The Relationships Among Spatiotemporal Gene Expression, Histology, and Biomechanics Following Full-Length Injury in the Murine Patellar Tendon

2011 ◽  
Author(s):  
Nathaniel A. Dyment ◽  
Namdar Kazemi ◽  
Lindsey E. Aschbacher-Smith ◽  
Nicolas J. Barthelery ◽  
Keith Kenter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Patellar Tendon ◽  
Expression Patterns ◽  
Tendon Healing ◽  
Full Length ◽  
Treatment Modalities ◽  
Type I ◽  
Biomechanical Assessment ◽  
Tendon Tissue Engineering ◽  
Natural Healing

Tendon and ligament injuries present a considerable socioeconomic impact as close to 50% of the 32 million musculoskeletal injuries in the US per year include these structures [1]. The inadequate healing in these tissues requires novel treatment modalities. Improving tendon tissue engineering dictates that we better understand the process of natural adult tendon healing. Type-I (Col1) and Type-II (Col2) collagens are important structural proteins in tendon as Col1 is the main collagen type found in the tendon midsubstance while Col2 is expressed at the insertion into bone during development, growth, and healing [2–3]. Expression of Col1 and Col2 has typically been analyzed via qPCR, western blotting, and immunohistochemistry (IHC) during healing. However, the temporal expression of these genes is still poorly understood on a cell-by-cell basis. Our lab has previously studied patellar tendon (PT) healing in NZW rabbits [4]. While the NZW rabbit allows for controlled injuries and accurate biomechanical assessment of healing, it lacks the genetic power that is offered in the mouse. Therefore, pOBCo13.6GFPtpz (Col1) and pCol2ECFP (Col2) double transgenic (DT) reporter mice were created to track spatiotemporal gene expression. Thus, the objectives of this study were to monitor changes in: 1) spatiotemporal Col1 and Col2 gene expression patterns, 2) tissue morphology, and 3) healing biomechanics following a full-length, central PT injury in Col1/Col2 DT mice and to compare these natural healing results to contralateral surgical shams and normal PT in age-matched controls.

Mechanical Stimulation Increases Collagen Type I and Collagen Type III Gene Expression of Stem Cell–Collagen Sponge Constructs for Patellar Tendon Repair

2007 ◽  
Vol 13 (6) ◽  
pp. 1219-1226 ◽  
Author(s):  
Natalia Juncosa-Melvin ◽  
Karl S. Matlin ◽  
Robert W. Holdcraft ◽  
Victor S. Nirmalanandhan ◽  
David L. Butler
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Patellar Tendon ◽  
Mechanical Stimulation ◽  
Collagen Type ◽  
Tendon Repair ◽  
Collagen Type I ◽  
Collagen Sponge ◽  
Type I ◽  
Collagen Type Iii

scholarly journals Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

2019 ◽  
Vol 117 (38) ◽  
pp. 23317-23322 ◽  
Author(s):  
Joaquín Sanz ◽  
Paul L. Maurizio ◽  
Noah Snyder-Mackler ◽  
Noah D. Simons ◽  
Tawni Voyles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Status ◽  
Social History ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Expression Patterns ◽  
Social Experience ◽  
Type I ◽  
Gene Expression Response ◽  
Expression Of Genes

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB–dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB– and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history—in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

scholarly journals Chloroflexi CL500-11 Populations That Predominate Deep-Lake Hypolimnion Bacterioplankton Rely on Nitrogen-Rich Dissolved Organic Matter Metabolism and C1Compound Oxidation

2015 ◽  
Vol 82 (5) ◽  
pp. 1423-1432 ◽  
Author(s):  
Vincent J. Denef ◽  
Ryan S. Mueller ◽  
Edna Chiang ◽  
James R. Liebig ◽  
Henry A. Vanderploeg
Keyword(s):  
Gene Expression ◽  
Organic Matter ◽  
Dissolved Organic Matter ◽  
Water Column ◽  
Lake Michigan ◽  
Expression Patterns ◽  
Metagenomic Data ◽  
Type I ◽  
Deep Lake ◽  
Additional Energy

ABSTRACTTheChloroflexiCL500-11 clade contributes a large proportion of the bacterial biomass in the oxygenated hypolimnia of deep lakes worldwide, including the world's largest freshwater system, the Laurentian Great Lakes. Traits that allow CL500-11 to thrive and its biogeochemical role in these environments are currently unknown. Here, we found that a CL500-11 population was present mostly in offshore waters along a transect in ultraoligotrophic Lake Michigan (a Laurentian Great Lake). It occurred throughout the water column in spring and only in the hypolimnion during summer stratification, contributing up to 18.1% of all cells. Genome reconstruction from metagenomic data suggested an aerobic, motile, heterotrophic lifestyle, with additional energy being gained through carboxidovory and methylovory. Comparisons to other available streamlined freshwater genomes revealed that the CL500-11 genome contained a disproportionate number of cell wall/capsule biosynthesis genes and the most diverse spectrum of genes involved in the uptake of dissolved organic matter (DOM) substrates, particularly peptides.In situexpression patterns indicated the importance of DOM uptake and protein/peptide turnover, as well as type I and type II carbon monoxide dehydrogenase and flagellar motility. Its location in the water column influenced its gene expression patterns the most. We observed increased bacteriorhodopsin gene expression and a response to oxidative stress in surface waters compared to its response in deep waters. While CL500-11 carries multiple adaptations to an oligotrophic lifestyle, its investment in motility, its large cell size, and its distribution in both oligotrophic and mesotrophic lakes indicate its ability to thrive under conditions where resources are more plentiful. Our data indicate that CL500-11 plays an important role in nitrogen-rich DOM mineralization in the extensive deep-lake hypolimnion habitat.

Differential expression of type I and type III collagen genes during tooth development

Development ◽  
1991 ◽  
Vol 111 (3) ◽  
pp. 691-698
Author(s):  
M.B. Andujar ◽  
P. Couble ◽  
M.L. Couble ◽  
H. Magloire
Keyword(s):  
Gene Expression ◽  
Type I Collagen ◽  
Tooth Development ◽  
Expression Patterns ◽  
Type Iii Collagen ◽  
Type I ◽  
Collagen Gene ◽  
Type Iii ◽  
Collagen Gene Expression ◽  
Collagen Genes

Collagen gene expression during mouse molar tooth development was studied by quantitative in situ hybridization techniques. Different expression patterns of type I and type III collagen mRNAs were observed in the various mesenchymal tissues that constitute the tooth germ. High concentration for pro-alpha 1(I) and pro-alpha 2(I) collagen mRNAs were found within the osteoblasts. We found that the cellular content of type I collagen mRNAs in the odontoblasts varies throughout the tooth formation: whereas mRNA concentration for pro-alpha 1(I) collagen decreases and that of pro-alpha 2(I) increases, during postnatal development. Moreover, different amounts of pro-alpha 1(I) and pro-alpha 2(I) collagen mRNAs were observed in crown and root odontoblasts, respectively. Type III collagen mRNAs were detected in most of the mesenchymal cells, codistributed with type I collagen mRNAs, except in odontoblasts and osteoblasts. Finally, this study reports differential accumulation of collagen mRNAs during mouse tooth development and points out that type I collagen gene expression is regulated by distinct mechanisms during odontoblast differentiation process. These results support the independent expression of the collagen genes under developmental tissue-specific control.

Growth Arrest-Specific 2 Gene Expression during Patellar Tendon Healing

2003 ◽  
Vol 173 (3) ◽  
pp. 138-146 ◽  
Author(s):  
K.K.H. Lee ◽  
D.Q. Cai ◽  
M.K. Tang ◽  
K.F. Tsang ◽  
W.H. Kwong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Patellar Tendon ◽  
Growth Arrest ◽  
Tendon Healing

scholarly journals Leveraging expression from multiple tissues using sparse canonical correlation analysis and aggregate tests improves the power of transcriptome-wide association studies

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1008973
Author(s):  
Helian Feng ◽  
Nicholas Mancuso ◽  
Alexander Gusev ◽  
Arunabha Majumdar ◽  
Megan Major ◽  
...  
Keyword(s):  
Gene Expression ◽  
Correlation Analysis ◽  
Canonical Correlation Analysis ◽  
Canonical Correlation ◽  
Association Studies ◽  
Expression Patterns ◽  
Small Sample ◽  
Type I ◽  
Sparse Canonical Correlation Analysis ◽  
Eqtl Data

Transcriptome-wide association studies (TWAS) test the association between traits and genetically predicted gene expression levels. The power of a TWAS depends in part on the strength of the correlation between a genetic predictor of gene expression and the causally relevant gene expression values. Consequently, TWAS power can be low when expression quantitative trait locus (eQTL) data used to train the genetic predictors have small sample sizes, or when data from causally relevant tissues are not available. Here, we propose to address these issues by integrating multiple tissues in the TWAS using sparse canonical correlation analysis (sCCA). We show that sCCA-TWAS combined with single-tissue TWAS using an aggregate Cauchy association test (ACAT) outperforms traditional single-tissue TWAS. In empirically motivated simulations, the sCCA+ACAT approach yielded the highest power to detect a gene associated with phenotype, even when expression in the causal tissue was not directly measured, while controlling the Type I error when there is no association between gene expression and phenotype. For example, when gene expression explains 2% of the variability in outcome, and the GWAS sample size is 20,000, the average power difference between the ACAT combined test of sCCA features and single-tissue, versus single-tissue combined with Generalized Berk-Jones (GBJ) method, single-tissue combined with S-MultiXcan, UTMOST, or summarizing cross-tissue expression patterns using Principal Component Analysis (PCA) approaches was 5%, 8%, 5% and 38%, respectively. The gain in power is likely due to sCCA cross-tissue features being more likely to be detectably heritable. When applied to publicly available summary statistics from 10 complex traits, the sCCA+ACAT test was able to increase the number of testable genes and identify on average an additional 400 additional gene-trait associations that single-trait TWAS missed. Our results suggest that aggregating eQTL data across multiple tissues using sCCA can improve the sensitivity of TWAS while controlling for the false positive rate.

scholarly journals A re-assessment of gene-tag classification approaches for describing var gene expression patterns during human Plasmodium falciparum malaria parasite infections

2017 ◽  
Vol 2 ◽  
pp. 86 ◽  
Author(s):  
George Githinji ◽  
Peter C. Bull
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Full Length ◽  
Endothelial Protein C Receptor ◽  
Gene Sequences ◽  
Sequence Features ◽  
Var Gene

PfEMP1 are variant parasite antigens that are inserted on the surface of Plasmodium falciparum infected erythrocytes (IE). Through interactions with various host molecules, PfEMP1 mediate IE sequestration in tissues and play a key role in the pathology of severe malaria. PfEMP1 is encoded by a diverse multi-gene family called var. Previous studies have shown that that expression of specific subsets of var genes are associated with low levels of host immunity and severe malaria. However, in most clinical studies to date, full-length var gene sequences were unavailable and various approaches have been used to make comparisons between var gene expression profiles in different parasite isolates using limited information. Several studies have relied on the classification of a 300 – 500 base-pair “DBLα tag” region in the DBLα domain located at the 5’ end of most var genes. We assessed the relationship between various DBLα tag classification methods, and sequence features that are only fully assessable through full-length var gene sequences. We compared these different sequence features in full-length var gene from six fully sequenced laboratory isolates. These comparisons show that despite a long history of recombination, DBLα sequence tag classification can provide functional information on important features of full-length var genes. Notably, a specific subset of DBLα tags previously defined as “group A-like” is associated with CIDRα1 domains proposed to bind to endothelial protein C receptor. This analysis helps to bring together different sources of data that have been used to assess var gene expression in clinical parasite isolates.

Use of nCounter mRNA Profiling to Identify at-arrival Gene Expression Patterns for Predicting Bovine Respiratory Disease in Beef Cattle

2021 ◽  
Author(s):  
Matthew Scott ◽  
Amelia Woolums ◽  
Cyprianna Swiderski ◽  
Alexis Thompson ◽  
Andy Perkins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Decision Tree ◽  
Beef Cattle ◽  
Respiratory Disease ◽  
Type I Interferon ◽  
Expression Patterns ◽  
Bovine Respiratory Disease ◽  
Type I ◽  
Complement Factor ◽  
Advanced Analysis

Abstract BackgroundTranscriptomics has identified at-arrival differentially expressed genes associated with bovine respiratory disease (BRD) development; however, their use as prediction molecules necessitates further evaluation. Therefore, we aimed to selectively analyze and corroborate at-arrival mRNA expression from multiple independent populations of beef cattle. In a nested case-control study, we evaluated the expression of 56 mRNA molecules from at-arrival blood samples of 234 cattle across seven populations via NanoString nCounter gene expression profiling. Analysis of mRNA was performed with nSolver Advanced Analysis software (p<0.05), comparing cattle groups based on the diagnosis of clinical BRD within 28 days of facility arrival (n=115 Healthy; n=119 BRD); BRD was further stratified for severity based on frequency of treatment and/or mortality (Treated_1, n=89; Treated_2+, n=30). Gene expression homogeneity of variance, receiver operator characteristic (ROC) curve, and decision tree analyses were performed between severity cohorts.ResultsIncreased expression of mRNAs involved in specialized pro-resolving mediator synthesis (ALOX15, HPGD), leukocyte differentiation (LOC100297044, GCSAML, KLF17), and antimicrobial peptide production (CATHL3, GZMB, LTF) were identified in Healthy cattle. BRD cattle possessed increased expression of CFB, and mRNA related to granulocytic processes (DSG1, LRG1, MCF2L) and type-I interferon activity (HERC6, IFI6, ISG15, MX1). Healthy and Treated_1 cattle were similar in terms of gene expression, while Treated_2+ cattle were the most distinct. ROC cutoffs were used to generate an at-arrival treatment decision tree, which classified 90% of Treated_2+ individuals. ConclusionsIncreased expression of complement factor B, pro-inflammatory, and type I interferon-associated mRNA hallmark the at-arrival expression patterns of cattle that develop severe clinical BRD. Here, we corroborate at-arrival mRNA markers identified in previous transcriptome studies and generate a prediction model to be evaluated in future studies. Further research is necessary to evaluate these expression patterns in a prospective manner.

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