ICAM1 K469E and E-selectin S128R polymorphisms could predispose to increased autoantibody production and TSH suppression in Graves’ disease

The etiopathogenesis of Graves’ disease (GD) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. Adhesion molecules such as intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and E-selectin are secreted from vascular endothelium and promote accummulation of leukocytes in damaged endothelial areas. This study examined the possible association of ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) single nucleotide polymorphisms (SNPs) with the occurence of GD. ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs in DNA from peripheral blood leukocytes of 171 patients with GD and 259 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. We did not find significant differences in the distributions of studied polymorphisms, nor in the haplotype frequencies between patients with GD and healthy control. However, the anti-TPO levels in E-selectin 128R allele carrying subjects (SR + RR) were higher than S128S genotype (p < 0.05). In addition, the decline of TSH levels was more prominent in ICAM1 469 E carrying subjects (KE + EE) in comparison with wild homozygotes (p < 0.05). Although there is not assosiation between ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs and susceptibility to GD, higher anti-TPO in E-selectin 128 SR + RR, and lower TSH in ICAM1 469 KE + EE subjects suspect that these genotypes are prone to increased antithyroid autoantibody production with more accentuated TSH suppression in GD. Further studies with a larger cohort, analyzing other polymorphisms in ICAM, VCAM1 and E-selectin genes are necessary to support our observations.     

Modeling mate-finding behavior of the swarming polychaete,Nereis succinea,with TangoInSilico,a scientific orkflow-based simulation system for sexual searching

Summary

Pheromones can be used as attractants for the opposite sex in many environments; however, little is known about the search strategies employed in responding to pheromones in the marine environment. The spawning behavior of males of the polychaete Nereis succinea is known to be triggered at close range by a high concentration (>～10^?7 M) of pheromone, cysteine glutathione disulfide (CSSG), released by females. Since CSSG also causes acceleration of swimming and increased turning, in addition to eliciting ejaculation, we proposed the hypothesis that these behaviors elicited by low concentrations of pheromone can be used by males to find females. The current study develops a computer simulation model of male and female N. succinea behavior for testing whether male responses to low concentrations of CSSG can facilitate finding females. Video recording of female swimming behavior in the field showed spontaneous loops, spirals, and circles that have been incorporated into the model. The scientific workflow paradigm within which the computer model has been developed also incorporates a data provenance system to enable systematic replay and testing of responses to individual parameters. Output of the model shows complex turning behavior leading to successful mating encounters at concentrations as low as 3×10^?9 M CSSG. Behavior resembling the output of the model was recorded in field observations. Application of the model in the future will be used to determine what pheromone concentrations produce significant increases in the probability of mating encounters.     

Grand Molecular Dynamics: A Method for Open Systems

We present a new molecular dynamics method for studying the dynamics of open systems. The method couples a classical system to a chemical potential reservior. In the formulation, following the extended system dynamics approach, we introduce a variable, v to represent the coupling to the chemical potential reservoir. The new variable governs the dynamics of the variation of number of particles in the system. The number of particles is determined by taking the integer part of v. The fractional part of the new variable is used to scale the potential energy and the kinetic energy of an additional particle: i.e., we introduce a fractional particle. We give the ansatz Lagrangians and equations of motion for both the isothermal and the adiabatic forms of grand molecular dynamics. The averages calculated over the trajectories generated by these equations of motion represent the classical grand canonical ensemble (μVT) and the constant chemical potential adiabatic ensemble (μVL) averages, respectively. The microcanonical phase space densities of the adiabatic and isothermal forms the molecular dynamics method are shown to be equivalent to adiabatic constant chemical potential ensemble, and grand canonical ensemble partition functions. We also discuss the extension to multi-component systems, molecular fluids, ionic solutions and the problems and solutions associated with the implementation of the method. The statistical expressions for thermodynamic functions such as specific heat; adiabatic bulk modulus, Grüneissen parameter and number fluctuations are derived. These expressions are used to analyse trajectories of constant chemical potential systems.     

New binary copper(II) complexes containing intercalating ligands: DNA interactions,an unusual static quenching mechanism of BSA and cytotoxic activities

New binary copper(II) complexes – [Cu(4-mphen)₂(NO₃)]NO₃·H₂O (1), [Cu(5-mphen)₂ (NO₃)]NO₃·H₂O (2), the known complex [Cu(dmphen)₂(NO₃)]NO₃ (3) and [Cu(tmphen)₂ (NO₃)]NO₃·H₂O (4) - (4-mphen: 4-methyl-1,10-phenanthroline, 5-mphen: 5-methyl-1,10-phenanthroline, dmphen: 4,7-dimethyl-1,10-phenanthroline, tmphen: 3,4,7,8-tetramethyl-1,10-phenanthroline), have been synthesized and characterized by CHN analysis, ESI-MS, FTIR and single-crystal X-ray diffraction techniques. Interaction of these complexes with calf thymus DNA (CT-DNA) has been investigated by absorption spectral titration, ethidium bromide (EB) and Hoechst 33,258 displacement assay and thermal denaturation measurement. These complexes cleaved pUC19 plasmid DNA in the absence and presence of an external agent. Notably, in the presence of H₂O₂ as an activator, the cleavage abilities of these complexes are obviously enhanced at low concentration. Addition of hydroxyl radical scavengers like DMSO shows significant inhibition of the DNA cleavage activity of these complexes. BSA quenching mechanism was investigated with regard to the type of quenching, binding constant, number of binding locations and the thermodynamic parameters. The experimental results suggested that the probable quenching mechanism was an unusual static process and hydrophobic forces play a dominant role. The CT-DNA and BSA binding efficiencies of these complexes follow the order: 4 > 3 > 1 > 2. Furthermore, in vitro cytotoxicities of these complexes on tumor cells lines (Caco-2, MCF-7 and A549) and healthy cell line (BEAS-2B) showed that these complexes exhibited anticancer activity with low IC₅₀ values. The effect of hydrophobicity of the methyl-substituted phenanthrolines on DNA and protein binding activities of these complexes is discussed.     

A Neutron Scattering Study of the Ternary Complex EF-Tu•GTP-valy1-tRNAVal 1A

Abstract

The complex formation between elongation factor Tu (EF-Tu), GTP, and valyl-tRNA^Val _1A has been investigated in a hepes buffer of “pH” 7.4 and 0.2 M ionic strength using the small-angle neutron scattering method at concentrations of D₂O where EF-Tu (42% D₂O) and tRNA (71% D₂O) are successively matched by the solvents. The results indicate that EF-Tu undergoes a conformational change and contracts as a result of the complex formation, since the radius of gyration decreases by 15% from 2.82 to 2.39 nm. tRNA^Val _1A, on the other hand, seems to mainly retain its conformation within the complex, since the radii of gyration for the free (after correction for interparticular scattering) and complexed form are essentially the same. 2.38 and 2.47 nm, respectively.     

Seasonal Variation in Human Salivary Cortisol Concentration

Measurement of cortisol concentration can contribute important information about an individual's ability to adjust to various environmental demands of both physical and psychosocial origin. However, one uncertainty that affects the possibilities of correctly interpreting and designing field studies is the lack of observations of the impact of seasonal changes on cortisol excretion. For this reason, the month‐to‐month changes in diurnal cortisol concentration, the awakening cortisol response (ACR), maximum morning concentration, and fall during the day were studied in a group of 24 healthy men and women 32 to 61 yrs of age engaged in active work. On one workday for 12 consecutive months, participants collected saliva at four time points for determination of cortisol: at awakening, +30 min, +8 h, and at 21:00 h. Data were analyzed by a repeated measures design with month (12 levels) and time‐of‐day (4 levels) as categorical predictors. Cortisol concentrations were analyzed on a log scale. The diurnal pattern of cortisol was similar across months (interaction between month and time of day: p>0.4). The main effects of month and time‐of‐day were statistically significant (p <0.001). Highest concentrations were observed in February, March, and April, and lowest concentrations were observed in July and August. There were no statistically significant effects in any of the other measures, or between men and women. In conclusion, a seasonal variation in salivary cortisol concentrations was detected in an occupationally active population. Thus, seasonal variation needs to be taken into account when designing and evaluating field studies and interventions and when making comparisons across studies.     

Population-response model for vibrotactile spatial summation

A computational model based on previous physiological and psychophysical data is presented for the human Pacinian (P) psychophysical channel. The model can predict the probability of detection in simple psychophysical tasks, and hence psychometric functions and thresholds. The model simulates stimulating variable and fixed glabrous skin sites with different-sized contactors and includes spatial variation of monkey P-fiber sensitivities. Therefore, it is especially suitable for studying spatial summation, i.e. the improvement of threshold with increasing contactor area. Selective contributions of neural integration (n.i.) and probability summation (p.s.) are also incorporated into the model. Model predictions are compared to psychophysical results of Gescheider et al. (). The performance of the model regarding the effects of contactor size is very good. In addition to predicting approximately 3?dB improvement of thresholds when the contactor area is doubled, the model also reveals nonlinear contributions of p.s. and n.i. Furthermore, the model asserts that thresholds are largely governed by neural integration when small contactors are used. These and other findings discussed in the article show that the presented model is a helpful tool for formulating testable hypotheses. Although the model can also simulate some temporal summation effects, simulation results do not conform well to previous data on temporal response properties. Thus, the model needs to be refined in that respect.