Caffeine is commonly used in
Dictyostelium
to inhibit the synthesis of the chemoattractant cAMP and, therefore, its secretion and the autocrine stimulation of cells, in order to prevent its ...interference with the study of chemoattractant-induced responses. However, the mechanism through which caffeine inhibits cAMP synthesis in
Dictyostelium
has not been characterized. Here, we report the effects of caffeine on the cAMP chemoattractant signaling network. We found that caffeine inhibits phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin complex 2 (mTORC2). Both PI3K and mTORC2 are essential for the chemoattractant-stimulated cAMP production, thereby providing a mechanism for the caffeine-mediated inhibition of cAMP synthesis. Our results also reveal that caffeine treatment of cells leads to an increase in cAMP-induced RasG and Rap1 activation, and inhibition of the PKA, cGMP, MyoII, and ERK1 responses. Finally, we observed that caffeine has opposite effects on F-actin and ERK2 depending on the assay and
Dictyostelium
strain used, respectively. Altogether, our findings reveal that caffeine considerably affects the cAMP-induced chemotactic signaling pathways in
Dictyostelium
, most likely acting through multiple targets that include PI3K and mTORC2.
The reaction of N‐(2,4‐dinitrophenyl)pyridinium chloride (saltCl−) with sodium salts of anionic dyes, such as acid red 52 (AR52), acid violet 49 (AV49), and coomassie brilliant blue G‐250 (CBBG250) ...involves an anion exchange between the chloride anion of salt(Cl−) and sulfonium anion of the dyes, resulting in the generation of novel Zincke salts, namely, salt(AR52), salt(AV49), and salt(CBBG250), respectively. Reactions of salt(AR52), salt(AV49), and salt(CBBG250) with piperazine in the absence of catalysts resulted in the opening of the pyridinium ring to yield ionic polymers comprising units of 5‐piperazinium‐2,4‐dienylideneammonium and the corresponding dye anion, namely polymer(AR52), polymer(AV49), and polymer(SBBG250), respectively. The corresponding model compounds for the polymers were also synthesized by reacting salt(AR52), salt(AV49), and salt(CBBG250) with piperidine. Polymer(AV49) and polymer(SBBG250) were found to be suitable for the detection of nucleosides, DNA, and proteins, realized by monitoring the changes in their UV–vis absorption spectra, arising from the anionic dyes within the polymers. The polymers and the model compounds were electrochemically oxidized in solution.
Trichoderma has been used as an alternative to synthetic pesticides to control a variety of phytopathogenic fungi, oomycetes, and nematodes. Although its mechanism of pathogen suppression has been ...extensively studied, how Trichoderma interacts with non-target microbes is not well understood. Here, we investigated how two Trichoderma biological control agents (BCAs) interact with rhizosphere bacteria isolated from a tomato plant via secreted proteins, metabolites, and volatile compounds (VCs). Culture filtrates (CFs) of T. virens and T. harzianum, containing secreted proteins and metabolites, strongly inhibited (>75% reduction in growth) 39 and 19, respectively, out of 47 bacterial strains tested. Their CFs inhibited the remaining strains at lower degrees. Both metabolites and proteins are involved in inhibiting bacteria, but they seem to antagonize each other in inhibiting some strains. Trichoderma and bacteria suppressed the growth of each other using VCs. The secretion of antibacterial and antifungal molecules by T. virens and T. harzianum was significantly affected by VCs from some bacteria, suggesting that both Trichoderma BCAs and rhizosphere bacteria use VCs to influence each other in multiple ways. In light of these results, we discuss how metabolite-mediated interactions can potentially affect the effectiveness of biocontrol.
Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci (cis-eQTLs) occur at the same genomic location as a methylation QTL ...(cis-meQTL), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other types of molecular QTLs can enhance our understanding of regulatory mechanisms.
USP8 is a deubiquitinating enzyme in the family of ubiquitin-specific proteases (USPs) which can remove ubiquitin from the substrate and protect the substrate from degradation. The upregulated or ...mutated USP8 becomes hyperactivated and stabilizes numerous oncogenes or proto-oncogenes leading to cancer progression and survival by activating multiple signaling pathways. Moreover, USP8 inhibition is also important to overcome anticancer drug-resistant. This review is the first study to find, combine, analyze, and represent the multiple oncogenic signaling pathways with their downstream and upstream regulation activated or enhanced by USP8, which will help the researchers to find any therapeutic strategy for drug discovery by inhibiting or suppressing the multi-targeted USP8.
This study develops an inventory model to solve the problems of supply uncertainty in response to demand which follows a Poisson distribution. A positive aspect of this model is the consideration of ...random inventory, delivery capacities and supplier’s reliability. Additionally, we assume supplier capacity follows an exponential distribution. This inventory model addresses the problem of a manufacturer having an imperfect production system with single supplier and single retailer and considers the quantity of product (Q), reorder points (r) and reliability factors (n) as the decision variables. The main contribution of our study is that we consider supplier may not be able to deliver the exact amount all the time a manufacturer needed. We also consider that the demand and the time interval between successive availability and unavailability of supplier and retailer follows a probability distribution. We use a genetic algorithm to find the optimal solution and compare the results with those obtained from simulated annealing algorithm. Findings reveal the optimal value of the decision variables to maximize the average profit in each cycle. Moreover, a sensitivity analysis was carried out to increase the understanding of the developed model. The methodology used in this study will help manufacturers to have a better understanding of the situation through the joint consideration of disruption of both the supplier and retailer integrated with random capacity and reliability.
Emerging data suggest that inorganic arsenic exposure and gut microbiome are associated with the risk of cardiovascular disease. The gut microbiome may modify disease risk associated with arsenic ...exposure. Our aim was to examine the inter-relationships between arsenic exposure, the gut microbiome, and carotid intima-media thickness (IMT)—a surrogate marker for atherosclerosis.
We recruited 250 participants from the Health Effects of Arsenic Longitudinal Study in Bangladesh, measured IMT and collected fecal samples in year 2015–2016. 16S rRNA gene sequencing was conducted on microbial DNA extracted from the fecal samples. Arsenic exposure was measured using data on arsenic concentration in drinking water wells over time to derive a time-weighted water arsenic index. Multivariable linear regression models were used to test the inter-relationships between arsenic exposure, relative abundance of selected bacterial taxa from phylum to genus levels, and IMT.
We identified nominally significant associations between arsenic exposure, measured using either time-weighted water arsenic or urinary arsenic, and the relative abundances of several bacterial taxa from the phylum Tenericutes, Proteobacteria, and Firmicutes. However, none of the associations retained significance after correction for multiple testing. The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with IMT after correction for multiple testing (P-value = 0.02 and 0.03, respectively). Every 1% increase in the relative abundance of Aeromonadaceae and Citrobacter was related to an 18.2-μm (95% CI: 7.8, 28.5) and 97.3-μm (95% CI: 42.3, 152.3) difference in IMT, respectively. These two taxa were also the only selected family and genus using the LASSO variable selection method. There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P for interaction = 0.04).
Our findings suggest a role of Citrobacter in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure.
•We identified nominally significant associations between arsenic exposure and the relative abundances of several bacterial taxa in the phylum Tenericutes, Proteobacteria, and Firmicutes. However, none of the associations retained significance after correction for multiple comparisons with FDR ≤ 5%.•The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with carotid IMT after adjustment for multiple comparisons with FDR ≤ 5%.•There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P-value = 0.04).•The data suggest that the gut microbiome may play an important role in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure.
•Assessing different drag models in liquid-irregular coarse particle fluidization.•Excellent agreement between irregular drag models and experimental data.•Higher apparent viscosity in dewatering ...zone than plug flow mixing zone.•Highest apparent viscosity in free settling regime.
Fluidization can enhance coarse particle separation. Here, a three-dimensional computational fluid dynamics (CFD) modeling in a fluidized bed flotation cell is performed to explore the complex insights of coarse irregular particle fluidization behaviours. To address the irregular property of the particle, the classical drag model is modified by incorporating the particle’s shape factor. Simulated particle volume fraction results and experimental data using a fluidized bed flotation cell showed that the irregular particle drag models had a relative error of 3.9% which was significantly better than that of the spherical particle drag models. Thereafter, the CFD model was applied to investigate the bed of low-density irregular coarse particles, 1600 kg/m3, and high-density irregular coarse particles, 2800 kg/m3, at low and high fluidization liquid velocities. It was shown that around 1.7-fold increased density of particles and liquid fluidization velocity increased the bed expansion height roughly 1.8-fold. The time-averaged pressure, volume fraction, apparent viscosity, and velocity of particles are analyzed to explore the fluidization behaviours, particularly within the free settling regime, plug-flow regime, and dewatering zone in the fluidized bed flotation cell. There was a higher apparent viscosity in the dewatering zone than in the plug-flow mixing zone, while the highest apparent viscosity was found in the free settling zone. The outcomes of these CFD studies are significant for the flotation of coarse particles in fluidized beds.
In this paper, a dual-band metamaterial absorber (MMA) ring with a mirror reflexed C-shape is introduced for X and Ku band sensing applications. The proposed metamaterial consists of two square ring ...resonators and a mirror reflexed C-shape, which reveals two distinctive absorption bands in the electromagnetic wave spectrum. The mechanism of the two-band absorber particularly demonstrates two resonance frequencies and absorption was analyzed using a quasi-TEM field distribution. The absorption can be tunable by changing the size of the metallic ring in the frequency spectrum. Design and analysis of the proposed meta-absorber was performed using the finite-integration technique (FIT)-based CST microwave studio simulation software. Two specific absorption peaks value of 99.6% and 99.14% are achieved at 13.78 GHz and 15.3 GHz, respectively. The absorption results have been measured and compared with computational results. The proposed dual-band absorber has potential applications in sensing techniques for satellite communication and radar systems.
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