The incorporation of iodine in thyroid hormone may stem from its role as a prehistoric signal of ecologic opportunity: an evolutionary perspective and implications for modern diseases

To optimize fitness under conditions of varying Darwinian opportunity, organisms demonstrate tremendous plasticity in their life-history strategies based on their perception of available resources. Higher-energy environments generally promote more aggressive life-history strategies, such as faster growth, larger adult size, greater genetic variation, shorter lifespan, larger brood sizes, and offspring ratio skewed towards the larger-sized gender. While numerous mechanisms regulate life-history plasticity including genetic imprinting, methylation, and growth factors, evidence suggests that thyroid hormone plays a central role. Given the pivotal adaptive role of thyroid hormone, the teleology of its dependence on dietary iodine for production remains unexplained. We hypothesize that iodine may have emerged as a substrate for production of thyroid hormone in prehistoric ecosystems because the former represented a reliable proxy for ecologic potential that enabled the latter to modulate growth, reproduction, metabolic rate, and lifespan. Such a scenario may have existed in early marine ecosystems where ocean-surface vegetation, which concentrates iodine for its antimicrobial and antioxidant properties, formed the basis of the food chain. Teleologic parallels can be drawn to the food-chain accumulation of antimicrobials that also exhibit antioxidant properties and promote adult size, brood size, and offspring quality by modulating central hormonal axes. As each higher species in the food chain tunes its life-history strategy based on iodine intake, the coupling of this functional role of iodine with its value as a resource signal to the next member of the food-chain may promote runaway evolution. Whereas predators in prehistoric ecosystems successfully tuned their life-history strategy using iodine as a major input, the strategy may prove maladaptive in modern humans for whom the pattern of iodine intake is decoupled from resource availability. Iodine acquired through sodium iodide supplementation may independently contribute to some biologic dysfunctions currently attributed to sodium.     

Apparent mitochondrial asymmetry in Xenopus eggs.

Cell polarity is manifest along the animal/vegetal axis in eggs of the frog, Xenopus laevis. Along this axis, maternal cytoplasmic components are asymmetrically distributed and are thought to underlie specification of distinct cell fates. To ascertain the molecular identities of such cytoplasmic components, we have used a monoclonal antibody that specifically stains the vegetal hemisphere of Xenopus eggs. The antigenic protein Vp67 (vegetal protein of 67 kDa) was identified through purification and cloning as a Xenopus homolog of the mitochondrial protein dihydrolipoamide acetyltransferase, a component of the pyruvate dehydrogenase complex. The identification of Vp67 as a mitochondrial protein could indicate that populations of mitochondria are asymmetrically distributed in Xenopus eggs.     

A modified human ELISPOT assay to detect specific responses to primary tumor cell targets

Background  

The desired outcome of cancer vaccination is to induce a potent T cell response which can specifically recognize and eliminate autologous tumor cells in vivo. Accordingly, immunological assays that demonstrate recognition of native tumor cells (tumor-specific) may be more clinically relevant than assays that demonstrate recognition of tumor protein or peptide (antigen-specific).     

Amino acid sequences of myosin essential and regulatory light chains from two clam species: Comparison with other molluscan myosin light chains

Summary We have determined the amino acid sequences of the essential light chains (ELC) and regulatory light chains (RLC) of myosin from two species of clam,Mercenaria mercenaria andMacrocallista nimbosa, using protein chemistry methods. The N-termini of all four proteins were blocked, and sequencing was carried out on various chemically and enzymatically produced peptide fragments. Cleavage of eitherMercenaria RLC (MRLC) orMacrocallista RLC (VLC) at its 3 Arg yielded four peptides, three of which could not be sequenced directly, due to an N-terminal blocking group and 2 Arg-Gln bonds in these proteins. The fourth peptide was partially and specifically cleaved at an unusually reactive residue, Met-64, which is invariant in all known RLC sequences. A comparison of all available molluscan ELC and RLC sequences was carried out in search of clues to functionally important features of these proteins in muscles which are regulated by a Ca²⁺-sensitive myosin. By analogy with other RLCs, VRLC and MRLC may be phosphorylated at Ser-11 by an endogenous kinase. All myosin light chains, like troponin C and calmodulin, contain four homologous regions, I to IV, each of which contains a twelve-residue potential Ca²⁺-binding loop flanked on either side by a pair of helices. All RLCs, including those from Ca²⁺-insensitive myosins, contain a divalent cation-binding site in region I. Clam and other molluscan ELCs contain a single Ca²⁺-binding site in region III. This site is present only in the ELCs of myosins that are regulated by direct binding of Ca²⁺. The ELC site III is likely to play a key role in the regulation of molluscan muscle contraction.     

Bladder acellular matrix as a substrate for studying in vitro bladder smooth muscle-urothelial cell interactions

The objective of this study was to evaluate the ability of bladder acellular matrix (BAM) to support the individual and combined growth of primary porcine bladder smooth muscle (SMC) and urothelial (UEC) cells. An in vitro co-culture system was devised to evaluate the effect of UEC on (i) SMC-mediated contraction of BAM discs, and (ii) SMC invasiveness into BAM. Cells were seeded onto BAM discs under 4 different culture conditions. Constructs were incubated for 1, 7, 14 and 28 days. Samples were then harvested for evaluation of matrix contraction. Immunohistochemistry (IHC) was utilized to examine cellular organization within the samples and conditioned media supernatants analyzed for net gelatinase activity. BAM contraction was significantly increased with co-culture. The same side co-culture configuration lead to a greater reduction in surface area than opposite side co-culture. IHC revealed enhanced SMC infiltration into BAM when co-culture was utilized. A significant increase in net gelatinase activity was also observed with the co-culture configuration. Enhanced infiltration and contractile ability of bladder SMCs with UEC co-culture may, in part, be due to an increase in gelatinase activity. The influence of bladder UECs on SMC behaviour in vitro indicates that BAM may contain some key inductive factors that serve to promote important bladder cell-cell and cell-matrix interactions.     

Chronic hyperplastic eosinophilic sinusitis as a predictor of aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a disease of intense eosinophilic inflammation that can produce fibrosis, hyperplasia, and remodeling. OBJECTIVE: To investigate the usefulness of quantifying severity of chronic hyperplastic eosinophilic sinusitis in predicting the presence of AERD. METHODS: Data were compared between asthmatic patients who reported exacerbations after aspirin ingestion and those who did not. The primary outcome measure was severity of sinusitis using a validated computed tomography (CT) scan-based scoring system. Indices of lower airway remodeling and other markers of inflammation were also evaluated. RESULTS: Twenty-one patients with AERD were compared with 19 patients with aspirin-tolerant asthma (ATA). Patients were well matched for asthma severity as shown by their similar lung function as measured by postbronchodilator forced expiratory volume in 1 second. Patients with AERD were distinguished by their sinus CT scores (AERD patients: 16.9; 95% confidence interval [CI], 13.4-21.3; ATA patients: 6.2; 95% CI, 4.2-9.1; P < .001), and they were considerably more likely to have nasal polyps (AERD patients: 90%; ATA patients: 26%; P < .001). In addition, AERD patients demonstrated increased total lung capacity (AERD patients: 107.9%; 95% CI, 99.9%-117.6%; ATA patients: 98.0%; 95% CI, 93.7%-102.5%; P = .05), reflecting a trend toward increased air trapping. No significant differences occurred in diffusing capacity, exhaled nitric oxide, eosinophilia, or exhaled breath condensate pH. CONCLUSIONS: AERD can be distinguished from ATA by the extent of hyperplasia on CT scan and the presence of nasal polyps. We hypothesize that AERD represents a remodeling process that affects both the upper and lower airways.     

Factor structure and validity of the parenting scale.

Confirmatory factor analyses based on the scoring derived from 5 prior studies of the Parenting Scale were conducted using a representatively recruited sample of 453 couples parenting 3-to 7-year-old children. Comparative analyses favored the Reitman et al. (2001) 2-factor scoring system as well as a 3-factor solution, including Lax, Overreactive, and Hostile discipline. This 3-factor solution demonstrated good fit across parent gender and child age and gender. Mothers rated themselves as more overreactive than fathers. The factor scores correlated significantly with several validity measures, including child behavior problems. The Hostile factor contributed significantly to the prediction of child behavior problems after controlling for Lax and Overreactive discipline. Both parents reported using more dysfunctional discipline than they thought they should.     

Using path analysis to understand executive function organization in preschool children

There continues to be no consensus definition of executive functions. One way to understand different executive function components is to study abilities at their emergence, that is, early in development, and use advanced statistical methods to understand the interrelations among executive processes. However, to fully determine the constructs of interest, these methods often require complete data on a large battery of tasks, which are difficult to obtain with young children. Path analysis is an alternative statistical technique that requires only a single measure of each construct, yet still allows researchers to investigate complex relations among measures, to compare nested models, and to compare model fit across groups. Therefore, 117 preschool children (ages 2 years 8 months to 6 years 0 months) completed several executive function tasks. Path analysis was used to determine the relations between complex problem solving and working memory, inhibition, and set shifting processes. The best-fitting model included paths from working memory and inhibition to problem solving, and a correlation between working memory and inhibition. Interestingly, in younger children, inhibition was the strongest predictor of problem solving, whereas working memory contributed more strongly in older children. Suggestions for useful statistical methods to investigate the relations among executive functions in children are discussed.     

Recombinant Helicobacter bilis Protein P167 for Mouse Serodiagnosis in a Multiplex Microbead Assay

Infection of mice with Helicobacter bilis is widespread in research and commercial mouse colonies. Therefore, sensitive, specific, and high-throughput assays are needed for rapid and accurate testing of mice in large numbers. This report describes a novel multiplex assay, based on fluorescent microbeads, for serodetection of H. bilis infection. The assay requires only a few microliters of serum to perform and is amenable to a high-throughput format. Individual microbead sets were conjugated to purified, H. bilis-specific, recombinant proteins P167C and P167D and bacterial membrane extracts from H. bilis and Helicobacter hepaticus. For detecting H. bilis infection in the microbead multiplex assay, P167C and P167D provided significantly higher sensitivities (94 and 100%, respectively) and specificities (100 and 95%, respectively) than membrane extract (78% sensitivity and 65% specificity). Microbead multiplex assay results were validated by enzyme-linked immunosorbent assay. Purified recombinant proteins showed low batch-to-batch variation; this feature allows for ease of quality control, assay robustness, and affordability. Thus, recombinant antigens are highly suitable in the multiplex microbead assay format for serodetection of H. bilis infection.