A meshfree particle based model for microscale shrinkage mechanisms of food materials in drying conditions

Cells are the fundamental building block of plant based food materials and many of the food processing born structural changes can fundamentally be derived as a function of the deformations of the cellular structure. In food dehydration the bulk level changes in porosity, density and shrinkage can be better explained using cellular level deformations initiated by the moisture removal from the cellular fluid. A novel approach is used in this research to model the cell fluid with Smoothed Particle Hydrodynamics (SPH) and cell walls with Discrete Element Methods (DEM), that are fundamentally known to be robust in treating complex fluid and solid mechanics. High Performance Computing (HPC) is used for the computations due to its computing advantages. Comparing with the deficiencies of the state of the art drying models, the current model is found to be robust in replicating drying mechanics of plant based food materials in microscale.

Pesticide discharge and water management in a paddy catchment in Japan

Concentrations of several pesticides were monitored in a paddy block and in the Kose river, which drains a paddy catchment in Fukuoka prefecture, Japan. Detailed water management in the block was also monitored to evaluate its effect on the pesticide contamination. The concentrations of applied pesticides in both block irrigation channel and drainage canal increased to tens of μg/L shortly after their applications. The increase in pesticide concentrations was well correlated with the open of irrigation and drainage gates in the pesticide-applied paddy plots only 1–3 days after pesticide application. High concentration of other pesticides, mainly herbicides, was also observed in the inflow irrigation and drainage waters, confirming the popularity of early irrigation and drainage after pesticide application in the area. The requirement of holding water after pesticide application (as a best management practice) issued by the authority was thus not properly followed. In a larger scale of the paddy catchment, the concentration of pesticides also increased significantly to several μg/L in the water of the Kose river shortly after the start of the pesticide application period either in downstream or mid–upstream areas, confirming the effect of current water management to the water quality. More extension and enforcement on water management should be done in order to control pesticide pollution from rice cultivation in Japan.

Pesticide exposure assessment in rice paddy areas: A Japanese perspective

This chapter provides an overview of the Japanese regulatory issues regarding pesticide use in rice paddies and an introduction of the new pesticide registration program. In addition, the experience of the environmental monitoring of pesticides and the modeling approaches used for the calculation of predicted environmental concentrations (PECs) in surface water and ground water systems adjacent to rice paddies in Japan are also discussed. Japan has been one of the major pesticide users in the world. Although having a long history in rice cultivation, the pesticide exposure assessment for paddy rice production received less attention compared with EU and US. Applications of up-to-date techniques and the development of realistic assessment procedures under specific climatic conditions as well as mitigation management practices for controlling pesticide contamination are important for an environmental-friendly rice production. Through the international cooperation and research exchanges, advances in pesticide risk assessment for rice paddies in Asian region and other rice-growing areas in the world would contribute to sustainable rice production. Transplanting of rice seedlings grows almost all rice paddies in Japan. The land preparation starts around April and June, and the harvest season lasts from August to October depending on the region and the rice varieties. Most of the rice paddies are treated with herbicides and other crop protection products, such as fungicides and insecticides that are applied during the crop season accordingly. Newly developed insecticides and fungicides are also applied during seedbed preparation.

Modeling approaches for pesticide exposure assessment in rice paddies

Pesticide use in paddy rice production may contribute to adverse ecological effects in surface waters. Risk assessments conducted for regulatory purposes depend on the use of simulation models to determine predicted environment concentrations (PEC) of pesticides. Often tiered approaches are used, in which assessments at lower tiers are based on relatively simple models with conservative scenarios, while those at higher tiers have more realistic representations of physical and biochemical processes. This chapter reviews models commonly used for predicting the environmental fate of pesticides in rice paddies. Theoretical considerations, unique features, and applications are discussed. This review is expected to provide information to guide model selection for pesticide registration, regulation, and mitigation in rice production areas.

Acute compensatory eating following exercise is associated with implicit hedonic wanting for food

The efficacy of exercise to promote weight loss could potentially be undermined by its influence on explicit or implicit processes of liking and wanting for food which in turn alter food preference. The present study was designed to examine hedonic and homeostatic mechanisms involved in the acute effects of exercise on food intake. 24 healthy female subjects were recruited to take part in two counterbalanced activity sessions; 50 min of high intensity (70% max heart rate) exercise (Ex) or no exercise (NEx). Subjective appetite sensations, explicit and implicit hedonic processes, food preference and energy intake (EI) were measured immediately before and after each activity session and an ad libitum test meal. Two groups of subjects were identified in which exercise exerted different effects on compensatory EI and food preference. After exercise, compensators (C) increased their EI, rated the food to be more palatable, and demonstrated increased implicit wanting. Compensators also showed a preference for high-fat sweet food compared with non-compensators (NC), independent of the exercise intervention. Exercise-induced changes in the hedonic response to food could be an important consideration in the efficacy of using exercise as a means to lose weight. An enhanced implicit wanting for food after exercise may help to explain why some people overcompensate during acute eating episodes. Some individuals could be resistant to the beneficial effects of exercise due to a predisposition to compensate for exercise-induced energy expenditure as a result of implicit changes in food preferences.

Protein complementation assay as a display system for screening protein libraries in the intracellular environment

A wide range of screening strategies have been employed to isolate antibodies and other proteins with specific attributes, including binding affinity, specificity, stability and improved expression. However, there remains no high-throughput system to screen for target-binding proteins in a mammalian, intracellular environment. Such a system would allow binding reagents to be isolated against intracellular clinical targets such as cell signalling proteins associated with tumour formation (p53, ras, cyclin E), proteins associated with neurodegenerative disorders (huntingtin, betaamyloid precursor protein), and various proteins crucial to viral replication (e.g. HIV-1 proteins such as Tat, Rev and Vif-1), which are difficult to screen by phage, ribosome or cell-surface display. This study used the β-lactamase protein complementation assay (PCA) as the display and selection component of a system for screening a protein library in the cytoplasm of HEK 293T cells. The colicin E7 (ColE7) and Immunity protein 7 (Imm7) *Escherichia coli* proteins were used as model interaction partners for developing the system. These proteins drove effective β-lactamase complementation, resulting in a signal-to-noise ratio (9:1 – 13:1) comparable to that of other β-lactamase PCAs described in the literature. The model Imm7-ColE7 interaction was then used to validate protocols for library screening. Single positive cells that harboured the Imm7 and ColE7 binding partners were identified and isolated using flow cytometric cell sorting in combination with the fluorescent β-lactamase substrate, CCF2/AM. A single-cell PCR was then used to amplify the Imm7 coding sequence directly from each sorted cell. With the screening system validated, it was then used to screen a protein library based the Imm7 scaffold against a proof-of-principle target. The wild-type Imm7 sequence, as well as mutants with wild-type residues in the ColE7- binding loop were enriched from the library after a single round of selection, which is consistent with other eukaryotic screening systems such as yeast and mammalian cell-surface display. In summary, this thesis describes a new technology for screening protein libraries in a mammalian, intracellular environment. This system has the potential to complement existing screening technologies by allowing access to intracellular proteins and expanding the range of targets available to the pharmaceutical industry.

Physical activity and regulation of food intake: current evidence

Objective: The evidence was reviewed on how physical activity could influence the regulation of food intake by either adjusting the sensitivity of appetite control mechanisms or by generating an energy deficit that could adjust the drive to eat. Design: Interventionist and correlational studies that had a significant influence on the relationship between physical activity and food intake were reviewed. Interventionist studies involve a deliberate imposition of physical activity with subsequent monitoring of the eating response. Correlational studies make use of naturally occurring differences in the levels of physical activity (between and within subjects) with simultaneous assessment of energy expenditure and intake. Subjects: Studies using lean, overweight, and obese men and women were included. Results: Only 19% of interventionist studies report an increase in energy intake after exercise; 65% show no change and 16% show a decrease in appetite. Of the correlational studies, approximately half show no relationship between energy expenditure and intake. These data indicate a rather loose coupling between energy expenditure and intake. A common sense view is that exercise is futile as a form of weight control because the energy deficit drives a compensatory increase in food intake. However, evidence shows that this is not generally true. One positive aspect of this is that raising energy expenditure through physical activity (or maintaining an active life style) can cause weight loss or prevent weight gain. A negative feature is that when people become sedentary after a period of high activity, food intake is not “down-regulated” to balance a reduced energy expenditure. Conclusion: Evidence suggests that a high level of physical activity can aid weight control either by improving the matching of food intake to energy expenditure (regulation) or by raising expenditure so that it is difficult for people to eat themselves into a positive energy balance.

Ryanodine receptor phosphorylation in human heart failure

Heart failure is a complex disorder, characterized by activation of the sympathetic nervous system, leading to dysregulated Ca2+ homeostasis in cardiac myocytes and tissue remodeling. In a variety of diseases, cardiac malfunction is associated with aberrant fluxes of Ca2+ across both the surface membrane and the internal Ca2+ store, the sarcoplasmic reticulum (SR). One prominent hypothesis residues is that in heart failure, the activity of the ryanodine receptor (RyR2) Ca2+ release channel in the SR is increased due to excess phosphorylation and that this contributes to excess SR Ca2+ leak in diastole, reduced SR Ca2+ load and decreased contractility (Huke & Bers, 2008). There is controversy over which serine residues in RyR2 are hyperphosphorylated in animal models of heart failure and whether this is via the CaMKII or the PKA-linked signaling pathway. S2808, S2814 and S2030 in RyR2 have been variously claimed to be hyperphosphorylated. Our aim was to examine the degree of phosphorylation of these residues in RyR2 from failing human hearts. The use of human tissue was approved by the Human Research Ethics Committee, The Prince Charles Hospital, EC28114. Left ventricular tissue samples were obtained from an explanted heart of a patient with endstage heart failure (Emery Dreifuss Muscular Dystrophy with cardiomyopathy) and non-failing tissue was from a patient with cystic fibrosis undergoing heart-lung transplantation with no history of heart disease. SR vesicles were prepared as described by Laver et al. (1995) and examined with SDS-Page and Western Blot. Transferred proteins were probed with antibodies to detect total protein phosphorylation, phosphorylation of RyR2 serine residues S2808, S2814, S2030 and for the key proteins calsequestrin, triadin, junctin and FKBP12.6. To avoid membrane stripping artifact, each membrane was exposed to one phosphorylation-specific antibody and signal densities quantified using Bio-Rad Quantity One software. We found no distinguishable difference between failing and healthy hearts in the protein expression levels of RyR2, triadin, junctin or calsequestrin. We found an expected upregulation of total RyR2 phosphorylation in the failing heart sample, compared to a matched amount of RyR2 (quantified using densiometry) in healthy heart. Probing with antibodies detecting only the phosphorylated form of the specific RyR2 residues showed that the increase in total RyR2 phosphorylation in the failing heart was due to hyperphosphorylation of S2808 and S2814. We found that S2030 phosphorylation levels were unchanged in human heart failure. Interestingly, we found that S2030 has a basal level of phosphorylation in the healthy human heart, different from the absence of basal phosphorylation recently reported in rodent heart (Huke & Bers, 2008). Finally, preliminary results indicate that less FKBP 12.6 is associated with RyR2 in the failing heart, possibly as a consequence of PKA activation. In conclusion, residues S2808 and S2814 are hyperphosphorylated in human heart failure, presumably due to upregulation of the CaMKII and/or PKA signaling pathway as a result of chronic activation of the sympathetic nervous system. Such changes in RyR2 phosphorylation are believed to contribute to the leaky RyR2 phenotype associated with heart failure, which increases the incidence of arrhythmia and contributes to the severely impaired contractile performance of the failing heart. Huke S & Bers DM. (2008). Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications 376, 80-85. Laver DR, Roden LD, Ahern GP, Eager KR, Junankar PR & Dulhunty AF. (1995). Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle. Journal of Membrane Biology 147, 7-22. Proceedings

Sequence Changes in Six Variants of Rice Tungro Bacilliform Virus and Their Phylogenetic Relationships

The DNA of three biological variants, G1, Ic and G2, which originated from the same greenhouse isolate of rice tungro bacilliform virus (RTBV) at the International Rice Research Institute (IRRI), was cloned and sequenced. Comparison of the sequences revealed small differences in genome sizes. The variants were between 95 and 99% identical at the nucleotide and amino acid levels. Alignment of the three genome sequences with those of three published RTBV sequences (Phi-1, Phi-2 and Phi-3) revealed numerous nucleotide substitutions and some insertions and deletions. The published RTBV sequences originated from the same greenhouse isolate at IRRI 20, 11 and 9 years ago. All open reading frames (ORFs) and known functional domains were conserved across the six variants. The cysteine-rich region of ORF3 showed the greatest variation. When the six DNA sequences from IRRI were compared with that of an isolate from Malaysia (Serdang), similar changes were observed in the cysteine-rich region in addition to other nucleotide substitutions and deletions across the genome. The aligned nucleotide sequences of the IRRI variants and Serdang were used to analyse phylogenetic relationships by the bootstrapped parsimony, distance and maximum-likelihood methods. The isolates clustered in three groups: Serdang alone; Ic and G1; and Phi-1, Phi-2, Phi-3 and G2. The distribution of phylogenetically informative residues in the IRRI sequences shared with the Serdang sequence and the differing tree topologies for segments of the genome suggested that recombination, as well as substitutions and insertions or deletions, has played a role in the evolution of RTBV variants. The significance and implications of these evolutionary forces are discussed in comparison with badnaviruses and caulimoviruses.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.

Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma

We report that 10% of melanoma tumors and cell lines harbor mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. These novel mutations include three truncating mutations and 20 missense mutations occurring at evolutionary conserved residues in FGFR2 as well as among all four FGFRs. The mutation spectrum is characteristic of those induced by UV radiation. Mapping of these mutations onto the known crystal structures of FGFR2 followed by in vitro and in vivo studies show that these mutations result in receptor loss of function through several distinct mechanisms, including loss of ligand binding affinity, impaired receptor dimerization, destabilization of the extracellular domains, and reduced kinase activity. To our knowledge, this is the first demonstration of loss-of-function mutations in a class IV receptor tyrosine kinase in cancer. Taken into account with our recent discovery of activating FGFR2 mutations in endometrial cancer, we suggest that FGFR2 may join the list of genes that play context-dependent opposing roles in cancer.

Predicting residue-wise contact orders in proteins by support vector regression

Background The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. Results We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. Conclusion The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences.

Urban food futures : ICTs and opportunities

Food is a vital foundation of all human life. It is essential to a myriad of political, socio-cultural, economic and environmental practices throughout history. However, those practices of food production, consumption, and distribution have the potential to now go through immensely transformative shifts as network technologies become increasingly embedded in every domain of contemporary life. Information and communication technologies (ICTs) are one of the key foundations of global functionality and sustenance today and undoubtedly will continue to present new challenges and opportunities for the future. As such, this Symposium will bring together leading scholars across disciplines to address challenges and opportunities at the intersection of food and ICTs in everyday urban environment. In particular, the discussion will revolve around the question: What are the key roles that network technologies play in re-shaping the food systems at micro- to macroscopic level? The symposium will contribute a unique perspective on urban food futures through the lens of network society paradigm where ICTs enable innovations in production, organisation, and communication within society. Some of the topics addressed will include encouraging transparency in food commodity chains; value of cultural understanding and communication in global food sustainability; and technologies to social inclusion; all of which evoke and examine the question surrounding networked individuals as changes catalysts for urban food futures. The event will provide an avenue for new discussions and speculations on key issues surrounding urban food futures in the network era, with a particular focus on bottom-up micro actions that challenge the existing food systems towards a broader sociocultural, political, technological, and environmental transformations. One central area of concern is that current systems of food production, distribution, and consumption do not ensure food security for the future, but rather seriously threaten it. With the recent unprecedented scale of urban growth and rise of middle-class, the problem continues to intensify. This situation requires extensive distribution networks to feed urban residents, and therefore poses significant infrastructural challenges to both the public and private sectors. The symposium will also address the transferability of citizen empowerment that network technologies enable as demonstrated in various significant global political transformations from the bottom-up, such as the recent Egyptian Youth Revolution. Another key theme of the discussion will be the role of ICTs (and the practices that they mediate) in fostering transparency in commodity chains. The symposium will ask what differences these technologies can make on the practices of food consumption and production. After discussions, we will initiate an international network of food-thinkers and actors that will function as a platform for knowledge sharing and collaborations. The participants will be invited to engage in planning for the on-going future development of the network.

Food insecurity among Australian children : potential determinants, health and developmental consequences

Children in food-insecure households may be at risk of poor health, developmental or behavioural problems. This study investigated the associations between food insecurity, potential determinants and health and developmental outcomes among children. Data on household food security, socio-demographic characteristics and children’s weight, health and behaviour were collected from households with children aged 3–17 years in socioeconomically disadvantaged suburbs by mail survey using proxy-parental reports (185 households). Data were analysed using logistic regression. Approximately one-in-three households (34%) were food insecure. Low household income was associated with an increased risk of food insecurity [odds ratio (OR), 16.20; 95% confidence interval (CI), 3.52–74.47]. Children with a parent born outside of Australia were less likely to experience food insecurity (OR, 0.42; 95% CI, 0.19–0.93). Children in food-insecure households were more likely to miss days from school or activities (OR, 3.52; 95% CI, 1.46–8.54) and were more likely to have borderline or atypical emotional symptoms (OR, 2.44; 95% CI, 1.11–5.38) or behavioural difficulties (OR, 2.35; 95% CI, 1.04–5.33). Food insecurity may be prevalent among socioeconomically disadvantaged households with children. The potential developmental consequences of food insecurity during childhood may result in serious adverse health and social implications.

Food and interaction design [Extended Abstract]

Food and interaction design presents an interesting challenge to the HCI community in attending to the pervasive nature of food, the socio-cultural differences in food practices and a changing global foodscape. To design for meaningful and positive interactions it is essential to identify daily food practices and the opportunities for the design of technology to support such practices. This workshop brings together a community of researchers and practitioners in human-food interaction to attend to the practical and theoretical difficulties in designing for human-food interactions in everyday life. Through a practical field study and workshop we explore themes of food experiences, health and wellbeing, sustainability and alternative food cultures.