Plasmodial Hsp40s: New avenues for antimalarial drug discovery

Malaria, an infectious disease caused by Plasmodium spp, is one of the world\u27s most dangerous diseases, accounting for more than half a million deaths yearly. The long years of co-habitation between the parasite and its hosts (human and mosquito), is a testimony to the parasite’s ability to escape the immune system and develop drug resistance mechanisms. Currently, an important search area for improved pharmacotherapy are molecular chaperones of the heat shock protein family, abundant in Plasmodium falciparum and contributing to its continuous survival and development. Thus far, small molecule inhibitor studies on P. falciparum Hsp70s and Hsp90s have indicated that they are promising antimalarial targets. However, not much attention has been given to Hsp40s as potential antimalarial drug targets. Hsp40s are known to function as chaperones by preventing protein aggregation, and as co-chaperones, by regulating the chaperone activities of Hsp70s to ensure proper protein folding. There are only a limited number of reviews on Hsp40s as drug targets, and the few reviews on plasmodial Hsp40s tend to focus largely on the intra-erythrocytic stage of the parasite life cycle. Therefore, this review will summarize what is known about Hsp40s throughout the malaria parasite life cycle, and critically evaluate their potential to serve as new avenues for antimalarial drug discovery

One Hundred and One Practical Non-Flesh Recipes

https://knowledge.e.southern.edu/foodiesguide-1910/1000/thumbnail.jp

Molecular analysis of the Vibrio alginolyticus sucrose utilization system cloned into Escherichia coli

Bibliography: pages 135-150.This dissertation represents a continuation of the research on the sucrose utilization system of the aerobic, collagenolytic, halotolerant, Gram-negative bacterium Vibrio alginolyticus. The V. alginolyticus sucrose utilization system originally cloned into Escherichia coli on plasmid pVS100 involves a sucrase enzyme (gene scrB), and a sucrose uptake system. Synthesis of the sucrase and sucrose uptake system in V. alginolyticus and E. coli(pVS100) is regulated. The nucleotide sequence and analysis of DNA regions encoding the sucrose uptake and regulatory functions are presented here. An investigation of the expression of the. V. alginolyticus sucrose utilization system in Bacillus subtilis is also presented

Exploration of new catalytic methodologies for heterocyclic synthesis and C-C Bond Formation.

Amino boronate based bifiinctional molecules have the potential to be powerful catalysts. Herein, a number of approaches to the bifimctional benzimidazole catalyst 1 are described, and the synthesis of a number of analogues are explored. Investigations into the potential of 2-(2-boronobenzene)- 2N-n-butylbenzimidazole sodium hydroxide salt 1 as a catalyst for a number of synthetic transformations, including an aza-version of the Baeyer-Villiger reaction (Equation 1), are described The 2-(2-boronobenzene)-N-n-butylbenzimidazole sodium hydroxide salt 1 is shown to be active in the aldol condensation reaction (Equation 2)， Knoevenagel reaction, and evidence for the promotion of the Michael reaction by 1 is presented. The mechanism by which the aldol condensation reaction is promoted by 1 is explored through kinetic studies

Vitamin D enzymes (CYP27A1, CYP27B1 and CYP24A1) and receptor expression in non-melanoma skin cancer

No abstract available for this paper

A Monte Carlo calculation of neutron reflection from various curved surfaces

Plane parallel neutron beams normally incident upon the curved surface of a solid reflector are studied with the Monte Carlo method. The geometries studied are cylindrical, parabolic, and hemispherical. It is shown that when the curved surface is cylindrical, a small focusing effect occurs in the reflected neutron beam. Parabolic and hemispherical surfaces do not show focusing . A study of the factors which determine the spatial dependence of the reflected flux shows that the probability of emergence of a neutron, traveling a fixed distance from a point inside the reflector, depends upon the curvature of the surface. It is only for cylindrical geometry that this probability as a function of distance shows a peak which results in focusing --Abstract, page ii

Exported J domain proteins of the human malaria parasite

The heat shock protein 40 (Hsp40) family, also called J domain proteins (JDPs), regulate their Hsp70 partners by ensuring that they are engaging the right substrate at the right time and in the right location within the cell. A number of JDPs can serve as co-chaperone for a particular Hsp70, and so one generally finds many more JDPs than Hsp70s in the cell. In humans there are 13 Hsp70s and 49 JDPs. The human malaria parasite, Plasmodium falciparum, has dedicated an unusually large proportion of its genome to molecular chaperones, with a disproportionately high number of JDPs (PfJDPs) of 49 members. Interestingly, just under half of the PfJDPs are exported into the host cell during the asexual stage of the life cycle, when the malaria parasite invades mature red blood cells. Recent evidence suggests that these PfJDPs may be functionalizing both host and parasite Hsp70s within the infected red blood cell, and thereby driving the renovation of the host cell towards pathological ends. PfJDPs have been found to localize to the host cytosol, mobile structures within the host cytosol (so called “J Dots”), the host plasma membrane, and specialized structures associated with malaria pathology such as the knobs. A number of these exported PfJDPs are essential, and there is growing experimental evidence that they are important for the survival and pathogenesis of the malaria parasite. This review critiques our understanding of the important role these exported PfJDPs play at the host-parasite interface

What are higher education teachers’ values and beliefs in relation to entrepreneurship, and how are these enacted in their teaching practice? Eight case studies in English higher education

My research was initiated by an increasing awareness of divisions between practice and theory in entrepreneurship teaching, the literature noting the subject being defined by action but having an inconsistent tradition of studying action. My thesis explores the issues that relate to this, for instance, the neoliberal restructuring of higher education, the nature of entrepreneurship research and who it is for, the relationship between professional and cognitive knowledge, the status of practice and commerciality within entrepreneurship teaching, and how these issues (and others) relate to the beliefs and understandings of participants and are enacted in teaching. I approach the research using a constructivist perspective as, given its concern with the links between experience and knowledge, it seems a relevant conceptual framework to explore entrepreneurship teaching that aims to develop the “knowing how” skills. This focus does not seek to diminish the role of cognitive knowledge, which the literature observes as systematically undervalued, rather, my research seeks to clarify the role of traditional and experiential forms of knowledge in relation to the purposes of entrepreneurship teaching. My research was carried out in three Russell Group universities, one post-1992 university, and one Plate Glass university, with eight participants who were identified and recruited via a purposive sampling method, with the help of two respected senior entrepreneurship researchers. Two of the participants then recommended their own contacts. The group was a mix of mostly mid-career entrepreneurship researchers and teachers, and contained some who had significant commercial experience, with most of the participants having less extensive or no commercial experience. Because the participants were experts in their field, they had the experience to contribute valuably to my research, which was carried out via observations and semi-structured interviews to allow them the space to discuss what they considered of value. The findings were subsequently analysed through a thematic approach, given that participants’ commentary was often at a thematic level. My thesis makes five theoretical claims: first, rather than viewing the divisions between theory and practice in entrepreneurship teaching as a given, my thesis explores how this arises out of a background of policy, organisational, disciplinary and ideological pressures that shape what teachers think and believe and explores how their teaching reflects the nature of their intersection with these pressures. Second, my thesis observes that entrepreneurship research is “about” the phenomenon of entrepreneurship and is not intended to inform action, and that academic incentives reward entrepreneurship teachers for research in their disciplinary area. Consequently, these continually reinforce the estrangement of practice from the main body of theory-led teaching, because of practice’s basis in strategy rather than entrepreneurship theory. Third, my research finds that there are considerable additional blocks to the teaching of practice – organisational, disciplinary and ideological, that perpetuate the prevalent engagement with theoretical knowledge. Fourth, I explore how the nature of entrepreneurship teaching is personal, observing that this is rooted in participants’ routes to their current role, and how the concerns of the research they are undertaking orient them either towards or away from commerciality, demonstrating that teaching “for” or “about” is not merely an operational choice, but reaches down to deep layers of meaning, and in doing so, asserts allegiance to one set of values or another. Finally, observing how the terminology of theory and practice has become overlapped, I explore the vernacular of entrepreneurship through understandings of knowledge drawn from educational theory, to clarify the nature and effect of practice-based teaching instruments

Towards more integrated human-nature relationships: A Local Area Spatial Development Framework for the Two Rivers Urban Park (TRUP) Site

In this dissertation, the author explores the theme and concept of enabling more integrated human-nature relationships through strategic spatial planning. The idea that ecological planning, at a number of scales, should be an integral part of the strategic spatial planning process, in order to enable this integration, was investigated, in the current context of environmental degradation as a result of unsustainable development trajectories, climate change uncertainty, social and economic inequality, the need for compaction, and the need to strategically develop well-located catalytic sites in the city. The notion of positive and sustainable spatial planning as an enabler of more integrated human-nature relationships is investigated in terms of ecological approaches to development. The current disconnection of humans and nature has long been attributed to anthropocentric , post-industrial, and consumerist paradigms which have encouraged unsustainable urban development models, usually with assumed inevitable negative effects on the natural environment. As a result, the natural world's carrying capacity, quality, and presence in urban areas, has been severely compromized. This has limited nature's capacity to provide the necessary life support systems for humans and development and essential goods and services. This study, therefore, suggests that a paradigm shift is necessary in terms of how urban development and the natural environment interact and in terms of fostering the conditions necessary for more integrated human-nature relationships. This paradigm shift is within the realm of possibility within the ecological and spatial planning discourses. This study develops and presents a local area spatial development framework for a well-located site in the Cape Town Metropolitan area: the Two Rivers Urban Park (TRUP) site. This SDF represents the development of a spatial model for as to how more-integrated human-nature relationships can be enabled through spatial planning on the site. The study presents a literature review of literature relevant to human-nature relationships, spatial planning, and ecological planning in order to establish a theoretical framework before conducting a multi-layer anaysis of the status quo of the site. A SDF is then presented to guide responsible, positive, and sustainable development on the site over a twenty year period (2016-2036). The implementation framework is then presented before the dissertation is concluded and the major findings, recommendations, and contributions of the study are discussed. The methods and techniques used for data collection, analysis, and interpretation included case study methods, discourse and policy analysis, desktop research, observations, non-structured interviews, mapping, aerial photography, Geographical Information Systems (GIS) analysis, and an iterative conceptual design process. The SDF was generated in response to the theoretical framework and contextual analysis of the site. The major conclusions and findings were that, through the process of developing the SDF, it is possible to exhibit how spatial and ecological planning may be integrated in order to enable and foster deeper connections between humans and nature. The framework seeks to exhibit good-practice pilot projects and strategic interventions which should be innovatively implemented in terms of satisfying the criteria of positive development, sustainability, and depper human-nature relationships. A series of intentional and conscious eco-village type communities are envisioned on the site, whose way of life is closely connected and integrated into a single socio-ecological system with nature. Recommendations for future planning and research are presented and a personal reflection articulated before the study is concluded