Metabolism of cruciferous phytoalexins by Alternaria brassicicola: metabolites and pathways

Phytoalexins are plant metabolites produced in response to different kinds of stress like pathogen attack, while not present in healthy plants. Cruciferous phytoalexins are produced under pathogen attack and different types of stress by crucifers such as oilseed crops (canola, rapeseed), vegetables (rutabaga, cauliflower, turnip) and condiments (wasabi, mustard). The fungal species Alternaria brassicicola (Schwein.) Wiltshire is an economically important pathogen that causes Alternaria black spot in many important crucifer species, namely in Brassica species. Although resistance to A. brassicicola within the commercially available Brassica species is not known, some ecotypes of the wild species Arabidopsis thaliana are resistant to this pathogen. In the first part of this thesis, synthesis of some important cruciferous phytoalexins (camalexin, 1-methylcamalexin, 6-methoxycamalexin, cyclobrassinin, brassilexin, rutalexin and rapalexin A), their antifungal activity and metabolism by the crucifer pathogen A. brassicicola was investigated. Almost all tested phytoalexins showed substantial activity against A. brassicicola except cyclobrassinin with moderate activity. Metabolic investigation has shown that A. brassicicola was able to detoxify camalexin to indole-3-thiocarboxamide (> 5 days), which was transformed further to indole-3-carbonitrile and carboxylic acid, respectively. With the aim of obtaining mechanistic clue on the biotransformation of camalexins, some camalexin derivatives and analogues were synthesized and their antifungal activity as well as metabolism by A. brassicicola was investigated. All camalexin derivatives and analogues showed strong antifungal activity against A. brassicicola. Metabolic investigation has shown that substituent at C-4′ or C-5′ positions of thiazolyl ring of camalexin stopped oxidative degradation of thiazolyl ring by A. brassicicola. In addition, it was obtained that oxidative degradation of the thiazolyl ring requires it to be attached to indole by C-2′. In comparison to camalexins, cyclobrassinin was quickly (ca. 8 hours) detoxified by A. brassicicola to S-methyl [(2-sulfanyl-1H-indolyl-3)methyl]carbamothioate, which was further oxidized to sulfinic and sulfonic acid derivatives. Similarly, A. brassicicola was able to detoxify brassilexin to 3-aminomethylinindole-2-thione (24 hours). Rutalexin was detoxified by A. brassicicola to a highly reactive metabolite that reacted with phomapyrone G, a secondary metabolite produced by A. brassicicola, to yield a stable adduct. All metabolites from biotransformation of mentioned phytoalexins were synthesized and their metabolism as well as antifungal activity against A. brassicicola was investigated. It was indicated that A. brassicicola can detoxify the cruciferous phytoalexins camalexin, 1-methylcamalexin, 6-methoxycamalexin, cyclobrassinin, brassilexin, and rutalexin. Rapalexin A with strong activity against A. brassicicola was resistant to metabolism. In the second part of this thesis, inhibition of brassinin detoxification by Leptosphaeria maculans was investigated. Potential inhibitors were designed and synthesized based on the camalexin scaffold and their inhibitory activity against BOLm was determined using cell-free extracts. Almost all tested compounds showed inhibitory activity against BOLm, however their activity was weaker than camalexin

Virtual University And Globalisation

Globalization as an inevitable process in the twenty-first century in economic, political and cultural dimensions creates changes in education and higher education. Virtual universities have important role in globalization. It is clear that globalization in higher education can affect on other area same economic, culture and etc. Virtual university with special programs and use of information and communication technology (ICT) can show the impact of globalization on society, the economy, and the world system. At virtual universities there are international programs that extend globalization. Globalization requires the existence and development of an advanced information and communications infrastructure. And at virtual university that is new phenomenon in new age we can provide these infrastructures. Also, globalization requires a different education that enhances the ability of learners to access, assess, adopt, and apply knowledge, to think independently to exercise appropriate judgment and to collaborate with others to make sense of new situations. In this paper researcher want to show the impact of keys factors at virtual university on the globalization. Keywords: Virtual University, Globalization, Higher education

Efficacy of Passiflora incarnate on anxiety relief before orthopedic surgery: A double blinded clinical trial study

Background and aims: Anxiety is the most prevalent feeling before surgery which could affect postoperative outcomes. Anti-anxiety properties of Passiflora incarnate have been reported in previous studies and this study was designed and conducted to determine properties of medicinal plant Passiflora incarnate on anxiety before orthopedic surgery in patients hospitalized in Ayatollah Kashani Hospital, Shahrekord. Methods: In this experimental study, 60 patients aged 25-50 years candidate for orthopedic surgery referring Ayatollah Kashani Hospital, Shahrekord were randomly assigned into two 30-individual groups of case and control. At the night before surgery, case group received oral Passiflora caerulea drop (500 mg, Passipy) and control group received placebo. On the day of surgery, by Spielberger Anxiety Inventory, the level of trait anxiety (individual anxious property) and state anxiety (individual anxious state) was recorded, and the patients' demographic characteristics were gathered by questionnaire. Results: There was no significant difference between two groups regarding to age, sex, and marital status. Mean score of state anxiety in case group (40.86±7.25) was lower than control group (50.63±4.58) (P=0.001), but mean score of trait anxiety was not significantly different between the two groups (P=0.303). Conclusion: Based on the results of this study, use of oral drop of Passiflora incarnate before orthopedic surgery helps to relieve patient's anxiety. Use of this extract is recommended for Anti-anxiety and sedative treatments

Isolated Trochlea Fracture: A Rare Case Report

Background: Trochlea fracture usually happens with other fractures such as capitellum fracture or medial or lateral condyle fracture and isolated trochlea fracture is very rare because of its location and there are only a few cases of isolated trochlea fracture that have been reported.   Case Report: We present here a 40-year-old man who suffered from an isolated trochlea fracture due to falling from three meters height on his flexed left elbow. After examination, imaging, and setting up a plan for surgery, the patient's fragment was fixed with two Herbert screws through anterior approach and after five years of follow-up which was the longest follow-up that had been reported, the patient’s elbow range of motion was 5° to full flexion with Mayo Elbow Performance Index (MEPI) of 85/100 and Disabilities of Arm, Shoulder, and Hand (DASH) score of 13.6/100.   Conclusion: Isolated trochlea fracture is very rare, and it is best treated with open reduction and secure internal fixation using anterior or medial approaches

Autophagy induction regulates influenza virus replication in a time-dependent manner

Autophagy plays a key role in host defence responses against microbial infections by promoting degradation of pathogens and participating in acquired immunity. The interaction between autophagy and viruses is complex, and this pathway is hijacked by several viruses. Influenza virus (IV) interferes with autophagy through its replication and increases the accumulation of autophagosomes by blocking lysosome fusion. Thus, autophagy could be an effective area for antiviral research.Methodology. In this study, we evaluated the effect of autophagy on IV replication. Two cell lines were transfected with Beclin-1 expression plasmid before (prophylactic approach) and after (therapeutic approach) IV inoculation.Results/Key findings. Beclin-1 overexpression in the cells infected by virus induced autophagy to 26 %. The log10haemagglutinin titre and TCID50 (tissue culture infective dose giving 50 % infection) of replicating virus were measured at 24 and 48 h post-infection. In the prophylactic approach, the virus titre was enhanced significantly at 24 h post-infection (P≤0.01), but it was not significantly different from the control at 48 h post-infection. In contrast, the therapeutic approach of autophagy induction inhibited the virus replication at 24 and 48 h post-infection. Additionally, we showed that inhibition of autophagy using 3-methyladenine reduced viral replication. Conclusion. This study revealed that the virus (H1N1) titre was controlled in a time-dependent manner following autophagy induction in host cells. Manipulation of autophagy during the IV life cycle can be targeted both for antiviral aims and for increasing viral yield for virus production

The relationship between web 2.0 technologies and students achievement in virtual university

This paper has been investigated the effectiveness of Web 2.0 technology in virtual universities. Web 2.0 tools refer to the Web-based applications that allow virtual students to collaborate, communicate, and share information in a virtual or online learning environment. The population has been virtual students in developed and developing countries that based on Krejcie and Morgans' table, 384 students have been selected as sample. The results show that there is relationship between the use of Wikis, Podcasts, Blogs, and Web 2.0 technologies and students achievement in virtual university. Also using the Web 2.0 technology creates changes in communication, learning strategy, teaching methods, and interaction between learners and instructors. In virtual university many Web 2.0 tools contain characteristics of social software that maintain the ability to connect users and allow users to create Web content through collaborative efforts. Wikis, podcasts, and blogs represent social software that allows learner to collaborate by exchanging information through the Internet. Interaction and collaboration encourage learners to construct their knowledge, which remains characteristic of a constructivist approach to learning

Molecular Cloning and Characterization of P4 Nuclease from Leishmania infantum

Parasite of the genus Leishmania is reliant on the salvage pathway for recycling of ribonucleotides. A class I nuclease enzyme also known as P4 nuclease is involved in salvage of purines in cutaneous Leishmania species but the relevant enzymes have not been characterized in Leishmania infantum (L. infantum). The aim of this study was to clone and characterize the gene encoding class I nuclease in L. infantum. DNA extracted from L. infantum was used for amplification of P4 nuclease gene (Li-P4) by PCR. The product was cloned, sequenced, and expressed in E. coli for further characterization. Analysis of the sequence of Li-P4 revealed that the gene consists of an ORF of 951 bp. Sequence similarity analysis indicated that Li-P4 has a high homology to relevant enzymes of other kintoplastids with the highest homology (88%) to p1/s1 class I nuclease from L. donovani. Western blotting of antirecombinant Li-P4 with promastigote and amastigote stages of L. infantum showed that this nuclease is present in both stages of parasite with higher expression in amastigote stage. The highly conserved nature of this essential enzyme in Leishmania parasites suggests it as a promising drug target for leishmaniasis

Autophagy modulators : mechanistic aspects and drug delivery systems

Funding: this work was supported by a grant from NMRC-CIRG to CTY. APK was supported by grants from National Medical Research Council of Singapore, NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust and by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative to Cancer Science Institute of Singapore, National University of Singapore. R.M. acknowledges financial supports of Kerman University of Medical Sciences.Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discusse