21 research outputs found
Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions
While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk
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
Temperature and hypoxia tolerance of selected fishes from a hyperthermal rockpool in the dry Tortugas, with notes on diversity and behavior
We documented the physical habitat characteristics and fish diversity of a hyperthermal rockpool on Loggerhead Key in the Dry Tortugas National Park during July 2000. Rockpool temperatures ranged from 30.5 °C to 35.8 °C and oxygen varied from 6.4 to 3.5 mg/L depending on depth and time of day. Seven fish species from five families inhabited the rockpool. Critical thermal maxima (CTMax) and critical oxygen minima (COM) were measured for three species. French grunt Haemulon flavolineatum was the most temperature tolerant fish (CTMax = 37.9 °C), followed by cocoa damselfish Pomacentrus variabilis (36.1 °C), and white mullet Mugil curema (35.0 °C), respectively. Cocoa damselfish were more tolerant of hypoxic conditions (COM = 0.8 mg/L) than either French grunt (1.2 mg/L) or white mullet (1.5 mg/L). French grunt and cocoa damselfish resorted to aquatic surface respiration at respective dissolved oxygen levels of 2.6 and 1.7 mg/L, whereas white mullet did not display this behavior at oxygen concentrations as low as 1.5 mg/L. High-temperature and low-oxygen responses of the three species were not exceptional, suggesting that behavior and not physiology is the major factor allowing Loggerhead Key fishes to exploit hyperthermal habitats
Temperature and hypoxia tolerance of selected fishes from a hyperthermal rockpool in the dry Tortugas, with notes on diversity and behavior
We documented the physical habitat characteristics and fish diversity of a hyperthermal rockpool on Loggerhead Key in the Dry Tortugas National Park during July 2000. Rockpool temperatures ranged from 30.5 °C to 35.8 °C and oxygen varied from 6.4 to 3.5 mg/L depending on depth and time of day. Seven fish species from five families inhabited the rockpool. Critical thermal maxima (CTMax) and critical oxygen minima (COM) were measured for three species. French grunt Haemulon flavolineatum was the most temperature tolerant fish (CTMax = 37.9 °C), followed by cocoa damselfish Pomacentrus variabilis (36.1 °C), and white mullet Mugil curema (35.0 °C), respectively. Cocoa damselfish were more tolerant of hypoxic conditions (COM = 0.8 mg/L) than either French grunt (1.2 mg/L) or white mullet (1.5 mg/L). French grunt and cocoa damselfish resorted to aquatic surface respiration at respective dissolved oxygen levels of 2.6 and 1.7 mg/L, whereas white mullet did not display this behavior at oxygen concentrations as low as 1.5 mg/L. High-temperature and low-oxygen responses of the three species were not exceptional, suggesting that behavior and not physiology is the major factor allowing Loggerhead Key fishes to exploit hyperthermal habitats
Three-dimensional structure of Mycoplasma pneumoniae's attachment organelle and a model for its role in gliding motility
Impacts of Argentine ants on mealybugs and their natural enemies in California’s coastal vineyards
Understanding Social Loafing: The Role of Justice Perceptions and Exchange Relationships
Quand les attitudes au travail sont tributaires de la progression de carrière: analyse dans le cadre de la modernisation de la gestion des ressources humaines
AACR calls on congress to take immediate action against COVID-19 and protect patients with cancer during the pandemic
On March 30, 2020, the AACR Board of Directors provided a letter to the U.S. Congressional leadership on behalf of its members in response to the COVID-19 public health emergency.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe