The Astropy Project supports and fosters the development of open-source and openly developed Python packages that provide commonly needed functionality to the astronomical community. A key element of ...the Astropy Project is the core package astropy, which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project.
We report a kindred in which two siblings suffered spontaneous venous thromboses in the second decade of life. Further investigation showed reduced coagulation factor V (FV) activity and activated ...protein C resistance (APCR) ratio but no other thrombophilic abnormalities. The reduction in APCR ratio persisted in a modified APCR assay in which FV activity was normalized between test and control plasmas. Analysis of the FV gene showed that the thrombotic individuals had a complex genotype that included two novel point mutations c.529G>T and c.1250T>C resulting in FV E119X and FV I359T substitutions inherited on different alleles. Individuals in the kindred with FV E119X or FV I359T substitutions alone were asymptomatic. We suggest that the FV I359T substitution confers pro‐thrombotic risk and APCR, but that this is only clinically manifest when co‐inherited with the FV E119X allele. The FV I359T substitution creates a new consensus sequence for N‐linked glycosylation within the FV heavy chain and we speculate that this abnormal glycosylation may disrupt activated protein C‐mediated proteolysis of the variant FV and FVa.
Background—Serum ferritin is normally a marker of iron overload. Ferritin genes are sited at chromosomes 19 and 11. Regulation of ferritin synthesis involves an interaction between an iron regulatory ...protein (IRP) and part of the ferritin mRNA designated the iron regulatory element (IRE). A disorder of ferritin synthesis resulting in hyperferritinaemia in the absence of iron overload has been described recently. Patients and methods—Hyperferriti- naemia in the absence of iron overload was detected in a patient who was investigated for possible haemochromatosis. Serum iron, transferrin saturation, and ferritin concentration were studied in 11 members of this patient’s family from three generations. Eight members had DNA samples analysed by direct cycle sequencing of the 5′ untranslated region of the L ferritin gene. Results—Six of the family members studied had serum ferritin concentrations greater than 900 μg/l. However, serum iron and transferrin saturation were normal in these subjects who all had evidence of cataracts. Three affected family members who had genetic studies of the L ferritin gene on chromosome 19 had an A to G point mutation which was not found in unaffected members. Conclusions—There was complete concordance between a mutated IRE, cataracts, and hyperferritinaemia in three generations of this family. This family study confirms the finding that hereditary hyperferritinaemia in the absence of iron overload is an autosomal dominant inherited disorder.
To describe the cataract morphology and genetic and biochemical findings in a four-generation family with hereditary hyperferritinemia cataract syndrome (HHCS).
Family members of the proband with ...HHCS were investigated. DNA sequencing was carried out to identify the iron responsive element (IRE) of the L-ferritin gene in affected and non-affected family members. Molecular modeling allowed prediction of the structure of the mutant IRE in affected cases. Serum ferritin and transferrin saturation were determined using standard methods. All family members underwent slit lamp examination by an ophthalmologist to document presence of cataract or lens status. Cataract morphology was documented where present.
This family with HHCS had the genetic heterozygous mutation G32C in the IRE of the L-ferritin mRNA. Lens opacities were detectable in young members of the family, and morphology of cataracts was consistent with previous reports. Biochemical testing demonstrated high serum ferritin levels in affected individuals.
The morphology of cataracts in HHCS seems to be similar in all cases. In the heterozygous G32C mutation, the age at onset of cataracts is very early. Greater awareness of this condition among ophthalmologists will lead to effective family counseling of those affected, by genetic testing or simple biochemical tests. Serum ferritin levels can be effectively used to screen for this condition in suspected families.
Kelp forests form an important biogenic habitat that responds to natural and human drivers. Global concerns exist about threats to kelp forests, yet long-term information is limited and research ...suggests that trends are geographically distinct. We examined distribution of the bull kelp Nereocystis luetkeana over 145 years in South Puget Sound (SPS), a semi-protected inner basin in a fjord estuary complex in the northeast Pacific Ocean. We synthesized 48 historical and modern Nereocystis surveys and examined presence/absence within 1-km segments along 452 km of shoreline. Compared to the earliest baseline in 1878, Nereocystis extent in 2017 decreased 63%, with individual sub-basins showing up to 96% loss. Losses have persisted for decades, across a range of climate conditions. In recent decades, Nereocystis predominantly occurred along shorelines with intense currents and mixing, where temperature and nutrient concentrations did not reach thresholds for impacts to Nereocystis performance, and high current speeds likely excluded grazers. Losses predominated in areas with elevated temperature, lower nutrient concentrations, and relatively low current velocities. The pattern of long-term losses in SPS contrasts with stability in floating kelp abundance during the last century in an area of the Salish Sea with greater wave exposure and proximity to oceanic conditions. These findings support the hypothesis that kelp beds along wave-sheltered shorelines exhibit greater sensitivity to environmental stressors. Additionally, shorelines with strong currents and deep-water mixing may provide refugia within sheltered systems.
IL-1 converting enzyme (ICE) specifically cleaves the human IL-1 beta precursor at two sequence-related sites: Asp27-Gly28 (site 1) and Asp116-Ala117 (site 2). Cleavage at Asp116-Ala117 results in ...the generation of mature, biologically active IL-1 beta. ICE is unusual in that preferred cleavage at Asp-X bonds (where X is a small hydrophobic residue), has not been described for any other eukaryotic protease. To further examine the substrate specificity of ICE, proteins that contain Asp-X linkages including transferrin, actin, complement factor 9, the murine IL-1 beta precursor, and human and murine IL-1 alpha precursors, were assayed for cleavage by 500-fold purified ICE. The human and murine IL-1 beta precursors were the only proteins cleaved by ICE, demonstrating that ICE is an IL-1 beta convertase. Analysis of human IL-1 beta precursor mutants containing amino acid substitutions or deletions within each processing site demonstrated that omission or replacement of Asp at site 1 or site 2 prevented cleavage by ICE. To quantitatively assess the substrate requirements of ICE, a peptide-based cleavage assay was established using a 14-mer spanning site 2. Cleavage between Asp P1 and Ala P1'2 was demonstrated. Replacement of Asp with Ala, Glu, or Asn resulted in a greater than 100-fold reduction in cleavage activity. The rank order in position P1' was Gly greater than Ala much greater than Leu greater than Lys greater than Glu. Substitutions at P2'-P4' and P6' had relatively little effect on cleavage activity. These results show that ICE is a highly specific IL-1 beta convertase with absolute requirements for Asp in P1 and a small hydrophobic amino acid in P1'.
Neonatal thrombocytopenia, defined as the presence of a circulating platelet count <150 × 109/L, is a common abnormality in babies admitted to neonatal intensive care units. Thrombocytopenia that is ...typically mild and self-limiting often accompanies neonatal stress in scenarios such as premature delivery or intrauterine growth restriction. However, the differential diagnosis of neonatal thrombocytopenia is wide and includes potentially life-threatening disorders, such as bacterial sepsis, viral infection, and necrotizing enterocolitis. Distinguishing these causes of thrombocytopenia from entities such as genetic thrombocytopenia and fetal and neonatal alloimmune thrombocytopenia is critical for the accurate quantitation of significant adverse events, such as intracranial bleeding, and for the selection of treatments, such as platelet transfusion. In this review, we focus on common differential diagnoses of neonatal thrombocytopenia and highlight how the landscape of diagnosis and management is changing with recent advances in genomic technology and the completion of pivotal clinical trials of platelet transfusion practice. Increasing evidence highlights the need for judicious and restrictive use of platelet transfusions in neonates.
Extratropical cyclones (ETCs) are the primary driver of large-scale episodic beach erosion along coastlines in temperate regions. However, key drivers of the magnitude and regional variability in ...rapid morphological changes caused by ETCs at the coast remain poorly understood. Here we analyze an unprecedented dataset of high-resolution regional-scale morphological response to an ETC that impacted southeast Australia, and evaluate the new observations within the context of an existing long-term coastal monitoring program. This ETC was characterized by moderate intensity (for this regional setting) deepwater wave heights, but an anomalous wave direction approximately 45 degrees more counter-clockwise than average. The magnitude of measured beach volume change was the largest in four decades at the long-term monitoring site and, at the regional scale, commensurate with that observed due to extreme North Atlantic hurricanes. Spatial variability in morphological response across the study region was predominantly controlled by alongshore gradients in storm wave energy flux and local coastline alignment relative to storm wave direction. We attribute the severity of coastal erosion observed due to this ETC primarily to its anomalous wave direction, and call for greater research on the impacts of changing storm wave directionality in addition to projected future changes in wave heights.
This data descriptor outlines a shared neuroimaging dataset from the UCLA Consortium for Neuropsychiatric Phenomics, which focused on understanding the dimensional structure of memory and cognitive ...control (response inhibition) functions in both healthy individuals (130 subjects) and individuals with neuropsychiatric disorders including schizophrenia (50 subjects), bipolar disorder (49 subjects), and attention deficit/hyperactivity disorder (43 subjects). The dataset includes an extensive set of task-based fMRI assessments, resting fMRI, structural MRI, and high angular resolution diffusion MRI. The dataset is shared through the OpenfMRI project, and is formatted according to the Brain Imaging Data Structure (BIDS) standard.
Most studies of folate metabolism and reproduction have been conducted after pregnancy and in folate-deficient populations. However, measurement of maternal folate status preconceptionally may be ...most relevant to certain folate-linked early processes preceding a successful pregnancy, and there has been a major increase in folate concentrations in women of childbearing age in high resource settings.
To examine associations between preconceptional biomarkers of maternal folate status (folate and homocysteine) and reproductive outcomes in folate-replete women.
Cohort nested within the Effects of Aspirin in Gestation and Reproduction trial, a block-randomized, double-blind, placebo-controlled trial whereby women were randomized to daily low-dose aspirin (81 mg/day) or placebo and all women received folic acid (400 μg/day). In total, 1228 women with 1–2 previous pregnancy losses and no documented infertility were recruited from 4 clinical sites in the United States (2006–2012) and were attempting pregnancy for up to 6 menstrual cycles. Log-binomial regression models were used to estimate relative risks and 95% confidence intervals between preconception serum folate and plasma homocysteine for anovulation, pregnancy, and pregnancy loss.
Greater plasma homocysteine was nonlinearly associated with greater risks of pregnancy loss only among women with 2 previous losses: a relative risk of 1.43 (95% confidence interval, 1.08–1.89) was found for plasma homocysteine concentrations at the study median of 8.0 μmol/L compared with a US population median of 6.0 μmol/L. No meaningful relationships were found between serum folate and any reproductive outcome or between plasma homocysteine and anovulation or becoming pregnant.
These data justify further study of the role of folate and homocysteine metabolism in normal and abnormal early pregnancy.
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