scholarly journals Uncovering bi-directional causal relationships between plasma proteins and psychiatric disorders: A proteome-wide study and directed network analysis

2019 ◽  
Author(s):  
Carlos Kwan-long Chau ◽  
Alexandria Lau ◽  
Pak-Chung Sham ◽  
Hon-Cheong So
Keyword(s):  
Psychiatric Disorders ◽  
Plasma Proteins ◽  
Large Scale ◽  
Progress Monitoring ◽  
Drug Repositioning ◽  
Directed Network ◽  
Public Health Burden ◽  
Protein Levels ◽  
Complex Relationships ◽  
The Uk

AbstractPsychiatric disorders represent a major public health burden yet their etiologies remain poorly understood, and treatment advances are limited. In addition, there are no reliable biomarkers for diagnosis or progress monitoring.Here we performed a proteome-wide causal association study covering 3522 plasma proteins and 24 psychiatric traits or disorders, based on large-scale GWAS data and the principle of Mendelian randomization (MR). We have conducted ~95,000 MR analyses in total; to our knowledge, this is the most comprehensive study on the causal relationship between plasma proteins and psychiatric traits.The analysis was bi-directional: we studied how proteins may affect psychiatric disorder risks, but also looked into how psychiatric traits/disorders may be causal risk factors for changes in protein levels. We also performed a variety of additional analysis to prioritize protein-disease associations, including HEIDI test for distinguishing functional association from linkage, analysis restricted to cis- acting variants and replications in independent datasets from the UK Biobank. Based on the MR results, we constructed directed networks linking proteins, drugs and different psychiatric traits, hence shedding light on their complex relationships and drug repositioning opportunities. Interestingly, many top proteins were related to inflammation or immune functioning. The full results were also made available online in searchable databases.In conclusion, identifying proteins causal to disease development have important implications on drug discovery or repurposing. Findings from this study may also guide the development of blood-based biomarkers for the prediction or diagnosis of psychiatric disorders, as well as assessment of disease progression or recovery.

Proteins Associated with Risk of Kidney Function Decline in the General Population

2021 ◽  
Vol 32 (9) ◽  
pp. 2291-2302
Author(s):  
Morgan E. Grams ◽  
Aditya Surapaneni ◽  
Jingsha Chen ◽  
Linda Zhou ◽  
Zhi Yu ◽  
...  
Keyword(s):  
Kidney Function ◽  
Plasma Proteins ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Proteomic Profiling ◽  
Content Type ◽  
Protein Levels ◽  
Time Periods ◽  
Egfr Decline

BackgroundProteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD.MethodsWe quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate <5%) in both time periods in 3249 participants in the Chronic Renal Insufficiency Cohort (CRIC) and 703 participants in the African American Study of Kidney Disease and Hypertension (AASK). We also compared the genetic determinants of protein levels with those from a meta-analysis genome-wide association study of eGFR.ResultsIn models adjusted for multiple covariates, including baseline eGFR and albuminuria, we identified 13 distinct proteins that were significantly associated with the composite end point in both time periods, including TNF receptor superfamily members 1A and 1B, trefoil factor 3, and β-trace protein. Of these proteins, 12 were also significantly associated in CRIC, and nine were significantly associated in AASK. Higher levels of each protein associated with higher risk of 50% eGFR decline or ESKD. We found genetic evidence for a causal role for one protein, lectin mannose-binding 2 protein (LMAN2).ConclusionsLarge-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

scholarly journals Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders

2019 ◽  
Vol 79 ◽  
pp. 152-158 ◽  
Author(s):  
Kristoffer Sølvsten Burgdorf ◽  
Betina B. Trabjerg ◽  
Marianne Giørtz Pedersen ◽  
Janna Nissen ◽  
Karina Banasik ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Large Scale ◽  
Large Scale Study

Origin and distribution of dolomite in Permian Rotliegend siliciclastic sandstones (Dutch Southern Permian Basin)

2019 ◽  
Vol 89 (10) ◽  
pp. 1055-1073 ◽  
Author(s):  
Nicolaas Molenaar ◽  
Marita Felder
Keyword(s):  
Large Scale ◽  
Permian Basin ◽  
Advective Flow ◽  
Gas Reservoirs ◽  
Carbonate Cement ◽  
Thin Section Petrography ◽  
The Uk ◽  
Pressure Dissolution ◽  
Dolomite Cement ◽  
Detrital Carbonate

ABSTRACT Dolomite is a common and volumetrically important mineral in many siliciclastic sandstones, including Permian Rotliegend sandstones (the Slochteren Formation). These sandstones form extensive gas reservoirs in the Southern Permian Basin in the Netherlands, Germany, Poland, and the UK. The reservoir quality of these sandstones is negatively influenced by the content and distribution of dolomite. The origin and the stratigraphic distribution of the dolomite is not yet fully understood. The aim of this study is to identify the origin of carbonate. The main methods used to achieve those aims are a combination of thin-section petrography, scanning electron microscopy (SEM and EDX), and XRD analyses. The present study shows that the typical dispersed occurrence of the dolomite is a consequence of dispersed detrital carbonate grains that served both as nuclei and source for authigenic dolomite cement. The dolomite cement formed syntaxial outgrowths and overgrowths around detrital carbonate grains. The study also shows that dolomite cement, often in combination with ankerite and siderite, precipitated during burial after mechanical compaction. Most of the carbonate grains consisted of dolomite before deposition. The carbonate grains were affected by compaction and pressure dissolution, and commonly have no well-defined outlines anymore. The distribution of dolomite cement in the Rotliegend sandstones was controlled by the presence of stable carbonate grains. Due to the restricted and variable content of carbonate grains and their dispersed occurrence, the cement is also dispersed and the degree of cementation heterogeneous. Our findings have important implications on diagenesis modeling. The presence of detrital carbonate excludes the need for external supply by any large-scale advective flow of diagenetic fluids. By knowing that the carbonate source is local and related to detrital grains instead of being externally derived from an unknown source, the presence of carbonate cement can be linked to a paleogeographic and sedimentological model.

scholarly journals Psychiatric disorders in China: strengths and challenges of contemporary research and clinical services

2021 ◽  
pp. 1-14
Author(s):  
Xiao Chang ◽  
Qiyong Gong ◽  
Chunbo Li ◽  
Weihua Yue ◽  
Xin Yu ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Disease Burden ◽  
Large Scale ◽  
Well Being ◽  
Research Quality ◽  
Psychiatric Research ◽  
Clinical Services ◽  
Contributing Factors ◽  
Brain Functions ◽  
Neuroscience Research

Abstract China accounts for 17% of the global disease burden attributable to mental, neurological and substance use disorders. As a country undergoing profound societal change, China faces growing challenges to reduce the disease burden caused by psychiatric disorders. In this review, we aim to present an overview of progress in neuroscience research and clinical services for psychiatric disorders in China during the past three decades, analysing contributing factors and potential challenges to the field development. We first review studies in the epidemiological, genetic and neuroimaging fields as examples to illustrate a growing contribution of studies from China to the neuroscience research. Next, we introduce large-scale, open-access imaging genetic cohorts and recently initiated brain banks in China as platforms to study healthy brain functions and brain disorders. Then, we show progress in clinical services, including an integration of hospital and community-based healthcare systems and early intervention schemes. We finally discuss opportunities and existing challenges: achievements in research and clinical services are indispensable to the growing funding investment and continued engagement in international collaborations. The unique aspect of traditional Chinese medicine may provide insights to develop a novel treatment for psychiatric disorders. Yet obstacles still remain to promote research quality and to provide ubiquitous clinical services to vulnerable populations. Taken together, we expect to see a sustained advancement in psychiatric research and healthcare system in China. These achievements will contribute to the global efforts to realize good physical, mental and social well-being for all individuals.

scholarly journals Genetic and Molecular Analysis of Region 88E9;88F2 in Drosophila melanogaster, Including the ear Gene Related to Human Factors Involved in Lineage-Specific Leukemias

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 1051-1065
Author(s):  
Claudia B Zraly ◽  
Yun Feng ◽  
Andrew K Dingwall
Keyword(s):  
Large Scale ◽  
Drosophila Genome ◽  
Embryonic Cells ◽  
Ems Mutagenesis ◽  
Recessive Lethal ◽  
Protein Levels ◽  
Late Embryogenesis ◽  
Complementation Groups ◽  
Mammalian Genes ◽  
Map Location

Abstract We identified and characterized the Drosophila gene ear (ENL/AF9-related), which is closely related to mammalian genes that have been implicated in the onset of acute lymphoblastic and myelogenous leukemias when their products are fused as chimeras with those of human HRX, a homolog of Drosophila trithorax. The ear gene product is present in all early embryonic cells, but becomes restricted to specific tissues in late embryogenesis. We mapped the ear gene to cytological region 88E11-13, near easter, and showed that it is deleted by Df(3R)ea5022rx1, a small, cytologically invisible deletion. Annotation of the completed Drosophila genome sequence suggests that this region might contain as many as 26 genes, most of which, including ear, are not represented by mutant alleles. We carried out a large-scale noncom-plementation screen using Df(3R)ea5022rx1 and chemical (EMS) mutagenesis from which we identified sevenc novel multi-allele recessive lethal complementation groups in this region. An overlapping deficiency, Df(3R)Po4, allowed us to map several of these groups to either the proximal or the distal regions of Df(3R)ea5022rx1. One of these complementation groups likely corresponds to the ear gene as judged by map location, terminal phenotype, and reduction of EAR protein levels.

scholarly journals Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK

Science ◽  
2021 ◽  
pp. eabf2946
Author(s):  
Louis du Plessis ◽  
John T. McCrone ◽  
Alexander E. Zarebski ◽  
Verity Hill ◽  
Christopher Ruis ◽  
...  
Keyword(s):  
Large Scale ◽  
Phylogenetic Analyses ◽  
Transmission Dynamics ◽  
Genetic Lineage ◽  
Size Dependent ◽  
Spatio Temporal ◽  
The Uk ◽  
Lineage Structure ◽  
And Control ◽  
Lineage Diversity

The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, while lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

scholarly journals Collateral impact of COVID-19: why should children continue to suffer?

2021 ◽  
Author(s):  
Prasad Nagakumar ◽  
Ceri-Louise Chadwick ◽  
Andrew Bush ◽  
Atul Gupta
Keyword(s):  
Young People ◽  
Large Scale ◽  
Hospital Admissions ◽  
Severe Disease ◽  
Children And Young People ◽  
Collateral Effects ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Set Up ◽  
The Uk

AbstractThe COVID-19 pandemic caused by SARS-COV-2 virus fortunately resulted in few children suffering from severe disease. However, the collateral effects on the COVID-19 pandemic appear to have had significant detrimental effects on children affected and young people. There are also some positive impacts in the form of reduced prevalence of viral bronchiolitis. The new strain of SARS-COV-2 identified recently in the UK appears to have increased transmissibility to children. However, there are no large vaccine trials set up in children to evaluate safety and efficacy. In this short communication, we review the collateral effects of COVID-19 pandemic in children and young people. We highlight the need for urgent strategies to mitigate the risks to children due to the COVID-19 pandemic. What is Known:• Children and young people account for <2% of all COVID-19 hospital admissions• The collateral impact of COVID-19 pandemic on children and young people is devastating• Significant reduction in influenza and respiratory syncytial virus (RSV) infection in the southern hemisphere What is New:• The public health measures to reduce COVID-19 infection may have also resulted in near elimination of influenza and RSV infections across the globe• A COVID-19 vaccine has been licensed for adults. However, large scale vaccine studies are yet to be initiated although there is emerging evidence of the new SARS-COV-2 strain spreading more rapidly though young people.• Children and young people continue to bear the collateral effects of COVID-19 pandemic

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