scholarly journals Transcriptional responses to social isolation : characterization of the neuropeptide parathyroid hormone 2

2021 ◽  
Author(s):  
◽  
Lukas Anneser
Keyword(s):  
Gene Expression ◽  
Parathyroid Hormone ◽  
Social Isolation ◽  
Environmental Changes ◽  
Model Organism ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Physiological Level ◽  
Brain Gene Expression ◽  
Social Species

Across the entire animal kingdom, sociality, i.e. the tendency of individual animals to form a group with conspecifics, is a common trait. Environmental changes have to be met with corresponding, quick adaptations. For social species, the presence of conspecifics is important for survival and if social animals are deprived of access to conspecifics, this can lead to strong and lasting changes on a physiological level as well as behaviour. Gene expression changes responsible for these adaptations have so far not been understood in detail. As social isolation leads to changes on a neuronal level, it is important to investigate the gene expression changes that are induced in the brain. In this thesis, next-generation RNA-sequencing was applied to zebrafish, a well-established model organism characterized by its high degree of companionship. Within the entire brain, gene expression was analysed in zebrafish that were raised either with conspecifis or in isolation, ranging from 5 to 21 days post fertilization. Using this approach, several genes were identified that were downregulated by social isolation. In this thesis, I focused on one of these consistently downregulated genes, parathyroid hormone 2 (pth2). The expression of pth2 was demonstrated to be bidirectionally regulated by the number of conspecifics present and to be responsive to changes in the social environment within 30 minutes. Regulation of pth2 does not occur by visual or chemosensory access to conspecifcs, but is mediated by mechanosensory perception of other fish via the lateral line. In an experiment using an artificial mechanical stimulation paradigm, it was shown that the features necessary to elicit pth2 transcription closely mimick the locomotion of actual zebrafish. Other, similar stimulation paradigms are not capable to induce this transcriptional response.

scholarly journals Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast

2008 ◽  
Vol 19 (1) ◽  
pp. 308-317 ◽  
Author(s):  
Dongrong Chen ◽  
Caroline R.M. Wilkinson ◽  
Stephen Watt ◽  
Christopher J. Penkett ◽  
W. Mark Toone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Stress Responses ◽  
Zinc Finger Protein ◽  
Transcriptional Response ◽  
Minor Role ◽  
Transcriptional Responses ◽  
Regulatory Pathways

Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1–like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.

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 Pneumolysin is responsible for differential gene expression and modifications in the epigenetic landscape of primary monocyte derived macrophages

2020 ◽  
Author(s):  
J. Cole ◽  
A. Angyal ◽  
R. D. Emes ◽  
T.J. Mitchell ◽  
M.J. Dickman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Epigenetic Modification ◽  
Transcriptional Response ◽  
Innate Immune ◽  
Global Changes ◽  
Innate Immune Responses ◽  
Transcriptional Responses ◽  
Tnf Α

AbstractEpigenetic modifications regulate gene expression in the host response to a diverse range of pathogens. The extent and consequences of epigenetic modification during macrophage responses to Streptococcus pneumoniae, and the role of pneumolysin, a key Streptococcus pneumoniae virulence factor, in influencing these responses, are currently unknown. To investigate this, we infected human monocyte derived macrophages (MDMs) with Streptococcus pneumoniae and addressed whether pneumolysin altered the epigenetic landscape and the associated acute macrophage transcriptional response using a combined transcriptomic and proteomic approach. Transcriptomic analysis identified 503 genes that were differentially expressed in a pneumolysin-dependent manner in these samples. Pathway analysis highlighted the involvement of transcriptional responses to core innate responses to pneumococci including modules associated with metabolic pathways activated in response to infection, oxidative stress responses and NFκB, NOD-like receptor and TNF signalling pathways. Quantitative proteomic analysis confirmed pneumolysin-regulated protein expression, early after bacterial challenge, in representative transcriptional modules associated with innate immune responses. In parallel, quantitative mass spectrometry identified global changes in the relative abundance of histone post translational modifications (PTMs) upon pneumococcal challenge. We identified an increase in the relative abundance of H3K4me1, H4K16ac and a decrease in H3K9me2 and H3K79me2 in a PLY-dependent fashion. We confirmed that pneumolysin blunted early transcriptional responses involving TNF-α and IL-6 expression. Vorinostat, a histone deacetylase inhibitor, similarly downregulated TNF production, reprising the pattern observed with pneumolysin. In conclusion, widespread changes in the macrophage transcriptional response are regulated by pneumolysin and are associated with global changes in histone PTMs. Modulating histone PTMs can reverse pneumolysin-associated transcriptional changes influencing innate immune responses, suggesting that epigenetic modification by pneumolysin plays a role in dampening the innate responses to pneumococci.Author summaryPneumolysin is a toxin that contributes to how Streptococcus pneumoniae, the leading cause of pneumonia, causes disease. In this study, the toxin alters gene expression in immune cells called macrophages, one of the first lines of defence against bacteria at sites of infection. Modulation involved multiple immune responses, including generation of chemical signals coordinating responses in immune cells termed cytokines. In addition, changes were observed in histone proteins that are involved in controlling gene expression in the cell. Pneumolysin reduced early production of the cytokine TNF-α and a medicine vorinostat that modifies these ‘epigenetic’ histone modifications had a similar affect, suggesting epigenetic mechanisms contribute to the ability of pneumolysin to reduce immune responses.

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 Salmonid gene expression biomarkers indicative of physiological responses to changes in salinity, temperature, but not dissolved oxygen

2018 ◽  
Author(s):  
Aimee Lee S. Houde ◽  
Arash Akbarzadeh ◽  
Oliver P. Günther ◽  
Shaorong Li ◽  
David A. Patterson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dissolved Oxygen ◽  
Oncorhynchus Tshawytscha ◽  
Environmental Changes ◽  
Multiple Stressors ◽  
Life Stage ◽  
Skin Pigmentation ◽  
Seawater Temperature ◽  
Life Stages ◽  
Transcriptional Responses

AbstractAn organism’s ability to respond effectively to environmental change is critical to their survival. Yet, life stage and overall condition can dictate tolerance thresholds to heightened environmental stressors, such that stress may not be equally felt across individuals within a species. Environmental changes can induce transcriptional responses in an organism, some of which reflect generalized responses, and others are highly specific to the type of change being experienced. Thus, if transcriptional biomarkers specific to a heightened environmental stressor, even under multi-stressor impacts, can be identified, the biomarkers could be then applied in natural environments to determine when and where individuals are experiencing such stressors. Here, we validate candidate gill gene expression biomarkers by experimentally challenging juvenile Chinook salmon (Oncorhynchus tshawytscha). A sophisticated experimental set-up (four trials) manipulated salinity (freshwater, brackish water, and seawater), temperature (10, 14, and 18°C), and dissolved oxygen (normoxia and hypoxia), in all 18 possible combinations, for up to six days during the pre-smolt, smolt, and de-smolt life stages. In addition, we also describe the changes in juvenile behaviour, plasma variables, gill Na+/K+- ATPase (NKA) activity, body size, body morphology, and skin pigmentation associated with salinity, temperature, dissolved oxygen, mortality, and smolt status. We statistically identified biomarkers specific to salinity and temperature treatments, as well as mortality across multiple stressors and life stages. Similar biomarkers for the dissolved oxygen treatment could not be identified in the data and we discuss our next steps using an RNA-seq study. This work demonstrates the unique power of gene expression biomarkers to identify a specific stressor even under multi-stressor conditions.

scholarly journals Glucose and glutamine availability regulate HepG2 transcriptional responses to low oxygen

2018 ◽  
Vol 3 ◽  
pp. 126 ◽  
Author(s):  
Alvina G. Lai ◽  
Donall Forde ◽  
Wai Hoong Chang ◽  
Fang Yuan ◽  
Xiaodong Zhuang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Transcriptional Response ◽  
Global Changes ◽  
Low Oxygen ◽  
Transcriptional Responses ◽  
Dna Hydroxymethylation ◽  
Modified Dna ◽  
The Impact

Background: Little is known about the impact of nutrients on cellular transcriptional responses, especially in face of environmental stressors such as oxygen deprivation. Hypoxia-inducible factors (HIF) coordinate the expression of genes essential for adaptation to oxygen-deprived environments. A second family of oxygen-sensing genes known as the alpha-ketoglutarate-dependent dioxygenases are also implicated in oxygen homeostasis and epigenetic regulation. The relationship between nutritional status and cellular response to hypoxia is understudied. In vitro cell culture systems frequently propagate cells in media that contains excess nutrients, and this may directly influence transcriptional response in hypoxia. Methods: We studied the effect of glucose and glutamine concentration on HepG2 hepatoma transcriptional response to low oxygen and expression of hypoxia inducible factor-1α (HIF-1α). Mass spectrometry confirmed low oxygen perturbation of dioxygenase transcripts resulted in changes in DNA methylation. Results: Under normoxic conditions, we observed a significant upregulation of both HIF-target genes and oxygen-dependent dioxygenases in HepG2 cells cultured with physiological levels of glucose or glutamine relative to regular DMEM media, demonstrating that excess glutamine/glucose can mask changes in gene expression. Under hypoxic conditions, CA9 was the most upregulated gene in physiological glutamine media while TETs and FTO dioxygenases were downregulated in physiological glucose. Hypoxic regulation of these transcripts did not associate with changes in HIF-1α protein expression. Downregulation of TETs suggests a potential for epigenetic modulation. Mass-spectrometry quantification of modified DNA bases confirmed our transcript data. Hypoxia resulted in decreased DNA hydroxymethylation, which correlated with TETs downregulation. Additionally, we observed that TET2 expression was significantly downregulated in patients with hepatocellular carcinoma, suggesting that tumour hypoxia may deregulate TET2 expression resulting in global changes in DNA hydroxymethylation.   Conclusion: Given the dramatic effects of nutrient availability on gene expression, future in vitro experiments should be aware of how excess levels of glutamine and glucose may perturb transcriptional responses.

scholarly journals Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila

2021 ◽  
Author(s):  
Lakbira Sheffield ◽  
Noah Sciambra ◽  
Alysa Evans ◽  
Eli Hagedorn ◽  
Casey Goltz ◽  
...  
Keyword(s):  
Rna Virus ◽  
Model Organism ◽  
Transcriptional Response ◽  
Innate Immune ◽  
Full Potential ◽  
Flock House Virus ◽  
Virus Infections ◽  
Transcriptional Responses ◽  
Disease Tolerance ◽  
Age Dependent

Abstract Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its full potential to investigate the response of the aged host to viral infection. Here we show that, in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House Virus (FHV) due to an age-dependent defect in disease tolerance. Relative to younger individuals, we find that older Drosophila mount transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. We show that loss of disease tolerance to FHV with age associates with a stronger regulation of genes involved in apoptosis, some genes of the Drosophila Immune deficiency (IMD) NF-kB pathway and genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and furthermore sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age.

scholarly journals Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

2017 ◽  
Vol 83 (7) ◽  
Author(s):  
Klara Bojanovič ◽  
Isotta D'Arrigo ◽  
Katherine S. Long
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Pseudomonas Putida ◽  
Cellular Response ◽  
Functional Characterization ◽  
Transcriptional Response ◽  
Stress Conditions ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Content Type

ABSTRACTBacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response ofPseudomonas putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through whichP. putidaresponds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings.IMPORTANCEThis study maps the complete transcriptional response ofP. putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization.

scholarly journals Isolation disrupts social interactions and destabilizes brain development in bumblebees

2021 ◽  
Author(s):  
Z Yan Wang ◽  
Grace C. McKenzie-Smith ◽  
Weijie Liu ◽  
Hyo Jin Cho ◽  
Talmo D Pereira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Development ◽  
Social Interactions ◽  
Social Isolation ◽  
Small Groups ◽  
Early Life ◽  
Brain Regions ◽  
Brain Gene Expression ◽  
Rearing Condition ◽  
The Impact

Social isolation, particularly in early life, leads to deleterious physiological and behavioral outcomes. Few studies, if any, have been able to capture the behavioral and neurogenomic consequences of early life social isolation together in a single social animal system. Here, we leverage new high-throughput tools to comprehensively investigate the impact of isolation in the bumblebee (Bombus impatiens) from behavioral, molecular, and neuroanatomical perspectives. We reared newly emerged bumblebees either in complete isolation, small groups, or in their natal colony, and then analyzed their behaviors while alone or paired with another bee. We find that when alone, individuals of each rearing condition show distinct behavioral signatures. When paired with a conspecific, bees reared in small groups or in the natal colony express similar behavioral profiles. Isolated bees, however, showed increased social interactions. To identify the neurobiological correlates of these differences, we quantified brain gene expression and measured the volumes of key brain regions for a subset of individuals from each rearing condition. Overall, we find that isolation increases social interactions and disrupts gene expression and brain development. Limited social experience in small groups is sufficient to preserve typical patterns of brain development and social behavior.

scholarly journals Shannon Entropy as a metric for conditional gene expression in Neurospora crassa

2020 ◽  
Author(s):  
Abigail J. Ameri ◽  
Zachary A. Lewis
Keyword(s):  
Gene Expression ◽  
Neurospora Crassa ◽  
Shannon Entropy ◽  
Single Gene ◽  
Constitutive Expression ◽  
Model Organism ◽  
Cell Types ◽  
Complex Life Cycle ◽  
Transcriptional Responses ◽  
Wide Range

AbstractNeurospora crassa has been an important model organism for molecular biology and genetics for over 60 years. N. crassa has a complex life cycle, with over 28 distinct cell types and is capable of transcriptional responses to many environmental conditions including nutrient availability, temperature, and light. To quantify variation in N. crassa gene expression, we analyzed public expression data from 97 conditions and calculated the Shannon Entropy value for Neurospora’s approximately 11,000 genes. Entropy values can be used to estimate the variability in expression for a single gene over a range of conditions and be used to classify individual genes as constitutive or condition-specific. Shannon entropy has previously been used measure the degree of tissue specificity of multicellular plant or animal genes. We use this metric here to measure variable gene expression in a microbe and provide this information as a resource for the N. crassa research community. Finally, we demonstrate the utility of this approach by using entropy values to identify genes with constitutive expression across a wide range of conditions and to identify genes that are activated exclusively during sexual development.

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