<Emphasis Type="Italic">Interleukin13</Emphasis> haplotypes and susceptibility of Iranian women to breast cancer

Interleukin-13 (IL-13) is a TH2 cytokine with direct and indirect immunoregulatory functions on cancer cells. The cytokine has been reported to have some polymorphic variations at the gene level associated with some immune related diseases including asthma and allergy. In the present study, association of three IL13 gene polymorphisms at positions −1512 A/C and −1055 C/T in the promoter and +2044 G/A in exon-4 was investigated in Iranian women with breast cancer and healthy controls. Genotyping of IL13 gene polymorphisms were performed by PCR–RFLP methods. Serum level of IL-13 was assessed by ELISA. Haplotypes were constructed from genotypic data using Arlequin 3.1 software package. Haplotype analysis revealed higher frequency of a three-locus haplotype, ACA (−1512A/−1055C/+2044A), in normal women than breast cancer patients (P < 0.025). Haplotype CCA, from the other hand, was observed with more frequency among patients than controls (P < 0.03). No statistically significant differences were found in the frequency of genotypes and alleles between patients and control group. No association was observed between investigated genotypes and other prognostic factors including tumor type, lymph node involvement and tumor size. IL-13 serum level was undetectable in both patients and control subjects. Despite observing no association between breast cancer and the single SNPs, results of this investigation suggest that the presence of CCA haplotype of IL13 gene may be associated with susceptibility of Iranian women to breast cancer.     

MODEM: a multi-agent hierarchical structure to model the human motor control system

In this study, based on behavioral and neurophysiological facts, a new hierarchical multi-agent architecture is proposed to model the human motor control system. Performance of the proposed structure is investigated by simulating the control of sit to stand movement. To develop the model, concepts of mixture of experts, modular structure, and some aspects of equilibrium point hypothesis were brought together. We have called this architecture MODularized Experts Model (MODEM). Human motor system is modeled at the joint torque level and the role of the muscles has been embedded in the function of the joint compliance characteristics. The input to the motor system, i.e., the central command, is the reciprocal command. At the lower level, there are several experts to generate the central command to control the task according to the details of the movement. The number of experts depends on the task to be performed. At the higher level, a “gate selector” block selects the suitable subordinate expert considering the context of the task. Each expert consists of a main controller and a predictor as well as several auxiliary modules. The main controller of an expert learns to control the performance of a given task by generating appropriate central commands under given conditions and/or constraints. The auxiliary modules of this expert learn to scrutinize the generated central command by the main controller. Auxiliary modules increase their intervention to correct the central command if the movement error is increased due to an external disturbance. Each auxiliary module acts autonomously and can be interpreted as an agent. Each agent is responsible for one joint and, therefore, the number of the agents of each expert is equal to the number of joints. Our results indicate that this architecture is robust against external disturbances, signal-dependent noise in sensory information, and changes in the environment. We also discuss the neurophysiological and behavioral basis of the proposed model (MODEM).     

Comparative thermostability of mesophilic and thermophilic alcohol dehydrogenases: Stability-determining roles of proline residues and loop conformations

The present study demonstrates the comparative thermal, conformational and kinetic stabilities of the three closely related enzymes; the mesophilic yeast alcohol dehydrogenase (YADH), horse liver alcohol dehydrogenase (HLADH), and the extreme-thermophilic Thermoanaerobacter brockii alcohol dehydrogenase (TBADH). The mid-point unfolding temperatures for TBADH and HLADH were at least 10 °C and 6 °C higher, respectively, than that of YADH. When YADH was completely inactivated by thermal stress, the residual activities of HLADH and TBADH were 70% and 100%, respectively. The optimum temperature (T_opt) activities of HLADH and TBADH were at least 40 °C and 55 °C higher, respectively, than that of YADH. Due to the higher rigidity of HLADH and TBADH, the enzymatic activation energies of HLADH and TBADH were higher than that of YADH. Geometric X-ray analysis indicated a comparatively higher coil (turn and loop) percentage in TBADH and HLADH than in YADH. Pairwise alignment for TBADH/HLADH exhibited a similarity score approximately 2.5-fold greater than that of the TBADH/YADH pair. Multiple alignments made with ClustalW revealed a higher number of conserved proline residues in the two most stable enzymes (HLADH/TBADH). These extra prolines tend to occur in surface loops and are likely to be responsible for the increased stability of TBADH and HLADH, by loop rigidification.     

Reproduction characteristics of a stunted population of rudd, <Emphasis Type="Italic">Scardinius erythrophthalmus</Emphasis> (Linnaeus, 1758) living in the Anzali Lagoon (the southwest Caspian Sea,Iran)

A total of 486 specimens of Scardinius erythrophthalmus caught in the Anzali lagoon, a large lagoon located in the southwest Caspian Sea (Iran), between March and June 2007 were examined. Age determination showed that the maximum ages observed were 4+ in males and 5+ in females. Isometric growth was identified from length-weight relationship in males, females and pooled data. There was no significant difference from parity in the overall sex ratio of 252 males to 234 females. The fish spawn from mid April to late May, with peak spawning in mid May with the highest average GSI value of 7.12 and 13.52 for males and females respectively. The absolute fecundity ranged between 1482–59620 eggs with the mean of 9287.87 eggs while relative fecundity ranged from 127.8 to 1737.6 eggs/g with the average of 709 eggs/g of body weight. Egg diameter ranged from 0.43 to 1.23 mm with a mean of 0.73 mm. The characteristics of rudd in the stunted population from the Anzali lagoon differ markedly from those of other localities of its range.     

Solid-phase extraction of tramadol from plasma and urine samples using a novel water-compatible molecularly imprinted polymer

In this study, a novel method is described for the determination of tramadol in biological fluids using molecularly imprinted solid-phase extraction (MISPE) as the sample clean-up technique combined with high-performance liquid chromatography (HPLC). The water-compatible molecularly imprinted polymers (MIPs) were prepared using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linker, chloroform as porogen and tramadol as template molecule. The novel imprinted polymer was used as a solid-phase extraction (SPE) sorbent for the extraction of tramadol from human plasma and urine. Various parameters affecting the extraction efficiency of the polymer have been evaluated. The optimal conditions for the MIP cartridges were studied. The MIP selectivity was evaluated by checking several substances with similar molecular structures to that of tramadol. The limit of detection (LOD) and limit of quantification (LOQ) for tramadol in urine samples were 1.2 and 3.5 μg L⁻¹, respectively. These limits for tramadol in plasma samples were 3.0 and 8.5 μg L⁻¹, respectively. The recoveries for plasma and urine samples were higher than 91%.     

Depletion of Aspergillus nidulans cotA causes a severe polarity defect which is not suppressed by the nuclear migration mutation nudA2

The Aspergillus nidulans homologue of Neurospora crassa cot-1, cotA, encoding a member of the NDR protein kinase family, has been cloned and expressed under the control of the conditional alcA promoter. Depletion of CotA by repression of the alcA promoter led to a severe growth defect accompanied by loss of polarity. Germlings show greatly enlarged volume of the spores and hyphae, accompanied by an increase in number of nuclei per compartment, though the nucleus/volume ratio is not significantly altered. The depleted CotA phenotype was not suppressed by a nuclear migration mutation nudA2. Double mutants showed an additive, defective phenotype, unlike the suppression of the cot-1 ts mutation by ropy mutations seen in N. crassa, suggesting a different relationship between nuclear migration and the cot signalling pathway in A. nidulans. A functional CotA–GFP fusion protein was found in punctate regions of fluorescence similar to the distribution reported for human NDR2, and as a cap at the hyphal tip.     

Intricate knots in proteins: Function and evolution

Our investigation of knotted structures in the Protein Data Bank reveals the most complicated knot discovered to date. We suggest that the occurrence of this knot in a human ubiquitin hydrolase might be related to the role of the enzyme in protein degradation. While knots are usually preserved among homologues, we also identify an exception in a transcarbamylase. This allows us to exemplify the function of knots in proteins and to suggest how they may have been created.     

Fatigue estimation using a novel multi-fractal detrended fluctuation analysis-based approach

This paper presents a novel multi-fractal detrended fluctuation analysis-based approach for fatigue estimation. This approach exploits the statistical self-similarity and long-range correlation of surface electromyography signals at different time scales in which the myoelectric manifestation of fatigue is more significant compared to the influence of varying force, muscle length (joint angle), and innervation zone. This approach provides a fatigue index which outperforms the conventional median frequency during cyclic and random contractions. This type of analysis is promising an efficient framework for analysis of surface electromyography signals with several potential applications.     

Measurement of Acute Phase Proteins in the Rat Brain: Contribution of Vascular Contents

A localized acute phase response occurs in the brain in Alzheimer's disease. Acute phase proteins have previously been measured in brain homogenates to quantify this response. The extent to which measurements of these proteins reflect brain parenchymal contents, as opposed to vascular contents, is unknown. In this study, the acute phase proteins ceruloplasmin (CP), complement factor 3 (C3), haptoglobin (HP), and albumin were measured in regional brain homogenates from phosphate buffered saline-perfused and sham-perfused rats (n = 7–9/group). Interleukin 1- (IL1-) and copper were also measured. Mean CP, C3, HP, and albumin concentrations in perfused specimens decreased by 94%, 88%, 90%, and 81% vs. sham-perfused specimens (all p < 0.001), while ILl- and copper were unchanged. These results suggest that acute phase protein measurements in brain homogenates reflect primarily vascular contents. However, IL1- and copper concentrations in brain homogenates are minimally influenced by vascular contents.