The topology, structure and PE interaction of LITAF underpin a Charcot-Marie-Tooth disease type 1C

BACKGROUND: Mutations in Lipopolysaccharide-induced tumour necrosis factor-α factor (LITAF) cause the autosomal dominant inherited peripheral neuropathy, Charcot-Marie-Tooth disease type 1C (CMT1C). LITAF encodes a 17 kDa protein containing an N-terminal proline-rich region followed by an evolutionarily-conserved C-terminal 'LITAF domain', which contains all reported CMT1C-associated pathogenic mutations. RESULTS: Here, we report the first structural characterisation of LITAF using biochemical, cell biological, biophysical and NMR spectroscopic approaches. Our structural model demonstrates that LITAF is a monotopic zinc-binding membrane protein that embeds into intracellular membranes via a predicted hydrophobic, in-plane, helical anchor located within the LITAF domain. We show that specific residues within the LITAF domain interact with phosphoethanolamine (PE) head groups, and that the introduction of the V144M CMT1C-associated pathogenic mutation leads to protein aggregation in the presence of PE. CONCLUSIONS: In addition to the structural characterisation of LITAF, these data lead us to propose that an aberrant LITAF-PE interaction on the surface of intracellular membranes contributes to the molecular pathogenesis that underlies this currently incurable disease.Wellcome-Beit Prize; Intermediate Clinical Fellowship (093809/Z/10/Z); Wellcome Trust Strategic Award 100140; Wellcome Trust grant 09302

What predicts medical lethality of suicide attempts in Asian youths?

This study explores youth suicide attempts in Singapore using multiple databases of comprehensive archivalrecords. Three years of medical records related to suicide attempters (N = 666) who were admitted to theemergency department of a large teaching hospital in Singapore were subjected to retrospective analysis.Compared to other age groups, a peak in suicide attempts (n = 207) was observed in youths aged between 15and 24 years old (76.3% females; 23.7% males, mean age = 19.30, SD = 2.89). The model using recognized riskand protective factors was significant in predicting medical lethality, and correctly classified 62.8% of highlethality cases. Only resolution of precipitant made a unique statistical significant contribution. Analysis wasseparately conducted for males and females. Implications of the findings are discussed

A Randomized Waitlist-Controlled Trial of an Intergenerational Arts and Heritage-Based Intervention in Singapore: Project ARTISAN

Loneliness has become a global major public health concern, with detrimental effects to the young and old. ARTISAN (Aspiration and Resilience Through Intergenerational Storytelling and Art-based Narratives) is a 5-week, 15-h participatory art and group-based intervention that focuses on resilience building and loneliness alleviation among the young and old through a structured multimodal framework held at a museum space. Developed with a Participatory Action Research (PAR) approach, this intervention is evaluated using an open-label waitlist randomized controlled trial design (RCT) comprised of community-dwelling youth and older adults randomized into an intervention group (n = 35) or a waitlist-control group (n = 33). Participants were assessed on standardized self-reported psychometric measures including loneliness, resilience, quality of life, social support, life satisfaction and national identity at three time points. Qualitative data generated during each intervention session as well as acceptability focus groups were recorded and transcribed. Linear mixed modeling analyses revealed that participants in the intervention group experienced improvements in life satisfaction compared to participants in the waitlist-control group (95% CI: 0.22 to 0.77, p &amp;lt; 0.001, Cohen's d = 0.53) immediately after the completion of ARTISAN. Subgroup analyses for youth participants indicated improvements in quality of life (95% CI: 0.16 to 0.52, p &amp;lt; 0.001, d = 1.31) and national identity (95% CI: 0.18 to 0.80, p = 0.002, d = 0.43) in comparison to the waitlist-control group. At 5-weeks follow-up, the intervention group participants continued to experience high levels of life satisfaction (95% CI: 0.04 to 0.42, p = 0.017, d = 0.47), enhancements in resilience (95% CI: 0.07 to 0.55, p = 0.011, d = 0.46), as well as a significant reduction in loneliness (95% CI: −0.34 to −0.08, p = 0.001, d = 0.61) compared to baseline, reflecting the effectiveness and positive residual effects of the ARTISAN intervention. Similarly, the qualitative findings provided support for the intervention and additional insights to the quantitative findings. This holistic intervention framework that integrates stories, arts and heritage for bridging and empowering lives fills a critical gap in knowledge and practice between the arts, health and citizenship, paving the way for further research in creating a more caring and inclusive society with the arts.Clinical Trials Registration:www.ClinicalTrials.gov, identifier: NCT03048708.</jats:p

The association between internet addiction and psychiatric co-morbidity: A meta-analysis

Background: This study evaluates the association between Internal Addiction (IA) and psychiatric co-morbidity in the literature.Methods: Meta-analyses were conducted on cross-sectional, case-control and cohort studies which examined the relationship between IA and psychiatric co-morbidity. Selected studies were extracted from major online databases. The inclusion criteria are as follows: 1) studies conducted on human subjects; 2) IA and psychiatric co-morbidity were assessed by standardised questionnaires; and 3) availability of adequate information to calculate the effect size. Random-effects models were used to calculate the aggregate prevalence and the pooled odds ratios (OR).Results: Eight studies comprising 1641 patients suffering from IA and 11210 controls were included. Our analyses demonstrated a significant and positive association between IA and alcohol abuse (OR = 3.05, 95% CI = 2.14-4.37, z = 6.12, P < 0.001), attention deficit and hyperactivity (OR = 2.85, 95% CI = 2.15-3.77, z = 7.27, P < 0.001), depression (OR = 2.77, 95% CI = 2.04-3.75, z = 6.55, P < 0.001) and anxiety (OR = 2.70, 95% CI = 1.46-4.97, z = 3.18, P = 0.001).Conclusions: IA is significantly associated with alcohol abuse, attention deficit and hyperactivity, depression and anxiety. © 2014 Ho et al.; licensee BioMed Central Ltd

Genetic diversity analysis and marker-trait associations in Amaranthus species

Amaranth (Amaranthus spp.) is a highly nutritious, underutilized vegetable and pseudo-cereal crop. It possesses diverse abiotic stress tolerance traits, is genetically diverse and highly phenotypically plastic, making it an ideal crop to thrive in a rapidly changing climate. Despite considerable genetic diversity there is a lack of detailed characterization of germplasm or population structures. The present study utilized the DArTSeq platform to determine the genetic relationships and population structure between 188 amaranth accessions from 18 agronomically important vegetable, grain, and weedy species. A total of 74, 303 SNP alleles were generated of which 63, 821 were physically mapped to the genome of the grain species A. hypochondriacus Population structure was inferred in two steps. First, all 188 amaranth accessions comprised of 18 species and second, only 120 A. tricolor accessions. After SNP filtering, a total of 8,688 SNPs were generated on 181 amaranth accessions of 16 species and 9,789 SNPs generated on 118. tricolor accessions. Both SNP datasets produced three major sub-populations (K = 3) and generate consistent taxonomic classification of the amaranth sub-genera Amaranthus Amaranthus, Amaranthus Acnida and Amaranthus albersia, although the accessions were poorly demarcated by geographical origin and morphological traits. A. tricolor accessions were well discriminated from other amaranth species. A genome-wide association study (GWAS) of 10 qualitative traits revealed an association between specific phenotypes and genetic variants within the genome and identified 22 marker trait associations (MTAs) and 100 MTAs (P≤0.01, P≤0.001) on 16 amaranth species and 118. datasets, respectively. The release of SNP markers from this panel has produced invaluable preliminary genetic information for phenotyping and cultivar improvement in amaranth species

Physiological Screening for Drought Tolerance Traits in Vegetable Amaranth (Amaranthus tricolor) Germplasm

Amaranth (Amaranthus tricolor), an underutilized climate smart crop, is highly nutritious and possesses diverse drought tolerance traits, making it an ideal crop to thrive in a rapidly changing climate. Despite considerable studies on the growth and physiology of plants subjected to drought stress, a precise trait phenotyping strategy for drought tolerance in vegetable amaranth is still not well documented. In this study, two drought screening trials were carried out on 44 A. tricolor accessions in order to identify potential drought-tolerant A. tricolor germplasm and to discern their physiological responses to drought stress. The findings revealed that a change in stem biomass was most likely the main mechanism of drought adaptation for stress recovery, and dark-adapted quantum yield (Fv/Fm) could be a useful parameter for identifying drought tolerance in amaranth. Three drought tolerance indices: geometric mean productivity (GMP), mean productivity (MP) and stress tolerance index (STI) identified eight drought-tolerant accessions with stable performance across the two screening trials. The highly significant genotypic differences observed in several physiological traits among the amaranth accessions indicate that the amaranth panel used in this study could be a rich source of genetic diversity for breeding purposes for drought tolerance traits