Selection of DNA nanoparticles with preferential binding to aggregated protein target.

High affinity and specificity are considered essential for affinity reagents and molecularly-targeted therapeutics, such as monoclonal antibodies. However, life's own molecular and cellular machinery consists of lower affinity, highly multivalent interactions that are metastable, but easily reversible or displaceable. With this inspiration, we have developed a DNA-based reagent platform that uses massive avidity to achieve stable, but reversible specific recognition of polyvalent targets. We have previously selected these DNA reagents, termed DeNAno, against various cells and now we demonstrate that DeNAno specific for protein targets can also be selected. DeNAno were selected against streptavidin-, rituximab- and bevacizumab-coated beads. Binding was stable for weeks and unaffected by the presence of soluble target proteins, yet readily competed by natural or synthetic ligands of the target proteins. Thus DeNAno particles are a novel biomolecular recognition agent whose orthogonal use of avidity over affinity results in uniquely stable yet reversible binding interactions

Natural nitration of CXCL12 reduces its signaling capacity and chemotactic activity in vitro and abrogates intra-articular lymphocyte recruitment in vivo

The chemokine CXCL12/stromal cell-derived factor-1 is important for leukocyte migration to lymphoid organs and inflamed tissues and stimulates tumor development. In vitro, CXCL12 activity through CXCR4 is abolished by proteolytic processing. However, limited information is available on in vivo effects of posttranslationally modified CXCL12. Natural CXCL12 was purified from the coculture supernatant of stromal cells stimulated with leukocytes and inflammatory agents. In this conditioned medium, CXCL12 with a nitration on Tyr(7), designated [3-NT(7)]CXCL12, was discovered via Edman degradation. CXCL12 and [3-NT(7)]CXCL12 were chemically synthesized to evaluate the biological effects of this modification. [3-NT(7)]CXCL12 recruited β-arrestin 2 and phosphorylated the Akt kinase similar to CXCL12 in receptor-transfected cells. Also the affinity of CXCL12 and [3-NT(7)]CXCL12 for glycosaminoglycans, the G protein-coupled chemokine receptor CXCR4 and the atypical chemokine receptor ACKR3 were comparable. However, [3-NT(7)]CXCL12 showed a reduced ability to enhance intracellular calcium concentrations, to generate inositol triphosphate, to phosphorylate ERK1/2 and to induce monocyte and lymphocyte chemotaxis in vitro. Moreover, nitrated CXCL12 failed to induce in vivo extravasation of lymphocytes to the joint. In summary, nitration on Tyr(7) under inflammatory conditions is a novel natural posttranslational regulatory mechanism of CXCL12 which may downregulate the CXCR4-mediated inflammatory and tumor-promoting activities of CXCL12

The EXPRES Stellar Signals Project II. State of the Field in Disentangling Photospheric Velocities

Measured spectral shifts due to intrinsic stellar variability (e.g., pulsations, granulation) and activity (e.g., spots, plages) are the largest source of error for extreme-precision radial-velocity (EPRV) exoplanet detection. Several methods are designed to disentangle stellar signals from true center-of-mass shifts due to planets. The Extreme-precision Spectrograph (EXPRES) Stellar Signals Project (ESSP) presents a self-consistent comparison of 22 different methods tested on the same extreme-precision spectroscopic data from EXPRES. Methods derived new activity indicators, constructed models for mapping an indicator to the needed radial-velocity (RV) correction, or separated out shape- and shift-driven RV components. Since no ground truth is known when using real data, relative method performance is assessed using the total and nightly scatter of returned RVs and agreement between the results of different methods. Nearly all submitted methods return a lower RV rms than classic linear decorrelation, but no method is yet consistently reducing the RV rms to sub-meter-per-second levels. There is a concerning lack of agreement between the RVs returned by different methods. These results suggest that continued progress in this field necessitates increased interpretability of methods, high-cadence data to capture stellar signals at all timescales, and continued tests like the ESSP using consistent data sets with more advanced metrics for method performance. Future comparisons should make use of various well-characterized data sets—such as solar data or data with known injected planetary and/or stellar signals—to better understand method performance and whether planetary signals are preserved

Evaluation de la prise en charge clinique et biologiques des infections à Clostridium difficile au Centre hospitalier de Valenciennes (étude rétrospective post-épidémique (2008-2010))

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Monopoly market : het gemak van online drugshandel verzilverd

Monopoly Market. Cashing in on the ease of selling drugs online The emergence of cryptomarkets has changed the way people buy and sell illicit drugs. Studying cryptomarkets provides us with unprecedented insights in both the demand and supply side, including what kind of illicit drugs people consume or how sellers respond to law enforcement activities. This article explains how Monopoly Market, a small drug cryptomarket, operates. To achieve this, a custom-built webscraper was developed to collect data on vendors, products and reviews. The results indicated that the majority of the transactions originated from the US and the UK and mainly involved domestic purchases. Cannabis-related products and synthetic drugs including (meth)amphetamine and MDMA were the most commonly sold products. Specific attention was also given to unraveling the role of COVID-19 on the functioning of Monopoly Market. The pandemic did not seem to have impacted the supply in a negative way as most packages have been delivered (on time). Yet, it created opportunities for vendors to strengthen their customer focus and marketing strategies. The results indicate that drug cryptomarkets, regardless of their size, are quite similar in their functioning although they might be less subject to fluctuations due to external conditions that disrupt their operation, such as a health pandemic. More detailed and multimethod research is however needed

Construire un système de reconnaissance de l'économie sociale en Wallonie

Ce rapport rend compte de la méthode de recherche et des principaux résultats de l'étude SECOIA commanditée par la Région Wallonne pour construire un dispositif de reconnaissance de l'économie socialeSECOI

BTN2A, a New Immune-Checkpoint Targeting Vg9Vd2 T Cell Cytotoxicity

International audienc

A prevention program for binge drinking among students based on mindfulness and implementation intention (ALCOMEDIIT): a randomized controlled trial

International audienceAbstract Background The emergence of new problematic alcohol consumption practices among young people requires new dynamics in prevention strategies. In this context, the ADUC project (Alcohol and Drugs at the University of Caen) aims to develop a better understanding of alcohol consumption, and in particular the practice of binge drinking (BD) in students, in order to develop relevant and adapted prevention tools. The ALCOMEDIIT study (Rin Normandie and IRESP funding; Agreement 20II31-00 - ADUC part 3) is a randomized controlled trial that focuses on the specific determinant of impulsivity. The main objective of this experiment is to assess a program for the prevention of BD practices based on motivational interviewing (MI) associated with implementation intention (II) and mindfulness meditation (MBM) in a student environment. Methods This study will include 170 healthy subjects who will be students at the university, alcohol users, with a BD score > 1 in the month preceding the inclusion but not presenting any specific disorder. The trial will be proposed by e-mail and students who meet the inclusion criteria will join either a control group which will benefit from a MI or an experimental group which will additionally benefit from an initiation to MBM with II (initial visit T0). In order to measure the effectiveness of the prevention program in terms of BD decrease, a follow-up at 1 month (T1) as well as a follow-up at 6 months (T6; exploratory) will be proposed to all participants. The total duration of this research protocol is 21 months. Discussion The purpose of this study is to evaluate the interest of associating mindfulness meditation practices and implementation of self-regulation strategies to optimize their use, with a motivational interview in an innovative prevention program aiming at reducing alcohol use and BD practice in the student population. Trial registration ClinicalTrials.gov Identifier: NCT05565989, September 30, 2022. https://clinicaltrials.gov/study/NCT05565989 Protocol version 2.0 (September 2022) No. ID-RCB : 2022-A00983-4