Extracellular acidity and oxygen availability conjointly control eukaryotic cell growth via modulation of cytoplasmic translation

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Duygu Dikicioglu
Keyword(s):  
Synergistic Effect ◽  
Synergistic Effects ◽  
Eukaryotic Cell ◽  
Oxygen Availability ◽  
Metabolic Responses ◽  
Strong Impact ◽  
Intracellular Amino Acid ◽  
Individual Effects ◽  
Two Factors ◽  
Modulation Of Gene Expression

AbstractBackgroundOxygen availability and extracellular acidity both have a strong impact on growth and cultivation characteristics of eukaryotes, however they are often considered in isolation, whereby a single parameter is varied at a time to identify its impact, rendering the investigation of synergistic effects created by two or more factors non-achievable. This study identified the synergistic effect between environmental pH and oxygen levels on the physiological and cellular characteristics of the simplest eukaryote, Saccharomyces cerevisiae.Materials and methodsThe physiological, transcriptomic, and metabolic responses of yeast were investigated during batch growth in a 2 × 2 factorial design setting; environmental pH and oxygen availability were either controlled at their optimal settings, or allowed to follow their own course during cultivation.ResultsSynergistic effects had a significant impact on yeast physiology, which was provoked further by both the modulation of gene expression by transcription, and the modification of metabolite pools. Genes involved in cytoplasmic translation, the extracellular and intracellular amino acid and their precursor metabolite pools were significantly responsive to concurrent variations in these two factors.ConclusionThe synergistic effect of extracellular acidity and oxygenation on eukaryotic landscape of growth-associated events was significantly more pronounced than their individual effects.

Platinum and cobalt intermetallic nanoparticles confined within MIL-101(Cr) for enhanced selective hydrogenation of the carbonyl bond in α,β-unsaturated aldehydes: synergistic effects of electronically modified Pt sites and Lewis acid sites

2021 ◽  
Author(s):  
Muhammad Zahid ◽  
Jiang Li ◽  
Ahmed Ismail ◽  
Francisco Zaera ◽  
Yujun Zhu
Keyword(s):  
Synergistic Effect ◽  
Reduction Method ◽  
Synergistic Effects ◽  
Acid Sites ◽  
Lewis Acid Sites ◽  
Unsaturated Aldehydes ◽  
Uniform Dispersion ◽  
Carbonyl Bond ◽  
Method Show ◽  
Intermetallic Nanoparticles

PtCo/MIL-101(Cr) with high uniform dispersion Pt–Co IMNs synthesized by a polyol reduction method show higher activity for selective catalytic hydrogenation of α,β-unsaturated aldehydes due to the synergistic effect of PtCo and MIL-101(Cr) support.

Synergistic Effects of 5-Fluorouracil in Combination with Diosmetin in Colorectal Cancer Cells

2021 ◽  
Vol 7 (1) ◽  
pp. 6
Author(s):  
Sareh Kamran ◽  
Ajantha Sinniah ◽  
Mohammed Abdullah Alshawsh
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Synergistic Effect ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Neoadjuvant Treatment ◽  
Software Tool ◽  
New Combination ◽  
Combination Regimen ◽  
Colorectal Cancer Cells

Colorectal cancer (CRC) is among the most commonly occurring cancers. The management of CRC includes laparoscopic surgery, radiotherapy, chemotherapies and neoadjuvant treatment. However, conventional chemotherapies have poor impact on combating CRC and are associated with severe toxic effects and high rates of relapse. Therefore, searching for a new combination regimen is a favorable consideration. The aim of this study was to elucidate the synergistic effect of 5-fluorouracil (5-FU) and diosmetin in an in vitro model on colorectal cancer cells. An MTT assay was conducted on HCT-116 cancer cells and they were treated with a concentration gradient of 5-FU and diosmetin individually and in combination. The combination index (CI) and dose reduction index (DRI) were calculated using CompuSyn software. Isobologram analysis and synergism determination were performed using the Combenefit software tool and the synergy score was calculated using the SynergyFinder 2.0 software tool. The apoptotic features of the cells were determined via an AO/PI double staining assay and an annexin V assay using a fluorescent microscope and the flow cytometry technique, respectively. The findings showed that the DRI of 5-FU was three-fold lower in the combination with a CI value of less than one, which indicates that there was a synergistic effect. The AO/PI microscopic results revealed signs of apoptosis and dead cells after 72 h of treatment. Flow cytometry analysis confirmed that the apoptotic effect of the combination was more prominent compared to 5-FU alone. The findings of this study offer a potential strategy for reducing the cytotoxicity and enhancing the efficacy of 5-FU on colorectal cancer cells through a synergistic study model.

scholarly journals A mechanism for evolution of the physical concepts network

2021 ◽  
Vol 24 (2) ◽  
pp. 24001
Author(s):  
V. Palchykov ◽  
M. Krasnytska ◽  
O. Mryglod ◽  
Yu. Holovatch
Keyword(s):  
Synergistic Effect ◽  
Complex Network ◽  
Empirical Analysis ◽  
Growth Models ◽  
Underlying Mechanism ◽  
Scientific Concepts ◽  
Network Growth ◽  
Preferential Selection ◽  
Network Characteristics ◽  
Two Factors

We suggest an underlying mechanism that governs the growth of a network of concepts, a complex network that reflects the connections between different scientific concepts based on their co-occurrences in publications. To this end, we perform empirical analysis of a network of concepts based on the preprints in physics submitted to the arXiv.org. We calculate the network characteristics and show that they cannot follow as a result of several simple commonly used network growth models. In turn, we suggest that a simultaneous account of two factors, i.e., growth by blocks and preferential selection, gives an explanation of empirically observed properties of the concepts network. Moreover, the observed structure emerges as a synergistic effect of these both factors: each of them alone does not lead to a satisfactory picture.

scholarly journals Synergistic effects of metal hydroxides and fumed nanosilica as fire retardants for polyethylene

2019 ◽  
Vol 2 (1) ◽  
pp. 30-48
Author(s):  
Giulia Fredi ◽  
Andrea Dorigato ◽  
Luca Fambri ◽  
José-Marie Lopez-Cuesta ◽  
Alessandro Pegoretti
Keyword(s):  
Mechanical Properties ◽  
Synergistic Effect ◽  
Silica Nanoparticles ◽  
Synergistic Effects ◽  
Metal Hydroxide ◽  
Flow Index ◽  
Fire Performance ◽  
Cone Calorimetry ◽  
Neat Polymer ◽  
Limiting Oxygen Index

AbstractThis work aims to study the synergistic effect of aluminum/magnesium hydroxide microfillers and organomodified fumed silica nanoparticles as flame retardants (FRs) for linear low-density polyethylene (LLDPE), and to select the best composition to produce a fire-resistant polyethylene-based single-polymer composite. The fillers were added to LLDPE at different concentrations, and the prepared composites were characterized to investigate the individual and combined effects of the fillers on the thermo-oxidation resistance and the fire performance, as well as the microstructural, physical, thermal and mechanical properties. Both filler types were homogeneously distributed in the matrix, with the formation of a network of silica nanoparticles at elevated loadings. Melt flow index (MFI) tests revealed that the fluidity of the material was not considerably impaired upon metal hydroxide introduction, while a heavy reduction of the MFI was detected for silica contents higher than 5 wt%. FRs introduction promoted a noticeable enhancement of the thermo-oxidative stability of the materials, as shown by thermogravimetric analysis (TGA) and onset oxidation temperature (OOT) tests, and superior thermal properties were measured on the samples combining micro- and nanofillers, thus evidencing synergistic effects. Tensile tests showed that the stiffening effect due to a high content of metal hydroxide microparticles was accompanied by a decrease in the strain at break, but nanosilica at low concentration contributed to preserve the ultimate mechanical properties of the neat polymer. The fire performance of the samples with optimized compositions, evaluated through limiting oxygen index (LOI) and cone calorimetry tests, was strongly enhanced with respect to that of the neat LLDPE, and also these tests highlighted the synergistic effect between micro- and nanofillers, as well as an interesting correlation between fire parameters and viscosity.

scholarly journals One-Step Hydrothermal Synthesis of Yellow and Green Emitting Silicon Quantum Dots with Synergistic Effect

Nanomaterials ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 466
Author(s):  
Zhixia Zhang ◽  
Chunjin Wei ◽  
Wenting Ma ◽  
Jun Li ◽  
Xincai Xiao ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Synergistic Effect ◽  
High Efficiency ◽  
Synergistic Effects ◽  
Biomedical Science ◽  
Future Application ◽  
Quantum Yields ◽  
Silicon Quantum Dots ◽  
Long Wavelength ◽  
One Step

The concept of synergistic effects has been widely applied in many scientific fields such as in biomedical science and material chemistry, and has further attracted interest in the fields of both synthesis and application of nanomaterials. In this paper, we report the synthesis of long-wavelength emitting silicon quantum dots based on a one-step hydrothermal route with catechol (CC) and sodium citrate (Na-citrate) as a reducing agent pair, and N-[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO) as silicon source. By controlling the reaction time, yellow-emitting silicon quantum dots and green-emitting silicon quantum dots were synthesized with quantum yields (QYs) of 29.4% and 38.3% respectively. The as-prepared silicon quantum dots were characterized by fluorescence (PL) spectrum, UV–visible spectrum, high resolution transmission electron microscope (HRTEM), Fourier transform infrared (FT-IR) spectrometry energy dispersive spectroscopy (EDS), and Zeta potential. With the aid of these methods, this paper further discussed how the optical performance and surface characteristics of the prepared quantum dots (QDs) influence the fluorescence mechanism. Meanwhile, the cell toxicity of the silicon quantum dots was tested by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium (MTT) bromide method, and its potential as a fluorescence ink explored. The silicon quantum dots exhibit a red-shift phenomenon in their fluorescence peak due to the participation of the carbonyl group during the synthesis. The high-efficiency and stable photoluminescence of the long-wavelength emitting silicon quantum dots prepared through a synergistic effect is of great value in their future application as novel optical materials in bioimaging, LED, and materials detection.

High thermoelectric performance of polycrystalline In4Se3−δ(CuI)x: synergistic effects of the Se-deficiency and CuI-doping

2016 ◽  
Vol 3 (12) ◽  
pp. 1566-1571 ◽  
Author(s):  
Yan-Chun Chen ◽  
Hua Lin ◽  
Li-Ming Wu
Keyword(s):  
Synergistic Effect ◽  
Power Factor ◽  
Figure Of Merit ◽  
Synergistic Effects ◽  
Thermoelectric Performance ◽  
Thermoelectric Figure Of Merit ◽  
Thermoelectric Figure ◽  
Se Deficiency

Synergistic effect of Se-deficiency and CuI-doping significantly enhances the thermoelectric figure-of-merit of the n-type polycrystalline In4Se3-based materials via improving the power factor. With In4Se2.95(CuI)0.01, ZT = 1.34 at 723 K, the highest value obtained for Pb-free polycrystalline In4Se3-based materials to date.

Synergistic effect of IgG4 antibody and CTLs causes tissue inflammation in IgG4-related disease

2019 ◽  
Vol 32 (3) ◽  
pp. 163-174
Author(s):  
Takanori Sasaki ◽  
Taiki Yajima ◽  
Tatsuro Shimaoka ◽  
Shuhei Ogawa ◽  
Takashi Saito ◽  
...  
Keyword(s):  
T Cells ◽  
Synergistic Effect ◽  
Plasma Cells ◽  
Synergistic Effects ◽  
Lymphoid Tissues ◽  
Irreversible Damage ◽  
Tissue Specific ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Igg4 Antibody

Abstract IgG4-related disease (IgG4-RD) is characterized by multi-organ irreversible damage resulting from tissue-specific infiltration of IgG4+ plasma cells and cytotoxic T lymphocytes (CTLs). However, whether IgG4 antibody contributes to the inflammation remains unclear. In this study, we established a mouse model that enabled us to evaluate the pathogenic function of IgG4 antibodies in response to a tissue-specific autoantigen using recombinant ovalbumin (OVA)-specific human IgG4 monoclonal antibody (rOVA-hIgG4 mAb) and the mice expressing OVA of the pancreatic islets (RIP-mOVA mice). We found no inflammatory effect of rOVA-hIgG4 mAb transfer alone; however, co-transfer with OVA-specific CD8 CTLs (OT-I T cells) induced tissue damage with dense lymphocytic inflammation in the pancreas of RIP-mOVA mice. rOVA-hIgG4 mAb caused accumulation of conventional DC1 cells (cDC1s) in the lymphoid tissues, and the dendritic cells (DCs) activated the OT-I T cells via cross-presentation. We also revealed that the synergistic effects of CTLs and antibodies were observed in the other subclasses including endogenous antibodies if they recognized the same antigen. The transfer of OVA-specific CD4 helper T cells (OT-II T cells) into RIP-mOVA mice induced the production of anti-OVA antibody, which had a synergistic effect, through acquisition of a T follicular helper (TFH) phenotype. Moreover, using OT-II T cells deficient in Bcl6 caused lower anti-OVA antibody production and inflammation with OT-I T cells. Our results indicated that autoreactive IgG4 antibodies play an important role of the tissue-specific CTL response in IgG4-RD.

scholarly journals The Performance of Wood Decking after Five Years of Exposure: Verification of the Combined Effect of Wetting Ability and Durability

Forests ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 903 ◽  
Author(s):  
Miha Humar ◽  
Davor Kržišnik ◽  
Boštjan Lesar ◽  
Christian Brischke
Keyword(s):  
Service Life ◽  
Synergistic Effects ◽  
Construction Materials ◽  
Exposure Dose ◽  
Decay Rates ◽  
Water Repellent ◽  
Factors Affecting ◽  
Wetting Ability ◽  
Two Factors ◽  
Moisture Performance

Wood is one of the most important construction materials, and its use in building applications has increased in recent decades. In order to enable even more extensive and reliable use of wood, we need to understand the factors affecting wood’s service life. A new concept for characterizing the durability of wood-based materials and for predicting the service life of wood has recently been proposed, based on material-inherent protective properties, moisture performance, and the climate- and design-induced exposure dose of wooden structures. This approach was validated on the decking of a model house in Ljubljana that was constructed in October 2013. The decay and moisture content of decking elements were regularly monitored. In addition, the resistance dose DRd, as the product of the critical dose Dcrit, and two factors taking into account the wetting ability of wood (kwa) and its inherent durability (kinh), were determined in the laboratory. DRd correlated well with the decay rates of the decking of the model house. Furthermore, the positive effect of thermal modification and water-repellent treatments on the outdoor performance of the examined materials was evident, as well as the synergistic effects between moisture performance and inherent durability.

scholarly journals Dynamics of DNA replication in a eukaryotic cell

2019 ◽  
Vol 116 (11) ◽  
pp. 4973-4982 ◽  
Author(s):  
Thomas Kelly ◽  
A. John Callegari
Keyword(s):  
Dna Replication ◽  
Single Molecule ◽  
Origin Recognition Complex ◽  
Complex Dynamics ◽  
Replication Timing ◽  
Eukaryotic Cell ◽  
Replication Initiation ◽  
Integrative Model ◽  
Genomic Locus ◽  
Two Factors

Each genomic locus in a eukaryotic cell has a distinct average time of replication during S phase that depends on the spatial and temporal pattern of replication initiation events. Replication timing can affect genomic integrity because late replication is associated with an increased mutation rate. For most eukaryotes, the features of the genome that specify the location and timing of initiation events are unknown. To investigate these features for the fission yeast, Schizosaccharomyces pombe, we developed an integrative model to analyze large single-molecule and global genomic datasets. The model provides an accurate description of the complex dynamics of S. pombe DNA replication at high resolution. We present evidence that there are many more potential initiation sites in the S. pombe genome than previously identified and that the distribution of these sites is primarily determined by two factors: the sequence preferences of the origin recognition complex (ORC), and the interference of transcription with the assembly or stability of prereplication complexes (pre-RCs). We suggest that in addition to directly interfering with initiation, transcription has driven the evolution of the binding properties of ORC in S. pombe and other eukaryotic species to target pre-RC assembly to regions of the genome that are less likely to be transcribed.

scholarly journals ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xiaonan Xi ◽  
Ning Liu ◽  
Qianqian Wang ◽  
Yahui Chu ◽  
Zheng Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Synergistic Effect ◽  
Glioma Cell ◽  
Synergistic Effects ◽  
Akt Pathway ◽  
Phase I Clinical Trials ◽  
Glioma Cell Proliferation ◽  
Pai 1

Abstract PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.

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