Identifying the transporters of different flavonoids in plants

We recently identified a new component of flavonoid transport pathways in Arabidopsis. The MATE protein FFT (Flower Flavonoid Transporter) is primarily found in guard cells and seedling roots, and mutation of the transporter results in floral and growth phenotypes. The nature of FFT’s substrate requires further exploration but our data suggest that it is a kaempferol diglucoside. Here we discuss potential partner H+-ATPases and possible redundancy among the close homologues within the large Arabidopsis MATE family

Using video feedback to improve early father-infant interaction: a pilot study.

Preventive interventions with parents of infants have tended to focus on mothers. Recent research focused on fathers suggests that their involvement in interventions might enhance effectiveness. One effective approach with mothers is the brief, home-based Video-feedback Intervention to promote Positive Parenting (VIPP). This paper is a report of a pilot study of VIPP with fathers to assess its feasibility. Five fathers were recruited from an existing longitudinal study of parents. The primary outcome was acceptability, assessed using a semi-structured questionnaire after completion of the intervention. All fathers completed all sessions of the intervention. Fathers rated the intervention as having had a significant impact on their understanding of their child's thoughts and feelings, and as having improved their communication and relationship with their baby. Fathers' feedback was generally positive. The flexibility to conduct sessions at home (or at fathers' places of work) and the flexible timing of sessions were identified as fundamental to successful delivery. The results of this pilot study are encouraging, as VIPP with fathers was feasible. In light of the modest sample size, and the use of a non-clinical sample, the intervention must be evaluated with larger, clinical samples to evaluate its efficacy with fathers

Maternal postnatal depression and anxiety and their association with child emotional negativity and behavior problems at two years

Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptom chronicity on children’s emotional and behavioral functioning at 24 months. Following postnatal screening mothers (n = 296) were identified as having MDD, GAD, MDD and GAD, or no disorder at 3 months postnatal; the average age was 32.3 (SD = 5.0), 91.9% self-identified as Caucasian, and 62.2% were married. Maternal disorder symptom severity was assessed by questionnaires and structured interview at 3, 6, 10, 14, and 24 months postpartum. At 24 months, child emotional negativity and behavior were assessed using questionnaires and by direct observation. Latent trait-state-occasion modeling was used to represent maternal disorder symptom chronicity; both stable trait and time-specific occasion portions of maternal symptomatology were examined in relation to child outcomes. Only the stable trait portion of maternal MDD and GAD symptom severity were related to maternal report of child behavior problems and higher levels of emotional negativity. Persistent maternal MDD, but not GAD, symptom severity was related to higher levels of child emotional negativity as measured observationally. These data suggest that children’s behavior problems and emotional negativity are adversely affected by persistent maternal depression, and possibly anxiety. This has implications for interventions to prevent negative effects of postnatal psychopathology on children

Attitudes and tolerance of private landowners shape the African wild dog conservation landscape in the greater Kruger National Park

The survival of wildlife ultimately relies on its acceptability to humans. The African wild dog Lycaon pictus is an endangered species that often comes into conflict with humans. Currently, the only viable population in South Africa resides in the Kruger National Park (KNP). To begin to understand the acceptability of wild dogs outside this important wild dog stronghold, we interviewed private landowners (n = 186) along the KNP western and southern boundaries. Respondents generally held positive attitudes towards wild dogs and had a good knowledge of them. Attitudes were also more positive when the property was part of a conservancy, indicating that the conservation landscape for wild dogs on private land outside the KNP is promising. However, the impact of edge effects such as disease transmission should not be ignored in future research, and creative solutions for mitigating these effects must be sought to ensure the future conservation of wild dogs.Jaguar Land Rover South Africa, Vaughan de la Harpe and his Climb for Kruger Wild Dogs Expedition, Richard Bosman and GCCL2 Management Services, and Rhodes University for the Henderson Prestigious Masters Postgraduate Scholarship.http://www.int-res.com/journals/esr/esr-homeam2018Mammal Research InstituteZoology and Entomolog

Predicting post one-year durability of glucose-lowering monotherapies in patients with newly-diagnosed type 2 diabetes mellitus – A MASTERMIND precision medicine approach (UKPDS 87)

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Aims: Predicting likely durability of glucose-lowering therapies for people with type 2 diabetes (T2D) could help inform individualised therapeutic choices. Methods: We used data from UKPDS patients with newly-diagnosed T2D randomised to first-line glucose-lowering monotherapy with chlorpropamide–glibenclamide–basal insulin or metformin. In 2339 participants who achieved one-year HbA1c values <7.5% (<59 mmol/mol)–we assessed relationships between one-year characteristics and time to monotherapy-failure (HbA1c ≥ 7.5% or requiring second-line therapy). Model validation was performed using bootstrap sampling. Results: Follow-up was median (IQR) 11.0 (8.0–14.0) years. Monotherapy-failure occurred in 72%–82%–75% and 79% for those randomised to chlorpropamide–glibenclamide–basal insulin or metformin respectively–after median 4.5 (3.0–6.6)–3.7 (2.6–5.6)–4.2 (2.7–6.5) and 3.8 (2.6– 5.2) years. Time-to-monotherapy-failure was predicted primarily by HbA1c and BMI values–with other risk factors varying by type of monotherapy–with predictions to within ±2.5 years for 55%–60%–56% and 57% of the chlorpropamide–glibenclamide–basal insulin and metformin monotherapy cohorts respectively. Conclusions: Post one-year glycaemic durability can be predicted robustly in individuals with newly-diagnosed T2D who achieve HbA1c values < 7.5% one year after commencing traditional monotherapies. Such information could be used to help guide glycaemic management for individual patients.Medical Research Council (MRC

Toward the Discovery of Vaccine Adjuvants: Coupling In Silico Screening and In Vitro Analysis of Antagonist Binding to Human and Mouse CCR4 Receptors

BACKGROUND: Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. METHODOLOGY: Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4(+) Tregs. SIGNIFICANCE: Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice