Causal and Putative Pathogenic Mutations Identified in 38.6% of Children with Primary SRNS in South Africa

The aim was to identify causal mutations in genes implicated in steroid resistant nephrotic syndrome (SRNS) within a South African population. We enrolled 119 children with primary NS; 71 SRNS and 48 steroid-sensitive NS. All children with SRNS underwent kidney biopsy. We first genotyped the NPHS2 gene for the p.V260E variant in all NS cases (n= 119) and controls (n= 219). To further identify additional variants, we performed whole-exome sequencing and interrogated ten genes (NPHS1, NPHS2, WT1, LAMB2, ACTN4, TRPC6, INF2, CD2AP, PLCE1, MYO1E) implicated in SRNS/FSGS in 56 SRNS cases and 29 controls; we also performed exome sequencing on two patients carrying the NPHS2 p.V260E mutation as positive controls. The overall detection rate of pathogenic mutations in children with SRNS was 27/70(38.57%): 15(21.43%) carried the NPHS2 p.V260E mutation and 12(17.14%) carried a pathogenic mutation in the heterozygous state in INF2 (n=8), CD2AP (n=3) or TRPC6 (n=1) genes. NPHS2 p.V260E homozygosity was specifically associated with biopsy-proven FSGS, accounting for 23.81% of Black children (15 of 63) with SR-FSGS. No causal mutations were identified in NPHS1, WT1, LAMB2, PLCE1, MYO1E and ACTN4. We report four novel variants in INF2, PLCE1, ACTN4 and TRPC6.Conclusion: The NPHS2 p.V260E mutation is a prevalent cause of SR-FSGS among Black South African children occurring in 23.81% of children with SRNS. Screening all Black African children presenting with NS for NPHS2 p.V260E will provide a precision diagnosis of SR-FSGS and inform clinical management.

Sex Differences in the Associations of Nutrient Patterns with Total and Regional Adiposity: A Study of Middle-Aged Black South African Men and Women

The study evaluated the association between nutrient patterns with body fat and regional adiposity in middle-aged black South African (SA) men and women and determined if this differed by sex. Body fat and regional adiposity (dual-energy x-ray absorptiometry), and dietary intake (7-day quantified food frequency questionnaire) were measured in black SA men (n = 414) and women (n = 346). Using principal component analysis, nutrient patterns were computed from 25 nutrients in the combined sample. Four nutrient patterns were extracted, explaining 67% of the variance in nutrient intake. Animal and fat, as well as the vitamin C, sugar, and potassium driven patterns, were positively associated with total adiposity. In contrast, the retinol and vitamin B12 pattern was associated with the centralisation of fat. Notably, the strength of the association between the animal-driven nutrient pattern and BMI was greater in men (1.14 kg/m2, 95% CI (0.63–1.66)) than in women (0.81 kg/m2, 95% CI (0.25–1.36)) (Pint = 0.017). In contrast, the plant-driven pattern was associated with higher abdominal subcutaneous adipose tissue (SAT) in women (44 cm2, 95% CI (22–67)) but not men (Pint = 1.54 × 10−4). These differences suggest that although men and women have similar nutrient patterns, their associations with the whole body and regional body fat are different.

Reduced CCR5 Expression and Immune Quiescence in Black South African HIV-1 Controllers

Unique Individuals who exhibit either suppressive HIV-1 control, or the ability to maintain low viral load set-points and preserve their CD4+ T cell counts for extended time periods in the absence of antiretroviral therapy, are broadly termed HIV-1 controllers. We assessed the extent to which black South African controllers (n=9), differ from uninfected healthy controls (HCs, n=22) in terms of lymphocyte and monocyte CCR5 expression (density and frequency of CCR5-expressing cells), immune activation as well as peripheral blood mononuclear cell (PBMC) mitogen-induced chemokine/cytokine production. In addition, relative CD4+ T cell CCR5 mRNA expression was assessed in a larger group of controllers (n=20) compared to HCs (n=10) and HIV-1 progressors (n=12). Despite controllers having significantly higher frequencies of activated CD4+ and CD8+ T cells (HLA-DR+) compared to HCs, CCR5 density was significantly lower in these T cell populations (P=0.039 and P=0.064, respectively). This lower CCR5 density was largely attributable to controllers with higher VLs (>400 RNA copies/ml). Significantly lower CD4+ T cell CCR5 density in controllers was maintained (P=0.036) when HCs (n=12) and controllers (n=9) were matched for age. CD4+ T cell CCR5 mRNA expression was significantly less in controllers compared to HCs (P=0.007) and progressors (P=0.002), whereas HCs and progressors were similar (P=0.223). The levels of soluble CD14 in plasma did not differ between controllers and HCs, suggesting no demonstrable monocyte activation. While controllers had lower monocyte CCR5 density compared to the HCs (P=0.02), significance was lost when groups were age-matched (P=0.804). However, when groups were matched for both CCR5 promoter haplotype and age (n=6 for both) reduced CCR5 density on monocytes in controllers relative to HCs was highly significant (P=0.009). Phytohemagglutinin-stimulated PBMCs from the controllers produced significantly less CCL3 (P=0.029), CCL4 (P=0.008) and IL-10 (P=0.028) compared to the HCs, which was largely attributable to the controllers with lower VLs (<400 RNA copies/ml). Our findings support a hypothesis of an inherent (genetic) predisposition to lower CCR5 expression in individuals who naturally control HIV-1, as has been suggested for Caucasian controllers, and thus, likely involves a mechanism shared between ethnically divergent population groups.

Detective Stories During Apartheid: H.I.E. Dhlomo as a Precursor of Drum

This article aims to contribute to the discussion of English-language crime fiction by black South African writers before 1994 by exploring H.I.E. Dhlomo’s relatively overlooked contribution to the genre in the first decade of apartheid. In particular, I intend to close read three detective stories written between the late 1940s and the early 1950s by Dhlomo, namely “Village Blacksmith Tragicomedy”, “Flowers”, and “Aversion to Snakes”, and compare them with the more celebrated stories published by Arthur Maimane in the popular magazine Drum a few years later. Notwithstanding their different re-elaboration of the tropes of crime fiction, I argue that both Dhlomo and Maimane resorted to this productive strand of popular literature to reassert a claim to knowledge denied to Africans, saturating their texts with new local meanings and exceeding Western genre conventions.

Human Hepatocyte Nuclear Factors (HNF1 and LXRb) Regulates CYP7A1 in HIV-Infected Black South African Women with Gallstone Disease: A Preliminary Study

Background: Female sex, high estrogen levels, aging, obesity and dyslipidemia are some of the risk factors associated with gallstone formation. HIV infected patients on combination antiretroviral therapy (cART) are more prone to hypercholesterolemia. Bile acid synthesis is initiated by cholesterol 7-alpha hydroxylase (CYP7A1) and regulated by hepatocyte nuclear factors (HNF1α, HNF4α and LXRb).Aim/ Objective: To evaluate the expression of HNF1α, HNF4α, LXRb and miRNAs (HNF4α specific: miR-194-5p and miR-122*_1) that regulate CYP7A1 transcription in HIV-infected Black South African women on cART and presenting with gallstones relative to HIV negative patients with gallstone disease. Methods: Females (n = 96) presenting with gallstone disease were stratified based on HIV status. The gene expression of CYP7A1, HNF1α, HNF4α, LXRb, miR-194-5p and miR-122*_1 was determined using RT-qPCR. Messenger RNA and miRNA levels were reported as fold change expressed as 2-ΔΔCt (RQ min; RQ max). Fold changes >2 and <0.5 were considered significant. Results: HIV-infected females were older in age (p = 0.0267) and displayed higher low-density lipoprotein cholesterol (LDL-c) (p = 0.0419), CYP7A1 [2.078-fold (RQ min: 1.278; RQ max: 3.381)], LXRb [2.595-fold (RQ min: 2.001; RQ max: 3.000)] and HNF1α [3.428 (RQ min: 1.806; RQ max: 6.507] levels. HNF4α [0.642-fold (RQ min: 0.266; RQ max: 1.55)], miR-194-5p [0.527-fold (RQ min: 0.37; RQ max: 0.752)] and miR-122*_1 [0.595-fold (RQ min: 0.332; RQ max: 1.066)] levels were lower in HIV-infected females. Conclusions: HIV-infected women with gallstone disease displayed higher LDL-c levels and increased bile acid synthesis which was evident by the elevated expression of CYP7A1, HNF1α and LXRb. This could have been further influenced by cART and aging.

Collective Psychological Ownership and Territorial Compensation in Australia and South Africa

Collective psychological ownership as a sense that a territory belongs to a group might explain attitudes of the White majority toward territorial compensation for Indigenous Peoples in settler societies. Ownership can be inferred from different general principles and we considered three key principles: autochthony (entitlements from first arrival), investment (entitlements from working the land), and formation (primacy of the territory in forming the collective identity). In two studies, among White Australians (Study 1, N = 475), and White South Africans (Study 2, N = 879), we investigated how support for these general principles was related to perceived ingroup (Anglo-Celtic/White South African) and outgroup (Indigenous Australian/Black South African) territorial ownership, and indirectly, to attitudes toward territorial compensation for the Indigenous outgroup. Endorsement of autochthony was related to stronger support for territorial compensation through higher perceived outgroup ownership, whereas investment was related to lower support through higher perceived ingroup ownership. Agreement with the formation principle was related to stronger support for compensation through higher outgroup ownership, and simultaneously to lower support through higher ingroup ownership.

Increased Risk for Type 2 Diabetes in Relation to Adiposity in Middle-Aged Black South African Men compared to Women

Aims: Despite a higher prevalence of overweight and obesity in black South African women compared to men, the prevalence of type 2 diabetes does not differ. We explored if this could be due to sex differences in insulin sensitivity, clearance and or beta cell function, and also sex-specific associations with total and regional adiposity. Methods: This cross-sectional study included 804 black South African men (n=388) and women (n=416). Dual-energy x ray absorptiometry was used to measure total and regional adiposity. Insulin sensitivity (Matsuda index), secretion (C peptide index) and clearance (C peptide/insulin ratio) were estimated from an oral glucose tolerance test. Results: After adjusting for sex differences in fat mass index, men were less insulin sensitive and had lower beta cell function than women (p<0.001), with the strength of the associations with measures of total and central adiposity being greater in men than women (p<0.001 for interactions). Further, the association between total adiposity and type 2 diabetes risk was also greater in men than women (relative risk ratio (95% confidence interval): 2.05 (1.42 to 2.96), p<0.001 vs. 1.38 (1.03 to 1.85), p=0.031). Conclusion: With increasing adiposity, particularly increased centralisation of body fat linked to decreased insulin sensitivity and beta cell function, Black African men are at greater risk for type 2 diabetes than their female counterparts.

Sex Differences in the Associations of Nutrient Patterns with Total and Regional Adiposity: A Study of Middle-Aged Black South African Men and Women

The study evaluated the association between nutrient patterns and body fat and regional adiposity in middle-aged black South African (SA) men and women and determined if this differed by sex. Body fat and regional adiposity (dual-energy x-ray absorptiometry), and dietary intake (7-day quantified food frequency questionnaire) were measured in black SA men (n=414) and women (n=346). Using principal component analysis, nutrient patterns were computed from 25 nutrients in the combined sample. Four nutrient patterns were extracted, explaining 67% of the variance in nutrient intake. Animal and fat, as well as the vitamin C, sugar and potassium driven patterns, were positively associated with total adiposity. In contrast, the retinol and vitamin B12 pattern was associated with the centralisation of fat. Notably, the strength of the association between the animal-driven nutrient pattern and BMI was greater in men (1.14 kg/m2, 95%CI (0.63-1.66)) than women (0.81 kg/m2, 95%CI (0.25-1.36)) (Pint=0.017). In contrast, the plant driven pattern was associated with higher abdominal subcutaneous adipose tissue (SAT) in women (44 cm2, 95%CI (22-67)) but not men (Pint =1.54 x 10-4). These interactions suggest that although men and women have similar nutrient patterns, the associations with the whole body and regional body fat are different.

Lucky Philip Dube: The Artiste in Search of a New Jurisprudence and Subaltern Redemption

Most musicians, in their songs, portray their philosophical vision of life as could be seen in the case of Lucky Philip Dube, the black South African reggae musician. His songs show that he adheres to the principle of ethical humanism and portrays him as a crusader of social justice. Thus, this essay shows the link between musical art and law by examining the commitment of Dube’s lyrical composition in fighting for a just legal system in his society. This essay therefore, analyses some of his lyrical productions in order to expound on the philosophical ideas underneath the songs and how they tie with the search of an alternative jurisprudence and humanism in postcolonial discourse and the liberation of the subaltern. From the perspective of natural law theory, this essay postulates that Dube’s songs criticise the injustice of the legal philosophy in his society and quest for an impartial jurisprudence – that of equality and justice in his society.