1.Gene expression versus sequence for predicting function: Glia Maturation Factor gamma is not a glia maturation factor.
Genomics, Proteomics & Bioinformatics 2003;1(1):52-57
It is standard practice, whenever a researcher finds a new gene, to search databases for genes that have a similar sequence. It is not standard practice, whenever a researcher finds a new gene, to search for genes that have similar expression (co-expression). Failure to perform co-expression searches has lead to incorrect conclusions about the likely function of new genes, and has lead to wasted laboratory attempts to confirm functions incorrectly predicted. We present here the example of Glia Maturation Factor gamma (GMF-gamma). Despite its name, it has not been shown to participate in glia maturation. It is a gene of unknown function that is similar in sequence to GMF-beta. The sequence homology and chromosomal location led to an unsuccessful search for GMF-gamma mutations in glioma. We examined GMF-gamma expression in 1432 human cDNA libraries. Highest expression occurs in phagocytic, antigen-presenting and other hematopoietic cells. We found GMF-gamma mRNA in almost every tissue examined, with expression in nervous tissue no higher than in any other tissue. Our evidence indicates that GMF-gamma participates in phagocytosis in antigen presenting cells. Searches for genes with similar sequences should be supplemented with searches for genes with similar expression to avoid incorrect predictions.
Animals
;
Cell Line
;
Cloning, Molecular
;
DNA, Complementary
;
metabolism
;
Databases as Topic
;
Expressed Sequence Tags
;
Gene Expression
;
Gene Library
;
Glia Maturation Factor
;
genetics
;
Humans
;
RNA, Messenger
;
metabolism
;
Rats
;
Sequence Analysis, DNA
2.Are gene expression microarray analyses reliable? A review of studies of retinoic acid responsive genes.
; Andreas KREMER ; Lynn MURRY ; Michael G WALKER
Genomics, Proteomics & Bioinformatics 2003;1(1):9-14
Microarray analyses of gene expression are widely used, but reports of the same analyses by different groups give widely divergent results, and raise questions regarding reproducibility and reliability. We take as an example recent published reports on microarray experiments that were designed to identify retinoic acid responsive genes. These reports show substantial differences in their results. In this article, we review the methodology, results, and potential causes of differences in these applications of microarrays. Finally, we suggest practices to improve the reliability and reproducibility of microarray experiments.
Animals
;
Blotting, Northern
;
Gene Expression Regulation
;
Genomics
;
methods
;
Humans
;
Oligonucleotide Array Sequence Analysis
;
methods
;
Reproducibility of Results
;
Tretinoin
;
chemistry
3.Hybrid microcatheter angioplasty for refractory cerebral vasospasm
Melanie WALKER ; Morgan P. ERDOES ; Chloe G. STRICKER ; Julie BOTHELL ; Cory M. KELLY ; Michael R. LEVITT
Journal of Cerebrovascular and Endovascular Neurosurgery 2021;23(2):159-168
Cerebral vasospasm is a significant cause of morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (aSAH). Intra-arterial chemical and mechanical angioplasty, performed alone or in combination, have been shown to ameliorate cerebral vasospasm and improve patient outcomes. Few options exist for patients who fail these traditional endovascular tactics. We propose a hybrid microcatheter technique that combines the mechanical benefit of transient high pressure induced by microcatheter fluid bolus with a low-dose vasodilator infusion. Five patients with moderate to severe symptomatic vasospasm who failed medical and traditional endovascular management were treated using a hybrid microcatheter technique. All angioplasty procedures were technically successful, and the degree of vasospasm improved following angioplasty. There were no complications related to the cerebral angioplasty procedures. None of the patients required repeat endovascular intervention. Hybrid microcatheter angioplasty may be a useful complement to mechanical or pharmacological techniques in the endovascular management of intractable cerebral vasospasm after aSAH.
4.Hybrid microcatheter angioplasty for refractory cerebral vasospasm
Melanie WALKER ; Morgan P. ERDOES ; Chloe G. STRICKER ; Julie BOTHELL ; Cory M. KELLY ; Michael R. LEVITT
Journal of Cerebrovascular and Endovascular Neurosurgery 2021;23(2):159-168
Cerebral vasospasm is a significant cause of morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (aSAH). Intra-arterial chemical and mechanical angioplasty, performed alone or in combination, have been shown to ameliorate cerebral vasospasm and improve patient outcomes. Few options exist for patients who fail these traditional endovascular tactics. We propose a hybrid microcatheter technique that combines the mechanical benefit of transient high pressure induced by microcatheter fluid bolus with a low-dose vasodilator infusion. Five patients with moderate to severe symptomatic vasospasm who failed medical and traditional endovascular management were treated using a hybrid microcatheter technique. All angioplasty procedures were technically successful, and the degree of vasospasm improved following angioplasty. There were no complications related to the cerebral angioplasty procedures. None of the patients required repeat endovascular intervention. Hybrid microcatheter angioplasty may be a useful complement to mechanical or pharmacological techniques in the endovascular management of intractable cerebral vasospasm after aSAH.
5.Gene identification and expression analysis of 86,136 Expressed Sequence Tags (EST) from the rice genome.
Yan ZHOU ; Jiabin TANG ; Michael G WALKER ; Xiuqing ZHANG ; Jun WANG ; Songnian HU ; Huayong XU ; Yajun DENG ; Jianhai DONG ; Lin YE ; Li LIN ; Jun LI ; Xuegang WANG ; Hao XU ; Yibin PAN ; Wei LIN ; Wei TIAN ; Jing LIU ; Liping WEI ; Siqi LIU ; Huanming YANG ; Jun YU ; Jian WANG
Genomics, Proteomics & Bioinformatics 2003;1(1):26-42
Expressed Sequence Tag (EST) analysis has pioneered genome-wide gene discovery and expression profiling. In order to establish a gene expression index in the rice cultivar indica, we sequenced and analyzed 86,136 ESTs from nine rice cDNA libraries from the super hybrid cultivar LYP9 and its parental cultivars. We assembled these ESTs into 13,232 contigs and leave 8,976 singletons. Overall, 7,497 sequences were found similar to existing sequences in GenBank and 14,711 are novel. These sequences are classified by molecular function, biological process and pathways according to the Gene Ontology. We compared our sequenced ESTs with the publicly available 95,000 ESTs from japonica, and found little sequence variation, despite the large difference between genome sequences. We then assembled the combined 173,000 rice ESTs for further analysis. Using the pooled ESTs, we compared gene expression in metabolism pathway between rice and Arabidopsis according to KEGG. We further profiled gene expression patterns in different tissues, developmental stages, and in a conditional sterile mutant, after checking the libraries are comparable by means of sequence coverage. We also identified some possible library specific genes and a number of enzymes and transcription factors that contribute to rice development.
Arabidopsis
;
genetics
;
DNA, Complementary
;
metabolism
;
Databases as Topic
;
Expressed Sequence Tags
;
Gene Library
;
Genome, Plant
;
Genomics
;
methods
;
Multigene Family
;
Open Reading Frames
;
Oryza
;
genetics
;
Quality Control
;
Software
6.Protocol and Rationale: A 24-week Double-blind, Randomized, Placebo Controlled Trial of the Efficacy of Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for Schizophrenia
Alyna TURNER ; John J MCGRATH ; Olivia M DEAN ; Seetal DODD ; Andrea BAKER ; Susan M COTTON ; James G SCOTT ; Bianca E KAVANAGH ; Melanie M ASHTON ; Adam J WALKER ; Ellie BROWN ; Michael BERK
Clinical Psychopharmacology and Neuroscience 2019;17(2):297-307
OBJECTIVE: Garcinia mangostana Linn., commonly known as mangosteen, is a tropical fruit with a thick pericarp rind containing bioactive compounds that may be beneficial as an adjunctive treatment for schizophrenia. The biological underpinnings of schizophrenia are believed to involve altered neurotransmission, inflammation, redox systems, mitochondrial dysfunction, and neurogenesis. Mangosteen pericarp contains xanthones which may target these biological pathways and improve symptoms; this is supported by preclinical evidence. Here we outline the protocol for a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp (1,000 mg/day), compared to placebo, in the treatment of schizophrenia. METHODS: We aim to recruit 150 participants across two sites (Geelong and Brisbane). Participants diagnosed with schizophrenia or schizoaffective disorder will be randomized to receive 24 weeks of either adjunctive 1,000 mg/day of mangosteen pericarp or matched placebo, in addition to their usual treatment. The primary outcome measure is mean change in the Positive and Negative Symptom Scale (total score) over the 24 weeks. Secondary outcomes include positive and negative symptoms, general psychopathology, clinical global severity and improvement, depressive symptoms, life satisfaction, functioning, participants reported overall improvement, substance use, cognition, safety and biological data. A 4-week post treatment interview at week 28 will explore post-discontinuations effects. RESULTS: Ethical and governance approvals were gained and the trial commenced. CONCLUSION: A positive finding in this study has the potential to provide a new adjunctive treatment option for people with schizophrenia and schizoaffective disorder. It may also lead to a greater understanding of the pathophysiology of the disorder.
Cognition
;
Depression
;
Fruit
;
Garcinia mangostana
;
Garcinia
;
Inflammation
;
Neurogenesis
;
Outcome Assessment (Health Care)
;
Oxidation-Reduction
;
Oxidative Stress
;
Psychopathology
;
Psychotic Disorders
;
Schizophrenia
;
Synaptic Transmission
;
Xanthones