24 research outputs found
Periodic and Quasiperiodic Motion of an Elongated Microswimmer in Poiseuille Flow
We study the dynamics of a prolate spheroidal microswimmer in Poiseuille flow
for different flow geometries. When moving between two parallel plates or in a
cylindrical microchannel, the swimmer performs either periodic swinging or
periodic tumbling motion. Although the trajectories of spherical and elongated
swimmers are qualitatively similar, the swinging and tumbling frequency
strongly depends on the aspect ratio of the swimmer. In channels with reduced
symmetry the swimmers perform quasiperiodic motion which we demonstrate
explicitely for swimming in a channel with elliptical cross section
Active Brownian Particles. From Individual to Collective Stochastic Dynamics
We review theoretical models of individual motility as well as collective
dynamics and pattern formation of active particles. We focus on simple models
of active dynamics with a particular emphasis on nonlinear and stochastic
dynamics of such self-propelled entities in the framework of statistical
mechanics. Examples of such active units in complex physico-chemical and
biological systems are chemically powered nano-rods, localized patterns in
reaction-diffusion system, motile cells or macroscopic animals. Based on the
description of individual motion of point-like active particles by stochastic
differential equations, we discuss different velocity-dependent friction
functions, the impact of various types of fluctuations and calculate
characteristic observables such as stationary velocity distributions or
diffusion coefficients. Finally, we consider not only the free and confined
individual active dynamics but also different types of interaction between
active particles. The resulting collective dynamical behavior of large
assemblies and aggregates of active units is discussed and an overview over
some recent results on spatiotemporal pattern formation in such systems is
given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely
SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease
One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials
Identification of Surface Exposed Elementary Body Antigens of Cowdria ruminantium the Causative Agent of Cowdriosis in Ruminants
This study sought to identify the surface exposed antigenic components of Cowdria ruminantium elementary body (EB) by biotin labeling, determine effect of reducing and non-reducing conditions and heat on the mobility of these antigens and their reactivity to antibodies from immunized animals by Western blotting. Six surface exposed antigens of the C. ruminantium EB were identified by biotin labeling with molecular masses of 21kDa, 28kDa, 31kDa, 62kDa, 74kDa and 115kDa and are therefore outer membrane proteins. The effect of reducing agents was to increase the number antigens bands, indicating there may be 2-5 antigenic (polypeptides) on the surface of the EB. On the other hand, heating did not affect the number of antigen bands. The identification of six surface exposed antigens of C. ruminantium and the successful purification of two of these antigens, makes it possible to use them for immunization so as to determine which of them induce protective responses.
Keywords: Cowdria ruminantium, Elementary body, biotin-labelling, surface antigens, mobilities, ruminants
[IJARD Vol.3 2002: 78-86
Expression by Lawsonia intracellularis of type III secretion system components during infection
Contact-dependent secretion systems, such as the type 111 secretion system (T3SS), have been shown to play significant roles in the pathogenicity of many Gram-negative bacterial pathogens. Lawsonia intracellularis is a novel, obligate intracellular Gram-negative bacterium, which has been identified as the etiological agent of proliferative enteropathies in numerous animal species. Analysis of the genome sequence of the L intracellularis strain PHE/MN1-00 has revealed the presence of a T3SS secretion system in this bacterium. In this study we aimed to determine whether this important virulence mechanism is also present in L intracellularis strain LR189/5/83. Using a PCR-based approach, we verified the presence of a genomic region encoding a T3SS. Specifically, a gene highly homologous to the yscN energiser component of the prototypic T3SS of Yersinia spp. was identified and termed lscN. Two further open reading frames (ORFs) contiguous with lscN were also identified: lscO and lscQ, which are also homologues of ORFs within the T3SS of Yersinia spp. To establish whether this T3SS may be functional, expression was monitored directly by RT-PCR and indirectly by detection of serological responses in vaccinated and infected animals. Transcripts for lscN and lscQ were detected and purified rLscQ was recognized by antiserum from infected pigs, indicating expression in vivo during infection. By analogy to other bacteria, this T3SS may be crucial for intracellular development and is likely to play a significant role in the virulence of this unusual pathogen