Role of anaxonic local neurons in the crossover to continuously varying exponents for avalanche activity.

Local anaxonic neurons with graded potential release are important ingredients of nervous systems, present in the olfactory bulb system of mammalians and in the human visual system, as well as in arthropods and nematodes. We develop a neuronal network model including both axonic and anaxonic neurons and monitor the activity tuned by the following parameters: the decay length of the graded potential in local neurons, the fraction of local neurons, the largest eigenvalue of the adjacency matrix, and the range of connections of the local neurons. Tuning the fraction of local neurons, we derive the phase diagram including two transition lines: a critical line separating subcritical and supercritical regions, characterized by power-law distributions of avalanche sizes and durations, and a bifurcation line. We find that the overall behavior of the system is controlled by a parameter tuning the relevance of local neuron transmission with respect to the axonal one. The statistical properties of spontaneous activity are affected by local neurons at large fractions and on the condition that the graded potential transmission dominates the axonal one. In this case the scaling properties of spontaneous activity exhibit continuously varying exponents, rather than the mean-field branching model universality class.

Superstatistical two-temperature Ising model.

The previous approach of the nonequilibrium Ising model was based on the local temperature in which each site or part of the system has its own specific temperature. We introduce an approach of the two-temperature Ising model as a prototype of the superstatistic critical phenomena. The model is described by two temperatures (T_{1},T_{2}) in a zero magnetic field. To predict the phase diagram and numerically estimate the exponents, we develop the Metropolis and Swendsen-Wang Monte Carlo method. We observe that there is a nontrivial critical line, separating ordered and disordered phases. We propose an analytic equation for the critical line in the phase diagram. Our numerical estimation of the critical exponents illustrates that all points on the critical line belong to the ordinary Ising universality class.

Endogenous neurosteroids influence synaptic GABAA receptors during postnatal development.

GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurones to appropriately influence the window for postsynaptic excitation. Conventionally, programmed expression changes to the subtype of synaptic GABAA R are primarily implicated in this plasticity. However, it is now evident that, in developing thalamic and cortical principal- and inter-neurones, an endogenous neurosteroid tone (eg, allopregnanolone) enhances synaptic GABAA R function. Furthermore, a cessation of steroidogenesis, as a result of a lack of substrate, or a co-factor, appears to be primarily responsible for early neonatal changes to GABAergic synaptic transmission, followed by further refinement, which results from subsequent alterations of the GABAA R subtype. The timing of this cessation of neurosteroid influence is neurone-specific, occurring by postnatal day (P)10 in the thalamus but approximately 1 week later in the cortex. Neurosteroid levels are not static and change dynamically in a variety of physiological and pathophysiological scenarios. Given that GABA plays an important role in brain development, abnormal perturbations of neonatal GABAA R-active neurosteroids may have not only a considerable immediate, but also a longer-term impact upon neural network activity. Here, we review recent evidence indicating that changes in neurosteroidogenesis substantially influence neonatal GABAergic synaptic transmission. We discuss the physiological relevance of these findings and how the interference of neurosteroid-GABAA R interaction early in life may contribute to psychiatric conditions later in life.

Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of developmental disorders affecting primarily the anterior segment of the eye, often leading to secondary glaucoma. Patients with ARS may also present with systemic changes, including dental defects, mild craniofacial dysmorphism, and umbilical anomalies. ARS is inherited in an autosomal-dominant fashion; the underlying defect in 40% of patients is mutations in PITX2 or FOXC1. Here, an overview of the clinical spectrum of ARS is provided. As well, the known underlying genetic defects, clinical diagnostic possibilities, genetic counseling and treatments of ARS are discussed in detail.

Helicobacter pylori infection and iron deficiency in patients with coronary artery disease.

The aim of this study was to investigate whether impact of the seropositivity to Helicobacter pylori (H pylori) infection on ferritin and iron levels is an independent risk factor for atherosclerosis in patients with cardiovascular disease. The anti H pylori IgG, IgA levels, serum ferritin and iron concentration of 86 patients with cardiovascular disease and 64 participants free of cardiovascular disease as control subjects were determined by ELISA assay. The results of present study showed that seropositivity to H pylori IgG and IgA levels of coronary artery disease (CAD) patients was higher than controls and CAD patients with negative anti H pylori IgG and IgA significantly. A significant negative correlation was found between seropositivity to H pylori IgG and IgA, ferritin and iron levels of CAD patients with seronegativity and seronegativity to H pylori IgG and IgA in comparison with controls. The achieved results from present study suggest that the involvement of H pylori infection in atherosclerosis process is based on the chronic inflammation which might facilitate the CAD-related pathologies. Moreover, impact of the presence of H pylori infection on reduction of the ferritin and iron levels of CAD patients as a risk factor independent of other classic factors including lipid profiles and inflammatory factors was remarkable.

The effect of Morus alba leaves extract and powder on resistin levels and liver transaminase enzymes activities in diabetes.

The current study was designed to investigate the changes of the resistin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels of diabetic rats after treatment with Morus alba leaves flavonoid extract (MLE) and Morus alba leaves powder (MLP). Thirty male wistar rats in five groups including control and diabetic groups were included. Diabetic groups consisted of diabetic control, sham and treated group with MLE and MLP. Type 2 diabetes was induced in rats by administration of streptozotocin (STZ) and - nicotinamide. The serum concentrations of resistin and insulin in the study groups were identified by ELISA. ALT and AST activities were assayed by spectrophotometer. For the first time, it was shown that the uptake of MLE and MLP by diabetic rats could significantly decrease the serum fasting blood sugar (FBS), resistin levels and enzymes activity of ALT and AST and increases the concentration of serum insulin significantly (P<0.05). in comparison with the sham group and diabetic control. The results showed that there was no significant difference between the anti-diabetic and inflammatory properties of MLE and MLP. In this study, the possible protective effect of MLE and MLP administration was evaluated against destructive effect of STZ on liver and pancreas function in diabetic rats. The results showed that these effects may play an important role in the regulating of adipokines secretion such as resistin and insulin secretion which are involved in the control of diabetes and obesity. MLE and MLP treatment could be useful agents in combination with other therapies in diabetes improvement.

Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

Immunolocalization of AMPA receptor subunits within the enteric nervous system of the mouse colon and the effect of their activation on spontaneous colonic contractions.

BACKGROUND: The appropriate expression of specific neurotransmitter receptors within the cellular networks that compose the enteric nervous system (ENS) is central to the regulation of gastrointestinal (GI) functions. While the ENS expression patterns of the neurotransmitter glutamate have been well documented, the localization of its receptors on ENS neurons remains to be fully characterized. We investigated the expression patterns of glutamate receptor AMPA subunits within ENS neurons of the mouse colon and the consequences of their pharmacological activation on spontaneous colonic contractility. METHODS: RT-PCR was used to detect individual AMPA receptor (GluR 1-4) subunit expression at the mRNA level in mouse colon tissue. Immunohistochemistry and confocal microscopy was used to localize the expression of the GluR1 and 4 subunits in colon tissue. Brain tissue was used as a positive control. Organ bath preparations were used to determine the effect of AMPA receptors activation on the force and frequency of colonic longitudinal smooth muscle spontaneous contractions. KEY RESULTS: GluR1, 3, 4 mRNA was detected in the mouse colon. Immunoreactivity for GluR1 and 4 subunits was detected on the somatic and dendritic surfaces of subpopulations of neurochemically defined ENS neurons. The pharmacological activation of AMPA receptors increased the force but not frequency of spontaneous colonic contractions. CONCLUSIONS & INFERENCES: Molecularly distinct AMPA receptor subtypes are differentially expressed within the neural networks of the mouse colon and have a direct role in motility. These data provide the rationale for the development of AMPA-selective ligands for the therapeutic delivery to the GIT in motility disorders.

Mutation analysis of the CYP21A2 gene in congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive enzymatic disorder involving the synthesis of adrenal corticosteroids. 21-Hydroxylase deficiency (21-OHD) is the most common form of the disease which is observed in more than 90% of patients with CAH. Early identification of mutations in the genes involved in this disease is critical. A marker of the disease, errors in the CYP21A2 gene, is thought to be part of the pathophysiology of CAH. Therefore, the identification of gene mutations would be very beneficial in the early detection of CAH. This research was a descriptive epidemiological study conducted on individuals elected by the inclusion criteria whom were referred to the Genetic Diagnosis Center of Tabriz during 2012 to 2013. After sampling and DNA extraction, PCR for the detection of mutations in the CYP21A2 gene was performed followed by sequencing. For data analysis, the results of sequencing were compared with the reference gene by blast, Gene Runner and MEGA-5 software. Obtained changes were compared with NCBI databases. The analysis of the sequencing determined the mutations located in Exons 6, 7, 8 and 10. The most frequent findings were Q318X (53%) and R356W (28%). Exon 6 cluster (7%), E431k (4%), V237E (2%), V281L (2%), E351K (2%), R426C (2%) were also frequent in our patients. The most frequent genotype was compound heterozygote, Q318X/R356W. Three rare mutations in our study were E431K, E351K and R426C. Observed mutation frequencies in this study were much higher than those reported in previous studies in Iranian populations. Thus, it seems that it is necessary to follow-up screening programs and use sequencing methods to better identify mutations in the development of the disease.

Detection of immunoglobulin IGH gene rearrangements on formalin-fixed, paraffin embedded tissue in lymphoid malignancies.

Human lymphomas are aggressive malignant diseases, which can be categorized based on their B and T cell lineage. B-cell lymphomas form around 90% of the total lymphoma cases, the remnants of malignancies arise from the T cell branch. Lymphomas are mostly characterized as clonal proliferations of specific tumor cells. The detection of malignant lymphomas are extensively investigated by their morphological features, immunohistochemistry and flowcytometric immunophenotyping, but in some of cases remained unknown. The BIOMED-2 protocols were used to determine the clonality of IGH gene rearrangements in patients with lymphoma. PCR amplification was performed on FFPE of 50 patients with B-cell lymphoma, which consisted of 11 cases with HLs, 25 cases of B-NHLs and 14 cases of B-LPD (lymphoproliferative disorders) that diagnosed as unclassifiable lymphoma. The rate of positive clonality was detected in 96% (24/25) of B-NHLs, whereas in 4% (1/25) of cases clonality was showed in a polyclonal pattern. In B-HLs, 82% (9/11) of cases showed clonality and 18% (2/11) of the cases showed polyclonality. The rate of positive clonality observed in 64.3% (9/14) of cases with B-LPD and 35.7% (5/14) of cases clonality was not detected in any of immunoglobulin gene family (FR1, FR2, FR3). In groups with DLBCL, clonality was detected in 95% (19/20) of the cases. In patients diagnosed with FL and MALTs 100% cases showed clonality for complete IGH. Our study revealed that EuroClonality BIOMED-2 protocols could be considered as a valuable and reliable method for clonality detection, especially in IGH analysis.

MYCN gene amplification in patients with neuroblastic tumors.

Although neuroblastic tumors are the most prevalent solid tumors, little is known about the genetic basis underlying their progression. The prognostic role for the MYCN gene in neuroblastic tumors is irrefutable. The aim of this study is to identify the frequency of MYCN gene amplification and its relationship with clinicopathological and prognostic factors in 40 patients with neuroblastic tumors by using real-time quantitative PCR. There was significant association between the age of older than 18 months and the high number of metastasis. 83.3% of metastatic neuroblastic tumors in patients aged more than 18 months were in stage 4, while it was about 12.5% in patients aged less than 18 months. We found an amplification of MYCN in 19 out of 40 patients. Also, we found MYCN gene amplification in 64% of neuroblastoma (NB) and 8% of gangelioneuroblastoma (GNB) cases. There was a significant association between the histological type of samples with MYCN gene amplification. Neuroblastic tumors have a varied range of MYCN gene amplification depend on histopathology types. No significant associations have been found between MYCN gene amplification and tumor evaluation, CNS involvement, metastasis, stage of disease and patients outcome.

Is C771G polymorphism of MLX interacting protein-like (MLXIPL) gene a novel genetic risk factor for non-alcoholic fatty liver disease?

In a recent study, a genome-wide scan has identified C771G (His241Gln) polymorphism of MLX interacting protein like (MLXIPL) gene that is associated with the level of plasma triglycerides. Since, no study has been reported on the association between MLXIPL gene and non-alcoholic fatty liver disease (NAFLD), we aimed to identify a connection between this genetic variation and NAFLD. Two hundred and thirteen patients with NAFLD and 252 healthy controls were entered into this study. MLXIPL genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Our study showed that the single nucleotide polymorphism (SNP) of MLXIPL is significantly associated with NAFLD. Significant differences between cases and controls were observed for MLXIPL genotype frequencies (p<0.002). The frequency of C allele of MLXIPL in patient group was higher than the control group (68.30% vs. 51.59%, respectively; p<0.05). C771G polymorphism in the MLXIPL gene potentially plays a significant role in pathophysiology of non-alcoholic fatty liver disease. Further research is needed to confirm this finding.

Corticotropin-releasing factor and urocortin regulate spine and synapse formation: structural basis for stress-induced neuronal remodeling and pathology.

Dendritic spines are important sites of excitatory neurotransmission in the brain with their function determined by their structure and molecular content. Alterations in spine number, morphology and receptor content are a hallmark of many psychiatric disorders, most notably those because of stress. We investigated the role of corticotropin-releasing factor (CRF) stress peptides on the plasticity of spines in the cerebellum, a structure implicated in a host of mental illnesses, particularly of a developmental origin. We used organotypic slice cultures of the cerebellum and restraint stress in behaving animals to determine whether CRF in vitro and stress in vivo affects Purkinje cell (PC) spine density. Application of CRF and urocortin (UCN) to cerebellar slice cultures increased the density of spines on PC signaling via CRF receptors (CRF-Rs) 1 and 2 and RhoA downregulation, although the structural phenotypes of the induced spines varied, suggesting that CRF-Rs differentially induce the outgrowth of functionally distinct populations of spines. Furthermore, CRF and UCN exert a trophic effect on the surface contact between synaptic elements by increasing active zones and postsynaptic densities and facilitating the alignment of pre- and post-synaptic membranes of synapses on PCs. In addition, 1 h of restraint stress significantly increased PC spine density compared with those animals that were only handled. This study provides unprecedented resolution of CRF pathways that regulate the structural machinery essential for synaptic transmission and provides a basis for understanding stress-induced mental illnesses.

Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method.

In this study, total crocin was extracted from saffron stigmas using crystallization method. Ethanol 80% was selected as the best extraction solvent. Crystallization process was carried out in one and two steps at different temperatures. Ethanol 80% was used as crystallization medium. Crocin crystals obtained from the first crystallization had low purity and thus were subjected to the second crystallization. The higher purity crystals were yielded in the second crystallization at -5 degrees C. The purity of crocin crystals was studied using UV-visible spectrophotometery and HPLC in comparison with Fluka product and methanolic extract of saffron stigmas. The results indicated that its purity was extremely higher, about 13 times, more than Fluka product. In spite of our expectation, the Fluka product was not a pure alpha-crocin sample; five other types of crocins in addition to an unknown impurity were seen in its chromatogram. The purity of crystallized total crocin in this work was more than 97%.

Auditory changes in patients undergoing orthognathic surgery.

During orthognathic surgery, especially on the maxilla, osteotomies and displacements cause paratubular muscle dysfunction due to edema and muscle traction. This can cause auditory dysfunction. The aim of this study was to determine the effects of orthognathic surgery on the auditory status of patients. 54 consecutive patients who met the inclusion criteria underwent audiometric tests 24h preoperatively, and 48 h 6 weeks and 8 weeks postoperatively (2 weeks after maxillomandibular fixation removal). Surgery was on the maxilla, mandible or both. The types of movements were recorded. Audiometric examinations included pure tone audiometry, tympanometry and Eustachian tube function test. In the maxillary and bimaxillary procedures, there was some auditory system dysfunction (p<0.05). At the end of the study, a few patients had some mild dysfunction (p<0/05). In conclusion, orthognathic surgery (mainly maxillary and bimaxillary procedures) can cause some auditory system dysfunction, which is mild and transient in most cases and requires no intervention.