Jill Craigie and the BBC: Postwar television, feminist histories and modern femininities

Using the BBC Written Archives Centre’s records, this working paper explores a documentary about the suffragettes written by feminist, socialist filmmaker Jill Craigie for the BBC in 1949 – illuminating her previously unconsidered efforts to bring the women’s movement to life in an innovative, modern way on the small screen. Although Craigie later withdrew from this project, this paper explores how archival traces of Craigie’s television work offer new insight into her postwar career as a filmmaker, writer and onscreen personality, and shine new light on her place in a feminist genealogy concerned with the historical fight for women’s rights. </jats:p

Development of NanoLuc-PEST expressing Leishmania mexicana as a new drug discovery tool for axenic- and intramacrophage-based assays

The protozoan parasite Leishmania causes leishmaniasis; a spectrum of diseases of which there are an estimated 1 million new cases each year. Current treatments are toxic, expensive, difficult to administer, and resistance to them is emerging. New therapeutics are urgently needed, however, screening the infective amastigote form of the parasite is challenging. Only certain species can be differentiated into axenic amastigotes, and compound activity against these does not always correlate with efficacy against the parasite in its intracellular niche. Methods used to assess compound efficacy on intracellular amastigotes often rely on microscopy-based assays. These are laborious, require specialist equipment and can only determine parasite burden, not parasite viability. We have addressed this clear need in the anti-leishmanial drug discovery process by producing a transgenic L. Mexicana cell line that expresses the luciferase NanoLuc-PEST. We tested the sensitivity and versatility of this transgenic strain, in comparison with strains expressing NanoLuc and the red-shifted firefly luciferase. We then compared the NanoLuc-PEST luciferase to the current methods in both axenic and intramacrophage amastigotes following treatment with a supralethal dose of Amphotericin B. NanoLuc-PEST was a more dynamic indicator of cell viability due to its high turnover rate and high signal:background ratio. This, coupled with its sensitivity in the intramacrophage assay, led us to validate the NanoLuc-PEST expressing cell line using the MMV Pathogen Box in a two-step process: i) identify hits against axenic amastigotes, ii) screen these hits using our bioluminescence-based intramacrophage assay. The data obtained from this highlights the potential of compounds active against M. tuberculosis to be re-purposed for use against Leishmania. Our transgenic L. Mexicana cell line is therefore a highly sensitive and dynamic system suitable for Leishmania drug discovery in axenic and intramacrophage amastigote models

Evaluation of NanoLuc, RedLuc and Luc2 as bioluminescent reporters in a cutaneous leishmaniasis model

New drugs for the treatment of human leishmaniasis are urgently needed, considering the limitations of current available options. However, pre-clinical evaluation of drug candidates for leishmaniasis is challenging. The use of luciferase-expressing parasites for parasite load detection is a potentially powerful tool to accelerate the drug discovery process. We have previously described the use of Leishmania amazonensis mutants expressing firefly luciferase (Luc2) for drug testing. Here, we describe three new mutant L. amazonensis lines that express different variants of luciferases: NanoLuc, NanoLuc-PEST and RedLuc. These mutants were evaluated in drug screening protocols. NanoLuc-parasites, in spite of high bioluminescence intensity in vitro, were shown to be inadequate in discriminating between live and dead parasites. Bioluminescence detection from intracellular amastigotes expressing NanoLuc-PEST, RedLuc or Luc2 proved more reliable than microscopy to determine parasite killing. Increased sensitivity was observed in vivo with RedLuc-expressing parasites as compared to NanoLuc-expressing L. amazonensis. Our data indicates that NanoLuc is not suitable for in vivo parasite burden determination. Additionally, RedLuc and the conventional luciferase Luc2 demonstrated equivalent sensitivity in an in vivo model of cutaneous leishmaniasis

The <i>N</i>-myristoylome of <i>Trypanosoma cruzi</i>

Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas’ disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage. Using a combination of label-free and stable isotope labelling of cells in culture (SILAC) based proteomic strategies in the presence and absence of the NMT inhibitor DDD85646, we identified 56 proteins enriched in at least two out of the three experimental approaches. Of these, 6 were likely to be false positives, with the remaining 50 commencing with amino acids MG at the N-terminus in one or more of the T. cruzi genomes. Most of these are proteins of unknown function (32), with the remainder (18) implicated in a diverse range of critical cellular and metabolic functions such as intracellular transport, cell signalling and protein turnover. In summary, we have established that 0.43–0.46% of the proteome is N-myristoylated in T. cruzi approaching that of other eukaryotic organisms (0.5–1.7%)

Concepts of patients with alopecia areata about their disease

BACKGROUND: Alopecia areata (AA) is a common and chronic skin disease with an unknown etiology. It may significantly affect the patient quality of life. This study was designed to evaluate the illness perception in patients with AA. METHODS: A questionnaire consisting of 25 questions about causes, timeline, consequences and control of disease were given to 80 patients with AA attending a skin clinic in Tehran, Iran. The impact of age, gender, duration of disease, education, extent of disease and family history of AA were also assessed. RESULTS: Eighty patients (38 male and 42 female) with a mean age of 27.5 years (SD = 9.3) and disease duration of 7.8 years (SD = 7.7) completed the questionnaire. 76.9% of the patients believed that the role of stress was the cause of disease. 17.1 % believed genetic background to be the main cause, this found to be more frequent in patients with positive family history of AA. More than half of patients believed that their illness had major consequences on their lives and 40% of patients believed that their illness would be likely to be permanent rather than temporary, more in patients with longer duration of disease. Only 57.5% of patients considered their treatments to be effective. CONCLUSION: AA may considerably affect various aspects of patients' lives. The patient knowledge about the causes and course of this disease is limited

First Detection of Leishmania infantum in Domestic Dogs from Burkina Faso (West Africa)

Background and Objective: Human Visceral Leishmaniasis (HVL) is a systemic neglected tropical diseases and potentially lethal disease caused by infection with protozoan parasites of the Leishmania genus. In the causal, agent of HVL is L. infantum and dogs are a major reservoir host. Visceral leishmaniasis is rarely found in West Africa and no cases have been reported to date in Burkina Faso. The purpose of the current study was to investigate the presence of L. infantum in population of domestic dogs in Bobo-Dioulasso city in Burkina Faso. Materials and Methods: The study was carried out in five districts of the city Bobo-Dioulasso, Burkina Faso. An active survey was conducted in households with dogs in five districts of the city for canine leishmaniasis screening. Epidemiological data and clinical signs were collected for each dog. Venous blood collection and skin lesions biopsies were performed in dogs after informed consent of the owners. The plasma was used for the immunological diagnosis (DiaMed-IT LEISH) and positive samples were confirmed by nested PCR. Results: A total of 85 dogs were included in the study. For the first time, the occurrence of L. infantum in Burkina Faso was confirmed in five domestic dogs presenting symptomatic signs by immunochromatographic tests. Biopsy samples were positive for L. infantum in PCR analysis. Conclusion: The findings indicated that L. infantum is circulating within canine populations in Bobo-Dioulasso. Infected dogs would be the reservoir hosts of this visceralising species. Several priorities for public and veterinary health research have been highlighted by this study

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124

A survey of prolapse practice in UK women’s health physiotherapists: what has changed in the last decade?

INTRODUCTION AND HYPOTHESIS: Prolapse is a common female problem, and conservative treatments such as pelvic floor muscle training (PFMT) are important options for women. Evidence supporting the effectiveness of PFMT for prolapse has grown over the last decade, and it was hypothesised that practice and practice guidelines would have developed in line with the evidence. To assess this, up-to-date information about the practice of physiotherapists working in women’s health regarding their treatment of prolapse was required. METHODS: An online survey sent to members of the Association of Chartered Physiotherapists in Women’s Health and the Chartered Physiotherapists Promoting Continence. Results were compared with those of an earlier survey undertaken in 2002. RESULTS: A 49 % response rate was achieved. The majority of respondents were senior physiotherapists (55 %) and had worked in women’s health for more than 10 years. Respondents were treating significantly more women with prolapse than a decade before: 36 % vs 14 % treated more than 50 women per year in 2002 and 2013 respectively (p < 0.001). Individualised PFMT (93 %), lifestyle advice (92 %) and biofeedback-assisted PFMT (83 %) were the most common treatment elements, with four being the average number of appointments. Forty-eight percent had changed their practice as a result of recent research; however, scepticism amongst medics, the referral of women directly for surgery, and constraints on resources were thought to be barriers to wider implementation of the evidence of PFMT for prolapse. CONCLUSIONS: There has been uptake of evidence-based prolapse practice by UK specialist physiotherapists in the last decade. Further research targeting the implementation of this evidence would be valuable in addressing potential barriers, and in supporting the need for physiotherapy in the treatment of prolapse