The Mid-infrared Evolution of the FU Orionis Disk

We present new SOFIA-FORCAST observations obtained in 2016 February of the archetypal outbursting low-mass young stellar object FU Orionis, and we compare the continuum, solid-state, and gas properties with mid-infrared data obtained at the same wavelengths in 2004 with Spitzer-IRS. In this study, we conduct the first mid-infrared spectroscopic comparison of an FUor over a long time period. Over a 12-year period, UBVR monitoring indicates that FU Orionis has continued its steady decrease in overall brightness by ~14%. We find that this decrease in luminosity occurs only at wavelengths ≾20 μm. In particular, the continuum shortward of the silicate emission complex at 10 μm exhibits a ~12% (~3σ) drop in flux density but no apparent change in slope; both the Spitzer and SOFIA spectra are consistent with a 7200 K blackbody. Additionally, the detection of water absorption is consistent with the Spitzer spectrum. The silicate emission feature at 10 μm continues to be consistent with unprocessed grains, unchanged over 12 years. We conclude that either the accretion rate in FU Orionis has decreased by ~12–14% over this time baseline or the inner disk has cooled, but the accretion disk remains in a superheated state outside the innermost region

Beta-catenin cleavage enhances transcriptional activation

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat552 in the nucleus of inflamed and cancerous cells. Nuclear chromatin bound localization of LMW pβ-Cat552 was blocked in cells by inhibition of proteasomal chymotrypsin-like activity but not by other protease inhibitors. K48 polyubiquitinated FS and LMW β-catenin were increased by treatment with bortezomib. Overexpressed in vitro double truncated β-catenin increased transcriptional activity, cell proliferation and growth of tumor xenografts compared to FS β-catenin. Serine 552-> alanin substitution abrogated K48 polyubiquitination, β-catenin nuclear translocation and tumor xenograft growth. These data suggest that a novel proteasome-dependent posttranslational modification of β-catenin enhances transcriptional activation. Discovery of this pathway may be helpful in the development of diagnostic and therapeutic tools in colitis and cancer

The Mid-infrared Evolution of the FU Orionis Disk

We present new SOFIA-FORCAST observations obtained in 2016 February of the archetypal outbursting low-mass young stellar object FU Orionis, and we compare the continuum, solid-state, and gas properties with mid-infrared data obtained at the same wavelengths in 2004 with Spitzer-IRS. In this study, we conduct the first mid-infrared spectroscopic comparison of an FUor over a long time period. Over a 12-year period, UBVR monitoring indicates that FU Orionis has continued its steady decrease in overall brightness by ~14%. We find that this decrease in luminosity occurs only at wavelengths ≾20 μm. In particular, the continuum shortward of the silicate emission complex at 10 μm exhibits a ~12% (~3σ) drop in flux density but no apparent change in slope; both the Spitzer and SOFIA spectra are consistent with a 7200 K blackbody. Additionally, the detection of water absorption is consistent with the Spitzer spectrum. The silicate emission feature at 10 μm continues to be consistent with unprocessed grains, unchanged over 12 years. We conclude that either the accretion rate in FU Orionis has decreased by ~12–14% over this time baseline or the inner disk has cooled, but the accretion disk remains in a superheated state outside the innermost region

Force-Velocity Measurements of a Few Growing Actin Filaments

The authors propose a new mechanism for actin-based force generation based on results using chains of actin-grafted magnetic colloids

Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493)

Elena+ Care for COVID-19, A Pandemic Lifestyle Care Intervention: Intervention Design and Study Protocol

Background: The current COVID-19 coronavirus pandemic is an emergency on a global scale, with huge swathes of the population required to remain indoors for prolonged periods to tackle the virus. In this new context, individuals’ health-promoting routines are under greater strain, contributing to poorer mental and physical health. Additionally, individuals are required to keep up to date with latest health guidelines about the virus, which may be confusing in an age of social-media disinformation and shifting guidelines. To tackle these factors, we developed Elena+, a smartphone-based and conversational agent (CA) delivered pandemic lifestyle care intervention.Methods: Elena+ utilizes varied intervention components to deliver a psychoeducation-focused coaching program on the topics of: COVID-19 information, physical activity, mental health (anxiety, loneliness, mental resources), sleep and diet and nutrition. Over 43 subtopics, a CA guides individuals through content and tracks progress over time, such as changes in health outcome assessments per topic, alongside user-set behavioral intentions and user-reported actual behaviors. Ratings of the usage experience, social demographics and the user profile are also captured. Elena+ is available for public download on iOS and Android devices in English, European Spanish and Latin American Spanish with future languages and launch countries planned, and no limits on planned recruitment. Panel data methods will be used to track user progress over time in subsequent analyses. The Elena+ intervention is open-source under the Apache 2 license (MobileCoach software) and the Creative Commons 4.0 license CC BY-NC-SA (intervention logic and content), allowing future collaborations; such as cultural adaptions, integration of new sensor-related features or the development of new topics.Discussion: Digital health applications offer a low-cost and scalable route to meet challenges to public health. As Elena+ was developed by an international and interdisciplinary team in a short time frame to meet the COVID-19 pandemic, empirical data are required to discern how effective such solutions can be in meeting real world, emergent health crises. Additionally, clustering Elena+ users based on characteristics and usage behaviors could help public health practitioners understand how population-level digital health interventions can reach at-risk and sub-populations

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research