Characterization of Retinal Structure in ATF6-Associated Achromatopsia

Purpose: Mutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM. Methods: Seven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM. Results: Foveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports. Conclusions: Our data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM

Co-resident Parents and Young People Aged 15–34: Who Does What Housework?

Young adults are now more likely to co-reside with their parents than previous generations, but domestic work patterns among this family type are largely unexplored. This study addresses this issue using Australian Bureau of Statistics Time Use Surveys (1992, 1997, 2006) and Poisson–Gamma regression analyses. It examines patterns in and correlates of domestic labor in two-generation households in which young people aged 15–34 co-reside with their parents (n = 1,946 households comprised of 2,806 young people and 5,129 parents). It differentiates between routine indoor tasks (cooking, cleaning, laundry), non-routine tasks (outdoor work, household management and maintenance, car care) and grocery shopping. Predictors of more time in some domestic activities by young people include being in neither employment nor education/training (NEET), being older, having a single parent and being in a non-English speaking household (young women). Young people being NEET, or female, are associated with less cooking time for mothers, but in the main when young people do perform domestic activities, they do not relieve their parents of those same activities, suggesting more time is spent by the household in total

Differential Influence of Clonal Integration on Morphological and Growth Responses to Light in Two Invasive Herbs

Background and aims: In contrast to seeds, high sensitivity of vegetative fragments to unfavourable environments may limit the expansion of clonal invasive plants. However, clonal integration promotes the establishment of propagules in less suitable habitats and may facilitate the expansion of clonal invaders into intact native communities. Here, we examine the influence of clonal integration on the morphology and growth of ramets in two invasive plants, Alternanthera philoxeroides and Phyla canescens, under varying light conditions. Methods: In a greenhouse experiment, branches, connected ramets and severed ramets of the same mother plant were exposed under full sun and 85 % shade and their morphological and growth responses were assessed. Key results: The influence of clonal integration on the light reaction norm (connection6light interaction) of daughter ramets was species-specific. For A. philoxeroides, clonal integration evened out the light response (total biomass, leaf mass per area, and stem number, diameter and length) displayed in severed ramets, but these connection6light interactions were largely absent for P. canescens. Nevertheless, for both species, clonal integration overwhelmed light effect in promoting the growth of juvenile ramets during early development. Also, vertical growth, as an apparent shade acclimation response, was more prevalent in severed ramets than in connected ramets. Finally, unrooted branches displayed smaller organ size and slower growth than connected ramets, but the pattern of light reaction was similar, suggesting mothe

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3σ (5σ) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3σ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Exoplanet biosignatures: A review of remotely detectable signs of life

In the coming years and decades, advanced space- and ground-based observatories will allow an unprecedented opportunity to probe the atmospheres and surfaces of potentially habitable exoplanets for signatures of life. Life on Earth, through its gaseous products and reflectance and scattering properties, has left its fingerprint on the spectrum of our planet. Aided by the universality of the laws of physics and chemistry, we turn to Earth’s biosphere, both in the present and through geologic time, for analog signatures that will aid in the search for life elsewhere. Considering the insights gained from modern and ancient Earth, and the broader array of hypothetical exoplanet possibilities, we have compiled a comprehensive overview of our current understanding of potential exoplanet biosignatures, including gaseous, surface, and temporal biosignatures. We additionally survey biogenic spectral features that are well known in the specialist literature but have not yet been robustly vetted in the context of exoplanet biosignatures. We briefly review advances in assessing biosignature plausibility, including novel methods for determining chemical disequilibrium from remotely obtainable data and assessment tools for determining the minimum biomass required to maintain short-lived biogenic gases as atmospheric signatures. We focus particularly on advances made since the seminal review by Des Marais et al. The purpose of this work is not to propose new biosignature strategies, a goal left to companion articles in this series, but to review the current literature, draw meaningful connections between seemingly disparate areas, and clear the way for a path forward

Exoplanet biosignatures: A review of remotely detectable signs of life

In the coming years and decades, advanced space- and ground-based observatories will allow an unprecedented opportunity to probe the atmospheres and surfaces of potentially habitable exoplanets for signatures of life. Life on Earth, through its gaseous products and reflectance and scattering properties, has left its fingerprint on the spectrum of our planet. Aided by the universality of the laws of physics and chemistry, we turn to Earth’s biosphere, both in the present and through geologic time, for analog signatures that will aid in the search for life elsewhere. Considering the insights gained from modern and ancient Earth, and the broader array of hypothetical exoplanet possibilities, we have compiled a comprehensive overview of our current understanding of potential exoplanet biosignatures, including gaseous, surface, and temporal biosignatures. We additionally survey biogenic spectral features that are well known in the specialist literature but have not yet been robustly vetted in the context of exoplanet biosignatures. We briefly review advances in assessing biosignature plausibility, including novel methods for determining chemical disequilibrium from remotely obtainable data and assessment tools for determining the minimum biomass required to maintain short-lived biogenic gases as atmospheric signatures. We focus particularly on advances made since the seminal review by Des Marais et al. The purpose of this work is not to propose new biosignature strategies, a goal left to companion articles in this series, but to review the current literature, draw meaningful connections between seemingly disparate areas, and clear the way for a path forward

Ideas and perspectives: Strengthening the biogeosciences in environmental research networks

Long-term environmental research networks are one approach to advancing local, regional, and global environmental science and education. A remarkable number and wide variety of environmental research networks operate around the world today. These are diverse in funding, infrastructure, motivating questions, scientific strengths, and the sciences that birthed and maintain the networks. Some networks have individual sites that were selected because they had produced invaluable long-term data, while other networks have new sites selected to span ecological gradients. However, all long-term environmental networks share two challenges. Networks must keep pace with scientific advances and interact with both the scientific community and society at large. If networks fall short of successfully addressing these challenges, they risk becoming irrelevant. The objective of this paper is to assert that the biogeosciences offer environmental research networks a number of opportunities to expand scientific impact and public engagement. We explore some of these opportunities with four networks: the International Long-Term Ecological Research Network programs (ILTERs), critical zone observatories (CZOs), Earth and ecological observatory networks (EONs), and the FLUXNET program of eddy flux sites. While these networks were founded and expanded by interdisciplinary scientists, the preponderance of expertise and funding has gravitated activities of ILTERs and EONs toward ecology and biology, CZOs toward the Earth sciences and geology, and FLUXNET toward ecophysiology and micrometeorology. Our point is not to homogenize networks, nor to diminish disciplinary science. Rather, we argue that by more fully incorporating the integration of biology and geology in long-term environmental research networks, scientists can better leverage network assets, keep pace with the ever-changing science of the environment, and engage with larger scientific and public audiences

Targeted Knockdown of Overexpressed VEGFA or VEGF164 in Müller cells maintains retinal function by triggering different signaling mechanisms

Abstract Oxygen-induced retinopathy (OIR) upregulates Müller cell vascular endothelial growth factor A (VEGFA) that causes intravitreal neovascularization similar to severe retinopathy of prematurity (ROP). Safety concerns exist with anti-VEGF treatment for ROP. We evaluated long-term knockdown of Müller cell-VEGFA with short-hairpin RNAs to VEGFA or VEGF164 via subretinal lentivirus delivery (L-VEGFAshRNA, L-VEGF164shRNA) on retinal structure and function in a rat OIR model. Lectin-stained retinal flat mounts analyzed for areas of avascular/total retina (AVA) and intravitreal neovascular/total retina (IVNV) showed initial significantly reduced IVNV by L-VEGFAshRNA and L-VEGF164shRNA compared to control, luciferase-shRNA lentivirus, without late recurrence. Spectral-domain optical coherence tomography (OCT) and immunohistochemical sections (IHC) demonstrated changes in retinal layer thicknesses in L-VEGFAshRNA or L-VEGF164shRNA  compared to control. Ganzfeld electroretinograms were increased in L-VEGFAshRNA or L-VEGF164shRNA compared to control. Erythropoietin (EPO), brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, neurotrophin-3 (NT-3) mRNAs were increased in L-VEGFAshRNA, but not L-VEGF164shRNA retinas. In cultured rat Müller cells, knockdown of VEGF upregulated NT-3 and EPO, whereas treatment with EPO activated neuroprotective signaling. Methods to reduce IVNV by selective knockdown of VEGFA, and particularly VEGF164, in Müller cells may have fewer deleterious effects than nonselective VEGFA inhibition to all cells in the retina