Kidney transplantation in low- and middle-income countries: the Transplant Links experience.

Paediatric kidney failure is a global problem responsible for significant childhood morbidity and mortality. The gold-standard treatment is kidney transplantation. However, the availability of kidney transplantation remains limited in some low- and middle-income countries (LMICs). Transplant Links Community (TLC) is a UK-based charity that mentors units in LMICs wishing to start kidney transplantation; the ultimate goal is for these units to become self-sufficient. TLC provides this support through in-person training visits and skill transfer, plus direct mentorship from the UK that is maintained over many years. From such mentoring programmes, it is evident that there are numerous challenges in the initial establishment and long-term maintenance of kidney transplant services, with specific and unique barriers applying to setting up paediatric transplant programmes compared to their adult counterparts. This review summarises TLC's first-hand experience of developing paediatric kidney transplantation services in LMICs over the past 15 years, the challenges encountered, and the major ongoing barriers that must be addressed to facilitate further progress in delivering transplantation services to children globally.

IgA Nephropathy: Emerging Mechanisms of Disease.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis reported across the world and is characterized by immunoglobulin A (IgA) dominant mesangial deposits, which are poorly O-glycosylated. This deposition leads to a cascade of glomerular and tubulointerstitial inflammation and fibrosis, which can progress to chronic kidney disease. The variability in rate of progression reflects the many genetic and environmental factors that drive IgAN. Here, we summarize the contemporary understanding of the disease mechanisms that drive IgAN and provide an overview of new and emerging therapies, which target these mechanisms.

Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA.

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via 'Proteomics of Isolated Chromatin fragments', applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.