Differential interaction between the C2B domain of synaptotagmin-I and the Drosophila stonedA and stonedB proteins

The stoned locus in Drosophila encodes two proteins StonedA (STNA) and StonedB (STNB), both of which have been suggested to act as adaptins in mediating synaptic vesicle recycling. A combination of immunological, genetic and biochemical studies have shown an interaction of STNA and STNB with the C2B domain of Synaptotagmin-I (SYT-1), an integral synaptic vesicle protein that mediates Ca2+-dependent exocytosis, as well as endocytosis. The C2B domain of SYT-1 contains an AP-2 binding site that controls the size of recycled vesicles, and a C-terminal tryptophan-containing motif that acts as an internalization signal. Investigation of SYT-1 mutations in Drosophila has shown that altering the Ca2+ binding region of the C2B domain, results in a reduction in the rate of vesicle recycling, implicating this region in SYT-I endocytosis. In this poster, we report the molecular dissection of the interactions between the STNA and STNB proteins and the C2B domain of SYT-1. Deletion of the AP-2 binding site decreased the binding of both STNA and STNB. However, C-terminal deletions of the C2B domain significantly increased STNB binding. In contrast, the same C-terminal deletions reduced the affinity of the C2B domain for STNA. The possible interactions of both STNB and STNA with the Ca2+ binding region of SYT-1 will be also investigated.

Changes in disability, physical/mental health states and quality of life during an 8-Week multimodal physiotherapy programme in patients with chronic non-specific neck pain: A prospective cohort study

Aim The aim of this study was to analyse the effect of an 8-week multimodal physiotherapy programme (MPP), integrating physical land-based therapeutic exercise (TE), adapted swimming and health education, as a treatment for patients with chronic non-specific neck pain (CNSNP), on disability, general health/mental states and quality of life. Methods 175 CNSNP patients from a community-based centre were recruited to participate in this prospective study. Intervention: 60-minute session (30 minutes of land-based exercise dedicated to improving mobility, motor control, resistance and strengthening of the neck muscles, and 30 minutes of adapted swimming with aerobic exercise keeping a neutral neck position using a snorkel). Health education was provided using a decalogue on CNSNP and constant repetition of brief advice by the physiotherapist during the supervision of the exercises in each session. Study outcomes: primary: disability (Neck Disability Index); secondary: physical and mental health states and quality of life of patients (SF-12 and EuroQoL-5D respectively). Differences between baseline data and that at the 8-week follow-up were calculated for all outcome variables. Results Disability showed a significant improvement of 24.6% from a mean (SD) of 28.2 (13.08) at baseline to 16.88 (11.62) at the end of the 8-week intervention. All secondary outcome variables were observed to show significant, clinically relevant improvements with increase ranges between 13.0% and 16.3% from a mean of 0.70 (0.2) at baseline to 0.83 (0.2), for EuroQoL-5D, and from a mean of 40.6 (12.7) at baseline to 56.9 (9.5), for mental health state, at the end of the 8-week intervention. Conclusion After 8 weeks of a MPP that integrated land-based physical TE, health education and adapted swimming, clinically-relevant and statistically-significant improvements were observed for disability, physical and mental health states and quality of life in patients who suffer CNSNP. The clinical efficacy requires verification using a randomised controlled study design.

Genome-wide interaction analysis reveals replicated epistatic effects on brain structure

The discovery of several genes that affect the risk for Alzheimer's disease ignited a worldwide search for single-nucleotide polymorphisms (SNPs), common genetic variants that affect the brain. Genome-wide search of all possible SNP-SNP interactions is challenging and rarely attempted because of the complexity of conducting approximately 1011 pairwise statistical tests. However, recent advances in machine learning, for example, iterative sure independence screening, make it possible to analyze data sets with vastly more predictors than observations. Using an implementation of the sure independence screening algorithm (called EPISIS), we performed a genome-wide interaction analysis testing all possible SNP-SNP interactions affecting regional brain volumes measured on magnetic resonance imaging and mapped using tensor-based morphometry. We identified a significant SNP-SNP interaction between rs1345203 and rs1213205 that explains 1.9% of the variance in temporal lobe volume. We mapped the whole brain, voxelwise effects of the interaction in the Alzheimer's Disease Neuroimaging Initiative data set and separately in an independent replication data set of healthy twins (Queensland Twin Imaging). Each additional loading in the interaction effect was associated with approximately 5% greater brain regional brain volume (a protective effect) in both Alzheimer's Disease Neuroimaging Initiative and Queensland Twin Imaging samples.

IdeaWall: Mixed mode distributed collaboration in enterprise environments

In early stages of design and modeling, computers and computer applications are often considered an obstacle, rather than a facilitator of the process. Most notably, brainstorms, process modeling with business experts, or development planning, are often performed by a team in front of a whiteboard. While "whiteboarding" is recognized as an effective tool, low-tech solutions that allow remote participants to contribute are still not generally available. This is a striking observation, considering that vast majority of teams in large organizations are distributed teams. And this has also been one of the key triggers behind the project described in this article, where a team of corporate researchers decided to identify state of the art technologies that could facilitate the scenario mentioned above. This paper is an account of a research project in the area of enterprise collaboration, with a strong focus on the aspects of human computer interaction in mixed mode environments, especially in areas of collaboration where computers still play a secondary role. It is describing a currently running corporate research project. © 2012 Springer-Verlag.

Indigenous ways with literacies: Transgenerational, multimodal, placed, and collective

This research describes some of the salient features of Indigenous ways of working with multimodal literacies in digital contexts of use that emerged within an Indigenous school community with the oversight of Aboriginal Elders. This is significant because the use of multimodal literacy practices among a growing number of Indigenous school community groups has not been an emphasis of multimodal literacy research to date. Furthermore, authentic examples of Indigenous multimodal texts are often difficult to locate within Euro-centric educational systems of postcolonial countries. The research was conducted over a full year with students from middle and upper primary (aged 8.5–12.5 years) in an Indigenous Independent school in South-East Queensland, Australia. The project applied participatory research methods in which the research agenda was negotiated with the cultural community. Indigenous ways of multimodal literacy practices emerged as transgenerational, multimodal, placed, and collective. The findings have implications for teachers and researchers to re-envisage Indigenous ways of multimodal literacy practices in the digital age.

Interaction design for tablet based edutainment systems for mathematical education of primary student

Mathematics has been perceived as the core area of learning in most educational systems around the world including Sri Lanka. Unfortunately, it is clearly visible that a majority of Sri Lankan students are failing in their basic mathematics when the recent grade five scholarship examination and ordinary level exam marks are analysed. According to Department of Examinations Sri Lanka , on average, over 88 percent of the students are failing in the grade 5 scholarship examinations where mathematics plays a huge role while about 50 percent of the students fail in there ordinary level mathematics examination. Poor or lack of basic mathematics skills has been identified as the root cause.

Multimodal imaging of the collagen and elastic fibre networks in the bovine intervertebral disc

INTRODUCTION. The intervertebral disc is the largest avascular structure in the human body, withstanding transient loads of up to nine times body weight during rigorous physical activity. The key structural elements of the disc are a gel-like nucleus pulposus surrounded by concentric lamellar rings containing criss-crossed collagen fibres. The disc also contains an elastic fiber network which has been suggested to play a structural role, but to date the relationship between the collagen and elastic fiber networks is unclear. CONCLUSION. The multimodal transmitted and reflected polarized light microscopy technique developed here allows clear differentiation between the collagen and elastic fiber networks of the intervertebral disc. The ability to image unstained specimens avoids concerns with uneven stain penetration or specificity of staining. In bovine tail discs, the elastic fiber network is intimately associated with the collagen network.

A novel grass pollen allergen mimotope identified by phage display peptide library inhibits allergen-human IgE antibody interaction

The aim of this study was to investigate the molecular basis of human IgE-allergen interaction by screening a phage-displayed peptide library with an allergen-specific human IgE-mimicking monoclonal antibody (mAb). A mAb that reacted with major grass pollen allergens was successfully identified and shown to inhibit human IgE-allergen interaction. Biopanning of a phage-displayed random peptide library with this mAb yielded a 12 amino acid long mimotope. A synthetic peptide based on this 12-mer mimotope inhibited mAb and human IgE binding to grass pollen extracts. Our results indicate that such synthetic peptide mimotopes of allergens have potential as novel therapeutic agents. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

On the interaction between radon progeny and particles generated by electronic and traditional cigarettes

During their entire lives, people are exposed to the pollutants present in indoor air. Recently, Electronic Nicotine Delivery Systems, mainly known as electronic cigarettes, have been widely commercialized: they deliver particles into the lungs of the users but a “second-hand smoke” has yet to be associated to this indoor source. On the other hand, the naturally-occurring radioactive gas, i.e. radon, represents a significant risk for lung cancer, and the cumulative action of these two agents could be worse than the agents separately would. In order to deepen the interaction between radon progeny and second-hand aerosol from different types of cigarettes, a designed experimental study was carried out by generating aerosol from e-cigarette vaping as well as from second-hand traditional smoke inside a walk-in radon chamber at the National Institute of Ionizing Radiation Metrology (INMRI) of Italy. In this chamber, the radon present in air comes naturally from the floor and ambient conditions are controlled. To characterize the sidestream smoke emitted by cigarettes, condensation particle counters and scanning mobility particle sizer were used. Radon concentration in the air was measured through an Alphaguard ionization chamber, whereas the measurement of radon decay product in the air was performed with the Tracelab BWLM Plus-2S Radon daughter Monitor. It was found an increase of the Potential Alpha-Energy Concentration (PAEC) due to the radon decay products attached to aerosol for higher particle number concentrations. This varied from 7.47 ± 0.34 MeV L−1 to 12.6 ± 0.26 MeV L−1 (69%) for the e-cigarette. In the case of traditional cigarette and at the same radon concentration, the increase was from 14.1 ± 0.43 MeV L−1 to 18.6 ± 0.19 MeV L−1 (31%). The equilibrium factor increases, varying from 23.4% ± 1.11% to 29.5% ± 0.26% and from 30.9% ± 1.0% to 38.1 ± 0.88 for the e-cigarette and traditional cigarette, respectively. These growths still continue for long time after the combustion, by increasing the exposure risk.

Optimizing the quantum dot: Plasmon interaction in a nano gap waveguide

Spontaneous emission (SE) of a Quantum emitter depends mainly on the transmission strength between the upper and lower energy levels as well as the Local Density of States (LDOS)[1]. When a QD is placed in near a plasmon waveguide, LDOS of the QD is increased due to addition of the non-radiative decay and a plasmonic decay channel to free space emission[2-4]. The slow velocity and dramatic concentration of the electric field of the plasmon can capture majority of the SE into guided plasmon mode (Гpl ). This paper focused on studying the effect of waveguide height on the efficiency of coupling QD decay into plasmon mode using a numerical model based on finite elemental method (FEM). Symmetric gap waveguide considered in this paper support single mode and QD as a dipole emitter. 2D simulation models are done to find normalized Гpl and 3D models are used to find probability of SE decaying into plasmon mode ( β) including all three decay channels. It is found out that changing gap height can increase QD-plasmon coupling, by up to a factor of 5 and optimally placed QD up to a factor of 8. To make the paper more realistic we briefly studied the effect of sharpness of the waveguide edge on SE emission into guided plasmon mode. Preliminary nano gap waveguide fabrication and testing are already underway. Authors expect to compare the theoretical results with experimental outcomes in the future

Synthesis of a multimodal molecular imaging probe based on a hyperbranched polymer architecture

Molecular imaging is utilised in modern medicine to aid in the diagnosis and treatment of disease by allowing its spatiotemporal state to be examined in vivo. This study focuses on the development of novel multimodal molecular imaging agents based on hyperbranched polymers that combine the complementary capabilities of optical fluorescence imaging and positron emission tomography-computed tomography (PET/CT) into one construct. RAFT-mediated polymerisation was used to prepare two hydrophilic hyperbranched polymers that were differentiated by their size and level of branching. The multiple functional end-groups facilitated covalent attachment of both near infrared fluorescent dyes for optical imaging, as well as a copper chelator allowing binding of 64Cu as a PET radio nuclei. In vivo multimodal imaging of mice using PET/CT and planar optical imaging was first used to assess the biodistribution of the polymeric materials and it was shown that the larger and more branched polymer had a significantly longer circulation time. The larger constructs were also shown to exhibit enhanced accumulation in solid tumours in a murine B16 melanoma model. Importantly, it was demonstrated that the PET modality gave rise to high sensitivity immediately after injection of the agent, while the optical modality facilitated extended longitudinal studies, thus highlighting how the complementary capabilities of the molecular imaging agents can be useful for studying various diseases, including cancer.

Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imagingin vivo

Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution 19F/1H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.

Theorising the impacts of digitally mediated social interaction on diasporic identity formation: A case of Chinese diaspora in Australia

With the scope of Chinese diaspora in Australia, this paper theorises the impacts of digitally mediated social interaction on diasporic identity formation in the new media landscape. People’s identity is the outcome of their social interactions with other individuals. In the new media landscape, digital media technologies are changing the way in which people communicate with others. On one hand, space and time are unprecedentedly compressed by media technologies so people can maintain more frequent and instant connections with others than before. On the other hand, the digital media technologies have constructed a virtual social space that might withdraw people from their physical social interactions. As we witness today, our social interactions are increasing digitally mediated, in the forms of posts and comments in social network sites, as well as the messages in social apps. As to the diasporic groups, this new media landscape is presenting a challenge to their identity formation. They physically live in the host countries but still keep close social and cultural connections with their homelands. Facilitated by digital media technologies, they are facing two platforms in which they can practice different identity performances: one is the digitally mediated social network; the other is the physical social network. In the case of Chinese diaspora, the situation is more complex due to the language factor and media censorship in Mainland China, which will be articulated in the main text. This paper aims to fill a gap between media studies and diaspora research. Most of existing research on the relationship between diasporic identity and media primarily focuses on the development of ethnic media institutions, and the production and consumption of ethnic media in the pre-digital media context. However, the process of globalisation and digital media technologies are increasing the homogeneity and hybridity of media content worldwide. In this new context, attributing the formation of different identities to the consumption of media content is arguable to some extent. Therefore, the overlapped area of new media studies and diaspora research still has space deserves further investigation.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10-8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10-6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.