Biology subjects

Marinelli, E.

Publications and source records attributed to Marinelli, E..

3 recordsLinked to original sources

bioRxiv2022

OligoArchive-DSM: Columnar Design for Error-Tolerant Database Archival using Synthetic DNA

The surge in demand for cost-effective, durable long-term archival media, coupled with density limitations of contemporary magnetic media, has resulted in synthetic DNA emerging as a promising new alternative. Today, the limiting factor for DNA-based data archival is the cost of writing (synthesis) and reading (sequencing) DNA. Newer techniques that reduce the cost often do so at the expense of reliability, as they introduce complex, technology-specific error patterns. In order to deal with such errors, it is important to design efficient pipelines that can carefully use redundancy to mask errors without amplifying overall cost. In this paper, we present OligoArchive-DSM (OA-DSM), an end-to-end DNA archival pipeline that can provide error-tolerant data storage at low read/write costs. Central to OA-DSM is a database-inspired columnar encoding technique that makes it possible to improve efficiency by enabling integrated decoding and consensus calling during data restoration.

bioengineering↗

bioRxiv2022

Blockade of TGF-β signaling reactivates HIV-1/SIV reservoirs and immune responses in vivo

Elevated levels of TGF-{beta}, a potent immunosuppressive factor, are present in HIV-1 infected individuals even after years of antiretroviral therapy (ART). TGF-{beta} plays a critical role in maintaining immune cells in a resting state by inhibiting cell activation and proliferation. Resting HIV-1 target cells represent one of the main cellular reservoirs after long term ART and the low inducibility of the latent provirus constitutes one of the major obstacles to "kick and kill" cure strategies. We hypothesized that releasing cells from TGF-{beta}-driven signaling would promote latency reversal. To test our hypothesis, we compared ex vivo models of HIV-1 latency reactivation with and without TGF-{beta} and a TGF-{beta} type 1 receptor (TGFBR1) inhibitor, galunisertib. We also tested the effect of galunisertib in SIV infected, ART treated macaques by monitoring SIV envelope (env) protein expression via PET/CT using the Cu64-anti gp120 Fab (7D3) probe, along with plasma and tissue viral loads (VL). Exogenous TGF-1{beta} reduced HIV-1 reactivation in U1 and ACH2 latency models. Galunisertib increased HIV-1 latency reversal both in ex vivo models and in PBMC from HIV-1 infected, cART treated aviremic donors. In vivo, oral galunisertib promoted increased SIV env protein total standardized uptake values (SUVtot) in PET/CT images of tissues (gut and lymph nodes) of 5 out of 7 aviremic, long-term ART-treated, SIV-infected, macaques. This increase correlated with an increase in SIV RNA in gut tissue. Two out of 7 animals also exhibited increases in plasma viral load. Higher anti-SIV T cell responses and anti-SIV env antibody titers were detected after galunisertib treatment in most animals. In summary, our data suggest that blocking TGF-{beta} signaling simultaneously increases retroviral reactivation events and enhances anti-SIV immune responses.

immunology↗

bioRxiv2021

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to be more common in the elderly, who show also more severe symptoms and a higher risk of hospitalization and death. Here we show that the expression of the Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV2 cell receptor, increases during aging in mouse and human lungs, and following telomere shortening or dysfunction in mammalian cells and in mouse models. This increase is regulated at the transcription level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Indeed, ATM inhibition or the selective inhibition of telomeric DDR, through the use of antisense oligonucleotides, prevents Ace2 upregulation following telomere damage, in cultured cells and in mice. We propose that during aging telomeric shortening, by triggering DDR activation, causes the upregulation of ACE2, the SARS-CoV2 cell receptor, thus making the elderly likely more susceptible to the infection.

cell biology↗