298 research outputs found
Reduction in the levels of CoQ biosynthetic proteins is related to an increase in lifespan without evidence of hepatic mitohormesis
Mitohormesis is an adaptive response induced by a mild mitochondrial stress that promotes longevity
and metabolic health in different organisms. This mechanism has been proposed as the cause of the
increase in the survival in Coq7+/â (Mclk1+/â) mice, which show hepatic reduction of COQ7, early
mitochondrial dysfunction and increased oxidative stress. Our study shows that the lack of COQ9 in
Coq9Q95X mice triggers the reduction of COQ7, COQ6 and COQ5, which results in an increase in life
expectancy. However, our results reveal that the hepatic CoQ levels are not decreased and, therefore,
neither mitochondrial dysfunction or increased oxidative stress are observed in liver of Coq9Q95X mice.
These data point out the tissue specific differences in CoQ biosynthesis. Moreover, our results suggest
that the effect of reduced levels of COQ7 on the increased survival in Coq9Q95X mice may be due to
mitochondrial mechanisms in non-liver tissues or to other unknown mechanisms.This work was supported by grants from Ministerio de
EconomĂa Competitividad, Spain, and the ERDF (Grant Number SAF2015-65786-R), from the ConsejeriÌa de
EconomiÌa, InnovacioÌn, Ciencia y Empleo, Junta de AndaluciÌa (grant number P10-CTS-6133) and from the
University of Granada (grant reference âUNETEâ, UCE-PP2017-06). AHG is a âFPU fellowâ from the Ministerio
de EducacioÌn Cultura y Deporte, Spain. MLS was a predoctoral fellow from the ConsejeriÌa de EconomiÌa,
InnovacioÌn, Ciencia y Empleo, Junta de AndaluciÌa. LCL was supported by the âRamoÌn y Cajalâ National
Programme, Ministerio de EconomiÌa y Competitividad, Spain (RYC-2011-07643)
(Dis)entangling Barad: Materialisms and ethics
In the wake of the widespread uptake of and debate surrounding the work of Karen Barad, this article revisits her core conceptual contributions. We offer descriptions, elaborations, problematizations and provocations for those intrigued by or invested in this body of work. We examine Baradâs use of quantum physics, which underpins her conception of the material world. We discuss the political strengths of this position but also note tensions associated with applying quantum physics to phenomena at macro-scales. We identify both frictions and unacknowledged affinities with science and technology studies in Baradâs critique of reflexivity and her concept of diffraction. We flesh out Baradâs overarching position of âagential realismâ, which contains a revised understanding of scientific apparatuses. Building upon these discussions, we argue that inherent in agential realism is both an ethics of inclusion and an ethics of exclusion. Existing research has, however, frequently emphasized entanglement and inclusion to the detriment of foreclosure and exclusion. Nonetheless, we contend that it is in the potential for an ethics of exclusion that Baradâs work could be of greatest utility within science and technology studies and beyond
The effect of temperature, gradient and load carriage on oxygen consumption, posture and gait characteristics
Purpose The purpose of this experiment was to evaluate the effect of load carriage in a range of temperatures to establish the interaction between cold exposure, the magnitude of change from unloaded to loaded walking and gradient. Methods Eleven participants (19-27 years) provided written informed consent before performing six randomly ordered walking trials in six temperatures (20°C, 10°C, 5°C, 0°C, -5°C and -10°C). Trials involved two unloaded walking bouts before and after loaded walking (18.2 kg) at 4 km.hrâ»Âč, on 0% and 10% gradients in 4 minute bouts. Results The change in absolute oxygen consumption (VÌOâ) from the first unloaded bout to loaded walking was similar across all six temperatures. When repeating the second unloaded bout, VÌOâ at both -5°C and-10°C was greater compared to the first. At -10°C, VÌOâ was increased from 1.60 ± 0.30 L.minâ»Âč to 1.89 ± 0.51 L.minâ»Âč. Regardless of temperature, gradient had a greater effect on VÌOâ and heart rate (HR) than backpack load. HR was unaffected by temperature. Stride length (SL) decreased with decreasing temperature but trunk forward lean was greater during cold exposure. Conclusion Decreased ambient temperature did not influence the magnitude of change in VÌOâ from unloaded to loaded walking. However, in cold temperatures, VÌOâ was significantly higher than in warm conditions. The increased VÌOâ in colder temperatures at the same exercise intensity is predicted to ultimately lead to earlier onset of fatigue and cessation of exercise. These results highlight the need to consider both appropriate clothing and fitness during cold exposure
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Experiences of dementia in a foreign country: qualitative content analysis of interviews with people with dementia
Background: Dementia is a worldwide health concern of epidemic proportions. Research in the field of subjective experience of dementia suffers from a lack of diversity of their participants including immigrants. Different portraits of life with dementia could help us understand how people with dementia conceptualise their experiences of dementia and how they live. Our study aimed to explore the subjective experiences of living with dementia among Iranian immigrants in Sweden.
Methods: Qualitative content analysis of interviews with fifteen people with dementia from Iranian immigrant backgrounds were conducted (8 females and 7 males).
Results: Three themes and seven associated sub-themes were revealed. The themes included: Being a person with dementia means living with forgetfulness (personal sphere), living with forgetfulness in the private sphere means feeling incompetent but still loved, living with forgetfulness in the public sphere means feeling confident and secure but also isolated.
Conclusions: Living with dementia for the participants meant living with forgetfulness. They experienced feeling incompetent but still loved within their families and feeling confident and secure but also isolated in the society. Educating people with dementia and their families about the course and process of dementia may help them understand the changes better and adjust their expectations. Our study can provide a basis for healthcare workers to understand the experiences of living with dementia from this specific perspective
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Adopting a healthy lifestyle when pregnant and obese - an interview study three years after childbirth
Background: Obesity during pregnancy is increasing and is related to life-threatening and ill-health conditions in both mother and child. Initiating and maintaining a healthy lifestyle when pregnant with body mass index (BMI) â„ 30 kg/m2 can improve health and decrease risks during pregnancy and of long-term illness for the mother and the child. To minimise gestational weight gain women with BMI â„ 30 kg/m2 in early pregnancy were invited to a lifestyle intervention including advice and support on diet and physical activity in Gothenburg, Sweden. The aim of this study was to explore the experiences of women with BMI â„ 30 kg/m2 regarding minimising their gestational weight gain, and to assess how health professionals' care approaches are reflected in the women's narratives.
Methods: Semi-structured interviews were conducted with 17 women who had participated in a lifestyle intervention for women with BMI â„ 30 kg/m2 during pregnancy 3 years earlier. The interviews were digitally recorded and transcribed in full. Thematic analysis was used.
Results: The meaning of changing lifestyle for minimising weight gain and of the professional's care approaches is described in four themes: the child as the main motivation for making healthy changes; a need to be seen and supported on own terms to establish healthy routines; being able to manage healthy activities and own weight; and need for additional support to maintain a healthy lifestyle.
Conclusions: To support women with BMI â„ 30 kg/m2 to make healthy lifestyle changes and limit weight gain during pregnancy antenatal health care providers should 1) address women's weight in a non-judgmental way using BMI, and provide accurate and appropriate information about the benefits of limited gestational weight gain; 2) support the woman on her own terms in a collaborative relationship with the midwife; 3) work in partnership to give the woman the tools to self-manage healthy activities and 4) give continued personal support and monitoring to maintain healthy eating and regular physical activity habits after childbirth involving also the partner and family
Building bridges between industry and academia: what is the profile of an industrial doctorate student?
info:eu-repo/semantics/acceptedVersio
Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)
Observational and epidemiological studies suggest that menopausal hormone therapy (MHT) reduces cardiovascular disease (CVD) risk. However, results from prospective trials showed neutral or adverse effects most likely due to differences in participant demographics, such as age, timing of initiation of treatment, and preexisting cardiovascular disease, which reflected in part the lack of basic science information on mechanisms of action of hormones on the vasculature at the time clinical trials were designed. The Kronos Early Estrogen Replacement Study (KEEPS) is a prospective, randomized, controlled trial designed, using findings from basic science studies, to test the hypothesis that MHT when initiated early in menopause reduces progression of atherosclerosis. KEEPS participants are younger, healthier, and within 3Â years of menopause thus matching more closely demographics of women in prior observational and epidemiological studies than women in the Womenâs Health Initiative hormone trials. KEEPS will provide information relevant to the critical timing hypothesis for MHT use in reducing risk for CVD
Mitochondrial Changes in Ageing Caenorhabditis elegans â What Do We Learn from Superoxide Dismutase Knockouts?
One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the âvicious cycleâ theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD). Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the âvicious cycleâ theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the âvicious cycleâ theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed
ROS release by PPARÎČ/ÎŽ-null fibroblasts reduces tumor load through epithelial antioxidant response.
Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARÎČ/ÎŽ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARÎČ/ÎŽ, using a FSPCre-Pparb/d <sup>-/-</sup> mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d <sup>-/-</sup> mice developed fewer intestinal polyps and survived longer when compared with Pparb/d <sup>fl/fl</sup> mice. The pre-treatment of FSPCre-Pparb/d <sup>-/-</sup> and Pparb/d <sup>fl/fl</sup> with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load. Gene expression analyses implicated an altered oxidative stress processes. Indeed, the FSPCre-Pparb/d <sup>-/-</sup> intestinal tumors have reduced oxidative stress than Pparb/d <sup>fl/fl</sup> tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARÎČ/ÎŽ expression. Therefore, our results establish a role for fibroblast PPARÎČ/ÎŽ in epithelial-mesenchymal communication for ROS homeostasis
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