A comparison of physical health and psychosocial variables as predictors of reaction time and serial learning performance in elderly men

Choice reaction time and serial learning tasks were studied in three groups of elderly men (aged 65 to 85), including (a) hospitalized veterans, (b) veteran outpatients, and (c) nonhospitalized veteran volunteers. Demographic variables, life satisfaction, and attitudes toward aging, as well as objective and subjective measures of physical impairment, were assessed in each group. The three groups differed on both reaction time and serial learning measures. Multivariate analysis revealed that objective physical health assessments were the best predictors of reaction time performance, whereas subjective assessments best predicted serial learning performance. More negative attitudes and life satisfaction were associated with impaired physical health, but these psychosocial measures were poor predictors of behavioral performance.     

Partial purification, characterization, and assay of a slightly acidic insulin-like peptide (ILAs) from human plasma.

An insulin radioreceptor assay (RRA) using human placental microsomal membranes was used to measure insulin-like activity (ILA) extracted from human plasma concentrates (Cohn fraction IV-4) by acid ethanol. The soluble activity (ILAs), chromatographed on Sephadex G-75 in 1 M acetic acid, migrated as a small molecule (fractional elution volume, 0.56) ahead of insulin (fractional elution volume, 0.70), whereas at neutral pH, ILAs migrated as a large molecular weight species. The ILAs peak from acid gel filtration on Sephadex was further purified by chromatography on carboxymethyl cellulose (CMC). The ILAs peak from both Sephadex and CMC diluted parallel to the porcine insulin standard in the insulin RRA and was totally unreactive in an insulin RIA. The CMC-purified material was iodinated and purified by binding to and elution from human placental membranes. The binding of [125I]ILAs to human placental membranes was inhibited only minimally by insulin and proinsulin and not at all by epidermal growth factor, nerve growth factor, glucagon, or lactogenic hormones, including human growth hormone. Multiplication-stimulating activity (MSA) inhibited in a manner parallel to ILAs. A Scatchard plot of the binding data was nonlinear. Sephadex ILAs was subjected to isoelectric focusing. The fractions assayed in both insulin and ILAs RRAs yielded comparable results. Peaks of ILA were observed at pHs 5.3, 6.6, and 8.4. When CMC-ILA was subjected to isoelectric focusing in polyacrylamide, a single peak of activity migrating between pH 6.2-6.8 was seen. [125I]ILAs focused at exactly the same pH. Electrophoresis of CMC-ILAs in acid-urea revealed a sharp peak of activity migrating with one of the five protein bands seen after staining. Again, [125I]ILAs comigrated with unlabeled ILAs. The molecular weight of ILAs, as determined on a calibrated Sephadex G-150 column at neutral pH, was 9,000-10,000 daltons. CMC-ILAs stimulated [14C]glucose incorporation into triglycerides of rat adipose tissue and augmented [3H]thymidine incorporation into human fibroblasts, chicken embryo fibroblasts, and BALB 3T3 cells as well as [35S]sulfate incorporation into macromolecules of rabbit chondrocyte culture medium. In summary, ILAs isolated on the basis of a RRA for insulin is a slightly acidic peptide with some of the biological activities expected of a somatomedin.     

Development and Psychometric Properties of a New Questionnaire to Assess Mental Health and Concerning Behaviors in Children and Young People with Autism Spectrum Disorder (ASD): The Assessment of Concerning Behavior (ACB) Scale

Journal of Autism and Developmental Disorders - Although 70% of autistic children and young people meet criteria for co-occurring psychiatric conditions, there are few screening measures...     

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.All living cells are surrounded by a lipid membrane. Eukaryotic cells also contain several internal membrane-bound organelles, which enable them to compartmentalize related biological functions and thereby to enhance the efficiency of these processes. Phospholipids are the predominant component of these membranes. Their hydrophilic head groups interact with the cytosol, whereas their hydrophobic side chains are either buried within the hydrophobic interior of a typical membrane bilayer or interact with the hydrophobic neutral lipid core of lipoproteins and lipid droplets (LDs). Phospholipids are generally defined by their organic head group with phosphatidylcholine (PC) constituting over 50% of all membrane phospholipids. PC was first isolated in the 19th century and the major enzymatic pathway involved in its synthesis was revealed by Kennedy and Weiss (1) in the 1950s. Cells synthesize PC in three consecutive steps (Fig. 1A): choline kinase phosphorylates choline before choline phosphate cytidylyltransferase 1 α (encoded by the PCYT1A gene) generates the high-energy donor CDP-choline in the rate-limiting step of the pathway. In the last step, DAG:CDP-choline cholinephosphotransferase (CPT) uses CDP-choline and diacylglycerol (DAG) to form PC (2, 3).Open in a separate windowFig. 1.Cosegregation of biallelic PCYT1A mutations with fatty liver, low HDL cholesterol levels, lipodystrophy, insulin-resistant diabetes, and short stature. (A) Schematic illustration of the Kennedy PC synthesis pathway. CK, choline kinase; CPT, CDP-choline:1,2-diacylglycerol cholinephosphotransferase; PCYT1A, choline-phosphate cytidylyltransferase A, CTP:phosphocholine-cytidylyltransferase. (B) Family pedigrees of both probands demonstrating that only compound heterozygous carriers of PCYT1A mutations manifest fatty liver (red), low HDL cholesterol (blue), lipodystrophy (yellow), and insulin resistance/type 2 diabetes (T2DM) (green). PCYT1A mutation status, height (Ht.), and body mass index (BMI) are indicated below each individual’s symbol. ND, not determined; WT, wild type. (C) The location of PCYT1A mutations E280del, V142M, and 333fs in relation to known functional domains of PCYT1A. Domain M, membrane binding domain; domain P, phosphorylated region. (D) Conservation around the V142(red*) and E280(red*) mutation sites. Sequence alignment of representative metazoan sequences in the region surrounding the mutated residues. Hydrophobic (blue) and polar (green) residues interacting with V142 are highlighted. Only residues different from the human sequence are shown. Sequence IDs: human (Homo sapiens) {"type":"entrez-protein","attrs":{"text":"P49585","term_id":"166214967"}}P49585, zebrafish (Danio rerio) F1QEN6, sea squirt (Ciona intestinalis) {"type":"entrez-protein","attrs":{"text":"XP_002130773.1","term_id":"198437270"}}XP_002130773.1, sea urchin (Strongylocentrotus purpuratus) H3I3V9, water flee (Daphnia pulex) E9G1P5, Drosophila (D. melanogaster) Q9W0D9, Caenorhabditis (C. elegans) {"type":"entrez-protein","attrs":{"text":"P49583","term_id":"32172439"}}P49583, Trichoplax (T. adherens) B3RI62. (E and F) Structure of the catalytic domain of PCYT1A highlighting the role of V142M in the core packing. The two chains in the dimer are shown in yellow and gray; the residues and the secondary structure units are highlighted in color in the yellow monomer A: loop L3 with V142, red; α-helix, green; and the interacting β-sheet, blue. The residues packing with V142 are shown in ball-and-stick and space-filling representations, the dimer stabilizing R140 is shown in ball-and-stick colored according to the atom type. E is a global view, and F is a zoomed-in view of the catalytic core.Membrane phospholipids are a defining feature of advanced life-forms so it is perhaps not surprising that the pathways involved in their synthesis are ancient, and mutations affecting them are rarely tolerated in evolution. Here, we describe the identification and characterization of pathogenic human loss-of-function mutations affecting the eponymous Kennedy pathway.