Interhemispheric white matter integrity in young people with bipolar disorder and at high genetic risk

White matter (WM) impairments have been reported in patients with bipolar disorder (BD) and those at high familial risk of developing BD. However, the distribution of these impairments has not been well characterized. Few studies have examined WM integrity in young people early in the course of illness and in individuals at familial risk who have not yet passed the peak age of onset. WM integrity was examined in 63 BD subjects, 150 high-risk (HR) individuals and 111 participants with no family history of mental illness (CON). All subjects were aged 12 to 30 years. This young BD group had significantly lower fractional anisotropy within the genu of the corpus callosum (CC) compared with the CON and HR groups. Moreover, the abnormality in the genu of the CC was also present in HR participants with recurrent major depressive disorder (MDD) (n = 16) compared with CON participants. Our findings provide important validation of interhemispheric abnormalities in BD patients. The novel finding in HR subjects with recurrent MDD – a group at particular risk of future hypo/manic episodes – suggests that this may potentially represent a trait marker for BD, though this will need to be confirmed in longitudinal follow-up studies

The desmosomal cadherin desmoglein-3 acts as a keratinocyte anti-stress protein via suppression of p53

Desmoglein-3 (Dsg3), the Pemphigus Vulgaris (PV) antigen (PVA), plays an essential role in keratinocyte cell–cell adhesion and regulates various signaling pathways involved in the progression and metastasis of cancer where it is upregulated. We show here that expression of Dsg3 impacts on the expression and function of p53, a key transcription factor governing the responses to cellular stress. Dsg3 depletion increased p53 expression and activity, an effect enhanced by treating cells with UVB, mechanical stress and genotoxic drugs, whilst increased Dsg3 expression resulted in the opposite effects. Such a pathway in the negative regulation of p53 by Dsg3 was Dsg3 specific since neither E-cadherin nor desmoplakin knockdown caused similar effects. Analysis of Dsg3−/− mouse skin also indicated an increase of p53/p21WAF1/CIP1 and cleaved caspase-3 relative to Dsg3+/− controls. Finally, we evaluated whether this pathway was operational in the autoimmune disease PV in which Dsg3 serves as a major antigen involved in blistering pathogenesis. We uncovered increased p53 with diffuse cytoplasmic and/or nuclear staining in the oral mucosa of patients, including cells surrounding blisters and the pre-lesional regions. This finding was verified by in vitro studies where treatment of keratinocytes with PV sera, as well as a characterized pathogenic antibody specifically targeting Dsg3, evoked pronounced p53 expression and activity accompanied by disruption of cell–cell adhesion. Collectively, our findings suggThe study was supported by the Barts and The London School of Medicine and Dentistry and Guizhou Medical University, China. The animal work was supported by Deutsche Forschungsgemeinschaft (TR-SFB 156). Jutamas Uttagomol was supported by a scholarship from Naresuan University, Thailand

Sniffing the city: issues of sousveillance in inner city London

This article reflects on a series of workshops run by the art/media/hacktivist collective Deptford.TV in collaboration with the Centre for Urban and Community Research (CUCR), Goldsmiths, University of London in 2009–2010 and in 2012. The aim of the workshops was to create short films using hacked CCTV material. Participants, equipped with digital video signal receivers, were led through the city by incoming surveillance camera signals. Receivers cached surveillance camera signals making a range of city spaces visible. The material was then stored on a shared video platform and reshuffled in personal narratives and montages of the city. Hackers and media artists call it ‘sousveillance’ and frame it as a critique of the ‘panopticon society’. I argue that this practice reveals an unusually realistic portrait of inner city London and its working-class population at their everyday work. My contention is that the absence of such activities in narratives of gentrification and the presumed end of manual work make this portrait particularly valuable. The article evaluates this emerging and ethically controversial practice of video recording, asking to what extent it can become a useful tool for urban scholars, visual sociologists and media artists. In conclusion, I argue that the exercise provides moments of self-discovery for the urban stroller, who – while practicing a sort of heroic immersion in inner city London – paradoxically becomes a watcher of scenes from life fabricated at a ‘safe’ distance; a middle way between urban ethnographer and flâneur

Impact of a mobile phone and web program on symptom and functional outcomes for people with mild-to-moderate depression, anxiety and stress: a randomised controlled trial.

Background Mobile phone-based psychological interventions enable real time self-monitoring and self-management, and large-scale dissemination. However, few studies have focused on mild-to-moderate symptoms where public health need is greatest, and none have targeted work and social functioning. This study reports outcomes of a CONSORT-compliant randomised controlled trial (RCT) to evaluate the efficacy of myCompass, a self-guided psychological treatment delivered via mobile phone and computer, designed to reduce mild-to-moderate depression, anxiety and stress, and improve work and social functioning. Method Community-based volunteers with mild-to-moderate depression, anxiety and/or stress (N= 720) were randomly assigned to the myCompass program, an attention control intervention, or to a waitlist condition for seven weeks. The interventions were fully automated, without any human input or guidance. Participants’ symptoms and functioning were assessed at baseline, post-intervention and 3-month follow-up, using the Depression, Anxiety and Stress Scale and the Work and Social Adjustment Scale. Results Retention rates at post-intervention and follow-up for the study sample were 72.1% (n= 449) and 48.6% (n= 350) respectively. The myCompass group showed significantly greater improvement in symptoms of depression, anxiety and stress and in work and social functioning relative to both control conditions at the end of the 7-week intervention phase (between-group effect sizes ranged from d= .22 to d= .55 based on the observed means). Symptom scores remained at near normal levels at 3-month follow-up. Participants in the attention control condition showed gradual symptom improvement during the post-intervention phase and their scores did not differ from the myCompass group at 3-month follow-up. Conclusions The myCompass program is an effective public health program, facilitating rapid improvements in symptoms and in work and social functioning for individuals with mild-to-moderate mental health problems

Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms

Stability and Hydrolyzation of Metal Organic Frameworks with Paddle-Wheel SBUs upon Hydration

Instability of most prototypical metal organic frameworks (MOFs) in the presence of moisture is always a limita- tion for industrial scale development. In this work, we examine the dissociation mechanism of microporous paddle wheel frameworks M(bdc)(ted)0.5 [M=Cu, Zn, Ni, Co; bdc= 1,4-benzenedicarboxylate; ted= triethylenediamine] in controlled humidity environments. Combined in-situ IR spectroscopy, Raman, and Powder x-ray diffraction measurements show that the stability and modification of isostructual M(bdc)(ted)0.5 compounds upon exposure to water vapor critically depend on the central metal ion. A hydrolysis reaction of water molecules with Cu-O-C is observed in the case of Cu(bdc)(ted)0.5. Displacement reactions of ted linkers by water molecules are identified with Zn(bdc)(ted)0.5 and Co(bdc)(ted)0.5. In contrast,. Ni(bdc)(ted)0.5 is less suscept- ible to reaction with water vapors than the other three compounds. In addition, the condensation of water vapors into the framework is necessary to initiate the dissociation reaction. These findings, supported by supported by first principles theoretical van der Waals density functional (vdW-DF) calculations of overall reaction enthalpies, provide the necessary information for de- termining operation conditions of this class of MOFs with paddle wheel secondary building units and guidance for developing more robust units