Perturbing Dynamin Reveals Potent Effects on the Drosophila Circadian Clock

BACKGROUND: Transcriptional feedback loops are central to circadian clock function. However, the role of neural activity and membrane events in molecular rhythms in the fruit fly Drosophila is unclear. To address this question, we expressed a temperature-sensitive, dominant negative allele of the fly homolog of dynamin called shibire(ts1) (shi(ts1)), an active component in membrane vesicle scission. PRINCIPAL FINDINGS: Broad expression in clock cells resulted in unexpectedly long, robust periods (>28 hours) comparable to perturbation of core clock components, suggesting an unappreciated role of membrane dynamics in setting period. Expression in the pacemaker lateral ventral neurons (LNv) was necessary and sufficient for this effect. Manipulation of other endocytic components exacerbated shi(ts1)'s behavioral effects, suggesting its mechanism is specific to endocytic regulation. PKA overexpression rescued period effects suggesting shi(ts1) may downregulate PKA pathways. Levels of the clock component PERIOD were reduced in the shi(ts1)-expressing pacemaker small LNv of flies held at a fully restrictive temperature (29 degrees C). Less restrictive conditions (25 degrees C) delayed cycling proportional to observed behavioral changes. Levels of the neuropeptide PIGMENT-DISPERSING FACTOR (PDF), the only known LNv neurotransmitter, were also reduced, but PERIOD cycling was still delayed in flies lacking PDF, implicating a PDF-independent process. Further, shi(ts1) expression in the eye also results in reduced PER protein and per and vri transcript levels, suggesting that shibire-dependent signaling extends to peripheral clocks. The level of nuclear CLK, transcriptional activator of many core clock genes, is also reduced in shi(ts1) flies, and Clk overexpression suppresses the period-altering effects of shi(ts1). CONCLUSIONS: We propose that membrane protein turnover through endocytic regulation of PKA pathways modulates the core clock by altering CLK levels and/or activity. These results suggest an important role for membrane scission in setting circadian period

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

A Legacy of Deviance: Historical Constructions of Chinese Immigrant Masculinity

“[W]omen are…believers in muscular manhood. These lank, scrawny limbs…he was more like a woman than a man.”–1870“What other men visit salons to get, the Asian gene pool provides for free…ladyboy fingers: soft and long.”–2004Despite a difference of over a century in publication dates, these excerpts from popular periodicals evince remarkably similar imaginings of the Asian male body. This correspondence is indicative of the ways in which contemporary non-normative constructions of Asian American masculinity suggest a historical linearity rooted in early American conceptions of Asian immigrant men.As the first group of Asian immigrants to warrant social visibility, an exploration of the social figuration of early Chinese immigrant laborers can serve as a basis for understanding this popularization of emasculation. Specifically, to the extent that this group also formed the foundational basis for a seemingly extant legacy of deviance today, an examination of how these pioneer Chinese men were descriptively bounded within popular spaces can expose both the parallels and points of departure from which we can more fully understand contemporary Asian American masculinity.This paper analyzes the textual imagery of Chinese immigrant laborers as captured in popular periodicals and print media between 1850 and 1924. In exploring perceptions of Chinese masculinity during this period, the projection of deviance is examined through three lenses of Chinese male non-normative constitution: the diasporic attribution of otherness as non-White aliens, queer domesticity as defined by family and occupation, and most visibly within the perceived and material deficit of agency

Over the edge: remapping the American West

From the Gold Rush to rush hour, the history of the American West is fraught with diverse, subversive, and at times downright eccentric elements. This provocative volume challenges traditional readings of western history and literature, and redraws the boundaries of the American West with absorbing essays ranging widely on topics from tourism to immigration, from environmental battles to interethnic relations, and from law to film. Taken together, the essays reassess the contributions of a diverse and multicultural America to the West, as they link western issues to global frontiers.Featuring the latest work by some of the best new writers both inside and outside academia, the original essays in Over the Edge confront the traditional field of western American studies with a series of radical, speculative, and sometimes outrageous challenges. The collection reads the West through Ben-Hur and the films of Mae West; revises the western American literary canon to include the works of African American and Mexican American writers; examines the implications of miscegenation law and American Indian blood quantum requirements; and brings attention to the historical participation of Mexican and Japanese American women, Native American slaves, and Alaskan cannery workers in community life

Sensitivity in detecting facial displays of emotion: Impact of maternal depression and oxytocin receptor genotype.

The current study examined sensitivity in detecting emotional faces among children of depressed and non-depressed mothers. A second goal was to examine the potential moderating role of the oxytocin receptor gene (OXTR rs53576), which has been linked to emotion recognition in the past. Participants included 247 children (ages 8–14). Children completed a forced choice emotion identification task. Maternal history of major depressive disorder during children’s lives was associated with children’s sensitivity in detecting emotional faces among children homozygous for the OXTR rs53576 G allele, but not among carriers of the A allele. Among G homozygotes, children of depressed mothers exhibited increased sensitivity in detecting sad faces, and reduced sensitivity in detecting happiness, compared to children of non-depressed mothers