FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB.

In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of GpsB, which adopts an atypical, asymmetric dimer, and demonstrates major conformational flexibility that can be mapped to a hinge region formed by a three-residue insertion exclusive to .

Naturally Occurring Mutations of SARS-CoV-2 Main Protease Confer Drug Resistance to Nirmatrelvir.

The SARS-CoV-2 main protease (M) is the drug target of Pfizer's oral drug nirmatrelvir. The emergence of SARS-CoV-2 variants with mutations in M raised the alarm of potential drug resistance. To identify potential clinically relevant drug-resistant mutants, we systematically characterized 102 naturally occurring M mutants located at 12 residues at the nirmatrelvir-binding site, among which 22 mutations in 5 residues, including S144M/F/A/G/Y, M165T, E166 V/G/A, H172Q/F, and Q192T/S/L/A/I/P/H/V/W/C/F, showed comparable enzymatic activity to the wild-type (/ < 10-fold change) while being resistant to nirmatrelvir ( > 10-fold increase).

Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir.

Unlabelled: The SARS-CoV-2 main protease (M ) is the drug target of Pfizer’s oral drug Paxlovid. The emergence of SARS-CoV-2 variants with mutations in M raised the alarm of potential drug resistance. In this study, we identified 100 naturally occurring M mutations located at the nirmatrelvir binding site, among which 20 mutants, including S144M/F/A/G/Y, M165T, E166G, H172Q/F, and Q192T/S/L/A/I/P/H/V/W/C/F, showed comparable enzymatic activity to the wild-type (k /K <10-fold change) and resistance to nirmatrelvir (K >10-fold increase).

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets.

The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g., cough, bronchospasm).

Pathways to 'recovery' and social reintegration: The experiences of long-term clients of methadone maintenance treatment in an Irish drug treatment setting.

Introduction: This paper examines the experiences of long-term clients of methadone maintenance treatment (MMT) in one area of Dublin in the context of a recent emphasis on rehabilitation and recovery in Irish drug policy.

Methods: In-depth qualitative interviews were conducted with 25 long-term clients of methadone maintenance treatment (MMT). All participants had first enrolled in methadone treatment at least ten years prior to participating in the research and a majority (n = 16) had first accessed MMT more than 20 years previously.

Identification and Characterization of an Amine Oxidase that Detoxifies Intact Fumonisins.

Fumonisin contamination of maize damaged by and related species is a major problem when it is grown under warm and dry conditions. Consumption of fumonisin contaminated food and feed is harmful to both humans and livestock. Novel tools for reducing or eliminating fumonisin toxicity may be useful to the agri-feed sector to deal with this worldwide problem.

AIDS, Sexual Health, and the Catholic Church in 1980s Ireland: A Public Health Paradox?

Our aim was to explore the paradoxical role of the Catholic Church during the early AIDS era in establishing a policy network committed to the principles of public health, even in instances in which these principles contradicted Catholic moral teaching. This article is rooted in a study that explored the transformational effects of AIDS on Irish sexual health policy during the initial decade of the epidemic; that is, as it unfolded in Ireland between 1982 and 1992. Our source material, consisting of 20 documents that had been unexplored for more than 25 years, was obtained from the Dublin AIDS Alliance Ltd.

Coolmine Therapeutic Community, Dublin: a 40-year history of Ireland's first voluntary drug treatment service.

Aim: To document the evolution over 40 years (from 1973 to 2013) of Coolmine Therapeutic Community (Ireland's first voluntary drug treatment service) against a background of broader drug policy developments in the Republic of Ireland and elsewhere during this period.

Methods: Data were gathered by means of archival research within Coolmine, complemented by semi-structured interviews with former clients, current and former Coolmine management and staff, and representatives of outsider stakeholder interests.

Results: Coolmines's history has three phases: (1) an early and uncontentious phase, in which external authorities provided financial support for Coolmine without questioning its work practices or outcomes; (2) a middle, controversial phase, in which Coolmine struggled for survival in an external policy environment now dominated by harm reduction strategies; and (3) a final phase in which, through the use of conventional corporate governance, Coolmine management sought to repair its damaged reputation by introducing evidence-based clinical practices.

Oxytetracycline interactions at the soil-water interface: effects of environmental surfaces on natural transformation and growth inhibition of Azotobacter vinelandii.

The mechanism of oxytetracycline (OTC) adsorption to a silty clay loam soil was investigated using sorption isotherm experiments, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction spectroscopy (XRD). Sorption data fit well to a cation-exchange capacity sorption model. Spectroscopic data indicate that the interactions between oxytetracycline and silty clay loam soil were primarily through electrostatic interactions between the protonated dimethylamino group of OTC and the negatively charged moieties on the surface of the soil.

Alcoholics Anonymous in Ireland: AA's first European experience.

Aims: To trace the evolution of Alcoholics Anonymous in Ireland from its establishment there in 1946, focusing on the efforts of early members to publicize the fellowship and negotiate a role for themselves in relation to existing religious and healthcare institutions.

Methods: Archival research, drawing mainly on primary sources in AA archives in New York and Dublin.

Results: Anticipated tensions between this fellowship, which had its roots in Evangelical Protestantism, and the politically powerful Roman Catholic Church in Ireland were skillfully avoided; initial hostility from the medical profession quickly dissipated; and AA distanced itself from policy debate on the wider topic of alcoholism as disease.

Cocaine use in Europe - a multi-centre study: patterns of use in different groups.

Aim: The study investigates patterns of cocaine powder and crack cocaine use of different groups in nine European cities.

Design, Setting, Participants: Multi-centre cross-sectional study conducted in Barcelona, Budapest, Dublin, Hamburg, London, Paris, Rome, Vienna, and Zurich. Data were collected by structured face-to-face interviews.