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Whereas nearly all previous observations of Cyg X-1 with good time resolution have been made when the source was in its low emission state, Ariel-6 has been fortunate to observe it during 1980 June-July mainly in its high state, i.e. with enhanced low energy emission. The fluctuations were studied on all time-scales down to 2 ms and appeared similar to those previously reported for the low state. The cross-correlation of rapid fluctuations between two bands above and below 3.5 keV however showed a small but significant asymmetry with the high energy emission delayed. [ABSTRACT FROM AUTHOR]

The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4) 2 tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9–6.8 Å resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4) 2 tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA. [Display omitted] • Cryo-EM unveils S. cerevisiae Hir complex structure with Asf1/H3/H4 • Higher-order dimer formed by Hir1/Hir2/Hir3/Hpc2 with 2/4/2/4 stoichiometry • Central cavity accommodates Hpc2-assisted histone tetramer assembly • Hir3 "Tail" supports DNA positioning for histone tetrasome formation Kim et al. reveal the molecular framework of the HIRA/Hir histone chaperone complex, unveiling its essential function in replication-independent chromatin assembly. It provides key molecular insights into histone deposition assisted by Asf1. [ABSTRACT FROM AUTHOR]

The transfusion transmission of hepatitis C and HIV to thousands of Canadian blood recipients was one of this country's largest public health catastrophes. In response to this crisis, and in an effort to prevent such a tragedy from occurring again, the Canadian blood system has undergone substantial reform. Variant Creutzfeldt-Jakob (vCJD) disease was the first infectious threat faced by the blood system since undergoing reform. The response at the time to this risk provides insights into the Canadian blood system's new approach to infectious threats. Our analysis of the decision-making concerning vCJD identifies two dominant themes characterizing the new blood system's approach to safety:1. the adoption of a precautionary approach to new risks which involves taking action in advance of definitive evidence, and2. risk aversion amongst policy makers, which has contributed to the adoption of safety measures with comparatively high cost-effectiveness ratios.Overall the principles governing the new blood system have contributed to the system both providing protection against emerging infectious risks and regaining the confidence of the public and recipients. However, the current set of policy factors will likely contribute to increasingly risk-averse policy making that will contribute to continued increases in the cost of the blood system. The challenge the blood system now faces is to find the appropriate balance between maximizing safety and ensuring the system remains affordable. [ABSTRACT FROM AUTHOR]

Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis. [ABSTRACT FROM AUTHOR]

Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) Kansas worked with 10 Kansas counties from November 2020 through June 2022 to form local health equity action teams (LHEATs), develop COVID-19 testing strategies, foster communication about COVID-19, and share best practices through a learning collaborative. Participating counties documented 693 distinct COVID-19 testing and 178 communication activities. Although the intervention was not associated with changes in the proportion of positive COVID-19 tests, LHEATs in the learning collaborative implemented new testing strategies and responded to emerging COVID-19 challenges. ( Am J Public Health . 2024;114(11):1202-1206. https://doi.org/10.2105/AJPH.2024.307771).