The role of negative maternal affective states and infant temperament in early interactions between infants with cleft lip and their mothers

OBJECTIVES: The study examined the early interaction between mothers and their infants with cleft lip, assessing the role of maternal affective state and expressiveness and differences in infant temperament. METHODS: Mother-infant interactions were assessed in 25 2-month-old infants with cleft lip and 25 age-matched healthy infants. Self-report and behavioral observations were used to assess maternal depressive symptoms and expressions. Mothers rated infant temperament. RESULTS: Infants with cleft lip were less engaged and their mothers showed more difficulty in interaction than control group dyads. Mothers of infants with cleft lip displayed more negative affectivity, but did not report more self-rated depressive symptoms than control group mothers. No group differences were found in infant temperament. CONCLUSIONS: In order to support the mother's experience and facilitate her ongoing parental role, findings highlight the importance of identifying maternal negative affectivity during early interactions, even when they seem have little awareness of their depressive symptoms.

Modulation of endothelial cell KCa3.1 Channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries

Arterial hyperpolarization to acetylcholine (ACh) reflects coactivation of KCa3.1 (IKCa) channels and KCa2.3 (SKCa) channels in the endothelium that transfers through myoendothelial gap junctions and diffusible factor(s) to affect smooth muscle relaxation (endothelium-derived hyperpolarizing factor [EDHF] response). However, ACh can differentially activate KCa3.1 and KCa2.3 channels, and we investigated the mechanisms responsible in rat mesenteric arteries. KCa3.1 channel input to EDHF hyperpolarization was enhanced by reducing external [Ca2+]o but blocked either with forskolin to activate protein kinase A or by limiting smooth muscle [Ca2+]i increases stimulated by phenylephrine depolarization. Imaging [Ca2+]i within the endothelial cell projections forming myoendothelial gap junctions revealed increases in cytoplasmic [Ca2+]i during endothelial stimulation with ACh that were unaffected by simultaneous increases in muscle [Ca2+]i evoked by phenylephrine. If gap junctions were uncoupled, KCa3.1 channels became the predominant input to EDHF hyperpolarization, and relaxation was inhibited with ouabain, implicating a crucial link through Na+/K+-ATPase. There was no evidence for an equivalent link through KCa2.3 channels nor between these channels and the putative EDHF pathway involving natriuretic peptide receptor-C. Reconstruction of confocal z-stack images from pressurized arteries revealed KCa2.3 immunostain at endothelial cell borders, including endothelial cell projections, whereas KCa3.1 channels and Na+/K+-ATPase {alpha}2/{alpha}3 subunits were highly concentrated in endothelial cell projections and adjacent to myoendothelial gap junctions. Thus, extracellular [Ca2+]o appears to modify KCa3.1 channel activity through a protein kinase A-dependent mechanism independent of changes in endothelial [Ca2+]i. The resulting hyperpolarization links to arterial relaxation largely through Na+/K+-ATPase, possibly reflecting K+ acting as an EDHF. In contrast, KCa2.3 hyperpolarization appears mainly to affect relaxation through myoendothelial gap junctions. Overall, these data suggest that K+ and myoendothelial coupling evoke EDHF-mediated relaxation through distinct, definable pathways.

Thromboxane A2 inhibition of SKCa after NO synthase block in rat middle cerebral artery

NO/prostanoid independent, EDHF-mediated hyperpolarization and dilation in rat middle cerebral arteries is mediated solely by endothelial cell IK(Ca). However, when the NO-pathway is also active, both SK(Ca) and IK(Ca) contribute to EDHF responses. As the SK(Ca) component can be inhibited by stimulation of thromboxane A(2) (TxA(2)) TP receptors and NO has the potential ability to inhibit thromboxane synthesis, we investigated whether TxA(2) might explain loss of functional input from SK(Ca) during NOS inhibition in cerebral arteries. EXPERIMENTAL APPROACH: Rat middle cerebral arteries were mounted in a wire myograph. Endothelium-dependent responses to the PAR2 agonist, SLIGRL were assessed as simultaneous changes in smooth muscle membrane potential and tension. KEY RESULTS: Responses were obtained in the presence of L-NAME as appropriate. Inhibition of TP receptors with either ICI 192,605 or SQ 29,548, did not affect EDHF mediated hyperpolarization and relaxation, but in their presence neither TRAM-34 nor apamin (to block IK(Ca) and SK(Ca) respectively) individually affected the EDHF response. However, in combination they virtually abolished it. Similar effects were obtained in the presence of the thromboxane synthase inhibitor, furegrelate, which additionally revealed an iberiotoxin-sensitive residual EDHF hyperpolarization and relaxation in the combined presence of TRAM-34 and apamin. CONCLUSIONS AND IMPLICATIONS: In the rat middle cerebral artery, inhibition of NOS leads to a loss of the SK(Ca) component of EDHF responses. Either antagonism of TP receptors or block of thromboxane synthase restores an input through SK(Ca). These data indicate that NO normally enables SK(Ca) activity in rat middle cerebral arteries.

Evidence for involvement of both IKCa and SKCa channels in hyperpolarizing responses of the rat middle cerebral artery

Endothelium-derived hyperpolarizing factor responses in the rat middle cerebral artery are blocked by inhibiting IKCa channels alone, contrasting with peripheral vessels where block of both IKCa and SKCa is required. As the contribution of IKCa and SKCa to endothelium-dependent hyperpolarization differs in peripheral arteries, depending on the level of arterial constriction, we investigated the possibility that SKCa might contribute to equivalent hyperpolarization in cerebral arteries under certain conditions. METHODS: Rat middle cerebral arteries (approximately 175 microm) were mounted in a wire myograph. The effect of KCa channel blockers on endothelium-dependent responses to the protease-activated receptor 2 agonist, SLIGRL (20 micromol/L), were then assessed as simultaneous changes in tension and membrane potential. These data were correlated with the distribution of arterial KCa channels revealed with immunohistochemistry. RESULTS: SLIGRL hyperpolarized and relaxed cerebral arteries undergoing variable levels of stretch-induced tone. The relaxation was unaffected by specific inhibitors of IKCa (TRAM-34, 1 micromol/L) or SKCa (apamin, 50 nmol/L) alone or in combination. In contrast, the associated smooth-muscle hyperpolarization was inhibited, but only with these blockers in combination. Blocking nitric oxide synthase (NOS) or guanylyl cyclase evoked smooth-muscle depolarization and constriction, with both hyperpolarization and relaxation to SLIGRL being abolished by TRAM-34 alone, whereas apamin had no effect. Immunolabeling showed SKCa and IKCa within the endothelium. CONCLUSIONS: In the absence of NO, IKCa underpins endothelium-dependent hyperpolarization and relaxation in cerebral arteries. However, when NOS is active SKCa contributes to hyperpolarization, whatever the extent of background contraction. These changes may have relevance in vascular disease states where NO release is compromised and when the levels of SKCa expression may be altered.

Can REDD+ reconcile local priorities and needs with global mitigation benefits? lessons from Angai Forest, Tanzania

The scope of the reducing emissions from deforestation and forest degradation (REDD) mechanism has broadened REDD+ to accommodate different country interests such as natural forests, protected areas, as well as forests under community-based management. In Tanzania the REDD+ mechanism is still under development and pilot projects are at an early stage. In this paper, we seek to understand how local priorities and needs could be met in REDD+ implementation and how these expectations match with global mitigation benefits. We examine the local priorities and needs in the use of land and forest resources in the Angai Villages Land Forest Reserve (AVLFR) in the Liwale District of Lindi Region in Tanzania. Primary data was collected in two villages, Mihumo and Lilombe, using semistructured key informant interviews and participatory rural appraisal methods. In addition, the key informant interviews were conducted with other village, district, and national level actors, as well as international donors. Findings show that in the two communities REDD+ is seen as something new and is generating new expectations among communities. However, the Angai villagers highlight three key priorities that have yet to be integrated into the design of REDD+: water scarcity, rural development, and food security. At the local level improved forest governance and sustainable management of forest resources have been identified as one way to achieve livelihood diversification. Although the national goals of REDD+ include poverty reduction, these goals are not necessarily conducive to the goals of these communities. There exist both structural and cultural limits to the ability of the Angai villages to implement these goals and to improve forestry governance. Given the vulnerability to current and future climate variability and change it will be important to consider how the AVLFR will be managed and for whose benefit?

Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries

Background and Purpose: Calcitonin gene‐related peptide (CGRP) is a potent vasodilator, implicated in the pathogenesis of migraine. CGRP activates a receptor complex comprising, calcitonin receptor‐like receptor (CLR) and receptor activity‐modifying protein 1 (RAMP1). In vitro studies indicate recycling of CLR•RAMP1 is regulated by degradation of CGRP in early endosomes by endothelin‐converting enzyme‐1 (ECE‐1). However, it is not known if ECE‐1 regulates the resensitization of CGRP‐induced responses in functional arterial tissue. Experimental Approach: CLR, ECE‐1a‐d and RAMP1 expression in rat mesenteric artery smooth muscle cells (RMA‐SMCs) and mesenteric arteries was analyzed by RT‐PCR and by immunofluorescence and confocal microscopy. CGRP‐induced signaling in cells was examined by measuring cAMP production and ERK activation. CGRP‐induced relaxation of arteries was measured by isometric wire myography. ECE‐1 was inhibited using the specific inhibitor, SM‐19712. Key Results: RMA‐SMCs and arteries contained mRNA for CLR, ECE‐1a‐d and RAMP1. ECE‐1 was present in early endosomes of RMA‐SMCs and in the smooth muscle layer of arteries. CGRP induced endothelium‐independent relaxation of arteries. ECE‐1 inhibition had no effect on initial CGRP‐induced responses but reduced cAMP generation in RMA‐SMCs and vasodilation in mesenteric arteries responses to subsequent CGRP challenges. Conclusions and Implications: ECE‐1 regulates the resensitization of responses to CGRP in RMA‐SMCs and mesenteric arteries. CGRP‐induced relaxation does not involve endothelium‐derived pathways. This is the first report of ECE‐1 regulating CGRP responses in SMCs and arteries. ECE‐1 inhibitors may attenuate an important vasodilatory pathway, implicated in primary headaches and may represent a new therapeutic approach for the treatment of migraine.

Behaviour change in the UK climate debate : an assessment of responsibility, agency and political dimensions

This paper explores the politics around the role of agency in the UK climate change debate. Government interventions on the demand side of consumption have increasingly involved attempts to obtain greater traction with the values, attitudes and beliefs of citizens in relation to climate change and also in terms of influencing consumer behaviour at an individual level. With figures showing that approximately 40% of the UK’s carbon emissions are attributable to household and transport behaviour, policy initiatives have progressively focused on the facilitation of “sustainable behaviours”. Evidence suggests however, that mobilisation of pro-environmental attitudes in addressing the perceived “value-action gap” has so far had limited success. Research in this field suggests that there is a more significant and nuanced “gap” between context and behaviour; a relationship that perhaps provides a more adroit reflection of reasons why people do not necessarily react in the way that policy-makers anticipate. Tracing the development of the UK Government’s behaviour change agenda over the last decade, we posit that a core reason for the limitations of this programme relates to an excessively narrow focus on the individual. This has served to obscure some of the wider political and economic aspects of the debate in favour of a more simplified discussion. The second part of the paper reports findings from a series of focus groups exploring some of the wider political views that people hold around household energy habits, purchase and use of domestic appliances, and transport behaviour-and discusses these insights in relation to the literature on the agenda’s apparent limitations. The paper concludes by considering whether the aims of the Big Society approach (recently established by the UK’s Coalition Government) hold the potential to engage more directly with some of these issues or whether they merely constitute a “repackaging” of the individualism agenda.

Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries

Background: In rat middle cerebral and mesenteric arteries the KCa2.3 component of endothelium-dependent hyperpolarization (EDH) is lost following stimulation of thromboxane (TP) receptors, an effect that may contribute to the endothelial dysfunction associated with cardiovascular disease. In cerebral arteries, KCa2.3 loss is associated with NO synthase inhibition, but is restored if TP receptors are blocked. The Rho/Rho kinase pathway is central for TP signalling and statins indirectly inhibit this pathway. The possibility that Rho kinase inhibition and statins sustain KCa2.3 hyperpolarization was investigated in rat middle cerebral arteries (MCA). Methods: MCAs were mounted in a wire myograph. The PAR2 agonist, SLIGRL was used to stimulate EDH responses, assessed by simultaneous measurement of smooth muscle membrane potential and tension. TP expression was assessed with rt-PCR and immunofluorescence. Results: Immunofluorescence detected TP in the endothelial cell layer of MCA. Vasoconstriction to the TP agonist, U46619 was reduced by Rho kinase inhibition. TP receptor stimulation lead to loss of KCa2.3 mediated hyperpolarization, an effect that was reversed by Rho kinase inhibitors or simvastatin. KCa2.3 activity was lost in L-NAME-treated arteries, but was restored by Rho kinase inhibition or statin treatment. The restorative effect of simvastatin was blocked after incubation with geranylgeranyl-pyrophosphate to circumvent loss of isoprenylation. Conclusions: Rho/Rho kinase signalling following TP stimulation and L-NAME regulates endothelial cell KCa2.3 function. The ability of statins to prevent isoprenylation and perhaps inhibit of Rho restores/protects the input of KCa2.3 to EDH in the MCA, and represents a beneficial pleiotropic effect of statin treatment.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer overall performance by adults with ASC (p<0.001) compared to the control group. When the 6 distinct basic emotions were analysed separately, the ASC group showed impaired performance across five out of six expressions (happy, sad, angry, afraid and disgusted). Parents of a child with ASC were not significantly worse than controls at recognising any of the basic emotions, after controlling for age and non-verbal IQ (all p>0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p<0.05) but not for self-reported empathy (p>0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed.

‘Purpose’ as a way of helping white trainee history teachers engage with diversity issues

Based on a three year action research project, this study examines one strand of that research, namely the impact that ‘purpose’, i.e. exploring the range of rationales for studying a subject, has in helping white trainee teachers embrace cultural and ethnic diversity within their teaching. Through ‘purpose’ trainees explored different reasons why history should be taught (and by implication what content should be taught and how it should be taught) and the relationship of these reasons to diversity. Focusing on ‘purpose’ appears to have a positive impact on many trainees from white, mono-ethnic backgrounds, enabling them to bring diversity into the school curriculum, in this case history teaching. It offers one way to counter concerns about issues of ‘whiteness’ in the teaching profession and by teaching a more relevant curriculum has a potential positive impact on the achievement of students from minority ethnic backgrounds.

Mapping evidence gaps in anti-corruption: assessing the state of the operationally relevant evidence on donors' actions and approaches to reducing corruption

This paper charts the current evidence on effectiveness of different anti-corruption reforms, and identifies significant evidence gaps. Despite a substantial amount of literature on corruption, this review found very few studies focusing on anti-corruption reforms, and even fewer that credibly assess issues of effectiveness and impact. The evidence was strong for only two types of interventions: public financial management (PFM) reforms and supreme audit institutions (SAIs). For PFM, the evidence in general showed positive results, whereas the effectiveness was mixed for SAIs. No strong evidence indicates that any of the interventions pursued have been ineffective, but there is fair evidence that anti-corruption authorities, civil service reforms and the use of corruption conditionality in aid allocation decisions in general have not been effective. The paper advocates more operationally-relevant research and rigorous evaluations to build up the missing evidence base, particularly in conflict-afflicted states, in regards to the private sector, and on the interactions and interdependencies between different anti-corruption interventions.

Managing the nutrition of plants and people

One definition of food security is having sufficient, safe, and nutritious food to meet dietary needs. This paper highlights the role of plant mineral nutrition in food production, delivering of essential mineral elements to the human diet, and preventing harmful mineral elements entering the food chain. To maximise crop production, the gap between actual and potential yield must be addressed. This gap is 15–95% of potential yield, depending on the crop and agricultural system. Current research in plant mineral nutrition aims to develop appropriate agronomy and improved genotypes, for both infertile and productive soils, that allow inorganic and organic fertilisers to be utilised more efficiently. Mineral malnutrition affects two-thirds of the world's population. It can be addressed by the application of fertilisers, soil amelioration, and the development of genotypes that accumulate greater concentrations of mineral elements lacking in human diets in their edible tissues. Excessive concentrations of harmful mineral elements also compromise crop production and human health. To reduce the entry of these elements into the food chain, strict quality requirements for fertilisers might be enforced, agronomic strategies employed to reduce their phytoavailability, and crop genotypes developed that do not accumulate high concentrations of these elements in edible tissues.