scholarly journals Murine Macrophage Transcriptional Responses to Bacillus anthracis Infection and Intoxication

2005 ◽  
Vol 73 (2) ◽  
pp. 1069-1080 ◽  
Author(s):  
Nicholas H. Bergman ◽  
Karla D. Passalacqua ◽  
Renee Gaspard ◽  
Lynne M. Shetron-Rama ◽  
John Quackenbush ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Bacterial Species ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Anthrax Lethal Toxin ◽  
Transcriptional Responses ◽  
Transcriptional Changes ◽  
Infected Cells ◽  
Induced Apoptosis

ABSTRACT Interactions between Bacillus anthracis and host macrophages represent critical early events in anthrax pathogenesis, but their details are not clearly understood. Here we report the first genomewide characterization of the transcriptional changes within macrophages infected with B. anthracis and the identification of several hundred host genes that were differentially expressed during this intracellular stage of infection. These loci included both genes that are known to be regulated differentially in response to many other bacterial pathogens and those that appear to be differentially regulated in response to B. anthracis but not other bacterial species that have been tested. These data provide a transcriptional basis for a variety of physiological changes observed during infection, including the induction of apoptosis caused by the infecting bacteria. The expression patterns underlying B. anthracis-induced apoptosis led us to test further the importance of one very highly induced macrophage gene, that for ornithine decarboxylase. Our data show that this enzyme plays an important and previously unrecognized role in suppressing apoptosis in B. anthracis-infected cells. We have also characterized the transcriptional response to anthrax lethal toxin in activated macrophages and found that, following toxin treatment, many of the host inflammatory response pathways are dampened. These data provide insights into B. anthracis pathogenesis as well as potential leads for the development of new diagnostic and therapeutic options.

scholarly journals Genome-Wide Systematic Characterization of the NPF Family Genes and Their Transcriptional Responses to Multiple Nutrient Stresses in Allotetraploid Rapeseed

2020 ◽  
Vol 21 (17) ◽  
pp. 5947 ◽  
Author(s):  
Hao Zhang ◽  
Shuang Li ◽  
Mengyao Shi ◽  
Sheliang Wang ◽  
Lei Shi ◽  
...  
Keyword(s):  
N Uptake ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Peptide Transporter ◽  
Future Research ◽  
Whole Genome ◽  
Transcriptional Responses ◽  
Ammonium Toxicity ◽  
Genome Wide

NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) family (NPF) proteins can transport various substrates, and play crucial roles in governing plant nitrogen (N) uptake and distribution. However, little is known about the NPF genes in Brassica napus. Here, a comprehensive genome-wide systematic characterization of the NPF family led to the identification of 193 NPF genes in the whole genome of B. napus. The BnaNPF family exhibited high levels of genetic diversity among sub-families but this was conserved within each subfamily. Whole-genome duplication and segmental duplication played a major role in BnaNPF evolution. The expression analysis indicated that a broad range of expression patterns for individual gene occurred in response to multiple nutrient stresses, including N, phosphorus (P) and potassium (K) deficiencies, as well as ammonium toxicity. Furthermore, 10 core BnaNPF genes in response to N stress were identified. These genes contained 6–13 transmembrane domains, located in plasma membrane, that respond discrepantly to N deficiency in different tissues. Robust cis-regulatory elements were identified within the promoter regions of the core genes. Taken together, our results suggest that BnaNPFs are versatile transporters that might evolve new functions in B. napus. Our findings benefit future research on this gene family.

scholarly journals Role of the cytoskeleton in muscle transcriptional responses to altered use

2013 ◽  
Vol 45 (8) ◽  
pp. 321-331 ◽  
Author(s):  
Gretchen A. Meyer ◽  
Simon Schenk ◽  
Richard L. Lieber
Keyword(s):  
Mechanical Response ◽  
Fiber Type ◽  
Transcriptional Response ◽  
Primary Component ◽  
Transcriptional Responses ◽  
Expression Of Genes ◽  
Elevated Expression ◽  
Transcriptional Changes ◽  
Type Shift ◽  
Future Work

In this work, the interaction between the loss of a primary component of the skeletal muscle cytoskeleton, desmin, and two common physiological stressors, acute mechanical injury and aging, were investigated at the transcriptional, protein, and whole muscle levels. The transcriptional response of desmin knockout ( des −/−) plantarflexors to a bout of 50 eccentric contractions (ECCs) showed substantial overlap with the response in wild-type ( wt) muscle. However, changes in the expression of genes involved in muscle response to injury were blunted in adult des −/− muscle compared with wt (fold change with ECC in des −/− and wt, respectively: Mybph, 1.4 and 2.9; Xirp1, 2.2 and 5.7; Csrp3, 1.8 and 4.3), similar to the observed blunted mechanical response (torque drop: des −/− 30.3% and wt 55.5%). Interestingly, in the absence of stressors, des −/− muscle exhibited elevated expression of many these genes compared with wt. The largest transcriptional changes were observed in the interaction between aging and the absence of desmin, including many genes related to slow fiber pathway (Myh7, Myl3, Atp2a2, and Casq2) and insulin sensitivity (Tlr4, Trib3, Pdk3, and Pdk4). Consistent with these transcriptional changes, adult des −/− muscle exhibited a significant fiber type shift from fast to slow isoforms of myosin heavy chain ( wt, 5.3% IIa and 71.7% IIb; des −/−, 8.4% IIa and 61.4% IIb) and a decreased insulin-stimulated glucose uptake ( wt, 0.188 μmol/g muscle/20 min; des −/−, 0.085 μmol/g muscle/20 min). This work points to novel areas of influence of this cytoskeletal protein and directs future work to elucidate its function.

scholarly journals Biphasic Modulation of Apoptotic Pathways in Cryptosporidium parvum-Infected Human Intestinal Epithelial Cells

2008 ◽  
Vol 77 (2) ◽  
pp. 837-849 ◽  
Author(s):  
Jin Liu ◽  
Mingqi Deng ◽  
Cheryl A. Lancto ◽  
Mitchell S. Abrahamsen ◽  
Mark S. Rutherford ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Expression Patterns ◽  
Nuclear Condensation ◽  
Successful Infection ◽  
Cell Gene Expression ◽  
Infected Cells ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
The Impact

ABSTRACT The impact of Cryptosporidium parvum infection on host cell gene expression was investigated by microarray analysis with an in vitro model using human ileocecal HCT-8 adenocarcinoma cells. We found changes in 333 (2.6%) transcripts at at least two of the five (6, 12, 24, 48, and 72 h) postinfection time points. Fifty-one of the regulated genes were associated with apoptosis and were grouped into five clusters based on their expression patterns. Early in infection (6 and 12 h), genes with antiapoptotic roles were upregulated and genes with apoptotic roles were downregulated. Later in infection (24, 48, and 72 h), proapoptotic genes were induced and antiapoptotic genes were downregulated, suggesting a biphasic regulation of apoptosis: antiapoptotic state early and moderately proapoptotic state late in infection. This transcriptional profile matched the actual occurrence of apoptosis in the infected cultures. Apoptosis was first detected at 12 h postinfection and increased to a plateau at 24 h, when 20% of infected cells showed nuclear condensation. In contrast, experimental silencing of Bcl-2 induced apoptosis in 50% of infected cells at 12 h postinfection. This resulted in a decrease in the infection rate and a reduction in the accumulation of meront-containing cells. To test the significance of the moderately proapoptotic state late in the infection, we inhibited apoptosis using pancaspase inhibitor Z-VAD-FMK. This treatment also affected the progression of C. parvum infection, as reinfection, normally seen late (24 h to 48 h), did not occur and accumulation of mature meronts was impaired. Control of host apoptosis is complex and crucial to the life of C. parvum. Apoptosis control has at least two components, early inhibition and late moderate promotion. For a successful infection, both aspects appear to be required.

scholarly journals Patterns of parent and offspring gene expression reflect canalization, not plasticity, in response to environmental stress

2021 ◽  
Author(s):  
Jeanette B Moss ◽  
Christopher B Cunningham ◽  
Elizabeth C McKinney ◽  
Allen J. Moore
Keyword(s):  
Gene Expression ◽  
Environmental Change ◽  
Environmental Stress ◽  
Behavioral Plasticity ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Behavioral Stability ◽  
The Face ◽  
Transcriptional Changes ◽  
Hostile Environments

Parenting buffers offspring from hostile environments, but it is not clear how or if the genes that underlie parenting change their expression under environmental stress. We recently demonstrated that for the subsocial carrion beetle, Nicrophorus orbicollis, temperature during parenting does not affect parenting phenotypes. Here, we ask if transcriptional changes associated with parenting are likewise robust to environmental stress. The absence of a transcriptional response for parenting under stress would suggest that the genetic programs for parenting and being parented are canalized. Conversely, a robust transcriptional response would suggest that plasticity of underlying gene expression is critical for maintaining behavioral stability, and that these mechanisms provide a potential target for selection in the face of environmental change. We test these alternatives by characterizing gene expression of parents and offspring with and without parent-offspring interactions under a benign and a stressful temperature. We found that parent-offspring interactions elicit distinct transcriptional responses of parents and larvae irrespective of temperature. We further detected robust changes of gene expression in beetles breeding at 24 degrees C compared to 20 degrees C irrespective of family interaction. However, no strong interaction between parent-offspring interaction and temperature was detected for either parents or larvae. We therefore conclude that canalization, not plasticity of gene expression, most likely explains the absence of behavioral plasticity under thermal stress. This result suggests that species may not have the genetic variation needed to respond to all environmental change, especially for complex phenotypes.

scholarly journals Cell Sorting-Assisted Microarray Profiling of Host Cell Response to Cryptosporidium parvum Infection

2009 ◽  
Vol 78 (3) ◽  
pp. 1040-1048 ◽  
Author(s):  
Yi-Lin Yang ◽  
Gregory A. Buck ◽  
Giovanni Widmer
Keyword(s):  
Cryptosporidium Parvum ◽  
Mammalian Cells ◽  
Transcriptional Response ◽  
Uninfected Cell ◽  
Direct Consequence ◽  
Cell Monolayers ◽  
Host Cell Response ◽  
Intracellular Parasites ◽  
Transcriptional Changes ◽  
Infected Cells

ABSTRACT To study the transcriptional response of mammalian cells to infection with the intracellular apicomplexan parasite Cryptosporidium parvum, infected and uninfected cells were recovered from C. parvum-infected cell monolayers. This approach, which contrasts with a more conventional experimental design that compares infected to uninfected cell monolayers, enabled the identification of functional categories of genes that are differentially transcribed as a direct consequence of the presence of intracellular parasites. Among several categories of upregulated genes, glycoprotein metabolism was significantly overrepresented. To investigate whether these transcriptional changes affected the composition of the surface of infected cells, cells were probed with fluorescently labeled lectins. Among a panel of seven lectins, soybean agglutinin, which recognizes N-acetyl-d-galactosamine, generated the largest difference in fluorescence between infected and uninfected cells. The origin of the fluorescent signal emitted by infected cells was further investigated and attributed to the overexpression of glycoprotein on the surface of infected cells, as well as the presence of glycoprotein located in the proximity of intracellular parasites.

scholarly journals Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation

2013 ◽  
Vol 45 (15) ◽  
pp. 653-666 ◽  
Author(s):  
Maia J. Benner ◽  
Matt L. Settles ◽  
Gordon K. Murdoch ◽  
Ronald W. Hardy ◽  
Barrie D. Robison
Keyword(s):  
Danio Rerio ◽  
Sodium Selenite ◽  
Large Scale ◽  
Transcriptional Response ◽  
Nutritional Intervention ◽  
Transcriptional Responses ◽  
Qrt Pcr ◽  
Short Period ◽  
Transcriptional Changes ◽  
The Brain

The potential benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. However, little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy, Se sufficient subjects. We evaluated the transcriptional response of Se-dependent genes, selenoproteins and the genes necessary for their synthesis (the selenoproteome), in the zebrafish ( Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency. We first used a microarray approach to analyze the response of the brain selenoproteome to dietary Se supplementation for 14 days and then assessed the immediacy and time-scale transcriptional response of the brain selenoproteome to 1, 7, and 14 days of Se supplementation by quantitative real-time PCR (qRT-PCR). The microarray approach did not indicate large-scale influences of Se on the brain transcriptome as a whole or the selenoproteome specifically; only one nonselenoproteome gene (si:ch73-44m9.2) was significantly differentially expressed. Our qRT-PCR results, however, indicate that increases of dietary Se cause small, but significant transcriptional changes within the brain selenoproteome, even after only 1 day of supplementation. These responses were dynamic over a short period of supplementation in a manner highly dependent on sex and the duration of Se supplementation. In nutritional intervention studies, it may be necessary to utilize methods such as qRT-PCR, which allow larger sample sizes, for detecting subtle transcriptional changes in the brain.

scholarly journals Permissive epigenetic landscape facilitates distinct transcriptional signatures of activating transcription factor 6 in the liver

2021 ◽  
Author(s):  
Anjana Ramdas Nair ◽  
Priyanka Lakhiani ◽  
Chi Zhang ◽  
Filippo Macchi ◽  
Kirsten C. Sadler
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Differentially Expressed ◽  
Small Subset ◽  
Gene Promoters ◽  
Transcriptional Responses ◽  
Functional Studies ◽  
Activating Transcription Factor

ABSTRACTProteostatic stress initiates a transcriptional response that is unique to the stress condition, yet the regulatory mechanisms underlying the distinct gene expression patterns observed in stressed cells remains unknown. Using a functional genomic approach, we investigated how activating transcription factor 6 (ATF6), a key transcription factor in the unfolded protein response (UPR), regulates target genes. We first designed a computational strategy to define Atf6 target genes based on the evolutionary conservation of predicted ATF6 binding in gene promoters, identifying 652 conserved putative Atf6 target (CPAT) genes. CPATs were overrepresented for genes functioning in the UPR, however, the majority functioned in cellular processes unrelated to proteostasis, including small molecule metabolism and development. Functional studies of stress-independent and toxicant based Atf6 activation in zebrafish livers showed that the pattern of CPAT expression in response to Atf6 overexpression, alcohol and arsenic was unique. Only 34 CPATs were differentially expressed in all conditions, indicating that Atf6 is sufficient to regulate a small subset of CPATs. Blocking Atf6 using Ceapins in zebrafish demonstrated that Atf6 is necessary for activation of these genes in response to arsenic. We investigated CPAT during physiologically mediated hepatocyte stress using liver regeneration in mice as a model. Over half of all CPATs were differentially expressed during this process. This was attributed to the permissive chromatin environment in quiescent livers on the promoters of these genes, characterized by the absence of H3K27me3 and enrichment of H3K4me3. Taken together, these data uncover a complex transcriptional response to Atf6 activation and implicate a permissive epigenome as a mechanism by which distinct transcriptional responses are regulated by Atf6.

scholarly journals Characterization of transcriptional response of Lactobacillus plantarum under acidic conditions provides insight into bacterial adaptation in fermentative environments

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sera Jung ◽  
Jong-Hee Lee
Keyword(s):  
Lactobacillus Plantarum ◽  
Raw Materials ◽  
Transcriptional Response ◽  
Bacterial Adaptation ◽  
Transcriptional Changes ◽  
Leucine Transport ◽  
Acidic Conditions ◽  
Ph Range ◽  
Insight Into

Abstract Lactic acid bacteria (LAB) play an important role in kimchi fermentation by metabolizing raw materials into diverse metabolites. Bacterial adaptation is therefore a crucial element of fermentation. In this study, we investigated the transcriptional changes of Lactobacillus plantarum under acidic conditions to evaluate the elements of bacterial adaptation critical for fermentation. Differentially expressed genes (DEGs) have shown that transport function is primarily affected by acidic conditions. Five of the 13 significantly down-regulated genes and 7 of the 25 significantly up-regulated genes were found to have transport-related functions. We quantified the intracellular leucine content of bacteria grown at different pH ranges, determining that optimal bacterial leucine transport could be controlled by acidity during fermentation. Inhibition of L. plantarum growth was investigated and compared with other LAB at a pH range of 6.2–5.0. Interestingly, valinomycin inhibited L. plantarum growth from pH 6.2 to 5.0. This showed that L. plantarum had a wider range of transport functions than other LAB. These results suggested that L. plantarum had robust transport functions, and that this was the crucial factor for bacterial adaptation during fermentation.

scholarly journals The Global Transcriptional Responses of Bacillus anthracis Sterne (34F2) and a ΔsodA1 Mutant to Paraquat Reveal Metal Ion Homeostasis Imbalances during Endogenous Superoxide Stress

2007 ◽  
Vol 189 (11) ◽  
pp. 3996-4013 ◽  
Author(s):  
Karla D. Passalacqua ◽  
Nicholas H. Bergman ◽  
Jung Yeop Lee ◽  
David H. Sherman ◽  
Philip C. Hanna
Keyword(s):  
Bacillus Anthracis ◽  
Parental Strain ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Oxidoreductase Activity ◽  
Posttranscriptional Control ◽  
Metal Ion Homeostasis ◽  
Superoxide Dismutase Gene

ABSTRACT Microarray analyses were conducted to evaluate the paraquat-induced global transcriptional response of Bacillus anthracis Sterne (34F2) to varying levels of endogenous superoxide stress. Data revealed that the transcription of genes putatively involved in metal/ion transport, bacillibactin siderophore biosynthesis, the glyoxalase pathway, and oxidoreductase activity was perturbed most significantly. A B. anthracis mutant lacking the superoxide dismutase gene sodA1 (ΔsodA1) had transcriptional responses to paraquat similar to, but notably larger than, those of the isogenic parental strain. A small, unique set of genes was found to be differentially expressed in the ΔsodA1 mutant relative to the parental strain during growth in rich broth independently of induced oxidative stress. The bacillibactin siderophore biosynthetic genes were notably overexpressed in Sterne and ΔsodA1 cells after treatment with paraquat. The bacillibactin siderophore itself was isolated from the supernatants and lysates of cells grown in iron-depleted medium and was detected at lower levels after treatment with paraquat. This suggests that, while transcriptional regulation of these genes is sensitive to changes in the redox environment, additional levels of posttranscriptional control may exist for bacillibactin biosynthesis, or the enzymatic siderophore pipeline may be compromised by intracellular superoxide stress or damage. The ΔsodA1 mutant showed slower growth in a chelated iron-limiting medium but not in a metal-depleted medium, suggesting a connection between the intracellular redox state and iron/metal ion acquisition in B. anthracis. A double mutant lacking both the sodA1 and sodA2 genes (ΔsodA1 ΔsodA2) was attenuated for growth in manganese-depleted medium, suggesting a slight level of redundancy between sodA1 and sodA2, and a role for the sod genes in manganese homeostasis.

scholarly journals Transcriptional responses to hyperplastic MRL signalling in Drosophila

Open Biology ◽  
2017 ◽  
Vol 7 (2) ◽  
pp. 160306 ◽  
Author(s):  
Vincent Jonchère ◽  
Nada Alqadri ◽  
John Herbert ◽  
Lauren Dodgson ◽  
David Mason ◽  
...  
Keyword(s):  
Serum Response Factor ◽  
Transcriptional Response ◽  
Size Control ◽  
Actin Dynamics ◽  
Transcriptional Responses ◽  
Rna Profiling ◽  
Related Transcription Factor ◽  
Transcriptional Changes ◽  
Wing Discs

Recent work has implicated the actin cytoskeleton in tissue size control and tumourigenesis, but how changes in actin dynamics contribute to hyperplastic growth is still unclear. Overexpression of Pico, the only Drosophila Mig-10/RIAM/Lamellipodin adapter protein family member, has been linked to tissue overgrowth via its effect on the myocardin-related transcription factor (Mrtf), an F-actin sensor capable of activating serum response factor (SRF). Transcriptional changes induced by acute Mrtf/SRF signalling have been largely linked to actin biosynthesis and cytoskeletal regulation. However, by RNA profiling, we find that the common response to chronic mrtf and pico overexpression in wing discs was upregulation of ribosome protein and mitochondrial genes, which are conserved targets for Mrtf/SRF and are known growth drivers. Consistent with their ability to induce a common transcriptional response and activate SRF signalling in vitro , we found that both pico and mrtf stimulate expression of an SRF-responsive reporter gene in wing discs. In a functional genetic screen, we also identified deterin , which encodes Drosophila Survivin, as a putative Mrtf/SRF target that is necessary for pico -mediated tissue overgrowth by suppressing proliferation-associated cell death. Taken together, our findings raise the possibility that distinct targets of Mrtf/SRF may be transcriptionally induced depending on the duration of upstream signalling.

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