226 research outputs found

    Looking back: Insider views on the Judicial Inspectorate for Correctional Services

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    The establishment of a constitutional democracy in South Africa necessitated widespread institutional reforms across state sectors. A key feature of such reforms was the emphasis on oversight and accountability as illustrated in reform endeavours pursued in the South African Police Service, courts and prisons. One such oversight mechanism – the Judicial Inspectorate for Correctional Services (JICS) – is the subject of this article. Drawing on qualitative interviews with people closely involved with the JICS since 1998, this article presents ‘insider views’ regarding the JICS. We conclude with incumbents’ views on the effectiveness of the JICS.

    Organised Crime and Law Enforcement in Southern Africa: The Challenges Confronting Research

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    From the early 1990s onwards, research and policies concerning organised crime in the southern African region have grown apace. But the quest for both quantitative and qualitative research is far from being satisfied. The paper uses an ambitious research project (titled Enhancing Regional Responses to Organised Crime, or EROC) as a case study in order to explore the dynamics which inform and shape research on organised crime from the point of project initiation through to project conceptualisation, data-gathering and analysis, the dissemination of findings, and the formulation of policy recommendations for effective law enforcement. The discussion provides an overview of the many challenges which research on organised crime and law enforcement strategies have to contend with in the southern African region. A critical analysis of the macro- and micro-processes which shape the development of research-based policy interventions in relation to organised crime can contribute to our appreciation of the problem of organised crime itself and of the prospects for police cooperation in the region

    NUB1 modulation of tau aggregation

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    The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway

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    Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway

    CRISPR-Cas9 correction of OPA1 c.1334G>A: p.R445H restores mitochondrial homeostasis in dominant optic atrophy patient-derived iPSCs.

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    Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy in the United Kingdom. DOA has an insidious onset in early childhood, typically presenting with bilateral, central visual loss caused by the preferential loss of retinal ganglion cells. 60%-70% of genetically confirmed DOA cases are associated with variants in OPA1, a ubiquitously expressed GTPase that regulates mitochondrial homeostasis through coordination of inner membrane fusion, maintenance of cristae structure, and regulation of bioenergetic output. Whether genetic correction of OPA1 pathogenic variants can alleviate disease-associated phenotypes remains unknown. Here, we demonstrate generation of patient-derived OPA1 c.1334G>A: p.R445H mutant induced pluripotent stem cells (iPSCs), followed by correction of OPA1 through CRISPR-Cas9-guided homology-directed repair (HDR) and evaluate the effect of OPA1 correction on mitochondrial homeostasis. CRISPR-Cas9 gene editing demonstrated an efficient method of OPA1 correction, with successful gene correction in 57% of isolated iPSCs. Correction of OPA1 restored mitochondrial homeostasis, re-establishing the mitochondrial network and basal respiration and ATP production levels. In addition, correction of OPA1 re-established the levels of wild-type (WT) mitochondrial DNA (mtDNA) and reduced susceptibility to apoptotic stimuli. These data demonstrate that nuclear gene correction can restore mitochondrial homeostasis and improve mtDNA integrity in DOA patient-derived cells carrying an OPA1 variant

    Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models

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    The photoreceptor outer segment is a highly specialized primary cilium that is essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A>G in CEP290, there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290-related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids by modulating the expression of rhodopsin and by targeting cilia and synaptic plasticity pathways. This work sheds light on the mechanism of action of eupatilin and supports its potential as a variant-independent approach for CEP290-associated ciliopathies

    Editorials

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    Trauma - today and tomorrowNeutron therapy - clinical considerationsDon Craib's legacyHealth informatic

    Non-IgE-mediated food allergies

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    Non-imunoglobulin E (IgE)-mediated conditions include combined IgE and cell-mediated conditions such as atopic dermatitis and eosinophilic oesophagitis, and pure T-cell-mediated conditions such as food protein-induced enterocolitis syndrome, allergic proctocolitis and enteropathy syndromes. Diagnosing mixed or non-IgE-mediated allergy is challenging. A clear cause-effect relationship between exposure to the suspected food and symptoms is not always possible, as symptoms develop over time and are more chronic in nature. Skin-prick tests and specific IgE to the allergen are usually negative. An elimination diet may be necessary to diagnose non-IgE-mediated type food allergy. The suspected allergen should be excluded from the diet for 2 - 6 weeks under dietetic guidance to assess for improvement of symptoms. After symptom improvement, a rechallenge is necessary to definitively prove causal relation.

    Books

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    Current Ocular Therapy. Ed. by F. T. Fraunfelder, F. Hampton Roy and S. Martha Meyer. Pp. xiii + 792. Illustrated. £55. Nonhmead: WB Saunders. 1989.Dysfunctional Uterine Bleeding and Menorrhagia. Bailliere's Clinical Obstetrics and Gynaecolcgy: International Practice and Research, June 1989. Ed. by J. O. Drife. Pp. 217 + 428. Illustrated. £18,50. Northmead: WE Saunders.1989.Treatment of Cancer. 2nd ed. Ed. by Karol Sikora and Keith E. Halnan. Pp. ix + 916. Illustrated. Price £99,50. London: Chapman and Hall Medical. 1990.Ocular Syndromes and Systemic Diseases. 2nd edition. Ed. by F. Hampton Roy. Pp. xlvii + 470. £40. Northmead: WE Saunders. 1989.Non-invasive Cardiac Imaging. British Medical Bulletin. Vol. 45, No. 4. Ed. by D. G. Gibson. Pp. 830 + 1109. Illustrated. £25 (UK) or £31,50 (overseas). New York: Churchill Livingstone. 1989.Laparoscopic Surgery. Bailliere's Clinical Obstetrics and Gynaecology: International Practice and Research, September 1989. Ed. by C. J. G. Sunon. Pp. 429 + 686. Illustrated. £18,50. Northmead: WB Saunders. 1989.Management ofMinor Head Injuries. Ed. by I. J. Swann and D. W. Yates. Pp. x + 102. Illustrated: £14,95. Hampshire: Chapman & Hall Medical. 1989.ABC of Child Abuse. Ed. by Roy Meadow. Pp. 59. Illustrated. London: BMJ. 1989.The Facts of Life. Ed. by Marina Petropulos. Pp. 1 + 222. Illustrated. R19,95 exc!. GST. Cape Town: Tafelberg. 1990.Physical Examination of the Heart and Circulation. 2nd ed. Ed. by Joseph K. Perloff. Pp. viii + 292. Illustrated. £17,95. Northmead: WB Saunders. 1989.Growth Regulation of Thyroid Gland and Thyroid Tumours: Frontiers ofHormone Research. Vo!. 18. Ed. by P. E. Goretzki, and H. D. Roher. Pp. viii + 163. Illustrated. £68,80. Basel: S. Karger. 1989.Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. 2nd revised ed. Ed. by P. Duus. Pp. x + 337. Illustrated. DM 370. Stungart: Georg Thieme Verlag. 1989
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