scholarly journals CaveCrawler: An interactive analysis suite for cavefish bioinformatics

2021 ◽  
Author(s):  
Annabel Perry ◽  
Suzanne E. McGaugh ◽  
Alex C. Keene ◽  
Heath Blackmon
Keyword(s):  
Gene Ontology ◽  
Animal Models ◽  
Functional Data ◽  
Convergent Evolution ◽  
Model Systems ◽  
Web Based ◽  
Astyanax Mexicanus ◽  
Interactive Analysis ◽  
Approaches To Study ◽  
Blind Cave

AbstractThe growing use of genomics data in diverse animal models provides the basis for identifying genomic and transcriptional differences across species and contexts. Databases containing genomic and functional data have played critical roles in the development of numerous genetic models but are lacking for most emerging models of evolution. There is a rapidly expanding use of genomic, transcriptional, and functional genetic approaches to study diverse traits of the Mexican tetra, Astyanax mexicanus. This species exists as two morphs, eyed surface populations and at least 30 blind cave populations, providing a system to study convergent evolution. We have generated a web-based analysis suite that integrates datasets from different studies to identify how gene transcription and genetic markers of selection differ between populations and across experimental contexts. Results can be processed with other analysis platforms including Gene Ontology (GO) to enable biological inference from cross-study patterns and identify future avenues of research. Furthermore, the framework that we have built A. mexicanus can readily applied to other emerging model systems.

scholarly journals Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Meghan O Altman ◽  
Jack R Bennink ◽  
Jonathan W Yewdell ◽  
Brantley R Herrin
Keyword(s):  
Influenza Virus ◽  
Animal Models ◽  
Convergent Evolution ◽  
Influenza A ◽  
Organic Molecules ◽  
Protein Antigens ◽  
Antigenic Sites ◽  
Foreign Proteins ◽  
Variable Lymphocyte Receptor ◽  
Globular Head

Immunoglobulins (Igs) are a crown jewel of jawed vertebrate evolution. Through recombination and mutation of small numbers of genes, Igs can specifically recognize a vast variety of natural and man-made organic molecules. Jawless vertebrates evolved a parallel system of humoral immunity, which recognizes antigens not with Ig, but with a structurally unrelated receptor called the variable lymphocyte receptor B (VLRB). We exploited the convergent evolution of Ig and VLRB antibodies (Abs) to investigate if intrinsic chemical features of foreign proteins determine their antigenicity and immunogenicity. Surprisingly, we find lamprey VLRB and mouse Ig responses to influenza A virus are extremely similar. Each focuses ∼80% of the response on hemagglutinin (HA), mainly through recognition of the major antigenic sites in the HA globular head domain. Our findings predict basic conservation of Ab responses to protein antigens, strongly supporting the use of animal models for understanding human Ab responses to viruses and protein immunogens.

scholarly journals Models of multiple system atrophy

2019 ◽  
Vol 51 (11) ◽  
pp. 1-10 ◽  
Author(s):  
He-Jin Lee ◽  
Diadem Ricarte ◽  
Darlene Ortiz ◽  
Seung-Jae Lee
Keyword(s):  
Animal Models ◽  
Multiple System Atrophy ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Lewy Bodies ◽  
Model Systems ◽  
Future Research ◽  
Cytoplasmic Inclusions ◽  
Cellular Models ◽  
Brain Extracts

AbstractMultiple system atrophy (MSA) is a neurodegenerative disease with diverse clinical manifestations, including parkinsonism, cerebellar syndrome, and autonomic failure. Pathologically, MSA is characterized by glial cytoplasmic inclusions in oligodendrocytes, which contain fibrillary forms of α-synuclein. MSA is categorized as one of the α-synucleinopathy, and α-synuclein aggregation is thought to be the culprit of the disease pathogenesis. Studies on MSA pathogenesis are scarce relative to studies on the pathogenesis of other synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies. However, recent developments in cellular and animal models of MSA, especially α-synuclein transgenic models, have driven advancements in research on this disease. Here, we review the currently available models of MSA, which include toxicant-induced animal models, α-synuclein-overexpressing cellular models, and mouse models that express α-synuclein specifically in oligodendrocytes through cell type-specific promoters. We will also discuss the results of studies in recently developed transmission mouse models, into which MSA brain extracts were intracerebrally injected. By reviewing the findings obtained from these model systems, we will discuss what we have learned about the disease and describe the strengths and limitations of the models, thereby ultimately providing direction for the design of better models and future research.

scholarly journals Animal model of intrahepatic metastasis of hepatocellular carcinoma: establishment and characteristic

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xuemei Li ◽  
Jike Hu ◽  
Baohong Gu ◽  
Maswikiti Ewetse Paul ◽  
Bofang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Cell Line ◽  
Cell Lines ◽  
Intrahepatic Metastasis ◽  
Model Systems ◽  
Large Tumor ◽  
Important Direction ◽  
Disease Study

Abstract One of the most important and striking characteristics of hepatocellular carcinoma (HCC) with intrahepatic metastasis, is that it results in extremely poor prognosis. Animal models have become a fundamental and very useful in research for disease study. However, some limitation has arisen from these model systems. We have therefore established a model of HCC with intrahepatic metastasis and noticed some differential appearances in different HCC cell lines. Luciferase-transfected HCC cell lines MHCC97-H and PLC/PRF/5 were inoculated into SCID mice via spleen. Observation the intrahepatic metastasis by bioluminescence imaging in vivo and comparing of the differential formation of metastatic lesions between different HCC cell lines by incorporating physical anatomy was done. Animal models for HCC intrahepatic metastasis were well established. However, there were some clearly noticed differences between MHCC97-H and PLC/PRF/5 cell lines. The group of MHCC97-H cell line readily metastasis in the liver, whereas group PLC/PRF/5 cell line developed extensive intrahepatic metastasis and formed large tumor in situ in the spleen. MHCC97-H and PLC/PRF/5 cell lines can be used to successfully establish a model of HCC intrahepatic metastasis with distinctive characteristics, which provides an important direction for the study of the mechanism of HCC intrahepatic metastasis, and may hopefully provide a basis for clinical treatment.

scholarly journals A hypomorphic cystathionine ß-synthase gene contributes to cavefish eye loss by disrupting optic vasculature

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Ma ◽  
Aniket V. Gore ◽  
Daniel Castranova ◽  
Janet Shi ◽  
Mandy Ng ◽  
...  
Keyword(s):  
Circulatory System ◽  
Astyanax Mexicanus ◽  
Transsulfuration Pathway ◽  
Key Enzyme ◽  
Surface Dwelling ◽  
Blind Cave ◽  
Vestigial Structures ◽  
Key Indicators ◽  
Evolutionary Descent ◽  
Eye Formation

Abstract Vestigial structures are key indicators of evolutionary descent, but the mechanisms underlying their development are poorly understood. This study examines vestigial eye formation in the teleost Astyanax mexicanus, which consists of a sighted surface-dwelling morph and multiple populations of blind cave morphs. Cavefish embryos initially develop eyes, but they subsequently degenerate and become vestigial structures embedded in the head. The mutated genes involved in cavefish vestigial eye formation have not been characterized. Here we identify cystathionine ß-synthase a (cbsa), which encodes the key enzyme of the transsulfuration pathway, as one of the mutated genes responsible for eye degeneration in multiple cavefish populations. The inactivation of cbsa affects eye development by increasing the transsulfuration intermediate homocysteine and inducing defects in optic vasculature, which result in aneurysms and eye hemorrhages. Our findings suggest that localized modifications in the circulatory system may have contributed to the evolution of vestigial eyes in cavefish.

Combining galiximab with the chemotherapeutic agents fludarabine or doxorubicin improves efficacy in animal models of lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3040-3040 ◽  
Author(s):  
H. K. Hariharan ◽  
T. Murphy ◽  
D. Clanton ◽  
L. Berquist ◽  
P. Chu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Clinical Benefit ◽  
Therapeutic Potential ◽  
Xenograft Model ◽  
Chemotherapeutic Agents ◽  
Model Systems ◽  
Anti Cd20

3040 Background: Galiximab, a primatized monoclonal antibody that binds with high affinity to CD80 and mediates antibody- dependent, cell-mediated cytotoxicity in vitro, is currently under investigation for the treatment of follicular non-Hodgkin’s lymphoma (NHL). In a phase I/II monotherapy study, galiximab produced an overall response rate of 11%, and tumor reductions were observed in 46% of patients. Initial clinical trials also demonstrate that galiximab is well tolerated and suggest that combining galiximab with rituximab (anti-CD20) provides clinical benefit. These results are consistent with preclinical studies in murine lymphoma xenograft model systems, which demonstrate the superiority of combination therapy. Methods: To further define the therapeutic potential of galiximab, the Raji subcutaneous and the SKW disseminated lymphoma murine xenograft models were used to define the in vivo efficacy of galiximab alone or in combination with fludarabine or doxorubicin. Similar studies were performed with rituximab. Results: In the Raji model, both galiximab and rituximab exhibited maximal inhibition of the growth of preestablished (150-mg) tumors at a dose of 3 mg/kg/wk. Interestingly, higher doses of galiximab (but not rituximab) showed reduced inhibition. Galiximab (3 mg/kg/wk) inhibited tumor growth alone (P<0.0001 vs. control) and showed significantly enhanced activity when combined with fludarabine (50 or 100 mg/kg daily for 5 days; P<0.0002 vs. galiximab alone and P<0.003 vs. fludarabine alone). Similar results were observed with rituximab. In the SKW model, treatment with galiximab (5 mg/kg/wk for 6 doses) significantly enhanced survival compared with a control (P<0.0001) or doxorubicin (2.5 mg/kg/day for 3 doses; P<0.0001). Studies combining fludarabine or doxorubicin with both galiximab and rituximab are ongoing. Conclusions: Studies in animal models of lymphoma indicate that galiximab may provide clinical benefit when used in combination with chemotherapeutic agents such as fludarabine and doxorubicin, and provide a rationale for the investigation of these novel chemoimmunotherapy combinations in clinical trials. No significant financial relationships to disclose.

scholarly journals Erratum to: Array2GO: a simple web-based tool to search gene ontology for analysis of multi genes expression

2011 ◽  
Vol 5 (1) ◽  
pp. 95-95
Author(s):  
Jun Sub Kim ◽  
Seung Jun Kim ◽  
Seung Yong Lee ◽  
Jeong Han ◽  
Yu Ri An ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Web Based ◽  
Genes Expression

scholarly journals Mining Gene Ontology Data with AGENDA

2012 ◽  
Vol 6 ◽  
pp. BBI.S9101
Author(s):  
Guvanch Ovezmyradov ◽  
Qianhao Lu ◽  
Martin C. Göpfert
Keyword(s):  
Gene Ontology ◽  
Open Source ◽  
Genetic Information ◽  
Collaborative Effort ◽  
Controlled Vocabularies ◽  
Web Based ◽  
Commercial Use ◽  
Diverse Species ◽  
Go Terms ◽  
The Web

The Gene Ontology (GO) initiative is a collaborative effort that uses controlled vocabularies for annotating genetic information. We here present AGENDA (Application for mining Gene Ontology Data), a novel web-based tool for accessing the GO database. AGENDA allows the user to simultaneously retrieve and compare gene lists linked to different GO terms in diverse species using batch queries, facilitating comparative approaches to genetic information. The web-based application offers diverse search options and allows the user to bookmark, visualize, and download the results. AGENDA is an open source web-based application that is freely available for non-commercial use at the project homepage. URL: http://sourceforge.net/projects/bioagenda .

scholarly journals An epigenetic mechanism for cavefish eye degeneration

2017 ◽  
Author(s):  
Aniket V. Gore ◽  
Kelly A. Tomins ◽  
James Iben ◽  
Li Ma ◽  
Daniel Castranova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Eye Development ◽  
Phenotypic Diversity ◽  
Phenotypic Variability ◽  
Epigenetic Mechanism ◽  
Gene Repression ◽  
Specific Gene ◽  
Astyanax Mexicanus ◽  
Eye Disorders ◽  
Blind Cave

Coding and non-coding mutations in DNA contribute significantly to phenotypic variability during evolution. However, less is known about the role of epigenetics in this process. Although previous studies have identified eye development genes associated with the loss of eyes phenotype in the Pachón blind cave morph of the Mexican tetra Astyanax mexicanus1-6, no inactivating mutations have been found in any of these genes2,3,7-10. Here we show that excess DNA methylation-based epigenetic silencing promotes eye degeneration in blind cave Astyanax mexicanus. By performing parallel analyses in Astyanax mexicanus cave and surface morphs and in the zebrafish Danio rerio, we have discovered that DNA methylation mediates eye-specific gene repression and globally regulates early eye development. The most significantly hypermethylated and down-regulated genes in the cave morph are also linked to human eye disorders, suggesting the function of these genes is conserved across the vertebrates. Our results show that changes in DNA methylation-based gene repression can serve as an important molecular mechanism generating phenotypic diversity during development and evolution.

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