Towards a more ecological urbanism: the Sheffield Abundance fruit harvesting project as critical urban learning assemblage

The overarching context of this research is the problem of sustainability in, or of, existing urban areas. Urban populations are expected to rise in the UK, without a corresponding rate of change to the physical form of cities. This research looks to the expertise of inhabitants in existing urban areas for understandings and practices that could address sustainability and that may complement or obviate physical urban design interventions. It seeks to explore the relationship between locality, local knowledge and broader themes of sustainability. The Abundance urban fruit harvesting project in Sheffield is taken as an example of collective local action by inhabitants in an existing urban area to address themes relevant to sustainability. Abundance participants find, harvest, distribute, map, and celebrate surplus produce, such as fruit, nuts and herbs in the city. Blurring boundaries of what is considered urban, rural, nature, or private, and bringing humans into closer connection with the ecological life of the city, could be said to increase ecological sensitivity. In terms of methodology, this study takes an inductive approach, informed by grounded theory. An ethnography of the Abundance fruit harvesting project in Sheffield is conducted over a full year. The thesis includes thick description that relates the practices involved, the spaces used, and the changed relations produced. This forms the basis for considering how sustainability is understood in the context of ‘bottom up’ community projects and practices in urban areas, and what implications this raises for ‘mainstream’ approaches to sustainable development in urban planning and design. As a learning assemblage, Abundance critiques aspects of conventional urbanism and draws together more ecological alternatives. The results constitute an original contribution to knowledge in that this is one of the first such studies of a project of this kind, and as it draws on interdisciplinary literature encompassing participatory urban design, sociology, anthropology and geography. In particular the key findings are: 1. grassroots collectives can practice a form of urban design that is vernacular and experiential; 2. this type of urban design can play a role that is tactical and critical in processes of urban development and change; 3. participants adopted an eco-centric understanding of sustainability (an assemblage or meshwork of ecological relations) which is rooted in entanglements with living and non-living others; 4. social learning is a way of inhabiting the city, and in this context makes a novel contribution to practice theory; 5. socially engaged arts practice and collective action by urban inhabitants offer routes to activating change in existing urban areas and; 6. the use of ethnographic methods can enhance urban design research

“Transfer Talk” in Talk about Writing in Progress: Two Propositions about Transfer of Learning

This article tracks the emergence of the concept of “transfer talk”—a concept distinct from transfer of learning—and teases out the implications of transfer talk for theories of transfer of learning. The concept of transfer talk was developed through a systematic examination of 30 writing center transcripts and is defined as “the talk through which individuals make visible their prior learning (in this case, about writing) or try to access the prior learning of someone else.” In addition to including a taxonomy of transfer talk and analysis of which types occur most often in this set of conferences, this article advances two propositions about the nature of transfer of learning: (1) transfer of learning may have an important social, even collaborative, component and (2) although meta-awareness about writing has long been recognized as valuable for transfer of learning, more automatized knowledge may play an important role as well

BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer

In sporadic epithelial ovarian cancer (EOC), the inactivation of BRCA1 through various mechanisms is a relatively common event. BRCA1 protein dysfunction results in the breakdown of various critical pathways in the cell, notably, the DNA damage response and repair pathway. Tumors from patients with BRCA1 germline mutations have an increased sensitivity to DNA damaging chemotherapeutic agents, such as cisplatin, due to defective DNA repair. Thus, inhibiting BRCA1 in sporadic EOC using novel targeted therapies is an attractive strategy for the treatment of advanced or recurrent EOC. Several classes of small molecule inhibitors that affect BRCA1 have now been tested in preclinical and clinical studies suggesting that this is a rational therapeutic approach. The aim of this paper is to provide an understanding of how BRCA1 has evolved into a promising target for the treatment of sporadic disease and to outline the main potential small molecule inhibitors of BRCA1 in EOC

Preclinical detection of PrP\u3csup\u3eSc\u3c/sup\u3e in nictitating membrane lymphoid tissue of sheep

SHEEP scrapie is the prototype of a heterogeneous group of transmissible spongiform encephalopathies (TSES) which occur in humans, cattle, cats, mink and cervids. TSEs are characterised by the deposition of prion proteins (Prp-Scrapie or PrpSc) in the central nervous system of affected individuals (Prusiner 1982). PrPSc and infectivity have also been detected in the lymphoreticular system of sheep well before symptoms occur (Hadlow and others 1982, Race and others 1992). Detection of PrpSc in lymphoid tissue, such as tonsils or peripheral lymph nodes, has been proposed as a preclinical diagnostic test for scrapie (Ikegami and others 1991, Schreuder and others 1996). This short communication reports the use of a non-invasive diagnostic assay based on biopsy of lymphoid nodules in the nictitating membrane of sheep. The nictitating membrane or third eyelid (palpebra tertia) of ruminant animals consists of a cartilaginous sheet with superficial lymphoid follicles and a seromucinous secretory gland beneath the conjunctiva of the bulbar surface (Slatter and Mills 1981). The lymphoid nodules are easily biopsied under local anaesthesia. Sheep were pretreated by topical administration of proparacaine hydrochloride (Ophthetic; Allergan) and the nictitating membrane was everted with disposable 1 x 2-toothed, 5½-inch forceps (Sklar 78055-1). Typically two clusters of lymphoid tissue were visualised above the more pale glandular tissue. A biopsy of one cluster of lymphoid tissue was collected using disposable Metzenbaum scissors (Sklar 30455) and a second set of forceps. Biopsied tissue was fixed in formalin and paraffin embedded using conventional methods. Sections typically contained four to seven lymphoid follicles

CD21-Positive Follicular Dendritic Cells A Possible Source of PrP\u3csup\u3eSc\u3c/sup\u3e in Lymph Node Macrophages of Scrapie-Infected Sheep

Natural sheep scrapie is a prion disease characterized by the accumulation of PrPSc in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrPSc. In this study, lymph nodes were analyzed for the presence of PrPSc and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus- specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus-specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrPSc by phagocytosis of CD21+ FDC processes. The results also suggest that follicular macrophages have proteases that process full-length PrPSc to N-terminally truncated PrPSc

CD21-Positive Follicular Dendritic Cells A Possible Source of PrP\u3csup\u3eSc\u3c/sup\u3e in Lymph Node Macrophages of Scrapie-Infected Sheep

Natural sheep scrapie is a prion disease characterized by the accumulation of PrPSc in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrPSc. In this study, lymph nodes were analyzed for the presence of PrPSc and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus- specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus-specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrPSc by phagocytosis of CD21+ FDC processes. The results also suggest that follicular macrophages have proteases that process full-length PrPSc to N-terminally truncated PrPSc

The effect of the histone deacetylase inhibitor M344 on BRCA1 expression in breast and ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>The inhibition of Breast Cancer 1 (BRCA1) expression sensitizes breast and ovarian cancer cells to platinum chemotherapy. However, therapeutically relevant agents that target BRCA1 expression have not been identified. Our recent report suggested the potential of the histone deacetylase (HDAC) inhibitor, M344, to inhibit BRCA1 expression. In this study, we further evaluated the effect of M344 on BRCA1 mRNA and protein expression, as well as its effect on cisplatin-induced cytotoxicity in various breast (MCF7, T-47D and HCC1937) and ovarian (A2780s, A2780cp and OVCAR-4) cancer cell lines.</p> <p>Results</p> <p>With the addition of M344, the platinum-sensitive breast and ovarian cancer cell lines that displayed relatively high BRCA1 protein levels demonstrated significant potentiation of cisplatin cytotoxicity in association with a reduction of BRCA1 protein. The cisplatin-resistant cell lines, T-47D and A2780s, elicited increased cytotoxicity of cisplatin with M344 and down regulation of BRCA1 protein levels. A2780s cells subjected to combination platinum and M344 treatment, demonstrated increased DNA damage as assessed by the presence of phosphorylated H2A.X foci in comparison to either treatment alone. Using Chromatin Immunoprecipitation, A2780s and MCF7 cells exposed to M344 alone and in combination with cisplatin, did not demonstrate enhanced acetylated Histone 4 at the <it>BRCA1 </it>promoter, suggesting an indirect effect on this promoter.</p> <p>Conclusions</p> <p>The enhanced sensitivity of HDAC inhibition to platinum may be mediated through a BRCA1-dependent mechanism in breast and ovarian cancer cells. The findings of this study may be important in the future design of clinical trials involving HDAC inhibitors using BRCA1 as a tumour biomarker.</p

PrP-C and PrP-Sc at the Fetal-Maternal Interface

Scrapie is a naturally occurring prion (PrP) disease causing a fatal neurodegenerative disorder in sheep and goats. Previous studies suggest that scrapie is transmitted naturally through exposure to the scrapie agent in wasted placentas of infected ewes. This study determined the distribution and biochemical properties of PrP cellular (PrP-C) and the distribution of PrP scrapie (PrP-Sc) in reproductive, placental, and selected fetal tissues and fetal fluids in sheep. Glycosylated, N-terminally truncated, proteinase K-sensitive PrP-C with apparent molecular masses of 23–37 kDa was present in reproductive, placental, and fetal tissues and fetal fluids. PrP-C was low or undetectable in intercotyledonary chorioallantois, amnion, urachus, amniotic fluid, and fetal urine. In pregnant ewes, cotyledonary chorioallantois, allantoic fluid, and caruncular endometrium contained higher levels of PrP-C than did intercaruncular endometrium, myometrium, oviduct, ovary, fetal bladder, or fetal kidney. Caruncular endometrial PrP-C was up-regulated during pregnancy. Despite the wide distribution of PrP-C in reproductive, placental, and selected fetal tissues and fetal fluid, PrP-Sc was detected only in caruncular endometrium and cotyledonary chorioallantois of pregnant scrapie-infected ewes. The embryo/fetus may not be exposed to scrapie in utero because it is separated physically from PrP-positive allantois and chorioallantois by PrP-negative amnion

Enlarged Dural Sac in Idiopathic Bronchiectasis Implicates Heritable Connective Tissue Gene Variants

Rationale: Patients with idiopathic bronchiectasis are predominantly female and have an asthenic body morphotype and frequent nontuberculous mycobacterial respiratory infections. They also demonstrate phenotypic features (scoliosis, pectus deformity, mitral valve prolapse) that are commonly seen in individuals with heritable connective tissue disorders