A study of failure in school with special reference to Indian secondary education in Natal.

Thesis (M.Ed.)-University of Durban-Westville, 1978.This is a study of the incidence of failure in Indian secondary education in Natal, in which academic performance was considered against the background of a number of variables such as socio-economic factors, family size, birth order, IQ, health, absenteeism, study and reading habits, parents' level of Western education, family income, participation in extra-curricular activities and certain behaviour and personality traits. A random sample of 1 787 pupils (1 092 boys and 695 girls) who wrote the Standard VII Academic Course examination in 1974 was selected from 16 Indian secondary schools in Natal. Data were obtained by administering a set of questionnaires to the pupils and the form-teachers. Data processing was done by the lCL computer service. The Chi-square statistical techniques was used to test for significance. The findings suggest that: (i) there are significant relationships between academic performance and the following variables: parents' level of Western education, religion, birth-order (especially among first-born boys) IQ and absenteeism; (ii) certain of the variables tested influenced the academic performance of the boys differently from those of the girls. These variables are family income, physical handicaps, reading habits and participation in extra-curricular activities. The trend was that these variables influenced the boys' performance more than the girls' performance. (iii) there were certain variables which were not significantly related to academic performance. These were: health of pupils, use of the library for borrowing books, fathers' occupation, having one's own room, family size, language commonly spoken at home and the number of times the pupils were transferred from one school to another Finally certain recommendations are suggested with a view to reducing failure at school

A critical study of aspects of the political, constitutional, administrative and professional development of Indian teacher education in South Africa with particular reference to the period 1965 to 1984.

Thesis (Ph.D.) - University of Natal, Pietermaritzburg, 1985.This study deals with the administrative and curricular development of Indian teacher education in South Africa for the period 1860 - 1984. It is set against the background of developments in the education system for Indians in this country. Historical and political events which have a direct bearing on Indian education are touched upon merely cursorily to give the reader the necessary background for a fuller appreciation of the Indian community's struggle for education in the country of their adoption. The study is divided into three parts. Part one comprising the first two chapters, provides a brief historical perspective of Indian education from 1860 to 1965. Chapter One deals with a brief review of the coming of the Indians to Natal and the origins and early development of education for the Indians. Chapter Two carries on the historical review with the emphasis on the early development of Indian teacher education. Part Two comprising four chapters deals with aspects of Indian education after it was transferred from provincial control to central State control in 1966. The Indian Education Act of 1965 (No. 61 of 1965) is taken as a point of departure. Chapter Three begins with a very brief discussion of the principles underlying the nationalisation of education in South Africa. The de Lange Report and the Government's reaction to its recommendations are considered against the new political dispensation. Chapter Four deals with such aspects as control and administration, involvement of Indians in the control of their education, school accommodation, growth in pupil enrolment and the school curricula are examined to assess growth and progress. Chapter Five is concerned with the control and administration of Indian teacher education after nationalisation of Indian education. Within the framework of this chapter recent developments such as the recommendations of the Gericke Commission leading to the National Education Policy Amendment Act (No. 75 of 1969) and the van Wyke de Vries Commission's recommendations for a closer co-operation with universities in respect of teacher education, are examined with a view to tracing their influence on Indian teacher education. Chapter Six attempts to examine demographic aspects which influence the demand for and supply of teachers in Indian education. Part Three comprising four chapters, examines contemporary issues and perspectives in Indian teacher education. Chapters Seven and Eight examine critically the teachers' courses at the Colleges of Education and the University of Durban-Westville respectively. Chapter Nine examines on a comparative basis structural changes and new developments in methodological skills in teacher education. Finally, in Chapter Ten proposals and recommendations are formulated with a view to achieving a properly structured institutional arrangement such as the college council and college senate to facilitate Indian teacher education

Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins

Some bacterial toxins and viruses have evolved the capacity to bind mammalian glycosphingolipids to gain access to the cell interior, where they can co-opt the endogenous mechanisms of cellular trafficking and protein translocation machinery to cause toxicity. Cholera toxin (CT) is one of the best-studied examples, and is the virulence factor responsible for massive secretory diarrhea seen in cholera. CT enters host cells by binding to monosialotetrahexosylganglioside (GM1 gangliosides) at the plasma membrane where it is transported retrograde through the trans-Golgi network (TGN) into the endoplasmic reticulum (ER). In the ER, a portion of CT, the CT-A1 polypeptide, is unfolded and then “retro-translocated” to the cytosol by hijacking components of the ER associated degradation pathway (ERAD) for misfolded proteins. CT-A1 rapidly refolds in the cytosol, thus avoiding degradation by the proteasome and inducing toxicity. Here, we highlight recent advances in our understanding of how the bacterial AB5 toxins induce disease. We highlight the molecular mechanisms by which these toxins use glycosphingolipid to traffic within cells, with special attention to how the cell senses and sorts the lipid receptors. We also discuss several new studies that address the mechanisms of toxin unfolding in the ER and the mechanisms of CT A1-chain retro-translocation to the cytosol

Ceramide structure dictates glycosphingolipid nanodomain assembly and function

Gangliosides such as GM1 present in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. Here the authors show that the acyl chain structure of GM1 determines the establishment of nanodomains when actively clustered by actin, which depended on membrane cholesterol and phosphatidylserine or superimposed by the GM1-binding bacterial cholera toxin

Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1

The incretin hormone Glucagon-like peptide 1 (GLP-1) requires delivery by injection for the treatment of Type 2 diabetes mellitus. Here, we test if the properties of glycosphingolipid trafficking in epithelial cells can be applied to convert GLP-1 into a molecule suitable for mucosal absorption. GLP-1 was coupled to the extracellular oligosaccharide domain of GM1 species containing ceramides with different fatty acids and with minimal loss of incretin bioactivity. When applied to apical surfaces of polarized epithelial cells in monolayer culture, only GLP-1 coupled to GM1-ceramides with short-or cis-unsaturated fatty acids trafficked efficiently across the cell to the basolateral membrane by transcytosis. In vivo studies showed mucosal absorption after nasal administration. The results substantiate our recently reported dependence on ceramide structure for trafficking the GM1 across polarized epithelial cells and support the idea that specific glycosphingolipids can be harnessed as molecular vehicles for mucosal delivery of therapeutic peptides

Oligomers of the ATPase EHD2 confine caveolae to the plasma membrane through association with actin

Caveolae are plasma membrane microdomains that play important roles in signalling and endocytosis. The ATPase EHD2 shuttles on and off the static population of caveolae in an ATPase cycledependent manner and links caveolae to actin filaments confining them to the plasma membrane

A Grafting Strategy for the Design of Improved G-Quadruplex Aptamers and High-Activity DNAzymes

Nucleic acid aptamers are generally obtained by in vitro selection. Some have G-rich consensus sequences with ability to fold into the four-stranded structures known as G-quadruplexes. A few G-quadruplex aptamers have proven to bind hemin to form a new class of DNAzyme with the peroxidase-like activity, which can be significantly promoted by appending an appropriate base-pairing duplex onto the G-quadruplex structures of aptamers. Knowing the structural role of base pairing, here we introduce a novel grafting strategy for the design of improved G-quadruplex aptamers and high-activity DNAzymes. To demonstrate this strategy, three existing G-quadruplex aptamers are chosen as the first generation. A base-pairing DNA duplex is grafted onto the G-quadruplex motif of the first generation aptamers. Consequently, three new aptamers with the quadruplex/duplex DNA structures are produced as the second generation. The hemin-binding affinities and DNAzyme functions of the second generation aptamers are characterized and compared with the first generation. The results indicate three G-quadruplex aptamers obtained by the grafting strategy have more excellent properties than the corresponding original aptamers. Our findings suggest that, if the structures and functions of existing aptamers are thoroughly known, the grafting strategy can be facilely utilized to improve the aptamer properties and thereby producing better next-generation aptamers. This provides a simple but effective approach to the design of nucleic acid aptamers and DNAzymes

Discovery of Dual-Action Membrane-Anchored Modulators of Incretin Receptors

The glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP-1) receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL) technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.Serial substitution of residue 7 in membrane-tethered GIP (tGIP) led to a wide range of activities at the GIP receptor, with [G(7)]tGIP showing enhanced efficacy compared to the wild type construct. In contrast, introduction of G(7) into the related ligands, tGLP-1 and tethered exendin-4 (tEXE4), did not affect signaling at the cognate GLP-1 receptor. Both soluble and tethered GIP and GLP-1 were selective activators of their respective receptors. Although soluble EXE4 is highly selective for the GLP-1 receptor, unexpectedly, tethered EXE4 was found to be a potent activator of both the GLP-1 and GIP receptors. Diverging from the pharmacological properties of soluble and tethered GIP, the newly identified GIP-R agonists, (i.e. [G(7)]tGIP and tEXE4) failed to trigger cognate receptor endocytosis. In an attempt to recapitulate the dual agonism observed with tEXE4, we conjugated soluble EXE4 to a lipid moiety. Not only did this soluble peptide activate both the GLP-1 and GIP receptors but, when added to receptor expressing cells, the activity persists despite serial washes.These findings suggest that conversion of a recombinant MTL to a soluble membrane anchored equivalent offers a means to prolong ligand function, as well as to design agonists that can simultaneously act on more than one therapeutic target

Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study

Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating ∼380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72×10−7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62×10−3 and 2.44×10−3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values<10−5 in the two samples. The PLCL1 gene's relevance to HF was also observed in a Chinese sample containing 403 females, including 266 with HF and 177 control subjects. A SNP of the PLCL1 gene, rs3771362 that is only ∼0.6 kb apart from the most significant SNP detected in our GWAS (rs7595412), achieved a p value of 7.66×10−3 (odds ratio = 0.26) for association with HF. Additional biological support for the role of PLCL1 in BS comes from previous demonstrations that the PLCL1 protein inhibits IP3 (inositol 1,4,5-trisphosphate)-mediated calcium signaling, an important pathway regulating mechanical sensing of bone cells. Our findings suggest that PLCL1 is a novel gene associated with variation in hip BS, and provide new insights into the pathogenesis of HF

Membrane Cholesterol Regulates Lysosome-Plasma Membrane Fusion Events and Modulates Trypanosoma cruzi Invasion of Host Cells

Trypanosoma cruzi, is the etiological agent of a neglected tropical malady known as Chagas' disease, which affects about 8 million people in Latin America. 30–40% of affected individuals develop a symptomatic chronic infection, with cardiomyopathy being the most prevalent condition. T. cruzi utilizes an interesting strategy for entering cells: T. cruzi enhances intracellular calcium levels, which in turn trigger the exocytosis of lysosomal contents. Lysosomes then donate their membrane for the formation of the parasitophorous vacuole. Membrane rafts, cholesterol-enriched microdomains in the host cell plasma membrane, have also been implicated in T. cruzi invasion process. Since both plasma membrane and lysosomes collaborate in parasite invasion, we decided to study the importance of these membrane domains for lysosomal recruitment and fusion during T. cruzi invasion into host cells. Our results show that drug dependent depletion of plasma membrane cholesterol changes raft organization and induces excessive lysosome exocytosis in the earlier stages of treatment, leading to a depletion of lysosomes near the cell cortex, which in turn compromises T. cruzi invasion. Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events of pre-docked lysosomes, reducing lysosome availability at the cell cortex and consequently compromising T. cruzi infection