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81.
82.
Matteo Zurlo Francesco Nicoli Davide Proietto Beatrice Dallan Cristina Zuccato Lucia Carmela Cosenza Jessica Gasparello Chiara Papi Elisabetta d'Aversa Monica Borgatti Chiara Scapoli Alessia Finotti Roberto Gambari 《Journal of cellular and molecular medicine》2023,27(3):353-364
Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β-Thalassemia). The objective of the present study was to analyse the activity of CD4+ and CD8+ T cells in β-Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN-γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4+ and CD8+ T cells, respectively. The main results of the present study are that treatment of β-Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN-γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β-Thalassemia patients are considered prone to immune deficiency. 相似文献
83.
Many viruses, including retroviruses, undergo frequent recombination, a process which can increase their rate of adaptive evolution. In the case of HIV, recombination has been responsible for the generation of numerous intersubtype recombinant variants with epidemiological importance in the AIDS pandemic. Although it is known that fragments of genetic material do not combine randomly during the generation of recombinant viruses, the mechanisms that lead to preferential recombination at specific sites are not fully understood. Here we reanalyze recent independent data defining (i) the structure of a complete HIV-1 RNA genome and (ii) favorable sites for recombination. We show that in the absence of selection acting on recombinant genomes, regions harboring RNA structures in the NL4-3 model strain are strongly predictive of recombination breakpoints in the HIV-1 env genes of primary isolates. In addition, we found that breakpoints within recombinant HIV-1 genomes sampled from human populations, which have been acted upon extensively by natural selection, also colocalize with RNA structures. Critically, junctions between genes are enriched in structured RNA elements and are also preferred sites for generating functional recombinant forms. These data suggest that RNA structure-mediated recombination allows the virus to exchange intact genes rather than arbitrary subgene fragments, which is likely to increase the overall viability and replication success of the recombinant HIV progeny. 相似文献
84.
Maila Giannandrea Maria Lidia Mignogna Salvatore Carrabino Matteo Vecellio Silvia Russo Lidia Larizza Hans-Hilger Ropers Vera Kalscheuer Cindy Skinner Jozef Gecz Hilde Van Esch Jamel Chelly Daniela Toniolo Patrizia D'Adamo 《American journal of human genetics》2010,86(2):185-195
Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients. One mutation in family X (D-23) introduced a stop codon seven amino acids after the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family, altered the 5′ splice site (c.215+1G > A) and normal splicing. Neither instance produced a protein. Mutations segregate with the disease in the families, and in some family members intellectual disabilities were associated with autism spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a novel RAB GTPase of unknown function, is a neuronal-specific protein that is localized to the Golgi compartment. Its downregulation leads to an alteration in the number and morphology of neurite growth cones and a significant reduction in presynaptic buttons, suggesting that RAB39B is required for synapse formation and maintenance. Our results demonstrate developmental and functional neuronal alteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities. 相似文献
85.
86.
A. M. Berghella Patrizia Pellegrini Tiziana Del Beato Matteo Marini Ennio Tomei Domenico Adorno Carlo Umberto Casciani 《Cancer immunology, immunotherapy : CII》1997,45(5):241-249
Current research has still not clarified the biological role of soluble interleukin(IL)-2 receptor (sIL-2R) and the significance
of its increase in the serum of colon cancer patients compared to healthy subjects. To address these questions at the immunological
level in a group of patients and healthy subjects, we determined the sIL-2R level in the serum and its release from peripheral
blood mononuclear cells (PBMC) as a function of tumour necrosis factor (TNF) α, IL-1α, IL-1β, IL-2, interferon (IFN) γ, IL-4,
IL-6 and IL-10 levels in the serum and PBMC production; and PBMC proliferative responses to IL-2, IL-4 and anti-CD3 monoclonal
antibody (CD3), variously combined. The level of sIL-2R in patients’ serum was higher than in healthy subjects and correlated
with the stage of advancement. Moreover, while in healthy subjects the serum level of sIL-2R was not significantly correlated
with other parameters, in patients it was positively related to IL-4, IL-6 and IL-10 serum levels, PBMC IL-4 production and
to the PBMC proliferative response to CD3 and CD3+IL-2; it was negatively correlated to IL-2 serum level and IL-1β PBMC release.
A negative connection between IFNγ serum level and the PBMC production of sIL-2R was also found. This suggests that the increase
of sIL-2R in the serum of patients, compared to healthy subjects, is involved in the inappropriate expansion of the T helper
(TH2) suppressive immune response, which we previously reported. The multivariate statistical method supported the above suggestions
and we also found that, in healthy subjects, the up- and down-regulation of sIL-2R in the serum within the physiological ranges
seems to have a regulating role in the relationships between TNFα, IFNγ and IL-4, IL-6, contributing to the operation of the
cytokine network between TH1 and TH2 cells. However, in patients compared to healthy subjects the increased sIL-2R serum level
seems to direct the immune response towards a suppressive type, which may be due to an alteration in the above-mentioned physiological
regulating role.
Received: 12 April 1997 / Accepted: 4 September 1997 相似文献
87.
Alessandro Petraglia Marcello Tomaselli Matteo Petit Bon Nicola Delnevo Giorgio Chiari Michele Carbognani 《Plant Ecology》2014,215(7):759-768
In snowbed habitats, characterized by a long-lasting snow cover, the timing of snowmelt can be included among the major factors controlling plant phenology. Nevertheless, only a few ecological studies have tested the responses of flowering phenology of species growing in very late snow-free habitats to an advanced snowmelt (AS) date. The aim of this study was to determine the impacts of an extremely earlier melt-out of snow on flowering phenology of vascular plant species inhabiting an alpine snowbed. The study was conducted in the high Gavia Valley (Italy, 2,700 m a.s.l.). On 30th May 2012, we removed manually the snow cover and set up an experiment with 5 AS and 5 control plots. Phenological observations of the most abundant vascular species were conducted every 4–6 days. Moreover, we calculated cumulative soil temperature and recorded the mortality of reproductive structures of three species. For several species flowering occurred earlier, and the prefloration period was extended in the AS treatment in comparison with the control. For the majority of species, cumulative soil temperatures in the AS treatment and the control were comparable, confirming that temperature exerts the main control on the flowering of the species inhabiting snowbeds. Earlier flowering species resulted more affected by an AS date in comparison with later flowering species. The mortality of reproductive structures did not increase in the AS treatments in comparison with the control suggesting that few and weak frost events in late spring do not affect the survival of reproductive structures of the species studied. 相似文献
88.
89.
Francesco Taus Marilina B. Santucci Emanuela Greco Matteo Morandi Ivana Palucci Sabrina Mariotti Noemi Poerio Roberto Nisini Giovanni Delogu Maurizio Fraziano 《PloS one》2015,10(5)
A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. 相似文献
90.