SGIP1 binding to the α-helical H9 domain of cannabinoid receptor 1 promotes axonal surface expression.

Endocannabinoid signalling mediated by cannabinoid receptor 1 (CB1R, also known as CNR1) is critical for homeostatic neuromodulation of both excitatory and inhibitory synapses. This requires highly polarised axonal surface expression of CB1R, but how this is achieved remains unclear. We previously reported that the α-helical H9 domain in the intracellular C terminus of CB1R contributes to axonal surface expression by an unknown mechanism. Here, we show in rat primary neuronal cultures that the H9 domain binds to the endocytic adaptor protein SGIP1 to promote CB1R expression in the axonal membrane. Overexpression of SGIP1 increases CB1R axonal surface localisation but has no effect on CB1R lacking the H9 domain (CB1RΔH9). Conversely, SGIP1 knockdown reduces axonal surface expression of CB1R but does not affect CB1RΔH9. Furthermore, SGIP1 knockdown diminishes CB1R-mediated inhibition of presynaptic Ca2+ influx in response to neuronal activity. Taken together, these data advance mechanistic understanding of endocannabinoid signalling by demonstrating that SGIP1 interaction with the H9 domain underpins axonal CB1R surface expression to regulate presynaptic responsiveness.

Attitudes and behaviours regarding e-cigarettes in people aged 15-30 years in the UK: a cross-sectional study.

BACKGROUND: The use of e-cigarettes has been rising in the UK, with 7·7% of people aged over 16 years currently vaping daily or occasionally. Young people aged 16-24 years have the highest proportion of vapers at 11·1%. Therefore, this study investigated behaviours, attitudes, and beliefs about e-cigarettes among people aged 15-30 year in the UK. METHODS: For this cross-sectional study, we administered an online survey to a representative sample of people aged 15-30 years in the UK (based on a web panel) between Oct 1, and Nov 30, 2021. Questions related to respondent demographics; use of vaping or smoking products; motivations, attitudes, and behaviours related to vaping; and exposure to e-cigarette advertising. Ever use was described as use even "just once or twice". We used multivariable logistic regression to identify factors associated with ever e-cigarette use. FINDINGS: 1009 participants responded to the survey (mean age 23 years, 520 [51·5%] women, 470 [46.6%] men) and were included in the study. 222 (22·3%) participants vaped at least monthly, with one in ten doing it daily. Current smokers were the most likely to use e-cigarettes (453, 44·9%), followed by previous smokers (288, 28·5%) and never smokers (23, 2·3%). Of the 222 participants vaping at least monthly, 199 (89·6%) had used e-cigarettes containing nicotine. The most common reasons for vaping were having friends who used e-cigarettes (103, 46·4%) and quitting or reducing smoking (89, 40·1%). Most participants agreed that e-cigarettes are addictive (698, 75·1%), help people quitting smoking (597, 64·2%), and are bad for health (584, 62·8%). Warning labels on e-cigarettes were seen by 611 (65·7%) participants, and 489 (52·6%) had been exposed to e-cigarette advertising, especially online. Previous or current tobacco smokers were nine and 22 times more likely to use e-cigarettes than never smokers, respectively (odds ratio [OR] 8·5, 95% CI 5·2-14·0 for previous smokers and 22·3, 12·2-40·7 for current smokers). Perceiving e-cigarettes as harmful was associated with a 40% lower likelihood of vaping (OR 0·6, 0·49-0·83). INTERPRETATION: Vaping seems relatively common among people aged 15-30 years in the UK, mainly among previous and current smokers. Caution should be taken as these findings might not be generalisable to the young UK population, and cross-sectional associations might not be causal. However, perceiving e-cigarettes as harmful might reduce their use, and many users seem unaware of their potential harms, which emphasises the need for further regulation on labelling, marketing, and sales. FUNDING: National Health and Medical Council.

Conceptualising commercial entities in public health: beyond unhealthy commodities and transnational corporations.

Most public health research on the commercial determinants of health (CDOH) to date has focused on a narrow segment of commercial actors. These actors are generally the transnational corporations producing so-called unhealthy commodities such as tobacco, alcohol, and ultra-processed foods. Furthermore, as public health researchers, we often discuss the CDOH using sweeping terms such as private sector, industry, or business that lump together diverse entities whose only shared characteristic is their engagement in commerce. The absence of clear frameworks for differentiating among commercial entities, and for understanding how they might promote or harm health, hinders the governance of commercial interests in public health. Moving forward, it is necessary to develop a nuanced understanding of commercial entities that goes beyond this narrow focus, enabling the consideration of a fuller range of commercial entities and the features that characterise and distinguish them. In this paper, which is the second of three papers in a Series on commercial determinants of health, we develop a framework that enables meaningful distinctions among diverse commercial entities through consideration of their practices, portfolios, resources, organisation, and transparency. The framework that we develop permits fuller consideration of whether, how, and to what extent a commercial actor might influence health outcomes. We discuss possible applications for decision making about engagement; managing and mitigating conflicts of interest; investment and divestment; monitoring; and further research on the CDOH. Improved differentiation among commercial actors strengthens the capacity of practitioners, advocates, academics, regulators, and policy makers to make decisions about, to better understand, and to respond to the CDOH through research, engagement, disengagement, regulation, and strategic opposition.

Host-interactor screens of Phytophthora infestans RXLR proteins reveal vesicle trafficking as a major effector-targeted process.

Pathogens modulate plant cell structure and function by secreting effectors into host tissues. Effectors typically function by associating with host molecules and modulating their activities. This study aimed to identify the host processes targeted by the RXLR class of host-translocated effectors of the potato blight pathogen Phytophthora infestans. To this end, we performed an in planta protein-protein interaction screen by transiently expressing P. infestans RXLR effectors in Nicotiana benthamiana leaves followed by coimmunoprecipitation and liquid chromatography-tandem mass spectrometry. This screen generated an effector-host protein interactome matrix of 59 P. infestans RXLR effectors x 586 N. benthamiana proteins. Classification of the host interactors into putative functional categories revealed over 35 biological processes possibly targeted by P. infestans. We further characterized the PexRD12/31 family of RXLR-WY effectors, which associate and colocalize with components of the vesicle trafficking machinery. One member of this family, PexRD31, increased the number of FYVE positive vesicles in N. benthamiana cells. FYVE positive vesicles also accumulated in leaf cells near P. infestans hyphae, indicating that the pathogen may enhance endosomal trafficking during infection. This interactome dataset will serve as a useful resource for functional studies of P. infestans effectors and of effector-targeted host processes.

Voluntary versus mandatory food labels, Australia.

Objective: To compare uptake of the voluntary Health Star Rating front-of-pack nutrition labelling system with uptake of a mostly mandatory country-of-origin label in Australia over a similar period. Methods: We used data on numbers and proportions of products carrying health stars and country-of-origin labelling recorded annually between 2015 and 2023 through surveys of four large Australian food retailers. We determined the proportion of products with health stars and country-of-origin labels for each year by dividing the number of products carrying each label by the total number eligible to carry that label. Findings: The uptake of the voluntary Health Star Rating increased steadily between 2014 and 2018, reaching a maximum of 42% (8587/20 286) of products in 2021 before decreasing to 39% (8572/22 147) in 2023. Mandatory country-of-origin labelling uptake rose rapidly and was found on 93% (17 567/18 923) of products in 2023. In categories where country-of-origin labelling was voluntary, uptake by 2023 was 48% (3313/6925). In our 2023 sample of 22 147 products, 11 055 (50%) carried country-of-origin labelling only, 7466 (35%) carried both health star and country-of-origin labelling, 1106 (5%) carried health star labels only and 2520 (11%) carried neither label. Conclusion: The experience with country-of-origin labelling shows that widespread and rapid food labelling change can be achieved when required by law. The Australian government should mandate the Health Star Rating without delay. Australia's experience supports other jurisdictions in implementing mandatory front-of-pack nutrition labelling as well as updates to global guidance to recognize mandatory labelling as best-practice in delivering benefits to consumers.

The use of private regulatory measures to create healthy food retail environments: a scoping review.

OBJECTIVE: Different forms of public and private regulation have been used to improve the healthiness of food retail environments. The aim of this scoping review was to systematically examine the types of private regulatory measures used to create healthy food retail environments, the reporting of the processes of implementation, monitoring, review and enforcement and the barriers to and enablers of these. DESIGN: Scoping review using the Johanna Briggs Institute guidelines. Ovid MEDLINE, PsycINFO, Embase, CINAHL Plus, Business Source Complete and Scopus databases were searched in October 2020 and again in September 2023 using terms for 'food retail', 'regulation' and 'nutrition'. Regulatory measure type was described by domain and mechanism. Deductive thematic analysis was used to identify reported barriers and enablers to effective regulatory governance processes using a public health law framework. SETTING: Food retail. PARTICIPANTS: Food retail settings using private regulatory measures to create healthier food retail environments. RESULTS: In total, 17 694 articles were screened and thirty-five included for review from six countries, with all articles published since 2011. Articles reporting on twenty-six unique private regulatory measures cited a mix of voluntary (n 16), mandatory (n 6) measures, both (n 2) or did not disclose (n 2). Articles frequently reported on implementation (34/35), with less reporting on the other regulatory governance processes of monitoring (15/35), review (6/35) and enforcement (2/35). CONCLUSIONS: We recommend more attention be paid to reporting on the monitoring, review and enforcement processes used in private regulation to promote further progress in improving the healthiness of food retail environments.

"There's just a lot of numbers and I just want to have a drink": The challenge of communicating the energy content of alcohol products.

Various governments are considering the implementation of energy labelling on alcohol products as one element of obesity prevention policies. However, little is known about the most effective ways to communicate energy information to consumers. The aim of the present study was to explore consumers' reactions to different energy information provision formats to assist the development of effective energy labels. Nine focus groups (n=83 participants) were conducted with Australian adults who reported drinking alcohol at least twice per month. Participants were exposed to an energy-only information label and labels displaying full nutrition information panels. A thematic analysis approach was used to identify key issues. While few participants were overtly enthusiastic about the mandatory display of energy values on alcohol products, there was general support for the provision of this information to assist those drinkers who could benefit from it. Substantial confusion was apparent as participants attempted to distil meaning from the provided information, particularly where it was expressed in terms of serving sizes and standard drinks. Full nutrition panels were especially problematic in terms of creating a health halo due to the nil or low values for multiple nutrients listed. This was especially notable for information relating to sugar content. Overall, there appears to be inadequate public understanding of the concept of dietary energy in alcoholic beverages and the various terms used to quantify its presence, which is likely to limit the utility of mandatory energy information provision requirements unless they are accompanied by effective community education.

Activation loop phosphorylation of a non-RD receptor kinase initiates plant innate immune signaling.

Receptor kinases (RKs) are fundamental for extracellular sensing and regulate development and stress responses across kingdoms. In plants, leucine-rich repeat receptor kinases (LRR-RKs) are primarily peptide receptors that regulate responses to myriad internal and external stimuli. Phosphorylation of LRR-RK cytoplasmic domains is among the earliest responses following ligand perception, and reciprocal transphosphorylation between a receptor and its coreceptor is thought to activate the receptor complex. Originally proposed based on characterization of the brassinosteroid receptor, the prevalence of complex activation via reciprocal transphosphorylation across the plant RK family has not been tested. Using the LRR-RK ELONGATION FACTOR TU RECEPTOR (EFR) as a model, we set out to understand the steps critical for activating RK complexes. While the EFR cytoplasmic domain is an active protein kinase in vitro and is phosphorylated in a ligand-dependent manner in vivo, catalytically deficient EFR variants are functional in antibacterial immunity. These results reveal a noncatalytic role for EFR in triggering immune signaling and indicate that reciprocal transphoshorylation is not a ubiquitous requirement for LRR-RK complex activation. Rather, our analysis of EFR along with a detailed survey of the literature suggests a distinction between LRR-RKs with RD- versus non-RD protein kinase domains. Based on newly identified phosphorylation sites that regulate the activation state of the EFR complex in vivo, we propose that LRR-RK complexes containing a non-RD protein kinase may be regulated by phosphorylation-dependent conformational changes of the ligand-binding receptor, which could initiate signaling either allosterically or through driving the dissociation of negative regulators of the complex.

Molecular Identification and Cellular Localization of a Corticotropin-Releasing Hormone-Type Neuropeptide in an Echinoderm.

BACKGROUND: Corticotropin-releasing hormone (CRH) mediates physiological responses to stressors in mammals by triggering pituitary secretion of adrenocorticotropic hormone, which stimulates adrenal release of cortisol. CRH belongs to a family of related neuropeptides that include sauvagine, urotensin-I, and urocortins in vertebrates and the diuretic hormone DH44 in insects, indicating that the evolutionary origin of this neuropeptide family can be traced to the common ancestor of the Bilateria. However, little is known about CRH-type neuropeptides in deuterostome invertebrates. METHODS: Here, we used mass spectrometry, mRNA in situ hybridization, and immunohistochemistry to investigate the structure and expression of a CRH-type neuropeptide (ArCRH) in the starfish Asterias rubens (phylum Echinodermata). RESULTS: ArCRH is a 40-residue peptide with N-terminal pyroglutamylation and C-terminal amidation, and it has a widespread pattern of expression in A. rubens. In the central nervous system comprising the circumoral nerve ring and 5 radial nerve cords, ArCRH-expressing cells and fibres were revealed in both the ectoneural region and the hyponeural region, which contains the cell bodies of motoneurons. Accordingly, ArCRH immunoreactivity was detected in innervation of the ampulla and podium of locomotory organs (tube feet), and ArCRH is the first neuropeptide to be identified as a marker for nerve fibres located in the muscle layer of these organs. ArCRH immunoreactivity was also revealed in protractile organs that mediate gas exchange (papulae), the apical muscle, and the digestive system. CONCLUSIONS: Our findings provide the first insights into CRH-type neuropeptide expression and function in the unique context of the pentaradially symmetrical body plan of an echinoderm.

Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network).

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Fifty shades of partnerships: a governance typology for public private engagement in the nutrition sector.

BACKGROUND: Multistakeholder collaboration has emerged as a dominant approach for engaging and mobilising non-state actors; notably embedded in the paradigm of the UN Sustainable Development Goals. Yet, considerable ambiguity and contestation surrounds the appropriate terms of public private engagement (PPE) with industry actors. MAIN BODY: This paper seeks to conceptualise different forms of engagement with the food industry in tackling diet-related noncommunicable disease, within the context of power asymmetries across engaged stakeholders. It does so by introducing the Governance Typology for Public Private Engagement in the Nutrition Sector, a typology for government-led engagement with food industry actors across three domains: (i) the form of industry and civil society actor engagement (i.e., rules of exercising institutional power), based on the degree of participation in formal decision-making as well as participation at different stages in the policy cycle; (ii) the type of industry actors being engaged (i.e., pre-existing power attributes), based on function, size, and product portfolios for profit; and (iii) the substantive policy focus of engagement. CONCLUSIONS: The Governance Typology for Public Private Engagement in the Nutrition Sector seeks to inform national level nutrition policy makers on good engagement practice with food industry actors and complements existing risk assessment tools. This typology has the potential to inform decision-making on public sector engagement with other industries that profit from products detrimental to human and planetary health.

Trends in sugar content of non-alcoholic beverages in Australia between 2015 and 2019 during the operation of a voluntary industry pledge to reduce sugar content.

OBJECTIVES: To investigate changes in mean sugar content of non-alcoholic beverages (overall and sugar-sweetened beverages (SSB)) available for purchase in Australia and to compare signatories v. non-signatories of the Australian Beverages Council voluntary pledge from 2018. DESIGN: Retrospective observational study. SETTING: Australia. PARTICIPANTS: About 1500 non-alcoholic beverages per year included in the FoodSwitch Monitoring Datasets for 2015-2019. RESULTS: Overall, mean sugar content fell by 1·3 g/100 ml (17·1 %) from 7·5 g/100 ml in 2015 to 6·2 g/100 ml in 2019. SSB have accounted for about 56 % of all beverages available for purchase since 2015. Between 2015 and 2019, the sugar content of SSB dropped by about 10 % (0·8 g/100 ml). Soft drinks and milk-based drinks were the categories with the largest decrease in sugar content. The greater reduction in sugar observed for beverages overall than SSB suggests at least some of the overall decrease in sugar content is due to the appearance of new products with low or no sugar rather than reformulation. Over the same period, beverages with added non-nutritive sweeteners increased from 41 % to 44 %. The decrease in sugar content for all beverages and SSB was, in general, larger for non-signatories than signatories of the voluntary industry pledge. CONCLUSIONS: Between 2015 and 2019, the small reduction in sugar content of non-alcoholic beverages in Australia resulted from the combined effects of introducing low- or no-sugar products and reformulation of some categories of SSB. Further policy and regulatory measures are required to reap the most benefit that sugar reduction among non-alcoholic beverages can bring to population health.

Chocolate unicorns and smiling teddy biscuits: analysis of the use of child-directed marketing on the packages of Australian foods.

OBJECTIVE: The use of food packaging as a vehicle for marketing to children is under investigated. Our objective was to determine the prevalence and types of child-directed promotional techniques used on food packaging in Australia. DESIGN: Based on existing literature and regulations, we developed a framework to classify on-pack child-directed promotional techniques involving the use of characters and other elements that appeal to children. We analysed the packaging of all products in eight food categories available for sale from supermarkets in 2019 and recorded the use of child-directed promotions on pack. We assessed the number and proportion of products displaying child-directed promotional techniques overall and assessed the healthiness of products using child-directed promotions against four indicators of healthiness to provide summary data overall and for the manufacturers who most frequently employed child-targeted strategies. SETTING: Data were collected from the FoodSwitch database in Sydney, Australia. RESULTS: 901/8006 (11·3 %) products displayed one or more child-directed on-pack element. Most frequent was on foods for infants and young children (n 315), confectionery (n 283), snack foods (n 172) and dairy (n 168). Personified characters were the most commonly used element (n 512). Products using child-directed promotional techniques scored poorly on all four indicators of healthiness: mean health star rating 2·34 (out of 5); 81 % ultra-processed and 6·1 % and 4·5 % products eligible to market to children under Western Pacific and Mexican nutrient profiling schemes, respectively. CONCLUSIONS: Australian children are targeted by promotional techniques on the packaging of unhealthy food products. Stronger regulation of these techniques is warranted to protect children's health.

E-cigarette attitudes and behaviours amongst 15-30-year-olds in the UK.

BACKGROUND: The use of e-cigarettes has been rising in the UK, particularly by young people. This study investigated behaviours, attitudes and beliefs about e-cigarettes amongst 15-30-year-olds in the UK. METHODS: An online survey was administered to a sample of 1009 15-30-year-olds in the UK. RESULTS: About one in five participants currently used e-cigarettes at least monthly, with 1 in 10 using them daily. Amongst those using e-cigarettes at least monthly, 90% had used e-cigarettes containing nicotine. E-cigarettes were mainly obtained from vape shops and used at home. Having friends who used e-cigarettes and using them to help quit/reduce smoking were the most common reasons for vaping. About half of participants had been exposed to e-cigarette advertising, especially online, and warning labels on e-cigarettes. Most participants agreed that e-cigarettes are addictive (75%), help people quitting smoking (64%) and are bad for health (63%). Previous or current tobacco smokers were 9 and 22 times more likely to use e-cigarettes than never smokers, respectively. Perceiving e-cigarettes as harmful was associated with a 40% lower likelihood of use. CONCLUSION: Raising awareness on the uncertain long-term consequences of vaping and regulation of marketing and sales are crucial to protect young people in the UK.

Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides.

BACKGROUND: Kisspeptins are neuropeptides that regulate reproductive maturation in mammals via G-protein-coupled receptor-mediated stimulation of gonadotropin-releasing hormone secretion from the hypothalamus. Phylogenetic analysis of kisspeptin-type receptors indicates that this neuropeptide signaling system originated in a common ancestor of the Bilateria, but little is known about kisspeptin signaling in invertebrates. RESULTS: Contrasting with the occurrence of a single kisspeptin receptor in mammalian species, here, we report the discovery of an expanded family of eleven kisspeptin-type receptors in a deuterostome invertebrate - the starfish Asterias rubens (phylum Echinodermata). Furthermore, neuropeptides derived from four precursor proteins were identified as ligands for six of these receptors. One or more kisspeptin-like neuropeptides derived from two precursor proteins (ArKPP1, ArKPP2) act as ligands for four A. rubens kisspeptin-type receptors (ArKPR1,3,8,9). Furthermore, a family of neuropeptides that act as muscle relaxants in echinoderms (SALMFamides) are ligands for two A. rubens kisspeptin-type receptors (ArKPR6,7). The SALMFamide neuropeptide S1 (or ArS1.4) and a 'cocktail' of the seven neuropeptides derived from the S1 precursor protein (ArS1.1-ArS1.7) act as ligands for ArKPR7. The SALMFamide neuropeptide S2 (or ArS2.3) and a 'cocktail' of the eight neuropeptides derived from the S2 precursor protein (ArS2.1-ArS2.8) act as ligands for ArKPR6. CONCLUSIONS: Our findings reveal a remarkable diversity of neuropeptides that act as ligands for kisspeptin-type receptors in starfish and provide important new insights into the evolution of kisspeptin signaling. Furthermore, the discovery of the hitherto unknown relationship of kisspeptins with SALMFamides, neuropeptides that were discovered in starfish prior to the identification of kisspeptins in mammals, presents a radical change in perspective for research on kisspeptin signaling.

Catatonic conundrum.

Differentiating between physical and psychological causes of confusion and psychosis poses a significant challenge to clinicians across all disciplines of medicine. This case report explores the clinical presentation and diagnostic journey of an adolescent girl. She presented to the emergency department with acutely altered behaviour and went on to re-present on multiple occasions over the following months with symptoms suggestive of psychosis. The team faced diagnostic difficulty differentiating between organic and non-organic causes of altered behaviour and mental state. This article explores the challenge faced by the team during the assessment and diagnosis of this patient.

A Nutrigenetic Update on CETP Gene-Diet Interactions on Lipid-Related Outcomes.

PURPOSE OF REVIEW: An abnormal lipid profile is considered a main risk factor for cardiovascular diseases and evidence suggests that single nucleotide polymorphisms (SNPs) in the cholesteryl ester transfer protein (CETP) gene contribute to variations in lipid levels in response to dietary intake. The objective of this review was to identify and discuss nutrigenetic studies assessing the interactions between CETP SNPs and dietary factors on blood lipids. RECENT FINDINGS: Relevant articles were obtained through a literature search of PubMed and Google Scholar through to July 2021. An article was included if it examined an interaction between CETP SNPs and dietary factors on blood lipids. From 49 eligible nutrigenetic studies, 27 studies reported significant interactions between 8 CETP SNPs and 17 dietary factors on blood lipids in 18 ethnicities. The discrepancies in the study findings could be attributed to genetic heterogeneity, and differences in sample size, study design, lifestyle and measurement of dietary intake. The most extensively studied ethnicities were those of Caucasian populations and majority of the studies reported an interaction with dietary fat intake. The rs708272 (TaqIB) was the most widely studied CETP SNP, where 'B1' allele was associated with higher CETP activity, resulting in lower high-density lipoprotein cholesterol and higher serum triglycerides under the influence of high dietary fat intake. Overall, the findings suggest that CETP SNPs might alter blood lipid profiles by modifying responses to diet, but further large studies in multiple ethnic groups are warranted to identify individuals at risk of adverse lipid response to diet.

Direct regulation of the NADPH oxidase RBOHD by the PRR-associated kinase BIK1 during plant immunity.

The rapid production of reactive oxygen species (ROS) burst is a conserved signaling output in immunity across kingdoms. In plants, perception of pathogen-associated molecular patterns (PAMPs) by surface-localized pattern recognition receptors (PRRs) activates the NADPH oxidase RBOHD by hitherto unknown mechanisms. Here, we show that RBOHD exists in complex with the receptor kinases EFR and FLS2, which are the PRRs for bacterial EF-Tu and flagellin, respectively. The plasma-membrane-associated kinase BIK1, which is a direct substrate of the PRR complex, directly interacts with and phosphorylates RBOHD upon PAMP perception. BIK1 phosphorylates different residues than calcium-dependent protein kinases, and both PAMP-induced BIK1 activation and BIK1-mediated phosphorylation of RBOHD are calcium independent. Importantly, phosphorylation of these residues is critical for the PAMP-induced ROS burst and antibacterial immunity. Our study reveals a rapid regulatory mechanism of a plant RBOH, which occurs in parallel with and is essential for its paradigmatic calcium-based regulation.

Association of lactation with maternal risk of type 2 diabetes: A systematic review and meta-analysis of observational studies.

AIM: To investigate the association between lactation and maternal risk of type 2 diabetes, including a potential graded association according to lactation duration. METHODS: A systematic review and meta-analysis of observational studies that investigated the reported association between lactation (irrespective of duration, intensity or mode) and maternal risk of type 2 diabetes was conducted. RESULTS: A total of 22 studies (17 cohort studies and five cross-sectional studies) were included in this systematic review, and 16 contributed to the meta-analysis. Studies that investigated the association of lactation with risk of type 2 diabetes in the first months after birth in women with gestational diabetes reported conflicting results. Studies with a longer follow-up showed a graded protective association for lactation and the risk of type 2 diabetes, with a potentially larger risk reduction in women with gestational diabetes than in those without gestational diabetes. Overall, ever versus never lactation was associated with a 27% lower risk of type 2 diabetes (RR 0.73, 95% CI [0.65, 0.83]). Each additional month of lactation was associated with a 1% lower risk of type 2 diabetes (RR 0.99, 95% CI [0.98, 0.99]). However, the overall quality of the studies was modest. CONCLUSIONS: Lactation is associated with a significantly reduced risk of maternal type 2 diabetes over the life course, particularly in women with gestational diabetes. The protective effect seems to increase with longer duration of lactation. Further research is warranted to understand whether this association is modified by exposure to other risk factors.

Prospective associations of the original Food Standards Agency nutrient profiling system and three variants with weight gain, overweight and obesity risk: results from the French NutriNet-Santé cohort.

Nutrient profiling systems (NPS) are used to classify foods according to their nutritional composition. However, investigating their prospective associations with health is key to their validation. The study investigated the associations of the original Food Standards Agency (FSA)-NPS and three variants (Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC), Health Star Rating NPS and the French High Council of Public Health NPS (HCSP-NPS)), with weight status. Individual dietary indices based on each NPS at the food level were computed to characterise the dietary quality of 71 403 French individuals from the NutriNet-Santé cohort. Associations of these indices with weight gain were assessed using mixed models and with overweight and obesity risks using Cox models. Participants with a higher dietary index (reflecting lower diet nutritional quality) were more likely to have a significant increase in BMI over time (ß-coefficients positive) and an increased risk of overweight (hazard ratio (HR) T3 v. T1 = 1·27 (95 % CI 1·17, 1·37)) for the HCSP-Dietary Index, followed by the original FSA-Dietary Index (HR T3 v. T1 = 1·18 (95 % CI 1·09, 1·28)), the NPSC-Dietary Index (HR T3 v. T1 = 1·14 (95 % CI 1·06, 1·24)) and the Health Star Rating-Dietary Index (HR T3 v. T1 = 1·12 (95 % CI 1·04, 1·21)). Whilst differences were small, the HCSP-Dietary Index appeared to show significantly greater association with overweight risk. Overall, these results show the validity of NPS derived from the FSA-NPS, supporting their use in public policies for chronic disease prevention.