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INTRODUCTION This study aimed to evaluate the LITE (Lifestyle Intervention for TEenagers) group programme, a family-based behavioural lifestyle intervention for overweight and obese adolescents. METHODS We conducted a two-arm randomised controlled trial that recruited overweight and obese adolescents who attended a tertiary care weight management clinic. Participants were randomised to the LITE programme or usual care. The primary outcome assessed was body mass index (BMI) z-score. Secondary outcomes of anthropometric measurements, metabolic profile, parenting and adolescents’ perception of family support were measured at baseline, three months and six months. Feasibility and acceptability of the LITE programme were also evaluated. RESULTS 61 adolescents were enrolled, with 31 in the LITE programme and 30 in usual care. At three months, participants in the programme had a greater reduction in weight (−0.18 ± 2.40 kg vs. 1.48 ± 1.97 kg; p = 0.107), waist circumference (−1.0 ± 3.1 cm vs. 2.4 ± 2.7 cm; p = 0.016), waist-height ratio (−0.01 ± 0.02 vs. 0.01 ± 0.02; p = 0.040) and systolic blood pressure (−3.8 ± 13.7 vs. 5.7 ± 13.1; p = 0.119) compared to the usual care group. There was no significant difference in BMI z-score. At six months, there were significant improvements in adolescents’ perception of family support for eating habits in the LITE group compared to the usual care group. The LITE programme had a good attendance rate of 67.7% and was well received. CONCLUSION The LITE programme showed feasibility and short-term clinical effectiveness in improving some clinical outcomes and improved adolescents’ perception of family support.

For many years dissipative quantum maps were widely used as informative models of quantum chaos. In this paper, a new scheme for generating good pseudo-random numbers (PRNG), based on quantum logistic map is proposed. Note that the PRNG merely relies on the equations used in the quantum chaotic map. The algorithm is not complex, which does not impose high requirement on computer hardware and thus computation speed is fast. In order to face the challenge of using the proposed PRNG in quantum cryptography and other practical applications, the proposed PRNG is subjected to statistical tests using well-known test suites such as NIST, DIEHARD, ENT and TestU01. The results of the statistical tests were promising, as the proposed PRNG successfully passed all these tests. Moreover, the degree of non-periodicity of the chaotic sequences of the quantum map is investigated through the Scale index technique. The obtained result shows that, the sequence is more non-periodic. From these results it can be concluded that, the new scheme can generate a high percentage of usable pseudo-random numbers for simulation and other applications in scientific computing.

Endoplasmic reticulum (ER) stress is emerging as a potential contributor to the onset of type 2 diabetes by making cells insulin-resistant. However, our understanding of the mechanisms by which ER stress affects insulin response remains fragmentary. Here we present evidence that the ER stress pathway acts via a conserved signaling mechanism involving the protein kinase PERK to modulate cellular insulin responsiveness. Insulin signaling via AKT reduces activity of FOXO transcription factors. In some cells, PERK can promote insulin responsiveness. However, we found that PERK also acts oppositely via phosphorylation of FOXO to promote FOXO activity. Inhibition of PERK improves cellular insulin responsiveness at the level of FOXO activity. We suggest that the protein kinase PERK may be a promising pharmacological target for ameliorating insulin resistance.

The topic of quantum chaos has begun to draw increasing attention in recent years. While a satisfactory definition for it is not settled yet in order to differentiate between its classical counterparts. Dissipative quantum maps can be characterized by sensitive dependence on initial conditions, like classical maps. Considering this property, an implementation of image encryption scheme based on the quantum logistic map is proposed. The security and performance analysis of the proposed image encryption is performed using well-known methods. The results of the reliability analysis are encouraging and it can be concluded that, the proposed scheme is efficient and secure. The results of this study also suggest application of other quantum maps such as quantum standard map and quantum baker map in cryptography and other aspects of security and privacy.

Mutations in immunoglobulin µ-binding protein 2 (Ighmbp2) cause distal spinal muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. However, despite extensive studies, the mechanism of disease-causing mutations remains elusive. Here we report the crystal structures of the Ighmbp2 helicase core with and without bound RNA. The structures show that the overall fold of Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense-mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large conformational changes in response to RNA binding, rotating 30° and 10°, respectively. The RNA binding and ATPase activities of Ighmbp2 are further enhanced by the R3H domain, located just downstream of the helicase core. Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure provides a molecular basis for understanding the disease-causing consequences of Ighmbp2 mutations.

Summary The diffusible signal factor (DSF)-dependent quorum sensing (QS) system adopts a novel protein-protein interaction mechanism to autoregulate the production of signal DSF. Here, we present the crystal structures of DSF synthase RpfF and its complex with the REC domain of sensor protein RpfC. RpfF is structurally similarity to the members of the crotonase superfamily and contains an N-terminal α/β spiral core domain and a C-terminal α-helical region. Further structural and mutational analysis identified two catalytic glutamate residues, which is the conserved feature of the enoyl-CoA hydratases/dehydratases. A putative substrate-binding pocket was unveiled and the key roles of the residues implicated in substrate binding were verified by mutational analysis. The binding of the REC domain may lock RpfF in an inactive conformation by blocking the entrance of substrate binding pocket, thereby negatively regulating DSF production. These findings provide a structural model for the RpfC-RpfF interaction-mediated QS autoinduction mechanism.

A small-sized symmetric thin ferroelectric (FE) film, assumed second order and in the FE phase, of thickness l is considered. The Landau-Devonshire free energy of the film is expressed using the Tilley-Zeks model. A special case, in which the polarization values at both film surfaces are zero, p± = 0, is assumed. The initial spontaneous polarization profile of the film at equilibrium is approximated using a cosine function. The Landau-Khalatnikov equation of motion is then used to obtain numerically the initial stable polarization profile; and to describe the dynamics of polarization reversal in the film under the action of a step driving electric fields. A finite-difference time domain method is utilized to simulate the switching process. Changes in the average polarization and the average polarization current during the switching are calculated and studied. The influence of temperature and thickness on switching is investigated.

Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5′ region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels.

In this paper, we present a derivation of the nonlinear susceptibility tensors for a two-sublattice uniaxial antiferromagnet up to the third-order effects within the standard definition by which the rf magnetization m is defined as a power series expansion in the rf fields h with the susceptibility tensors as the coefficients. The starting point is the standard set of torque equations of motion for this problem. A complete set of tensor elements is derived for the case of a single-frequency input wave. Within a circular polarization frame (pnz) expressions are given for the first-order susceptibility, second-harmonic generation, optical rectification, third-harmonic generation and intensity-dependent susceptibility. Some of the coefficients with representative resonance features in the far infrared are illustrated graphically and we conclude with a brief discussion of the implications of the resonance features arising from the calculations and their potential applications.

We derive the equations of motion from which nonlinear field- and frequency-dependent magnetic susceptibilities defined by M = + + may be calculated for a Heisenberg ferromagnet. Explicit expressions are given, in the circular polarization frame, for the second- and third-order effects that arise for a single-frequency input wave, namely second-harmonic generation, optical rectification, third-harmonic generation and intensity-dependent susceptibility. Illustrative graphs are presented for a few of the coefficients and the paper concludes with a brief discussion of the implications for multistability of a magnetic Fabry-P?rot resonator.

The transmission of electromagnetic radiation at normal incidence through a magnetic film is considered for film thickness L small enough to require the inclusion of exchange effects arising from the wave-number component . We apply the continuum form of the dynamical equations with parametrized spin boundary conditions including pinned and unpinned spins as special cases. For applied field normal to the interfaces (Faraday geometry) the propagating modes are circularly polarized but because of the exchange there are two modes, say optical and spin, in each polarization. Equations for the transmission are given in a general form that allows for partial mirrors at the interfaces and applies to a film on a substrate as well as a free-standing film. Computed transmission spectra show that spin-wave fringes are unlikely to be observable for ferromagnets but can be significant in antiferromagnets. Some discussion is given of the implications for the characterization of antiferromagnetic film systems by means of far-infrared spectroscopy.

We discuss the transmission of electromagnetic radiation through a Fabry - Perot resonator in the microwave or far-infrared frequency ranges where the magneto-optic properties are governed by a gyromagnetic permeability tensor. We restrict our attention to normally incident radiation but consider both Faraday (magnetic field normal to plate) and Voigt (field parallel to plate) geometries for ferromagnets and antiferromagnets. The effect of partially reflecting mirrors is included. It is shown that provided one uses the polarization eigenmodes, circular for Faraday geometry and plane for Voigt geometry, the transmission and reflection can be expressed by general formulae in terms of single-interface reflection and transmission coefficients. The resonator can be regarded as a magnetic-field tunable polarizer and it is shown how inclusion of mirrors sharpens the properties.

This thesis is composed of two separate projects on the proteins RpfF and Ighmbp2, and their functional role in quorum sensing and neurodegenerative disorder, respectively. The details of the RpfF protein and the helicase domain of Ighmbp2 protein are presented in Chapters 1 to 5 and Chapters 6 to 10, respectively. Quorum sensing is a form of communication in bacterial cells to allow coordination of gene expression in response to fluctuations in cell-population density. The pathogen Xanthomonas campestris pathovar campestris (Xcc) uses a small diffusible molecule named diffusible signal factor (DSF) as its quorum sensing signal to assess the population density and regulate virulence factor production. DSF regulates a cluster of genes designated as rpfABCDEFG which are important for the production of virulence factors such as extracellular enzymes and extracellular polysaccharides in Xcc. Recent studies have indicated that the regulation of DSF biosynthesis involves the interaction of RpfC and RpfF proteins. However, the mechanism of how RpfC regulates RpfF activity is not well understood. The crystal structure of the enoyl-CoA hydratase RpfF at a resolution of 1.8 Å is presented in this study. RpfF adopts a self-associating fold such that the C-terminal helix wrap round the N-terminal α/β core domain. Structural homology search in the Protein Data Bank revealed that RpfF is structurally similar to members of the hydratase/ isomerase superfamily. Further structural and mutational analyses identified Glu141 and Glu161 as conserved glutamate residues positioned in the catalytic pocket and are critical to RpfF activity in the DSF biosynthesis pathway. Superposition with ligand-bound enoyl-CoA hydratase showed that the C-terminal helix of RpfF is positioned at the entrance of the catalytic pocket and is in steric hinderance with the Co-A moiety of the substrate. In addition, the structure of RpfF in complex with REC domain of RpfC shows the REC domain interacting with the C-terminal helix of RpfF. These findings suggest that interaction with RpfC may lock RpfF in an inactive conformation, therefore having a negative regulating effect on DSF production. The second part of the thesis examines the Ighmbp2 protein which is implicated in the neurodegenerative disease spinal muscular atrophy with respiratory distress type I (SMARD1). Most of the genetic mutations causing SMARD1 occur in the region of the Ighmbp2 gene coding for the helicase domain. Although several studies have pointed out Ighmbp2 involvement in DNA replication, transcription, pre-mRNA splicing, and RNA metabolism, its exact role remains elusive. Based on sequence alignment and biochemical studies, Ighmbp2 protein has been classified as a member of the helicase superfamily I that can unwind RNA and DNA duplexes in the 5’ → 3’ direction in an ATP-dependent manner. To have a better understanding of this protein from the structural perspective, crystal structures of the helicase domain of Ighmbp2 in the free and ssRNA-bound states are obtained. The helicase domain of Ighmbp2 has high structural similarity with the helicase domain of Upf1, a protein in the Upf1-like subfamily. Upon ssRNA binding, conformation changes were observed in domains 1A and 1B. Data from surface plasmon resonance experiments showed that the presence of a R3H domain, located at the C-terminus of Ighmbp2, enhances Ighmbp2 nucleic acid binding ability. This highlights the importance of accessory domains in regulating helicase enzymatic activities. Based on Ighmbp2 helicase structure, the implications of SMARD1 causing mutations in Ighmbp2 are addressed from the structural perspective. DOCTOR OF PHILOSOPHY (SBS)

The type III secretion system (T3SS) of Pseudomonas aeruginosa is a key virulence determinant whose expression is induced by polyamine signals from mammalian host. SpuD and SpuE were postulated to be spermidine-preferential binding proteins, which regulate the polyamine content in this bacterial pathogen. In this study, we found that SpuD is a putrescine-preferential binding protein, while SpuE binds to spermidine exclusively. We have determined the crystal structures of SpuD in free form and in complex with putrescine and SpuE in free form and in complex with spermidine. Upon ligand binding, SpuD and SpuE undergo an "open-to-closed" conformational switch with the resultant closed ligand-bound forms, SpuD-putrescine and SpuE-spermidine, similar to their Escherichia coli counterparts PotF-putrescine and PotD-spermidine, respectively. Structural comparison suggested that two aromatic residues, Trp271 of SpuE and Phe273 of SpuD in segment II region, are the key structural determinants for putrescine/spermidine recognition specificity. Mutagenesis combined with isothermal titration calorimetry showed that substitution of Trp271 by Phe enabled SpuE to gain substantial binding affinity for putrescine, while replacement of Phe273 by Trp reduced the binding affinity of SpuD toward putrescine by 250-fold. Altogether, these results revealed the molecular mechanism governing polyamine recognition specificity by SpuD and SpuE and provide the basis for further structural and functional studies of polyamine signal importation system in P. aeruginosa.

The second harmonic generation of antiferromagnetic and dielectric multilayers is analysed by using a conventional nonlinear optics approach and transfer matrix formalism. The theoretical modelling of the multilayers is configured in Voigt geometry in order to observe second harmonic transmission and reflection through the film system, with the assumption of weak nonlinearity and no depletion of incident waves. With these, some of the linear and second harmonic transmissions and reflections are calculated numerically and shown graphically.

In this issue of Structure, Romano and colleagues show that RNase AS specifically hydrolyses adenylate-containing RNA and affects mycobacterial virulence. This study reveals the structural basis underlying the substrate specificity of this enzyme.

Second-harmonic generation of an antiferromagnetic film in Voigt geometry is calculated and analyzed. This calculation is carried out with an assumption of weak nonlinearity in a two-sublattice antiferromagnetic system. Second-harmonic waves are analyzed by the conventional approach of ordinary nonlinear optics.

SummaryThe SOSS1 complex comprising SOSSA, SOSSB1, and SOSSC senses single-stranded DNA (ssDNA) and promotes repair of DNA double-strand breaks (DSBs). But how SOSS1 is assembled and recognizes ssDNA remains elusive. The crystal structure of the N-terminal half of SOSSA (SOSSAN) in complex with SOSSB1 and SOSSC showed that SOSSAN serves as a scaffold to bind both SOSSB1 and SOSSC for assembly of the SOSS1 complex. The structures of SOSSAN/B1 in complex with a 12 nt ssDNA and SOSSAN/B1/C in complex with a 35 nt ssDNA showed that SOSSB1 interacts with both SOSSAN and ssDNA via two distinct surfaces. Recognition of ssDNA with a length of up to nine nucleotides is mediated solely by SOSSB1, whereas neither SOSSC nor SOSSAN are critical for ssDNA binding. These results reveal the structural basis of SOSS1 assembly and provide a framework for further study of the mechanism governing longer ssDNA recognition by the SOSS1 complex during DSB repair.