Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic ...abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin-binding protein cyclase-associated protein 2 (
), the sheddase a disintegrin and metalloproteinase 10 (
), and the synapse-associated protein 97 (
). Our analysis of the SCZ post-mortem brain indicated increased
mRNA in DLPFC and decreased
mRNA in the hippocampus of SCZ patients, compared to non-psychiatric control subjects, while the
transcript was unaffected. Conversely, no differences in
,
, and
protein levels were detected between SCZ and control individuals in both brain regions. To assess whether
and
transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson's and Alzheimer's disease. Interestingly, also in Parkinson's disease patients, we found a selective reduction of
mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered
expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies.
Extracorporeal photopheresis (ECP) as a part of multimodality therapy, is one of the treatments for Sézary syndrome (SS) and advanced stage mycosis fungoides (MF). This study aims to describe ...cutaneous and peripheral blood responses of patients with MF and SS who received multimodality therapy.
In this cross-sectional retrospective study, patients with MF or SS who received ECP treatment in combination with at least one additional systemic treatment between 2011 and 2018 were included. ECP consisted of a two-session cycle every 2 to 4 weeks. Cutaneous and blood responses were evaluated with updated criteria.
Twenty-eight patients (11 (39%) with MF and 17 (51%) with SS) were included. Their median age at diagnosis was 63 (57-67) years. The median number of treatments before ECP was 2 (1-3). Seven out of 11 patients with MF (63%) underwent an assessment of cutaneous response. Five patients (70%) presented a partial response; 1 (15%), stable disease, and 1 (15%) progressive disease. Thirteen of the 17 patients with SS (76%) underwent evaluation. One patient (8%) presented a complete cutaneous response; 6 (46%), a partial response; 5 (38%), stable disease; and 1 (8%), progressive disease. None of them relapsed during the study period in both groups. No ECP-related adverse effects occurred during the study.
Most patients with SS and MF who underwent multimodality therapy with ECP had favorable cutaneous and blood response. It is safe to combine ECP with other treatments. Studies with large numbers of patients are necessary to assess the effects of ECP on patient survival.
We report on a novel phenomenon of particle cosmology, which features specific cosmological phase transitions via quantum tunnelings through multiple vacua. The latter is inspired by the axiverse ...ideas, and enables to probe the associated new physics models through a potential observation of specific patterns in the stochastic gravitational waves background. Multiple vacua may induce the nucleation of co-existing bubbles over the phase transition epoch, hence enhancing the overall process of bubbles' nucleation. Our detailed analysis of semi-analytical and numerical solutions to the bounce equations of the path integral in three vacua case has enabled us to determine the existence of three instanton solutions. This new mechanism of cosmological phase transitions clearly predicts a possibly sizeable new source of gravitational waves, with its energy spectrum being featured with particular patterns, which could be probed by the future gravitational wave interferometers.
Gravitational instability of exotic compact objects Addazi, Andrea; Marcianò, Antonino; Yunes, Nicolás
The European physical journal. C, Particles and fields,
2020/1, Letnik:
80, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Exotic compact objects with physical surfaces a Planckian distance away from where the horizon would have been are inspired by quantum gravity. Most of these objects are defined by a classical ...spacetime metric, such as boson stars, gravastars and wormholes. We show that these classical objects are gravitationally unstable because accretion by ordinary and dark matter, and by gravitational waves, forces them to collapse into a black hole by the Hoop conjecture. To avoid collapse, either their surface must be a macroscopic distance away from the horizon, or they must violate the null energy condition.
Background. Progressive multifocal leukoencephalopathy (PML) is a rare, severe, otherwise fatal viral infection of the white matter of the brain caused by the polyomavirus JC virus, which typically ...occurs only in immunocompromised patients. One patient with dominant gain-of-function (GOF) mutation in signal transducer and activator of transcription 1 (STAT1) with chronic mucocutaneous candidiasis and PML was reported previously. We aim to identify the molecular defect in 3 patients with PML and to review the literature on PML in primary immune defects (PIDs). Methods. STAT1 was sequenced in 3 patients with PML. U3C cell lines were transfected with STAT1 and assays to search for STAT1 phosphorylation, transcriptional response, and target gene expression were performed. Results. We identified 3 new unrelated cases of PML in patients with GOF STAT1 mutations, including the novel STAT1 mutation, L400Q. These STAT1 mutations caused delayed STAT1 dephosphorylation and enhanced interferon-gamma–driven responses. In our review of the literature regarding PML in primary immune deficiencies we found 26 cases, only 54% of which were molecularly characterized, the remainder being syndromically diagnosed only. Conclusions. The occurrence of PML in 4 cases of STAT1 GOF suggests that STAT1 plays a critical role in the control of JC virus in the central nervous system.
String memories ... lost and regained Addazi, Andrea; Bianchi, Massimo; Firrotta, Maurizio ...
Nuclear physics. B,
April 2021, 2021-04-00, 2021-04-01, Letnik:
965
Journal Article
Recenzirano
Odprti dostop
We discuss stringy α′ corrections to the gravitational wave signal generated in the merging of two black holes. We model the merging with two BPS compact massive objects in the heterotic string, ...described by standard vertex operators or coherent states. Despite the expected cubic suppression in α′ w.r.t. the General Relativity result in the low-energy expansion, at tree level the infinite tower of string resonances leaves a clear footprint on the gravitational wave signals within the sensitivity region of aLIGO/VIRGO and future interferometers. Including loop effects that broaden and destabilise the string resonances suggests a sort of lost stringy memory effect that can be regained through the analysis of the quasi normal modes in the ring-down phase.
Zymomonas mobilis, a Gram-negative bacteria observed in some popular beverages, is considered safe and has been studied for its potential therapeutic benefits. In this study, we explored its effects ...on the inflammatory process, tissue integrity, differential gene expression, and microbiota composition in an experimental dextran sulfate sodium (DSS)-induced colitis model in mice. As a result, Z. mobilis alleviated the symptoms caused by DSS administration, as indicated by reduced weight loss, disease activity index, a significant reduction in the colon weight/length ratio, and histopathological improvement. Also, Z. mobilis could restore the mucosal barrier as well as increase the expression of Muc3 and Ocln genes. An analysis of 16S rRNA sequences showed that Z. mobilis alters gut microbiota, increasing Akkermansia muciniphila abundance and decreasing Escherichia coli. Furthermore, Z. mobilis seems to be involved in potentiating a regulatory phenotype by inducing immunomodulatory genes like Tgfb, Il5, Il10, and Foxp3 and reducing the relative mRNA expression of proinflammatory cytokines TNF, Il6, and Il17. Our data suggest that Z. mobilis could alleviate disease progression and be considered a possible probiotic adjuvant for pathologies of the bowel.
We inspect the possibility that neutron star interiors are a mixture of ordinary matter and mirror dark matter. This is a scenario that can be naturally envisaged according to well studied accretion ...mechanisms, including the Bondi–Hoyle one. We show that the inclusion of mirror dark matter in neutron star models lowers the maximum neutron star mass for a given equation of state, and that it decreases the tidal deformability of a given neutron star. These general features imply that, given an equation of state, one can constrain the maximum viable amount of mirror dark matter in neutron stars in order to consistently fulfil existing maximum mass and tidal deformability constraints. Conversely, using tidal deformability measurements to rule out equations of state requires making assumptions on the amount of mirror dark matter contained in neutron stars. Finally, the presence of mirror dark matter also modifies the universal relation that links the tidal deformability of a neutron star to its compactness. Therefore, caution is mandatory when considering exotic models, such as the ones discussed in this paper.
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