STING trafficking activates MAPK-CREB signaling to trigger regulatory T cell differentiation.

The Type-I interferon (IFN-I) response is the major outcome of stimulator of interferon genes (STING) activation in innate cells. STING is more abundantly expressed in adaptive T cells; nevertheless, its intrinsic function in T cells remains unclear. Intriguingly, we previously demonstrated that STING activation in T cells activates widespread IFN-independent activities, which stands in contrast to the well-known STING-mediated IFN response. Here, we have identified that STING activation induces regulatory T cells (Tregs) differentiation independently of IRF3 and IFN. Specifically, the translocation of STING from the endoplasmic reticulum to the Golgi activates mitogen-activated protein kinase (MAPK) activity, which subsequently triggers transcription factor cAMP response element-binding protein (CREB) activation. The activation of the STING-MAPK-CREB signaling pathway induces the expression of many cytokine genes, including interleukin-2 (IL-2) and transforming growth factor-beta 2 (TGF-ß2), to promote the Treg differentiation. Genetic knockdown of MAPK p38 or pharmacological inhibition of MAPK p38 or CREB markedly inhibits STING-mediated Treg differentiation. Administration of the STING agonist also promotes Treg differentiation in mice. In the Trex1-/- autoimmune disease mouse model, we demonstrate that intrinsic STING activation in CD4+ T cells can drive Treg differentiation, potentially counterbalancing the autoimmunity associated with Trex1 deficiency. Thus, STING-MAPK-CREB represents an IFN-independent signaling axis of STING that may have profound effects on T cell effector function and adaptive immunity.

The value of twinned pollinator-pollen metabarcoding: bumblebee pollination service is weakly partitioned within a UK grassland community.

Predicting ecological impact of declining bumblebee (Bombus) populations requires better understanding of interactions between pollinator partitioning of floral resources and plant partitioning of pollinator resources. Here, we combine Cytochrome Oxidase 1 (CO1) barcoding for bumblebee identification and rbcL metabarcoding of pollen carried by bees in three species-rich UK pastures. CO1 barcoding assigned 272 bees to eight species, with 33 individuals belonging to the cryptic Bombus lucorum complex (16 B. lucorum and 17 B. cryptarum). Seasonal bias in capture rates varied by species, with B. pratorum found exclusively in June/July and B. pascuorum more abundant in August. Pollen metabarcoding coupled with PERMANOVA and NMDS analyses revealed all bees carried several local pollen species and evidence of pollen resource partitioning between some species pairings, with Bombus pratorum carrying the most divergent pollen load. There was no evidence of resource partitioning between the two cryptic species present, but significantly divergent capture rates concorded with previous suggestions of separation on the basis of foraging behaviour being shaped by local/temporal differences in climatic conditions. Considering the bee carriage profile of pollen species revealed no significant difference between the nine most widely carried plant species. However, there was a sharp, tipping point change in community pollen carriage across all three sites that occurred during the transition between late July and early August. This transition resulted in a strong divergence in community pollen carriage between the two seasonal periods in both years. We conclude that the combined use of pollen and bee barcoding offers several benefits for further study of plant-pollinator interactions at the landscape scale.

Promoting Health Behavior Change in the Preconception Period: Combined Approach to Intervention Planning.

BACKGROUND: Half of women begin pregnancy above the healthy weight range, increasing the risk of complications and adversely affecting the lifelong health of their babies. Maternal obesity remains the strongest risk factor for offspring obesity across childhood, adolescence, and adulthood. Previous research suggests that women should be encouraged to be within a healthy weight range before conception to improve health outcomes. OBJECTIVE: We outlined the intervention planning and design process to develop an evidence-informed eHealth intervention to promote weight management. The intervention, based on psychological theories and behavior change techniques, has been developed for women affected by overweight or obesity who intend to become pregnant. The Begin Better web application is part of an integrated program being evaluated in a clinical trial to assess if weight management before pregnancy can influence clinical outcomes for mothers and babies. METHODS: Our intervention development process was guided by intervention mapping and person-based methods. This study documents steps 2 to 4 of a 6-step iterative intervention mapping approach informed by the Information-Motivation-Behavioral Skills model and the findings of a previous interview study. We defined behavior change objectives for each of the Information-Motivation-Behavioral Skills behavioral determinants as well as theory-based behavior change techniques and practical strategies. We also used persuasive system design principles to assist in translating these strategies into a digital environment. RESULTS: The resultant intervention comprises nutritional and physical activity content along with psychological strategies, which are notably absent from mainstream weight management programs. Strategies to increase motivation, garner social support, and promote self-care are integral to maintaining engagement with the intervention, which aims to improve lifestyle behaviors and enhance well-being. Important elements include tracking mechanisms for percentage progress toward goals to enable feedback on behaviors and outcomes; in-application messages of praise on entry of goals or habits; and strategies to prompt habit formation and action planning via small, easily achievable steps toward positive change. CONCLUSIONS: Design decisions and processes for idea generation about intervention content, format, and delivery are often not reported. In this study, we respond to this gap in the literature and outline a process that is potentially transferable to the development of other interventions.

Creating Healthy Change in the Preconception Period for Women with Overweight or Obesity: A Qualitative Study Using the Information-Motivation-Behavioural Skills Model.

Worldwide, half of women begin a pregnancy with overweight or obesity, which increases the risk of pregnancy and birth complications and adversely affects the lifelong health of the offspring. In order for metabolic changes to influence the gestational environment, research suggests that weight loss should take place before conception. This study aimed to understand women's emotional and social contexts, knowledge, motivations, skills and self-efficacy in making healthy change. Semi-structured interviews conducted with twenty-three women with overweight or obesity, informed by the Information-Motivation-Behavioural Skills (IMB) model, were analysed using reflexive thematic analysis. Information-related themes identified included poor health risk knowledge, healthy food decisions and health versus convenience. The Motivation themes comprised taking responsibility, flexible options, social expectations, interpersonal challenges and accountability. Behavioural Skills entailed themes such as the mental battle, time management, self-care and inspiration. An environmental factor was identified in affordability-limiting access to healthier alternatives. Women wanted simple, flexible options that considered family commitments, time and budgetary constraints. Unprompted, several mentioned the importance of psychological support in managing setbacks, stress and maintaining motivation. Strategies for enhancing self-efficacy and motivational support are required to enable longstanding health behaviour change. Findings will inform intervention mapping development of an eHealth solution for women preconception.

Replacing Sanger with Next Generation Sequencing to improve coverage and quality of reference DNA barcodes for plants.

We estimate the global BOLD Systems database holds core DNA barcodes (rbcL + matK) for about 15% of land plant species and that comprehensive species coverage is still many decades away. Interim performance of the resource is compromised by variable sequence overlap and modest information content within each barcode. Our model predicts that the proportion of species-unique barcodes reduces as the database grows and that 'false' species-unique barcodes remain >5% until the database is almost complete. We conclude the current rbcL + matK barcode is unfit for purpose. Genome skimming and supplementary barcodes could improve diagnostic power but would slow new barcode acquisition. We therefore present two novel Next Generation Sequencing protocols (with freeware) capable of accurate, massively parallel de novo assembly of high quality DNA barcodes of >1400 bp. We explore how these capabilities could enhance species diagnosis in the coming decades.