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Immunity to Visceral Leishmaniasis Using Genetically Defined Live-Attenuated Parasites  [PDF]
Angamuthu Selvapandiyan,Ranadhir Dey,Sreenivas Gannavaram,Ines Lakhal-Naouar,Robert Duncan,Poonam Salotra,Hira L. Nakhasi
Journal of Tropical Medicine , 2012, DOI: 10.1155/2012/631460
Abstract: Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). Drug treatments are expensive and often result in the development of drug resistance. No vaccine is available against leishmaniasis. Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans. However, individuals who recover from natural infection are protected from reinfection and develop life-long protection, suggesting that infection may be a prerequisite for immunological memory. Thus, genetically altered live-attenuated parasites with controlled infectivity could achieve such memory. In this paper, we discuss development and characteristics of genetically altered, live-attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges and other considerations in the use of live-attenuated parasites. 1. Introduction Leishmaniasis is caused by protozoan parasites of the genus Leishmania of the family Trypanosomatidae and is transmitted by the sand fly vector. It infects about 12 million individuals globally in tropical and subtropical regions, with ~2 million new clinical cases (0.5 million visceral leishmaniasis (VL) and 1.5 million cutaneous leishmaniasis (CL)) reported annually with an estimated death toll of ~50,000 persons/year [1]. The three major clinical forms of leishmaniasis, VL, CL, and MCL are the result of infection by different species of the parasite and the immune response of the host. VL, fatal if not treated, is caused by L. donovani, L. infantum, and L. chagasi [2, 3]. More than 90% of the visceral cases in the world are reported from Bangladesh, Brazil, India, and Sudan. Most affected patients (70%) are children under 15 years of age who already suffer from concurrent malnutrition and other secondary illnesses. The major clinical symptoms for VL are characterized by prolonged and irregular fever, splenomegaly, and hepatomegaly [3]. CL causes lesions that are self-healing and are caused by L. major, L. tropica, or L. aethiopica in the old world and by L. mexicana or L. braziliensis complex in the new world [4]. MCL is potentially life threatening and affects the mucosal region of infected individuals, typically seen in the Central and South America and caused by L. braziliensis, L. amazonensis, L. panamensis, and L. guyanensis [3]. In the Leishmania life cycle,
Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition  [cached]
Jogdand Prajakta S,Singh Susheel K,Christiansen Michael,Dziegiel Morten H
Malaria Journal , 2012, DOI: 10.1186/1475-2875-11-235
Abstract: Background Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays. Although traditionally parasites are counted microscopically, a faster, more accurate and less subjective method for counting parasites is desirable. In this study mitochondrial dye (Mitotracker Red CMXRos) was used for obtaining reliable live parasite counts through flow cytometry. Methods Both asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination of Giemsa-stained thin smears. A comparison of the ability of CMXRos to stain live and compromised parasites (induced by either medium starvation or by anti-malarial drug treatment) was carried out. Finally, parasite counts obtained by CMXRos staining through flow cytometry were used to determine specific growth inhibition index (SGI) in an antibody-dependent cellular inhibition (ADCI) assay. Results Mitotracker Red CMXRos can reliably detect live intra-erythrocytic stages of P. falciparum. Comparison between staining of live with compromised parasites shows that CMXRos predominantly stains live parasites with functional mitochondria. Parasite counts obtained by CMXRos staining and flow cytometry were highly reproducible and can reliably determine the ability of IgG from hyper-immune individuals to inhibit parasite growth in presence of monocytes in ADCI assay. Further, a dose-dependent parasite growth inhibitory effect could be detected for both total IgG purified from hyper-immune sera and affinity purified IgGs against the N-terminal non-repeat region of GLURP in ADCI assays coupled with determination of parasite counts through CMXRos staining and flow cytometry. Conclusions A flow cytometry method based on CMXRos staining for detection of live parasite populations has been optimized. This is a rapid and sensitive method with high inter-assay reproducibility which can reliably determine the anti-parasite effect mediated by antibodies in functional in vitro assays such as ADCI assay.
An Ethical Approach to the Concept of Toleration: Understanding Tolerance as a Political Virtue  [PDF]
Ivón Cepeda Mayorga
Open Journal of Philosophy (OJPP) , 2014, DOI: 10.4236/ojpp.2014.44059
Abstract: The concept of toleration is commonly argued in political discourses and debates, when people refer to diversity and pluralism, as a form of respect and understanding. However, this does not represent an improvement at the moment of dealing with issues where a variety of values, conceptions and beliefs arises. In addition, even though when the idea of toleration was developed during Enlightenment, nowadays it seems to lead to a misconception of the term, following a connotation of a passive indifference about diversity. Due to this, the main objective of this text is to analyze the concept of toleration from an ethical perspective that allows thinking about it in terms of a political virtue needed to face the challenges of diversity inside society. In order to show this, the text presents an analysis of different conceptions of the term, in order to highlight the positive notion of toleration; after that, the text moves on, reviewing the idea of toleration from a hermeneutical perspective, as a form to reinforce the positive characteristics of the term, and path to solve the query between tolerance and intolerance. Finally, as a conclusion, it underlines that understanding the concept of toleration from an ethical perspective implies a praxis develop in daily circumstances.
Understanding Heat Stress Tolerance of Suspended Cells in the Model Plant Populus euphratica  [PDF]
Joana Silva-Correia,Herlander Azevedo,Teresa Lino-Neto,Rui Manuel Tavares
ISRN Forestry , 2012, DOI: 10.5402/2012/243694
Abstract: A comprehensive understanding of the physiological responses of plants to extreme temperatures is essential for future strategies for plant improvement. Obvious advantages can result from the study of highly adapted plant species, such as the model tree Populus euphratica Olivier that naturally thrives under extreme temperatures, saline soils, and drought. The present paper addresses the issue of P. euphratica thermotolerance using a cell suspension model system. P. euphratica suspended cells were subjected to a range of temperatures (from 5 up to 75°C) for 20 min, and cultures were evaluated for cell viability and biomass content at specific time points. The results have shown that cell viability was only affected after a temperature stress higher than 40°C, although in these conditions it was observed that a cell growth increases after the recovery period. In contrast, a total decline in cell viability was observed in suspended cells treated at 50°C or higher temperatures, which did not show growth recovery capacity. Therefore, the known natural tolerance of P. euphratica to thermal stress was not observable at the cellular level. The greater susceptibility to high temperatures in suspended cells as compared to field plants suggests that high thermotolerance can only be achieved when cells are integrated into a tissue. 1. Introduction Plants often grow under unfavorable conditions that extensively alter their development and productivity. One such environmental challenge is exposure to adverse temperatures, which can significantly affect many essential metabolic processes and disrupt an extensive range of cellular components. Heat stress can vary in severity, depending upon the intensity and extent of the stress as well as the rate of temperature variation. As sessile organisms, plants have developed several metabolic responses that minimize injuries caused by the constant exposure of plants to daily temperature fluctuations and their association with other abiotic factors [1]. The deeper knowledge on plant abiotic stress resistance has been fundamental in the development of effective engineering strategies leading to enhanced stress tolerance. Plant transformation with genes conferring thermal tolerance has been successfully achieved [2, 3]. However, many molecular mechanisms involved in thermotolerance are likely still unknown. A successful strategy for the assignment of gene function has been the study of species that are naturally adapted to survive in extreme environments. The advantages of using members of the poplar genus (Populus) as genomic
Understanding Tolerance of Ambiguity of EFL Learners in Reading Classes at Tertiary Level  [PDF]
Novitas-ROYAL , 2009,
Abstract: This study aimed to explore tolerance of ambiguity (AT) of a group of tertiary level Turkish EFL learners at a state university in Turkey. To do this, 188 preparation year students were administered a Second Language Tolerance of Ambiguity Scale with some demographic questions. Statistical analysis indicated students on average have lower tolerance for ambiguity in the process of learning, with female students reporting less tolerance than male students. Students’ AT, their self-perceived success, and strategy training they received correlated significantly. Suggestions for further research and classroom practice are offered in the light of the findings and current literature.
Towards a Better Understanding of the Evolution of Specialized Parasites of Fungus-Growing Ant Crops
Sze Huei Yek,Jacobus J. Boomsma,Michael Poulsen
Psyche , 2012, DOI: 10.1155/2012/239392
Abstract: Fungus-growing ants have interacted and partly coevolved with specialised microfungal parasites of the genus Escovopsis since the origin of ant fungiculture about 50 million years ago. Here, we review the recent progress in understanding the patterns of specificity of this ant-parasite association, covering both the colony/population level and comparisons between phylogenetic clades. We use a modified version of Tinbergen's four categories of evolutionary questions to structure our review in complementary approaches addressing both proximate questions of development and mechanism, and ultimate questions of (co)adaptation and evolutionary history. Using the same scheme, we identify future research questions that are likely to be particularly illuminating for understanding the ecology and evolution of Escovopsis parasitism of the cultivar maintained by fungus-growing ants.
Understanding photonic quantum-logic gates: The road to fault tolerance  [PDF]
Till J. Weinhold,Alexei Gilchrist,Kevin J. Resch,Andrew C. Doherty,Jeremy L. O'Brien,Geoffrey J. Pryde,Andrew G. White
Physics , 2008,
Abstract: Fault-tolerant quantum computing requires gates which function correctly despite the presence of errors, and are scalable if the error probability-per-gate is below a threshold value. To date, no method has been described for calculating this probability from measurements on a gate. Here we introduce a technique enabling quantitative benchmarking of quantum-logic gates against fault-tolerance thresholds for any architecture. We demonstrate our technique experimentally using a photonic entangling-gate. The relationship between experimental errors and their quantum logic effect is non-trivial: revealing this relationship requires a comprehensive theoretical model of the quantum-logic gate. We show the first such model for any architecture, and find multi-photon emission--a small effect previously regarded as secondary to mode-mismatch--to be the dominant source of logic error. We show that reducing this will move photonic quantum computing to within striking distance of fault-tolerance.
Toward understanding transcriptional regulatory networks in abiotic stress responses and tolerance in rice
Daisuke Todaka, Kazuo Nakashima, Kazuo Shinozaki, Kazuko Yamaguchi-Shinozaki
Rice , 2012, DOI: 10.1186/1939-8433-5-6
Abstract: In most crops, actual yields are only 20% of attainable yields (Boyer 1982). In crop production, a dominant factor limiting yield is abiotic stress such as excess or deficient water, high or low temperature, and high salinity (Boyer 1982). Therefore, improvement of abiotic stress tolerance might increase actual yields extensively in the most crops. As plants are sessile by nature they have evolved adaptive mechanisms against abiotic stress conditions. Recent progress in molecular biology has opened the door to uncovering the adaptive mechanisms at the molecular level in plants (Yamaguchi-Shinozaki & Shinozaki 2005, 2006).A large number of abiotic stress responsive genes have been reported in a variety of plants including rice and Arabidopsis. These genes induced during stress conditions function not only in the protection of cells from stress by production of important metabolic proteins, but also in the regulation of genes, including transcription factors (TFs), for signal transduction in the stress responses. These TFs regulate expression of multiple downstream target genes under stress conditions. These regulatory systems are achieved through specific cis-elements in the promoter regions of target genes, which are termed 'regulons'. Several regulons involved in abiotic stress responses have been identified in Arabidopsis (Nakashima et al. 2009; Qin et al. 2011). The dehydration-responsive element binding protein 1 (DREB1)/C-repeat binding factor (CBF) regulon functions in the cold stress response, whereas the DREB2 regulon acts in heat and osmotic stress responses (Mizoi et al. 2011). The abscisic acid (ABA) responsive element (ABRE) binding protein (AREB)/ABRE binding factor (ABF) regulon functions in ABA-dependent gene expression under osmotic stress conditions (Fujita et al. 2011). In addition, the NAC regulon is shown to be involved in osmotic stress responses (Nakashima et al. 2009).Rice (Oryza sativa L.) is a staple crop for more than half of the world's po
Cost of Virtual Machine Live Migration in Clouds: A Performance Evaluation  [PDF]
William Voorsluys,James Broberg,Srikumar Venugopal,Rajkumar Buyya
Computer Science , 2011, DOI: 10.1007/978-3-642-10665-1_23
Abstract: Virtualization has become commonplace in modern data centers, often referred as "computing clouds". The capability of virtual machine live migration brings benefits such as improved performance, manageability and fault tolerance, while allowing workload movement with a short service downtime. However, service levels of applications are likely to be negatively affected during a live migration. For this reason, a better understanding of its effects on system performance is desirable. In this paper, we evaluate the effects of live migration of virtual machines on the performance of applications running inside Xen VMs. Results show that, in most cases, migration overhead is acceptable but cannot be disregarded, especially in systems where availability and responsiveness are governed by strict Service Level Agreements. Despite that, there is a high potential for live migration applicability in data centers serving modernInternet applications. Our results are based on a workload covering the domain of multi-tier Web 2.0 applications.
'A high degree of understanding and tolerance': veranderende denke oor die moderne gereformeerde kerklied  [cached]
D. Kruger
Koers : Bulletin for Christian Scholarship , 2007, DOI: 10.4102/koers.v72i4.219
Abstract: 'A high degree of understanding and tolerance': changing thoughts on the modern reformed church song Currently, churches worldwide are experiencing an unparalleled increase in new hymns. Consequently, the requirements of the modern congregational song are much more challenging and demanding. Although the principles of music theory remain a primary criterion for the evaluation of the congregational song, aspects concerning the spiritual requirements, musical taste and culture of the modern church member are becoming increasingly relevant when thinking about the congregational song. In this article the author gives a general overview as to the nature of the modern church song against the background of liturgical renewal within the reformed tradition. The profile of the postmodern church member as regards spiritual needs, musical taste and culture is outlined and connected with the current sensitivity of spirituality and emotional experience through worship and song. Lastly a connection is made between the current trends of hymnological thought and the reformed principles. It is argued that greater tolerance and understanding can lead towards a reforming, rather than a reformed attitude towards the modern congregational song. The discussion is illustrated with examples from the “Liedboek van die kerk” (2001).
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