Genomic and functional characterization of G protein-coupled receptors in the human pathogen Schistosoma mansoni and the model planarian Schmidtea mediterranea

G protein-coupled receptors (GPCRs) constitute the largest known superfamily of integral membrane proteins, and represent a particularly lucrative set of chemotherapeutic targets. These seven transmembrane receptors play a central role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing prominent human pathogens as well as established model organisms in the realm of developmental and stem cell biology. There exists ample motivation to elucidate the structural and functional properties of GPCRs in this phylum. The availability of whole genome sequence data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first genome-wide analyses of platyhelminth GPCRs. Extensive efforts were made to delineate the receptor complements of these organisms. Further work primarily focuses on validation of a novel method for elucidating receptor function in the native cell membrane environment. Together, these genomic and functional data improve our understanding of basic platyhelminth receptor biology and shed light on a promising set of anthelmintic drug targets. Application of a transmembrane-focused it in silico protocol led to the discovery of 116 S. mansoni and 333 S. mediterranea GPCRs, followed by extensive curation of underlying gene models. Phylogenetic analysis of the resulting dataset confirmed the presence of the primary metazoan GRAFS families and revealed novel lineage-specific receptor groupings, including a large platyhelminth-specific Rhodopsin-like subfamily (PROF1) and a planarian-specific Adhesion-like family (PARF1). Support vector machines (SVMs) were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification. PROF1 receptors were further revealed as neuronally-expressed endoGPCRs via whole mount in situ hybridization. In light of the unreliable nature of heterologous approaches to GPCR deorphanization, a novel loss-of-function assay was developed for ascertaining the ligand and G protein coupling properties of GPCRs in their native cell membrane environment. RNA interference (RNAi) was used in conjunction with a cAMP radioimmunoassay (RIA) to monitor second messenger modulation in response to the translational suppression of individual receptors. This strategy was applied to the deorphanization of both neuropeptide and aminergic GPCRs, allowing for the determination of Gαs and Gαi/o-mediated signaling. Loss-of-function phenotypic assays were performed in parallel. While these results establish the potential of this approach, future work can lead to further optimizations and the eventual adaptation of this protocol to higher-throughput platforms

The Relationship between Iranian EFL Teachers’ Personality and Their Teaching Preference

The present study sought to investigate the relationship between Iranian EFL teachers’ personality types and their teaching preferences. Besides, it attempted to take the notion of gender into account. The participants included 100 EFL teachers and university instructors from seven English language institutes in Shiraz, and two universities in Fars Province. Availability sampling was used for this aim. The Myers-Briggs Type Indicator (MBTI) questionnaire and Teaching Activities Preference (TAP) questionnaire were used to collect the data. The design of the study was survey method; so, both descriptive and inferential statistics were used. Based on the analyses undertaken, the following results were obtained: 1) there was a significant relationship between the personality and teaching preference, 2) Male and female EFL teachers’ (from Shiraz English language institutes) teaching preferences were statistically the same. The results could be used by teachers, university instructors, syllabus designers and, in general, all groups involved in education

Critical concentration of Glucose changes human serum albumin conformation: Circular Dichroism (CD)and UV Spectroscopyapproaches

HSA plays an important role in transporting metabolites and drugs throughout the vascular system.  In as much as its performance is very vital in the presents of different kinds of ligands at the specific body temperatures, its examination is crucial. This molecule can undergo increased glycation in diabetes. Therefore, glucose as the one of the most fundamental ligands dealing with albumin in human body is examined in this study at 100 mg/dl concentration in correspond to normal condition on human body, 175 mg/dl as a kidney glucose tolerance point and also 400 mg/dl as the critical point at the two most important temperatures in diabetic patients. Thermal conformational changes of (HSA) are important. These conformational alterations are accompanied by a mild alteration of secondary structures. For this reason, possible secondarystructural changes of HSA in presence of glucose has beeninvestigated by circular dichroism (CD) using Hepes bufferat the normal temperature 37˚C and 42˚C as a high fever condition.UV spectroscopystudies confirmed CD findings and indicate that critical concentration of glucoselead to generation of new structural feature of albumin similar to 42oC. However, as the temperature increases from 37˚C to 42˚C this process is no more capable of responding to glucose concentration changes.These results indicate that the native form of HSA is changed in the severe diabetic condition; likewise, same consequences can be achieved as the temperature arises from 37˚C to 42˚C

Multimedia in Language teaching

ABSTRACT Language teaching have been concerned for many researchers to find a better method and better material in teaching language. The aim of this research is to study the role of multimedia as a material for teaching language. Multimedia help to stimulate one of the most important aspects of teaching -curiosity. Some studies that were comparing advantages and disadvantages of traditional teaching texts and multimedia didactic means show that the differences in in education are mainly caused by content of communication. On the basis of pedagogical experiences it can be said that media bring qualitative change. This is achieved by interactive communication, simulation of authentic environment, individualization of study -respecting everybody´s own pace of studying, etc. As a result, a fear from making a mistake is decreased (computer enables learners to make a mistake without losing their social status). Interaction has a primary role in the field of multimedia. Self-activity of a student supports the most effective method in the teaching process -active teaching, or teaching by doi .Nowadays, the stereotyped traditional teaching methods and environment are unpopular while multimedia technology featuring audio, visual, animation effects naturally and humanely makes us more access to information. Besides, with such characteristics as abundantinformation and crossing time and space, multimedia technology offers a sense of reality and functions very well, which greatly cultivates students' interest and motivation in study and their involvement in class activities

Willingness to Communicate in L2: Theoretical Roots and Pedagogical Implications

Abstract. This literature review paper provides the readers with the presentation of the theoretical and empirical issues pertinent to willingness to communicate in L2. In this paper, first the roots of this variable are presented, then different conceptualizations of the variable are discussed in brief. It also provides the readers with the review of the most prominent studies conducted on willingness to communicate. The last section of this paper deals with the pedagogical implications related to willingness to communicate

Chronic myeloid leukemia as a stem cell-derived malignancy

Chronic myeloid leukemia (CML) is a myeloproliferative disease of the hematopoietic stem cells, characterized by the presence of the Philadelphia (Ph) chromosome. Although imatinib inhibits the BCR-ABL kinase activity, clinical experiences confirm that imatinib may not target CML stem cells in vivo. The identification of signaling pathways responsible for the self-renewal properties of leukemic stem cells in CML will help in the discovery of novel therapeutic targets. Here we review signaling pathways including Wnt/β-catenin, Hedgehog, Alox5, and Foxo which play crucial roles in the maintenance of stem cell functions in CML. It is thought that inhibition of key genes that are part of self-renewal associated signaling pathways may provide an effective way to reduce aberrant stem cell renewal in CML

Duchenne muscular dystrophy (DMD) protein- protein interaction mapping

ObjectiveDuchenne muscular dystrophy as one of the mortal diseases is prominent to study in terms of molecular investigation. In this study, the protein interaction map of this muscle-wasting condition is generated to gain a better knowledge of interactome profile of DMD.Materials & Methods Applying Cytoscape and String Database, the protein-protein interaction network was constructed and the gene ontology of the constructed network was analyzed for biological process, molecular function, and cell component annotations.ResultsThe results indicate that among 100 proteins that are related to DMD, Dystrophin, Utrophin, Caveolin 3, and Myogenic differentiation 1 play key roles in DMD network. In addition, the gene ontology analysis showed that regulation processes, kinase activity and sarcoplasmic reticulum are the highlighted biological processes, molecular function, and cell component enrichments respectively for the proteins related to DMD.  ConclusionIn conclusion, the central proteins and the enriched ontologies can be suggested as possible prominent agents in DMD; however, the validation studies may be required

Interaction network prediction and analysis of Anorexia Nervosa

ObjectivesAnorexia Nervosa (AN) as a mental condition is a common eating disorder among young women. This study aims to shed lights on molecular behavior of this serious disorder in terms of protein interacting profile to provide further insight about its complexity.Materials & MethodsThe AN related genes were extracted from STRING database and included in interactome via Cytoscape software. The central nodes of the network were enriched via gene ontology (GO) by ClueGO+CluePedia and the action relationship between the nodes were determined by CluePedia.ResultsSix genes including LEP, INS, POMC, GCG, SST, and ALB were introduced as hub-bottlenecks that among them LEP, INS, and POMC were the super hub-bottlenecks based on further analysis. Action map analysis showed prominent role of hubs relative to bottlenecks in the network. Regulation of behavior, regulation of carbohydrate biosynthetic process, and regulation of appetite are the top associated processes for the identified hub genes.ConclusionThe topological analysis proposed the five hub-bottlenecks as the most central genes in the network, these genes and their contributing biological terms may suggest additional importance in AN pathogenesis and thereby possible candidates for therapeutic usage.  However, further studies is required to justify these findings.

New Molecular Aspects of Cardiac Arrest; Promoting Cardiopulmonary Resuscitation Approaches

Introduction: Cardiopulmonary resuscitation (CPR) is a method to improve survival of patients with cardiac arrest. This study aimed to identify the key genes affected five minutes after cardiac arrest, hoping to elevate the efficacy of CPR.Methods: In this bioinformatics study differentially expressed genes of six pigs were downloaded from GEO and screened. The significant and characterized genes were analyzed via calculating fold change and protein-protein interaction (PPI) networks. The crucial nodes were determined based on centrality parameters and their related biological processes were investigated via ClueGO.Results: 17 significant up-regulated (LogFC ≥ 2) and 22 down-regulated (LogFC < -0.5) genes were detected. Transthyretin (TTR logFC = 4.59) and Gonadotropin-releasing hormone receptor (GNRHR logFC = 3.84) had higher logFC among up-regulated and down-regulated genes, respectively. The critical genes including four up-regulated and five down-regulated genes were detected from network analysis. GNRHR and Prolactin precursor (PRL) were among the most important down res 5 minutes after cardiac arrest and Beta-2 adrenergic receptor and Cadherin-1 were among the most important up regulated gens. Conclusion: The introduced potential biomarkers could reveal a new molecular aspect for CPR performance and pituitary gland protection was highlighted in this respect.