Distorted Icons in Contemporary Art: An Examination into How We Know What We Know and Why

The purpose of this exhibition, Distorted Icons in Contemporary Art: An Examination into How We Know What We Know and Why, is to explore the nature of icons, specifically contemporary renditions of modern or traditional icons. Colloquially, icons are a symbol of something well-known or an image that is easily recognizable. Traditionally, icons refer to religious figures, most commonly devotional paintings in Roman Catholic and Orthodox Greek churches and are used as a means of prayer to represent peace, piety and faith. However, what constitutes an icon in Western contemporary culture has changed significantly. Devotional images have been replaced by celebrities as cultural icons, relying on politicians, TV personalities, singers and even more recently TikTokers to influence our everyday life

Determinants of precocious B-cell aging in European adolescents living with perinatally acquired HIV-1 after over 10 years of suppressive therapy [preprint]

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2nd year of life and achieved virus suppression within the 1st year of ART, with majority of patient maintaining suppression until analysis and 5/40 experiencing viral Spike (transient elevation of HIV-1 VL, 50-999 copies/ml). We employed a multiomics approach including deep immunological B and T cell phenotype in PBMC, with aging B cells defined by the expression of T-bet and CD11c; plasma proteomics analysis by mass spectrometry and serum level of anti-measles antibodies as correlates of humoral response. We found that individuals with expansion of aging B cell, defined by the expression of T-bet+CD11c+, were those starting treatment later, presenting detectable levels of cell-associated HIV-1 RNA, history of Spikes, and a higher frequency of exhausted T-cells, including those expressing PD-1, LAG3, TIGIT. Accordingly, the proteomic analysis revealed that subjects with expansion of aging B cells and exhausted T cells had enrichment of proteins involved in immune inflammation and complement activation pathways, such as CLU and APCS which are also involved in tumor progression. Signs of precocious aging were associated with a reduced capacity to maintain virological memory against measles vaccination. To our knowledge, this is the first study focusing on precocious B-cell aging and dysfunctionality in PHIV with long-term virological suppression. Our experimental strategy enabled identification of clinical, viral, cellular and plasma soluble markers associated with B-cells aging. Our results pave the way to further define risk of disease progression or lymphoproliferative disorders in PHIV

Non-volcanic CO2 and CH4 degassing in an actively extending orogen, southern Apennines, Italy

The southern Apennines fold and thrust belt has been undergoing post-orogenic extension since ca. 700 kyr. Crustal extension controls active tectonics and seismogenesis in the mountain chain [1], with seismicity being characterized by low to moderate magnitude events punctuated by strong earthquakes [2]. Effective decoupling between deep and shallow structural levels is related to the strong rheological contrast produced by a fluid-saturated, clay-rich mélange zone interposed between buried autochthonous carbonates – continuous with those exposed in the Apulian foreland – and the allochthonous units. This mélange zone also acts as a seal preventing the migration of deep-seated aqueous fluids – as well as oil in the Basilicata region, which hosts the largest Europe’s onshore oil fields – towards the surface. On the other hand, the mountain belt is characterized by substantial gas flow, recorded as both distributed soil gas emissions and vigorous gas vents, associated with active faults at the surface. We measured a CO2 flux up to 34000 g/m-2 per day at a gas vent, as well as large amounts of He (up to 52 ppm), Rn (up to 228 kBq/m3) and CH4 (up to 5000 ppm). Overpressured CO2, which has been proposed as triggering normal fault earthquakes in the Apennines, has been interpreted as mostly of mantle origin. However, our new results from isotope analyses carried out on the carbon contained in both CO2 and CH4 indicate a dominant thermogenic origin for these gases, probably associated with the emplacement of magmatic sills within the lower section of the thick carbonate platform succession occurring at the base of the sedimentary cover in the southern Apennines. Our results bear major implication concerning the postulated occurrence of crustal faults allowing fluids to migrate directly from mantle depths to the surface

Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1). Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts. Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission

Blood CXCR3(+) CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals

We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investi-gated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment con-taining inducible replication competent virus in treated aviremic HIV-infected individuals

Targeted protein degradation tools: overview and future perspectives

Targeted protein inactivation (TPI) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. These systems act in a reversible manner and reduce off-target effects exceeding the limitations of CRISPR/Cas9 and RNA interference, respectively. Several TPI have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. However, unlike chemical tools such as PROTACs (PROteolysis TArgeting Chimeras), which work in a wild-type genomic background, TPI technologies require adding an aminoacidic signal sequence (tag) to the protein of interest (POI). On the other hand, the design and optimization of PROTACs are very laborious and time-consuming. In this review, we focus on anchor-away, deGradFP, auxin-inducible degron (AID) and dTAG technologies and discuss their recent applications and advances. Finally, we propose nano-grad, a novel nanobody-based protein degradation tool, which specifically proteolyzes endogenous tag-free target protein

Intervista a Derrick de Kerckhove

Questa che presentiamo è la trascrizione e rielaborazione di un’intervista che è cominciata il 19 novembre 2014 presso l’Università di Napoli Federico II ed è continuata ‘virtualmente’ tramite lo scambio di e-­‐‑mail. La conversazione iniziale, già di per sé stimolante e ricca di spunti, si è quindi ampliata ulteriormente grazie alle risposte e agli approfondimenti che Derrick De Kerckhove ci ha ancora gentilmente offerto. Emblematiche della sua generosità intellettuale ci sembrano le parole con cui ha voluto chiudere l’intervista e che ci piace riportare qui in apertura: «Ritengo l’intervista uno dei modi di fare ricerca tra i più intelligenti e interessanti che esistano. Mi fa pensare a cose nuove. È davvero una forma di ‘intelligenza connettiva’, e permette di fare ottime riflessioni. È una bella sfida»

Measuring the Success of HIV-1 Cure Strategies

HIV-1 eradication strategies aim to achieve viral remission in the absence of antiretroviral therapy (ART). The development of an HIV-1 cure remains challenging due to the latent reservoir (LR): long-lived CD4 T cells that harbor transcriptionally silent HIV-1 provirus. The LR is stable despite years of suppressive ART and is the source of rebound viremia following therapy interruption. Cure strategies such as "shock and kill" aim to eliminate or reduce the LR by reversing latency, exposing the infected cells to clearance via the immune response or the viral cytopathic effect. Alternative strategies include therapeutic vaccination, which aims to prime the immune response to facilitate control of the virus in the absence of ART. Despite promising advances, these strategies have been unable to significantly reduce the LR or increase the time to viral rebound but have provided invaluable insight in the field of HIV-1 eradication. The development and assessment of an HIV-1 cure requires robust assays that can measure the LR with sufficient sensitivity to detect changes that may occur following treatment. The viral outgrowth assay (VOA) is considered the gold standard method for LR quantification due to its ability to distinguish intact and defective provirus. However, the VOA is time consuming and resource intensive, therefore several alternative assays have been developed to bridge the gap between practicality and accuracy. Whilst a cure for HIV-1 infection remains elusive, recent advances in our understanding of the LR and methods for its eradication have offered renewed hope regarding achieving ART free viral remission