 4.25 g/dL dextrose) became significant as early as 1 h after PDF addition and reached a plateau at 4–5 h. This pattern was unchanged after exposure to 1.5 g/dL dextrose PDF or freshly prepared PDF, indicating that effects were independent on the dextrose strength and manufacturing procedures but strictly dependent on PDF composition. Molecular studies revealed that PDF exposure inactivated the physiological volume recovery from hypertonic shrinkage, accompanied by an abnormal Ca2+ signaling: a progressive intracellular Ca2+ ([Ca2+]i) rise resulting from an increased Ca2+ entry. PDF also affected cytoskeleton integrity: early dissolution of actin filaments occurred well before the appearance of typical apoptosis features. Lastly, the PDF dependent apoptosis was almost completely prevented by the contemporary Ca2+ concentration decrease and K+ addition. This study suggests that the PDF dependent apoptosis arises from the extreme volume perturbations in mesothelial cells, turned out unable to regulate their volume back once exposed to a hyperosmolal medium containing high Ca2+ levels in the absence of K+, such PDF. 相似文献
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486.
Nicola Scichilone Maria T Ventura Matteo Bonini Fulvio Braido Caterina Bucca Marco Caminati Stefano Del Giacco Enrico Heffler Carlo Lombardi Andrea Matucci Manlio Milanese Roberto Paganelli Giovanni Passalacqua Vincenzo Patella Erminia Ridolo Giovanni Rolla Oliviero Rossi Domenico Schiavino Gianenrico Senna Gundi Steinhilber Alessandra Vultaggio Giorgio Canonica 《Clinical and molecular allergy : CMA》2015,13(1)
The prevalence of asthma in the most advanced ages is similar to that of younger ages. However, the concept that older individuals may suffer from allergic asthma has been largely denied in the past, and a common belief attributes to asthma the definition of “rare” disease. Indeed, asthma in the elderly is often underdiagnosed or diagnosed as COPD, thus leading to undertreatment of improper treatment. This is also due to the heterogeneity of clinical and functional presentations of geriatric asthma, including the partial loss of reversibility and the lower occurrence of the allergic component in this age range. The older asthmatic patients are also characterized the coexistence of comorbid conditions that, in conjunction with age-associated structural and functional changes of the lung, may contribute to complicate the management of asthma. The current review addresses the main issues related to the management of allergic asthma in the geriatric age. In particular, the paper aims at revising current pharmacological and non pharmacological treatments for allergic asthmatics of advanced ages, primarily focusing on their safety and efficacy, although most behaviors are an arbitrary extrapolation of what has been tested in young ages. In fact, age has always represented an exclusion criterion for eligibility to clinical trials. Experimental studies and real life observations specifically testing the efficacy and safety of therapeutic approaches in allergic asthma in the elderly are urgently needed. 相似文献
487.
Pietro Zingaretti Anna Maria Petta Gianluca Cruciani Grazia Fernanda Spitoni 《Somatosensory & motor research》2019,36(1):90-96
The development of somatosensation and affective touch acquires a central role throughout our lives, for several reasons. In adults, these functions are driven by different, neuroanatomically and functionally segregated fibres. To date, very little is known about the basic features of these fibres in childhood and this lack of knowledge is mirrored in the affective touch domain, where there are no studies on the main physiological features of the tactile processes linked to the stimulation of the hairy skin, namely the preferential site of affective touch. Thus, our study aims to analyze (1) tactile sensitivity and tactile acuity of children’s hairy forearms; (2) a possible dissociation between somatosensation and the affective touch; and (3) the presence/absence of the perception of affective touch already in childhood. To these aims, participants (160 children, aged 6 to 14?years), were administered with the Von Frey (tactile sensitivity) and the 2 Point Discrimination (tactile acuity) tests. Affective touch was measured following the classic protocol and pleasantness ratings were recorded. Our findings showed a correlation between age and somatosensation, suggesting a progressive reduction of sensitivity and acuity as age grows. Further, there was no overlap between affective touch and somatosensation, suggesting a behavioural segregation. Lastly, we found higher pleasantness ratings for Affective versus Neutral stimulations at all ages and an enhanced preference for Affective as age grows. We concluded that both somatosensation and affective touch are already present as two separate components of touch in childhood and change as a function of age. 相似文献
488.
Displacement studies of [3H]-[D-Ala2-MePhe4-Gly-ol5]-enkephalin ([3H]-DAGO) and [3H]-[D-Ala2-D-Leu5]-enkephalin ([3H]-DADL) by the corresponding unlabeled ligands show that there are at least three classes of sites which bind these enkephalin analogs with high affinity. Using computer modeling, the introduction of the third site significantly improved the goodness of fit in ten consecutive experiments. These sites appear to correspond to the mu, delta and mu 1 sites, with mean dissociation constants of 11, 1.3 and 0.9 nM for DADL and 2.5, 300 and 0.3 nM for DAGO, respectively. 相似文献
489.
Fulvio Esposito Anna Maria Santroni Annette Habluetzel Vincenzo Grelloni Antonello Pessi Stefania Lombardi Giancarlo Falcioni Maurizio Brunori 《International journal for parasitology》1990,20(8):1109-1111
The synthetic peptide (NANP)20, reproducing the tandem-repeated epitope of the circumsporozoite protein of Plasmodium (Laverania) falciparum, was entrapped into murine, autologous erythrocytes by a hypotonic dialysis method. Mice immunized intravenously with minute amounts of encapsulated peptide produced considerable antibody titres. This result indicates that intraerythrocytic antigen administration may have a potential as an immunization system for humans, since it dispenses with adjuvants and carrier molecules. 相似文献
490.