scholarly journals Integration of absolute multi-omics reveals translational and metabolic interplay in mixed-kingdom microbiomes

2019 ◽  
Author(s):  
F. Delogu ◽  
B.J. Kunath ◽  
M.Ø. Arntzen ◽  
T.R. Hvidsten ◽  
P.B. Pope
Keyword(s):  
Model Organisms ◽  
Bacterial Populations ◽  
Community Function ◽  
Protein Levels ◽  
Original Culture ◽  
Minimal Subset ◽  
Methanothermobacter Thermoautotrophicus ◽  
Absolute Measurements ◽  
Per Gene ◽  
Insight Into

AbstractMicrobiology is founded on well-known model organisms. For example, the majority of our fundamental knowledge regarding the quantitative levels of DNA, RNA, and protein backdates to keystone pure culture-based studies. Nowadays, meta-omic approaches allow us to directly access the molecules that constitute microbes and microbial communities, however due to a lack of absolute measurements, many original culture-derived “microbiology statutes” have not been updated or adapted to more complex microbiome settings. Within a cellulose-degrading and methanogenic consortium, we temporally measured genome-centric absolute RNA and protein levels per gene, and obtained a protein-to-RNA ratio of 102-104 for bacterial populations, whereas Archaeal RNA/protein dynamics (103-105: Methanothermobacter thermoautotrophicus) were more comparable to Eukaryotic representatives humans and yeast. The linearity between transcriptome and proteome had a population-specific change over time, highlighting a minimal subset of four functional carriers (cellulose degrader, fermenter, syntrophic acetate-oxidizer and methanogen) that coordinated their respective metabolisms, cumulating in the overarching community phenotype of converting polysaccharides to methane. Our findings show that upgrading multi-omic toolkits with traditional absolute measurements unlocks the scaling of core biological questions to dynamic and complex microbiomes, creating a deeper insight into inter-organismal relationships that drive the greater community function.

scholarly journals Integration of absolute multi-omics reveals dynamic protein-to-RNA ratios and metabolic interplay within mixed-domain microbiomes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
F. Delogu ◽  
B. J. Kunath ◽  
P. N. Evans ◽  
M. Ø. Arntzen ◽  
T. R. Hvidsten ◽  
...  
Keyword(s):  
Basic Knowledge ◽  
Biological Feature ◽  
Bacterial Populations ◽  
Community Function ◽  
Protein Levels ◽  
Protein Molecules ◽  
Absolute Measurements ◽  
Per Gene ◽  
Insight Into ◽  
Over Time

Abstract While the field of microbiology has adapted to the study of complex microbiomes via modern meta-omics techniques, we have not updated our basic knowledge regarding the quantitative levels of DNA, RNA and protein molecules within a microbial cell, which ultimately control cellular function. Here we report the temporal measurements of absolute RNA and protein levels per gene within a mixed bacterial-archaeal consortium. Our analysis of this data reveals an absolute protein-to-RNA ratio of 102–104 for bacterial populations and 103–105 for an archaeon, which is more comparable to Eukaryotic representatives’ humans and yeast. Furthermore, we use the linearity between the metaproteome and metatranscriptome over time to identify core functional guilds, hence using a fundamental biological feature (i.e., RNA/protein levels) to highlight phenotypical complementarity. Our findings show that upgrading multi-omic toolkits with traditional absolute measurements unlocks the scaling of core biological questions to dynamic and complex microbiomes, creating a deeper insight into inter-organismal relationships that drive the greater community function.

scholarly journals Transgenic Epigenetics: Using Transgenic Organisms to Examine Epigenetic Phenomena

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Lori A. McEachern
Keyword(s):  
Molecular Mechanisms ◽  
Model Organism ◽  
Evolutionary Conservation ◽  
Model Organisms ◽  
Valuable Insight ◽  
Epigenetic Control ◽  
Transgenic Organisms ◽  
Epigenetic Analysis ◽  
Insight Into ◽  
Epigenetic Processes

Non-model organisms are generally more difficult and/or time consuming to work with than model organisms. In addition, epigenetic analysis of model organisms is facilitated by well-established protocols, and commercially-available reagents and kits that may not be available for, or previously tested on, non-model organisms. Given the evolutionary conservation and widespread nature of many epigenetic mechanisms, a powerful method to analyze epigenetic phenomena from non-model organisms would be to use transgenic model organisms containing an epigenetic region of interest from the non-model. Interestingly, while transgenic Drosophila and mice have provided significant insight into the molecular mechanisms and evolutionary conservation of the epigenetic processes that target epigenetic control regions in other model organisms, this method has so far been under-exploited for non-model organism epigenetic analysis. This paper details several experiments that have examined the epigenetic processes of genomic imprinting and paramutation, by transferring an epigenetic control region from one model organism to another. These cross-species experiments demonstrate that valuable insight into both the molecular mechanisms and evolutionary conservation of epigenetic processes may be obtained via transgenic experiments, which can then be used to guide further investigations and experiments in the species of interest.

scholarly journals Loss of YY1 Impacts the Heterochromatic State and Meiotic Double-Strand Breaks during Mouse Spermatogenesis

2009 ◽  
Vol 29 (23) ◽  
pp. 6245-6256 ◽  
Author(s):  
Su Wu ◽  
Yueh-Chiang Hu ◽  
Huifei Liu ◽  
Yang Shi
Keyword(s):  
Structural Integrity ◽  
Critical Role ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Model Organisms ◽  
Global Changes ◽  
Strand Breaks ◽  
Yin Yang 1 ◽  
Insight Into

ABSTRACT The progression of spermatogenesis involves global changes in chromatin structure and conformation. However, our understanding of the regulation of chromatin changes in germ cells remains limited. Here we describe both in vivo RNA interference and genetic mouse knockout studies that identify a critical role for Yin Yang 1 (YY1) in mammalian spermatogenesis. In the YY1-deficient spermatocytes, we find a significant decrease in the global level of the heterochromatin markers (H3K9me3 and HP1-gamma) and a concomitant increase in the double-strand break (DSB) signals on chromosomes (gamma-H2AX, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and Rad51) at the leptotene/zygotene stages of spermatocytes. These findings support a link between chromatin modifications and meiotic DSB formation, as has been seen in other model organisms. We propose that a depletion of YY1 may alter the structural integrity of heterochromatin, rendering it more accessible to the DSB machinery. In addition, YY1-deficient spermatocytes show univalent formation, increased aneuploidy, and pachytene cell death, which are likely due to defects in DNA repair. Taken together, this study identifies an important role for YY1 in mouse meiosis and provides new insight into mechanisms that regulate mammalian spermatogenesis.

scholarly journals Neuronal regeneration in the goldfish telencephalon following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) insult

FACETS ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 358-374 ◽  
Author(s):  
Maddie J. Venables ◽  
Lei Xing ◽  
Connor C. Edington ◽  
Vance L. Trudeau
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Model Organism ◽  
Model Organisms ◽  
Neuronal Regeneration ◽  
Regenerative Ability ◽  
Mptp Toxicity ◽  
Insight Into ◽  
Recovery Of Motor Function ◽  
Rapid Incorporation

The constitutive regenerative ability of the goldfish central nervous system makes them an excellent model organism to study neurogenesis. Intraperitoneal injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to deplete tyrosine hydroxylase-positive neurons in the adult goldfish telencephalon. We report novel information on the ability of the goldfish to regenerate (∼3–4 d post-MPTP insult) damaged neurons in telencephalic tissue by observing the rapid incorporation of bromodeoxyuridine into newly generated cells, which precedes the recovery of motor function in MPTP-treated animals. Specifically, the telencephalon area telencephali pars dorsalis in female goldfish, which is associated with fish motor activity, regenerates following MPTP toxicity. The remarkable ability of goldfish to rapidly regenerate damaged neurons provides insight into their use as model organisms to study neuroregenerative abilities within a few days following injury. We provide evidence that goldfish are able to regenerate neurons in ∼3–4 d to both replenish and recover baseline catecholaminergic levels, thus enabling the fish to reestablish basic activities such as swimming. The study of neuron regeneration in the damaged goldfish brain will increase our understanding of vertebrate neurogenesis and regeneration processes following central nervous system injury.

scholarly journals Single-cell intracellular epitope and transcript detection revealing signal transduction dynamics

2020 ◽  
Author(s):  
Francesca Rivello ◽  
Erik van Buijtenen ◽  
Kinga Matuła ◽  
Jessie A.G.L. van Buggenum ◽  
Paul Vink ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Single Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Protein Levels ◽  
Inhibitory Drug ◽  
Insight Into ◽  
Transcript Detection

AbstractCurrent high-throughput single-cell multi-omics methods cannot concurrently map changes in (phospho)protein levels and the associated gene expression profiles. We present QuRIE-seq (Quantification of RNA and Intracellular Epitopes by sequencing) and use multi-factor omics analysis (MOFA+) to map signal transduction over multiple timescales. We demonstrate that QuRIE-seq can trace the activation of the B-cell receptor pathway at the minute and hour time-scale and provide insight into the mechanism of action of an inhibitory drug, Ibrutinib.

scholarly journals CoCoCoNet: Conserved and Comparative Co-expression Across a Diverse Set of Species

2020 ◽  
Author(s):  
John Lee ◽  
Manthan Shah ◽  
Sara Ballouz ◽  
Megan Crow ◽  
Jesse Gillis
Keyword(s):  
Alternative Model ◽  
Model Systems ◽  
Model Organisms ◽  
Disease Genes ◽  
Gene Module ◽  
Link Type ◽  
Network Properties ◽  
Gene Modules ◽  
Human Disease Genes ◽  
Insight Into

ABSTRACTCo-expression analysis has provided insight into gene function in organisms from Arabidopsis to Zebrafish. Comparison across species has the potential to enrich these results, for example by prioritizing among candidate human disease genes based on their network properties, or by finding alternative model systems where their co-expression is conserved. Here, we present CoCoCoNet as a tool for identifying conserved gene modules and comparing co-expression networks. CoCoCoNet is a resource for both data and methods, providing gold-standard networks and sophisticated tools for on-the-fly comparative analyses across 14 species. We show how CoCoCoNet can be used in two use cases. In the first, we demonstrate deep conservation of a nucleolus gene module across very divergent organisms, and in the second, we show how the heterogeneity of autism mechanisms in humans can be broken down by functional groups, and translated to model organisms. CoCoCoNet is free to use and available to all at https://milton.cshl.edu/CoCoCoNet, with data and R scripts available at ftp://milton.cshl.edu/data.

scholarly journals MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile

2021 ◽  
Vol 15 ◽  
Author(s):  
Sandra Jacinto ◽  
Patrícia Guerreiro ◽  
Rita Machado de Oliveira ◽  
Teresa Cunha-Oliveira ◽  
Maria João Santos ◽  
...  
Keyword(s):  
Metabolic Profile ◽  
Mitochondrial Protein ◽  
Protein Levels ◽  
Exact Function ◽  
Selective Channel ◽  
Molecular Effects ◽  
Cellular Abnormalities ◽  
Insight Into

Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be important in the maintenance of mitochondrial membrane potential (ΔΨm). To obtain more information about the role of MPV17 in human disease, we investigated the effect of MPV17 knockdown and of selected known MPV17 mutations associated with MPV17 disease in vitro. We used different approaches in order to evaluate the cellular consequences of MPV17 deficiency. We found that lower levels of MPV17 were associated with impaired mitochondrial respiration and with a quiescent energetic metabolic profile. All the mutations studied destabilized the protein, resulting in reduced protein levels. We also demonstrated that different mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of ΔΨm, and mislocalization of MPV17 protein. Our study provides novel insight into the molecular effects of MPV17 mutations and opens novel possibilities for testing therapeutic strategies for a devastating group of disorders.

scholarly journals miR-577 suppressed the metastasis, EMT and viability via NF-κB pathway by targeting CXCL5 through in hepatocellular carcinoma

2020 ◽  
Author(s):  
Lirui Tu ◽  
Jing Liu ◽  
Wei Li ◽  
Xiuguang Song ◽  
Hongwei Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cell Invasion ◽  
Great Role ◽  
Transwell Assay ◽  
Protein Levels ◽  
Xenograft Growth ◽  
Kaplan Meier ◽  
Insight Into

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant cancer worldwide. miR-577 have a role in inhibiting cell viability, metastasis in many tumors. This research was to explore the great role of miR-577 in hepatocellular carcinoma. Methods RT-qPCR and western blot were performed to evaluate the the miR-577 and genes mRNA and protein levels. Transwell assay and CCK-8 were applied to measure the viable and invasive abilities. Meanwhile, Kaplan-Meier method was used to assess the survival of HCC patients. Results miR-577 was downregulated in HCC tissues, which predicted a worse overall survival in HCC. miR-577 targeted to CXCL5 and mediated its expression in HCC. miR-577 suppressed cell invasion and EMT in HuH-7 cells. miR-577 inhibited cell viability via NF-κB pathway. In addition, miR-577 overxpression impaired the xenograft growth of HuH-7 cells. Conclusion miR-577 inhibited cell invasion, EMT and viability via NF-κB pathway by targeting to CXCL5 in HCC. The newly identified miR-577/CXCL5 axis provides novel insight into the pathogenesis of hepatocellular carcinoma.

scholarly journals The genetic and epigenetic profile of serum S100β in the Lothian Birth Cohort 1936 and its relationship to Alzheimer’s disease

2021 ◽  
Vol 6 ◽  
pp. 306
Author(s):  
Danni A Gadd ◽  
Robert I McGeachan ◽  
Robert F Hillary ◽  
Daniel L McCartney ◽  
Sarah E Harris ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Birth Cohort ◽  
Brain Inflammation ◽  
Joint Analysis ◽  
Mendelian Randomisation ◽  
Protein Levels ◽  
S100β Protein ◽  
Lothian Birth Cohort ◽  
Insight Into

Background: Circulating S100 calcium-binding protein (S100β) is a marker of brain inflammation that has been associated with a range of neurological conditions. To provide insight into the molecular regulation of S100β and its potential causal associations with Alzheimer’s disease, we carried out genome- and epigenome-wide association studies (GWAS/EWAS) of serum S100β levels in older adults and performed Mendelian randomisation with Alzheimer’s disease. Methods: GWAS (N=769, mean age 72.5 years, sd = 0.7) and EWAS (N=722, mean age 72.5 years, sd = 0.7) of S100β levels were performed in participants from the Lothian Birth Cohort 1936. Conditional and joint analysis (COJO) was used to identify independent loci. Expression quantitative trait locus (eQTL) analyses were performed for lead loci that had genome-wide significant associations with S100β. Bidirectional, two-sample Mendelian randomisation was used to test for causal associations between S100β and Alzheimer’s disease. Colocalisation between S100β and Alzheimer’s disease GWAS loci was also examined. Results: We identified 154 SNPs from chromosome 21 that associated (P<5x10-8) with S100β protein levels. The lead variant was located in the S100β gene (rs8128872, P=5.0x10-17). We found evidence that two independent causal variants existed for both transcription of S100β and S100β protein levels in our eQTL analyses. No CpG sites were associated with S100β levels at the epigenome-wide significant level (P<3.6x10-8); the lead probe was cg06833709 (P=5.8x10-6), which mapped to the LGI1 gene. There was no evidence of a causal association between S100β levels and Alzheimer’s disease or vice versa and no evidence for colocalisation between S100β and Alzheimer’s disease loci. Conclusions: These data provide insight into the molecular regulators of S100β levels. This context may aid in understanding the role of S100β in brain inflammation and neurological disease.

scholarly journals miRNA-144-5p/ITGA3 Suppressed the Tumor-Promoting Behaviors of Thyroid Cancer Cells by Downregulating ITGA3

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jizong Zhang ◽  
Yan Zhong ◽  
Yiming Sang ◽  
Guanghui Ren
Keyword(s):  
Thyroid Cancer ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Luciferase Assay ◽  
Cell Behaviors ◽  
Protein Levels ◽  
Related Cell ◽  
Cancer Genome Atlas ◽  
Thyroid Cancer Cells ◽  
Insight Into

Objective. To ascertain the mechanism of miRNA-144-5p and ITGA3 in thyroid cancer (TC). Methods. From The Cancer Genome Atlas (TCGA), RNA expression profiles were obtained for the expression analysis of miRNAs and mRNAs in TC. qRT-PCR and western blot were utilized to measure the expression of miRNA-144-5p and ITGA3 at RNA and protein levels, respectively. The association between miRNA-144-5p and ITGA3 was validated by the dual-luciferase assay. CCK-8, scratch healing, transwell, and flow cytometry assays were employed to evaluate tumor-related cell behaviors. Results. Low-expressed miRNA-144-5p and high-expressed ITGA3 were found in TC cells relative to normal cells. miRNA-144-5p expression was positively associated with suppressive effects on proliferative, invasive, and migratory ability of TC cells while negatively associated with cell apoptosis. miRNA-144-5p inhibited ITGA3 expression in TC, and its overexpression remarkably reversed the tumor-promoting effects of overexpressed ITGA3 on the biological functions of TC. Conclusion. It is verified in our study that cell growth of TC is inhibited by the miRNA-144-5p/ITGA3 axis, which represents an underlying target for TC. This research proposed a new insight into the strategy of TC treatment.

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