Gene expression changes related to immune processes associate with cognitive endophenotypes of schizophrenia

Schizophrenia is a heterogeneous disorder characterized by a spectrum of symptoms and many different underlying causes. Thus, instead of using the broad diagnosis, intermediate phenotypes can be used to possibly decrease the underlying complexity of the disorder. Alongside the classical symptoms of delusions and hallucinations, cognitive deficits are a core feature of schizophrenia. To increase our understanding of the biological processes related to these cognitive deficits, we performed a genome-wide gene expression analysis. A battery of 14 neuropsychological tests was administered to 844 individuals from a Finnish familial schizophrenia cohort. We grouped the applied neuropsychological tests into five factors for further analysis. Cognitive endophenotypes, whole blood mRNA, genotype, and medication use data were studied from 47 individuals. Expression level of several RNA probes were significantly associated with cognitive performance. The factor representing Verbal Working Memory was associated with altered expression levels of 11 probes, of which one probe was also associated with a specific sub-measure of this factor (WMS-R Digit span backward). While, the factor Processing speed was related to one probe, which additionally associated among 55 probes with a specific sub-measure of this factor (WAIS-R Digit symbol). Two probes were associated with the measure recognition memory performance. Enrichment analysis of these differentially expressed probes highlighted immunological processes. Our findings are in line with genome-wide genetic discoveries made in schizophrenia, suggesting that immunological processes may be of biological interest for future drug design towards schizophrenia and the cognitive dysfunctions that underlie it.Peer reviewe

The first human report of mobile colistin resistance gene, mcr-1, in Finland

Colistin resistance mediated by mobile mcr-1 gene has raised concern during the last years. After steep increase in mcr-1 reports, other mcr-gene variants (mcr-2 to mcr-5) have been revealed as well. In 2016, a clinical study was conducted on asymptomatic stool carriage of extended spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae among Finnish adults. All suspected ESBL producing bacterial isolates were first tested by phenotypic ESBL-confirmation methods, and then further analyzed with whole genome sequencing to identify the resistance genes. We found one study subject carrying a colistin resistant E.coli with a transferrable mcr-1 gene. This multi-drug resistant isolate, although initially suspected to be an ESBL producer, did not carry any ESBL genes, but was proven to carry several other resistance genes by using whole genome sequencing. Sequence type was ST93. The mcr-1 gene was connected to IncX4 plasmid which suggests that the colistin resistance gene locates in the respective plasmid. Here, we report the finding of a mcr-1 harboring human E.coli isolate from Finland. Clinical antimicrobial resistance (AMR) rates are low in Finland, and mobile colistin resistance has not been reported previously. This highlights the importance of AMR surveillance also in populations with low levels of resistance

A multicenter study on Leigh syndrome: Disease course and predictors of survival

Background: Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. Methods. This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. Results: A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, w

Food and nutrient intake in relation to mental wellbeing

BACKGROUND: We studied food consumption and nutrient intake in subjects with depressed mood, anxiety and insomnia as indices of compromised mental wellbeing. METHODS: The study population consisted of 29,133 male smokers aged 50 to 69 years who entered the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study in 1985–1988. This was a placebo-controlled trial to test whether supplementation with alpha-tocopherol or beta-carotene prevents lung cancer. At baseline 27,111 men completed a diet history questionnaire from which food and alcohol consumption and nutrient intake were calculated. The questionnaire on background and medical history included three symptoms on mental wellbeing, anxiety, depression and insomnia experienced in the past four months. RESULTS: Energy intake was higher in men who reported anxiety or depressed mood, and those reporting any such symptoms consumed more alcohol. Subjects reporting anxiety or depressed mood had higher intake of omega-3 fatty acids and omega-6 fatty acids. CONCLUSIONS: Our findings conflict with the previous reports of beneficial effects of omega-3 fatty acids on mood

Strong Magnetic Field Fluctuations within Filamentary Auroral Density Cavities Interpreted as VLF Saucer Sources

The Geoelectrodynamics and Electro-Optical Detection of Electron and SuprathermalIon Currents (GEODESIC) sounding rocket encountered more than 100 filamentary densitycavities associated with enhanced plasma waves at ELF (3 kHz) and VLF (310 kHz)frequencies and at altitudes of 800990 km during an auroral substorm. These cavities weresimilar in size (20 m diameter in most cases) to so-called lower-hybrid cavities (LHCs)observed by previous sounding rockets and satellites; however, in contrast, many of theGEODESIC cavities exhibited up to tenfold enhancements in magnetic wave powerthroughout the VLF band. GEODESIC also observed enhancements of ELF and VLFelectric fields both parallel and perpendicular to the geomagnetic field B0 within cavities,though the VLF E field increases were often not as large proportionally as seen in themagnetic fields. This behavior is opposite to that predicted by previously published theoriesof LHCs based on passive scattering of externally incident auroral hiss. We argue thatthe GEODESIC cavities are active wave generation sites capable of radiating VLF wavesinto the surrounding plasma and producing VLF saucers, with energy supplied by cold,upward flowing electron beams composing the auroral return current. This interpretation issupported by the observation that the most intense waves, both inside and outside cavities,occurred in regions where energetic electron precipitation was largely inhibited orabsent altogether. We suggest that the wave-enhanced cavities encountered by GEODESICwere qualitatively different from those observed by earlier spacecraft because of thefortuitous timing of the GEODESIC launch, which placed the payload at apogee within asubstorm-related return current during its most intense phase, lasting only a few minutes

Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia.

Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). This complex orchestrates the attachment of the GPI anchor to the C terminus of precursor proteins in the endoplasmic reticulum. Here, we report bi-allelic mutations in GPAA1 in ten individuals from five families. Using whole-exome sequencing, we identified two frameshift mutations (c.981_993del [p.Gln327Hisfs∗102] and c.920delG [p.Gly307Alafs∗11]), one intronic splicing mutation (c.1164+5C>T), and six missense mutations (c.152C>T [p.Ser51Leu], c.160_161delinsAA [p.Ala54Asn], c.527G>C [p.Trp176Ser], c.869T>C [p.Leu290Pro], c.872T>C [p.Leu291Pro], and c.1165G>C [p.Ala389Pro]). Most individuals presented with global developmental delay, hypotonia, early-onset seizures, cerebellar atrophy, and osteopenia. The splicing mutation was found to decrease GPAA1 mRNA. Moreover, flow-cytometry analysis of five available individual samples showed that several GPI-anchored proteins had decreased cell-surface abundance in leukocytes (FLAER, CD16, and CD59) or fibroblasts (CD73 and CD109). Transduction of fibroblasts with a lentivirus encoding the wild-type protein partially rescued the deficiency of GPI-anchored proteins. These findings highlight the role of the transamidase complex in the development and function of the cerebellum and the skeletal system

The spatio-relational nature of urban innovation systems: Universities, knowledge intensive business service firms, and collaborative networks

The need to better identify the spatio-relational nature of urban innovation systems and spaces is increasingly acknowledged. The aim of this paper, therefore, is to provide an enhanced understanding of the knowledge networks existing between urban Knowledge Intensive Business Services firms (KIBS) and universities, which are often key components of such systems and spaces. Drawing on an analysis of urban KIBS firms and universities in the UK, it is found that the nature of firms, the location in which they are based, and the research intensity of their university partners are important determinants of the spatiality and localisation of the networks they form. The results show that the smallest urban KIBS firms have the highest propensity to engage in local links with universities, suggesting that they rely most significantly on their own urban innovation system for collaborative network ties. Keywords : innovation systems; urban innovation spaces; knowledge-based development; proximity; networks; KIBS; universities

Emirati women do not shy away from competition: evidence from a patriarchal society in transition

We explore gender attitudes towards competition in the United Arab Emirates—a traditionally patriarchal society which in recent times has adopted numerous policies to empower women and promote their role in the labor force. The experimental treatments vary whether individuals compete in single-sex or mixed-sex groups. In contrast to previous studies, women in our sample are not less willing to compete than men. In fact, once we control for individual performance, Emirati women are more likely to select into competition. Our analysis shows that neither women nor men shy away from competition, and both compete more than what would be optimal in monetary terms as the fraction of men in their group increases. We offer a detailed survey of the literature and discuss possible reasons for the lack of gender differences in our experiment

Contribution of astrocytes to familial risk and clinical manifestation of schizophrenia

Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)-derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron-astrocyte co-cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ.Peer reviewe

Repetition and severity of suicide attempts across the life cycle: a comparison by age group between suicide victims and controls with severe depression

<p>Abstract</p> <p>Background</p> <p>Suicide attempts have been shown to be less common in older age groups, with repeated attempts generally being more common in younger age groups and severe attempts in older age groups. Consistently, most studies have shown an increased suicide risk after attempts in older age. However, little is known about the predictive value of age on repeated and severe suicide attempts for accomplished suicide. The aim of the present study was to investigate the reduced incidence for initial, repeated, or severe suicide attempts with age in suicide victims and controls by gender.</p> <p>Methods</p> <p>The records of 100 suicide victims and matched controls with severe depression admitted to the Department of Psychiatry, Lund University Hospital, Sweden between 1956 and 1969, were evaluated and the subjects were monitored up to 2006. The occurrence of suicide attempts (first, repeated, or severe, by age group) was analysed for suicide victims and controls, with gender taken into consideration.</p> <p>Results</p> <p>There was a reduced risk for an initial suicide attempt by older age in females (suicide victims and controls) and male controls (but not suicide victims). The risk for repeated suicide attempts appeared to be reduced in the older age groups in female controls as compared to female suicide victims. The risk for severe suicide attempts seemed reduced in the older age groups in female suicide victims. This risk was also reduced in male controls and in male controls compared to male suicide victims.</p> <p>Conclusion</p> <p>In the older age groups repeated attempts appeared to be predictive for suicide in women and severe attempts predictive in men.</p