Substituted BEDT-TTF derivatives: synthesis, chirality, properties and potential applications

The increasing availability of functionalized BEDT-TTF derivatives in both racemic and enantiopure forms opens up great opportunities for preparing multifunctional materials and chiral conducting systems in the form of crystals, thin films and polymers. Functionalities such as amino and carboxyl will allow attachment to other molecular systems, while intermolecular interactions between substituents, e.g. hydrogen bonding and halegon- - - halegon interactions, provides additional tools for designing solid state radical cation structures. In this review the syntheses of substituted derivatives of BEDT-TTF and closely related donors are surveyed, along with the structures and properties of the radical cation salts so far prepared, as a stimulus for future application of these versatile and attractive molecules. Particular attention is paid to the preparation of single enantiomers, and to the stereochemical consequences of the synthetic procedures

An information theoretic characterisation of auditory encoding.

The entropy metric derived from information theory provides a means to quantify the amount of information transmitted in acoustic streams like speech or music. By systematically varying the entropy of pitch sequences, we sought brain areas where neural activity and energetic demands increase as a function of entropy. Such a relationship is predicted to occur in an efficient encoding mechanism that uses less computational resource when less information is present in the signal: we specifically tested the hypothesis that such a relationship is present in the planum temporale (PT). In two convergent functional MRI studies, we demonstrated this relationship in PT for encoding, while furthermore showing that a distributed fronto-parietal network for retrieval of acoustic information is independent of entropy. The results establish PT as an efficient neural engine that demands less computational resource to encode redundant signals than those with high information content

Engaging Families in Weight Management

Purpose: Approximately 50% of families who initiate a weight management programme (WMP) will not complete. It is fundamental to understand why participants initiate and complete a programme, and to ensure that programmes are effectively designed and delivered. This study examined the reasoning for family (young person and parent) engagement in three different and diverse WMPs. Methods: A multiple instrumental case study approach was employed. Three community-based WMPs participated: MoreLife, SHINE, and Weigh to Go. Clear design and implementation differences existed between WMPs. Multiple WMPs were recruited to examine the generalisability of research findings, and extract key features associated with participant engagement. Thirty families took part (~10 per programme). Data were collected early in the programme (0-2 weeks) and immediately after completion or dropout (within two weeks). Young people took part in a Participatory Action Research (PAR) session (interactive activities to generate meaningful information), and parents completed semi-structured interviews. A deductive line of inquiry was used; questions were based upon participant characteristics, environmental interactions, psychological processes and programme interactions. Interview data was transcribed verbatim and analysed alongside the PAR data using content and thematic analysis (themes presented in italics). Results: Preliminary findings indicate that families often engage in a WMP for non-weight related reasons. Such reasons include: management of mental health, to improve self -esteem, and to create friendships. Families remain in a WMP when: the programme suits their needs, they fit in amongst other participants, strong relationships are fostered with staff, and have strong support networks. Numerous families completing programmes prioritised WMP attendance above other leisure activities, and had plans in place to ensure they could attend each session. Low engagement was due to situational factors (e.g. logistic barriers [transport, timing…]) rather than programme dissatisfaction. Conclusions: Families attend community-based WMPs for reasons beyond weight management. Additionally, the families identified unique WMP features (e.g. maintenance programmes and non-clinical staff) which encourage programme attendance. Such features can be replicated in multiple, diverse settings. Understanding participant engagement is critical to designing and implementing efficacious WMPs

fMRI evidence for a cortical hierarchy of pitch pattern processing

Pitch patterns, such as melodies, consist of two levels of structure: a global level, comprising the pattern of ups and downs, or contour; and a local level, comprising the precise intervals that make up this contour. An influential neuropsychological model suggests that these two levels of processing are hierarchically linked, with processing of the global structure occurring within the right hemisphere in advance of local processing within the left. However, the predictions of this model and its anatomical basis have not been tested in neurologically normal individuals. The present study used fMRI and required participants to listen to consecutive pitch sequences while performing a same/different one-back task. Sequences, when different, either preserved (local) or violated (global) the contour of the sequence preceding them. When the activations for the local and global conditions were contrasted directly, additional activation was seen for local processing in right planum temporale and posterior superior temporal sulcus (pSTS). The presence of additional activation for local over global processing supports the hierarchical view that the global structure of a pitch sequence acts as a “framework” on which the local detail is subsequently hung. However, the lateralisation of activation seen in the present study, with global processing occurring in left pSTS and local processing occurring bilaterally, differed from that predicted by the neuroanatomical model. A re-examination of the individual lesion data on which the neuroanatomical model is based revealed that the lesion data equally well support the laterality scheme suggested by our data. While the present study supports the hierarchical view of local and global processing, there is an evident need for further research, both in patients and neurologically normal individuals, before an understanding of the functional lateralisation of local and global processing can be considered established

Bench-to-bedside review: Inhaled nitric oxide therapy in adults

Nitric oxide (NO) is an endogenous mediator of vascular tone and host defence. Inhaled nitric oxide (iNO) results in preferential pulmonary vasodilatation and lowers pulmonary vascular resistance. The route of administration delivers NO selectively to ventilated lung units so that its effect augments that of hypoxic pulmonary vasoconstriction and improves oxygenation. This 'Bench-to-bedside' review focuses on the mechanisms of action of iNO and its clinical applications, with emphasis on acute lung injury and the acute respiratory distress syndrome. Developments in our understanding of the cellular and molecular actions of NO may help to explain the hitherto disappointing results of randomised controlled trials of iNO

eQED: an efficient method for interpreting eQTL associations using protein networks

Analysis of expression quantitative trait loci (eQTLs) is an emerging technique in which individuals are genotyped across a panel of genetic markers and, simultaneously, phenotyped using DNA microarrays. Because of the spacing of markers and linkage disequilibrium, each marker may be near many genes making it difficult to finely map which of these genes are the causal factors responsible for the observed changes in the downstream expression. To address this challenge, we present an efficient method for prioritizing candidate genes at a locus. This approach, called ‘eQTL electrical diagrams' (eQED), integrates eQTLs with protein interaction networks by modeling the two data sets as a wiring diagram of current sources and resistors. eQED achieved a 79% accuracy in recovering a reference set of regulator–target pairs in yeast, which is significantly higher than the performance of three competing methods. eQED also annotates 368 protein–protein interactions with their directionality of information flow with an accuracy of approximately 75%

Do parent and child outcome expectations align when attending a weight management programme?

Background: Childhood weight management programmes (WMP) are used within the UK to stem the rising prevalence of pediatric obesity. These WMPs often provide children and young people (CYP) and their family’s with methods of stabilising and reducing the severity of the weight issue. That said, low engagement in WMPs is often encountered but the reasoning is not well known. Misaligned and unrealistic outcome expectations have been hypothesised as a reason for low engagement. This paper explores 1) the parent and CYP outcome expectations of a WMP, and 2) the qualitative level of agreement between parent and CYP expectations. Methods: 30 families were recruited from three, UK-based WMPs (10 families per programme). Qualitative research methods were used to examine both the parent and CYP outcome expectations. Participatory research methods were used with CYP and semi-structured interviews with parents. Data were collected from parents and CYP independently, and notably, were collected from participants within two weeks of starting a WMP. Data were analysed using thematic analysis. In separate analyses, the alignment between parent and CYP responses were examined. Results: Preliminary findings indicate that parents reported 24 different outcome expectations (varying from ‘anger management’ to ‘weight management [not loss]’ to ‘understanding consequences of obesity’), whilst CYP reported 25 expectations (ranging from ‘aesthetic improvement’ to ‘physical activity opportunities’ to ‘not wanting to attend’). Weight loss was the most cited outcome expectation amongst parents and CYP, however friendship, CYP confidence, dietary education, and the reinforcement of parent messages were also strongly cited. Of note, weight loss was not always cited as the primary outcome expectation. The qualitative level of agreement between CYP and parents shall be reported. Conclusions: Families do not always initiate a WMP for the sole purpose of weight loss and management. Practitioners would benefit from understanding what families hope to achieve during their attendance, and subsequently tailor the programme, comments and feedback to reflect this. By tailoring messages and feedback directly to the family expectations, families may see a greater benefit in WMP attendance and therefore be encouraged to persist in treatment. Attendance and weight-related outcomes are strongly correlated

BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production.

BACKGROUND: Bone morphogenetic proteins (BMPs) and their receptors, such as bone morphogenetic protein receptor (BMPR) II, have been implicated in a wide variety of disorders including pulmonary arterial hypertension (PAH). Similarly, endothelin-1 (ET-1), a mitogen and vasoconstrictor, is upregulated in PAH and endothelin receptor antagonists are used in its treatment. We sought to determine whether there is crosstalk between BMP signalling and the ET-1 axis in human pulmonary artery endothelial cells (HPAECs), possible mechanisms involved in such crosstalk and functional consequences thereof. METHODOLOGY/PRINCIPAL FINDING: Using western blot, real time RT-PCR, ELISA and small RNA interference methods we provide evidence that in HPAECs BMP-9, but not BMP-2, -4 and -6 significantly stimulated ET-1 release under physiological concentrations. This release is mediated by both Smad1 and p38 MAPK and is independent of the canonical Smad4 pathway. Moreover, knocking down the ALK1 receptor or BMPR II attenuates BMP-9 stimulated ET-1 release, whilst causing a significant increase in prepro ET-1 mRNA transcription and mature peptide release. Finally, BMP-9 induced ET-1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation. CONCLUSIONS/SIGNIFICANCE: Although our data does not support an important role for BMP-9 as a source of increased endothelial ET-1 production seen in human PAH, BMP-9 stimulated ET-1 production is likely to be important in angiogenesis and vascular stability. However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH

31P magnetic resonance spectroscopy as a predictor of efficacy in photodynamic therapy using differently charged zinc phthalocyanines

Photodynamic therapy (PDT) is a developing approach to the treatment of solid tumours which requires the combined action of light and a photosensitizing drug in the presence of adequate levels of molecular oxygen. We have developed a novel series of photosensitizers based on zinc phthalocyanine which are water-soluble and contain neutral (TDEPC), positive (PPC) and negative (TCPC) side-chains. The PDT effects of these sensitizers have been studied in a mouse model bearing the RIF-1 murine fibrosarcoma line studying tumour regrowth delay, phosphate metabolism by magnetic resonance spectroscopy (MRS) and blood flow, using D2O uptake and MRS. The two main aims of the study were to determine if MRS measurements made at the time of PDT treatment could potentially be predictive of ultimate PDT efficacy and to assess the effects of sensitizer charge on PDT in this model. It was clearly demonstrated that there is a relationship between MRS measurements during and immediately following PDT and the ultimate effect on the tumour. For all three drugs, tumour regrowth delay was greater with a 1-h time interval between drug and light administration than with a 24-h interval. In both cases, the order of tumour regrowth delay was PPC > TDEPC = TCPC (though the data at 24 h were not statistically significant). Correspondingly, there were greater effects on phosphate metabolism (measured at the time of PDT or soon after) for the 1-h than for the 24-h time interval. Again effects were greatest with the cationic PPC, with the sequence being PPC > TDEPC > TCPC. A parallel sequence was observed for the blood flow effects, demonstrating that reduction in blood flow is an important factor in PDT with these sensitizers. © 1999 Cancer Research Campaig