14 research outputs found

    A Theoretical Model of a Molecular-Motor-Powered Pump

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    The motion of a cylindrical bead in a fluid contained within a two-dimensional channel is investigated using the boundary element method as a model of a biomolecular-motor-powered microfluidics pump. The novelty of the pump lies in the use of motor proteins (kinesin) to power the bead motion and the few moving parts comprising the pump. The performance and feasibility of this pump design is investigated using two model geometries: a straight channel, and a curved channel with two concentric circular walls. In the straight channel geometry, it is shown that increasing the bead radius relative to the channel width, increases the flow rate at the expense of increasing the force the kinesins must generate in order to move the bead. Pump efficiency is generally higher for larger bead radii, and larger beads can support higher imposed loads. In the circular channel geometry, it is shown that bead rotation modifies the force required to move the bead and that shifting the bead inward slightly reduces the required force. Bead rotation has a minimal effect on flow rate. Recirculation regions, which can develop between the bead and the channel walls, influence the stresses and force on the bead. These results suggest this pump design is feasible, and the kinesin molecules provide sufficient force to deliver pico- to atto- l/s flows.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44478/1/10544_2005_Article_6168.pd

    SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

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    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

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    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

    Fungos micorrízicos arbusculares na recuperação de florestas ciliares e fixação de carbono no solo

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    A associação micorrízica arbuscular estabelecida entre os fungos micorrízicos arbusculares (FMAs - Filo Glomeromycota) e as raízes das plantas tem papel fundamental na sobrevivência e nutrição das plantas. Nesta revisão, é salientado que a tríade floresta ciliar-fixação de carbono-fungos micorrízicos arbusculares deve ser considerada uma estratégia ambientalmente correta para recuperar áreas outrora ocupadas por florestas ciliares. São apresentadas brevemente as classes de solos que ocorrem em ambientes ripários e a entrada de carbono (C) nos ecossistemas terrestres. Posteriormente, é enfatizado que os fungos micorrízicos arbusculares possuem papel importante no processo de fixação de carbono no solo, visto seus efeitos na absorção de nutrientes pelas plantas e aumento na produção de biomassa vegetal em espécies arbóreas, principalmente espécies pioneiras e secundárias iniciais, utilizadas na recuperação de florestas ciliares. Outrossim, as hifas externas desses fungos impactam a estrutura do solo tanto fisicamente, pela ação física das hifas, como bioquimicamente, pela produção de uma glicoproteína. As estruturas diferenciadas pelos fungos, como esporos e hifas, também servem como via de entrada de C no solo, por meio de componentes celulares ricos em C. A recuperação de florestas ciliares pelo plantio de espécies arbóreas resulta na emergência de um novo serviço ambiental: a fixação de C, a qual pode ser incrementada quando no processo de recuperação seja considerada a inoculação com fungos micorrízicos arbusculares

    Persistent effects of pre-Columbian plant domestication on Amazonian forest composition

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