Optimal assessment and quantification of iodine nutrition in pregnancy and lactation : laboratory and clinical methods, controversies and future directions

Iodine intake must be boosted during pregnancy to meet the demands for increased production and placental transfer of thyroid hormone essential for optimal foetal development. Failure to meet this challenge results in irreversible brain damage, manifested in severity from neurological cretinism to minor or subtle deficits of intelligence and behavioural disorders. Attention is now being focused on explaining observational studies of an association between insufficient iodine intake during pregnancy and mild degrees of intellectual impairment in the offspring and confirming a cause and effect relationship with impaired maternal thyroid function. The current qualitative categorisation of iodine deficiency into mild, moderate and severe by the measurement of the median urinary iodine concentration (MUIC) in a population of school-age children, as a proxy measure of dietary iodine intake, is inappropriate for defining the degree or severity of gestational iodine deficiency and needs to be replaced. This review examines progress in analytical techniques for the measurement of urinary iodine concentration and the application of this technology to epidemiological studies of iodine deficiency with a focus on gestational iodine deficiency. We recommend that more precise definitions and measurements of gestational iodine deficiency, beyond a spot UIC, need to be developed. We review the evidence for hypothyroxinaemia as the cause of intrauterine foetal brain damage in gestational iodine deficiency and discuss the many unanswered questions, from which we propose that further clinical studies need to be designed to address the pathogenesis of neurodevelopmental impairments in the foetus and infant. Agreement on the testing instruments and standardization of processes and procedures for Intelligence Quotient (IQ) and psychomotor tests needs to be reached by investigators, so that valid comparisons can be made among studies of gestational iodine deficiency and neurocognitive outcomes. Finally, the timing, safety and the efficacy of prophylactic iodine supplementation for pregnant and lactating women needs to be established and confirmation that excess intake of iodine during pregnancy is to be avoided

Nonequilibrium candidate Monte Carlo: A new tool for efficient equilibrium simulation

Metropolis Monte Carlo simulation is a powerful tool for studying the equilibrium properties of matter. In complex condensed-phase systems, however, it is difficult to design Monte Carlo moves with high acceptance probabilities that also rapidly sample uncorrelated configurations. Here, we introduce a new class of moves based on nonequilibrium dynamics: candidate configurations are generated through a finite-time process in which a system is actively driven out of equilibrium, and accepted with criteria that preserve the equilibrium distribution. The acceptance rule is similar to the Metropolis acceptance probability, but related to the nonequilibrium work rather than the instantaneous energy difference. Our method is applicable to sampling from both a single thermodynamic state or a mixture of thermodynamic states, and allows both coordinates and thermodynamic parameters to be driven in nonequilibrium proposals. While generating finite-time switching trajectories incurs an additional cost, driving some degrees of freedom while allowing others to evolve naturally can lead to large enhancements in acceptance probabilities, greatly reducing structural correlation times. Using nonequilibrium driven processes vastly expands the repertoire of useful Monte Carlo proposals in simulations of dense solvated systems

Functional Dynamics of PDZ Binding Domains: A Normal Mode Analysis

PDZ (Post-synaptic density-95/discs large/zonula occludens-1) domains are relatively small (80 to 120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino-acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible of communication between distant regions of the protein, in agreement with recent Nuclear Magnetic Resonance (NMR) experiments. Thus PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbonding events.Comment: 25 pages, 10 figures, submitted to Biophysical Journa

Ecological and Behavioural Correlates of Intracellular Buffering Capacity in the Muscles of Antarctic Fishes

Five species of antarctic fishes can be arranged in order of increasing anaerobic capacity of the white muscles for burst swimming: Rhigophila dearborni (Zoarcidae), icefish (Channichthyidae), Dissostichus mawsoni, Trematomus centronotus, and Pagothenia borchgrevinki (Nototheniidae). This order reflects in-creasing dependence on anaerobic work done during short bursts of speed during prey capture or predator avoidance. Buffer capacity (beta) for white muscle was lower than that of behaviourally equivalent fish from lower latitudes and beta is itself temperature-dependent

Small poly-L-lysines improve cationic lipid-mediated gene transfer in vascular cells in vitro and in vivo

The potential of two small poly-L-lysines ( sPLLs), low molecular weight sPLL ( LMW-L) containing 7 - 30 lysine residues and L18 with 18 lysine repeats, to enhance the efficiency of liposome-mediated gene transfer ( GT) with cationic lipid DOCSPER {[}1,3- dioleoyloxy- 2-( N-5-carbamoyl-spermine)-propane] in vascular smooth muscle cells ( SMCs) was investigated. Dynamic light scattering was used for determination of particle size. Confocal microscopy was applied for colocalization studies of sPLLs and plasmid DNA inside cells. GT was performed in proliferating and quiescent primary porcine SMCs in vitro and in vivo in porcine femoral arteries. At low ionic strength, sPLLs formed small complexes with DNA ( 50 100 nm). At high ionic strength, large complexes ( 11 mu m) were observed without any significant differences in particle size between lipoplexes ( DOCSPER/ DNA) and lipopolyplexes ( DOCSPER/ sPLL/ DNA). Both sPLLs were colocalized with DNA inside cells 24 h after transfection, protecting DNA against degradation. DOCSPER/ sPLL/ DNA formulations enhanced GT in vitro up to 5- fold, in a porcine model using local periadventitial application up to 1.5- fold. Both sPLLs significantly increased liposome- mediated GT. Poly-L-lysine L18 was superior to LMW-L since it enabled maximal GT at a 10-fold lower concentration. Thus, sPLLs may serve as enhancers for GT applications in SMCs in vitro and in vivo using local delivery. Copyright (c) 2007 S. Karger AG, Basel

Salt intake and iodine status of women in Samoa

The objective of this study was to determine iodine nutrition status and whether iodine status differs across salt intake levels among a sample of women aged 18-45 years living in Samoa. A cross-sectional survey was completed and 24-hr urine samples were collected and assessed for iodine (n=152) and salt excretion (n=119). The median urinary iodine concentration (UIC) among the women was 88 μg/L (Interquartile range (IQR)=54-121 μg/L). 62% of the women had a UIC <100 μg/L. The crude estimated mean 24-hr urinary salt excretion was 6.6 (standard deviation 3.2) g/day. More than two-thirds (66%) of the women exceeded the World Health Organization recommended maximum level of 5 g/day. No association was found between median UIC and salt excretion (81 μg/L iodine where urinary salt excretion >=5 g/day versus 76 μg/L where urinary salt excretion <5 g/day; p=0.4). Iodine nutrition appears to be insufficient in this population and may be indicative of iodine deficiency disorders in Samoan women. A collaborative approach in monitoring iodine status and salt intake will strengthen both programs and greatly inform the level of iodine fortification required to ensure optimal iodine intake as population salt reduction programs take effect

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (<100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

A class of quasi-sparse companion pencils

In this paper, we introduce a general class of quasi-sparse potential companion pencils for arbitrary square matrix polynomials over an arbitrary field, which extends the class introduced in [B. Eastman, I.-J. Kim, B. L. Shader, K.N. Vander Meulen, Companion matrix patterns. Linear Algebra Appl. 436 (2014) 255-272] for monic scalar polynomials. We provide a canonical form, up to permutation, for companion pencils in this class. We also relate these companion pencils with other relevant families of companion linearizations known so far. Finally, we determine the number of different sparse companion pencils in the class, up to permutation.This work has been partially supported by theMinisterio de Economía y Competitividad of Spain through grants MTM2015-68805-REDT and MTM2015-65798-P

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction