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Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and cardiovascular disease1. Thermogenesis by adipocytes can counteract obesity and metabolic diseases2,3. In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP-purportedly via a phosphorylation cycle4-to drive thermogenic respiration. However, the proteins that control this futile creatine cycle are unknown. Here we show that creatine kinase B (CKB) is indispensable for thermogenesis resulting from the futile creatine cycle, during which it traffics to mitochondria using an internal mitochondrial targeting sequence. CKB is powerfully induced by thermogenic stimuli in both mouse and human adipocytes. Adipocyte-selective inactivation of Ckb in mice diminishes thermogenic capacity, increases predisposition to obesity, and disrupts glucose homeostasis. CKB is therefore a key effector of the futile creatine cycle.
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Tecido Adiposo/metabolismo , Creatina Quinase Forma BB/metabolismo , Creatina/metabolismo , Termogênese , Adipócitos/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/enzimologia , Animais , Creatina Quinase Forma BB/deficiência , Creatina Quinase Forma BB/genética , AMP Cíclico/metabolismo , Metabolismo Energético/genética , Feminino , Glucose/metabolismo , Homeostase , Humanos , Masculino , Camundongos , Mitocôndrias/metabolismo , Obesidade/enzimologia , Obesidade/genética , Obesidade/metabolismo , Transdução de SinaisRESUMO
AIM: To qualitatively explore the experiences of individuals with Gestational Diabetes Mellitus (GDM) in Australia, and to recognise opportunities for leveraging digital health to enhance the support of GDM management. METHOD: A cross sectional online survey assessed the experiences of individuals with GDM, the healthcare system and their digital health usage. Respondents (recruited via a national diabetes registry or social media) were adults receiving GDM care within Australia in the last 5 years, who responded to any of three open-ended questions (n = 815) exploring positive, negative and other GDM experiences. Thematic analysis was utilised, and themes were mapped to the socio-ecological systems framework. RESULTS: At a system level, themes related to (1) accessibility of care including the value of digital health and the inflexible or inconsistent perception of the (2) implementation of guidelines. At an interpersonal level, themes covered the need for adequate (3) health information provision, and (4) supportive care, as well as highlighting (5) experiences of stigma including a desire for greater awareness of GDM. Individual-level themes included: (6) differential barriers to accessing care; (7) negative emotional burden; (8) internalisation of stigma; (9) dietary freedom and social impact and (10) opportunity for change derived from having GDM. CONCLUSION: Findings suggest a demand for more supportive, person-centred GDM care, improved information provision and individualised implementation of clinical guidelines. Such mechanisms may support reduced barriers to accessing care or negative psychosocial impacts of GDM. Though not central to the identified experiences, digital health tools may help address the need for optimised GDM care.
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BACKGROUND: The present study aims to share insights and lessons learnt by dietitians providing individualised care to people living with disabilities in the community. This is important to build the evidence to inform dietetic best practice standards. METHODS: The study involved a cross-sectional data audit of dietitian reports for clients living with a disability seen at a metropolitan dietitian clinic in South Australia. Content analysis of the reports was conducted. Initial coding occurred deductively followed by inductive qualitative content analysis. RESULTS: Thirty-one participants consented to have their dietitian reports included in the study. Intellectual disabilities made up the majority (48%) of disabilities reported in the sample. Nutrition diagnoses predominantly related to energy imbalances (54%). Barriers to dietary change included a reliance on others and limitations in the disability support system. Kitchen skills and cooking were the most often employed nutrition strategy suggested by dietitians. Following dietetic intervention, improvements were seen in the types of foods people with a disability consumed along with changes to their body weight. Dietitians reported the importance of effective communication with the care team and providing engaging methods to instigate dietary behaviour change. CONCLUSIONS: The present study highlights that there are opportunities to build on individualised dietetic care provided to people living with disabilities. These opportunities include addressing excess energy consumption, fostering collaborations with other health providers and understanding how to better work with carers. Further research is required to understand how to progress these opportunities forward and to understand the generalisability of the findings.
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Dietética , Nutricionistas , Humanos , Estudos Transversais , Estado Nutricional , Peso CorporalRESUMO
ISSUES ADDRESSED: How health promotion is implemented varies and it is often not clear what activities are in place in a region. Understanding the extent of health promotion activities helps planning activities. METHODS: This research involved a rapid audit of the types of health promotion activities in a suburban region of South Australia. This analysis was guided by the WHO Ottawa Charter's principles. To better understand population needs and which health promoting activities may help, an epidemiological, demographic and social determinants of health profile of southern Adelaide described disease patterns and health inequities. RESULTS: While there was evidence of a range of health promoting activities, most concerned individual or behavioural services. A key finding was the small number of activities that the state health department and local health system were responsible for. Alongside local government, NGOs provided the bulk of health promotion activities. In addition, there were no overarching health promotion strategies or coordinating bodies to evaluate the activities. The epidemiological, demographic and social determinants of health profile found persistent health and social inequities. CONCLUSION: This rapid audit of health promotion in a region enabled a quick assessment of the current health promotion situation and provided evidence of gaps and areas where policy change should be advocated. SO WHAT?: The key findings distilled from this research were designed to inform policy priorities to shift health promotion in southern Adelaide onto a trajectory consistent with the Ottawa Charter and prevent further focus on individualised behaviour change strategies known as 'lifestyle drift'.
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Promoção da Saúde , Governo Local , Política de Saúde , Humanos , Estilo de Vida , Austrália do SulRESUMO
Obesity results from energy imbalance, when energy intake exceeds energy expenditure. Brown adipose tissue (BAT) drives non-shivering thermogenesis which represents a powerful mechanism of enhancing the energy expenditure side of the energy balance equation. The best understood thermogenic system in BAT that evolved to protect the body from hypothermia is based on the uncoupling of protonmotive force from oxidative phosphorylation through the actions of uncoupling protein 1 (UCP1), a key regulator of cold-mediated thermogenesis. Similarly, energy expenditure is triggered in response to caloric excess, and animals with reduced thermogenic fat function can succumb to diet-induced obesity. Thus, it was surprising when inactivation of Ucp1 did not potentiate diet-induced obesity. In recent years, it has become clear that multiple thermogenic mechanisms exist, based on ATP sinks centered on creatine, lipid, or calcium cycling, along with Fatty acid-mediated UCP1-independent leak pathways driven by the ADP/ATP carrier (AAC). With a key difference between cold- and diet-induced thermogenesis being the dynamic changes in purine nucleotide (primarily ATP) levels, ATP-dependent thermogenic pathways may play a key role in diet-induced thermogenesis. Additionally, the ubiquitous expression of AAC may facilitate increased energy expenditure in many cell types, in the face of over feeding. Interest in UCP1-independent energy expenditure has begun to showcase the therapeutic potential that lies in refining our understanding of the diversity of biochemical pathways controlling thermogenic respiration.
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Tecido Adiposo Marrom/metabolismo , Metabolismo Energético/fisiologia , Obesidade/metabolismo , Termogênese/fisiologia , Proteína Desacopladora 1/metabolismo , Trifosfato de Adenosina/metabolismo , Adipócitos/metabolismo , Animais , Cálcio/metabolismo , Creatina Quinase/metabolismo , Dieta , Retículo Endoplasmático/metabolismo , Ácidos Graxos/metabolismo , Mitocôndrias/metabolismo , Fosforilação OxidativaRESUMO
BACKGROUND: Mindful eating has been introduced as a strategy to help prevent overweight and obesity. AIM: The purpose of this research was to develop a simple system dynamics model to investigate the impact of different interventions on population level mindfulness, mindful eating and healthy weight over a 10-year period. METHODS: A model was constructed and outcomes analysed following the addition of four mindful eating interventions, including decreasing busyness (formal and informal work), promotion of mindful eating (e.g. classes and media), promotion of mindfulness, reduction of external eating cues (decreased portion sizes and variety) or a combination of all interventions. RESULTS: The model projected that if the current situation was to continue over the next 10-year period, there would be a small decrease of 0.6% in the healthy-weight population despite a 42% increase in people practising mindfulness and 40% increase in people eating mindfully. Of the four interventions introduced, decreasing busyness had the greatest impact on the number of people practising mindfulness, eating mindfully and of a healthy weight. However, when all four interventions were introduced together this resulted in the greatest (19%) increase in the proportion of healthy-weight people. CONCLUSIONS: The study suggests that mindful eating can be improved through intervention, however, the interventions will not greatly contribute to improving the healthy-weight population unless implemented in combination.
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Peso Corporal , Dieta Saudável , Nível de Saúde , Atenção Plena , Obesidade/prevenção & controle , Sobrepeso/prevenção & controle , Humanos , Obesidade/psicologia , Sobrepeso/psicologiaRESUMO
BACKGROUND: The aim of this study was to describe stunting in infants and young children in the ethnic communities of northern Thailand and to explore associations with dietary diversity and household factors including food security. METHODS: A cross-sectional survey of households with children under 5 years from eight villages. Adult respondents provided information on foods consumed by each child and details of the household. Heights and weights of children were measured. RESULTS: Adults from 172 households and 208 children participated. Overall, 38% of children were stunted. Exclusive breastfeeding was rare, but the proportion consuming breastmilk at 24 months (75%) was high. Few children (7%) aged 6-11 months met minimum dietary diversity. Stunted children were less likely than non-stunted children to meet minimum dietary diversity (63 versus 82%). Widespread food insecurity did not discriminate between stunted and non-stunted children. Stunting was elevated when households had little land and few animals. CONCLUSIONS: Stunting was widespread in children under 5 years of age, in part reflecting poor dietary diversity, especially at age 6-11 months. Stunting was worst in households with least assets. Small increases in land or animals, or equivalent resources, appear to be required to improve child nutrition in extremely poor families.
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Dieta/estatística & dados numéricos , Abastecimento de Alimentos/estatística & dados numéricos , Transtornos do Crescimento/epidemiologia , Adulto , Pré-Escolar , Dieta/etnologia , Etnicidade/estatística & dados numéricos , Características da Família , Feminino , Transtornos do Crescimento/etnologia , Transtornos do Crescimento/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tailândia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To gain an in-depth understanding of infant and young child feeding practices, accompanying beliefs and their sociocultural context in the Karen and Lua ethnic communities of northern Thailand. DESIGN: A two-day workshop and thirty in-depth interviews were undertaken in June 2014. Dialogue occurred with the assistance of translators and was recorded, transcribed and translated. A detailed thematic analysis was undertaken. SETTING: Northern Thai indigenous communities in which one-third of the children under 5 years of age are stunted. SUBJECTS: People with various roles in the local health system and twenty-six villagers who cared for infants and young children. RESULTS: Predominant breast-feeding was said to occur for 1 to 3 months but was not exclusive due to early introduction of water and/or rice. Exclusive breast-feeding for 6 months was impeded by the need for mothers to return to farming work, with the early introduction of solids enabling infants to be cared for by other family members. Low variety in complementary foods was typical during infancy, with few local foods having appropriate texture and special preparation of foods rarely described. A pervasive underlying issue is women's responsibility to labour and lack of time to care for their young children. Poverty and food insecurity also featured in participants' accounts. CONCLUSIONS: In combination, women's limited time to care, poverty and food insecurity are perpetuating poor nutrition of children in early life. Agricultural solutions that are being explored should also attend to the burden of work for women.
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Aleitamento Materno , Características Culturais , Métodos de Alimentação , Alimentos Infantis , Dieta , Feminino , Humanos , Lactente , Entrevistas como Assunto , Masculino , Pobreza , População Rural , TailândiaRESUMO
That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption. We find that, although germline Ucp1-/- mice succumb to cold-induced hypothermia with complete penetrance, most mice with the inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase b (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold intolerance. Following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature brown adipocytes that coordinately restore UCP1 and CKB expression. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy-through UCP1 and CKB-to promote cold-induced energy dissipation.
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Adipócitos Marrons , Tecido Adiposo Marrom , Animais , Camundongos , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Termogênese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Creatina Quinase Forma BB/metabolismoRESUMO
Gestational Diabetes Mellitus (GDM) is a common medical complication of pregnancy, which is associated with increased risk of future diabetes. mHealth (mobile health, in this paper applications abbreviated to apps) can facilitate health modifications to decrease future risks. This study aims to understand mHealth app use and preferences among women with past GDM and healthcare professionals (HCP) in Australia. An explorative cross-sectional online survey was disseminated via social media, a national diabetes registry, and professional networks. Descriptive analyses were conducted on valid responses (women with prior GDM: n = 1475; HCP: n = 75). One third (33%) of women with prior GDM have used health apps, and a further 80% of non-app users were open to using a health app if recommended by their HCP. Over half (53%) of HCPs supported health information delivery via mHealth, although only 14% had recommended a health app to women post-GDM, and lack of knowledge about mHealth apps was common. Health app users reported that they preferred tracking features, while non-users desired credible health and dietary information and plans. Expanding mHealth app use could facilitate healthy behaviours, but endorsement by HCPs is important to women and is still currently lacking.
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Diabetes Gestacional , Aplicativos Móveis , Telemedicina , Gravidez , Humanos , Feminino , Diabetes Gestacional/terapia , Estudos Transversais , Cuidado Pós-Natal , Dieta , Exercício FísicoRESUMO
Background: The use of digital technologies has expanded rapidly in recent years, particularly with the onset of COVID-19. Digital technologies have been implemented in nursing and healthcare to support necessary care. Aims: This research explored how nursing and healthcare researchers engage with digital technologies, including the types of technologies, facilitators, barriers and suggested improvements to enable engagement. Methods: Semi-structured interviews were conducted with 36 nursing and healthcare researchers from an Australian University. Interviews were recorded, transcribed, coded and thematically analysed using the COREQ checklist. Results: Four major types of digital technologies were engaged by nursing and healthcare researchers. These included monitoring, intervention, communication and data collection and analysis technologies. The research setting provided the overarching systems and policies that could delay actions or provide necessary supports. Access to experts, good communication, sharing digital technology information, and time and funding were identified as important. Conclusion: This research highlights that nursing and healthcare researchers are engaging with digital technologies but there are areas for improvement that are underpinned by the research setting and need to be considered to ensure effective use of digital technologies in nursing and healthcare research.
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There is a dearth of public health data and research focusing on lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) populations during the coronavirus ("COVID") pandemic. This study evaluated how COVID has impacted health, social, and occupational areas of functioning of the LGBTQ+ community. A community survey was distributed via email by local LGBTQ+ community organizations between September and December 2020. Participants (cisgender, heterosexual people, n = 63; cisgender sexual minority people, n = 184; and gender minority people, n = 74) were asked how COVID has impacted their life circumstances (i.e., physical health, mental health, financial stability, meeting basic needs, and social connectedness). A multivariate analysis of covariance was tested with these groups, demographic and HIV serostatus variables as independent variables and covariates, and outcomes as dependent variables. Compared to cisgender, heterosexual people, significantly more cisgender sexual minority people reported worsening physical health, and significantly more gender minority people reported worsening of all outcomes. Significantly more gender minority people reported worsening financial stability than cisgender sexual minority people. COVID has contributed to a worsening of life circumstances among the LGBTQ+ community, especially for gender minority people. More research is needed to create proactive, equitable, culturally-focused responses and interventions to pandemics.
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COVID-19 , Minorias Sexuais e de Gênero , Pessoas Transgênero , Feminino , Heterossexualidade , Humanos , SARS-CoV-2 , Pessoas Transgênero/psicologiaRESUMO
Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis1. Aside from cAMP signalling downstream of ß-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α1-adrenergic receptor (AR) and ß3-AR signalling induces the expression of thermogenic genes of the futile creatine cycle2,3, and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo. NA triggers physical and functional coupling between the α1-AR subtype (ADRA1A) and Gαq to promote adipocyte thermogenesis in a manner that is dependent on the effector proteins of the futile creatine cycle, creatine kinase B and tissue-non-specific alkaline phosphatase. Combined Gαq and Gαs signalling selectively in adipocytes promotes a continual rise in whole-body energy expenditure, and creatine kinase B is required for this effect. Thus, the ADRA1A-Gαq-futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis.
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Creatina , Termogênese , Creatina/metabolismo , Termogênese/genética , Adipócitos/metabolismo , Metabolismo Energético/genética , Creatina Quinase/metabolismoRESUMO
BACKGROUND: Nutrition-sensitive agriculture (NSA) interventions can contribute to improved food security and household dietary diversity. As well as undertaking trials, contextual factors that influence sustainability need to be scoped. OBJECTIVE: To explore locals' views of an NSA initiative, designed to improve food security and reduce malnutrition in children younger than 5 years, scoping future prospects 6 months after the conclusion of the trial. METHODS: The initiative that was formally trialed over 6 months (November 2014 to April 2015) entailed keeping hens and home gardens. It occurred in the ethnic hill tribes of northern Thailand. In November 2015, 20 in-depth interviews were undertaken with villagers who had been involved in the initiative. Dialogue occurred in Thai with assistance of a translator and was recorded, transcribed, and translated to English. A detailed thematic analysis was undertaken. RESULTS: Eggs produced by the hens were appreciated and fed to children, and the message of providing children with an egg a day was widely remembered. Subsequently, the hens ceased laying or died. The home gardens had seasonal scarcity of water. Less visible, but fundamental, women lacked time for these activities due to heavy burdens of farm labor. CONCLUSION: Keeping hens has potential to become a sustainable activity. Home gardens need water infrastructure to be viable. Women do not necessarily have spare capacity for such initiatives. The required labor needs deliberation by villagers.
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Galinhas , Desnutrição , Agricultura , Animais , Feminino , Abastecimento de Alimentos , Humanos , Estado Nutricional , TailândiaRESUMO
Food costs are a barrier to healthier diet selections, particularly for low socioeconomic households who regularly choose processed foods containing refined grains, added sugars, and added fats. In this study, the objectives were to: (i) identify the nutrient density-to-cost ratio of Australian foods; (ii) model the impact of substituting foods with lower nutrient density-to-cost ratio with those with the highest nutrient density-to-cost ratio for diet quality and affordability in low and medium socioeconomic households; and (iii) evaluate food processing levels. Foods were categorized, coded for processing level, analysed for nutrient density and cost, and ranked by nutrient density-to-cost ratio. The top quartile of nutrient dense, low-cost foods included 54% unprocessed (vegetables and reduced fat dairy), 33% ultra-processed (fortified wholegrain bread and breakfast cereals <20 g sugars/100 g), and 13% processed (fruit juice and canned legumes). Using substitution modelling, diet quality improved by 52% for adults and 71% for children across all households, while diet affordability improved by 25% and 27% for low and medium socioeconomic households, respectively. The results indicate that the quality and affordability of the Australian diet can be improved when nutritious, low-cost foods are selected. Processing levels in the healthier modelled diets suggest that some ultra-processed foods may provide a beneficial source of nutrition when consumed within national food group recommendations.
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Dieta Saudável , Dieta , Adulto , Austrália , Criança , Custos e Análise de Custo , Características da Família , HumanosRESUMO
AIM: In Australian adults, this study seeks to describe the experiences and factors associated with the perceived outcomes of using a very low calorie diet (VLCD) program for ≥4 weeks. METHODS: A mixed method study using the method perspective was conducted to analyse individual semi-structured interviews conducted via videoconference and cross-sectional survey data. Australians 18 to 65 years were eligible if they were currently consuming at least one VLCD product daily for ≥4 weeks or had ceased consumption within 4 weeks. Interviews were thematically analysed. RESULTS: Weight loss (19 kg [SD: 18 kg]) and duration (5 months [SD: 5 months]) of VLCD product use of the 31 participants (female: 97%, 44 [SD: 11] years, body mass index >30 kg/m2 : 84%) were strongly correlated (r = 0.73, P < .001). Participants' experiences were influenced by a journey of learning from their previous weight loss attempts, discerned the VLCD program as credible, and chose to commence the VLCD due to a convergence of internal motivators. Early health-related outcomes were a reinforcing stimulus and participants developed new health behaviours but felt dependent on the VLCD long term. Throughout these experiences the participants identified various individual, program structure, and environment related factors which either facilitated their VLCD program use or created barriers to achieving their goals. Health care professionals were minimally engaged. CONCLUSIONS: A model of care to support facilitators and overcome barriers would mean more meaningful engagement of health care professionals to ultimately improve the experience and adherence of the VLCD program users in Australia.
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Restrição Calórica , Austrália , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Redução de PesoRESUMO
Adipocyte biology has been intensely researched in recent years due to the emergence of obesity as a serious global health concern and because of the realization that adipose tissue is more than simply a cell type that stores and releases lipids. The plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. The capacity for white adipocytes to store chemical energy in lipid droplets is key for protecting other organs from the toxic effects of ectopic lipid deposition. In contrast, thermogenic (brown and beige) adipocytes combust macronutrients to generate heat. The thermogenic activity of adipocytes allows them to protect themselves and other tissues from lipid overaccumulation. Advances in brown fat biology have uncovered key molecular players involved in adipocyte determination, differentiation, and thermogenic activation. It is now, well appreciated that three distinct adipocyte types exist: white, beige, and brown. Moreover, functional differences are present within adipocyte subtypes located in anatomically distinct locations. Adding to this complexity is the recent realization from single-cell sequencing studies that adipocyte progenitors are also heterogeneous. Understanding the molecular details of how to increase the number of thermogenic fat cells and their activation may delineate some of the pathophysiological basis of obesity and obesity-related diseases. Here, we review recent advances that have extended our understanding of the central role that adipose tissue plays in energy balance and the mechanisms that control their amount and function.
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Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Metabolismo Energético/genética , Regulação da Expressão Gênica , Obesidade/genética , Termogênese/genética , Animais , Humanos , Modelos Genéticos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
BACKGROUND: Early life experiences shape individual attachment, creating a template for regulating emotions in interpersonal situations, likely to persist across the lifespan. Research has shown that individual attachment creates vulnerability for depression, and also impacts the Hypothalamic-Pituitary-Adrenal (HPA) axis. Still, the relationship between attachment and the HPA axis in depressed individuals is unclear. Cortisol awakening response (CAR) has been recently investigated as a possibly useful physiological marker related to attachment insecurity and depression risk. However, research exploring the relationship between the CAR and attachment in individuals with chronic depression in either the presence or the absence of comorbid anxiety is lacking. The purpose of the current study was to fill this gap, by comparing the CAR in individuals with chronic depression with/without comorbid anxieties and controls. In addition, we also wanted to explore the relationship between attachment and the CAR in this group and to explore their predictive role for later depression severity. METHODS: Individuals experiencing a current depressive episode at least six months in length (cMDD; n = 63) and healthy controls (HC; n = 57) were enrolled in the study (total n = 120). Participants completed a structured clinical diagnostic interview (SCID-I) as well as measures of depression severity (Beck Depression Inventory-II (BDI-II) and Hamilton Rating Scale for Depression) and attachment dimensions (Experiences in Close Relationships scale; ECR) at baseline. In addition, participants provided salivary samples at four time points (i.e. 0 (S1), 30, 45 and 60 min) following awakening on two consecutive days. S1 cortisol, the area under the curve with respect to ground (AUCg) and increase (AUCi) were calculated based on the average values across both days. The HC and cMDD groups were compared on all measures. The CAR for individuals with cMDD alone (n = 14) and individuals with cMDD with two or more comorbid anxiety disorders (cMDD ≥ 2Anx; n = 30) were also compared. A subset of participants (n = 59) agreed to return for follow up one year later. Participants returning for follow up repeated the BDI-II and ECR. No salivary samples were collected at follow-up. RESULTS: The cMDD group had significantly lower S1 cortisol and AUCg compared to the HC group (both p ≤ 0.02). cMDD and cMDD ≥ 2Anx groups did not differ in their CAR. Regression analyses revealed that depression severity and the attachment interaction term was associated with lower S1 and AUCg cortisol (p < 0.01). Greater attachment avoidance was positively associated with S1 cortisol (p = 0.02), while mean awakening time on sample days was negatively associated with S1 cortisol. We also found a significant interaction between the attachment dimensions such that at low levels of attachment anxiety, attachment avoidance had a positive relationship with S1 cortisol and AUCg. The opposite relationship existed when attachment anxiety was high. Higher baseline BDI-II score and higher baseline attachment anxiety were predictive of higher scores on the BDI-II one-year later (both p < 0.05). CONCLUSIONS: The current findings bring evidence that depression severity is associated with blunting of the CAR irrespective of the comorbid status with anxiety disorders. In addition, attachment avoidance may protect against the CAR blunting in individuals with low attachment anxiety. However, individuals with high attachment anxiety and avoidance might have additional CAR blunting. Attachment anxiety might be a good predictor of future depression severity.
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Depressão/metabolismo , Hidrocortisona/metabolismo , Apego ao Objeto , Adulto , Ansiedade , Transtornos de Ansiedade , Doença Crônica/psicologia , Ritmo Circadiano/fisiologia , Depressão/complicações , Depressão/fisiopatologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química , Vigília/fisiologiaRESUMO
The mite Varroa destructor is a serious threat to honeybee populations. Selective breeding for Varroa mite tolerance could be accelerated by biomarkers within individual bees that could be applied to evaluate a colony phenotype. Previously, we demonstrated differences in kinase-mediated signaling between bees from colonies of extreme phenotypes of mite susceptibility. We expand these findings by defining a panel of 19 phosphorylation events that differ significantly between individual pupae from multiple colonies with distinct Varroa mite tolerant phenotypes. The predictive capacity of these biomarkers was evaluated by analyzing uninfested pupae from eight colonies representing a spectrum of mite tolerance. The pool of biomarkers effectively discriminated individual pupae on the basis of colony susceptibility to mite infestation. Kinome analysis of uninfested pupae from mite tolerant colonies highlighted an increased innate immune response capacity. The implication that differences in innate immunity contribute to mite susceptibility is supported by the observation that induction of innate immune signaling responses to infestation is compromised in pupae of the susceptible colonies. Collectively, biomarkers within individual pupae that are predictive of the susceptibility of colonies to mite infestation could provide a molecular tool for selective breeding of tolerant colonies.
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Abelhas/imunologia , Biomarcadores/metabolismo , Olho/imunologia , Tolerância Imunológica/imunologia , Infestações por Ácaros/imunologia , Pupa/imunologia , Varroidae/imunologia , Animais , Abelhas/metabolismo , Olho/metabolismo , Interações Hospedeiro-Parasita/imunologia , Pupa/metabolismoRESUMO
In eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones and redox proteins including SCO1, SCO2, and COA6, a recently discovered protein whose molecular function is unknown. To uncover the molecular mechanism by which COA6 and SCO proteins mediate copper delivery to COX2, we have solved the solution structure of COA6, which reveals a coiled-coil-helix-coiled-coil-helix domain typical of redox-active proteins found in the mitochondrial inter-membrane space. Accordingly, we demonstrate that COA6 can reduce the copper-coordinating disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. Finally, our determination of the interaction surfaces and reduction potentials of COA6 and its client proteins provides a mechanism of how metallochaperone and disulfide reductase activities are coordinated to deliver copper to CcO.