Elements in the hair of workers at a workshop, foundry, and match factory

The levels of seven elements determined in the hair were compared between male controls and industrial workers from Madras (South India). Particularly, the concentrations of Cd, Cr, Cu, Mn, and Ni in the foundry workers and Cu, Mn, and Ni in the workers of a workshop and match factory were observed to be higher than that of controls working in the office. In addition, the occupation, age, and period of service of workers had an influence, but diet, smoking habits, income of family, and hair color had no influence on the element levels in the hair.     

Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine

Migraine is a common neurovascular brain disorder characterised by recurrent attacks of severe headache that may be accompanied by various neurological symptoms. Migraine is thought to result from activation of the trigeminovascular system followed by vasodilation of pain-producing intracranial blood vessels and activation of second-order sensory neurons in the trigeminal nucleus caudalis. Calcitonin gene-related peptide (CGRP) is a mediator of neurogenic inflammation and the most powerful vasodilating neuropeptide, and has been implicated in migraine pathophysiology. Consequently, genes involved in CGRP synthesis or CGRP receptor genes may play a role in migraine and/or increase susceptibility. This study investigates whether variants in the gene that encodes CGRP, calcitonin-related polypeptide alpha (CALCA) or in the gene that encodes a component of its receptor, receptor activity modifying protein 1 (RAMP1), are associated with migraine pathogenesis and susceptibility. The single nucleotide polymorphisms (SNPs) rs3781719 and rs145837941 in the CALCA gene, and rs3754701 and rs7590387 at the RAMP1 locus, were analysed in an Australian Caucasian population of migraineurs and matched controls. Although we find no significant association of any of the SNPs tested with migraine overall, we detected a nominally significant association (p = 0.031) of the RAMP1 rs3754701 variant in male migraine subjects, although this is non-significant after Bonferroni correction for multiple testing.     

Constitutive Laws and Failure Models for Compact Bones Subjected to Dynamic Loading

Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra- and macro-structures. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0, 45 and 90° to the longitudinal axis of the bone and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model.     

A Digital Model for the Venous Junctions

The venous network in the lower limbs is composed of a considerable number of confluent junctions. Each of these singularities introduces some blood flow disturbances. Each physiological junction is unique, in terms of its geometry as well as the blood flow rate. In order to account for this great variability, we developed a numerical model based on the use of the N3S code (a software package for solving Navier-Stokes equations). To test the validity of the model, one of the numerical simulations is compared with the data obtained in the corresponding experimental configuration. The velocity measurements were carried out with an ultrasonic pulsed Doppler velocimeter. We also measured pressure differences using differential sensors. The numerical computations were then used to obtain the values of the flow variables at any point, with various geometrical and flow configurations. As far as the velocity field is concerned, a very marked three-dimensional pattern with swirls was observed. The pressure evolution was also strongly disturbed, with a non-linear decrease. All these data indicate that confluence effects cannot be neglected when evaluating pressure decreases. With a tool of this kind, it is possible to accurately predict the disturbances associated with any geometrical configuration or any flow rate.     

Element profiles in blood and teeth samples of children with congenital heart diseases in comparison with healthy ones

BackgroundSome elements were claimed to play a role in the pathogenesis of congenital heart defects (CHD) and influence the general well-being and health of these children.ObjectivesWe aimed to assess the levels of some elements simultaneously in the blood and teeth samples of children with cyanotic and acyanotic CHD compared with healthy children.MethodsA total of 39 children with CHD (11 with cyanotic and 28 with acyanotic CHD) and 42 age- and sex-adjusted controls were enrolled. Levels of 13 elements, including magnesium, phosphorus, calcium, chromium, manganese, iron, copper, zinc, strontium, cadmium, lead, mercury, and molybdenum, were assessed using inductively coupled plasma mass spectrometry.ResultsChildren with cyanotic and acyanotic CHD had significantly lower teeth calcium and calcium/phosphorus ratio as compared to the controls after adjusting for confounders. The mean blood iron level was found to be significantly higher in the cyanotic CHD group compared to the other groups. In addition, children with acyanotic CHD had significantly higher teeth copper levels, higher blood molybdenum and lower blood magnesium levels compared to the healthy control group. Blood cadmium and mercury levels were found to be significantly elevated in both the cyanotic and acyanotic CHD groups compared to the healthy control group. There were no differences in toxic metal levels of teeth in cases with CHD.ConclusionMonitoring adequate and balanced gestational micronutrient intake might support not only maternal health but also fetal cardiac development and infant well-being. Supplementation of magnesium should be evaluated in patients having CHD.     

Target Capture during Mos1 Transposition

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide.     

Is the Sudlow site I of human serum albumin more generous to adopt prospective anti-cancer bioorganic compound than that of bovine: A combined spectroscopic and docking simulation approach

A comparative biophysical study on the individual conformational adaptation embraced by two homologous serum albumins (SA) (bovine and human) towards a potential anticancer bioorganic compound 2-(6-chlorobenzo[d] thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)- dione (CBIQD) is apparent from the discrimination in binding behavior and the ensuing consequences accomplished by combined in vitro optical spectroscopy, in silico molecular docking and molecular dynamics (MD) simulation. The Sudlow site I of HSA although anion receptive, harbors neutral CBIQD in Sudlow site I (subdomain IIA, close to Trp) of HSA, while in BSA its prefers to snugly fit into Sudlow site II (subdomain IIIA, close to Tyr). Based on discernable diminution of HSA mean fluorescence lifetime as a function of biluminophore concentration, facile occurrence of fluorescence resonance energy transfer (FRET) is substantiated as the probable quenching mechanism accompanied by structural deformations in the protein ensemble. CBIQD establishes itself within HSA close to Trp214, and consequently reduces the micropolarity of the cybotactic environment that is predominantly constituted by hydrophobic amino acid residues. The stronger association of CBIQD with HSA encourages an allosteric modulation leading to slight deformation in its secondary structure whereas for BSA the association is comparatively weaker. Sudlow site I of HSA is capable to embrace a favorable conformation like malleable gold to provide room for incoming CBIQD, whereas for BSA it behaves more like rigid cast-iron which does not admit any change thus forcing CBIQD to occupy an altogether different binding location i.e. the Sudlow site II. The anticancer CBIQD is found to be stable within the HSA scaffold as vindicated by root mean square deviation (RMSD) and root mean square fluctuation (RMSF) obtained by MD simulation. A competitively inhibited esterase-like activity of HSA upon CBIQD binding to Lys199 and Arg257 residues, plausibly envisions that similar naphthalimide based prodrugs, bearing ester functionality, can be particularly activated by Sudlow site I of HSA. The consolidated spectroscopic research described herein may encourage design of naphthalimide based pro-drugs for effective in vivo biodistribution using HSA-based drug delivery systems.