133 research outputs found
Negative regulation of HIV-1 expression by the natural isoform C-terminus truncated STAT5 (STAT5Δ)
Naturally C-Terminally truncated STAT5 (STAT5Δ): a novel negative controller of HIV-1 transcription and expression
Castelsantangelo sul Nera, Macerata. Indagini, strategie e scenari per la ricostruzione | Castelsantangelo sul Nera, Macerata. Surveys, strategies and scenarios for the reconstruction
A partire dal 2018, il Politecnico di Torino è stato coinvolto tra le sedi universitarie firmatarie di una convenzione con l’Amministrazione Comunale di
Castelsantangelo sul Nera, dedicata alla promozione di studi e ricerche per la ricostruzione di un territorio duramente colpito dalle sequenze sismiche registrate nel 2016. La convenzione è stata promossa nell’ambito del programma di ricerca “FARB - Imparando dalle catastrofi”, sviluppato, tra febbraio
2017 e marzo 2019, da un gruppo di ricerca istituito presso il Dipartimento di Architettura e Studi Urbani del Politecnico di Milano. I rilievi svolti sul
campo, la raccolta di documenti d’archivio, l’elaborazione di mappe tematiche, sviluppate in ambiente GIS, hanno costituito le attività propedeutiche all’elaborazione di scenari progettuali, che gli autori hanno portato a compimento, formalizzando il contributo della ricerca universitaria alla rinascita del territorio e della comunità di Castelsantangelo sul Nera
Heterogeneity of Signal Transducer and Activator of Transcription Binding Sites in the Long-Terminal Repeats of Distinct HIV-1 Subtypes
HIV-1 can be subdivided into distinct subtypes; the consequences of such a genomic variability remain largely speculative. The long terminal repeats (LTR) control HIV transcription and reflect the major differences of distinct viral subtypes. Three regions in the HIV-1 subtype B LTR are close matches to the Signal Transducer and Activator of Transcription (STAT) consensus sequence. Here, we show heterogeneity in these putative STAT binding sites among HIV-1 LTR subtypes A through G. Transfection of constitutively activated STAT5 lead to transcriptional activation of HIV-1 expression in 293T cells transfected with a reporter assay driven by HIV-1 LTR subtype B. Constitutively activated STAT5 transactivated the LTR of various subtypes in U937 cells with different potency. These findings support and expand the potential relevance of STAT5 activation in HIV infection and may bear relevance for a differential regulation of latency and expression of different subtypes of HIV-1
Post-entry events of efficient R5 vs. inefficient X4 HIV-1 replication in primary CD4+T lymphocytes, a transcriptome analysis
Osteoimmunology of Spondyloarthritis
: The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. we summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA
COVID-19 teleassistance and teleconsultation: a matched case-control study (MIRATO project, Lombardy, Italy)
BackgroundDuring the COVID-19 pandemic, telemedicine has been recognised as a powerful modality to shorten the length of hospital stay and to free up beds for the sicker patients. Lombardy, and in particular the areas of Bergamo, Brescia, and Milan, was one of the regions in Europe most hit by the COVID-19 pandemic. The primary aim of the MIRATO project was to compare the incidence of severe events (hospital readmissions and mortality) in the first three months after discharge between COVID-19 patients followed by a Home-Based Teleassistance and Teleconsultation (HBTT group) program and those discharged home without Telemedicine support (non-HBTT group).MethodsThe study was designed as a matched case-control study. The non-HBTT patients were matched with the HBTT patients for sex, age, presence of COVID-19 pneumonia and number of comorbidities. After discharge, the HBTT group underwent a telecare nursing and specialist teleconsultation program at home for three months, including monitoring of vital signs and symptoms. Further, in this group we analysed clinical data, patients' satisfaction with the program, and quality of life.ResultsFour hundred twenty-two patients per group were identified for comparison. The median age in both groups was 70 ± 11 years (62% males). One or more comorbidities were present in 86% of the HBTT patients and 89% in the non-HBTT group (p = ns). The total number of severe events was 17 (14 hospitalizations and 3 deaths) in the HBTT group and 40 (26 hospitalizations and 16 deaths) in the non-HBTT group (p = 0.0007). The risk of hospital readmission or death after hospital discharge was significantly lower in HBTT patients (Log-rank Test p = 0.0002). In the HBTT group, during the 3-month follow-up, 5,355 teleassistance contacts (13 ± 4 per patient) were performed. The number of patients with one or more symptoms declined significantly: from 338 (78%) to 183 (45%) (p < 0.00001). Both the physical (ΔPCS12: 5.9 ± 11.4) component and the mental (ΔMCS12: 4.4 ± 12.7) component of SF-12 improved significantly (p < 0.0001). Patient satisfaction with the program was very high in all participants.ConclusionsCompared to usual care, an HBTT program can reduce severe events (hospital admissions/mortality) at 3-months from discharge and improve symptoms and quality of life.Clinical trial registrationwww.ClinicalTrials.gov, NCT04898179
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BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology
Background
Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear.
Methods
Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed.
Results
Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with AD-related traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant.
Conclusions
Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD
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