scholarly journals Comparative Transcriptomics Analyses in Livers of Mice, Humans, and Humanized Mice Define Human-Specific Gene Networks

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2566
Author(s):  
Chengfei Jiang ◽  
Ping Li ◽  
Xiangbo Ruan ◽  
Yonghe Ma ◽  
Kenji Kawai ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Gene Networks ◽  
Liver Cells ◽  
Biological Processes ◽  
Divergent Gene ◽  
Specific Regulation ◽  
The Impact ◽  
Gene Regulations ◽  
Human And Mouse ◽  
Human Specific

Mouse is the most widely used animal model in biomedical research, but it remains unknown what causes the large number of differentially regulated genes between human and mouse livers identified in recent years. In this report, we aim to determine whether these divergent gene regulations are primarily caused by environmental factors or some of them are the result of cell-autonomous differences in gene regulation in human and mouse liver cells. The latter scenario would suggest that many human genes are subject to human-specific regulation and can only be adequately studied in a human or humanized system. To understand the similarity and divergence of gene regulation between human and mouse livers, we performed stepwise comparative analyses in human, mouse, and humanized livers with increased stringency to gradually remove the impact of factors external to liver cells, and used bioinformatics approaches to retrieve gene networks to ascertain the regulated biological processes. We first compared liver gene regulation by fatty liver disease in human and mouse under the condition where the impact of genetic and gender biases was minimized, and identified over 50% of all commonly regulated genes, that exhibit opposite regulation by fatty liver disease in human and mouse. We subsequently performed more stringent comparisons when a single specific transcriptional or post-transcriptional event was modulated in vitro or vivo or in liver-specific humanized mice in which human and mouse hepatocytes colocalize and share a common circulation. Intriguingly and strikingly, the pattern of a high percentage of oppositely regulated genes persists under well-matched conditions, even in the liver of the humanized mouse model, which represents the most closely matched in vivo condition for human and mouse liver cells that is experimentally achievable. Gene network analyses further corroborated the results of oppositely regulated genes and revealed substantial differences in regulated biological processes in human and mouse cells. We also identified a list of regulated lncRNAs that exhibit very limited conservation and could contribute to these differential gene regulations. Our data support that cell-autonomous differences in gene regulation might contribute substantially to the divergent gene regulation between human and mouse livers and there are a significant number of biological processes that are subject to human-specific regulation and need to be carefully considered in the process of mouse to human translation.

Fluorescent potentiometric dyes for membrane-potential imaging

1994 ◽  
Vol 52 ◽  
pp. 166-167
Author(s):  
Leslie M. Loew
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Quantitative Imaging ◽  
Optical Recording ◽  
Biological Processes ◽  
Major Focus ◽  
The Past ◽  
Excitable Systems ◽  
Major Application ◽  
The Impact

A major application of potentiometric dyes has been the multisite optical recording of electrical activity in excitable systems. After being championed by L.B. Cohen and his colleagues for the past 20 years, the impact of this technology is rapidly being felt and is spreading to an increasing number of neuroscience laboratories. A second class of experiments involves using dyes to image membrane potential distributions in single cells by digital imaging microscopy - a major focus of this lab. These studies usually do not require the temporal resolution of multisite optical recording, being primarily focussed on slow cell biological processes, and therefore can achieve much higher spatial resolution. We have developed 2 methods for quantitative imaging of membrane potential. One method uses dual wavelength imaging of membrane-staining dyes and the other uses quantitative 3D imaging of a fluorescent lipophilic cation; the dyes used in each case were synthesized for this purpose in this laboratory.

scholarly journals Genome-wide analysis and expression profile of the bZIP gene family in poplar

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kai Zhao ◽  
Song Chen ◽  
Wenjing Yao ◽  
Zihan Cheng ◽  
Boru Zhou ◽  
...  
Keyword(s):  
Salt Stress ◽  
Systems Biology ◽  
Gene Family ◽  
Stress Responses ◽  
Metal Ion ◽  
Gene Networks ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Biological Processes

Abstract Background The bZIP gene family, which is widely present in plants, participates in varied biological processes including growth and development and stress responses. How do the genes regulate such biological processes? Systems biology is powerful for mechanistic understanding of gene functions. However, such studies have not yet been reported in poplar. Results In this study, we identified 86 poplar bZIP transcription factors and described their conserved domains. According to the results of phylogenetic tree, we divided these members into 12 groups with specific gene structures and motif compositions. The corresponding genes that harbor a large number of segmental duplication events are unevenly distributed on the 17 poplar chromosomes. In addition, we further examined collinearity between these genes and the related genes from six other species. Evidence from transcriptomic data indicated that the bZIP genes in poplar displayed different expression patterns in roots, stems, and leaves. Furthermore, we identified 45 bZIP genes that respond to salt stress in the three tissues. We performed co-expression analysis on the representative genes, followed by gene set enrichment analysis. The results demonstrated that tissue differentially expressed genes, especially the co-expressing genes, are mainly involved in secondary metabolic and secondary metabolite biosynthetic processes. However, salt stress responsive genes and their co-expressing genes mainly participate in the regulation of metal ion transport, and methionine biosynthetic. Conclusions Using comparative genomics and systems biology approaches, we, for the first time, systematically explore the structures and functions of the bZIP gene family in poplar. It appears that the bZIP gene family plays significant roles in regulation of poplar development and growth and salt stress responses through differential gene networks or biological processes. These findings provide the foundation for genetic breeding by engineering target regulators and corresponding gene networks into poplar lines.

scholarly journals Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Carmeli ◽  
Zoltán Kutalik ◽  
Pashupati P. Mishra ◽  
Eleonora Porcu ◽  
Cyrille Delpierre ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Cohort Studies ◽  
Early Life ◽  
Life Experiences ◽  
Socioeconomic Disadvantage ◽  
Mediating Role ◽  
The Impact ◽  
The Relationship

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

scholarly journals The role of insulin in the modulation of glucagon-dependent control of phenylalanine hydroxylation in isolated liver cells

1987 ◽  
Vol 242 (3) ◽  
pp. 655-660 ◽  
Author(s):  
M J Fisher ◽  
A J Dickson ◽  
C I Pogson
Keyword(s):  
Cyclic Amp ◽  
Insulin Action ◽  
Phenylalanine Hydroxylase ◽  
Liver Cells ◽  
Phosphorylation State ◽  
Isolated Liver Cells ◽  
The Impact ◽  
Isolated Liver ◽  
Stimulation Of

The stimulation of phenylalanine hydroxylation in isolated liver cells by sub-maximally effective concentrations of glucagon (less than 0.1 microM) is antagonized by insulin (0.1 nM-0.1 microM). This phenomenon is a consequence of a decrease in the glucagon-stimulated phosphorylation of phenylalanine hydroxylase from liver cells incubated in the presence of insulin. The impact of insulin on the phosphorylation state and activity of the hydroxylase is mimicked by incubation of liver cells in the presence of orthovanadate (10 microM). A series of cyclic AMP and cyclic GMP analogues enhanced phenylalanine hydroxylation: in each case insulin diminished the stimulation of flux. These results are discussed in the light of the characteristics of insulin action on other metabolic processes.

scholarly journals СЕЗОННА МІНЛИВІСТЬ БІОГЕННИХ РЕЧОВИН У РІЧЦІ ВОРСКЛА

2014 ◽  
pp. 115-120 ◽  
Author(s):  
Н. І. Авраменко
Keyword(s):  
Seasonal Variability ◽  
Direct Relationship ◽  
Nutrient Content ◽  
Water Runoff ◽  
Biological Processes ◽  
Biological Factors ◽  
Cyclical Fluctuations ◽  
Vital Functions ◽  
Main Factors ◽  
The Impact

Розглядаються основні чинники, що найбільшевпливають на сезонну мінливість біогенних речовин урічці Ворскла. Встановлено, що важливу роль віді-грають природні циклічні коливання водного стоку ійого зарегулювання. Зазначено пряму залежністьміж життєдіяльністю гідробіонтів та сезоннимвмістом біогенних речовин у водоймах. Наведено ре-зультати досліджень із вивчення впливу гідробіологі-чних (фотосинтетичних) процесів та біологічногофактора на коливання значень вмісту біогенних ре-човин. Підкреслюється, що рівень вмісту біогеннихречовин лімітує розвиток біологічних процесів у воді.Визначено, що мінливість біогенних елементів у річ-ковій воді має чітко виражений сезонний характер.Встановлено залежність між величиною водногостоку й розвитком гідробіологічних процесів. Охарак-теризовано евтрофікаційні процеси річки Ворскла, зякої проводився збір агроекологічної інформації. Specified is the main factors that have the greatest impact on the seasonal variability of nutrients in the river Vorskla. Found that an important role is played by the natural cyclical fluctuations in water flow and its regulation of . Specified is a direct relationship between the vital functions of aquatic and seasonal content of nutrients in water bodies . The results of research on the impact of hydrobiological ( photosynthetic ) processes and biological factors on fluctuations in the values ​​of nutrient content . Emphasized that the levels of nutrients limiting the development of biological processes in the water. Determined that the variability of nutrients in river water has a distinctly seasonal. The dependence on the magnitude of water runoff and the development of hydrobiological processes.

scholarly journals Nitrogen availability modulates the host control of the barley rhizosphere microbiota

2019 ◽  
Author(s):  
Rodrigo Alegria Terrazas ◽  
Senga Robertson-Albertyn ◽  
Aileen Mary Corral ◽  
Carmen Escudero-Martinez ◽  
Katharin Balbirnie-Cumming ◽  
...  
Keyword(s):  
Plant Growth ◽  
Microbial Communities ◽  
Biological Processes ◽  
N Application ◽  
Plant Soil ◽  
Unplanted Soil ◽  
Bacterial Microbiota ◽  
Soil Feedback ◽  
The Impact ◽  
Barley Genotypes

AbstractBackgroundSince the dawn of agriculture, human selection on plants has progressively differentiated input-demanding productive crops from their wild progenitors thriving in marginal areas. Barley (Hordeum vulgare), the fourth most cultivated cereal globally, is a prime example of this process. We previously demonstrated that wild and domesticated barley genotypes host distinct microbial communities in their rhizosphere. Here, we tested the hypothesis that microbiota diversification is modulated by, and responds to, nitrogen (N) application in soil and assessed the impact of microbiota taxonomic and functional compositions on plant growth.MethodsWe grew two wild (H. vulgare ssp. spontaneum) and an ‘Elite’ domesticated (H. vulgare ssp. vulgare) barley genotypes in an agricultural soil treated with and without N inputs. By using a two-pronged 16S rRNA gene amplicon sequencing and comparative metagenomics approach, we determined the impact of N application on taxonomic composition and metabolic potential of the microbial communities exposed to limiting and replete N supplies. We then implemented a plant-soil feedback experiment to assess microbiotas’ recruitment cues and contribution to plant growth.ResultsN availability emerged as a modulator of the recruitment cues of the barley bacterial microbiota as evidenced by the increased number of bacterial genera differentially recruited between unplanted soil and rhizosphere communities under N-limiting conditions. This recruitment pattern mirrored the impact of the host genotype on rhizosphere bacteria. The characterisation of the assembled metagenomes of plants exposed to N-limiting conditions revealed a metabolic specialisation of the rhizosphere microbiota compared to unplanted soil controls. This specialisation is underpinned predominantly by bacteria and is manifested by the enrichment of a core set of biological processes sustaining the adaptation of polymicrobial communities such as N utilisation, quorum sensing and motility across genotypes. The quantitative variation in a group of these biological processes defined host signatures in the barley rhizosphere metagenome. Finally, a plant-soil feedback experiment revealed that the host-mediated taxonomic diversification of the bacterial microbiota is associated with barley growth under sub-optimal N supplies.ConclusionsOur results suggest that under N limiting conditions, a substrate-driven selection process underpins the assembly of barley rhizosphere microbiota. Host-microbe and microbe-microbe interactions fine-tune this process at the taxonomic and functional level across kingdoms. The disruption of these recruitment cues negatively impacts plant growth.

scholarly journals The RhoA-ROCK pathway in the regulation of T and B cell responses

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2295 ◽  
Author(s):  
Edd Ricker ◽  
Luvana Chowdhury ◽  
Woelsung Yi ◽  
Alessandra B. Pernis
Keyword(s):  
Immune Responses ◽  
Biological Processes ◽  
Dynamic Interactions ◽  
Cell Responses ◽  
Important Mediator ◽  
Downstream Effectors ◽  
Wide Range ◽  
Response To Stress ◽  
The Impact ◽  
Rho Kinases

Effective immune responses require the precise regulation of dynamic interactions between hematopoietic and non-hematopoietic cells. The Rho subfamily of GTPases, which includes RhoA, is rapidly activated downstream of a diverse array of biochemical and biomechanical signals, and is emerging as an important mediator of this cross-talk. Key downstream effectors of RhoA are the Rho kinases, or ROCKs. The ROCKs are two serine-threonine kinases that can act as global coordinators of a tissue’s response to stress and injury because of their ability to regulate a wide range of biological processes. Although the RhoA-ROCK pathway has been extensively investigated in the non-hematopoietic compartment, its role in the immune system is just now becoming appreciated. In this commentary, we provide a brief overview of recent findings that highlight the contribution of this pathway to lymphocyte development and activation, and the impact that dysregulation in the activation of RhoA and/or the ROCKs may exert on a growing list of autoimmune and lymphoproliferative disorders.

scholarly journals Comparative Transcriptomic Signature of the Simulated Microgravity Response in Caenorhabditis elegans

2019 ◽  
Author(s):  
İrem Çelen ◽  
Aroshan Jayasinghe ◽  
Jung H. Doh ◽  
Chandran R. Sabanayagam
Keyword(s):  
Caenorhabditis Elegans ◽  
Simulated Microgravity ◽  
Space Station ◽  
Integrative Approach ◽  
Biological Processes ◽  
Rna Seq ◽  
Transcriptomic Response ◽  
Transcriptomic Signature ◽  
Ground Conditions ◽  
The Impact

AbstractBackgroundGiven the growing interest in human exploration of space, it is crucial to identify the effect of space conditions on biological processes. The International Space Station (ISS) greatly helps researchers determine these effects. However, the impact of the ISS-introduced potential confounders (e.g., the combination of radiation and microgravity exposures) on the biological processes are often neglected, and separate investigations are needed to uncover the impact of individual conditions.ResultsHere, we analyze the transcriptomic response of Caenorhabditis elegans to simulated microgravity and observe the maintained transcriptomic response after return to ground conditions for four, eight, and twelve days. Through the integration of our data with those in NASA GeneLab, we identify the gravitome, which we define as microgravity-responsive transcriptomic signatures. We show that 75% of the simulated microgravity-induced changes on gene expression persist after return to ground conditions for four days while most of these changes are reverted after twelve days return to ground conditions. Our results from integrative RNA-seq and mass spectrometry analyses suggest that simulated microgravity affects longevity regulating insulin/IGF-1 and sphingolipid signaling pathways.ConclusionsOur results address the sole impact of simulated microgravity on transcriptome by controlling for the other space-introduced conditions and utilizing RNA-seq. Using an integrative approach, we identify a conserved transcriptomic signature to microgravity and its sustained impact after return to the ground. Moreover, we present the effect of simulated microgravity on distinct ceramide profiles. Overall, this work can provide insights into the sole effect of microgravity on biological systems.

scholarly journals Viscoelasticity and cell jamming state transition

2021 ◽  
Author(s):  
Ivana Pajic-Lijakovic ◽  
Milan Milivojevic
Keyword(s):  
Residual Stress ◽  
Wound Healing ◽  
Cell Migration ◽  
State Transition ◽  
State Transitions ◽  
Collective Cell Migration ◽  
Biological Processes ◽  
Cell Mobility ◽  
Controversial Topic ◽  
The Impact

Although collective cell migration (CCM) is a highly coordinated migratory mode, perturbations in the form of jamming state transitions and vice versa often occur even in 2D. These perturbations are involved in various biological processes, such as embryogenesis, wound healing and cancer invasion. CCM induces accumulation of cell residual stress which has a feedback impact to cell packing density. Density-mediated change of cell mobility influences the state of viscoelasticity of multicellular systems and on that base the jamming state transition. Although a good comprehension of how cells collectively migrate by following molecular rules has been generated, the impact of cellular rearrangements on cell viscoelasticity remains less understood. Thus, considering the density driven evolution of viscoelasticity caused by reduction of cell mobility could result in a powerful tool in order to address the contribution of cell jamming state transition in CCM and help to understand this important but still controversial topic. In addition, five viscoelastic states gained within three regimes: (1) convective regime, (2) conductive regime, and (3) damped-conductive regime was discussed based on the modeling consideration with special emphasis of jamming and unjamming states.

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