Mixed genotype hepatitis C infections and implications for treatment

No abstract available

Photon-induced proton knockout from 208Pb

No abstract available

State of the world’s plants and fungi 2020

Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity

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

Lactoferrin-induced reduction of vanB vancomycin resistance in enterococci

The mucosal protein lactoferrin (LF) reduces the MIC of vancomycin for staphylococcal isolates sensitive to this glycopeptide. The purpose of this research was to investigate the effect of LF on the MIC of vancomycin for vanB resistant isolates of Enterococcusfaecalis (Efs1) and E. faecium (Efm1). At a concentration of 2048 μg/ml, LF reduced the MIC of vancomycin 16-fold for Efs1 and eight-fold for Efm1. The cell wall precursors of Efs1 were examined following growth in media supplemented with LF, d-alanine or d-lactate. The precursors were extracted from harvested cells by ether and ion exchange chromatography and the amino acid and lactate composition was determined. Compared with that of unsupplemented media, d-alanine or LF supplementation caused an increase in the d-alanine content of the precursors. Concomitantly, the d-lactate content was reduced. Exogenous d-lactate did not affect the composition of the precursors. This suggests that LF caused an increase in the pool of pentapeptide cell wall precursors. The LF-induced reduction in the vancomycin resistance of enterococci at in vivo concentrations suggests a potential use for this protein as an adjunctive agent to vancomycin

Estimation of the titre of Mycoplasma mycoides subspecies mycoides SC vaccine strain T144 by pH and spectrophotometry

No abstract available

Interactions between the constitutive host defences of tears and Staphylococcus epidermidis

As part of the normal microbiota of the external eye, Staphylococcus epidermidis has probably developed strategies to overcome tear defences. The interaction of this bacteria with constitutive tear proteins was examined. Isolates of S. epidermidis grown in 10% serum or artificial tear fluid containing lysozyme or lactoferrin were resistant to the action of these proteins. Using ELISA, cell wall binding of C3, vitronectin and lactoferrin differed quantitatively between strains and in closed-eye compared to open-eye conditions. No differences were observed between ocular and non-ocular strains. This suggests that ocular isolates originate from the general host microbiota and S. epidermidis isolates are resistant to individual constitutive tear proteins

Susceptibility of Escherichia coli O157 and non-O157 isolates to lactate

Aims: To examine the effect of temperature on the antimicrobial efficacy of lactate and propionate against O157 and non-O157 Escherichia coli isolates. Methods and Results: Lactate and, to a lesser extent, propionate effectively reduced viability at 37 °C. Ethanol enhanced this effect. Reducing the temperature to 20 or 5 °C caused an increase in survival in the presence of these organic acids with or without ethanol. At 20 °C the ΔpH, membrane potential and intracellular lactate anion concentration were less than at 37 °C. Conclusions: The efficacy of lactate and propionate against E. coli O157 and non-O157 isolates is reduced at lower temperatures, perhaps due to the reduction in the ΔpH, membrane potential and intracellular lactate anion concentration. Significance and Impact of the Study: These findings suggest that the usefulness of organic acids as decontaminants for E. coli O157 is temperature dependent

Escherichia coli O157 and non-O157 isolates are more susceptible to L-lactate than to D-lactate

The antimicrobial effect of L-lactate was much greater than that of D-lactate over a range of concentrations for Escherichia coli O157 and non-O157 strains. Despite this, the intracellular pHs and membrane potentials of L-lactate- and D-lactate-treated cells were similar, suggesting that these factors are not involved in the antimicrobial action of L-lactate