Gerard Cagney's research while affiliated with University College Dublin and other places
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Publications (178)
The complement cascade is a major component of the immune defence against infection, and there is increasing evidence for a role of dysregulated complement in major psychiatric disorders. We undertook a directed proteomic analysis of the complement signalling pathway (n = 29 proteins) using data-independent acquisition. Participants were recruited...
Triple-negative breast cancer (TNBC) is a subtype of breast cancer without a targeted form of therapy. Unfortunately, up to 70% of patients with TNBC develop resistance to treatment. A known contributor to chemoresistance is dysfunctional mitochondrial apoptosis signaling. We set up a phenotypic small-molecule screen to reveal vulnerabilities in TN...
Schizophrenia is a heterogeneous disorder associated with many genetic and environmental risk factors that could affect brain development. It is unknown whether adolescent-onset and adult-onset schizophrenia have similar aetiology. To address this we used discovery-based proteomics to find proteins differentially expressed in olfactory neurosphere-...
Importance
Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies.
Objective
To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (P...
Background
Individuals at clinical high risk (CHR) of psychosis have an approximately 20% probability of developing psychosis within 2 years, as well as an associated risk of non-psychotic disorders and functional impairment. People with subclinical psychotic experiences (PEs) are also at risk of future psychotic and non-psychotic disorders and dec...
We have developed a platform for quantitative genetic interaction mapping using viral infectivity as a functional readout and constructed a viral host-dependency epistasis map (vE-MAP) of 356 human genes linked to HIV function, comprising >63,000 pairwise genetic perturbations. The vE-MAP provides an expansive view of the genetic dependencies under...
Stenotrophomonas maltophilia is an emerging global opportunistic pathogen that has been appearing with increasing prevalence in cystic fibrosis (CF). A secreted protease from S. maltophilia has been reported as its chief potential virulence factor. Here, using the reference clinical strain S. maltophilia K279a, the major secreted proteases were ide...
SETD1A is a SET domain-containing methyltransferase involved in epigenetic regulation of transcription. It is the main catalytic component of a multiprotein complex that methylates lysine 4 of histone H3, a histone mark associated with gene activation. In humans, six related protein complexes with partly nonredundant cellular functions share severa...
Apolipoproteins, which play important roles in lipid metabolism, innate immunity and synaptic signalling, have been implicated in first episode psychosis and schizophrenia. This is the first study to investigate plasma apolipoprotein expression in children with psychotic experiences that persist into adulthood. Here, using semi-targeted proteomic a...
Background
Exposure to infectious microorganisms has been implicated as an important risk factor in the development of psychotic disorders. Epidemiological and laboratory evidence suggests that exposure at various developmental periods may increase psychosis risk, from in utero through to childhood and adult life. Individuals who meet clinical high...
Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable comp...
Cell differentiation is directed by extracellular cues and intrinsic epigenetic modifications, which control chromatin organization and transcriptional activation. Central to this process is PRC2, which modulates the di- and trimethylation of lysine 27 on histone 3; however, little is known concerning the direction of PRC2 to specific loci. Here, w...
Background
The identification of early biomarkers of psychotic experiences (PEs) is of interest as early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study...
Synovial sarcoma tumours contain a characteristic fusion protein, SS18-SSX, which drives disease development. Targeting oncogenic fusion proteins presents an attractive therapeutic opportunity. However, SS18-SSX has proven intractable for therapeutic intervention. Using a domain-focused CRISPR screen we identified the bromodomain of BRD9 as a criti...
Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the corresponding datasets at the protein complex and fun...
Evidence exists to support the role the dairy derived proteins whey and casein in glycaemic management. The objective of the present was use a cell screening method to identify a suitable casein hydrolysate and to examine its ability to impact on glycaemia related parameters in animal models and in humans. Following screening for ability to stimula...
Background
The identification of early biomarkers of psychotic disorder is important because early treatment is associated with improved outcome. We have previously shown that altered complement and coagulation pathway associated proteins are associated pathway with psychotic disorder at age 18. In the current study we test the hypothesis that alte...
Background
The identification of early biomarkers of psychotic disorder is important because early treatment is associated with improved outcome. We have previously shown that altered complement and coagulation pathway associated proteins are associated pathway with psychotic disorder at age 18. In the current study we test the hypothesis that alte...
Background
The OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial may help in the identification of predictors of treatment response. Medication naïve patients with first episode schizophrenia or schizophreniform disorder were enrolled in the study and treated open-label for a four-week period with amisulpride. PAN...
The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2), little is known about their differential funct...
The Polycomb repressor complex 2 (PRC2) is composed of the core subunits Ezh1/2, Suz12, and Eed, and it mediates all di- and tri-methylation of histone H3 at lysine 27 in higher eukaryotes. However, little is known about how the catalytic activity of PRC2 is regulated to demarcate H3K27me2 and H3K27me3 domains across the genome. To address this, we...
Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organ...
Controversially, histone deacetylase inhibitors (HDACi) are in clinical trial for the treatment of inherited retinal degeneration. Utilizing the zebrafish dyeucd6 model, we determined if treatment with HDACi can rescue cone photoreceptor-mediated visual function. dye exhibit defective visual behaviour and retinal morphology including ciliary margin...
TGFbeta resides at the center of therapeutic approaches for the treatment of renal fibrosis, however despite significant efforts in this area, few intervention studies have demonstrated clinical efficacy. At the core of this issue remains a fundamental gap in our knowledge of gene expression. We recently demonstrated that silencing of the TGFbeta t...
The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Par...
Prenatal iron deficiency (pID) has been described to increase the risk for neurodevelopmental disorders such as autism and schizophrenia; however, the precise molecular mechanisms are still unknown. Here, we utilized high throughput mass spectrometry to examine the proteomic effects of pID in adulthood on the rat frontal cortex area (FCA). In addit...
Sin3a is the central scaffold protein of the prototypical Hdac1/2 chromatin repressor complex, crucially required during early embryonic development for the growth of pluripotent cells of the inner cell mass. Here, we compare the composition of the Sin3a-Hdac complex between pluripotent embryonic stem (ES) and differentiated cells by establishing a...
In this study, we carry out a systematic characterisation of the YIPF family of proteins with respect to their subcellular localisation profile, membrane topology and functional effects on the endomembrane system. YIPF proteins primarily localise to the Golgi complex and can be grouped into trans-Golgi-localising YIPFs (YIPF1 and YIPF2) and cis-Gol...
Background: The identification of early biomarkers of psychotic disorder is important because early treatment is associated with improved outcome. In the current study, our objective was to identify peripheral protein biomarkers and underlying molecular alterations in children that predict the future development of psychotic disorder.
Methods: The...
Scientific Reports 7 : Article number: 42407 10.1038/srep42407 ; published online: 14 February 2017 ; updated: 09 May 2017 The original version of this Article contained errors in the spelling of the authors Letizia De Chiara, Darrell Andrews, Ariane Watson, Giorgio Oliviero, Gerard Cagney and John Crean which were incorrectly given as L.
Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor and facilitated plasticity in a manner distinct from...
Excess blood vessel growth contributes to the pathology of metastatic cancers and age-related retinopathies. Despite development of improved treatments, these conditions are associated with high economic costs and drug resistance. Bevacizumab (Avastin®), a monoclonal antibody against vascular endothelial growth factor (VEGF) is used clinically to t...
Introduction: Recent evidence supports an association between systemic abnormalities and the pathology of psychotic disorders which has led to the search for peripheral blood-based biomarkers.
Areas covered: Here, we summarize blood biomarker findings in schizophrenia from the literature identified by two methods currently driving biomarker discove...
Polyhydroxybutyrate (PHB) is an important biopolymer accumulated by bacteria and associated with cell survival and stress response. Here, we make two surprising findings in the PHB-accumulating species Rhodospirillum rubrum S1. We first show that the presence of PHB promotes the increased assimilation of acetate preferentially into biomass rather t...
Polycomb proteins assemble to form complexes with important roles in epigenetic regulation. The Polycomb Repressive Complex 2 (PRC2) modulates the di- and tri-methylation of lysine 27 on histone H3, each of which are associated with gene repression. Although three subunits, EZH1/2, SUZ12 and EED, form the catalytic core of PRC2, a wider group of pr...
Food protein hydrolysates are complex mixtures that are increasingly being analysed by tandem mass spectrometry. Given a single starting material, many alternative peptide profiles are achievable under varying hydrolysis conditions. To date, characterisation of the relative similarities and differences between such peptide profiles remains largely...
Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory act...
This dataset reports on the analysis of mouse hippocampus by LC–MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). Label free quantitative (LFQ) analysis of the mass spectrometry data identified 1008 quantifiable proteins, 115 of which were found to be differentially expressed between the tw...
PCGF1 encodes one of six human Polycomb RING finger homologs that are linked to transcriptional repression and developmental gene regulation. Individual PCGF proteins define discrete Polycomb Repressor Complex 1 (PRC1) multi-protein complexes with diverse subunit composition whose functions are incompletely understood. PCGF1 is a component of a var...
Native gel electrophoresis enables separation of cellular proteins in their non-denatured state. In experiments aimed at analysing proteins in higher order or multimeric assemblies (i.e. protein complexes) it offers some advantages over rival approaches, particularly as an interface technology with mass spectrometry. Here we separated fractions fro...
Background:
Maternal infection is a risk factor for schizophrenia but the molecular and cellular mechanisms are not fully known. Myelin abnormalities are amongst the most robust neuropathological changes observed in schizophrenia, and preliminary evidence suggests that prenatal inflammation may play a role.
Methods:
Label-free liquid chromatogra...
Regulation of gene expression by proteins associated with chromatin is a major, yet poorly understood, feature of differentiation and development. Recent genomic studies have highlighted the role of chromatin regulatory proteins in pathologies affecting cellular proliferation and cell cycle, such as cancer. Mass spectrometry-based proteomics approa...
The prefrontal cortex is associated with mental health illnesses including schizophrenia, depression, bipolar disorder and autism spectrum disorders. It richly expresses neuroreceptors which are the target for antipsychotics. However as the precise mechanism of action of antipsychotic medications are not known, proteomic studies of the effects of a...
Omega-3 fatty acid (n-3 FA) deficiency is an environmental risk factor for schizophrenia, yet characterization of the consequences of deficiency at the protein level in the brain is limited. We aimed to identify the protein pathways disrupted as a consequence of chronic n-3 deficiency in the hippocampus of mice. Fatty acid analysis of the hippocamp...
The primary enzyme involved in polyphosphate (polyP) synthesis, polyP kinase (ppk), has been deleted in Pseudomonas putida KT2440. This has resulted in a threefold to sixfold reduction in polyhydroxyalkanoate (PHA) accumulation compared with the wild type under conditions of nitrogen limitation, with either temperature or oxidative (H2O2) stress, w...
Mitochondria are the main font of ATP, the principal energy source of the cell, and ROS (Reactive Oxygen Species), important signaling molecules. Mitochondrial morphogenesis and function depend on a hierarchical network of mechanisms in which proteases appear to be center stage. The invadolysin gene encodes an essential, conserved metalloprotease o...
In the budding yeast Saccharomyces cerevisiae the subunits of any given protein complex are either mostly essential, or mostly non-essential, suggesting that essentiality is a property of molecular machines rather than individual components. There are exceptions to this rule however, i.e. non-essential genes in largely essential complexes, and esse...
Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ∼11,000 pairwise knockdowns in mouse fibrobla...
Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb repressive complex 2 (PRC2) componen...
To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe, providing phenotypic signatur...
Depletion of Pcl3 does not affect ESC differentiation to all three germ layers. (A) Protein levels of Pcl3 in scramble and Pcl3 shRNA clones assessed by immunoblot of lysates immunoprecipitated and probed with anti-Pcl3. For a positive control, Pcl3-TAP was immunoprecipitated and probed for FlagM2. Each lane represents a different clone. (B) Immuno...
Supplemental methods. Detailed description of the microarray and ChIP-sequencing methods as well as a list of the antibodies and primers used.
(DOC)
Pcl3 co-localizes with Suz12. (A) Aligning Suz12 and Pcl3 ChIP-seq reads at Pcl3 peak centers shows genome-wide co-localization of Pcl3 with Suz12. (B) To estimate the percentage overlap between Suz12 and Pcl3 binding sites, a sensitivity analysis was performed by varying the Skellam distribution p-value cutoff for calling peaks, ranging between 10...
Gene expression changes upon Pcl3 knockdown by microarray. Microarray data indicating fold changes in gene expression in ESCs expressing Pcl3 shRNA as compared to scramble shRNA ESCs. Comparison included six control samples and six Pcl3 shRNA clones.
(XLS)
Pcl3 knockdown causes the most significant depletion of Suz12 and H3K27me3 on chromosome 11. (A) Number of sequenced and aligned reads for ChIP-sequencing. (B) Partial sums of order statistics of binned read counts in the scramble and Pcl3 shRNA cells were computed, and their ratios are plotted for the Suz12 FlagM2 ChIP and H3K27me3 ChIP. The theor...
Pcl3 misregulates a subset of genes. (A, C) Relative expression of genes that either increased or decreased upon Pcl3 knockdown as measured by qRT-PCR and microarray. Cells were collected following selection for Pcl3 depletion, approximately 3–4 weeks. Microarray and qRT-PCR were performed with 2–6 clones each for control and Pcl3 knockdown ESCs. q...
Gene expression changes in pre-plated Pcl3 shRNA ESCs by microarray. Microarray data indicating fold changes in gene expression in pre-plated ESCs expressing Pcl3 shRNA as compared to scramble shRNA ESCs. Comparison included two scramble clones and two Pcl3 shRNA clones.
(XLS)
Depletion of Suz12 and Pcl3. (A) Quantification of H3K27me3 depletion in Pcl3 shRNA treated cells. Graph shows an approximate 80% decrease in H3K27me3 levels and represents ten experiments using 2–6 clones each. (B) qRT-PCR and (C) immunoblot indicating levels of Suz12 in cells treated with increasing amounts of Suz12 siRNA 48 hrs and 72 hrs post-t...
Suz12-TAP and Pcl3-V5 localize to the nucleus. (A) Schematic of recombination events performed to create Suz12Suz12TAP/+. The wild type endogenous allele is not pictured. Not to scale. (B) Staining of Suz12Suz12TAP/+ with anti-FlagM2 (red), which overlays with nuclei stained with DAPI (blue). Scale bar 10 µm. (C) Suz12 expression levels in wild typ...
Polycomb repressive complex 2 (PRC2) trimethylates lysine 27 of histone H3 (H3K27me3) to regulate gene expression during diverse biological transitions in development, embryonic stem cell (ESC) differentiation, and cancer. Here, we show that Polycomb-like 3 (Pcl3) is a component of PRC2 that promotes ESC self-renewal. Using mass spectrometry, we id...
Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection....
Significantly enriched functional annotation terms associated with gene occupying the 'positive' node of an NPP triplet.
Network of selected NNN motifs with genetic interactions between the nodes. Functional complexes or pathways are highlighted in elliptical bubbles.
List of triplet motifs extracted from the E-MAP compendium.
Genes showing most significant skewness towards positive or negative interactions.
Modules of selected PPP motifs with physical interactions between the nodes.
Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks.
We examined triplet motifs in a network of quantitativ...
Functional enrichment among individual genes pairs in epistatic triplet motifs tested using an independent dataset. A) Explanation of the scoring system. Edges in a triplet are arranged in order of increasing epistasis strength (i, ii, iii), with each position denoted '1' or '0' depending on whether the edge or adjoining nodes share a property. B)...
Table of features associated with members of triplet motifs.
Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals.
The study included 34 renal transplant patients with histologically proven CAN and...
Mapping epistatic (or genetic) interactions has emerged as an important network biology approach for establishing functional relationships among genes and proteins. Epistasis networks are complementary to physical protein interaction networks, providing valuable insight into both the function of individual genes and the overall wiring of the cell....
Epistatic Miniarray Profiling(E-MAP) quantifies the net effect on growth rate of disrupting pairs of genes, often producing phenotypes that may be more (negative epistasis) or less (positive epistasis) severe than the phenotype predicted based on single gene disruptions. Epistatic interactions are important for understanding cell biology because th...
Predicted interactions between the RNA and Signalling datasets.
Predicted interactions between the Chromosome and RNA datasets.
Under conditions of hypoxia, most eukaryotic cells undergo a shift in metabolic strategy, which involves increased flux through the glycolytic pathway. Although this is critical for bioenergetic homeostasis, the underlying mechanisms have remained incompletely understood. Here, we report that the induction of hypoxia-induced glycolysis is retained...
While extremely large datasets describing gene sequences, mRNA transcripts, protein abundance, and metabolite concentrations are increasingly commonplace, these represent only starting ‘parts lists’ that are usually insufficient to unlock mechanistic insights on their own right. Fortunately, as Network Biology: Methods and Applications examines, co...
Supplementary Tables 1,2,4,5,6,7,8,10 and Supplementary Figures 1,2,3,4,5 and Supplementary References
Supplementary Table 9
Citations
... Several accessary units of PRC2 contain "reader" domains for H3K36me3. PHF19 (PHD finger protein 19) and PHF1 are known to facilitate the recruitment of PRC2 through their Tudor domains (Hunkapiller et al, 2012). Both Tudor domains of PHF1 and PHF19 act as readers for H3K36me3, and it is believed that the recognition of H3K36me3 by PHF1/19 initiates PRC2 targeting, H3K27me3 deposition, and silencing of actively transcribed genes (Ballar e et al, 2012;Brien et al, 2012;Musselman et al, 2012;Cai et al, 2013). ...
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... Besides, projecting a mixture network to unipartite is an alternative choice [21], but information will lost in such a process just as that for a bipartite network [8,27], and only one vertex set, rather than both, can be assigned to modules after the transformation. Furthermore, imputation methods can be used to convert the second type of mixture networks to unipartite ones by predicting missing values [28], but the performance of a community detection algorithm will then depend on the performance of an imputation method been used. Thus, models specific for mixture networks are necessary. ...
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... A different approach to identify differential complement profiles is to compare the plasma protein composition of psychiatric patients with healthy controls before clinical onset. A proteomic study was performed on plasma samples of children [41]. Decreased C4b-binding protein alpha chain (C4BPA) and C4b-binding protein beta chain (C4BPB) levels were found in children preceding the onset of psychotic disorder [41]. ...
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... Polyphosphate accumulation in bacteria has been described to happen under several stress conditions, such as low pH, osmotic stress, or nutrient limitations, and might have various physiological functions: energy source, reservoir for phosphorus, among others (Kornberg et al., 1999). Additionally, some studies show that PHA and polyphosphate metabolism (production and utilization) are particularly linked, as evidenced by PHA depolymerase or polyphosphate kinase mutant strains of R. eutropha H16 (Tumlirsch et al., 2015) and P. putida KT2440 (Casey et al., 2013), which have differential PHA and polyphosphate production profiles. ...
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... In contrast to the restricted expression of most other FOX proteins, FOXK1/2 are ubiquitously expressed, suggesting a fundamentally important general role. Mechanistically, these proteins are generally thought to act in a repressive manner through binding to the co-repressor SIN3A and a range of other co-repressor proteins (6)(7)(8)(9)(10)(11)(12)(13). This repressive activity of FOXK proteins has been shown to be crucial in suppressing autophagy programmes (14). ...
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... In another study, a protein analysis was conducted in blood samples taken from 12year-old individuals who experienced psychotic events at the age of 18. Compared with age-matched controls, an upregulation of six proteins was seen in the patient group, comprising vitronectin, complement C1r subcomponent like protein, C8B, C8A, complement factor H, and C5 [57]. The increased C5 levels observed in individuals experiencing psychosis may reflect an increased complement activity during postnatal neurodevelopment. ...
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... On the contrary, the PHA-negative mutant maintained the same level of RuBisCO activity over the entire growth period. Since RuBisCO controls the redox potential in cells of R. rubrum, the presence of PHA most likely substituted RuBisCO in this role (Narancic et al., 2016). Similarly, in H. seropedicae, inactivation of PHA synthesis perturbed redox balance and increased oxidative stress (Batista et al., 2018). ...
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... During recent years, CSD has been widely used to investigate the neurobiological mechanisms of resilience (for e.g. Berton et al., 2006;Krishnan et al., 2007;Chaudhury et al., 2013;Dias et al., 2014;Friedman et al., 2014;Tse et al., 2014;Focking et al., 2018;Li et al., 2018), via both the stratification of resilient versus susceptible animals and for the proof-of-concept of resilience-promoting targeted manipulations. The performance of mice in the social interaction test has been used as the major behavioral readout criterion. ...
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... Indeed, pre-clinical and human studies suggest altered polyunsaturated fatty acids (PUFAs), phospholipids, sphingolipids, including specifically sphingomyelin and ceramide, in psychotic patients' brains, as well as in the periphery/circulation [176][177][178]. Lipid disturbances were also recently observed in the period preceding the onset of psychosis [179,180]. Madrid-Gambin et al. performed integrative lipidomic and proteomic analysis of samples from 12-year old children, who had psychotic experiences at the age of 18 years and controls (ALSPAC cohort) [179]. Multiple LPCs and PCs were found increased in children who went on to have psychotic experiences later in life. ...
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... Here, we identify quininib and 1,4-dihydroxy quininib to significantly alter the secretion of cancer-associated inflammatory and angiogenic factors from UM cell lines. In agreement, the anti-angiogenic and anti-inflammatory actions of CysLT 1 antagonists are known in other contexts [32,33,59]. CysLTs modulate vascular permeability through upregulation of VEGF expression [60] and CysLT 1 antagonists modulate vascular permeability through reduction of VEGF expression in mice [61] and in human asthmatic patients [62]. ...
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