Results of genetic analysis of 11 341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States.

Background: Hemophilia A (HA) and hemophilia B (HB) are rare inherited bleeding disorders. Although causative genetic variants are clinically relevant, in 2012 only 20% of US patients had been genotyped.

Objectives: My Life, Our Future (MLOF) was a multisector cross-sectional US initiative to improve our understanding of hemophilia through widespread genotyping.

Long-term outcomes of biliary atresia patients surviving with their native livers.

Portoenterostomy (PE) has remained as the generally accepted first line surgical treatment for biliary atresia (BA) for over 50 years. Currently, close to half of BA patients survive beyond 10 years with their native livers, and most of them reach adulthood without liver transplantation (LT). Despite normalization of serum bilirubin by PE, ductular reaction and portal fibrosis persist in the native liver.

Neurocognitive and Motor Functions in Biliary Atresia Patients: A Cross-sectional, Prospective National Cohort Study.

Objectives: The aim of the study was to evaluate the neurocognitive and motor development of biliary atresia (BA) patients in childhood and adolescence and to identify risk factors for impaired outcome.

Methods: We invited all BA patients between ages 1 and 20 years followed up at Helsinki University Children's Hospital in Finland between 1 January 2019 to 31 January 2020 to participate. All participants underwent age-appropriate validated neurocognitive tests.

Impaired Bone Health in Children With Biliary Atresia.

Objectives: The aim of the study was to examine the frequency of rickets and bone fractures and to assess areal bone mineral density (aBMD) in childhood among patients with biliary atresia (BA).

Methods: We gathered data on all patients diagnosed with BA in Finland that survived to ≥1 year of age between 1 January 2000 to 30 June 2018. Data on gestational age, birth weight, postsurgical medications, and history of rickets and bone fractures were collected retrospectively.

Growth of children with biliary atresia living with native livers: impact of corticoid therapy after portoenterostomy.

We addressed growth of biliary atresia (BA) patients living with native livers between ages 0-6 and effects of post-surgical corticosteroid treatment on growth. Growth charts of 28 BA patients born in Finland between 1987 and 2017 were retrospectively evaluated. Dosage and length of corticosteroid treatment and hydrocortisone substitution were reviewed.

Evaluation of the confusion matrix method in the validation of an automated system for measuring feeding behaviour of cattle.

The aim of the present study was to evaluate empirically confusion matrices in device validation. We compared the confusion matrix method to linear regression and error indices in the validation of a device measuring feeding behaviour of dairy cattle. In addition, we studied how to extract additional information on classification errors with confusion probabilities.

Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative.

Hemophilia A and B are rare, X-linked bleeding disorders. My Life, Our Future (MLOF) is a collaborative project established to genotype and study hemophilia. Patients were enrolled at US hemophilia treatment centers (HTCs).

Starch storage in the stems of wheat plants: localization and temporal changes.

Background And Aims: Carbohydrate temporarily accumulates in wheat stems during the early reproductive growth phase, predominantly as water soluble carbohydrate (WSC), and is subsequently remobilized during grain filling. Starch has also been reported as a minor storage carbohydrate component in wheat stems, but the details are lacking.

Methods: The accumulation and localization of starch in wheat stem and leaf sheath tissue over a developmental period from 6 d before anthesis to 35 d after anthesis was investigated.

Large scale transcriptome analysis of the effects of nitrogen nutrition on accumulation of stem carbohydrate reserves in reproductive stage wheat.

We investigated the molecular basis of the long-term adaptation to nitrogen (N) limitation of wheat plants grown in a simulated crop canopy, with a focus on the stage when carbon (C) reserves are accumulated in stems for later remobilization to grain. A cDNA microarray representing approximately 36,000 unique sequences was used to compare gene expression in a number of above-ground organs at anthesis. Fructan accumulation in stems was accompanied by elevated transcripts for a suite of fructosyltransferases (FTs) and for a fructan 6-exohydrolase (6-FEH) in the low N compared to high N stems.

Genotypic variation in water-soluble carbohydrate accumulation in wheat.

The water-soluble carbohydrate (WSC) that accumulates in the stems of wheat during growth can be an important contributor to grain filling, particularly under conditions when assimilation is limited, such as during end-of-season drought. WSC concentration was measured at anthesis across a diverse set of wheat genotypes over multiple environments. Environmental differences in WSC concentration were large (means for the set ranging between 108 and 203 mg g dry weight), and there were significant and repeatable differences in WSC accumulation among genotypes (means ranging from 112 to 213 mg g dry weight averaged across environments), associated with large broad-sense heritability (H = 0.

An association between manganese superoxide dismutase polymorphism and outcome of chemotherapy in acute myeloid leukemia.

Manganese superoxide dismutase (MnSOD) protects cells against oxidative stress by eliminating superoxides. Hypothetically, decreased MnSOD levels in cancer might lead to increased oxidative stress and, thus, to increased sensitivity of cells to chemotherapy agents. Eighty-nine patients with acute myeloid leukemia (AML) were analyzed for a functional C to T polymorphism of MnSOD, which could potentially lead to decreased enzyme concentrations inside mitochondria.

The capacity of green oilseeds to utilize photosynthesis to drive biosynthetic processes.

Seeds of many plant species are green during embryogenesis. To directly assess the influence of light on the physiological status of green oilseeds in planta, Brassica napus and soybean (Glycine max) seeds were rapidly dissected from plants growing in the light or dark. The activation state of malate dehydrogenase, which reflects reduced thioredoxin and NADP/NADPH ratios, was found to be as high in seeds exposed to light as in leaves and to decrease in the dark.

Arabidopsis genes involved in acyl lipid metabolism. A 2003 census of the candidates, a study of the distribution of expressed sequence tags in organs, and a web-based database.

The genome of Arabidopsis has been searched for sequences of genes involved in acyl lipid metabolism. Over 600 encoded proteins have been identified, cataloged, and classified according to predicted function, subcellular location, and alternative splicing. At least one-third of these proteins were previously annotated as "unknown function" or with functions unrelated to acyl lipid metabolism; therefore, this study has improved the annotation of over 200 genes.

Contrapuntal networks of gene expression during Arabidopsis seed filling.

We have used cDNA microarrays to examine changes in gene expression during Arabidopsis seed development and to compare wild-type and mutant wrinkled1 (wri1) seeds that have an 80% reduction in oil. Between 5 and 13 days after flowering, a period preceding and including the major accumulation of storage oils and proteins, approximately 35% of the genes represented on the array changed at least twofold, but a larger fraction (65%) showed little or no change in expression. Genes whose expression changed most tended to be expressed more in seeds than in other tissues.

Fatty acid synthesis: from CO2 to functional genomics.

For over 25 years there has been uncertainty over the pathway from CO(2) to acetyl-CoA in chloroplasts. On the one hand, free acetate is the most effective substrate for fatty acid synthesis by isolated chloroplasts, and free acetate concentrations reported in leaf tissue (0.1-1 mM) appear adequate to saturate fatty acid synthase.

Electron flow to oxygen in higher plants and algae: rates and control of direct photoreduction (Mehler reaction) and rubisco oxygenase.

Linear electron transport in chloroplasts produces a number of reduced components associated with photosystem I (PS I) that may subsequently participate in reactions that reduce O2. The two primary reactions that have been extensively studied are: first, the direct reduction of O2 to superoxide by reduced donors associated with PS I (the Mehler reaction), and second, the rubisco oxygenase (ribulose 1,5-bisphosphate carboxylase oxygenase EC 4.1.

Microarray analysis of developing Arabidopsis seeds.

To provide a broad analysis of gene expression in developing Arabidopsis seeds, microarrays have been produced that display approximately 2,600 seed-expressed genes. DNA for genes spotted on the arrays were selected from >10,000 clones partially sequenced from a cDNA library of developing seeds. Based on a series of controls, sensitivity of the arrays was estimated at one to two copies of mRNA per cell and cross hybridization was estimated to occur if closely related genes have >70% to 80% sequence identity.

Photosynthetic electron sinks in transgenic tobacco with reduced amounts of Rubisco: little evidence for significant Mehler reaction.

Transgenic tobacco (Nicotiana tabacum L. cv. W38) plants with an antisense gene directed against the mRNA of the small subunit of Rubisco were used to investigate the role of O2 as an electron acceptor during photosynthesis.

G239T mutation in Repeat 1 of human IRBP: possible implications for more than one binding site in a single repeat.

Purpose: Interphotoreceptor retinoid-binding protein(IRBP) is a four-repeat protein found in the interphotoreceptor space. Each repeat can bind retinoids and fatty acids. The purpose of this study was to examine the effects of the single amino acid substitution, G239T, versus the wild type sequence of human IRBP Repeat 1, on ligand binding at equilibrium, ligand off rates, and protection of retinol from degradation.

Effects of dispersed point substitutions in Repeat 1 of human interphotoreceptor retinoid binding protein (IRBP).

Purpose: The purpose of this study was to measure the effects of mutations on the retinol binding capability of human Repeat 1 of interphotoreceptor retinoid-binding protein (IRBP). First, we predicted important functional amino acids by several computer programs. We also noted the lack of shared functions between Tail-specific protease (Tsp) and IRBP, which bear sequence similarity, and this aided in predicting functional residues.

Prediction of structural and functional relationships of Repeat 1 of human interphotoreceptor retinoid-binding protein (IRBP) with other proteins.

Purpose: We compared the structure and function of interphotoreceptor retinoid-binding protein (IRBP) related proteins and predicted domain and secondary structure within each repeat of IRBP and its relatives. We tested whether tail specific protease (Tsp), which bears sequence similarity to IRBP Domain B, binds fatty acids or retinoids, and whether IRBP possessed protease activity resembling Tsp's catalytic function. These tests helped us to learn whether the primary sequence similarities of family members extended to higher order structural and functional levels.

The role of chloroplast electron transport and metabolites in modulating Rubisco activity in tobacco. Insights from transgenic plants with reduced amounts of cytochrome b/f complex or glyceraldehyde 3-phosphate dehydrogenase.

Leaf metabolites, adenylates, and Rubisco activation were studied in two transgenic tobacco (Nicotiana tabacum L. cv W38) types. Plants with reduced amounts of cytochrome b/f complex (anti-b/f) have impaired electron transport and a low transthylakoid pH gradient that restrict ATP and NADPH synthesis.