University of Iowa

About: University of Iowa is a education organization based out in Iowa City, Iowa, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 49229 authors who have published 109171 publications receiving 5021465 citations. The organization is also known as: UI & The University of Iowa.

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Abstract: Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.

Absorption and retention of lead by infants.

Abstract: Summary: Eighty-nine metabolic balance studies were performed with 12 normal infants ranging in age from 14–746 days. Intake and fecal and urinary excretions of lead were determined and net absorption and net retention were calculated. Subjects were fed milk or formula and commercially prepared strained foods. Intakes of lead ranged from 0.83–22.61 μg/kg/day with a mean of 9.43 μg/kg/day. Urinary excretion averaged 1.02 (SD 0.68) μg/kg/day and was positively correlated with lead intake (Fig. 1). Fecal excretion was highly correlated with intake of lead (Fig. 2); fecal excretion exceeded intake in 10 studies. In 61 balance studies with lead intakes greater than 5 μg/kg/day, net absorption averaged 41.5% of lead intake and net retention averaged 31.7% of intake. Retention of lead was highly correlated with lead intake (Fig. 3). Urinary plus fecal excretion of lead exceeded intake in 19 of 28 balances in which lead intakes were less than 5 μg/kg/day. Absorption and retention of lead were inversely correlated with intake of calcium (Fig. 4). Absorption and retention of lead accounted for greater percentages of intake of lead in this study of infants and young children than have been reported in studies of older subjects. Speculation: Highly efficient absorption and retention of ingested lead by young children may be partly responsible for the high prevalence of lead intoxication in this age group.

Knowledge without awareness: an autonomic index of facial recognition by prosopagnosics

Abstract: Prosopagnosia, the inability to recognize visually the faces of familiar persons who continue to be normally recognized through other sensory channels, is caused by bilateral cerebral lesions involving the visual system. Two patients with prosopagnosia generated frequent and large electrodermal skin conductance responses to faces of persons they had previously known but were now unable to recognize. They did not generate such responses to unfamiliar faces. The results suggest that an early step of the physiological process of recognition is still taking place in these patients, without their awareness but with an autonomic index.

On Delay Fault Testing in Logic Circuits

Abstract: Correct operation of a logic circuit requires propagation delays of all paths in the circuit to be smaller than the intended "clock interval." Random or deterministic tests, conducted at the normal clocking rate, can be used to insure that path delays in manufactured circuits meet the specifications. Algorithms, based on a five-valued logic system, to accurately calculate the detection probability of path delay faults by random delay tests as well as to derive deterministic tests to detect path delay faults are proposed. The results can be used to determine the test length for a desired confidence level in testing a path fault when random tests are used, and to generate a test set for a list of delay faults when deterministic tests are used.

A genome-wide scan for common alleles affecting risk for autism

Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.