We are fighting for the liberation of our people: Justifications of violence by activist youth in Diepkloof, Soweto

African Studies Seminar series. Paper presented 28 August 1995This paper, which seeks to understand youths' own justifications for engaging in acts of collective violence, is based on a case study of activist youth and their organisations in Diepkloof, Soweto. The research was conducted during the period 1991 - 1993. While the specificities and peculiarities of any particular area make generalisations difficult, many of the conditions under which Diepkloof youth live, as well as their experiences, are probably very similar to those of youth in other townships in Soweto, the Gauteng province, and indeed, South Africa. Consequently, while the research claims to give insight into the consciousness of activist youth in Diepkloof, some of these findings may be applicable to youth in other townships

Dancing with the devil? Participatory action research with police in South Africa

At the present moment, major changes are being proposed to the way that policing should be done in South Africa. These changes do not seem to be informed by any research agenda or by a long term strategic approach aimed at 'smarter policing'. This paper reflects on the possible partnerships that (academic) researchers and police could form with the shared objective of bring about change in police organisations. These collaborative research arrangements are undoubtedly difficult. Police and academic researchers continue to operate in silos and the two groups have distinctive institutional cultures, which are sometimes at odds with one another. However, as this paper tries to demonstrate, collaborative research is possible. This article is in many ways a personal reflection on my own research collaborations with the police using a participatory action research approach

POLICE AS WORKERS: Police labour rights in Southern Africa and beyond

Efforts by police organisations to unionise and to increase their social and labour rights is an international phenomenon, and one that is becoming  more vigorous in the Southern African region. However, many governments are wary of police unions and limit their rights, or refuse to recognise them at all. This gave impetus to the formation of the International Council of Police Representative Associations (ICPRA), in September 2006. Two of ICPRA’s aims are to assist and advise police unions all over the world and to provide the international police union movement with a voice for influencing policing futures. In South Africa, the Police and Civil Rights Union (POPCRU) is assisting police in the subregion and has become a symbol of what is possible for police even in repressive states. In a rapidly changing police labour environment, police unions have the capacity to confront existing (undemocratic) occupational cultures, to promote organisational accord and to forge positive reform

Critical changes in hypothalamic gene networks in response to pancreatic cancer as found by single-cell RNA sequencing

OBJECTIVE: Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. In particular, the hypothalamus may play a central role in cachexia, given that it has direct access to peripheral signals because of its anatomical location and attenuated blood–brain barrier. Furthermore, this region has a critical role in regulating appetite and metabolism. METHODS: To provide a detailed analysis of the hypothalamic response to cachexia, we performed single-cell RNA-seq combined with RNA-seq of the medial basal hypothalamus (MBH) in a mouse model for pancreatic cancer. RESULTS: We found many cell type-specific changes, such as inflamed endothelial cells, stressed oligodendrocyes and both inflammatory and moderating microglia. Lcn2, a newly discovered hunger suppressing hormone, was the highest induced gene. Interestingly, cerebral treatment with LCN2 not only induced many of the observed molecular changes in cachexia but also affected gene expression in food-intake decreasing POMC neurons. In addition, we found that many of the cachexia-induced molecular changes found in the hypothalamus mimic those at the primary tumor site. CONCLUSION: Our data reveal that multiple cell types in the MBH are affected by tumor-derived factors or host factors that are induced by tumor growth, leading to a marked change in the microenvironment of neurons critical for behavioral, metabolic, and neuroendocrine outputs dysregulated during cachexia. The mechanistic insights provided in this study explain many of the clinical features of cachexia and will be useful for future therapeutic development

POPIA Code of Conduct for Research

No abstrac

Corrigendum: POPIA Code of Conduct for Research

No abstrac

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment