A large number of observations from the Parkes 64 m diameter radio telescope, recorded with high time resolution, are publicly available. We have reprocessed all of the observations obtained during ...the first four years (from 1997-2001) of the Parkes Multibeam Receiver system in order to identify transient events, and have built a database that records the 568,736,756 pulse candidates generated during this search. We have discovered a new fast radio burst (FRB), FRB 010305, with a dispersion measure (DM) of 350 5 cm−3 pc and explored why so few FRBs have been discovered in data prior to 2001. After accounting for the dispersion smearing across the channel bandwidth and the sky regions surveyed, the number of FRBs is found to be consistent with model predictions. We also present five single pulse candidates from unknown sources, but with Galactic DMs. We extract a diverse range of sources from the database, which can be used, for example, as a training set of data for new software being developed to search for FRBs in the presence of radio frequency interference.
In this randomized trial involving infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth than was fresh-embryo transfer after the ...first transfer.
In vitro fertilization (IVF) is widely performed as an infertility treatment and has resulted in the births of more than 5 million infants worldwide.
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However, there are concerns about the safety of the procedures for women and for their infants.
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The ovarian hyperstimulation syndrome (which is caused by ovarian enlargement, an increase in vascular permeability and abdominal ascites, and intravascular hemoconcentration) is a potentially life-threatening complication of ovarian stimulation.
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Pregnancies conceived by means of IVF are associated with greater risks of maternal and neonatal complications, including preeclampsia, preterm delivery, low birth weight, and congenital anomalies, than are spontaneous pregnancies. . . .
Short sleep has been implicated in higher risk of obesity in humans, and is associated with insulin resistance. However, the effects of fragmented sleep (SF) rather than curtailed sleep on glucose ...homeostasis are unknown.
Wild-type and NADPH oxidase 2 (Nox2) null male mice were subjected to SF or sleep control conditions for 3 days to 3 weeks. Systemic and visceral adipose tissue (VAT) insulin sensitivity tests, glucose tolerance test, fluorescence-activated cell sorting and immunohistochemistry for macrophages and its sub-types (M1 and M2), and Nox expression and activity were examined.
Here we show that SF in the absence of sleep curtailment induces time-dependent insulin resistance, in vivo and also in vitro in VAT. Oxidative stress pathways were upregulated by SF in VAT, and were accompanied by M1 macrophage polarization. SF-induced oxidative stress, inflammation and insulin resistance in VAT were completely abrogated in genetically altered mice lacking Nox2 activity.
These studies imply that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of insulin resistance via activation of oxidative stress and inflammatory pathways, thereby opening the way for therapeutic strategies.
Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus ...disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.
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•Developed monkey CRISPR library to screen pathogenic coronaviruses in Vero-E6 cells•Screens identified genes that are SARS-CoV-2, MERS-CoV, and pan-coronavirus specific•Therapeutic targets, including SMARCA4, identified for SARS-CoV-2 infection•HMGB1 is novel regulator of ACE2 expression and critical for viral entry
To identify potential therapeutic targets for SARS-CoV-2 and related pathogenic coronaviruses, Wei et al. conduct genome-wide CRISPR screens in Vero-E6 cells using SARS-CoV-2, MERS-CoV, and pseudoviruses presenting SARS-CoV-1 or SARS-CoV-2 spike proteins. They identify pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively, and demonstrate that HMGB1 is critical for SARS lineage viral entry because it has a critical role in ACE2 expression.
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