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Craft Harrell posted an update 6 months, 3 weeks ago
Influenza viruses have an error-prone polymerase complex that facilitates a mutagenic environment. Antigenic mutants swiftly arise from this environment with the capacity to persist in both humans and economically important livestock even in the face of vaccination. Furthermore, influenza viruses can adjust the antigenicity of the haemagglutinin (HA) protein, the primary influenza immunogen, using one of four molecular mechanisms. Two prominent mechanisms are (1) enhancing binding avidity of HA toward cellular receptors to outcompete antibody binding and (2) amino acid substitutions that introduce an N-linked glycan on HA that sterically block antibody binding. In this study we investigate the impact that adsorptive mutation and N-linked glycosylation have on receptor-binding, viral fitness, and antigenicity. We utilize the H9N2 A/chicken/Pakistan/SKP-827/16 virus which naturally contains HA residue T180 that we have previously shown to be an adsorptive mutant relative to virus with T180A. We find that the addition of N-linked glycans can be beneficial or deleterious to virus replication depending on the background receptor binding avidity. We also find that in some cases, an N-linked glycan can trump the effect of an avidity enhancing substitution with respect to antigenicity. Taken together these data shed light on a potential route to the generation of a virus which is “fit” and able to overcome vaccine pressure.Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. selleckchem However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90β, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90β interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90β is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.
Placenta accreta spectrum constitutes one of the most complicated challenges in modern obstetrics. Given the conflicting data regarding the added value of MRI in the diagnosis of invasive placentation, we aim to assess individual and combined ability of multiple sonographic and MRI signs to diagnose placenta accreta spectrum in suspected cases.
We assessed 28 cases of suspected placenta accreta spectrum in the third trimester. All cases underwent ultrasound assessment as well as MRI scan. Diagnosis was confirmed during surgery. The value of sonographic and MRI signs in the detection of placenta accreta spectrum was assessed.
A total of 23 cases were diagnosed with placenta accreta spectrum during cesarean delivery. Overall, ultrasound was found to be more sensitive and specific compared to MRI (sensitivity of 0.96 and specificity of 0.6 in ultrasound vs. sensitivity of 0.83 and specificity of 0.4 in MRI). However, the use of a post-hoc structured model improved MRI performance to a similar level of ultrasound (sensitivity of 0.96 and specificity of 0.6).
Ultrasound is superior to MRI in the detection of placenta accreta spectrum. However, MRI performance can be greatly improved by the use of a structured scoring system.
Ultrasound is superior to MRI in the detection of placenta accreta spectrum. However, MRI performance can be greatly improved by the use of a structured scoring system.
The prevalence of preexisting type 2 diabetes mellitus (T2DM) in the United States is on the rise. Women of advanced maternal age (AMA, ≥35 years) are more likely to have preexisting T2DM in pregnancy because glucose intolerance increases with age. Diabetes in pregnancy is associated with significant maternal and neonatal morbidity and mortality, and earlier treatment initiation improves pregnancy outcomes. However, maternal age is not currently recognized as an independent risk factor that warrants diabetes screening prior to the traditional screen at 24-28 weeks gestation.
To evaluate the cost-effectiveness of screening all AMA women with a first trimester fasting plasma glucose (FPG) test for earlier diagnosis and management of preexisting T2DM.
A decision-analytic model was created to compare pregnancy outcomes in AMA women who undergo a first trimester FPG test vs third trimester oral glucose tolerance test alone. Probabilities were obtained from the literature. Outcomes examined included preeclamper oral glucose tolerance test alone, performing a first trimester FPG screen in AMA women is cost-saving and more effective.
Compared to third trimester oral glucose tolerance test alone, performing a first trimester FPG screen in AMA women is cost-saving and more effective.
The inhalation of air-borne toxicants is associated with adverse health outcomes which can be somewhat mitigated by enhancing endogenous anti-oxidant capacity. Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine), present in high abundance in skeletal and cardiac muscle. This multi-functional dipeptide has anti-oxidant properties, can buffer intracellular pH, chelate metals, and sequester aldehydes such as acrolein. Due to these chemical properties, carnosine may be protective against inhaled pollutants which can contain metals and aldehydes and can stimulate the generation of electrophiles in exposed tissues. Thus, assessment of carnosine levels, or levels of its acrolein conjugates (carnosine-propanal and carnosine-propanol) may inform on level of exposure and risk assessment.
We used established mass spectroscopy methods to measure levels of urinary carnosine (
= 605) and its conjugates with acrolein (
= 561) in a subset of participants in the Louisville Healthy Heart Study (mean age = 51 ± 10; 52% male).
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