Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth

Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity.     

Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation

Allele-specific DNA methylation (ASM) is a hallmark of imprinted genes, but ASM in the larger nonimprinted fraction of the genome is less well characterized. Using methylation-sensitive SNP analysis (MSNP), we surveyed the human genome at 50K and 250K resolution, identifying ASM as recurrent genotype call conversions from heterozygosity to homozygosity when genomic DNAs were predigested with the methylation-sensitive restriction enzyme HpaII. Using independent assays, we confirmed ASM at 16 SNP-tagged loci distributed across various chromosomes. At 12 of these loci (75%), the ASM tracked strongly with the sequence of adjacent SNPs. Further analysis showed allele-specific mRNA expression at two loci from this methylation-based screen--the vanin and CYP2A6-CYP2A7 gene clusters--both implicated in traits of medical importance. This recurrent phenomenon of sequence-dependent ASM has practical implications for mapping and interpreting associations of noncoding SNPs and haplotypes with human phenotypes.     

Experimental verification of a conserved intronic microRNA located in the human <Emphasis Type="Italic">TrkC</Emphasis> gene with a cell type-dependent apoptotic function

Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis induction and tumorigenesis. We hypothesized that, similar to p75^NTR receptor, some of the diverse functions of TrkC could be mediated by a microRNA (miRNA) embedded within the gene. Here, we experimentally verified the expression and processing of two bioinformatically predicted miRNAs named TrkC-miR1-5p and TrkC-miR1-3p. Transfecting a DNA fragment corresponding to the TrkC-premir1 sequence in HEK293t cells caused ~300-fold elevation in the level of mature TrkC-miR1 and also a significant downregulation of its predicted target genes. Furthermore, endogenous TrkC-miR1 was detected in several cell lines and brain tumors confirming its endogenous generation. Furthermore, its orthologous miRNA was detected in developing rat brain. Accordingly, TrkC-miR1 expression was increased during the course of neural differentiation of NT2 cell, whereas its suppression attenuated NT2 differentiation. Consistent with opposite functions of TrkC, TrkC-miR1 overexpression promoted survival and apoptosis in U87 and HEK293t cell lines, respectively. In conclusion, our data report the discovery of a new miRNA with overlapping function to TrkC.     

A Cu-Cr alloy with nano and microscale Cr particles produced in a water-cooled copper mold

Microstructures have profound effects on the hardness and strength of Cu-Cr alloys. The microstructures of a Cu-Cr alloy cast in a water-cooled copper mold were studied in the present work. The scanning electron microscopy (SEM) results show that there are the copper matrix saturated with chromium, spherical precipitates of chromium separated from liquid phase during cooling before the initiation of solidification, and a eutectic phase in grain boundary areas. To investigate the effect of age-hardening treatment on the microstructures and properties of the material, some samples were subsequently age-hardened in a salt bath and investigated by transmission electron microscopy (TEM). The results show that coherent precipitates with the diameter of 11 nm are detectable in the samples before and after the age-hardening stage. Of course, the volume fraction of coherent precipitates is higher after the aging process.     

Impact of late-onset Alzheimer’s genetic risk factors on beta-amyloid endocytic production

The increased production of the 42 aminoacids long beta-amyloid (Aβ42) peptide has been established as a causal mechanism of the familial early onset Alzheimer’s disease (AD). In contrast, the causal mechanisms of the late-onset AD (LOAD), that affects most AD patients, remain to be established. Indeed, Aβ42 accumulation has been detected more than 30 years before diagnosis. Thus, the mechanisms that control Aβ accumulation in LOAD likely go awry long before pathogenesis becomes detectable. Early on, APOE4 was identified as the biggest genetic risk factor for LOAD. However, since APOE4 is not present in all LOAD patients, genome-wide association studies of thousands of LOAD patients were undertaken to identify other genetic variants that could explain the development of LOAD. PICALM, BIN1, CD2AP, SORL1, and PLD3 are now with APOE4 among the identified genes at highest risk in LOAD that have been implicated in Aβ42 production. Recent evidence indicates that the regulation of the endocytic trafficking of the amyloid precursor protein (APP) and/or its secretases to and from sorting endosomes is determinant for Aβ42 production. Thus, here, we will review the described mechanisms, whereby these genetic risk factors can contribute to the enhanced endocytic production of Aβ42. Dissecting causal LOAD mechanisms of Aβ42 accumulation, underlying the contribution of each genetic risk factor, will be required to identify therapeutic targets for novel personalized preventive strategies.     

How to Make Iranian Banks Customer Oriented with Use of Customer Relationship Management Concepts? Methodology and Comprehensive Architecture

This paper focuses on finding solutions to two important questions regarding making Iranian banks customer-oriented with the use of customer relationship management (CRM) concepts: What is a practical architecture for the CRM of a bank that can bring about benefits of CRM to the organization, and what is the method to achieve such architecture? This research uses an Action Research (AR) approach in one of the largest Iranian banks to achieve answers to the aforementioned questions. In brief, it concentrates on the AR cycle and its reflexes. In the plan stage, extended literature review, pioneer banks studies, and benchmarking provide a preliminary plan. Later, in the act stage this plan can be confirmed, extended, or customized based on more precise examination of the organization, managers and employees’ interviews, and customer opinion surveys. In the check stage, university and bank experts will review the plans and in the last stage of the cycle, reflected results, lessons, and experiences that help system design in the second bank will be discussed. The efficient method of achieving the CRM architecture (which in the beginning we had only general knowledge about) as well as the improvements that can be done based on experts’ opinions in order to receive more applicable results, are among the issues that will be discussed in this paper.     

The Critical Heuristics of Iranian Banking Credit System: Analysis of the Antithetical Opinions of the Beneficiaries

Systemic Practice and Action Research - Considering the unfortunate intensification of the Non-performing loans in Iran`s credits system makes it vital to study the current system shortcomings....     

Culture of a new medicinal leech: growth,survival and reproduction of Hirudo orientalis Utevsky and Trontelj, 2005 under laboratory conditions

The increasing demands for medicinal leeches around the world has increased the need for new sources of leeches. To assess the feasibility of culturing a new medicinal leech species, growth, survival and reproduction of Hirudo orientalis was investigated under laboratory conditions (28°C; 9.5D:14.5L light regime; monthly feeding by sheep blood) from hatching until sexual maturity. Several interesting results emerged from this study. (1) The first copulation was observed in 5.5-month-old leeches and cocoon deposition started by six months. (2) Cocoon length and diameter did not differ significantly between six- and nine-month-old leeches, but the percentage of leeches depositing cocoons was significantly higher in the nine-month old group. (3) The growth curve was saltatory, similar to other sanguivorous species. The mean (±SE) wet weight of 6-month-old individuals was 4.70 (±0.86) g. (4) Weight gain rate decreased with increasing age. (5) Mortality only occurred in the one-, seven- and eight-month age groups at the rate of 5.7%, 23.1% and 14.3%, respectively.     

Process mineralogy as a key factor affecting the flotation kinetics of copper sulfide minerals

The aim of this study is to apply process mineralogy as a practical tool for further understanding and predicting the flotation kinetics of the copper sulfide minerals. The minerals' composition and association, grain distribution, and liberation within the ore samples were analyzed in the feed, concentrate, and the tailings of the flotation processes with two pulp densities of 25 wt% and 30 wt%. The major copper-bearing minerals identified by microscopic analysis of the concentrate samples included chalcopyrite(56.2 wt%), chalcocite(29.1 wt%),covellite(6.4 wt%), and bornite(4.7 wt%). Pyrite was the main sulfide gangue mineral(3.6 wt%) in the concentrates. A 95% degree of liberation with d_(80) 80 μm was obtained for chalcopyrite as the main copper mineral in the ore sample. The recovery rate and the grade in the concentrates were enhanced with increasing chalcopyrite particle size. Chalcopyrite particles with a d_(80) of approximately 100 μm were recovered at the early stages of the flotation process. The kinetic studies showed that the kinetic second-order rectangular distribution model perfectly fit the flotation test data. Characterization of the kinetic parameters indicated that the optimum granulation distribution range for achieving a maximum flotation rate for chalcopyrite particles was between the sizes 50 and 55 μm.