Molecular mechanism of photoperiod sensing

ELF3 and GI are two important components of the Arabidopsis circadian clock. They are not only essential for the oscillator function but are also pivotal in mediating light inputs to the oscillator. Lack of either results in a defective oscillator causing severely compromised output pathways, such as photoperiodic flowering and hypocotyl elongation. Although single loss of function mutants of ELF3 and GI have been well-studied, their genetic interaction remains unclear. We generated an elf3 gi double mutant to study their genetic relationship in clock-controlled growth and phase transition phenotypes. We found that ELF3 and GI repress growth during the night and the day, respectively. We also provide evidence that ELF3, for which so far only a growth inhibitory role has been reported, can also act as a growth promoter under certain conditions. Finally, circadian clock assays revealed that ELF3 and GI are essential Zeitnehmers that enable the oscillator to synchronize the endogenous cellular mechanisms to external environmental signals. In their absence, the circadian oscillator fails to synchronize to the light dark cycles even under diurnal conditions. Consequently, clock-mediated photoperiod-responsive growth and development is completely lost in plants lacking both genes, suggesting that ELF3 and GI together convey photoperiod sensing to the central oscillator. Since ELF3 and GI are conserved across flowering plants and represent important breeding and domestication targets, our data highlight the possibility of developing photoperiod-insensitive crops by manipulating the combination of these two key genes

Photoperiod sensing of the circadian clock is controlled by EARLY FLOWERING 3 and GIGANTEA

ELF3 and GI are two important components of the Arabidopsis circadian clock. They are not on-ly essential for the oscillator function but are also pivotal in mediating light inputs to the oscillator. Lack of either results in a defective oscillator causing severely compromised output pathways, such as photoperiodic flowering and hypocotyl elongation. Although single loss of function mu-tants of ELF3 and GI have been well-studied, their genetic interaction remains unclear. We gen-erated an elf3 gi double mutant to study their genetic relationship in clock-controlled growth and phase transition phenotypes. We found that ELF3 and GI repress growth differentially during the night and the day, respectively. Circadian clock assays revealed that ELF3 and GI are essential Zeitnehmers that enable the oscillator to synchronize the endogenous cellular mechanisms to external environmental signals. In their absence, the circadian oscillator fails to synchronize to the light-dark cycles even under diurnal conditions. Consequently, clock-mediated photoperiod-responsive growth and development are completely lost in plants lacking both genes, suggesting that ELF3 and GI together convey photoperiod sensing to the central oscillator. Since ELF3 and GI are conserved across flowering plants and represent important breeding and domestication targets, our data highlight the possibility of developing photoperiod-insensitive crops by adjusting the allelic combination of these two key genes

GALEX J201337.6+092801: The lowest gravity subdwarf B pulsator

We present the recent discovery of a new subdwarf B variable (sdBV), with an exceptionally low surface gravity. Our spectroscopy of J20136+0928 places it at Teff = 32100 +/- 500, log(g) = 5.15 +/- 0.10, and log(He/H) = -2.8 +/- 0.1. With a magnitude of B = 12.0, it is the second brightest V361 Hya star ever found. Photometry from three different observatories reveals a temporal spectrum with eleven clearly detected periods in the range 376 to 566 s, and at least five more close to our detection limit. These periods are unusually long for the V361 Hya class of short-period sdBV pulsators, but not unreasonable for p- and g-modes close to the radial fundamental, given its low surface gravity. Of the ~50 short period sdB pulsators known to date, only a single one has been found to have comparable spectroscopic parameters to J20136+0928. This is the enigmatic high-amplitude pulsator V338 Ser, and we conclude that J20136+0928 is the second example of this rare subclass of sdB pulsators located well above the canonical extreme horizontal branch in the HR diagram.Comment: 5 pages, accepted for publication in ApJ Letter

The Case for a Nationwide Child Development Account Policy: A Policy Brief Developed by CDA Experts and Researchers

In this policy brief, prominent Child Development Account (CDA) experts and researchers present the case for a nationwide policy to provide CDAs and build assets for all children in the United States. The authors identify principles for CDA policy design. In a companion brief, they discuss policy and practice changes to make college savings (529) plans far more inclusive

Redesigning College Savings (529) Plans to Achieve Inclusive Child Development Accounts: A Policy Brief Developed by CDA Experts and Researchers

In this policy brief, prominent Child Development Account (CDA) experts and researchers recommend changes in policies and practices for state college savings (529) plans. If adopted, the changes would make possible the use of the 529 plans to deliver CDAs for all children in the United States. In a companion brief, they present the case for a nationwide CDA policy and identify design principles

First Kepler results on compact pulsators - VIII. Mode identifications via period spacings in g-mode pulsating subdwarf B stars

We investigate the possibility of nearly equally spaced periods in 13 hot subdwarf B (sdB) stars observed with the Kepler spacecraft and one observed with CoRoT. Asymptotic limits for gravity (g-)mode pulsations provide relationships between equal-period spacings of modes with differing degrees ℓ and relationships between periods of the same radial order n but differing degrees ℓ. Period transforms, Kolmogorov-Smirnov tests and linear least-squares fits have been used to detect and determine the significance of equal-period spacings. We have also used Monte Carlo simulations to estimate the likelihood that the detected spacings could be produced randomly. Period transforms for nine of the Kepler stars indicate ℓ= 1 period spacings, with five also showing peaks for ℓ= 2 modes. 12 stars indicate ℓ= 1 modes using the Kolmogorov-Smirnov test while another shows solely ℓ= 2 modes. Monte Carlo results indicate that equal-period spacings are significant in 10 stars above 99 per cent confidence, and 13 of the 14 are above 94 per cent confidence. For 12 stars, the various methods find consistent period spacings to within the errors, two others show some inconsistencies, likely caused by binarity, and the last has significant detections but the mode assignment disagrees between the methods. We use asymptotic period spacing relationships to associate observed periods of variability with pulsation modes for ℓ= 1 and 2. From the Kepler first-year survey sample of 13 multiperiodic g-mode pulsators, five stars have several consecutive overtones making period spacings easy to detect, six others have fewer consecutive overtones but period spacings are readily detected, and two stars show marginal indications of equal-period spacings. We also examine a g-mode sdB pulsator observed by CoRoT with a rich pulsation spectrum, and our tests detect regular period spacings. We use Monte Carlo simulations to estimate the significance of the detections in individual stars. From the simulations, it is determined that regular period spacings in 10 of the 14 stars are very unlikely to be random, another two are moderately unlikely to be random and two are mostly unconstrained. We find a common ℓ= 1 period spacing spanning a range from 231 to 272 s allowing us to correlate pulsation modes with 222 periodicities and that the ℓ= 2 period spacings are related to the ℓ= 1 spacings by the asymptotic relationship forumla⁠. We briefly discuss the impact of equal-period spacings which indicate low-degree modes with a lack of significant mode trappings

Linking compact dwarf starburst galaxies in the resolve survey to downsized blue nuggets

Abstract We identify and characterize compact dwarf starburst (CDS) galaxies in the RESOLVE survey, a volume-limited census of galaxies in the local universe, to probe whether this population contains any residual “blue nuggets,” a class of intensely star-forming compact galaxies first identified at high redshift z. Our 50 low-z CDS galaxies are defined by dwarf masses (stellar mass M* < 109.5 M⊙), compact bulged-disk or spheroid-dominated morphologies (using a quantitative criterion, \mu _\Delta > 8.6), and specific star formation rates above the defining threshold for high-z blue nuggets (log SSFR [Gyr−1] > −0.5). Across redshifts, blue nuggets exhibit three defining properties: compactness relative to contemporaneous galaxies, abundant cold gas, and formation via compaction in mergers or colliding streams. Those with halo mass below Mhalo ∼ 1011.5 M⊙ may in theory evade permanent quenching and cyclically refuel until the present day. Selected only for compactness and starburst activity, our CDS galaxies generally have Mhalo ≲ 1011.5 M⊙ and gas-to-stellar mass ratio ≳1. Moreover, analysis of archival DECaLS photometry and new 3D spectroscopic observations for CDS galaxies reveals a high rate of photometric and kinematic disturbances suggestive of dwarf mergers. The SSFRs, surface mass densities, and number counts of CDS galaxies are compatible with theoretical and observational expectations for redshift evolution in blue nuggets. We argue that CDS galaxies represent a maximally-starbursting subset of traditional compact dwarf classes such as blue compact dwarfs and blue E/S0s. We conclude that CDS galaxies represent a low-z tail of the blue nugget phenomenon formed via a moderated compaction channel that leaves open the possibility of disk regrowth and evolution into normal disk galaxies

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification