Int J Mol Sci. 2021 Mar 17;22(6):3083. doi: 10.3390/ijms22063083.

ABSTRACT

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancers with poor prognosis. The etiology of triple-negative breast cancer (TNBC) is involved in various biological signal cascades and multifactorial aberrations of genetic, epigenetic and microenvironment. New therapeutic for TNBC is urgently needed because surgery and chemotherapy are the only available modalities nowadays. A better understanding of the molecular mechanisms would be a great challenge because they are triggered by cascade signaling pathways, genetic and epigenetic regulations, and drug-target interactions. This would allow the design of multi-molecule drugs for the TNBC and non-TNBC. In this study, in terms of systems biology approaches, we proposed a systematic procedure for systems medicine design toward TNBC and non-TNBC. For systems biology approaches, we constructed a candidate genome-wide genetic and epigenetic network (GWGEN) by big databases mining and identified real GWGENs of TNBC and non-TNBC assisting with corresponding microarray data by system identification and model order selection methods. After that, we applied the principal network projection (PNP) approach to obtain the core signaling pathways denoted by KEGG pathway of TNBC and non-TNBC. Comparing core signaling pathways of TNBC and non-TNBC, essential carcinogenic biomarkers resulting in multiple cellular dysfunctions including cell proliferation, autophagy, immune response, apoptosis, metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), and cell differentiation could be found. In order to propose potential candidate drugs for the selected biomarkers, we designed filters considering toxicity and regulation ability. With the proposed systematic procedure, we not only shed a light on the differences between carcinogenetic molecular mechanisms of TNBC and non-TNBC but also efficiently proposed candidate multi-molecule drugs including resveratrol, sirolimus, and prednisolone for TNBC and resveratrol, sirolimus, carbamazepine, and verapamil for non-TNBC.

PMID:33802957 | DOI:10.3390/ijms22063083

Microorganisms. 2021 Mar 17;9(3):620. doi: 10.3390/microorganisms9030620.

ABSTRACT

HAC1 encodes a key transcription factor that transmits the unfolded protein response (UPR) from the endoplasmic reticulum (ER) to the nucleus and regulates downstream UPR genes in Saccharomyces cerevisiae. In response to the accumulation of unfolded proteins in the ER, Ire1p oligomers splice HAC1 pre-mRNA (HAC1u) via a non-conventional process and allow the spliced HAC1 (HAC1i) to be translated efficiently. However, leaky splicing and translation of HAC1u may occur in non-UPR cells to induce undesirable UPR. To control accidental UPR activation, multiple fail-safe mechanisms have been proposed to prevent leaky HAC1 splicing and translation and to facilitate rapid degradation of translated Hac1up and Hac1ip. Among proposed regulatory mechanisms is a degron sequence encoded at the 5' end of the HAC1 intron that silences Hac1up expression. To investigate the necessity of an intron-encoded degron sequence that specifically targets Hac1up for degradation, we employed publicly available transcriptomic data to quantify leaky HAC1 splicing and translation in UPR-induced and non-UPR cells. As expected, we found that HAC1u is only efficiently spliced into HAC1i and efficiently translated into Hac1ip in UPR-induced cells. However, our analysis of ribosome profiling data confirmed frequent occurrence of leaky translation of HAC1u regardless of UPR induction, demonstrating the inability of translation fail-safe to completely inhibit Hac1up production. Additionally, among 32 yeast HAC1 surveyed, the degron sequence is highly conserved by Saccharomyces yeast but is poorly conserved by all other yeast species. Nevertheless, the degron sequence is the most conserved HAC1 intron segment in yeasts. These results suggest that the degron sequence may indeed play an important role in mitigating the accumulation of Hac1up to prevent accidental UPR activation in the Saccharomyces yeast.

PMID:33802931 | DOI:10.3390/microorganisms9030620

Healthcare (Basel). 2021 Mar 3;9(3):269. doi: 10.3390/healthcare9030269.

ABSTRACT

In a previous article [...].

PMID:33802363 | DOI:10.3390/healthcare9030269

Cells. 2021 Mar 10;10(3):615. doi: 10.3390/cells10030615.

ABSTRACT

Muscle-enriched A-type lamin-interacting protein (Mlip) is a recently discovered Amniota gene that encodes proteins of unknown biological function. Here we report Mlip's direct interaction with chromatin, and it may function as a transcriptional co-factor. Chromatin immunoprecipitations with microarray analysis demonstrated a propensity for Mlip to associate with genomic regions in close proximity to genes that control tissue-specific differentiation. Gel mobility shift assays confirmed that Mlip protein complexes with genomic DNA. Blocking Mlip expression in C2C12 myoblasts down-regulates myogenic regulatory factors (MyoD and MyoG) and subsequently significantly inhibits myogenic differentiation and the formation of myotubes. Collectively our data demonstrate that Mlip is required for C2C12 myoblast differentiation into myotubes. Mlip may exert this role as a transcriptional regulator of a myogenic program that is unique to amniotes.

PMID:33802236 | DOI:10.3390/cells10030615

Int J Mol Sci. 2021 Mar 10;22(6):2819. doi: 10.3390/ijms22062819.

ABSTRACT

Targetable alterations in cancer offer novel opportunities to the drug discovery process. However, pre-clinical testing often requires solubilization of these drugs in cosolvents like dimethyl sulfoxide (DMSO). Using a panel of cell lines commonly used for in vitro drug screening and pre-clinical testing, we explored the DMSO off-target effects on functional signaling networks, drug targets, and downstream substrates. Eight Non-Small Cell Lung Cancer (NSCLC) cell lines were incubated with three concentrations of DMSO (0.0008%, 0.002%, and 0.004% v/v) over time. Expression and activation levels of 187 proteins, of which 137 were kinases and downstream substrates, were captured using the Reverse Phase Protein Array (RPPA). The DMSO effect was heterogeneous across cell lines and varied based on concentration, exposure time, and cell line. Of the 187 proteins measured, all were statistically different in at least one comparison at the highest DMSO concentration, followed by 99.5% and 98.9% at lower concentrations. Only 46% of the proteins were found to be statistically different in more than 5 cell lines, indicating heterogeneous response across models. These cell line specific alterations modulate response to in vitro drug screening. Ultra-low DMSO concentrations have broad and heterogeneous effects on targetable signaling proteins. Off-target effects need to be carefully evaluated in pre-clinical drug screening and testing.

PMID:33802212 | DOI:10.3390/ijms22062819

Int J Mol Sci. 2021 Mar 10;22(6):2797. doi: 10.3390/ijms22062797.

ABSTRACT

The phytohormone auxin is involved in almost every process of a plant's life, from germination to plant development. Nowadays, auxin research connects synthetic chemistry, plant biology and computational chemistry in order to develop innovative and safe compounds to be used in sustainable agricultural practice. In this framework, we developed new fluorescent compounds, ethanolammonium p-aminobenzoate (HEA-pABA) and p-nitrobenzoate (HEA-pNBA), and investigated their auxin-like behavior on two main commercial vegetables cultivated in Europe, cucumber (Cucumis sativus) and tomato (Solanumlycopersicum), in comparison to the model plant Arabidopsis (Arabidopsis thaliana). Moreover, the binding modes and affinities of two organic salts in relation to the natural auxin indole-3-acetic acid (IAA) into TIR1 auxin receptor were investigated by computational approaches (homology modeling and molecular docking). Both experimental and theoretical results highlight HEA-pABA as a fluorescent compound with auxin-like activity both in Arabidopsis and the commercial cucumber and tomato. Therefore, alkanolammonium benzoates have a great potential as promising sustainable plant growth stimulators to be efficiently used in vegetable crops.

PMID:33802041 | DOI:10.3390/ijms22062797

Animals (Basel). 2021 Mar 10;11(3):763. doi: 10.3390/ani11030763.

ABSTRACT

The effects of specific feeding positions upon the horse's shape variations of the back and neck postures as well as the variations of the mandibular angle have never been objectively studied. For this reason, geometric morphometrics was applied. Six horses, aged 14 ± 8 years (mean ± standard deviation, SD), were video-recorded while using three different feeding positions: on the ground-control position (CP); neck held 15 ± 3° below withers height with low hay net position (LP); neck held 15 ± 3° above withers height with high hay net position (HP). Data were analyzed using principal component analysis (PCA), multivariate analysis of variance (MANOVA), and partial least squares (PLS). A mixed model procedure was applied to evaluate differences in the magnitude of the mandibular angle. Whilst differences between individual horses were confirmed by canonical variate analysis (CVA), PCA analysis showed that a characteristic feeding position could also be identified on a group level. During the HP hay net position, the back and neck postures as well the mandibular angle were different compared to those exhibited by horses feeding from CP. In LP hay net position, the back posture more closely resembled those exhibited while feeding from CP; however, no similarity between LP and CP was found for neck posture and mandibular angle. Since only a few degrees of variation of the feeding position can influence back and neck postures, this aspect should be further investigated. The right compromise between horse welfare, horse safety, and management practices need to be further explored and long-term effects should be investigated.

PMID:33801885 | DOI:10.3390/ani11030763

Methods Protoc. 2021 Mar 10;4(1):20. doi: 10.3390/mps4010020.

ABSTRACT

RNA in situ hybridization (ISH) is used to visualize spatio-temporal gene expression patterns with broad applications in biology and biomedicine. Here we provide a protocol for mRNA ISH in developing pupal wings and abdomens for model and non-model Drosophila species. We describe best practices in pupal staging, tissue preparation, probe design and synthesis, imaging of gene expression patterns, and image-editing techniques. This protocol has been successfully used to investigate the roles of genes underlying the evolution of novel color patterns in non-model Drosophila species.

PMID:33801802 | DOI:10.3390/mps4010020

Pathogens. 2021 Mar 2;10(3):283. doi: 10.3390/pathogens10030283.

ABSTRACT

Alphaviruses are a genus of the Togaviridae family and are widely distributed across the globe. Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), cause encephalitis and neurological sequelae while chikungunya virus (CHIKV) and Sindbis virus (SINV) cause arthralgia. There are currently no approved therapeutics or vaccines available for alphaviruses. In order to identify novel therapeutics, a V5 epitope tag was inserted into the N-terminus of the VEEV E2 glycoprotein and used to identify host-viral protein interactions. Host proteins involved in protein folding, metabolism/ATP production, translation, cytoskeleton, complement, vesicle transport and ubiquitination were identified as VEEV E2 interactors. Multiple inhibitors targeting these host proteins were tested to determine their effect on VEEV replication. The compound HA15, a GRP78 inhibitor, was found to be an effective inhibitor of VEEV, EEEV, CHIKV, and SINV. VEEV E2 interaction with GRP78 was confirmed through coimmunoprecipitation and colocalization experiments. Mechanism of action studies found that HA15 does not affect viral RNA replication but instead affects late stages of the viral life cycle, which is consistent with GRP78 promoting viral assembly or viral protein trafficking.

PMID:33801554 | DOI:10.3390/pathogens10030283

Int J Environ Res Public Health. 2021 Mar 2;18(5):2435. doi: 10.3390/ijerph18052435.

ABSTRACT

Mercury (Hg) pollution is a global threat to human and environmental health because of its toxicity, mobility and long-term persistence. Although costly engineering-based technologies can be used to treat heavily Hg-contaminated areas, they are not suitable for decontaminating agricultural or extensively-polluted soils. Emerging phyto- and bioremediation strategies for decontaminating Hg-polluted soils generally involve low investment, simple operation, and in situ application, and they are less destructive for the ecosystem. Current understanding of the uptake, translocation and sequestration of Hg in plants is reviewed to highlight new avenues for exploration in phytoremediation research, and different phytoremediation strategies (phytostabilization, phytoextraction and phytovolatilization) are discussed. Research aimed at identifying suitable plant species and associated-microorganisms for use in phytoremediation of Hg-contaminated soils is also surveyed. Investigation into the potential use of transgenic plants in Hg-phytoremediation is described. Recent research on exploiting the beneficial interactions between plants and microorganisms (bacteria and fungi) that are Hg-resistant and secrete plant growth promoting compounds is reviewed. We highlight areas where more research is required into the effective use of phytoremediation on Hg-contaminated sites, and conclude that the approaches it offers provide considerable potential for the future.

PMID:33801363 | DOI:10.3390/ijerph18052435

Int J Mol Sci. 2021 Mar 21;22(6):3191. doi: 10.3390/ijms22063191.

ABSTRACT

Drought is one of the main causes of mortality in holm oak (Quercus ilex) seedlings used in reforestation programs. Although this species shows high adaptability to the extreme climate conditions prevailing in Southern Spain, its intrinsic genetic variability may play a role in the differential response of some populations and individuals. The aim of this work was to identify proteins and derived proteotypic peptides potentially useful as putative markers for drought tolerance in holm oak by using a targeted post-acquisition proteomics approach. For this purpose, we used a set of proteins identified by shotgun (LC-MSMS) analysis in a drought experiment on Q. ilex seedlings from four different provenances (viz. the Andalusian provinces Granada, Huelva, Cadiz and Seville). A double strategy involving the quantification of proteins and target peptides by shotgun analysis and post-acquisition data analysis based on proteotypic peptides was used. To this end, an initial list of proteotypic peptides from proteins highly represented under drought conditions was compiled that was used in combination with the raw files from the shotgun experiment to quantify the relative abundance of the fragment's ion peaks with the software Skyline. The most abundant peptides under drought conditions in at least two populations were selected as putative markers of drought tolerance. A total of 30 proteins and 46 derived peptides belonging to the redox, stress-related, synthesis,-folding and degradation, and primary and secondary metabolism functional groups were thus identified. Two proteins (viz., subtilisin and chaperone GrpE protein) were found at increased levels in three populations, which make them especially interesting for validation drought tolerance markers in subsequent experiments.

PMID:33800973 | DOI:10.3390/ijms22063191

Int J Mol Sci. 2021 Mar 6;22(5):2664. doi: 10.3390/ijms22052664.

ABSTRACT

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (HMGCR, PCSK9, LDLR, FXR, IDOL, and PPAR). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds.

PMID:33800828 | DOI:10.3390/ijms22052664

Biology (Basel). 2021 Mar 28;10(4):275. doi: 10.3390/biology10040275.

ABSTRACT

Periodic assessments of population status and trends to detect natural influences and human effects on coastal dolphin are often limited by lack of baseline information. Here, we investigated for the first time the site-fidelity patterns and estimated the population size of bottlenose dolphins (Tursiops truncatus) at the Tiber River estuary (central Mediterranean, Tyrrhenian Sea, Rome, Italy) between 2017 and 2020. We used photo-identification data and site-fidelity metrics to study the tendency of dolphins to remain in, or return to, the study area, and capture-recapture models to estimate the population abundance. In all, 347 unique individuals were identified. The hierarchical cluster analysis highlighted 3 clusters, labeled resident (individuals encountered at least five times, in three different months, over three distinct years; n = 42), part-time (individuals encountered at least on two occasions in a month, in at least two different years; n = 73), and transient (individuals encountered on more than one occasion, in more than 1 month, none of them in more than 1 year; n = 232), each characterized by site-fidelity metrics. Open POPAN modeling estimated a population size of 529 individuals (95% CI: 456-614), showing that the Capitoline (Roman) coastal area and nearby regions surrounding the Tiber River estuary represent an important, suitable habitat for bottlenose dolphins, despite their proximity to one of the major urban centers in the world (the city of Rome). Given the high number of individuals in the area and the presence of resident individuals with strong site fidelity, we suggest that conservation plans should not be focused only close to the Tiber River mouths but extended to cover a broader scale of area.

PMID:33800538 | DOI:10.3390/biology10040275

Biomedicines. 2021 Mar 7;9(3):265. doi: 10.3390/biomedicines9030265.

ABSTRACT

Mesenchymal stem cells (MSCs) can be harvested from different sites in the oral cavity, representing a reservoir of cells useful for regenerative purposes. As direct comparisons between at least two types of MSCs deriving from the same patient are surprisingly rare in scientific literature, we isolated and investigated the osteoinductive potential of dental pulp stem cells (DPSCs) and buccal fat pad stem cells (BFPSCs). MSCs were isolated from the third molar dental pulp and buccal fat pads of 12 patients. The number of viable cells was quantified through manual count. Proliferation and osteodifferentiation assays, flow cytometry analysis of cell phenotypes, and osteocalcin release in vitro were performed. The isolation of BFPSCs and DPSCs was successful in 7 out of 12 (58%) and 3 out of 12 (25%) of retrieved samples, respectively. The yield of cells expressing typical stem cell markers and the level of proliferation were higher in BFPSCs than in DPSCs. Both BFP-SCs and DPSCs differentiated into osteoblast-like cells and were able to release a mineralized matrix. The release of osteocalcin, albeit greater for BFPSCs, did not show any significant difference between BFPSCs and DPSCs. The yield of MSCs depends on their site of origin as well as on the protocol adopted for their isolation. Our data show that BFP is a valuable source for the derivation of MSCs that can be used for regenerative treatments.

PMID:33800030 | DOI:10.3390/biomedicines9030265

Molecules. 2021 Mar 7;26(5):1448. doi: 10.3390/molecules26051448.

ABSTRACT

The endocannabinoid system (ECS) is involved in the modulation of several basic biological processes, having widespread roles in neurodevelopment, neuromodulation, immune response, energy homeostasis and reproduction. In the adult central nervous system (CNS) the ECS mainly modulates neurotransmitter release, however, a substantial body of evidence has revealed a central role in regulating neurogenesis in developing and adult CNS, also under pathological conditions. Due to the complexity of investigating ECS functions in neural progenitors in vivo, we tested the suitability of the ST14A striatal neural progenitor cell line as a simplified in vitro model to dissect the role and the mechanisms of ECS-regulated neurogenesis, as well as to perform ECS-targeted pharmacological approaches. We report that ST14A cells express various ECS components, supporting the presence of an active ECS. While CB1 and CB2 receptor blockade did not affect ST14A cell number, exogenous administration of the endocannabinoid 2-AG and the synthetic CB2 agonist JWH133 increased ST14A cell proliferation. Phospholipase C (PLC), but not PI3K pharmacological blockade negatively modulated CB2-induced ST14A cell proliferation, suggesting that a PLC pathway is involved in the steps downstream to CB2 activation. On the basis of our results, we propose ST14A neural progenitor cells as a useful in vitro model for studying ECS modulation of neurogenesis, also in prospective in vivo pharmacological studies.

PMID:33800024 | DOI:10.3390/molecules26051448

Cancers (Basel). 2021 Mar 7;13(5):1138. doi: 10.3390/cancers13051138.

ABSTRACT

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

PMID:33799965 | DOI:10.3390/cancers13051138

Immunol Cell Biol. 2021 Apr 2. doi: 10.1111/imcb.12456. Online ahead of print.

ABSTRACT

High-dimensional cytometry represents an exciting new era of immunology research, enabling the discovery of new cells and prediction of patient responses to therapy. A plethora of analysis and visualisation tools and programmes are now available for both new and experienced users; however, the transition from low-dimensional to high-dimensional cytometry requires a change in the way users think about experimental design and data analysis. Data from high-dimensional cytometry experiments are often under-utilised, due to both the size of the data and the number of possible combinations of markers, as well as to a lack of understanding of the processes required to generate meaningful data. In this article, we explain the concepts behind designing high-dimensional cytometry experiments and provide considerations for new and experienced users to design and carry out high-dimensional experiments to maximise quality data collection.

PMID:33797774 | DOI:10.1111/imcb.12456

J Cell Commun Signal. 2021 Apr 2. doi: 10.1007/s12079-021-00614-6. Online ahead of print.

ABSTRACT

The apelin receptor (APLNR) is a class A (rhodopsin-like) G-protein coupled receptor with a wide distribution throughout the human body. Activation of the apelin/APLNR system regulates AMPK/PI3K/AKT/mTOR and RAF/ERK1/2 mediated signaling pathways. APLNR activation orchestrates several downstream signaling cascades, which play diverse roles in physiological effects, including effects upon vasoconstriction, heart muscle contractility, energy metabolism regulation, and fluid homeostasis angiogenesis. We consolidated a network map of the APLNR signaling map owing to its biomedical importance. The curation of literature data pertaining to the APLNR system was performed manually by the NetPath criteria. The described apelin receptor signaling map comprises 35 activation/inhibition events, 38 catalysis events, 4 molecular associations, 62 gene regulation events, 113 protein expression types, and 4 protein translocation events. The APLNR signaling pathway map data is made freely accessible through the WikiPathways Database ( https://www.wikipathways.org/index.php/Pathway:WP5067 ).

PMID:33797707 | DOI:10.1007/s12079-021-00614-6

Oecologia. 2021 Apr 1. doi: 10.1007/s00442-021-04901-2. Online ahead of print.

ABSTRACT

Animal space use is affected by spatio-temporal variation in food availability and/or population density and varies among individuals. This inter-individual variation in spacing behaviour can be further influenced by sex, body condition, social dominance, and by the animal's personality. We used capture-mark-recapture and radio-tracking to examine the relationship between space use and personality in Eurasian red squirrels (Sciurus vulgaris) in three conifer forests in the Italian Alps. We further explored to what extent this was influenced by changes in food abundance and/or population density. Measures of an individual's trappability and trap diversity had high repeatability and were used in a Principal Component Analysis to obtain a single personality score representing a boldness-exploration tendency. Males increased home-range size with low food abundance and low female density, independent of their personality. However, bolder males used larger core-areas that overlapped less with other males than shy ones, suggesting different resource (food, partners) utilization strategies among personality types. For females, space use-personality relationships varied with food abundance, and bolder females used larger home ranges than shy ones at low female density, but the trend was opposite at high female density. Females' intrasexual core-area overlap was negatively related to body mass, with no effect of personality. We conclude that relationships between personality traits and space use in free-ranging squirrels varied with sex, and were further influenced by spatio-temporal fluctuations in food availability. Moreover, different personality types (bold-explorative vs. shy) seemed to adopt different space-use strategies to increase access to food and/or partners.

PMID:33796927 | DOI:10.1007/s00442-021-04901-2

Netw Syst Med. 2021 Mar 8;4(1):51-59. doi: 10.1089/nsm.2020.0014. eCollection 2021.

ABSTRACT

Background: Transcriptional regulation of gene expression is crucial for the adaptation and survival of bacteria. Regulatory interactions are commonly modeled as Gene Regulatory Networks (GRNs) derived from experiments such as RNA-seq, microarray and ChIP-seq. While the reconstruction of GRNs is fundamental to decipher cellular function, even GRNs of economically important bacteria such as Corynebacterium glutamicum are incomplete. Materials and Methods: Here, we analyzed the predictive power of GRNs if used as in silico models for gene expression and investigated the consistency of the C. glutamicum GRN with gene expression data from the GEO database. Results: We assessed the consistency of the C. glutamicum GRN using real, as well as simulated, expression data and showed that GRNs alone cannot explain the expression profiles well. Conclusion: Our results suggest that more sophisticated mechanisms such as a combination of transcriptional, post-transcriptional regulation and signaling should be taken into consideration when analyzing and constructing GRNs.

PMID:33796877 | PMC:PMC8006670 | DOI:10.1089/nsm.2020.0014