Glucose Metabolism and Carcinogenesis: The Impact of the Tumor Suppressor p53

The tumor suppressor protein, p53 responds to cellular stress such as DNA damage, oncogenic activation and hypoxia by transactivating downstream genes that are responsible for apoptosis, DNA repair, senescence, cell cycle arrest and cell cycle progression. However, emerging trends show that p53 also plays multifaceted roles in regulating glucose metabolism. It promotes oxidative phosphorylation, suppresses glycolysis at multiple points as well as controlling glutamine and lipid metabolism. Current findings suggest that p53 actions have potential to influence the Warburg Effect, that is, characteristic of cancer cells. The Warburg phenomenon is characterized by their preference for glycolysis to oxidative phosphorylation for ATP generation, irrespective of adequate oxygen supply. This is often in concomitance with enhanced glucose uptake and leads to increased lactate production and anabolic processes such as lipid synthesis and de novo nucleic acid synthesis. The molecular underpinnings of the Warburg Effect are still poorly understood. These important differences between cancer and normal cells have induced interest in glucose metabolism as a drug target. This chapter focuses on the influence p53 exerts on glucose metabolism as well as on the implications of the Warburg phenomenon in carcinogenesis and a review of the ever-increasing number of p53 regulators

The Drosophila ankyrin repeat protein cactus has a predominantly α-helical secondary structure

AbstractThe cactus protein is the Drosophila homologue of the mammalian IKB family of cytoplasmic anchor proteins. We have expressed in E. coli and purified a cactus fusion protein, CACT-Bgl. CACT-Bgl protein contains the six ankyrin repeat sequences which are necessary for specific binding to the Drosophila rel family transcription factor dorsal. We show that the purified CACT-Bgl protein can bind specifically to dorsal and, using circular dichroism spectroscopy, that the protein adopts a largely α-helical secondary structure. A further analysis of the ankyrin repeat domains of cactus, using an improved secondary structure prediction program indicates that the N-terminal of the repeat will form into a loop structure and the C-terminal section into an interrupted, amphipathic α-helix. On the basis of these findings we propose that the ankyrin repeats of cactus fold together into helical bundles interconnected by diverged loops

Coleopteran Antimicrobial Peptides: Prospects for Clinical Applications

Antimicrobial peptides (AMPs) are activated in response to septic injury and have important roles in vertebrate and invertebrate immune systems. AMPs act directly against pathogens and have both wound healing and antitumor activities. Although coleopterans comprise the largest and most diverse order of eukaryotes and occupy an earlier branch than Drosophila in the holometabolous lineage of insects, their immune system has not been studied extensively. Initial research reports, however, indicate that coleopterans possess unique immune response mechanisms, and studies of these novel mechanisms may help to further elucidate innate immunity. Recently, the complete genome sequence of Tribolium was published, boosting research on coleopteran immunity and leading to the identification of Tribolium AMPs that are shared by Drosophila and mammals, as well as other AMPs that are unique. AMPs have potential applicability in the development of vaccines. Here, we review coleopteran AMPs, their potential impact on clinical medicine, and the molecular basis of immune defense

Access to information on higher education as a barrier for rural learners of Tyolomnqa Village, Eastern Cape

Worldwide, there is a large body of research that convincingly demonstrates the benefits of Higher Education (HE) in the socio-economic status of individuals who have gone through and qualified with certificates, diplomas and degrees. But access to HE does not just benefit individuals, it also has benefits for communities or broader society (access to HE may benefit individual scholars, but can also benefit economically the entire families and poverty stricken communities such as those from Tsholomnqa village where this study was conducted). However, in South Africa, there is limited research that focuses on the importance of and challenges of access to HE as confronted by rural scholars. This research presents findings from a mixed method based study which sought to probe key issues relating to access to HE and challenges facing rural scholars regarding access to information on HE. The study involved as many as 209 Grade 12 learners from two high schools in the rural area of Tsholomnqa village in the Eastern Cape Province, a province associated with high levels of poverty, inequalities and unemployment in South Africa. The findings reveal that rural scholars about to qualify for university access information on HE information primarily from the internet. However, it was found that issues such as not having data or smartphones to search the internet and lack of support from their parents and teachers including universities affected their self-efficacy and self-esteem. The implications of these findings suggest that HE institutions must target and strengthen outreach and visibility in rural schools

Traditional leadership and the use of cultural laws in land administration: implications for rural women's land rights in a transforming South Africa

This dissertation critically examines how traditional leaders use cultural laws to allocate land to women and to allow women to participate in land administration in communal areas. Given the government's commitment to gender equity in all spheres of life as stipulated in Section 9 (3) of the South African Constitution (Act 108 of 1996), the dissertation examines whether related legislation and policy (such as CLARA and TLGFA) alone can guarantee equitable access to land for women and their participation in land administration structures in communal areas where patriarchy dominates. In essence, the study interrogates whether state intervention through formalizing laws that govern land matters do achieve gender equity while cultural laws still exist in communal areas. Based on the view that land in communal areas is held by the state and administered by traditional leaders who have historically discriminated against women, the dissertation employs a case study method to examine whether cultural laws are exercised when women apply for a piece of land at the three levels of traditional authority viz: village, sub-village and traditional council levels in the Matolweni village of the Nqadu Tribal Authority. Although women are often the de facto rights holders in rural areas as a result of male migration to urban areas, findings seem to indicate that it is difficult and/or sometimes impossible to translate paper laws into practice while cultural laws are still operating. For effective transformation to occur, the study recommends that unless a strong women's rural movement emerges, coupled with a socialist feminist position that advocates for a radical transformation of rural society to defeat the patriarchal norms and standards, traditional leaders will continue to discriminate against women in land issues

An evaluation of the expanded public works programme in the Buffalo City Metropolitan Municipality, Eastern Cape Province

The evaluation of the EPWP within the BCMM will assist the municipality in enhancing the metropolitan’s capacity to deliver the services of the EPWP by ensuring that challenges are addressed, an integrated approach is adopted and that the programme implementation receives the necessary support in order to develop communities. Cabinet has adopted the EPWP as its main tool for creating job opportunities. It has been approved as a conceptual framework with a specific role and targets for each municipality programme. The EPWP also engages the creation of job opportunities for unemployed people which enables them to participate in the economy; eventually they will make a contribution to their communities’ development and to the country as a whole. (National EPWP Guidelines, 2003:4). The EPWP is significant because it aims to expand the creation of temporary job opportunities which will give unemployed and poor people some income. The BCMM has focused on strengthening and expanding its EPWP, predominantly in the infrastructure sector. The emphasis has been on job creation through intensive methods in housing and infrastructure projects, as well as on improving reporting, monitoring and evaluation. Thus, the decision was taken to house the EPWP unit within the Directorate of Infrastructure Services for efficient administration, as most infrastructure projects are implemented within the directorate. To improve the implementation of the EPWP, and to be effective within the metropolitan, the programme should incorporate all activities within the municipality. Therefore, every project implemented, as per the municipality’s Integrated Development Plan (IDP), should be required to promote all possible EPWP opportunities. All existing projects should be restructured in order to promote greater employment opportunities. The municipality needs to increase emphasis on labour intensive construction methods, the rollout of the EPWP in the social and environmental and culture sectors, and the municipality should evince a greater level of EPWP participation

Assessing the Impact of Collective Marketing of Paddy Rice in Innovation Platforms by Smallholder Producers in Benin

Market access is a major constraint of smallholder rice producers in sub-Saharan Africa (SSA). There is increasing evidence that acting collectively offers one way for smallholders to participate more efficiently in the market. This chapter aimed to identify the determinants of participation in collective marketing of rice in innovation platforms in Benin and quantify its impact on household income and food security. Unlike previous studies, we used the local average treatment effect parameter to assess the impact of collective marketing of rice. Data were collected from a random sample of 257 smallholder rice producers. Results showed that participation in collective marketing increased the income of rice farmers on average by USD 148/ha. Main determinants of participation in collective marketing of rice were membership in a farmer group, training, and agreement on price. This chapter concludes that better training and well-functioning farmer groups sustain the impact of collective marketing of rice on food security

Pathways and Network Based Analysis of Candidate Genes to Reveal Cross-Talk and Specificity in the Sorghum (Sorghum bicolor (L.) Moench) Responses to Drought and It's Co-occurring Stresses

Drought alone or in combination with other stresses forms the major crop production constraint worldwide. Sorghum, one of the most important cereal crops is affected by drought alone or in combination with co-occurring stresses; notwithstanding, sorghum has evolved adaptive responses to combined stresses. Furthermore, an impressive number of sorghum genes have been investigated for drought tolerance. However, the molecular mechanism underling drought response remains poorly understood. We employed a systems biology approach to elucidate regulatory and broad functional features of these genes. Their interaction network would provide insight into understanding the molecular mechanisms of drought tolerance and underpinning signal pathways. Functional analysis was undertaken to determine significantly enriched genesets for pathways involved in drought tolerance. Analysis of distinct pathway cross-talk network was performed and drought-specific subnetwork was extracted. Investigation of various data sources such as gene expression, regulatory pathways, sorghumCyc, sorghum protein-protein interaction (PPI) and Gene Ontology (GO) revealed 14 major drought stress related hub genes (DSRhub genes). Significantly enriched genesets have shown association with various biological processes underlying drought-related responses. Key metabolic pathways were significantly enriched in the drought-related genes. Systematic analysis of pathways cross-talk and gene interaction network revealed major cross-talk pathway modules associated with drought tolerance. Further investigation of the major DSRhub genes revealed distinct regulatory genes such as ZEP, NCED, AAO, and MCSU and CYP707A1. These were involved in the regulation of ABA biosynthesis and signal transduction. Other protein families, namely, aldehyde and alcohol dehydrogenases, mitogene activated protein kinases (MAPKs), and Ribulose-1,5-biphosphate carboxylase (RuBisCO) were shown to be involved in the drought-related responses. This shows a diversity of complex functional features in sorghum to respond to various abiotic stresses. Finally, we constructed a drought-specific subnetwork, characterized by unique candidate genes that were associated with DSRhub genes. According to our knowledge, this is the first in sorghum drought investigation that introduces pathway and network-based candidate gene approach for analysis of drought tolerance. We provide novel information about pathways cross-talk and signaling networks used in further systems level analysis for understanding the molecular mechanism behind drought tolerance and can, therefore, be adapted to other model and non-model crops