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"Macmillan, Alex"
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Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS
by
Battle, Andrew R
,
Sokabe, Masahiro
,
Deplazes, Evelyne
in
Bacteria
,
Biological Sciences
,
Cell membranes
2012
Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study, we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechanosensitivity simultaneously using the patch-clamp technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.
Journal Article
Updating greenhouse gas emission estimates in the New Zealand-specific dietary life cycle-assessment (LCA) database
2026
Background. Estimating environmental impacts has become an integral part of dietary assessments. These estimations rely on available life cycle assessment (LCA) data and databases of LCA information, which should be as recent and context specific as possible. Objectives. We aimed to update the existing New Zealand (NZ) dietary LCA database with recently available NZ data and provide documentation to streamline regular future updates. Following the update, we also aimed to investigate the impact of the updated database on emission estimates for dietary intakes in the population. Methods. A search was developed and conducted on November 18th, 2024. Recently published or identified LCA data for food items produced in NZ were integrated into the database. A comparison of the estimates of total greenhouse gas emissions due to dietary intake between the original database and updated database was conducted on existing NZ dietary intake data. Results and discussion. Updates in nine food items resulted in small net emissions decreases in fourteen food categories of the New Zealand Adult Nutrition Survey 2008/09. The estimate of average daily emissions due to dietary intake per adult in NZ decreased by approximately 1%, from 4.99 kgCO2eq to 4.91 kgCO2eq. This resulted in a decreased estimate of 350 tCO2eq per day for the entire population. Small changes in LCA data can accumulate to substantial effects over the entire population; however, a 1% decrease in production emissions over 15 years shows that efficiencies in status quo patterns of food production alone are vastly inadequate to meet Paris obligations. More transformative changes will rapidly be needed.
Journal Article
Overcoming resistance and rebalancing power: shifting gears for cross sectoral collaboration on transport and climate change
2023
We should be moving towards transport systems that allow us to travel easily and cheaply around towns and cities by walking, cycling, and public transport, using cars only when necessary
Journal Article
Evidence on the longitudinal construct validity of major generic and utility measures of health-related quality of life in teens with depression
by
Clarke, Gregory N.
,
MacMillan, Alex L.
,
Lynch, Frances L.
in
Adolescent
,
Depression - diagnosis
,
Depression - psychology
2018
Purpose To examine the longitudinal construct validity in the assessment of changes in depressive symptoms of widely used utility and generic HRQL instruments in teens. Methods 392 teens enrolled in the study and completed HRQL and diagnostic measures as part of the baseline interview. HRQL measures included EuroQol (EQ-5D-3L), Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3), Quality of WeilBeing Scale (QWB), Pediatrie Quality of Life Inventory (PEDS-QL), RAND-36 (SF-6D), and Quality of Life in Depression Scale (QLDS). Youth completed follow-up interviews 12 weeks after baseline. Sixteen youth (4.1%) were lost to follow-up. We examined correlations between changes in HRQL instruments and the Children's Depression Rating Scale-Revised (CDRS-R) and assessed clinically meaningful change in multi-attribute utility HRQL measures using mean change (MC) and standardized response mean (SRM) among youth showing at least moderate (20%) improvement in depression symptomology. Results Spearman's correlation coefficients demonstrated moderate correlation between changes in CDRS-R and the HUI2 (r=0.38), HUB (r=0.42), EQ-5D-3L (r=0.36), SF-6D (r=0.39), and PEDS-QL (r=0.39) and strong correlation between changes in CDRS-R and QWB (r=0.52) and QLDS (r=-0.71). Effect size results are also reported. Among multi-attribute utility measures, all showed clinically meaningful improvements in the sample of youth with depression improvement (HUI2, MC=0.20, SRM=0.97; HUI3, MC=0.32, SRM=1.17; EQ-5D-3L, MC=0.08, SRM=0.51; QWB, MC=0.11, SRM=0.86; and SF-6D, MC=0.12, SRM=1.02). Conclusions Findings support the longitudinal construct validity of included HRQL instruments for the assessment of change in depression outcomes in teens. Results of this study can help inform researchers about viable instruments to include in economic evaluations for this population.
Journal Article
Measuring Health-related Quality of Life in Teens With and Without Depression
by
Clarke, Gregory N.
,
Lynch, Frances L.
,
MacMillan, Alex L.
in
Adolescent
,
Adolescents
,
Depression - diagnosis
2016
PURPOSE:To provide empirical evidence on the performance of common measures in assessing health-related quality of life (HRQL) in depressed and nondepressed youth. These measures can be used in research trials, cost-effectiveness studies, and to help develop policy for treating youth depression.
BACKGROUND:Depression is one of the most common mental disorders among adolescents, with a chronic, episodic course marked by considerable impairment. Data on HRQL for teens with depression could more fully demonstrate the burden of depression and help to evaluate the comparative effectiveness of teen depression services, which in turn can be used to inform public and clinical policies.
METHODS:We collected data on depression and HRQL from 392 depressed and nondepressed teens aged 13–17.
RESULTS:Generic mental health, disease-specific, and generic preference-based measures of HRQL all do a reasonable job of distinguishing teens with and without depression and between teens with differing levels of depression. Generic mental health and disease-specific measures provide valuable information on burden of disease and perform well. For the purpose of economic evaluation, the HUI-3 and EQ-5D perform somewhat better than other preference-based measures. These results can aid future research on teens with depression by helping to guide which HRQL instruments are most useful in this population and can help to quantify the burden of depression in teens for policy and clinical planning.
Journal Article
The Climate Change Act will now shape the nation’s health : an assessment of the first policy recommendations to reach our zero carbon target
2021
Assesses, from the perspective of the medical profession, the response of the Climate Change Commission under its mandate pursuant to the Climate Change Response (Zero Carbon) Amendment Act 2019 to develop emissions budgets so that New Zealand reaches zero carbon emissions before 2050 and significantly reduces other greenhouse gas emissions. Sets out evidence-based actions, in order of priority, recommended to multi-solve for climate change, health and health equity in the transport sector. Argues the need to ensure that policies being designed are an opportunity for wellbeing rather than locking in further health harm. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Journal Article
Heterologously-expressed and Liposome-reconstituted Human Transient Receptor Potential Melastatin 4 Channel (TRPM4) is a Functional Tetramer
2016
Mutation, irregular expression and sustained activation of the Transient Receptor Potential Channel, type Melastatin 4 (TRPM4), have been linked to various cardiovascular diseases. However, much remains unknown about the structure of this important ion channel. Here, we have purified a heterologously expressed TRPM4-eGFP fusion protein and investigated the oligomeric state of TRPM4-eGFP in detergent micelles using crosslinking, native gel electrophoresis, multi-angle laser light scattering and electron microscopy. Our data indicate that TRPM4 is tetrameric, like other TRP channels studied to date. Furthermore, the functionality of liposome reconstituted TRPM4-eGFP was examined using electrophysiology. Single-channel recordings from TRPM4-eGFP proteoliposomes showed inhibition of the channel using Flufenamic acid, a well-established inhibitor of TRPM4, suggesting that the channels are functional upon reconstitution. Our characterisation of the oligomeric structure of TRPM4 and the ability to reconstitute functional channels in liposomes should facilitate future studies into the structure, function and pharmacology of this therapeutically relevant channel.
Journal Article
Local-Indigenous Autonomy and Community Streetscape Enhancement: Learnings from Māori and Te Ara Mua—Future Streets Project
2021
In settler countries, attention is now extending to the wellbeing benefits of recognising and promoting the Indigenous cultural identity of neighbourhoods as a contributing factor to more equitable and healthier communities. Re-indigenisation efforts to (re)implement cultural factors into urban design can be challenging and ineffective without the leadership and collaboration of local-Indigenous peoples. Undertaken in Aotearoa New Zealand, Te Ara Mua — Future Street project, demonstrated that co-design has critical potential in the reclamation of Indigenous autonomy, increased local-Indigenous presence and revitalisation of cultural identity. Employing a Kaupapa Māori (Māori-centred) research approach, we focused on the workings and perspectives of mana whenua (local-Indigenous peoples) and community stakeholder engagement in Te Ara Mua. An Indigenous theoretical framework, Te Pae Mahutonga, was utilised in the data analysis to explore perspectives of Indigenous collective agency, empowerment, and wellbeing. Our research demonstrates that developing capacity amongst Indigenous communities is integral for effective engagement and that the realisation of autonomy in urban design projects has broader implications for Indigenous sovereignty, spatial justice and health equity. Significantly, we argue that future community enhancement strategies must include not only re-designing and re-imagining initiatives, but also re-indigenising.
Journal Article
Government climate and health equity priorities must prompt a deeper re-think of health and healthcare for the 21st century
2018
Comments on the implications of the directive by the Minister of Health for action by District Health Boards (DHB) to address climate change in ways that protect and promote health, with a priority to reduce health inequities. Outlines practical examples of what DHBs can do to respond to this expectation. Looks at Earth’s nine ecosystem limits that humans have exceeded, and the consequences for human wellbeing. Argues for a reorientation of the conversation around equitable and sustainable health and healthcare incorporating Māori models of wellbeing. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Journal Article