The legal response to safeguarding local environmental quality

Local environmental quality is best understood as a measure of the aesthetic complexion of public space in the urban environment. Anti‐social acts causing damage to the physical environment of local communities have, traditionally, attracted little moral opprobrium; and the role of local authorities in safeguarding local environmental quality has been undervalued. However, this is an issue that has been proven to have a significant impact on the quality of life of local communities, particularly those in deprived neighbourhoods. This paper argues, therefore, that we need to develop a comprehensive legal framework to safeguard local environmental quality in the future. This problem has so far been tackled as nuisance, local environmental crime or anti‐social behaviour. The paper concludes that an approach based on measures to tackle incivility in society is to be preferred; thus, the Anti‐social Behaviour, Crime and Policing Act 2014 will be particularly significant in this regard. However, some amendments to this legislation will be required to ensure its effective application to the problems of local environmental quality. Further measures should also be taken to support citizen participation and education as part of a comprehensive legal framework for safeguarding the local environment.</jats:p

Snail family genes disrupt cell death and are required for stem cell maintenance in the Drosophila melanogaster ovary

Cell death is an integral part of oogenesis in the fruit fly, Drosophila melanogaster. When the fly is starved of protein, some pre-vitellogenic egg chambers die apoptotically. As egg chambers mature, excess germline cells die via a non-apoptotic, developmentally programmed death. Overexpression of the transcription factor escargot was found to block both death events in the ovary, which is very unusual. escargot overexpression blocked starvation-dependent death upstream of caspases, but still needed a death signal to produce undead egg chambers. In maturing egg chambers, escargot overexpression blocked death more effectively than disrupting both apoptosis and autophagy, indicating that it must affect non-apoptotic, non-autophagic death mechanisms. RNA-Seq and a genetic modifier screen were used to identify potential escargot targets that inhibit cell death. Studies were also undertaken to characterize the loss-of-function phenotype of escargot in the ovary. escargot is a member of the Snail family of transcription factors that play integral roles in development and gene regulation throughout Bilaterian organisms. In Drosophila melanogaster, the genes snail, escargot, and worniu are critical for stem cells in neuroblasts, gut, and testis, but a role in the ovary had not been shown. To analyze Snail family function in the ovary, I made a triple deficiency that removed the three Snail family members, called ΔSF. Surprisingly, ΔSF homozygous follicle stem cells are rapidly lost. Follicle stem cell loss was rescued by the expression of escargot or worniu but not snail, indicating that there is shared capability between genes. Moreover, follicle stem cells did not linger in the germarium, and their loss was not prevented by blocking apoptosis, indicating that the ΔSF defect is a failure of stem cell maintenance. Together, the results described in this dissertation show that Snail genes are needed for the normal function of the Drosophila ovary, and that escargot can regulate multiple kinds of cell death. Understanding Snail family genes is particularly important for the study of cancer, as they are implicated in mechanisms underlying the cancer stem cell state. Analysis of the highly conserved Snail family genes in Drosophila illuminates their function and dysfunction in human health and disease

Insights into the Mycobacterial Response to Nitrogen Limitation; Characterisation of the GlnR Regulon

The ability to sense and initiate a response to situations of nitrogen-limitation is essential for bacterial survival. In extensively investigated organisms, the nitrogen-stress response consists of changes in intracellular metabolite levels, post-translational modification of proteins (such as metabolic enzymes) and a transcriptomic response mediated by a global response regulator. However, in mycobacteria the nitrogen stress response has not been comprehensively investigated. In this study mycobacterial nitrogen limiting conditions were optimised and the mechanism of GlnR activation investigated; M. smegmatis GlnR requires a highly conserved aspartate residue (D48), corresponding to a putative phosphorylation site, for function. In addition, a ChIP-seq approach combined with global expression analyses, permitted characterisation of the GlnR mediated global transcriptomic response stimulated during nitrogen. In M. smegmatis, 52 GlnR binding sites were identified, controlling the expression of at least 103 genes in response to nitrogen limitation. The majority of GlnR regulated genes were involved in nitrogen uptake and nitrogen scavenging. A consensus GlnR DNA binding motif was identified and AC-n9-AC DNA residues shown to be essential for GlnR:DNA binding. In M. tuberculosis 36 GlnR binding sites were identified in nitrogen limitation, however no consensus GlnR:DNA binding motif could be determined. Initial analysis suggests GlnR may be involved in a general stress response in M. tuberculosis, rather than mediating a nitrogen scavenging response as observed in M. smegmatis. This study provides the first global analysis of nitrogen limitation in mycobacteria and identifies GlnR as the main nitrogen response regulator. From this analysis it appears that the role of GlnR is different in M. tuberculosis compared to M. smegmatis, which may provide key insights into how pathogenic and non-pathogenic species survive nutrient limiting conditions.Open Acces