Recreation noise in acoustic mapping

As far as most of citizens complains are about noise coming from recreational activities, usually related with the presence of people in the street around bars, pubs, parties and other activities carried out in public spaces, it seems reasonable to include this kind of noise source in the strategic noise maps, especially if the main objective of the noise mapping is to draw action plans. A methodology is proposed to analyze that kind of noise environments including short-term and long-term measurements, obtaining the acoustic indicators Ln and Lden as well as number of people exposed to those indicators. The results obtained in six different cities show that similar trends can be found for commercial streets in different cities, showing an increase of 5 dBA in Leq between 5 p.m and 8 p.m compared to the average value of Leq during the rest of day time. Night recreational noise seems more variable and an in field study must be carried out. It has also been found that around 10% of population is exposed to noise coming from commercial streets.Peer ReviewedPostprint (published version

Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

SARS-CoV-2; Inhibition; ZincSARS-CoV-2; Inhibició; ZincSARS-CoV-2; Inhibición; ZincZinc pyrithione (1a), together with its analogues 1b–h and ruthenium pyrithione complex 2a, were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent in vitro inhibition of cathepsin L (IC50=1.88 ± 0.49 µM) and PLPro (IC50=0.50 ± 0.07 µM), enzymes involved in SARS-CoV-2 entry and replication, respectively, as well as antiviral entry and replication properties in an ex vivo system derived from primary human lung tissue. Zinc complexes 1b–h expressed comparable in vitro inhibition. On the contrary, ruthenium complex 2a and the ligand pyrithione a itself expressed poor inhibition in mentioned assays, indicating the importance of the selection of metal core and structure of metal complex for antiviral activity. Safe, effective, and preferably oral at-home therapeutics for COVID-19 are needed and as such zinc pyrithione, which is also commercially available, could be considered as a potential therapeutic agent against SARS-CoV-2.The authors acknowledge the financial support from the Slovenian Research Agency ARRS [Research Core Funding No. P1-0175 together with an increase in research programme funding related to the COVID-19 pandemic], and the grant from the Health Department of the Government of Catalonia [DGRIS 1_5] and the Fundació La Marató TV3 [Grants 202104FMTV3 and 202112FMTV3] to M.G. and MJ.B. MJ.B is supported by the Miguel Servet Program funded by the Spanish Health Institute Carlos III [CP17/00179]

Entrectinib—A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells

COVID-19; Drug repurposing; Viral cell entry assaysCOVID-19; Reutilización de medicamentos; Ensayos de entrada de células viralesCOVID-19; Reutilització de medicaments; Assajos d'entrada de cèl·lules viralsSince the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug.This research was funded by the Spanish Ministry of Science, Innovation, and Universities (FPU16/01209 to M.T.-F.); the Health department of the Government of Catalonia (DGRIS 3_9 to A.P.G. and J.S. and DGRIS 1_5 to M.J.B. and M.G.)

Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1

HIV-1; Siglec-1; CervixVIH-1; Siglec-1; CèrvixVIH-1; Siglec-1; CérvixAntigen presenting cells from the cervical mucosa are thought to amplify incoming HIV-1 and spread infection systemically without being productively infected. Yet, the molecular mechanism at the cervical mucosa underlying this viral transmission pathway remains unknown. Here we identified a subset of HLA-DR+ CD14+ CD11c+ cervical DCs at the lamina propria of the ectocervix and the endocervix that expressed the type-I interferon inducible lectin Siglec-1 (CD169), which promoted viral uptake. In the cervical biopsy of a viremic HIV-1+ patient, Siglec-1+ cells harbored HIV-1-containing compartments, demonstrating that in vivo, these cells trap viruses. Ex vivo, a type-I interferon antiviral environment enhanced viral capture and trans-infection via Siglec-1. Nonetheless, HIV-1 transfer via cervical DCs was effectively prevented with antibodies against Siglec-1. Our findings contribute to decipher how cervical DCs may boost HIV-1 replication and promote systemic viral spread from the cervical mucosa, and highlight the importance of including inhibitors against Siglec-1 in microbicidal strategies

Mobilization of xanthine oxidase from the gastrointestinal tract in acute pancreatitis

BACKGROUND: Xanthine oxidoreductase has been proposed to play a role in the development of local and systemic effects of acute pancreatitis. Under physiologic conditions, the enzyme exists mainly as xanthine dehydrogenase (XDH) but can be converted by proteolytic cleavage to its superoxide-generating form xanthine oxidase (XOD). In addition to its intracellular location XDH/XOD is also associated to the polysaccharide chains of proteoglycans on the external endothelial cell membrane. In the early stages of acute pancreatitis, this enzyme seems to be arising from its mobilization from the gastrointestinal endothelial cell surface. Taking into account the ability of α-amylase to hydrolyze the internal α-1,4 linkages of polysaccharides, we wanted to elucidate the involvement of α-amylase in XDH/XOD mobilization from the gastrointestinal endothelial cell surface and the relevance of the ascitic fluid (AF) as the source of α-amylase in experimental acute pancreatitis. METHODS: Acute pancreatitis was induced in male Wistar rats by intraductal administration of 5% sodium taurocholate. In another experimental group 3000 U/Kg α-amylase was i.v. administered. The concentrations of XDH, XOD and α-amylase in plasma and AF and myeloperoxidase (MPO) in lung have been evaluated. In additional experiments, the effect of peritoneal lavage and the absorption of α-amylase present in the AF by an isolated intestine have been determined. RESULTS: Similar increase in XDH+XOD activity in plasma was observed after induction of acute pancreatitis and after i.v. administration of α-amylase. Nevertheless, the conversion from XDH to XOD was only observed in the pancreatitis group. Lung inflammation measured as MPO activity was observed only in the pancreatitis group. In addition peritoneal lavage prevented the increase in α-amylase and XDH+XOD in plasma after induction of pancreatitis. Finally, it was observed that α-amylase is absorbed from the AF by the intestine. CONCLUSIONS: During the early stages of acute pancreatitis, α-amylase absorbed from AF through the gastrointestinal tract could interfere with the binding of XDH/XOD attached to glycoproteins of the endothelial cells. Proteolytic enzymes convert XDH into its oxidase form promoting an increase in circulating XOD that has been reported to be one of the mechanisms involved in the triggering of the systemic inflammatory process

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA–positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART

Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations

CD4+ T cell; HIV-1; Latent reservoirCélula T CD4 +; VIH-1; Reservorio latenteCèl·lula T CD4 +; VIH-1; Reservori latentLatency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.This study was supported by the American National Institutes of Health (grant R21AI118411 to MJB), the Spanish Secretariat of Science and Innovation and FEDER funds (grant SAF2015-67334-R [MINECO/FEDER]), a unrestricted research grant from Bristol-Myers Squibb S.A.U (PfC-2015 AI424-564) to MJB, the Spanish "Ministerio de Economia y Competitividad, Instituto de Salud Carlos III"(ISCIII, PI17/01470) to M.G, a research grant from Gilead Sciences (GLD17-00204) to M. B, GeSIDA and the Spanish AIDS network "Red Tematica Cooperativa de Investigacion en SIDA" (RD16/0025/0007) to ER. The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179) to MJB. The "Pla estrategic de recerca i innovacioen salut" (PERIS), from the Catalan Government to MG

Adhesion Molecules Associated with Female Genital Tract Infection

Altres ajuts: Marie Curie Career Integration Grant i una beca Fundació Dexeus Salut de la DonaEfforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes

Antiviral drug candidates for entry inhibition of SARS-CoV-2

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EC50 and CC50 of 39 antiviral drug candidates

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