350 research outputs found

    Facile crystallization of Escherichia coli ketol-acid reductoisomerase

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    Ketol-acid reductoisomerase (EC 1.1.1.86) catalyses the second reaction in the biosynthesis of branched-chain amino acids. The reaction involves an Mg2+-dependent alkyl migration followed by an NADPH-dependent reduction of the 2-keto group. Here, the crystallization of the Escherichia coli enzyme is reported. A form with a C-terminal hexahistidine tag could be crystallized under 18 different conditions in the absence of NADPH or Mg2+ and a further six crystallization conditions were identified with one or both ligands. With the hexahistidine tag on the N-terminus, 20 crystallization conditions were found, some of which required the presence of NADPH, NADP(+), Mg2+ or a combination of ligands. Finally, the selenomethionine-substituted enzyme with the N-terminal tag crystallized under 15 conditions. Thus, the enzyme is remarkably easy to crystallize. Most of the crystals diffract poorly but several data sets were collected at better than 3.2 Angstrom resolution; attempts to phase them are currently in progress

    Are the natural sciences ready for truth, healing, and reconciliation with Indigenous peoples in Canada? Exploring ‘settler readiness’ at a world-class freshwater research station

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    This is the final version. Available on open access from Springer via the DOI in this recordThe Experimental Lakes Area in Northwestern Ontario, Canada, is a globally prominent freshwater research facility, conducting impactful whole-of-lake experiments on so-called ‘pristine’ lakes and watersheds. These lakes are located in traditional Anishinaabe (Indigenous) territory and the home of 28 Treaty #3 Nations, something rarely acknowledged until now. Indeed, Indigenous peoples in the area have historically been excluded from the research facility’s governance and research. Shortly after it changed hands in 2014—from the federal government to the not-for-profit International Institute of Sustainable Development (IISD)—the Truth and Reconciliation Commission (TRC) of Canada released its Calls to Action to all Canadians. The newly named International Institute of Sustainable Development-Experimental Lakes Area (IISD-ELA) began to respond with a number of initiatives aimed to develop relationships with local Indigenous peoples and communities. In this paper, from the perspectives of IISD-ELA staff members, we share findings from an exploratory study into the relationships beginning to develop between IISD-ELA and Treaty #3 Nations. We used semi-structured interviews (n = 10) to identify how staff perceived their initial efforts and contextualize those with the current literature on meaningfully engagement in reconciliation. Our analysis highlights perceived barriers, including time, resources, and funding constraints, as well as an acknowledged lack of cultural awareness and sensitivity training. Participants also recognized the need to engage Indigenous knowledge holders and embrace their ways of knowing at the research station. While the study is small in scale, as an international leader in freshwater science, transparency in the IISD-ELA’s journey in reconciliation has the potential to inform, influence, and ‘unsettle’ settler-colonial scientists, field stations, and institutions across the country and beyond.Canada Research Chairs Progra

    Tropospheric Carbon Monoxide Measurements from the Scanning High-Resolution Interferometer Sounder on 7 September 2000 in Southern Africa During SAFARI 2000

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    [1] Retrieved tropospheric carbon monoxide (CO) column densities are presented for more than 9000 spectra obtained by the University of Wisconsin-Madison (UWis) Scanning High-Resolution Interferometer Sounder (SHIS) during a flight on the NASA ER-2 on 7 September 2000 as part of the Southern African Regional Science Initiative (SAFARI 2000) dry season field campaign. Enhancements in tropospheric column CO were detected in the vicinity of a controlled biomass burn in the Timbavati Game Reserve in northeastern South Africa and over the edge of the river of smoke in south central Mozambique. Relatively clean air was observed over the far southern coast of Mozambique. Quantitative comparisons are presented with in situ measurements from five different instruments flying on two other aircraft: the University of Washington Convair-580 (CV) and the South African Aerocommander JRB in the vicinity of the Timbavati fire. Measured tropospheric CO columns (extrapolated from 337 to 100 mb) of 2.1 × 1018 cm−2 in background air and up to 1.5 × 1019 cm−2 in the smoke plume agree well with SHIS retrieved tropospheric CO columns of (2.3 ± 0.25) × 1018 cm−2 over background air near the fire and (1.5 ± 0.35) × 1019 cm−2 over the smoke plume. Qualitative comparisons are presented with three other in situ CO profiles obtained by the South African JRA aircraft over Mozambique and northern South Africa showing the influence of the river of smoke

    Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

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    We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

    Evaluation of a 'virtual' approach to commissioning health research

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    BACKGROUND: The objective of this study was to evaluate the implementation of a 'virtual' (computer-mediated) approach to health research commissioning. This had been introduced experimentally in a DOH programme – the 'Health of Londoners Programme' – in order to assess whether is could enhance the accessibility, transparency and effectiveness of commissioning health research. The study described here was commissioned to evaluate this novel approach, addressing these key questions. METHODS: A naturalistic-experimental approach was combined with principles of action research. The different commissioning groups within the programme were randomly allocated to either the traditional face-to-face mode or the novel 'virtual' mode. Mainly qualitative data were gathered including observation of all (virtual and face-to-face) commissioning meetings; semi-structured interviews with a purposive sample of participants (n = 32/66); structured questionnaires and interviews with lead researchers of early commissioned projects. All members of the commissioning groups were invited to participate in collaborative enquiry groups which participated actively in the analysis process. RESULTS: The virtual process functioned as intended, reaching timely and relatively transparent decisions that participants had confidence in. Despite the potential for greater access using a virtual approach, few differences were found in practice. Key advantages included physical access, a more flexible and extended time period for discussion, reflection and information gathering and a more transparent decision-making process. Key challenges were the reduction of social cues available in a computer-mediated medium that require novel ways of ensuring appropriate dialogue, feedback and interaction. However, in both modes, the process was influenced by a range of factors and was not technology driven. CONCLUSION: There is potential for using computer-mediated communication within the research commissioning process. This may enhance access, effectiveness and transparency of decision-making but further development is needed for this to be fully realised, including attention to process as well as the computer-mediated medium

    Using liminality to understand mothers’ experiences of long-term breastfeeding: ‘Betwixt and between’, and ‘matter out of place’

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    © 2015, © The Author(s) 2015. Breastmilk is widely considered as the optimum nutrition source for babies and an important factor in both improving public health and reducing health inequalities. Current international/national policy supports long-term breastfeeding. UK breastfeeding initiation rates are high but rapidly decline, and the numbers breastfeeding in the second year and beyond are unknown. This study used the concept of liminality to explore the experiences of a group of women breastfeeding long-term in the United Kingdom, building on Mahon-Daly and Andrews. Over 80 breastfeeding women were included within the study, which used micro-ethnographic methods (participant observation in breastfeeding support groups, face-to-face interviews and online asynchronous interviews via email). Findings about women’s experiences are congruent with the existing literature, although it is mostly dated and from outside the United Kingdom. Liminality was found to be useful in providing insight into women’s experiences of long-term breastfeeding in relation to both time and place. Understanding women’s experience of breastfeeding beyond current usual norms can be used to inform work with breastfeeding mothers and to encourage more women to breastfeed for longer

    Moxibustion for cephalic version: a feasibility randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) has been used to correct a breech presentation. Evidence of effectiveness and safety from systematic reviews is encouraging although significant heterogeneity has been found among trials. We assessed the feasibility of conducting a randomised controlled trial of moxibustion plus usual care compared with usual care to promote cephalic version in women with a breech presentation, and examined the views of women and health care providers towards implementing a trial within an Australian context.</p> <p>Methods</p> <p>The study was undertaken at a public hospital in Newcastle, New South Wales, Australia. Women at 34-36.5 weeks of gestation with a singleton breech presentation (confirmed by ultrasound), were randomised to moxibustion plus usual care or usual care alone. The intervention was administered over 10 days. Clinical outcomes included cephalic presentation at birth, the need for ECV, mode of birth; perinatal morbidity and mortality, and maternal complications. Feasibility outcomes included: recruitment rate, acceptability, compliance and a sample size for a future study. Interviews were conducted with 19 midwives and obstetricians to examine the acceptability of moxibustion, and views on the trial.</p> <p>Results</p> <p>Twenty women were randomised to the trial. Fifty one percent of women approached accepted randomisation to the trial. A trend towards an increase in cephalic version at delivery (RR 5.0; 95% CI 0.7-35.5) was found for women receiving moxibustion compared with usual care. There was also a trend towards greater success with version following ECV. Two babies were admitted to the neonatal unit from the moxibustion group. Compliance with the moxibustion protocol was acceptable with no reported side effects. Clinicians expressed the need for research to establish the safety and efficacy of moxibustion, and support for the intervention was given to increase women's choices, and explore opportunities to normalise birth. The sample size for a future trial is estimated to be 381 women.</p> <p>Conclusion</p> <p>Our findings should be interpreted with caution as the study was underpowered to detect statistical differences between groups. Acceptance by women and health professionals towards moxibustion suggest further research is warranted.</p> <p>Trial Registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000985280.aspx">ACTRN12609000985280</a></p
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