We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Although health care workers (HCWs) can serve as ambassadors of COVID-19 vaccine acceptance, surveys have found low acceptance rates among HCWs (eg, 33.5%). 1 However, those surveys were conducted before the issuance of vaccine emergency use authorizations (EUAs) by the US Food and Drug Administration (FDA). We surveyed all employees of a health care system on the eve of vaccine distribution to encourage them to receive a COVID-19 vaccine, assess their intentions to do so, and understand reasons for hesitancy. Methods This analysis of nonidentifiable administrative survey data did not constitute human participant research and was not subject to institutional review board approval or consent requirements, in accordance with 45 CFR §46.102(e)(1). This study follows the American Association for Public Opinion Research (AAPOR) reporting guideline. On December 4, 2020, an announcement concerning anticipated vaccine availability was emailed to all employees. The announcement contained a link to a 5-question online survey and stated that employees' time-sensitive response was needed to guide vaccine distribution. Reminders Open Access. This is an open access article distributed under the terms of the CC-BY License.

A major challenge in controlling the COVID-19 pandemic is the high false-negative rate of the commonly used RT-PCR methods for SARS-CoV-2 detection in clinical samples. Accurate detection is particularly challenging in samples with low viral loads that are below the limit of detection (LoD) of standard one- or two-step RT-PCR methods. In this study, we implemented a three-step approach for SARS-CoV-2 detection and quantification that employs reverse transcription, targeted cDNA preamplification, and nano-scale qPCR based on a commercially available microfluidic chip. Using SARS-CoV-2 synthetic RNA and plasmid controls, we demonstrate that the addition of a preamplification step enhances the LoD of this microfluidic RT-qPCR by 1000-fold, enabling detection below 1 copy/µL. We applied this method to analyze 182 clinical NP swab samples previously diagnosed using a standard RT-qPCR protocol (91 positive, 91 negative) and demonstrate reproducible and quantitative detection of SARS-CoV-2 over five orders of magnitude (<1 to 106 viral copies/µL). Crucially, we detect SARS-CoV-2 with relatively low viral load estimates (<1 to 40 viral copies/µL) in 17 samples with negative clinical diagnosis, indicating a potential false-negative rate of 18.7% by clinical diagnostic procedures. In summary, this three-step nano-scale RT-qPCR method can robustly detect SARS-CoV-2 in samples with relatively low viral loads (<1 viral copy/µL) and has the potential to reduce the false-negative rate of standard RT-PCR-based diagnostic tests for SARS-CoV-2 and other viral infections.

Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus,-actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of-actin in osteogenesis,-actin wild-type (WT) and-actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast-like cells using small molecules in vitro. It is discovered that loss of-actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for-actin in osteogenic reprogramming through a mitochondria-based mechanism that controls cell-mediated mineralization is proposed.

In the eukaryotic cell nucleus, cytoskeletal proteins are emerging as essential players in nuclear function. In particular, actin regulates chromatin as part of ATP-dependent chromatin remodeling complexes, it modulates transcription and it is incorporated into nascent ribonucleoprotein complexes, accompanying them from the site of transcription to polyribosomes. The nuclear actin pool is undistinguishable from the cytoplasmic one in terms of its ability to undergo polymerization and it has also been implicated in the dynamics of chromatin, regulating heterochromatin segregation at the nuclear lamina and maintaining heterochromatin levels in the nuclear interiors. One of the next frontiers is, therefore, to determine a possible involvement of nuclear actin in the functional architecture of the cell nucleus by regulating the hierarchical organization of chromatin and, thus, genome organization. Here, we discuss the repertoire of these potential actin functions and how they are likely to play a role in the context of cellular differentiation. ARTICLE HISTORY

A single crystal of the cis-dimer of nitrosobenzene was directly observed by photocrystallography to transition to a pair of monomers and reversibly redimerize. The remarkable displacement of the nitrogen atoms within the crystalmoving a total distance of 2.97(5) Å for the two atomssuggests that the breadth of solid-state photochemical reaction systems susceptible to X-ray diffraction studies need not be limited to those with very small atomic displacements.

Healthcare workers (HCWs) have been recommended to receive first priority for limited COVID-19 vaccines. They have also been identified as potential ambassadors of COVID-19 vaccine acceptance, helping to ensure that sufficient members of a hesitant public accept COVID-19 vaccines to achieve population immunity. Yet HCWs themselves have shown vaccine hesitancy in other contexts and the few prior surveys of U.S. HCW intentions to receive a COVID-19 vaccine report acceptance rates of only 28% to 34%. However, it is unknown whether HCW acceptance remains low following mid-November announcements of the efficacy of the first COVID-19 vaccines and the issuance of two emergency use authorizations (EUA) in December. We report the results of a December 2020 survey (N = 16,158; response rate 61%) administered by a large Pennsylvania health system to determine the intentions of its employees to receive a vaccine when it is offered to them. In a mixed sample of individuals serving in patient-facing and other roles, 55% would decide to receive a COVID-19 vaccine when offered, 16.4% would not, and 28.5% reported being undecided. The distribution of responses varied little across hospital campuses, between those in patient-facing roles and other HCWs, or by area or department of work. The higher rate of COVID-19 vaccine acceptance we observe may reflect the framing and timing of our survey. Among hesitant respondents, an overwhelming majority (90.3%) reported concerns about unknown risks and insufficient data. Other commonly reported concerns included known side effects (57.4%) and wanting to wait until they see how it goes with others (44.4%). We observed a substantial increase in self-reported intent to receive a COVID-19 vaccine after an FDA advisory committee voted to recommend an EUA. Among respondents who completed the survey after that point in time, 79% intend to receive a COVID-19 vaccine (n = 1155). Although only suggestive, this trend offers hope that rates of COVID-19 vaccine acceptance may be higher among HCWs and, perhaps, the general public than more hypothetical survey results have indicated.

Healthcare workers (HCWs) have been recommended to receive first priority for limited COVID-19 vaccines. They have also been identified as potential ambassadors of COVID-19 vaccine acceptance, helping to ensure that sufficient members of a hesitant public accept COVID-19 vaccines to achieve population immunity. Yet HCWs themselves have shown vaccine hesitancy in other contexts and the few prior surveys of U.S. HCW intentions to receive a COVID-19 vaccine report acceptance rates of only 28% to 34%. However, it is unknown whether HCW acceptance remains low following mid-November announcements of the efficacy of the first COVID-19 vaccines and the issuance of two emergency use authorizations (EUA) in December. We report the results of a December 2020 survey (N = 16,158; response rate 61%) administered by a large Pennsylvania health system to determine the intentions of its employees to receive a vaccine when it is offered to them. In a mixed sample of individuals serving in patient-facing and other roles, 55% would decide to receive a COVID-19 vaccine when offered, 16.4% would not, and 28.5% reported being undecided. The distribution of responses varied little across hospital campuses, between those in patient-facing roles and other HCWs, or by area or department of work. The higher rate of COVID-19 vaccine acceptance we observe may reflect the framing and timing of our survey. Among hesitant respondents, an overwhelming majority (90.3%) reported concerns about unknown risks and insufficient data. Other commonly reported concerns included known side effects (57.4%) and wanting to wait until they see how it goes with others (44.4%). We observed a substantial increase in self-reported intent to receive a COVID-19 vaccine after an FDA advisory committee voted to recommend an EUA. Among respondents who completed the survey after that point in time, 79% intend to receive a COVID-19 vaccine (n = 1155). Although only suggestive, this trend offers hope that rates of COVID-19 vaccine acceptance may be higher among HCWs and, perhaps, the general public than more hypothetical survey results have indicated.