Towards sustainable urban development: the social acceptability of high-rise buildings in a Ghanaian city

Over the years, many city managers, policy makers and academics alike have turned to high-rise buildings as pathway to sustainable urban development. However, the sustainability of such types of development in various geographical contexts, especially in sub-Saharan Africa, is a subject less explored. Amidst the promotion of high-rise development in a rapidly urbanizing metropolis in Ghana, Kumasi, the research empirically examined the social acceptability of high-rise residential facilities and the institutional capacity for their effective management. By conducting face-to-face interviews with sampled households, and critical public service providers in the metropolis, the study uncovered that, contrary to the evidence from many Asian cities, there is generally low social acceptability of high-rise developments, and a weak institutional capacity for effective service delivery. The research concludes that, whilst it is tempting to embrace high-rise buildings as sustainable development pathway, it is crucial they are pursued with much circumspection. In addition to their design being tailored to the local needs of the people for whom they are built, the promotion of high-rise development should recognize the importance of effective service delivery, and general social acceptability

Towards sustainable urban development: the social acceptability of high-rise buildings in a Ghanaian city

Over the years, many city managers, policy makers and academics alike have turned to high-rise buildings as pathway to sustainable urban development. However, the sustainability of such types of development in various geographical contexts, especially in sub-Saharan Africa, is a subject less explored. Amidst the promotion of high-rise development in a rapidly urbanizing metropolis in Ghana, Kumasi, the research empirically examined the social acceptability of high-rise residential facilities and the institutional capacity for their effective management. By conducting face-to-face interviews with sampled households, and critical public service providers in the metropolis, the study uncovered that, contrary to the evidence from many Asian cities, there is generally low social acceptability of high-rise developments, and a weak institutional capacity for effective service delivery. The research concludes that, whilst it is tempting to embrace high-rise buildings as sustainable development pathway, it is crucial they are pursued with much circumspection. In addition to their design being tailored to the local needs of the people for whom they are built, the promotion of high-rise development should recognize the importance of effective service delivery, and general social acceptability

HIF-1 Regulates Iron Homeostasis in Caenorhabditis elegans by Activation and Inhibition of Genes Involved in Iron Uptake and Storage

Caenorhabditis elegans ftn-1 and ftn-2, which encode the iron-storage protein ferritin, are transcriptionally inhibited during iron deficiency in intestine. Intestinal specific transcription is dependent on binding of ELT-2 to GATA binding sites in an iron-dependent enhancer (IDE) located in ftn-1 and ftn-2 promoters, but the mechanism for iron regulation is unknown. Here, we identify HIF-1 (hypoxia-inducible factor -1) as a negative regulator of ferritin transcription. HIF-1 binds to hypoxia-response elements (HREs) in the IDE in vitro and in vivo. Depletion of hif-1 by RNA interference blocks transcriptional inhibition of ftn-1 and ftn-2 reporters, and ftn-1 and ftn-2 mRNAs are not regulated in a hif-1 null strain during iron deficiency. An IDE is also present in smf-3 encoding a protein homologous to mammalian divalent metal transporter-1. Unlike the ftn-1 IDE, the smf-3 IDE is required for HIF-1–dependent transcriptional activation of smf-3 during iron deficiency. We show that hif-1 null worms grown under iron limiting conditions are developmentally delayed and that depletion of FTN-1 and FTN-2 rescues this phenotype. These data show that HIF-1 regulates intestinal iron homeostasis during iron deficiency by activating and inhibiting genes involved in iron uptake and storage

Towards sustainable urban development: the social acceptability of high-rise buildings in a Ghanaian city

Over the years, many city managers, policy makers and academics alike have turned to high-rise buildings as pathway to sustainable urban development. However, the sustainability of such types of development in various geographical contexts, especially in sub-Saharan Africa, is a subject less explored. Amidst the promotion of high-rise development in a rapidly urbanizing metropolis in Ghana, Kumasi, the research empirically examined the social acceptability of high-rise residential facilities and the institutional capacity for their effective management. By conducting face-to-face interviews with sampled households, and critical public service providers in the metropolis, the study uncovered that, contrary to the evidence from many Asian cities, there is generally low social acceptability of high-rise developments, and a weak institutional capacity for effective service delivery. The research concludes that, whilst it is tempting to embrace high-rise buildings as sustainable development pathway, it is crucial they are pursued with much circumspection. In addition to their design being tailored to the local needs of the people for whom they are built, the promotion of high-rise development should recognize the importance of effective service delivery, and general social acceptability

HBO1 is required for the maintenance of leukaemia stem cells

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)1. Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings