Glitter-like iridescence within the bacteroidetes especially Cellulophaga spp.: optical properties and correlation with gliding motility.

This is the final version of the article. Available from the publisher via the DOI in this record.Iridescence results from structures that generate color. Iridescence of bacterial colonies has recently been described and illustrated. The glitter-like iridescence class, created especially for a few strains of Cellulophaga lytica, exhibits an intense iridescence under direct illumination. Such color appearance effects were previously associated with other bacteria from the Bacteroidetes phylum, but without clear elucidation and illustration. To this end, we compared various bacterial strains to which the iridescent trait was attributed. All Cellulophaga species and additional Bacteroidetes strains from marine and terrestrial environments were investigated. A selection of bacteria, mostly marine in origin, were found to be iridescent. Although a common pattern of reflected wavelengths was recorded for the species investigated, optical spectroscopy and physical measurements revealed a range of different glitter-like iridescence intensity and color profiles. Importantly, gliding motility was found to be a common feature of all iridescent colonies. Dynamic analyses of "glitter" formation at the edges of C. lytica colonies showed that iridescence was correlated with layer superposition. Both gliding motility, and unknown cell-to-cell communication processes, may be required for the establishment, in time and space, of the necessary periodic structures responsible for the iridescent appearance of Bacteroidetes.PV acknowledges the support of AFOSR grant FA9550-10-1-0020. BK was a PhD student with a grant from the Ministe`re de la recherche et de l’enseignement supe´rieur. ER acknowledges the support of CNRS grant AIR75515 (‘‘Bacte´ridescence’’ project). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

TalkingBoogie: Collaborative Mobile AAC System for Non-verbal Children with Developmental Disabilities and Their Caregivers

Augmentative and alternative communication (AAC) technologies are widely used to help non-verbal children enable communication. For AAC-aided communication to be successful, caregivers should support children with consistent intervention strategies in various settings. As such, caregivers need to continuously observe and discuss children's AAC usage to create a shared understanding of these strategies. However, caregivers often find it challenging to effectively collaborate with one another due to a lack of family involvement and the unstructured process of collaboration. To address these issues, we present TalkingBoogie, which consists of two mobile apps: TalkingBoogie-AAC for caregiver-child communication, and TalkingBoogie-coach supporting caregiver collaboration. Working together, these applications provide contextualized layouts for symbol arrangement, scaffold the process of sharing and discussing observations, and induce caregivers' balanced participation. A two-week deployment study with four groups (N=11) found that TalkingBoogie helped increase mutual understanding of strategies and encourage balanced participation between caregivers with reduced cognitive loads.SNU Undergraduate Research Program through the Faculty of Liberal Education, Seoul National University (2019-23) National Research Foundation of Korea Grant funded by the Korean Government (NRF-2019S1A5A2A01045980

Supporting Self-Regulation of Children with ADHD Using Wearables: Tensions and Design Challenges

The design of wearable applications supporting children with Attention Deficit Hyperactivity Disorders (ADHD) requires a deep understanding not only of what is possible from a clinical standpoint but also how the children might understand and orient towards wearable technologies, such as a smartwatch. Through a series of participatory design workshops with children with ADHD and their caregivers, we identified tensions and challenges in designing wearable applications supporting the self-regulation of children with ADHD. In this paper, we describe the specific challenges of smartwatches for this population, the balance between self-regulation and co-regulation, and tensions when receiving notifications on a smartwatch in various contexts. These results indicate key considerations—from both the child and caregiver viewpoints—for designing technological interventions supporting children with ADHD

An extended multisensory temporal binding window in autism spectrum disorders

Autism spectrum disorders (ASD) form a continuum of neurodevelopmental disorders, characterized by deficits in communication and reciprocal social interaction, as well as by repetitive behaviors and restricted interests. Sensory disturbances are also frequently reported in clinical and autobiographical accounts. However, surprisingly few empirical studies have characterized the fundamental features of sensory and multisensory processing in ASD. The current study is structured to test for potential differences in multisensory temporal function in ASD by making use of a temporally dependent, low-level multisensory illusion. In this illusion, the presentation of a single flash of light accompanied by multiple sounds often results in the illusory perception of multiple flashes. By systematically varying the temporal structure of the audiovisual stimuli, a “temporal window” within which these stimuli are likely to be bound into a single perceptual entity can be defined. The results of this study revealed that children with ASD report the flash-beep illusion over an extended range of stimulus onset asynchronies relative to children with typical development, suggesting that children with ASD have altered multisensory temporal function. These findings provide valuable new insights into our understanding of sensory processing in ASD and may hold promise for the development of more sensitive diagnostic measures and improved remediation strategies

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer