In embryonic stem cells (ESCs), a core transcription factor (TF) network establishes the gene expression program necessary for pluripotency. To address how interactions between four key TFs ...contribute to
regulation in mouse ESCs, we assayed two massively parallel reporter assay (MPRA) libraries composed of binding sites for SOX2, POU5F1 (OCT4), KLF4, and ESRRB. Comparisons between synthetic
-regulatory elements and genomic sequences with comparable binding site configurations revealed some aspects of a regulatory grammar. The expression of synthetic elements is influenced by both the number and arrangement of binding sites. This grammar plays only a small role for genomic sequences, as the relative activities of genomic sequences are best explained by the predicted occupancy of binding sites, regardless of binding site identity and positioning. Our results suggest that the effects of transcription factor binding sites (TFBS) are influenced by the order and orientation of sites, but that in the genome the overall occupancy of TFs is the primary determinant of activity.
Objective: Although there is growing evidence that alcohol use at the daily level is associated with positive but not negative affect, results are mixed when examining marijuana use and simultaneous ...alcohol and marijuana (SAM) use (i.e., use with overlapping effects). In addition, less is known about these daily level associations among diverse samples of adolescents and young adults. The present study will address these gaps. Method: Participants (N = 1,006; 57.3% female, 43.1% White, Non-Hispanic, ages 15−25; Mage = 20.0) were part of a study on substance use that consisted of a 3-week ecological momentary assessment (EMA) burst design (eight surveys per week, up to 2×/day) that was repeated quarterly over a 12-month period. Results: Within-person results indicated that on days with elevated positive affect, participants reported consuming more drinks, whereas positive affect was not significant for hours high from marijuana. In addition, on days with elevated negative affect, participants reported fewer hours high from marijuana. No association was found between negative affect and number of drinks. Finally, within-person results indicated that on alcohol or marijuana days with elevated positive affect, individuals were more likely to report SAM use. There was no association found between negative affect and SAM use. Conclusions: Results have implications such that in-the-moment interventions for alcohol and SAM use may be more salient when individuals have higher positive affect than average, whereas such interventions may be more relevant for marijuana use when negative affect is lower compared to average levels.
Public Health Significance Statement
On days when adolescents and young adults experienced stronger positive affect, they consumed more drinks but did not spend more hours high from marijuana, whereas on days when they experienced stronger negative affect, participants reported fewer hours high from marijuana but did not consume more drinks. In addition, on days when participants used alcohol or marijuana and had higher positive affect, but not negative affect, they were more likely to report simultaneous alcohol and marijuana (SAM) use. Results suggest in-the-moment interventions for alcohol and SAM use may be more salient when adolescents and young adults have higher than average positive affect, whereas such interventions may be more relevant for marijuana use when negative affect is lower compared to average levels.
During the coronavirus disease of 2019 (COVID-19) pandemic, overseas military bases faced unique challenges to preserve force health protection while simultaneously caring for military beneficiaries. ...The response to the rapidly evolving challenges surrounding transmission of the severe acute respiratory syndrome coronavirus 2 in Okinawa, Japan, required innovative solutions. One innovative solution was the COVID-19 Operational Response Cell established at Camp Courtney, Marine Corps Base Camp Smedley D. Butler. This interview describes the COVID-19 Response Cell operations and essential lessons learned by a Navy Nurse Corps officer working with III Marine Expeditionary Force, a forward-deployed force in the U.S. Indo-Pacific Command.
The 2019/2020 summer of Antarctic heatwaves Robinson, Sharon A.; Klekociuk, Andrew R.; King, Diana H. ...
Global change biology,
June 2020, 2020-Jun, 2020-06-00, 20200601, Letnik:
26, Številka:
6
Journal Article
Recenzirano
Odprti dostop
This summer, a heatwave across Antarctica saw temperatures soar above average. Temperatures above zero are especially significant because they accelerate ice melt. Casey Station had its highest ...temperature ever, reaching a maximum of 9.2°C and minimum of 2.5°C. The highest temperature in Antarctica was 20.75°C on 9 February. Here we discuss the biological implications of such extreme events.
Background
Some studies have suggested disparities in access to robotic colorectal surgery, however, it is unclear which factors are most meaningful in the determination of approach relative to ...laparoscopic or open surgery. This study aimed to identify the most influential factors contributing to robotic colorectal surgery utilization.
Methods
We conducted a systematic review and random-effects meta-analysis of published studies that compared the utilization of robotic colorectal surgery versus laparoscopic or open surgery. Eligible studies were identified through PubMed, EMBASE, CINAHL, Cochrane CENTRAL, PsycINFO, and ProQuest Dissertations in September 2021.
Results
Twenty-nine studies were included in the analysis. Patients were less likely to undergo robotic versus laparoscopic surgery if they were female (OR = 0.91, 0.84–0.98), older (OR = 1.61, 1.38–1.88), had Medicare (OR = 0.84, 0.71–0.99), or had comorbidities (OR = 0.83, 0.77–0.91). Non-academic hospitals had lower odds of conducting robotic versus laparoscopic surgery (OR = 0.73, 0.62–0.86). Additional disparities were observed when comparing robotic with open surgery for patients who were Black (OR = 0.78, 0.71–0.86), had lower income (OR = 0.67, 0.62–0.74), had Medicaid (OR = 0.58, 0.43–0.80), or were uninsured (OR = 0.29, 0.21–0.39).
Conclusion
When determining who undergoes robotic surgery, consideration of factors such as age and comorbid conditions may be clinically justified, while other factors seem less justifiable. Black patients and the underinsured were less likely to undergo robotic surgery. This study identifies nonclinical disparities in access to robotics that should be addressed to provide more equitable access to innovations in colorectal surgery.
Graphical Abstract
During C. elegans development, microRNAs (miRNAs) function as molecular switches that define temporal gene expression and cell lineage patterns in a dosage-dependent manner. It is critical, ...therefore, that the expression of miRNAs be tightly regulated so that target mRNA expression is properly controlled. The molecular mechanisms that function to optimize or control miRNA levels during development are unknown. Here we find that mutations in lin-42, the C. elegans homolog of the circadian-related period gene, suppress multiple dosage-dependent miRNA phenotypes including those involved in developmental timing and neuronal cell fate determination. Analysis of mature miRNA levels in lin-42 mutants indicates that lin-42 functions to attenuate miRNA expression. Through the analysis of transcriptional reporters, we show that the upstream cis-acting regulatory regions of several miRNA genes are sufficient to promote highly dynamic transcription that is coupled to the molting cycles of post-embryonic development. Immunoprecipitation of LIN-42 complexes indicates that LIN-42 binds the putative cis-regulatory regions of both non-coding and protein-coding genes and likely plays a role in regulating their transcription. Consistent with this hypothesis, analysis of miRNA transcriptional reporters in lin-42 mutants indicates that lin-42 regulates miRNA transcription. Surprisingly, strong loss-of-function mutations in lin-42 do not abolish the oscillatory expression patterns of lin-4 and let-7 transcription but lead to increased expression of these genes. We propose that lin-42 functions to negatively regulate the transcriptional output of multiple miRNAs and mRNAs and therefore coordinates the expression levels of genes that dictate temporal cell fate with other regulatory programs that promote rhythmic gene expression.
Abstract
Between 15 and 19 March 2022, East Antarctica experienced an exceptional heat wave with widespread 30°–40°C temperature anomalies across the ice sheet. In Part I, we assessed the ...meteorological drivers that generated an intense atmospheric river (AR) that caused these record-shattering temperature anomalies. Here, we continue our large collaborative study by analyzing the widespread and diverse impacts driven by the AR landfall. These impacts included widespread rain and surface melt that was recorded along coastal areas, but this was outweighed by widespread high snowfall accumulations resulting in a largely positive surface mass balance contribution to the East Antarctic region. An analysis of the surface energy budget indicated that widespread downward longwave radiation anomalies caused by large cloud-liquid water contents along with some scattered solar radiation produced intense surface warming. Isotope measurements of the moisture were highly elevated, likely imprinting a strong signal for past climate reconstructions. The AR event attenuated cosmic ray measurements at Concordia, something previously never observed. Last, an extratropical cyclone west of the AR landfall likely triggered the final collapse of the critically unstable Conger Ice Shelf while further reducing an already record low sea ice extent.
Significance Statement
Using our diverse collective expertise, we explored the impacts from the March 2022 heat wave and atmospheric river across East Antarctica. One key takeaway is that the Antarctic cryosphere is highly sensitive to meteorological extremes originating from the midlatitudes and subtropics. Despite the large positive temperature anomalies driven from strong downward longwave radiation, this event led to huge amounts of snowfall across the Antarctic interior desert. The isotopes in this snow of warm airmass origin will likely be detectable in future ice cores and potentially distort past climate reconstructions. Even measurements of space activity were affected. Also, the swells generated from this storm helped to trigger the final collapse of an already critically unstable Conger Ice Shelf while further degrading sea ice coverage.
The present study is the first ecologically valid, daily level test of the prototype willingness model (PWM), a model previously tested with hypothetical scenarios to investigate the social reaction ...and reasoned pathways toward engaging in health-risk behavior. The purpose of the present study is to examine whether days with elevated alcohol-favorable PWM cognitions are also associated with greater intentions and willingness to drink and increased drinking behavior on that day. Participants included 15-25-year-olds (N = 124; 57.3% female; Mage =18.7; SD = 2.87) who were part of an ecological momentary assessment study on drinking cognitions (including willingness, intentions, perceived vulnerability, social norms, prototype favorability) and alcohol use, reported across 3 weeks. Analyses accounted for the multilevel structure of the data and the various outcome distributions. Findings supported and advanced the PWM by using real-time, real-world daily data that captured within-person variation of PWM cognitions across days and showed daily level associations between PWM cognitions and alcohol use and negative consequences among adolescents and young adults, thus supporting the social reaction and reasoned pathways at the daily level. Current results may improve interventions by precisely informing the use of technology to bring interventions to adolescents and young adults in moments when they are at highest risk (i.e., days with higher than usual PMW alcohol cognitions).
Article Note: Presented at the Society for Academic Emergency Medicine Annual Meeting, May 2019, Las Vegas, NV. The authors have no relevant financial information or potential conflicts of interest ...to disclose. Author contributions: DMK, ASG, and JPV designed the study; JPV and KKH were responsible for managing and analyzing the data; DMK, JPV, and CJ drafted the manuscript; and all authors contributed substantially to its revision. DMK takes responsibility for the paper as a whole. Supervising Editor: Jess M. Pines, MD. Byline: Dana M. King, J. Priyanka Vakkalanka, Christian Junker, Karisa K. Harland, Andrew S. Nugent
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