38 research outputs found
Ambiguities in the partial-wave analysis of pseudoscalar-meson photoproduction
Ambiguities in pseudoscalar-meson photoproduction, arising from incomplete
experimental data, have analogs in pion-nucleon scattering. Amplitude
ambiguities have important implications for the problems of amplitude
extraction and resonance identification in partial-wave analysis. The effect of
these ambiguities on observables is described. We compare our results with
those found in earlier studies.Comment: 12 pages of text. No figure
P-wave excited baryons from pion- and photo-induced hyperon production
We report evidence for , , ,
, , and , and find
indications that might have a companion state at 1970\,MeV. The
controversial is not seen. The evidence is derived from a
study of data on pion- and photo-induced hyperon production, but other data are
included as well. Most of the resonances reported here were found in the
Karlsruhe-Helsinki (KH84) and the Carnegie-Mellon (CM) analyses but were
challenged recently by the Data Analysis Center at GWU. Our analysis is
constrained by the energy independent scattering amplitudes from either
KH84 or GWU. The two amplitudes from KH84 or GWU, respectively, lead to
slightly different branching ratios of contributing resonances but the
debated resonances are required in both series of fits.Comment: 22 pages, 28 figures. Some additional sets of data are adde
A chromosome-level Amaranthus cruentus genome assembly highlights gene family evolution and biosynthetic gene clusters that may underpin the nutritional value of this traditional crop
Traditional crops historically provided accessible and affordable nutrition to millions of rural dwellers but have been neglected, with most modern agricultural systems over reliant on a small number of internationally-traded crops. Traditional crops are typically well-adapted to local agro-ecological conditions and many are nutrient-dense. They can play a vital role in local food systems through enhanced nutrition (especially where diets are dominated by starch crops), food security and livelihoods for smallholder farmers, and a climate-resilient and biodiverse agriculture. Using short-read, long-read and phased sequencing technologies we generated a high-quality chromosome-level genome assembly for Amaranthus cruentus, an under-researched crop with micronutrient- and protein-rich leaves and gluten-free seed, but lacking improved varieties, with respect to productivity and quality traits. The 370.9 MB genome demonstrates a shared whole genome duplication with a related species, Amaranthus hypochondriacus. Comparative genome analysis indicates chromosomal loss and fusion events following genome duplication that are common to both species, as well as fission of chromosome 2 in A. cruentus alone, giving rise to a haploid chromosome number of 17 (versus 16 in A. hypochondriacus). Genomic features potentially underlying the nutritional value of this crop include two A. cruentus-specific genes with a likely role in phytic acid synthesis (an anti-nutrient), expansion of ion transporter gene families, and identification of biosynthetic gene clusters conserved within the amaranth lineage. The A. cruentus genome assembly will underpin much-needed research and global breeding efforts to develop improved varieties for economically viable cultivation and realisation of the benefits to global nutrition security and agrobiodiversity
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
High-quality chromosome-scale assembly of the walnut (Juglans regia L.) reference genome
The release of the first reference genome of walnut (Juglans regia L.) enabled many achievements in the
characterization of walnut genetic and functional variation. However, it is highly fragmented, preventing the integration of
genetic, transcriptomic, and proteomic information to fully elucidate walnut biological processes. Findings: Here, we report
the new chromosome-scale assembly of the walnut reference genome (Chandler v2.0) obtained by combining Oxford
Nanopore long-read sequencing with chromosome conformation capture (Hi-C) technology. Relative to the previous
reference genome, the new assembly features an 84.4-fold increase in N50 size, with the 16 chromosomal pseudomolecules
assembled and representing 95% of its total length. Using full-length transcripts from single-molecule real-time sequencing,
we predicted 37,554 gene models, with a mean gene length higher than the previous gene annotations. Most of the new
protein-coding genes (90%) present both start and stop codons, which represents a significant improvement compared with
Chandler v1.0 (only 48%). We then tested the potential impact of the new chromosome-level genome on different areas of
walnut research. By studying the proteome changes occurring during male flower development, we observed that the
virtual proteome obtained from Chandler v2.0 presents fewer artifacts than the previous reference genome, enabling the
identification of a new potential pollen allergen in walnut. Also, the new chromosome-scale genome facilitates in-depth
studies of intraspecies genetic diversity by revealing previously undetected autozygous regions in Chandler, likely resulting
from inbreeding, and 195 genomic regions highly differentiated between Western and Eastern walnut cultivars. Conclusion:
Overall, Chandler v2.0 will serve as a valuable resource to better understand and explore walnut biology
Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms
Inhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90α N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition. We have also determined the first structure of the N-terminal domain of HSP90β, complexed with PU3. The structures allow a detailed rationale to be developed for the observed affinity of the PU3 class of compounds for HSP90 and also provide a structural framework for design of compounds with improved binding affinity and drug-like properties