Using electrostatic potentials to predict DNA-binding sites on DNA-binding proteins

A method to detect DNA-binding sites on the surface of a protein structure is important for functional annotation. This work describes the analysis of residue patches on the surface of DNA-binding proteins and the development of a method of predicting DNA-binding sites using a single feature of these surface patches. Surface patches and the DNA-binding sites were initially analysed for accessibility, electrostatic potential, residue propensity, hydrophobicity and residue conservation. From this, it was observed that the DNA-binding sites were, in general, amongst the top 10% of patches with the largest positive electrostatic scores. This knowledge led to the development of a prediction method in which patches of surface residues were selected such that they excluded residues with negative electrostatic scores. This method was used to make predictions for a data set of 56 non-homologous DNA-binding proteins. Correct predictions made for 68% of the data set

Does written emotional disclosure improve the psychological and physical health of caregivers? A systematic review and meta-analysis

There are 5.8 million caregivers providing support to the infirm, disabled or elderly in the United Kingdom. Caregivers experience adverse physical and mental health outcomes and increased mortality. Low cost, effective interventions are needed to increase the wellbeing of caregivers. Written emotional disclosure (WED) has been shown to improve health in a range of populations. This systematic review and meta-analysis aimed to establish whether WED improves the psychological and physical health of caregivers. Searches were conducted in Medline, EMBASE, CINAHL, BNI, PsycINFO, Cochrane Library from 1986 to 2015. Ten trials investigating WED (625 participants) met the inclusion criteria. Results from four studies (n=118) indicated that WED reduces trauma (SMD=-0.46, 95% CI -0.82, -0.09). Data from three studies (n=102) suggest that WED improves general psychological health (SMD=-0.46, 95% CI -0.86, -0.06). There was no evidence that WED improves depression, anxiety, physical symptoms, quality of life or burden. Observations suggest WED may be more effective for caregivers of less than 5 years. Studies were highly heterogeneous in regards to caregiver age, relationship to care recipient, impairment of care recipient, follow up period and outcome measures, with high or unclear bias often observed. More rigorous RCTs, with clearly described interventions and standardised outcome measures, are needed to confirm these findings

Immediate replacement of fishing with dairying by the earliest farmers of the NE Atlantic archipelagos

The appearance of farming, from its inception in the Near East around 12 000 years ago, finally reached the northwestern extremes of Europe by the fourth millennium BC or shortly thereafter. Various models have been invoked to explain the Neolithization of northern Europe; however, resolving these different scenarios has proved problematic due to poor faunal preservation and the lack of specificity achievable for commonly applied proxies. Here, we present new multi-proxy evidence, which qualitatively and quantitatively maps subsistence change in the northeast Atlantic archipelagos from the Late Mesolithic into the Neolithic and beyond. A model involving significant retention of hunter–gatherer–fisher influences was tested against one of the dominant adoptions of farming using a novel suite of lipid biomarkers, including dihydroxy fatty acids, ω-(o-alkylphenyl)alkanoic acids and stable carbon isotope signatures of individual fatty acids preserved in cooking vessels. These new findings, together with archaeozoological and human skeletal collagen bulk stable carbon isotope proxies, unequivocally confirm rejection of marine resources by early farmers coinciding with the adoption of intensive dairy farming. This pattern of Neolithization contrasts markedly to that occurring contemporaneously in the Baltic, suggesting that geographically distinct ecological and cultural influences dictated the evolution of subsistence practices at this critical phase of European prehistory

Acoustofluidic measurements on polymer-coated microbubbles: primary and secondary Bjerknes forces

The acoustically-driven dynamics of isolated particle-like objects in microfluidic environments is a well-characterised phenomenon, which has been the subject of many studies. Conversely, very few acoustofluidic researchers looked at coated microbubbles, despite their widespread use in diagnostic imaging and the need for a precise characterisation of their acoustically-driven behaviour, underpinning therapeutic applications. The main reason is that microbubbles behave differently, due to their larger compressibility, exhibiting much stronger interactions with the unperturbed acoustic field (primary Bjerknes forces) or with other bubbles (secondary Bjerknes forces). In this paper, we study the translational dynamics of commercially-available polymer-coated microbubbles in a standing-wave acoustofluidic device. At increasing acoustic driving pressures, we measure acoustic forces on isolated bubbles, quantify bubble-bubble interaction forces during doublet formation and study the occurrence of sub-wavelength structures during aggregation. We present a dynamic characterisation of microbubble compressibility with acoustic pressure, highlighting a threshold pressure below which bubbles can be treated as uncoated. Thanks to benchmarking measurements under a scanning electron microscope, we interpret this threshold as the onset of buckling, providing a quantitative measurement of this parameter at the single-bubble level. For acoustofluidic applications, our results highlight the limitations of treating microbubbles as a special case of solid particles. Our findings will impact applications where knowing the buckling pressure of coated microbubbles has a key role, like diagnostics and drug delivery

Distraction Control Processes in Free Recall: Costs and Benefits to Performance

How is semantic memory influenced by individual differences under conditions of distraction? This question was addressed by observing how visual target words—drawn from a single category—were recalled whilst ignoring spoken distracter words that were either members of the same, or members of a different (single) category. Distracter words were presented either synchronously or asynchronously with target words. Recall performance was correlated with participants’ working memory capacity (WMC), which was taken to be an index of the capacity for distracter inhibition. Distraction was greater from semantically similar words and distraction was greater when the words were presented synchronously. WMC was related to disruption only with synchronous, not asynchronous, presentation. Subsequent experiments found more distracter inhibition – as measured by subsequent negative priming of distracters – amongst individuals with higher WMC but this may be dependent on targets and distracters being comparable category exemplars: With less dominant category members as distracters, target recall was impaired – relative to control – only amongst individuals with low WMC. The results demonstrate distracter inhibition occurring only in conditions where target-distracter selection is challenging. Inhibition incurs costs to subsequent performance, but there is an immediate price for not inhibiting

Determining optimal outcome measures in a trial investigating no routine gastric residual volume measurement in critically ill children

Background Choosing trial outcome measures is important. When outcomes are not clinically relevant or important to parents/patients, trial evidence is less likely to be implemented into practice. This study aimed to determine optimal outcome measures for a trial of no routine gastric residual volume measurement in critically ill children. Methods: A mixed methods approach: a focused literature review, parent and clinician interviews, a modified two-round Delphi and a stakeholder consensus meeting. Results: The review generated 13 outcomes. 14 Pediatric Intensive Care Unit (PICU) parents proposed 3 additional outcomes, these 16 were then rated by 28 clinicians in Delphi round 1. Six further outcomes were proposed, and 22 outcomes were rated in the second round. No items were voted ‘consensus out’. The 18 ‘no-consensus’ items were voted in a face-to-face meeting by 30 participants. The final 12 outcome measures were: Time to reach energy targets; ventilator associated pneumonia; vomiting; time enteral feeds withheld per 24 hour; necrotizing enterocolitis; length of invasive ventilation; PICU length of stay; mortality; change in weight and markers of feed intolerance: parenteral nutrition administered; feed formula altered and changing to post-pyloric feeds all secondary to feed intolerance. Conclusion: We have identified 12 outcomes for a trial of no gastric residual volume measurement through a multi-stage process, seeking views of parents and clinicians. Clinical Relevancy statement: Twelve relevant outcomes have been identified for a trial of no routine gastric residual volume measurement in critically ill children

Modulation of endoglin expression in islets of langerhans by VEGF reveals a novel regulator of islet endothelial cell function

Background: endoglin/CD105 is an auxiliary receptor for transforming growth factor-? with established roles in vascular remodelling. It has recently been shown that heterozygous endoglin deficiency in mice decreases insulin secretion in an animal model of obesity, highlighting a potential role for endoglin in the regulation of islet function. We have previously identified two different populations of endoglin expressing cells in human and mouse islets which are: (i) endothelial cells (ECs) and (ii) islet mesenchymal stromal cells. The contribution of islet EC endoglin expression to islet development and sensitivity to VEGF is unknown and is the focus of this study.Results: in vitro culture of mouse islets with VEGF164 for 48 h increased endoglin mRNA levels above untreated controls but VEGF did not modulate VEGFR2, CD31 or CD34 mRNA expression or islet viability. Removal of EC-endoglin expression in vivo reduced islet EC area but had no apparent effect on islet size or architecture.Conclusion: EC-specific endoglin expression in islets is sensitive to VEGF and plays partial roles in driving islet vascular development, however such regulation appears to be distinct to mechanisms required to modulate islet viability and siz