Protection of Cells from \u3cem\u3eAlu\u3c/em\u3e-RNA-Induced Degeneration and Inhibitors for Protecting Cells

A method of protecting a cell includes inhibiting an inflammasome, MyD88, IL-18, VDAC1, VDAC2, caspase-8, and/or NFκB of the cell. Administering an inhibitor of MyD88, IL-18, VDAC1, VDAC2, caspase-8, and/or NFκB can protect the cell from Alu-RNA-induced degeneration. Protecting a cell, such as an retinal pigment epithelium (RPE), can be therapeutically useful in the context of age-related macular degeneration and geographic atrophy

Magnetic resonance imaging in locally advanced rectal cancer : quantitative evaluation of the complete response to neoadjuvant therapy

Purpose: To assess the diagnostic performance of diffusion-weighted imaging (DWI) for the discrimination of complete responder (CR) from the non-complete responder (n-CR) in patients with locally advanced rectal cancer (LARC) undergoing chemotherapy and radiation (CRT). Material and methods: Between December 2009 and January 2014, 32 patients (33 lesions: one patient had two synchronous lesions) were enrolled in this retrospective study. All patients underwent a pre- and post-CRT conventional MRI study completed with DWI. For both data sets (T2-weighted and DWI), the pre- and post-CRT tumour volume (VT2; VDWI) and the tumour volume reduction ratio (ΔV%) were determined as well as pre- and post-CRT apparent diffusion coefficient (ADC) and ADC change (ΔADC%). Histopathological findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DWI volumetry, as well as ADC. Results: The area under the ROC curve (AUC) revealed a good accuracy of pre- and post-CRT values of VT2 (0.86; 0.91) and VDWI (0.82; 1.00) as well as those of ΔVT2% (0.84) and ΔVDWI% (1.00) for the CR assessment, with no statistical difference. The AUC of pre- and post-CRT ADC (0.53; 0.54) and that of ΔADC% (0.58) were significantly lower. Conclusions: Both post-CRT VDWI and ΔVDWI% (AUC = 1) are very accurate for the assessment of the CR, in spite of no significant differences in comparison to the conventional post-CRT VT2 (AUC = 0.91) and ΔVT2% (AUC = 0.84). On the contrary, both ADC and ΔADC% values are not reliable

Tomografia Geoelettrica 3D ad alta risoluzione nell’area di San Gregorio Magno (SA)

Nell’ambito delle attività di ricerca del progetto “TESIRA”, in cui partecipano il Dipartimento di Scienze della Terra dell’Ambiente e delle Risorse (DISTAR) dell’Università degli Studi di Napoli “Federico II”, l’Istituto di Scienze del Patrimonio Culturale del Consiglio Nazionale delle Ricerche CNR – ISPC e l'Istituto Nazionale di Geofisica e Vulcanologia sede di Roma (INGV), il gruppo di geofisica di Napoli dell’ISPC,ha condotto nell’area test del comune di San Gregorio Magno, SGM, (SA) un’indagine di tomografia geoelettrica 3D (ERT), per l’individuazione e la ricostruzione tridimensionale delle strutture presenti nel sottosuolo connesse con la faglia di SGM. In particolare in questo rapporto tecnico si riportano le procedure di acquisizione ed elaborazione di dati di tomografia geoelettrica 3D

Measurement of gravitational and thermal effects in a liquid-actuated torsion pendulum

We describe a proof-of-principle experiment aiming to investigate the inverse-square law of gravitation at the centimeter scale. The sensor is a two-stage torsion pendulum, while actuation is accomplished by a variable liquid mass. The time-varying gravitational force is related to the level of the circulating fluid in one or two containers at a short distance from the test mass, with all moving mechanical parts positioned at a large distance. We provide a description of the apparatus and present the first results. We identified a systematic effect of thermal origin, producing offsets of few fNm in torque and of about 10 pN in force. When this effect is neutralized, the measurements agree well with the predictions of simulations. We also discuss the upcoming instrument upgradations and the expected sensitivity improvement that will allow us to perform measurements with adequate accuracy to investigate the unexplored regions of the α−λ parameter space of a Yukawa-like deviation from the Newtonian potential

Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator

In mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary gland cells, AGO1 associates with transcriptional enhancers of estrogen receptor α (ERα) and that this association is up-regulated by treating the cells with estrogen (E2), displaying a positive correlation with the activation of these enhancers.Moreover, we show that AGO1 interacts with ERα and that this interaction is also increased by E2 treatment, but occurs in the absence of RNA. We show that AGO1 acts positively as a coactivator in estradiol-triggered transcription regulation by promoting ERα binding to its enhancers. Consistently, AGO1 depletion decreases long-range contacts between ERα enhancers and their target promoters. Our results point to a role of AGO1 in transcriptional regulation in human cells that is independent from small RNA binding.Fil: Gómez Acuña, Luciana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Nazer, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Rodríguez Seguí, Santiago Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Pozzi, María Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Buggiano, Valeria Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Marasco, Luciano Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Agirre, Eneritz. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: He, Cody. University of Chicago; Estados UnidosFil: Alló, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile liver inflammation. Our findings suggest that NRTIs are ripe for drug repurposing in P2X7-driven diseases

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist