Structures of two fimbrial adhesins, AtfE and UcaD, from the uropathogen Proteus mirabilis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146321/1/ayd2jb5004.pd

Master Equation for the Motion of a Polarizable Particle in a Multimode Cavity

We derive a master equation for the motion of a polarizable particle weakly interacting with one or several strongly pumped cavity modes. We focus here on massive particles with complex internal structure such as large molecules and clusters, for which we assume a linear scalar polarizability mediating the particle-light interaction. The predicted friction and diffusion coefficients are in good agreement with former semiclassical calculations for atoms and small molecules in weakly pumped cavities, while the current rigorous quantum treatment and numerical assessment sheds a light on the feasibility of experiments that aim at optically manipulating beams of massive molecules with multimode cavities.Comment: 30 pages, 5 figure

Structural basis for Acinetobacter baumannii biofilm formation

Acinetobacter baumannii-a leading cause of nosocomial infections-has a remarkable capacity to persist in hospital environments and medical devices due to its ability to form biofilms. Biofilm formation is mediated by Csu pili, assembled via the "archaic" chaperone-usher pathway. The X-ray structure of the CsuC-CsuE chaperone-adhesin preassembly complex reveals the basis for bacterial attachment to abiotic surfaces. CsuE exposes three hydrophobic finger-like loops at the tip of the pilus. Decreasing the hydrophobicity of these abolishes bacterial attachment, suggesting that archaic pili use tip-fingers to detect and bind to hydrophobic cavities in substrates. Antitip antibody completely blocks biofilm formation, presenting a means to prevent the spread of the pathogen. The use of hydrophilic materials instead of hydrophobic plastics in medical devices may represent another simple and cheap solution to reduce pathogen spread. Phylogenetic analysis suggests that the tip-fingers binding mechanism is shared by all archaic pili carrying two-domain adhesins. The use of flexible fingers instead of classical receptor-binding cavities is presumably more advantageous for attachment to structurally variable substrates, such as abiotic surfaces

A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid α-synuclein (αSyn), we reveal that colonization with curli-producing Escherichia coli promotes αSyn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate αSyn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. We propose that exposure to microbial amyloids in the gastrointestinal tract can accelerate αSyn aggregation and disease in the gut and the brain

Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD)? protocol for a feasibility randomised controlled trial

Introduction: Heavy drinkers in contact with alcohol services do not routinely have access to testing to establish the severity of potential liver disease. Transient elastography by FibroScan can provide this information. A recent systematic review suggested providing feedback to patients based on markers of liver injury can be an effective way to reduce harmful alcohol intake. This randomised control trial (RCT) aims to establish the feasibility of conducting a larger national trial to test the effectiveness of FibroScan advice and Alcohol Recovery Video Stories (ARVS) in changing high-risk drinking behaviour in community alcohol services common to UK practice.Methods and analysis: This feasibility trial consists of three work packages (WP). WP1: To draft a standardised script for FibroScan operators to deliver liver disease-specific advice to eligible participants having FibroScan. WP2: To create a video library of ARVS for use in the feasibility RCT (WP3). WP3: To test the feasibility of the trial design, including the FibroScan script and video stories developed in WP1 and WP2 in a one-to-one individual randomised trial in community alcohol services. Semi-structured interviews will be conducted at 6 months follow-up for qualitative evaluation. Outcomes will be measures of the feasibility of conducting a larger RCT. These outcomes will relate to: participant recruitment and follow-up, intervention delivery, including the use of the Knowledge of LIver Fibrosis Affects Drinking trial FibroScan scripts and videos, clinical outcomes, and the acceptability and experience of the intervention and trial-related procedures. Data analysis will primarily be descriptive to address the feasibility aims of the trial. All proposed analyses will be documented in a Statistical Analysis Plan.Ethics and dissemination: This trial received favourable ethical approval from the West of Scotland Research Ethics Service (WoSRES) on 20 January 2021, REC reference: 20/WS/0179. Results will be submitted for publication to a peer-reviewed journal.Trial registration number ISRCTN16922410

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Characteristics of alcohol recovery narratives: Systematic review and narrative synthesis

Background and aims Narratives of recovery from alcohol misuse have been analysed in a range of research studies. This paper aims to produce a conceptual framework describing the characteristics of alcohol misuse recovery narratives that are in the research literature, to inform the development of research, policy, and practice. Methods Systematic review was conducted following PRISMA guidelines. Electronic searches of databases (Ovid MEDLINE, EMBASE, CINHAL, PsychInfo, AMED and SCOPUS), grey literature, and citation searches for included studies were conducted. Alcohol recovery narratives were defined as “first-person lived experience accounts, which includes elements of adversity, struggle, strength, success, and survival related to alcohol misuse, and refer to events or actions over a period of time”. Frameworks were synthesised using a three-stage process. Sub-group analyses were conducted on studies presenting analyses of narratives with specific genders, ages, sexualities, ethnicities, and dual diagnosis. The review was prospectively registered (PROSPERO CRD42021235176). Results 32 studies were included (29 qualitative, 3 mixed-methods, 1055 participants, age range 17-82years, 52.6% male, 46.4% female). Most were conducted in the United States (n = 15) and Europe (n = 11). No included studies analysed recovery narratives from lower income countries. Treatment settings included Alcoholic Anonymous (n = 12 studies), other formal treatment, and ‘natural recovery’. Eight principle narrative dimensions were identified (genre, identity, recovery setting, drinking trajectory, drinking behaviours, stages, spirituality and religion, and recovery experience) each with types and subtypes. All dimensions were present in most subgroups. Shame was a prominent theme for female narrators, lack of sense of belonging and spirituality were prominent for LGBTQ+ narrators, and alienation and inequality were prominent for indigenous narrators. Conclusions Review provides characteristics of alcohol recovery narratives, with implications for both research and healthcare practice. It demonstrated knowledge gaps in relation to alcohol recovery narratives of people living in lower income countries, or those who recovered outside of mainstream services