scholarly journals Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers

2018 ◽  
Author(s):  
Stephen J. Popper ◽  
Fiona R. Strouts ◽  
Janet C. Lindow ◽  
Henry K. Cheng ◽  
Magelda Montoya ◽  
...  
Keyword(s):  
Natural Infection ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Neutralizing Antibody ◽  
Transcript Abundance ◽  
Denv Infection ◽  
Fold Change ◽  
Specific Gene ◽  
Transcriptional Responses ◽  
Post Vaccination

Background: Several promising live attenuated virus (LAV) dengue vaccines are in development, but information about innate immune responses and early correlates of protection are lacking. Methods: We characterized human genome-wide transcripts in whole blood from 10 volunteers at 11 time-points after immunization with the dengue virus type 3 (DENV-3) component of the NIH dengue vaccine candidate TV003 and from 30 hospitalized children with acute primary DENV-3 infection. We compared day-specific gene expression patterns with subsequent neutralizing antibody (NAb) titers. Results: The transcriptional response to vaccination was largely confined to days 5-20 and was dominated by an interferon-associated signature and a cell cycle signature that peaked on days 8 and 14, respectively. Changes in transcript abundance were much greater in magnitude and scope in symptomatic natural infection than following vaccination (maximum fold-change >200 versus 21 post-vaccination; 3,210 versus 286 transcripts with significant fold-change), but shared gene modules were induced in the same sequence. The abundance of 131 transcripts on days 8 and 9 post-vaccination was strongly correlated with NAb titers measured 6 weeks post-vaccination. Conclusions: LAV dengue vaccination elicits early transcriptional responses that mirror those found in symptomatic natural infection and provide candidate early markers of protection against DENV infection.

scholarly journals Transcriptome Profiling Reveals Spatial-temporal Dynamics of Gene Expression Essential for Soybean Seed Development

2020 ◽  
Author(s):  
Hengyou Zhang ◽  
Zhenbin Hu ◽  
Yuming Yang ◽  
Xiaoqian Liu ◽  
Haiyan Lv ◽  
...  
Keyword(s):  
Seed Development ◽  
Temporal Dynamics ◽  
Expression Patterns ◽  
Soybean Seed ◽  
Transcriptome Profiling ◽  
Transcript Abundance ◽  
Specific Gene ◽  
Oilseed Crop ◽  
Seed Formation ◽  
Developing Seeds

Abstract Background: Seeds are the economic basis of oilseed crops, especially for soybean, thus far the most widely cultivated oilseed crop worldwide. Seed development is accompanied with a multitude of diverse cellular processes and revealing the underlying regulatory activities is critical for seed improvement. Results: Here, we profiled transcriptomes of developing seeds (20, 25, 30, 40 days after flowering) representing key points of seed development from early to full development. We identified a set of highly-abundant genes and highlighted the importance of these genes to support nutrient accumulation and transcriptional regulation in developing seeds. We identified 8,925 differentially expressed genes that exhibited temporal expression patterns over the course and had expression specificities in distinct tissues including seeds and non-seed tissues (roots, stems, leaves). Genes with specificities to non-seed tissues have tissue-specialized roles while remain relatively low transcript abundance in developing seeds, exhibiting their supportive roles spatially for seed development. Co-expression network analysis identified several under-explored genes in soybean that bridge tissue-specific gene modules. Conclusions: Our study provides a global view of gene activities and biological processes critical for seed formation in soybean and prioritizes a set of genes for further study. The results shed insight into the mechanism controlling seed development and storage reserves.

scholarly journals Early whole blood transcriptional responses to radiation-attenuated Plasmodium falciparum sporozoite vaccination in malaria naïve and malaria pre-exposed adult volunteers

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fergal J. Duffy ◽  
Ying Du ◽  
Jason Carnes ◽  
Judith E. Epstein ◽  
Stephen L. Hoffman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Plasmodium Falciparum ◽  
Whole Blood ◽  
Inflammatory Responses ◽  
Protective Efficacy ◽  
Transcriptional Response ◽  
Interferon Response ◽  
Transcriptional Responses ◽  
Post Vaccination ◽  
Adult Participants

Abstract Background Vaccination with radiation-attenuated Plasmodium falciparum sporozoites is known to induce protective immunity. However, the mechanisms underlying this protection remain unclear. In this work, two recent radiation-attenuated sporozoite vaccination studies were used to identify potential transcriptional correlates of vaccination-induced protection. Methods Longitudinal whole blood RNAseq transcriptome responses to immunization with radiation-attenuated P. falciparum sporozoites were analysed and compared across malaria-naïve adult participants (IMRAS) and malaria-experienced adult participants (BSPZV1). Parasite dose and method of delivery differed between trials, and immunization regimens were designed to achieve incomplete protective efficacy. Observed protective efficacy was 55% in IMRAS and 20% in BSPZV1. Study vaccine dosings were chosen to elicit both protected and non-protected subjects, so that protection-associated responses could be identified. Results Analysis of comparable time points up to 1 week after the first vaccination revealed a shared cross-study transcriptional response programme, despite large differences in number and magnitude of differentially expressed genes between trials. A time-dependent regulatory programme of coherent blood transcriptional modular responses was observed, involving induction of inflammatory responses 1–3 days post-vaccination, with cell cycle responses apparent by day 7 in protected individuals from both trials. Additionally, strongly increased induction of inflammation and interferon-associated responses was seen in non-protected IMRAS participants. All individuals, except for non-protected BSPZV1 participants, showed robust upregulation of cell-cycle associated transcriptional responses post vaccination. Conclusions In summary, despite stark differences between the two studies, including route of vaccination and status of malaria exposure, responses were identified that were associated with protection after PfRAS vaccination. These comprised a moderate early interferon response peaking 2 days post vaccination, followed by a later proliferative cell cycle response steadily increasing over the first 7 days post vaccination. Non-protection is associated with deviations from this model, observed in this study with over-induction of early interferon responses in IMRAS and failure to mount a cell cycle response in BSPZV1.

scholarly journals Changes in DnaA-Dependent Gene Expression Contribute to the Transcriptional and Developmental Response of Bacillus subtilis to Manganese Limitation in Luria-Bertani Medium

2010 ◽  
Vol 192 (15) ◽  
pp. 3915-3924 ◽  
Author(s):  
Sharon E. Hoover ◽  
Weihong Xu ◽  
Wenzhong Xiao ◽  
William F. Burkholder
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Bacillus Subtilis ◽  
Dna Replication ◽  
Alkylating Agents ◽  
Transcriptional Response ◽  
Sos Response ◽  
Replication Initiation ◽  
Specific Gene ◽  
Transcriptional Responses

ABSTRACT The SOS response to DNA damage in bacteria is a well-known component of the complex transcriptional responses to genotoxic environmental stresses such as exposure to reactive oxygen species, alkylating agents, and many of the antibiotics targeting DNA replication. However, bacteria such as Bacillus subtilis also respond to conditions that perturb DNA replication via a transcriptional response mediated by the replication initiation protein DnaA. In addition to regulating the initiation of DNA replication, DnaA directly regulates the transcription of specific genes. Conditions that perturb DNA replication can trigger the accumulation of active DnaA, activating or repressing the transcription of genes in the DnaA regulon. We report here that simply growing B. subtilis in LB medium altered DnaA-dependent gene expression in a manner consistent with the accumulation of active DnaA and that this was part of a general transcriptional response to manganese limitation. The SOS response to DNA damage was not induced under these conditions. One of the genes positively regulated by DnaA in Bacillus subtilis encodes a protein that inhibits the initiation of sporulation, Sda. Sda expression was induced as cells entered stationary phase in LB medium but not in LB medium supplemented with manganese, and the induction of Sda inhibited sporulation-specific gene expression and the onset of spore morphogenesis. In the absence of Sda, manganese-limited cells initiated spore development but failed to form mature spores. These data highlight that DnaA-dependent gene expression may influence the response of bacteria to a range of environmental conditions, including conditions that are not obviously associated with genotoxic stress.

scholarly journals Patterns of thaumarchaeal gene expression in culture and diverse marine environments

2017 ◽  
Author(s):  
Paul Carini ◽  
Christopher L. Dupont ◽  
Alyson E. Santoro
Keyword(s):  
Gene Expression ◽  
Metabolic Regulation ◽  
Ammonia Oxidation ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Transcript Abundance ◽  
Ammonium Transporter ◽  
Growth State ◽  
Marine Habitats ◽  
Gene Coding

AbstractThaumarchaea are ubiquitous in marine habitats where they participate in carbon and nitrogen cycling. Although metatranscriptomes suggest thaumarchaea are active microbes in marine waters, we understand little about how thaumarchaeal gene expression patterns relate to substrate utilization and activity. Here, we report the global transcriptional response of the marine ammonia-oxidizing thaumarchaeon ‘CandidatusNitrosopelagicus brevis’ str. CN25 to ammonia limitation using RNA-Seq. We further describe the genome and transcriptome ofCa. N. brevis str. U25, a new strain capable of urea utilization. Ammonia limitation in CN25 resulted in reduced expression of transcripts coding for ammonia oxidation proteins, and increased expression of a gene coding an Hsp20-like chaperone. Despite significantly different transcript abundances across treatments, two ammonia monooxygenase subunits (amoAB), a nitrite reductase (nirK), and both ammonium transporter genes were always among the most abundant transcripts, regardless of growth state.Ca. N. brevis str. U25 cells expressed a urea transporter 139-fold more than the urease catalytic subunitureC. Gene co-expression networks derived from culture transcriptomes and ten thaumarchaea-enriched metatranscriptomes revealed a high degree of correlated gene expression across disparate environmental conditions and identified a module of genes, includingamoABCandnirK, that we hypothesize to represent the core ammonia oxidation machinery.Originality-Significance StatementDiscovering gene function in fastidious or uncultivated lineages remains one of the biggest challenges in environmental microbiology. Here, we use an approach that combines controlled laboratory experiments within situtranscript abundance data from the environment to identify genes that share similar transcription patterns in marine ammonia-oxidizing thaumarchaea. These findings demonstrate how transcriptomes from microbial cultures can be used together with complex environmental samples to identify suites of co-expressed genes that are otherwise enigmatic and provide new insights into the mechanism of ammonia oxidation. Our results add to the growing body of literature showing that relatively small changes in transcript abundance are linked to large changes in growth in organisms with reduced genomes, suggesting they have limited capacity for metabolic regulation or that they rely on mechanisms other than transcriptional regulation to deal with a fluctuating environment.

scholarly journals Transcriptome profiling reveals the spatial-temporal dynamics of gene expression essential for soybean seed development

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hengyou Zhang ◽  
Zhenbin Hu ◽  
Yuming Yang ◽  
Xiaoqian Liu ◽  
Haiyan Lv ◽  
...  
Keyword(s):  
Seed Development ◽  
Temporal Dynamics ◽  
Expression Patterns ◽  
Critical Time ◽  
Soybean Seed ◽  
Transcript Abundance ◽  
Specific Gene ◽  
Oilseed Crop ◽  
Seed Formation ◽  
Developing Seeds

Abstract Background Seeds are the economic basis of oilseed crops, especially soybeans, the most widely cultivated oilseed crop worldwide. Seed development is accompanied by a multitude of diverse cellular processes, and revealing the underlying regulatory activities is critical for seed improvement. Results In this study, we profiled the transcriptomes of developing seeds at 20, 25, 30, and 40 days after flowering (DAF), as these stages represent critical time points of seed development from early to full development. We identified a set of highly abundant genes and highlighted the importance of these genes in supporting nutrient accumulation and transcriptional regulation for seed development. We identified 8925 differentially expressed genes (DEGs) that exhibited temporal expression patterns over the course and expression specificities in distinct tissues, including seeds and nonseed tissues (roots, stems, and leaves). Genes specific to nonseed tissues might have tissue-associated roles, with relatively low transcript abundance in developing seeds, suggesting their spatially supportive roles in seed development. Coexpression network analysis identified several underexplored genes in soybeans that bridge tissue-specific gene modules. Conclusions Our study provides a global view of gene activities and biological processes critical for seed formation in soybeans and prioritizes a set of genes for further study. The results of this study help to elucidate the mechanism controlling seed development and storage reserves.

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 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 Seroprevalence and Dynamics of anti-SARS-CoV-2 antibody among healthcare workers following ChAdOx1 nCoV-19 vaccination

2021 ◽  
Author(s):  
Soma Sarkar ◽  
Shantanab das ◽  
Kabita Choudhury ◽  
Saibal Mukherjee ◽  
Raghunath Chatterjee
Keyword(s):  
Health Care Workers ◽  
Healthcare Workers ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Exposed Group ◽  
Detectable Amount ◽  
Significant Drop ◽  
Post Vaccination ◽  
Care Workers ◽  
Regular Contact

Abstract Background The serological evaluations of IgG, IgM, and IgA to the SARS-CoV-2 proteins are widely used for the epidemiological assessment of COVID-19. The Health Care Workers (HCWs) are presumably exposed to a higher risk of acquiring the disease owing to their regular contact with the patients. Methods COVID-19 prevalence was investigated by classifying 313 HCWs into four groups based on their degree of exposure and estimating the IgG and total antibody. The serological assessment of the anti-SARS-CoV-2 antibody was conducted 21 days post-vaccination of first or both doses of the ChAdOx1 nCoV-19 vaccine among 174 HCWs. The vaccinated HCWs were followed up for 3 months for SARS-CoV-2 infection. Findings The levels of anti-SARS-CoV-2 IgG were comparable among different groups, but the seroprevalence gradually decreased from the most exposed to the less exposed group. The neutralizing antibody was positively correlated with IgG as well as total antibody. IgG was marginally decreased after 2 months followed by a significant drop after 4-6 months post-infection. However, 80% of the HCWs developed a detectable amount of IgG after the first dose of vaccination, the median titer of which was comparable to the seropositive HCWs after natural infection. Almost 100% of the HCWs developed antibodies after the second dose of vaccine with boosting effect among the seropositive HCWs. Although ~11.5% of the vaccinated HCWs were infected with the SARS-CoV-2, ~94% of them showed mild symptoms and recovered in home isolation without any O2 support. Interpretations The varying level of seroprevalence among the four groups suggested a stratified spread of the disease. One dose of SARS-CoV-2 vaccination was found to be effective in terms of the antibody titer, while the second dose was required to cover the larger population. The effectiveness of the ChAdOx1 nCoV-19 vaccine was noticeable due to the low rate of post-vaccination infection with moderate or severe symptoms.

scholarly journals Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers

2018 ◽  
Vol 218 (12) ◽  
pp. 1911-1921 ◽  
Author(s):  
Stephen J Popper ◽  
Fiona R Strouts ◽  
Janet C Lindow ◽  
Henry K Cheng ◽  
Magelda Montoya ◽  
...  
Keyword(s):  
Natural Infection ◽  
Neutralizing Antibody ◽  
Transcriptional Responses ◽  
Antibody Titers

scholarly journals Transcriptome analysis and molecular mechanism of linseed (Linum usitatissimum L.) drought tolerance under repeated drought using single-molecule long-read sequencing

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei Wang ◽  
Lei Wang ◽  
Ling Wang ◽  
Meilian Tan ◽  
Collins O. Ogutu ◽  
...  
Keyword(s):  
Dna Repair ◽  
Drought Tolerance ◽  
Single Molecule ◽  
Linum Usitatissimum ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Enrichment Analysis ◽  
Resistant Variety ◽  
Proline Biosynthesis ◽  
Interacting Protein

Abstract Background Oil flax (linseed, Linum usitatissimum L.) is one of the most important oil crops., However, the increases in drought resulting from climate change have dramatically reduces linseed yield and quality, but very little is known about how linseed coordinates the expression of drought resistance gene in response to different level of drought stress (DS) on the genome-wide level. Results To explore the linseed transcriptional response of DS and repeated drought (RD) stress, we determined the drought tolerance of different linseed varieties. Then we performed full-length transcriptome sequencing of drought-resistant variety (Z141) and drought-sensitive variety (NY-17) under DS and RD stress at the seedling stage using single-molecule real-time sequencing and RNA-sequencing. Gene Ontology (GO) and reduce and visualize GO (REVIGO) enrichment analysis showed that upregulated genes of Z141 were enriched in more functional pathways related to plant drought tolerance than those of NY-17 were under DS. In addition, 4436 linseed transcription factors were identified, and 1190 were responsive to stress treatments. Moreover, protein-protein interaction (PPI) network analysis showed that the proline biosynthesis pathway interacts with stress response genes through RAD50 (DNA repair protein 50) interacting protein 1 (RIN-1). Finally, proline biosynthesis and DNA repair structural gene expression patterns were verified by RT- PCR. Conclusions The drought tolerance of Z141 may be related to its upregulation of drought tolerance genes under DS. Proline may play an important role in linseed drought tolerance by maintaining cell osmotic and protecting DNA from ROS damage. In summary, this study provides a new perspective to understand the drought adaptability of linseed.

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