The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon‐induced protein that forms ...parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS‐CoV‐2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS‐CoV‐2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS‐CoV‐2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS‐CoV‐2 and highlight the multiple distinct mechanisms by which SARS‐CoV‐2 subverts tetherin function.
Synopsis
The anti‐viral restriction factor Tetherin blocks the egress of SARS‐CoV‐2. Expression of ORF3a and Spike protein antagonises tetherin to allow SARS‐CoV‐2 escape.
Tetherin loss aids SARS‐CoV‐2 viral spread.
SARS‐CoV‐2 ORF3a alters tetherin localization by impairing retrograde traffic and enhances virus release.
SARS‐CoV‐2 Spike causes tetherin downregulation.
The anti‐viral restriction factor Tetherin blocks the egress of SARS‐CoV‐2. Expression of ORF3a and Spike protein antagonises tetherin to allow SARS‐CoV‐2 escape.
Modern data analysis methods, such as optimization algorithms or deep learning have been successfully applied to a number of biotechnological and medical questions. For these methods to be efficient, ...a large number of high-quality and reproducible experiments needs to be conducted, requiring a high degree of automation. Here, we present an open-source hardware and low-cost framework that allows for automatic high-throughput generation of large amounts of cell biology data. Our design consists of an epifluorescent microscope with automated XY stage for moving a multiwell plate containing cells and a perfusion manifold allowing programmed application of up to eight different solutions. Our system is very flexible and can be adapted easily for individual experimental needs. To demonstrate the utility of the system, we have used it to perform high-throughput Ca
imaging and large-scale fluorescent labeling experiments.
B.1.1.7 lineage SARS-CoV-2 is more transmissible, leads to greater clinical severity, and results in modest reductions in antibody neutralization. Subgenomic RNA (sgRNA) is produced by discontinuous ...transcription of the SARS-CoV-2 genome. Applying our tool (periscope) to ARTIC Network Oxford Nanopore Technologies genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA is significantly increased in B.1.1.7 (alpha) infections (n = 879). This increase is seen over the previous dominant lineage in the UK, B.1.177 (n = 943), which is independent of genomic reads, E cycle threshold and days since symptom onset at sampling. A noncanonical sgRNA which could represent ORF9b is found in 98.4% of B.1.1.7 SARS-CoV-2 infections compared with only 13.8% of other lineages, with a 16-fold increase in median sgRNA abundance. We demonstrate that ORF9b protein levels are increased 6-fold in B.1.1.7 compared to a B lineage virus in vitro. We hypothesise that increased ORF9b in B.1.1.7 is a direct consequence of a triple nucleotide mutation in nucleocapsid (28280:GAT > CAT, D3L) creating a transcription regulatory-like sequence complementary to a region 3' of the genomic leader. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles to evaluate emerging potential variants of concern.
Background
Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disabilities with unknown etiology. Recent studies suggest the contribution of immune dysfunction and oxidative stress in ...its pathophysiology. The present study aimed to investigate the serum level of thioredoxin (Trx), as a marker of oxidative stress and some inflammatory cytokines, and to evaluate their role in children with ASD.
Results
Concentrations of Trx, IL-1β, IL-8, and TNF-α were significantly higher in children with ASD compared with matched controls. There were no association between cytokine levels and the severity of clinical manifestations, according to CARS classification of severity.
Conclusion
The present study provides support for the idea that physiological abnormalities, such as oxidative stress and immune dysfunction, may contribute in the pathophysiology of ASD.
The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains ...underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity. Sensitivity for SARS-CoV-2 seroprevalence was enhanced when N and M IgG detection was combined. These findings indicate that screening for M seroconversion may be a good approach for detecting additional vaccine breakthrough infections and highlight the potential to use HCM as a rapidly deployable method to identify the most immunogenic targets of newly emergent pathogens.
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•HCM can detect SARS-CoV-2 N and S IgG responses with high specificity and sensitivity•SARS-CoV-2 M antibodies are a third high seroprevalence marker (85% of patients with COVID-19)•Anti-M IgG often displays a shallower time-dependent decline than N IgG post infection•Screening for SARS-CoV-2 M antibodies alongside N can boost serological sensitivity
Biological sciences; Immunology; Microbiology; Cell biology
In developing countries, toxic heavy metals are a threatening catastrophe to human health, particularly in the vulnerable group of pregnant mothers and their fetuses. Fortunately, the placenta can be ...a protective barrier to the fetuses.
To explore the relationship between serum lead, cadmium and arsenic levels in pregnant mothers and their newborns, to address the placental barrier in this situation.
A cross-sectional study was conducted on 100 pregnant mothers at the time of labour and their newborns. Serum cadmium, lead, and arsenic levels were measured using the Inductively Coupled Plasma Mass Spectrometry.
All the studied heavy metals concentrations showed a significant elevation in the maternal blood relative to the cord blood. There was a significant association between the maternal lead and both fetal lead and arsenic. Meanwhile, a negative but insignificant correlation was recorded between the maternal cadmium and each of the fetal cadmium, lead, and arsenic.
The study findings indicated a weak relation between maternal and fetal blood heavy metals, except for the influence of maternal lead, so it can be assumed that the placental barriers are partially protective against those toxic pollutants, putting into consideration the influence of their different natures.
A potential and cost-effective treatment method utilizing thermally activated bentonite was evaluated for the treatment of highly loaded real petroleum processing wastewater (COD = 4500 mg/L) in ...order to reduce its COD and improve the corrosion properties. A save discharging COD limit of the treated effluent (800 mg/L) is achieved by using 6 g/L of calcinated bentonite after reaching the steady state (1 h of shaking) at pH 5. The durability of bentonite is proved. The corrosion behavior of the treated wastewater was investigated for mild steel by using electrochemical and weight loss measurements. The results proved that the corrosion rate of the wastewater was slightly reduced after the treatment process. More improvement of the corrosion resistance was achieved by adding sodium hexa-meta-phosphate (SHMP) corrosion inhibitor to the treated water. Tri-methyl ammonium bromide (CTAB) biocide was also added before discharging into municipal networks.
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•Bentonite is used for removing of hazardous organics from petroleum wastewater.•The activated bentonite was more effective than the non-activated of about 20%.•The treatment method is considered to be cost effective and reliable technology.•Durability of bentonite is proved during the treatment process.•Corrosion control of municipal pipelines is considered for treated wastewater.
This study was conducted to evaluate the effects of adding different levels of the combination of fibrolytic enzymes and probiotics (a mixture of bacteria and yeast) on the performance of fattening ...lambs. Thirty-two male Ossimi lambs (weighing 39 ± 0.24 kg) were divided into four groups randomly (eight animals each). The first group (control ration, G1) was fed on a ration of 60% concentrate feed mixture (CFM), 20% Egyptian clover (EC), and 20% wheat straw (WS). The second (G2), third (G3), and fourth (G4) groups were fed a control ration supplemented with Calfo Care
at concentrations of 0.5, 1, and 2 kg/ton diet of dry matter (DM). Results showed that the G2 and G3 rations significantly (
≤ 0.05) increased the DM, organic matter, crude protein, crude fiber, and ether extract digestibility compared with the G1 and G4 rations. Moreover, the G2 and G3 rations increased (
≤ 0.05) the percentages of total digestible nutrients (TDN), starch values (SV), and digestible crude protein (DCP) compared with the G1 and G4 rations. Both the G2 and G3 rations significantly (
≤ 0.05) increased the TDN, SV, and DCP as kg/day or g/kg w
and kg or g/100 kg body weight compared with the G1 and G4 rations. Conversely, the G1 ration significantly decreased the feed conversion of DM, TDN, SV, and DCP compared with the experimental groups. Furthermore, the G2, G3, and G4 rations significantly (
≤ 0.05) increased the total weight gain by 25.34%, 52.20%, and 3.79%, respectively, compared with the G1 ration. The G2, G3, and G4 rations also (
≤ 0.05) increased the concentrations of most hematological parameters, including triiodothyronine, total protein, albumin, and glucose, compared with the G1 ration. Finally, the best net profit was recorded with the G3 ration, followed by the G2, G4, and G1 rations.
Continuous circulation of influenza A(H5N1) virus among poultry in Egypt has created an epicenter in which the viruses evolve into newer subclades and continue to cause disease in humans. To detect ...influenza viruses in Egypt, since 2009 we have actively surveyed various regions and poultry production sectors. From August 2010 through January 2013, >11,000 swab samples were collected; 10% were positive by matrix gene reverse transcription PCR. During this period, subtype H9N2 viruses emerged, cocirculated with subtype H5N1 viruses, and frequently co-infected the same avian host. Genetic and antigenic analyses of viruses revealed that influenza A(H5N1) clade 2.2.1 viruses are dominant and that all subtype H9N2 viruses are G1-like. Cocirculation of different subtypes poses concern for potential reassortment. Avian influenza continues to threaten public and animal health in Egypt, and continuous surveillance for avian influenza virus is needed.
Avian influenza virus subtype H9N2 has been circulating in the Middle East since the 1990s. For uncertain reasons, H9N2 was not detected in Egyptian farms until the end of 2010. Circulation of H9N2 ...viruses in Egyptian poultry in the presence of the enzootic highly pathogenic H5N1 subtype adds a huge risk factor to the Egyptian poultry industry. In this study, 22 H9N2 viruses collected from 2011 to 2013 in Egypt were isolated and sequenced. The genomic signatures and protein sequences of these isolates were analyzed. Multiple mammalian-host-associated mutations were detected that favor transmission from avian to mammalian hosts. Other mutations related to virulence were also identified. Phylogenetic data showed that Egyptian H9N2 viruses were closely related to viruses isolated from neighboring Middle Eastern countries, and their HA gene resembled those of viruses of the G1-like lineage. No reassortment was detected with H5N1 subtypes. Serological analysis of H9N2 virus revealed antigenic conservation among Egyptian isolates. Accordingly, continuous surveillance that results in genetic and antigenic characterization of H9N2 in Egypt is warranted.
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