The roles of family history of dyslexia, language, speech production and phonological processing in predicting literacy progress

It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6-year-old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. Word reading and spelling were retested 6 months later, and text reading accuracy and reading comprehension were tested 3 years later. The children with FRD were at increased risk of developing difficulties in reading accuracy, but not reading comprehension. Four groups were compared: good and poor readers with and without FRD. In most cases good readers outperformed poor readers regardless of family history, but there was an effect of family history on naming and nonword repetition regardless of literacy outcome, suggesting a role for speech production skills as an endophenotype of dyslexia. Phonological processing predicted spelling, while language predicted text reading accuracy and comprehension. FRD was a significant additional predictor of reading and spelling after controlling for speech production, language and phonological processing, suggesting that children with FRD show additional difficulties in literacy that cannot be fully explained in terms of their language and phonological skills. It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6-year-old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. © 2014 John Wiley & Sons Ltd.

A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling:implications for family B G-protein-coupled receptors

Calcitonin receptor like-receptor is a family B G-protein coupled receptor (GPCR). It requires receptor activity modifying protein (RAMP) 1 to give a calcitonin gene-related peptide (CGRP) receptor. Little is known of how members of this receptor family function. Proline residues often form important kinks in alpha-helices. Therefore, all proline residues within the transmembrane helices of the receptor (Pro241, Pro244 in helix 4, Pro275 in helix 5, Pro321 and Pro331 in helix 6) were mutated to alanine. Pro241 Pro275, and Pro321 are highly conserved throughout all family B GPCRs. The binding of CGRP and its ability to stimulate cAMP production were investigated in mutant and wild-type receptors after transient transfection into COS-7 cells with RAMP1. The P321A mutation significantly decreased the pEC(50) for CGRP and reduced its affinity but did not change cell-surface expression. Antagonist binding [CGRP(8-37) and 1-piperidinecarboxamide N-[2-[[5amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3 5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quina zolinyl) (BIBN4096BS)] was little altered by the mutation. Adrenomedullin-mediated signaling was disrupted when P321A was coexpressed with RAMP1, RAMP2, or RAMP3. The P331A mutant produced a moderate reduction in CGRP binding and receptor activation. Mutation of the other residues had no effect on receptor function. Thus, Pro321 and Pro331 are required for agonist binding and receptor activation. Modeling suggested that Pro321 induces a bend in helix 6, bringing its C terminus near that of helix 3, as seen in many family A GPCRs. This is abolished in P321A. P321A-I325P predicted to restore this conformation, showed wild-type activation. Modeling can also rationalize the effects of transmembrane proline mutants previously reported for another family B GPCR, the VPAC(1) receptor.

Transglutaminase 2 null macrophages respond to lipopolysaccharide stimulation by elevated proinflammatory cytokine production due to an enhanced αvβ3 integrin-induced Src tyrosine kinase signaling

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with several additional biochemical functions. Loss of TG2 in vivo results in impaired phagocytosis of apoptotic cells and altered proinflammatory cytokine production by macrophages engulfing apoptotic cells leading to autoimmunity. It has been proposed that TG2 acts as an integrin ß(3) coreceptor in the engulfment process, while altered proinflammatory cytokine production is related to the lack of latent TGFß activation by TG2 null macrophages. Here we report that TG2 null macrophages respond to lipopolysaccharide treatment by elevated IL-6 and TNFa production. Though TGFß has been proposed to act as a feed back regulator of proinflammatory cytokine production in LPS-stimulated macrophages, this phenomenon is not related to the lack of active TGFß production. Instead, in the absence of TG2 integrin ß(3) maintains an elevated basal Src family kinase activity in macrophages, which leads to enhanced phosphorylation and degradation of the I?Ba. Low basal levels of I?Ba explain the enhanced sensitivity of TG2 null macrophages to signals that regulate NF-?B. Our data suggest that TG2 null macrophages bear a proinflammatory phenotype, which might contribute to the enhanced susceptibility of these mice to develop autoimmunity and atherosclerosis.

Optimizing PCB assembly for family setup strategy

Purpose – The purpose of this paper is to investigate the optimization for a placement machine in printed circuit board (PCB) assembly when family setup strategy is adopted. Design/methodology/approach – A complete mathematical model is developed for the integrated problem to optimize feeder arrangement and component placement sequences so as to minimize the makespan for a set of PCB batches. Owing to the complexity of the problem, a specific genetic algorithm (GA) is proposed. Findings – The established model is able to find the minimal makespan for a set of PCB batches through determining the feeder arrangement and placement sequences. However, exact solutions to the problem are not practical due to the complexity. Experimental tests show that the proposed GA can solve the problem both effectively and efficiently. Research limitations/implications – When a placement machine is set up for production of a set of PCB batches, the feeder arrangement of the machine together with the component placement sequencing for each PCB type should be solved simultaneously so as to minimize the overall makespan. Practical implications – The paper investigates the optimization for PCB assembly with family setup strategy, which is adopted by many PCB manufacturers for reducing both setup costs and human errors. Originality/value – The paper investigates the feeder arrangement and placement sequencing problems when family setup strategy is adopted, which has not been studied in the literature.

The role of the extracellular loops of the CGRP receptor, a family B GPCR

The CGRP (calcitonin gene-related peptide) receptor is a family B GPCR (G-protein-coupled receptor). It consists of a GPCR, CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). RAMP1 is needed for CGRP binding and also cell-surface expression of CLR. There have been few systematic studies of the ECLs (extracellular loops) of family B GPCRs. However, they are likely to be especially important for the interaction of the N-termini of the peptide agonists that are the natural agonists for these receptors. We have carried out alanine scans on all three ECLs of CLR, as well as their associated juxtamembrane regions. Residues within all three loops influence CGRP binding and receptor activation. Mutation of Ala203 and Ala206 on ECL1 to leucine increased the affinity of CGRP. Residues at the top of TM (transmembrane) helices 2 and 3 influenced CGRP binding and receptor activation. L351A and E357A in TM6/ECL3 reduced receptor expression and may be needed for CLR association with RAMP1. ECL2 seems especially important for CLR function; of the 16 residues so far examined in this loop, eight residues reduce the potency of CGRP at stimulating cAMP production when mutated to alanine.

Production, purification and characterization of recombinant, full-length human claudin-1

The transmembrane domain proteins of the claudin superfamily are the major structural components of cellular tight junctions. One family member, claudin-1, also associates with tetraspanin CD81 as part of a receptor complex that is essential for hepatitis C virus (HCV) infection of the liver. To understand the molecular basis of claudin-1/CD81 association we previously produced and purified milligram quantities of functional, full-length CD81, which binds a soluble form of HCV E2 glycoprotein (sE2). Here we report the production, purification and characterization of claudin-1. Both yeast membrane-bound and detergent-extracted, purified claudin-1 were antigenic and recognized by specific antibodies. Analytical ultracentrifugation demonstrated that extraction with n-octyl-ß-d-glucopyranoside yielded monodispersed, dimeric pools of claudin-1 while extraction with profoldin-8 or n-decylphosphocholine yielded a dynamic mixture of claudin-1 oligomers. Neither form bound sE2 in line with literature expectations, while further functional analysis was hampered by the finding that incorporation of claudin-1 into proteoliposomes rendered them intractable to study. Dynamic light scattering demonstrated that claudin-1 oligomers associate with CD81 in vitro in a defined molar ratio of 1:2 and that complex formation was enhanced by the presence of cholesteryl hemisuccinate. Attempts to assay the complex biologically were limited by our finding that claudin-1 affects the properties of proteoliposomes. We conclude that recombinant, correctly-folded, full-length claudin-1 can be produced in yeast membranes, that it can be extracted in different oligomeric forms that do not bind sE2 and that a dynamic preparation can form a specific complex with CD81 in vitro in the absence of any other cellular components. These findings pave the way for the structural characterization of claudin-1 alone and in complex with CD81.

Sustainable agricultural production:an investigation in Brazilian semi-arid livestock farms

This paper investigates the environmental sustainability and competitiveness perceptions of small farmers in a region in northern Brazil. The main data collection instruments included a survey questionnaire and an analysis of the region's strategic plan. In total, ninety-nine goat and sheep breeding farmers were surveyed. Data analysis methods included descriptive statistics, cluster analysis, and chi-squared tests. The main results relate to the impact of education, land size, and location on the farmers' perceptions of competitiveness and environmental issues. Farmers with longer periods of education have higher perception scores about business competitiveness and environmental sustainability than those with less formal education. Farmers who are working larger land areas also have higher scores than those with smaller farms. Lastly, location can yield factors that impact on farmers' perceptions. In our study, farmers located in Angicos and Lajes had higher perception scores than Pedro Avelino and Afonso Bezerra, despite the geographical proximity of these municipalities. On the other hand, three other profile variables did not impact on farmers' perceptions, namely: family income, dairy production volume, and associative condition. The authors believe the results and insights can be extended to livestock farming in other developing countries and contribute generally to fostering effective sustainable development policies, mainly in the agribusiness sector. © 2013 Elsevier Ltd. All rights reserved.

Bifunctional SO4/ZrO2 catalysts for 5-hydroxymethylfufural (5-HMF) production from glucose

The telescopic conversion of glucose to fructose and then 5-hydroxymethylfurfural (5-HMF), the latter a potential, bio-derived platform chemical feedstock, has been explored over a family of bifunctional sulfated zirconia catalysts possessing tuneable acid-base properties. Characterisation by acid-base titration, XPS, XRD and Raman reveal that submonolayer SO4 coverages offer the ideal balance of basic and Lewis-Brønsted acid sites required to respectively isomerise glucose to fructose, and subsequently dehydrate fructose to 5-HMF. A constant acid site normalised turnover frequency is observed for fructose dehydration to 5-HMF, confirming a common Brønsted acid site is responsible for this transformation. This journal is © The Royal Society of Chemistry.

Bifunctional SO4/ZrO2 catalysts for 5-hydroxymethylfufural (5-HMF) production from glucose

The telescopic conversion of glucose to fructose and then 5-hydroxymethylfurfural (5-HMF), the latter a potential, bio-derived platform chemical feedstock, has been explored over a family of bifunctional sulfated zirconia catalysts possessing tuneable acid-base properties. Characterisation by acid-base titration, XPS, XRD and Raman reveal that submonolayer SO4 coverages offer the ideal balance of basic and Lewis-Brønsted acid sites required to respectively isomerise glucose to fructose, and subsequently dehydrate fructose to 5-HMF. A constant acid site normalised turnover frequency is observed for fructose dehydration to 5-HMF, confirming a common Brønsted acid site is responsible for this transformation. This journal is © The Royal Society of Chemistry.

Holonic supply chain:a study from family-based manufacturing perspective

In the contemporary business environment, to adhere to the need of the customers, caused the shift from mass production to mass-customization. This necessitates the supply chain (SC) to be effective flexible. The purpose of this paper is to seek flexibility through adoption of family-based dispatching rules under the influence of inventory system implemented at downstream echelons of an industrial supply chain network. We compared the family-based dispatching rules in existing literature under the purview of inventory system and information sharing within a supply chain network. The dispatching rules are compared for Average Flow Time performance, which is averaged over the three product families. The performance is measured using extensive discrete event simulation process. Given the various inventory related operational factors at downstream echelons, the present paper highlights the importance of strategically adopting appropriate family-based dispatching rule at the manufacturing end. In the environment of mass customization, it becomes imperative to adopt the family-based dispatching rule from the system wide SC perspective. This warrants the application of intra as well as inter-echelon information coordination. The holonic paradigm emerges in this research stream, amidst the holistic approach and the vital systemic approach. The present research shows its novelty in triplet. Firstly, it provides leverage to manager to strategically adopting a dispatching rule from the inventory system perspective. Secondly, the findings provide direction for the attenuation of adverse impact accruing from demand amplification (bullwhip effect) in the form of inventory levels by appropriately adopting family-based dispatching rule. Thirdly, the information environment is conceptualized under the paradigm of Koestler's holonic theory.