Evaluation of mRNA expression levels of cyp51a and mdr1, candidate genes for voriconazole resistance in Aspergillus flavus

Background: Voriconazole Resistance (VRC-R) in Aspergillus flavus isolates impacts the management of aspergillosis, since azoles are the first choice for prophylaxis and therapy. However, to the best of our knowledge, the mechanisms underlying voriconazole resistance are poorly understood. Objectives: The present study was designed to evaluate mRNA expression levels of cyp51A and mdr1 genes in voriconazole resistant A. flavus by a Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique. Materials and Methods: Five A. flavus isolates with resistance to VRC were examined by a RT-PCR approach. Results: Four out of five isolates revealed cyp51A and mdr1 mRNA overexpression. Interestingly, the isolate, which was negative for cyp51A and mdr1 mRNA expression showed a high voriconazole Minimum Inhibitory Concentration (MIC). Furthermore, a computational-based analysis predicted that voriconazole resistance could be mediated through cooperation with a network protein interaction. Conclusions: Our experimental and in silico findings may provide new insight in the complex molecular pathways of drug resistance and also could assist design an efficient therapeutic strategy for aspergillosis treatment. © 2015 Ahvaz Jundishapur University of Medical Sciences

Expression of neuronal nitric oxide synthase during embryonic development of the rat optic vesicle

The expression of neuronal nitric oxide synthase during the development of rat optic vesicle from embryonic day E14 to E18 was analyzed by histochemical procedures. The samples were frozen and cut on a cryostat and then studied by using the light microscope. Expression of nNOS was first seen on E14 in cells of Cajal-Retzius located in the marginal zone of optic vesicle. NADPH-d persisted in this layer throughout the embryonic period and began to decrease on E20. At E16, the optic vesicle has four NADPH-d positive layers. At E18, NADPH-d reactivity observed at low magnification showed five clearly defined layers. In the late stages, the most notable feature was a decrease in histochemical reaction of the marginal zone and at these stages, the layer IV showed less staining than the rest of the cortical plate. The observations suggest that nitric oxide is synthesized during embryonic life processes and this is related to maturational processes. © 2007 Asian Network for Scientific Information

Comprehensive genotype‐phenotype correlation in AP‐4 deficiency syndrome; Adding data from a large cohort of Iranian patients

Mutations in adaptor protein complex‐4 (AP‐4) genes have first been identified in 2009, causing a phenotype termed as AP‐4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype‐phenotype correlation of the AP‐4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease‐causing variants in AP‐4 complex subunits, using next‐generation sequencing. Furthermore, by comparing genotype‐phenotype findings of those affected individuals with previously reported patients, we further refine the genotype‐phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP‐4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders

Using fahp-vikor for operation selection in the flexible job-shop scheduling problem: A case study in textile industry

Scheduling of Flexible Job Shop Systems is a combinatorial problem which has been addressed by several heuristics and meta-heuristics. Nevertheless, the operation selection rules of both methods are limited to an ordered variant wherein priority-dispatching rules are not simultaneously deemed in the reported literature. Therefore, this paper presents the application of dispatching algorithm with operation selection based on Fuzzy Analytic Hierarchy Process (FAHP) and VIKOR methods while considering setup times and transfer batches. Dispatching, FAHP, and VIKOR algorithms are first defined. Second, a multi-criteria decision-making model is designed for operation prioritization. Then, FAHP is applied to calculate the criteria weights and overcome the uncertainty of human judgments. Afterwards, VIKOR is used to select the operation with the highest priority. A case study in the textile industry is shown to validate this approach. The results evidenced, compared to the company solution, a reduction of 61.05% in average delay

Satellites around Milky Way Analogs: Tension in the Number and Fraction of Quiescent Satellites Seen in Observations versus Simulations

We compare the star-forming properties of satellites around Milky Way (MW) analogs from the Stage II release of the Satellites Around Galactic Analogs Survey (SAGA-ii) to those from the APOSTLE and Auriga cosmological zoom-in simulation suites. We use archival GALEX UV imaging as a star formation indicator for the SAGA-ii sample and derive star formation rates (SFRs) to compare with those from APOSTLE and Auriga. We compare our detection rates from the NUV and FUV bands to the SAGA-ii Hα detections and find that they are broadly consistent with over 85% of observed satellites detected in all three tracers. We apply the same spatial selection criteria used around SAGA-ii hosts to select satellites around the MW-like hosts in APOSTLE and Auriga. We find very good overall agreement in the derived SFRs for the star-forming satellites as well as the number of star-forming satellites per host in observed and simulated samples. However, the number and fraction of quenched satellites in the SAGA-ii sample are significantly lower than those in APOSTLE and Auriga below a stellar mass of M ∗ ∼ 108 M o˙, even when the SAGA-ii incompleteness and interloper corrections are included. This discrepancy is robust with respect to the resolution of the simulations and persists when alternative star formation tracers are employed. We posit that this disagreement is not readily explained by vagaries in the observed or simulated samples considered here, suggesting a genuine discrepancy that may inform the physics of satellite populations around MW analogs

Analysing the impact of rescheduling time in hybrid manufacturing control

Hybrid manufacturing control architectures merge the benefits of hierarchical and heterarchical approaches. Disturbances can be handled at upper or lower decision levels, depending on the type of disturbance, its impact and the time the control system has to react. This paper focuses particularly on a disturbance handling mechanism at upper decision levels using a rescheduling manufacturing method. Such rescheduling is more complex that the offline scheduling since the control system must take into account the current system status, obtain a satisfactory performance under the new conditions, and also come up with a new schedule in a restricted amount of time. Then, this paper proposes a simple and generic rescheduling method which, based on the satisfying principle, analyses the trade-off between the rescheduling time and the performance achieved after a perturbation. The proposed approach is validated on a simulation model of a realistic assembly cell and results demonstrate that adaptation of the rescheduling time might be beneficial in terms of overall performance and reactivity.info:eu-repo/semantics/publishedVersio

Detection of Echinococcus multilocularis in Carnivores in Razavi Khorasan Province, Iran Using Mitochondrial DNA

Echinococcus multilocularis causes alveolar echinococcosis, a serious zoonotic disease present in many areas of the world. The parasite is maintained in nature through a life cycle in which adult worms in the intestine of carnivores transmit infection to small mammals, predominantly rodents, via eggs in the feces. Humans may accidentally ingest eggs of E. multilocularis through contact with the definitive host or by direct ingestion of contaminated water or foods, causing development of a multivesicular cyst in the viscera, especially liver and lung. We found adult E. multilocularis in the intestine and/or eggs in feces of all wild carnivores examined and in some stray and domestic dogs in villages of Chenaran region, northeastern Iran. The life cycle of E. multilocularis is being maintained in this area by wild carnivores, and the local population and visitors are at risk of infection with alveolar echinococcosis. Intensive health initiatives for control of the parasite and diagnosis of this potentially fatal disease in humans, in this area of Iran, are needed

Iranome: A catalogue of genomic variations in the Iranian population

Considering the application of human genome variation databases in precision medicine, population-specific genome projects are continuously being developed. However, the Middle Eastern population is underrepresented in current databases. Accordingly, we established Iranome database (www.iranome.com) by performing whole exome sequencing on 800 individuals from eight major Iranian ethnic groups representing the second largest population of Middle East. We identified 1,575,702 variants of which 308,311 were novel (19.6%). Also, by presenting higher frequency for 37,384 novel or known rare variants, Iranome database can improve the power of molecular diagnosis. Moreover, attainable clinical information makes this database a good resource for classifying pathogenicity of rare variants. Principal components analysis indicated that, apart from Iranian-Baluchs, Iranian-Turkmen, and Iranian-Persian Gulf Islanders, who form their own clusters, rest of the population were genetically linked, forming a super-population. Furthermore, only 0.6% of novel variants showed counterparts in "Greater Middle East Variome Project", emphasizing the value of Iranome at national level by releasing a comprehensive catalog of Iranian genomic variations and also filling another gap in the catalog of human genome variations at international level. We introduce Iranome as a resource which may also be applicable in other countries located in neighboring regions historically called Greater Iran (Persia)