IASDR 2015 Interplay Exhibition 2-5 NOV 2015

It has been said that we are living in a golden age of innovation. New products, systems and services aimed to enable a better future, have emerged from novel interconnections between design and design research with science, technology and the arts. These intersections are now, more than ever, catalysts that enrich daily activities for health and safety, education, personal computing, entertainment and sustainability, to name a few. Interactive functions made possible by new materials, technology, and emerging manufacturing solutions demonstrate an ongoing interplay between cross-disciplinary knowledge and research. Such interactive interplay bring up questions concerning: (i) how art and design provide a focus for developing design solutions and research in technology; (ii) how theories emerging from the interactions of cross-disciplinary knowledge inform both the practice and research of design and (iii) how research and design work together in a mutually beneficial way. The IASDR2015 INTERPLAY EXHIBITION provides some examples of these interconnections of design research with science, technology and the arts. This is done through the presentation of objects, artefacts and demonstrations that are contextualised into everyday activities across various areas including health, education, safety, furniture, fashion and wearable design. The exhibits provide a setting to explore the various ways in which design research interacts across discipline knowledge and approaches to stimulate innovation. In education, Designing South African Children’s Health Education as Generative Play (A Bennett, F Cassim, M van der Merwe, K van Zijil, and M Ribbens) presents a set of toolkits that resulted from design research entailing generative play. The toolkits are systems that engender pleasure and responsibility, and are aimed at cultivating South African’s youth awareness of nutrition, hygiene, disease awareness and prevention, and social health. In safety, AVAnav: Avalanche Rescue Helmet (Jason Germany) delivers an interactive system as a tool to contribute to reduce the time to locate buried avalanche victims. Helmet-mounted this system responds to the contextual needs of rescuers and has since led to further design research on the interface design of rescuing devices. In apparel design and manufacturing, Shrinking Violets: Fashion design for disassembly (Alice Payne) proposes a design for disassembly through the use of beautiful reversible mono-material garments that interactively responds to the challenges of garment construction in the fashion industry, capturing the metaphor for the interplay between technology and craft in the fashion manufacturing industry. Harvest: A biotextile future (Dean Brough and Alice Payne), explores the interplay of biotechnology, materiality and textile design in the creation of sustainable, biodegradable vegan textile through the process of a symbiotic culture of bacteria and yeast (SCOBY). SCOBY is a pellicle curd that can be harvested, machine washed, dried and cut into a variety of designs and texture combinations. The exploration of smart materials, wearable design and micro-electronics led to creative and aesthetically coherent stimulus-reactive jewellery; Symbiotic Microcosms: Crafting Digital Interaction (K Vones). This creation aims to bridge the gap between craft practitioner and scientific discovery, proposing a move towards the notion of a post-human body, where wearable design is seen as potential ground for new human-computer interactions, affording the development of visually engaging multifunctional enhancements. In furniture design, Smart Assistive chair for older adults (Chao Zhao) demonstrates how cross-disciplinary knowledge interacting with design strategies provide solution that employed new technological developments in older aged care, and the participation of multiple stakeholders: designers, health care system and community based health systems. In health, Molecular diagnosis system for newborns deafness genetic screening (Chao Zhao) presents an ambitious and complex project that includes a medical device aimed at resolving a number of challenges: technical feasibility for city and rural contexts, compatibility with standard laboratory and hospital systems, access to health system, and support the work of different hospital specialists. The interplay between cross-disciplines is evident in this work, demonstrating how design research moves forward through technology developments. These works exemplify the intersection between domains as a means to innovation. Novel design problems are identified as design intersects with the various areas. Research informs this process, and in different ways. We see the background investigation into the contextualising domain (e.g. on-snow studies, garment recycling, South African health concerns, the post human body) to identify gaps in the area and design criteria; the technologies and materials reviews (e.g. AR, biotextiles) to offer plausible technical means to solve these, as well as design criteria. Theoretical reviews can also inform the design (e.g. play, flow). These work together to equip the design practitioner with a robust set of ‘tools’ for design innovation – tools that are based in research. The process identifies innovative opportunity and criteria for design and this, in turn, provides a means for evaluating the success of the design outcomes. Such an approach has the potential to come full circle between research and design – where the design can function as an exemplar, evidencing how the research-articulated problems can be solved. Core to this, however, is the evaluation of the design outcome itself and identifying knowledge outcomes. In some cases, this is fairly straightforward that is, easily measurable. For example the efficacy of Jason Germany’s helmet can be determined by measuring the reduced response time in the rescuer. Similarly the improved ability to recycle Payne’s panel garments can be clearly determined by comparing it to those recycling processes (and her identified criteria of separating textile elements!); while the sustainability and durability of the Brough & Payne’s biotextile can be assessed by documenting the growth and decay processes, or comparative strength studies. There are however situations where knowledge outcomes and insights are not so easily determined. Many of the works here are open-ended in their nature, as they emphasise the holistic experience of one or more designs, in context: “the end result of the art activity that provides the health benefit or outcome but rather, the value lies in the delivery and experience of the activity” (Bennet et al.) Similarly, reconfiguring layers of laser cut silk in Payne’s Shrinking Violets constitutes a customisable, creative process of clothing oneself since it “could be layered to create multiple visual effects”. Symbiotic Microcosms also has room for facilitating experience, as the work is described to facilitate “serendipitous discovery”. These examples show the diverse emphasis of enquiry as on the experience versus the product. Open-ended experiences are ambiguous, multifaceted and differ from person to person and moment to moment (Eco 1962). Determining the success is not always clear or immediately discernible; it may also not be the most useful question to ask. Rather, research that seeks to understand the nature of the experience afforded by the artefact is most useful in these situations. It can inform the design practitioner by helping them with subsequent re-design as well as potentially being generalizable to other designers and design contexts. Bennett et. al exemplify how this may be approached from a theoretical perspective. This work is concerned with facilitating engaging experiences to educate and, ultimately impact on that community. The research is concerned with the nature of that experience as well, and in order to do so the authors have employed theoretical lenses – here these are of flow, pleasure, play. An alternative or complementary approach to using theory, is using qualitative studies such as interviews with users to ask them about what they experienced? Here the user insights become evidence for generalising across, potentially revealing insight into relevant concerns – such as the range of possible ‘playful’ or experiences that may be afforded, or the situation that preceded a ‘serendipitous discovery’. As shown, IASDR2015 INTERPLAY EXHIBITION provides a platform for exploration, discussion and interrogation around the interplay of design research across diverse domains. We look forward with excitement as IASDR continues to bring research and design together, and as our communities of practitioners continue to push the envelope of what is design and how this can be expanded and better understood with research to foster new work and ultimately, stimulate innovation.

Counselling and predictive testing for familial adenomatous polyposis in a rural South Indian community

Background—Mutations of the APC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome.Aims—To conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer. Methods—All direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model.Results—The baseline analysis predicted that screening a prototype FAP family would cost $4975/£3109 by molecular testingand $8031/£5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if the APC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/ £4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives. Conclusions—In FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be noncarriers.

Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm

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Y-chromosome evidence of southern origin of the East Asian - Specific haplogroup O3-M122

The prehistoric peopling of East Asia by modern humans remains controversial with respect to early population migrations. Here, we present a systematic sampling and genetic screening of an East Asian-specific Y-chromosome haplogroup (O3-M122) in 2,332 individuals from diverse East Asian populations. Our results indicate that the O3-M122 lineage is dominant in East Asian populations, with an average frequency of 44.3%. The microsatellite data show that the O3-M122 haplotypes in southern East Asia are more diverse than those in northern East Asia, suggesting a southern origin of the O3-M122 mutation. It was estimated that the early northward migration of the O3-M122 lineages in East Asia occurred similar to 25,000-30,000 years ago, consistent with the fossil records of modern humans in East Asia.

A simplified protocol for routine total DNA isolation from salmonid fishes

An efficient total DNA isolation protocol, suitable for routine population genetic screening purposes is described. This phenol based extraction can utilize fresh, frozen or ethanol preserved tissues.

Misfolding of galactose 1-phosphate uridylyltransferase can result in type I galactosemia

Type I galactosemia is a genetic disorder that is caused by the impairment of galactose-1-phosphate uridylyltransferase (GALT; EC 2.7.7.12). Although a large number of mutations have been detected through genetic screening of the human GALT (hGALT) locus, for many it is not known how they cause their effects. The majority of these mutations are missense, with predicted substitutions scattered throughout the enzyme structure and thus causing impairment by other means rather than direct alterations to the active site. To clarify the fundamental, molecular basis of hGALT impairment we studied five disease-associated variants p.D28Y, p.L74P, p.F171S, p.F194L and p.R333G using both a yeast model and purified, recombinant proteins. In a yeast expression system there was a correlation between lysate activity and the ability to rescue growth in the presence of galactose, except for p.R333G. Kinetic analysis of the purified proteins quantified each variant's level of enzymatic impairment and demonstrated that this was largely due to altered substrate binding. Increased surface hydrophobicity, altered thermal stability and changes in proteolytic sensitivity were also detected. Our results demonstrate that hGALT requires a level of flexibility to function optimally and that altered folding is the underlying reason of impairment in all the variants tested here. This indicates that misfolding is a common, molecular basis of hGALT deficiency and suggests the potential of pharmacological chaperones and proteostasis regulators as novel therapeutic approaches for type I galactosemia.

Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements

Retinitis pigmentosa (RP) is a devastating form of retinal degeneration, with significant social and professional consequences. Molecular genetic information is invaluable for an accurate clinical diagnosis of RP due to its high genetic and clinical heterogeneity. Using a gene capture panel that covers 163 of the currently known retinal disease genes, including 48 RP genes, we performed a comprehensive molecular screening in a collection of 123 RP unsettled probands from a wide variety of ethnic backgrounds, including 113 unrelated simplex and 10 autosomal recessive RP (arRP) cases. As a result, 61 mutations were identified in 45 probands, including 38 novel pathogenic alleles. Interestingly, we observed that phenotype and genotype were not in full agreement in 21 probands. Among them, eight probands were clinically reassessed, resulting in refinement of clinical diagnoses for six of these patients. Finally, recessive mutations in CLN3 were identified in five retinal degeneration patients, including four RP probands and one cone-rod dystrophy patient, suggesting that CLN3 is a novel non-syndromic retinal disease gene. Collectively, our results underscore that, due to the high molecular and clinical heterogeneity of RP, comprehensive screening of all retinal disease genes is effective in identifying novel pathogenic mutations and provides an opportunity to discover new genotype-phenotype correlations. Information gained from this genetic screening will directly aid in patient diagnosis, prognosis, and treatment, as well as allowing appropriate family planning and counseling.

Deciphering the molecular role of DJ-1 in the etiology of Parkinson’s and Huntingtons’s disease

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2014

Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value.OBJECTIVE This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers.METHODS The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2.RESULTS Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes.CONCLUSION M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family.

Progress in the genetics of common obesity and type 2 diabetes

The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.

Are poor responders patients at higher risk for producing aneuploid embryos in vitro?

Purpose To test the hypothesis that aged women with poor ovarian response express an increase on embryo chromosomal alterations when compared to aged women who presented normal response.Methods Couples undergoing intracytoplasmic sperm injection cycles with preimplantation genetic screening, were subdivided into two groups: Poor Responder group (n = 34), patients who produced a parts per thousand currency sign4 oocytes; and Normoresponder group (n = 50), patients who produced a parts per thousand yen5 oocytes. Groups were compared regarding cycles' outcomes and aneuploidy frequency.Results There were no significant differences between and groups regarding the fertilization rate (p = 0.6861), clinical pregnancy (p = 0.9208), implantation (p = 0.6863), miscarriage (p = 0.6788) and the percentage of aneuploid embryos (p = 0.270). Embryo transfer rate was significantly lower on poor responder group (p = 0.0128) and logistic regression confirmed the influence of poor response on the chance of embryo transfer (p = 0.016).Conclusions Aged females responding poorly to gonadotrophins are not at a higher risk for producing aneuploid embryos in vitro.

Comparative Cytogenetic Analysis of the Genus Symphysodon (Discus Fishes, Cichlidae): Chromosomal Characteristics of Retrotransposons and Minor Ribosomal DNA

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Molecular and Cytogenetic Analyses on Brazilian Youths with Pervasive Developmental Disorders

The Pervasive Developmental Disorders (PDDs) constitute a group of behavioral and neurobiological impairment conditions whose main features are delayed communicative and cognitive development. Genetic factors are reportedly associated with PDDs and particular genetic abnormalities are frequently found in specific diagnostic subgroups such as the autism spectrum disorders. This study evaluated cytogenetic and molecular parameters in 30 youths with autism or other PDDs. The fragile X syndrome was the most common genetic abnormality detected, presented by 1 patient with autism and 1 patient with PPD not-otherwise specified (PPD-NOS). One girl with PDD-NOS was found to have tetrasomy for the 15q11-q13 region, and one patient with autism exhibited in 2/100 metaphases an inv(7)(p15q36), thus suggesting a mosaicism 46,XX/46,XX,inv(7)(p15q36) or representing a coincidental finding. The high frequency of chromosomopathies support the hypothesis that PDDs may develop as a consequence to chromosomal abnormalities and justify the cytogenetic and molecular assessment in all patients with PDDs for establishment of diagnosis.

Use of a synthetic lethal screen to identify genes related to TIF51A in Saccharomyces cerevisiae

The putative eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for cell viability and the only cellular protein known to contain the unusual amino acid residue hypusine. eIF5A has been implicated in translation initiation, cell proliferation, nucleocytoplasmic transport, mRNA decay, and actin polarization, but the precise biological function of this protein is not clear. However, eIF5A was recently shown to be directly involved with the translational machinery. A screen for synthetic lethal mutations was carried out with one of the temperature-sensitive alleles of TIF51A (tif51A-3) to identify factors that functionally interact with eIF5A and revealed the essential gene YPT1. This gene encodes a small GTPase, a member of the rab family involved with secretion, acting in the vesicular trafficking between endoplasmatic reticulum and the Golgi. Thus, the synthetic lethality between TIF51A and YPT1 may reveal the connection between translation and the polarized distribution of membrane components, suggesting that these proteins work together in the cell to guarantee proper protein synthesis and secretion necessary for correct bud formation during G1/ S transition. Future studies will investigate the functional interaction between eIF5A and Ypt1 in order to clarify this involvement of eIF5A with vesicular trafficking. ©FUNPEC-RP.

Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.