Identification of the Abundant Hydroxyproline-Rich Glycoproteins in the Root Walls of Wild-Type Arabidopsis, an ext3 Mutant Line, and Its Phenotypic Revertant

Extensins are members of the cell wall hydroxyproline-rich glycoprotein (HRGP) superfamily that form covalently cross-linked networks in primary cell walls. A knockout mutation in EXT3 (AT1G21310), the gene coding EXTENSIN 3 (EXT3) in Arabidopsis Landsberg erecta resulted in a lethal phenotype, although about 20% of the knockout plants have an apparently normal phenotype (ANP). In this study the root cell wall HRGP components of wild-type, ANP and the ext3 mutant seedlings were characterized by peptide fractionation of trypsin digested anhydrous hydrogen fluoride deglycosylated wall residues and by sequencing using LC-MS/MS. Several HRGPs, including EXT3, were identified in the wild-type root walls but not in walls of the ANP and lethal mutant. Indeed the ANP walls and walls of mutants displaying the lethal phenotype possessed HRGPs, but the profiles suggest that changes in the amount and perhaps type may account for the corresponding phenotypes

Age and African-American race impact the validity and reliability of the asthma control test in persistent asthmatics

Abstract Background The Asthma Control Test (ACT) is widely used to assess asthma control, yet the validity and reliability of the test have not been specifically evaluated in adolescents or African-Americans. We conducted a prospective psychometric study of the ACT in African-American (AA) and non-African-American (nAA) adolescents with persistent asthma, with emphasis on the clinical utility of the test for medical decision making. Methods Participants completed the ACT and performed spirometry. A physician conducted a guidelines-based assessment of asthma control, blinded to the ACT score. Study procedures were repeated 6–8 weeks later. The ACT-based asthma control assessment was compared to physician assessment. Results For baseline and follow-up visits, internal consistency, as measured using Cronbach’s alpha, was 0.80 and 0.81 in AA teens and 0.80 and 0.83 in nAA teens. Intraclass correlation coefficients were 0.59 and 0.76 in AA and nAA teens, respectively, with stable asthma control over time. Agreement between ACT and physician assessment was moderate in AA teens and fair in nAA teens. An ACT score of ≤19 showed reduced sensitivity for not well controlled asthma in both groups, while a score of ≤21 had the greatest area under the ROC curve. ACT scores were marginally responsive to change in control status. Conclusions Concerns for the ACT’s ability to detect uncontrolled asthma in adolescents emphasizes the need for a more comprehensive evaluation of asthma control in clinical settings. A higher threshold ACT score to define not well controlled asthma may be needed if the ACT is to be used for medical decision making. Trial registration ClinicalTrials.gov: NCT02671643 , NCT02662413

PEARLS: Near Infrared Photometry in the JWST North Ecliptic Pole Time Domain Field

We present Near-Infrared (NIR) ground-based Y, J, H, and K imaging obtained in the James Webb Space Telescope North Ecliptic Pole Time Domain Field (TDF) using the MMT-Magellan Infrared Imager and Spectrometer (MMIRS) on the MMT.These new observations cover a field of approximately 230 arcmin^2 in Y, H, and K and 313 arcmin^2 in J. Using Monte Carlo simulations we estimate a 1 sigma depth relative to the background sky of (Y, J, H, K}) = (23.80, 23.53, 23.13, 23.28) in AB magnitudes for point sources at a 95% completeness level. These observations are part of the ground-based effort to characterize this region of the sky, supplementing space-based data obtained with Chandra, NuSTAR, XMM, AstroSat, HST, and JWST. This paper describes the observations and reduction of the NIR imaging and combines these NIR data with archival imaging in the visible, obtained with the Subaru Hyper-Suprime-Cam, to produce a merged catalog of 57,501 sources. The new observations reported here, plus the corresponding multi-wavelength catalog, will provide a baseline for time-domain studies of bright sources in the TDF.Comment: 23 pages, 10 figures. Accepted for publication in ApJS. Images and catalogs available at https://doi.org/10.5281/zenodo.7934393. Data description available under ancillary files and at the Zenodo site. Added a reference, fixed typos in metadat

PEARLS: Near-infrared Photometry in the JWST North Ecliptic Pole Time Domain Field * * Partly based on observations taken with the MMT, a joint facility operated by the University of Arizona and the Smithsonian Institution.

We present near-infrared (NIR) ground-based Y, J, H, and K imaging obtained in the James Webb Space Telescope (JWST) North Ecliptic Pole Time Domain Field (NEP TDF) using the MMT-Magellan Infrared Imager and Spectrometer on the MMT. These new observations cover a field of approximately 230 arcmin2 in Y, H, and K, and 313 arcmin2 in J. Using Monte Carlo simulations, we estimate a 1σ depth relative to the background sky of (Y, J, H, K) = (23.80, 23.53, 23.13, 23.28) in AB magnitudes for point sources at a 95% completeness level. These observations are part of the ground-based effort to characterize this region of the sky, supplementing space-based data obtained with Chandra, NuSTAR, XMM, AstroSat, Hubble Space Telescope, and JWST. This paper describes the observations and reduction of the NIR imaging and combines these NIR data with archival imaging in the visible, obtained with the Subaru Hyper-Suprime-Cam, to produce a merged catalog of 57,501 sources. The new observations reported here, plus the corresponding multiwavelength catalog, will provide a baseline for time-domain studies of bright sources in the NEP TDF

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

Purpose Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. Methods Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. Results Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. Conclusions This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features

Age and African-American race impact the validity and reliability of the asthma control test in persistent asthmatics

Abstract Background The Asthma Control Test (ACT) is widely used to assess asthma control, yet the validity and reliability of the test have not been specifically evaluated in adolescents or African-Americans. We conducted a prospective psychometric study of the ACT in African-American (AA) and non-African-American (nAA) adolescents with persistent asthma, with emphasis on the clinical utility of the test for medical decision making. Methods Participants completed the ACT and performed spirometry. A physician conducted a guidelines-based assessment of asthma control, blinded to the ACT score. Study procedures were repeated 6–8 weeks later. The ACT-based asthma control assessment was compared to physician assessment. Results For baseline and follow-up visits, internal consistency, as measured using Cronbach’s alpha, was 0.80 and 0.81 in AA teens and 0.80 and 0.83 in nAA teens. Intraclass correlation coefficients were 0.59 and 0.76 in AA and nAA teens, respectively, with stable asthma control over time. Agreement between ACT and physician assessment was moderate in AA teens and fair in nAA teens. An ACT score of ≤19 showed reduced sensitivity for not well controlled asthma in both groups, while a score of ≤21 had the greatest area under the ROC curve. ACT scores were marginally responsive to change in control status. Conclusions Concerns for the ACT’s ability to detect uncontrolled asthma in adolescents emphasizes the need for a more comprehensive evaluation of asthma control in clinical settings. A higher threshold ACT score to define not well controlled asthma may be needed if the ACT is to be used for medical decision making. Trial registration ClinicalTrials.gov: NCT02671643, NCT02662413

Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force

International audienceAlthough the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder