scholarly journals Glabralysins, Potential New β-Pore-Forming Toxin Family Members from the Schistosomiasis Vector Snail Biomphalaria glabrata

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 65
Author(s):  
Damien Lassalle ◽  
Guillaume Tetreau ◽  
Silvain Pinaud ◽  
Richard Galinier ◽  
Neil Crickmore ◽  
...  
Keyword(s):  
Structure Prediction ◽  
Tertiary Structure ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Biomphalaria Glabrata ◽  
Amino Acid Identity ◽  
New Family ◽  
New Genes ◽  
High Degree ◽  
Trematode Parasites

Biomphalaria glabrata is a freshwater Planorbidae snail. In its environment, this mollusk faces numerous microorganisms or pathogens, and has developed sophisticated innate immune mechanisms to survive. The mechanisms of recognition are quite well understood in Biomphalaria glabrata, but immune effectors have been seldom described. In this study, we analyzed a new family of potential immune effectors and characterized five new genes that were named Glabralysins. The five Glabralysin genes showed different genomic structures and the high degree of amino acid identity between the Glabralysins, and the presence of the conserved ETX/MTX2 domain, support the hypothesis that they are pore-forming toxins. In addition, tertiary structure prediction confirms that they are structurally related to a subset of Cry toxins from Bacillus thuringiensis, including Cry23, Cry45, and Cry51. Finally, we investigated their gene expression profiles in snail tissues and demonstrated a mosaic transcription. We highlight the specificity in Glabralysin expression following immune stimulation with bacteria, yeast or trematode parasites. Interestingly, one Glabralysin was found to be expressed in immune-specialized hemocytes, and two others were induced following parasite exposure.

scholarly journals n-3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions

2013 ◽  
Vol 72 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mechanisms Of Action ◽  
Lipid Mediators ◽  
Functional Responses ◽  
New Family ◽  
Epa And Dha ◽  
Novel Interactions

Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.

scholarly journals Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Amanda L. Brown ◽  
Trevor A. Day ◽  
Christopher V. Dayas ◽  
Doug W. Smith
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Acid Decarboxylase ◽  
Cell Groups ◽  
Midbrain Dopamine ◽  
High Degree ◽  
Midbrain Dopamine Neurons

The ability to microdissect individual cells from the nervous system has enormous potential, as it can allow for the study of gene expression in phenotypically identified cells. However, if the resultant gene expression profiles are to be accurately ascribed, it is necessary to determine the extent of contamination by nontarget cells in the microdissected sample. Here, we show that midbrain dopamine neurons can be laser-microdissected to a high degree of enrichment and purity. The average enrichment for tyrosine hydroxylase (TH) gene expression in the microdissected sample relative to midbrain sections was approximately 200-fold. For the dopamine transporter (DAT) and the vesicular monoamine transporter type 2 (Vmat2), average enrichments were approximately 100- and 60-fold, respectively. Glutamic acid decarboxylase (Gad65) expression, a marker for GABAergic neurons, was several hundredfold lower than dopamine neuron-specific genes. Glial cell and glutamatergic neuron gene expression were not detected in microdissected samples. Additionally, SN and VTA dopamine neurons had significantly different expression levels of dopamine neuron-specific genes, which likely reflects functional differences between the two cell groups. This study demonstrates that it is possible to laser-microdissect dopamine neurons to a high degree of cell purity. Therefore gene expression profiles can be precisely attributed to the targeted microdissected cells.

Gene Expression Profiling Reveals Fundamental Differences between Leukemic Stem Cells (Lin-CD34+CD38−) and Mature Blasts (Lin−CD34+CD38+) of Acute Myeloid Leukaemia (AML) Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1377-1377
Author(s):  
Kazem Zibara ◽  
Daniel Pearce ◽  
David Taussig ◽  
Spyros Skoulakis ◽  
Simon Tomlinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Populations ◽  
Leukemic Stem Cells ◽  
Significant Differential Expression ◽  
New Genes

Abstract The identification of LSC has important implications for future research as well as for the development of novel therapies. The phenotypic description of LSC now enables their purification and should facilitate the identification of genes that are preferentially expressed in these cells compared to normal HSC. However, gene-expression profiling is usually conducted on mononuclear cells of AML patients from either peripheral blood and/or bone marrow. These samples contain a mixture of blasts cells, normal hematopoietic cells and limited number of leukemic stem cells. Thus, this results in a composite profile that obscure differences between LSC and blasts cells with low proliferative potential. The aim of this study was to compare the gene expression profile of highly purified LSC versus leukemic blasts in order to identify genes that might have important roles in driving the leukemia. For this purpose, we analyzed the gene expression profiles of highly purified LSCs (Lin−CD34+CD38−) and more mature blast cells (Lin−CD34+CD38+) isolated from 7 adult AML patients. All samples were previously tested for the ability of the Lin−CD34+CD38− cells but not the Lin−CD34+CD38+ fraction to engraft using the non-obese diabetic/severe combined immuno-deficiency (NOD-SCID) repopulation assay. Affymetrix microarrays (U133A chip), containing 22,283 genes, were used for the analysis. Comparison of Lin-CD34+CD38- cell population to the Lin−CD34+CD38+ cell fraction showed 5421 genes to be expressed in both fractions. Comparative analysis of gene-expression profiles showed statistically significant differential expression of 133 genes between the 2 cell populations. Most of the genes were downregulated in the LSC-enriched fraction, compared to the more differentiated fraction. Gene ontology was used to determine the categories of the up-regulated transcripts. These transcripts, which are selectively expressed, include a number of known genes (e.g., receptors, signalling genes, proliferation and cell cycle genes and transcription factors). These genes play important roles in differentiation, self-renewal, migration and adhesion of HSCs. Among the genes showing the highest differences in expression levels were the following: ribonucleotide reductase M2 polypeptide, thymidylate synthetase, ZW10 interactor, cathepsin G, azurocidin 1, topoisomerase II, CDC20, nucleolar and spindle associated protein 1, Rac GTPase activating protein 1, leukocyte immunoglobulin-like receptor, proliferating cell nuclear antigen, myeloperoxidase, cyclin A1 (RRM2, TYMS, ZWINT, CTSG, AZU1, TOP2A, CDC20, NUSAP1, RACGAP1, LILRB2, PCNA, MPO, CCNA1). Some transcripts detected have not been implicated in HSC functions, and others have unknown function so far. This work identifies new genes that might play a role in leukemogenesis and cancer stem cells. It also leads to a better description and understanding of the molecular phenotypes of these 2 cell populations. Hence, in addition to being a more efficient way to further understand the biology of LSC, this should also provide a more efficient way of identifying new therapeutics and diagnostic targets.

scholarly journals Information topology of gene expression profile in dopaminergic neurons

2017 ◽  
Author(s):  
Mónica Tapia Pacheco ◽  
Pierre Baudot ◽  
Martial A. Dufour ◽  
Christine Formisano-Tréziny ◽  
Simone Temporal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dopaminergic Neurons ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Combinatorial Structure ◽  
Maximum Information ◽  
Midbrain Neurons ◽  
High Degree ◽  
Multivariate Mutual Information ◽  
Gene Expression Levels

SUMMARY PARAGRAPHExtracting high-degree interactions and dependences between variables (pairs, triplets, … k-tuples) is a challenge posed by all omics approaches1, 2. Here we used multivariate mutual information (Ik) analysis3 on single-cell retro-transcription quantitative PCR (sc-RTqPCR) data obtained from midbrain neurons to estimate the k-dimensional topology of their gene expression profiles. 41 mRNAs were quantified and statistical dependences in gene expression levels could be fully described for 21 genes: Ik analysis revealed a complex combinatorial structure including modules of pairs, triplets (up to 6-tuples) sharing strong positive, negative or zero Ik, corresponding to co-varying, clustering and independent sets of genes, respectively. Therefore, Ik analysis simultaneously identified heterogeneity (negative Ik) of the cell population under study and regulatory principles conserved across the population (homogeneity, positive Ik). Moreover, maximum information paths enabled to determine the size and stability of such transcriptional modules. Ik analysis represents a new topological and statistical method of data analysis.

scholarly journals A New Assessment of Thioester-Containing Proteins Diversity of the Freshwater Snail Biomphalaria glabrata

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 69 ◽  
Author(s):  
David Duval ◽  
Remi Pichon ◽  
Damien Lassalle ◽  
Maud Laffitte ◽  
Benjamin Gourbal ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Variable Region ◽  
Biomphalaria Glabrata ◽  
Freshwater Snail ◽  
Innate Immune ◽  
Immune Functions ◽  
Wide Range ◽  
Animal Phyla ◽  
Related Proteins

Thioester-containing proteins (TEPs) superfamily is known to play important innate immune functions in a wide range of animal phyla. TEPs are involved in recognition, and in the direct or mediated killing of several invading organisms or pathogens. While several TEPs have been identified in many invertebrates, only one TEP (named BgTEP) has been previously characterized in the freshwater snail, Biomphalaria glabrata. As the presence of a single member of that family is particularly intriguing, transcriptomic data and the recently published genome were used to explore the presence of other BgTEP related genes in B. glabrata. Ten other TEP members have been reported and classified into different subfamilies: Three complement-like factors (BgC3-1 to BgC3-3), one α-2-macroblobulin (BgA2M), two macroglobulin complement-related proteins (BgMCR1, BgMCR2), one CD109 (BgCD109), and three insect TEP (BgTEP2 to BgTEP4) in addition to the previously characterized BgTEP that we renamed BgTEP1. This is the first report on such a level of TEP diversity and of the presence of macroglobulin complement-related proteins (MCR) in mollusks. Gene structure analysis revealed alternative splicing in the highly variable region of three members (BgA2M, BgCD109, and BgTEP2) with a particularly unexpected diversity for BgTEP2. Finally, different gene expression profiles tend to indicate specific functions for such novel family members.

Gene Expression Model of Survival and Transformation in Follicular Lymphoma (FL): A Study by the LLMPP.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2606-2606
Author(s):  
N.A. Johnson ◽  
T. Nayar ◽  
S.S. Dave ◽  
G. Wright ◽  
A. Rosenwald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Cross Validation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Survival Model ◽  
Transformation Model ◽  
Previous Model ◽  
New Genes

Abstract Background: FL is a common NHL that has a broad spectrum of clinical outcomes. Over time some pts will transform to an aggressive histology (Tly) associated with inferior survival. In 2004, the LLMPP constructed a model that was predictive of overall survival (OS) based on the gene expression profiles (GEP) of 191 specimens taken from pts with untreated FL. The genes associated with survival were derived from the non-neoplastic immune response (IR) cells. However the risk of developing Tly was not addressed in this study. Thus we re-analyzed the GEP with updated clinical data. Our goal was to validate our previous model with extended follow-up and to create a model that would predict the risk of developing TLy. Methods: 170 of 191 previously untreated FL pts had updated clinical information but only 142 had transformation outcome. Transformation was defined as biopsy proven DLBCL or clinically based on the presence of at least one of the following: hypercalcemia, a sudden rise in LDH >twice baseline, unusual extranodal growth or rapid discordant nodal growth. Raw CEL files from Affymetrix U133A arrays were pre-processed and normalized using Bioconductor’s GCRMA package. Models were developed using SignS package (http://signs/bioinfo.cnio.es/), with 10 times cross-validation. All gene lists produced in these analyses were then re-tested for association with outcome using Bioconductor’s Globaltest package. Over Representation Analysis of signature components was performed using Dchip. Results: The median OS of these patients was 8 yrs. A new 7-component survival model (85 genes) was developed that was significantly associated with survival (p= 2.9×10−13). In Globaltest, these gene lists were associated with survival at a level of (p=2.6×10−5). The previous model using IR-1 and IR-2 signatures was associated with survival at a level of p=2.6×10−4. Although there is little overlap between the 2 models, the new model confirms the importance of IR genes and extracellular matrix genes as being prognostically important. Interestingly, one component containing 10 genes on chromosome 6q was associated with a superior survival (p<1×107). 27% developed Tly over a median follow-up time of 11.2 yrs (69% biopsy proven). Our transformation model included 53 genes divided into 3 components (p=0.001). The Globaltest analysis for association of these genes with transformation was significant (p=0.018). 54 genes overlapped between the survival genes and transformation genes that were present in >1 cross validation run. These were significantly enriched in genes important in immune response like T cell and macrophage activation. Conclusion: Our survival model is stable and confirms the importance of key genes involved in the immune response and lymph node remodeling. It also introduces new genes that are potentially important for survival. Our transformation model may shed light on the mechanisms involved in the progression of FL to DLBCL but it is less stable and less reliable than our survival model at predicting outcome.

A Shared Gene-Expression Signature in Innate-Like Lymphocytes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3903-3903
Author(s):  
Tetsuya Yamagata ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Signature ◽  
Cell Types ◽  
Self Recognition ◽  
Distinct Cell ◽  
Invariant Structures ◽  
Small Set ◽  
High Degree

Abstract Innate and adaptive immunity are the two major arms of the immune system. They rely on very distinct cell-types, primarily distinguished by the source of diversity for non-self recognition, of germline or somatic origin. There exists, however, a subset of lymphocytes whose receptors require rearrangement but result in semi-invariant structures with a high degree of self-specificity. We hypothesized that these innate-like lymphocytes might share a common gene transcription signature. To test this notion, we made pair-wise comparisons of the gene-expression profiles of innate-like lymphocytes and closely paired adaptive system counterparts (NKT vs. CD4T, CD8ααT vs. CD8αβT, B1 vs. B2), and bioinformatically extracted common features and common genes distinguishing innate from adaptive cell-types. A statistically significant “innate signature” was indeed distilled, composed of a small set of genes over- and under-expressed in innate vs. adaptive lymphocytes. Particularly intriguing was the high representation of interferon-inducible GTPases crucial for resistance against intracellular pathogens, and of small G proteins involved in intracellular vacuole maturation and trafficking. Overall, this combined expression pattern can thus be designated as an “innate signature” among lymphocytes.

scholarly journals Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain

2018 ◽  
Vol 29 (9) ◽  
pp. 3828-3835 ◽  
Author(s):  
Qilong Xin ◽  
Laura Ortiz-Terán ◽  
Ibai Diez ◽  
David L Perez ◽  
Julia Ginsburg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Connectivity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Genetic Sequence ◽  
Cortical Areas ◽  
Cortical Regions ◽  
High Degree ◽  
The Brain

Abstract Individual differences in humans are driven by unique brain structural and functional profiles, presumably mediated in part through differential cortical gene expression. However, the relationships between cortical gene expression profiles and individual differences in large-scale neural network organization remain poorly understood. In this study, we aimed to investigate whether the magnitude of sequence alterations in regional cortical genes mapped onto brain areas with high degree of functional connectivity variability across individuals. First, human genetic expression data from the Allen Brain Atlas was used to identify protein-coding genes associated with cortical areas, which delineated the regional genetic signature of specific cortical areas based on sequence alteration profiles. Thereafter, we identified brain regions that manifested high degrees of individual variability by using test-retest functional connectivity magnetic resonance imaging and graph-theory analyses in healthy subjects. We found that rates of genetic sequence alterations shared a distinct spatial topography with cortical regions exhibiting individualized (highly-variable) connectivity profiles. Interestingly, gene expression profiles of brain regions with highly individualized connectivity patterns and elevated number of sequence alterations are devoted to neuropeptide-signaling-pathways and chemical-synaptic-transmission. Our findings support that genetic sequence alterations may underlie important aspects of brain connectome individualities in humans. Significance Statement: The neurobiological underpinnings of our individuality as humans are still an unsolved question. Although the notion that genetic variation drives an individual’s brain organization has been previously postulated, specific links between neural connectivity and gene expression profiles have remained elusive. In this study, we identified the magnitude of population-based sequence alterations in discrete cortical regions and compared them to the brain topological distribution of functional connectivity variability across an independent human sample. We discovered that brain regions with high degree of connectional individuality are defined by increased rates of genetic sequence alterations; these findings specifically implicated genes involved in neuropeptide-signaling pathways and chemical-synaptic transmission. These observations support that genetic sequence alterations may underlie important aspects of the emergence of the brain individuality across humans.

scholarly journals Transcriptional Regulators and Human-Specific/Primate-Specific Genes in Neocortical Neurogenesis

2020 ◽  
Vol 21 (13) ◽  
pp. 4614 ◽  
Author(s):  
Samir Vaid ◽  
Wieland B. Huttner
Keyword(s):  
Gene Expression ◽  
Cognitive Abilities ◽  
Temporal Dynamics ◽  
De Novo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Transcriptional Regulators ◽  
New Genes ◽  
Recent Part ◽  
Spatio Temporal

During development, starting from a pool of pluripotent stem cells, tissue-specific genetic programs help to shape and develop functional organs. To understand the development of an organ and its disorders, it is important to understand the spatio-temporal dynamics of the gene expression profiles that occur during its development. Modifications in existing genes, the de-novo appearance of new genes, or, occasionally, even the loss of genes, can greatly affect the gene expression profile of any given tissue and contribute to the evolution of organs or of parts of organs. The neocortex is evolutionarily the most recent part of the brain, it is unique to mammals, and is the seat of our higher cognitive abilities. Progenitors that give rise to this tissue undergo sequential waves of differentiation to produce the complete sets of neurons and glial cells that make up a functional neocortex. We will review herein our understanding of the transcriptional regulators that control the neural precursor cells (NPCs) during the generation of the most abundant class of neocortical neurons, the glutametergic neurons. In addition, we will discuss the roles of recently-identified human- and primate-specific genes in promoting neurogenesis, leading to neocortical expansion.

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