Hot Deformation Behavior of Non-Alloyed Carbon Steels

The hot deformation behavior of selected non-alloyed carbon steels was investigated by isothermal continuous uniaxial compression tests. Based on the analysis of experimentally determined flow stress curves, material constants suitable for predicting peak flow stress σ_p, peak strain ε_p and critical strain ε_crDRX necessary to induce dynamic recrystallization and the corresponding critical flow stresses σ_crDRX were determined. The validity of the predicted critical strains ε_crDRX was then experimentally verified. Fine dynamically recrystallized grains, which formed at the boundaries of the original austenitic grains, were detected in the microstructure of additionally deformed specimens from low-carbon investigated steels. Furthermore, equations describing with perfect accuracy a simple linear dependence of the critical strain ε_crDRX on peak strain ε_p were derived for all investigated steels. The determined hot deformation activation energy Q decreased with increasing carbon content (also with increasing carbon equivalent value) in all investigated steels. A logarithmic equation described this dependency with reasonable accuracy. Individual flow stress curves of the investigated steels were mathematically described using the Cingara and McQueen model, while the predicted flow stresses showed excellent accuracy, especially in the strains ranging from 0 to ε_p.     

Natural Cellulosic Fiber Reinforced Concrete: Influence of Fiber Type and Loading Percentage on Mechanical and Water Absorption Performance

The paper reports experimental research regarding the mechanical characteristics of concrete reinforced with natural cellulosic fibers like jute, sisal, sugarcane, and coconut. Each type of natural fiber, with an average of 30 mm length, was mixed with a concrete matrix in varying proportions of 0.5% to 3% mass. The tensile and compressive strength of the developed concrete samples with cellulosic fiber reinforcement gradually increased with the increasing proportion of natural cellulosic fibers up to 2%. A further increase in fiber loading fraction results in deterioration of the mechanical properties. By using jute and sisal fiber reinforcement, about 11.6% to 20.2% improvement in tensile and compressive strength, respectively, was observed compared to plain concrete, just by adding 2% of fibers in the concrete mix. Bending strength increased for the natural fiber-based concrete with up to 1.5% fiber loading. However, a decrease in bending strength was observed beyond 1.5% loading due to cracks at fiber−concrete interface. The impact performance showed gradual improvement with natural fiber loading of up to 2%. The water absorption capacity of natural cellulosic fiber reinforced concrete decreased substantially; however, it increased with the loading percent of fibers. The natural fiber reinforced concrete can be commercially used for interior or exterior pavements and flooring slabs as a sustainable construction material for the future.     

Impact of Carbon Particle Character on the Cement-Based Composite Electrical Resistivity

Electroconductive cement-based composites are modern materials that are commonly used in many industries such as the construction industry, among others. For example, these materials can be used as sensors for monitoring changes in construction, grounding suspension, and resistance heating materials, etc. The aim of the research presented in this article is to monitor the impact of carbon particle character on cement-based electroconductive composites. Four types of graphite were analyzed. Natural and synthetic types of graphite, with different particle sizes and one with improved electrically conductive properties, were tested. For the analysis of the electrical conductivity of powder raw materials, a new methodology was developed based on the experience of working with these materials. Various types of graphite were tested in pure cement paste (80% cement, 20% graphite) as well as in a composite matrix, which consisted of cement (16.8%), a mixture of silica sand 0–4 mm (56.4%), graphite filler (20.0%) ground limestone (6.7%) and super plasticizers (0.1%). The resistivity and physical-mechanical properties of the composite material were determined. Furthermore, the resistivity of the test samples was measured with a gradual decrease in saturation. It may be concluded that graphite fillers featuring very fine particles and high specific surface are most suitable and most effective for creating electrically conductive silicate composites. The amount, shape and, in particular, the fineness of the graphite filler particles thus creates suitable conditions for the creation of an integrated internal electricity-conductive network. In the case of the use of a coarse type of graphite or purely non-conductive fillers, the presence of an electrolyte, for example, in the form of water, is necessary to achieve a low resistivity. Samples with fine types of graphite fillers achieved stable resistivity values when the sample humidity changed. The addition of graphite fillers caused a large decrease in the strength of the samples.     

Confirmed cannibalism in wild boar and its possible role in African swine fever transmission

For the monitoring of wild boar interactions with conspecific carcasses, seven wild boar carcasses were placed in different sites in the Czech Republic during winter season. Data were collected by camera traps. In total, 732 visits were recorded of wild boars at the carcass sites. Direct contact with the carcass was detected in 81% of the records. Cannibalism was observed in 9.8% of all recorded visits. The first direct contact was observed on average 30 days after the carcass had been placed in its respective site. Cannibalism was observed on average after 70 days. The effect of sex‐age class on direct contact was not proven in our study. The presented findings show that cannibalism in wild boar can play a substantial role in the ASF epidemic. These results highlighted the importance of the removal of infected carcasses from the habitat, which is crucial for African swine fever eradication.     

Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome

1. The underlying microbial metabolic activity toward xenobiotics is among the least explored factors contributing to the inter-individual variability in drug response.

2. Here, we analyzed the effect of microbiota on a non-steroidal anti-inflammatory drug nabumetone.

3. First, we cultivated the drug with the selected gut commensal and probiotic bacteria under both aerobic and anaerobic conditions and analyzed its metabolites by high-performance liquid chromatography (HPLC) with UV detection. To analyze the effect of microbiota on nabumetone pharmacokinetics in vivo, we administered a single oral dose of nabumetone to rodents with intentionally altered gut microbiome - either rats treated for three days with the antibiotic imipenem or to germ-free mice. Plasma levels of its main active metabolite 6 methoxy-2-naphthylacetic acid (6-MNA) were analyzed at pre-specified time intervals using HPLC with UV/fluorescence detection.

4. We found that nabumetone is metabolized by bacteria to its non-active metabolites and that this effect is stronger under anaerobic conditions. Although in vivo, none of the pharmacokinetic parameters of 6-MNA was significantly altered, there was a clear trend towards an increase of the AUC, Cmax and t_1/2 in rats with reduced microbiota and germ-free mice.     

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown that CXCL10/CXCR3 interactions drive effector Th1 polarization via STAT1, STAT4, and STAT5 phosphorylation, while CXCL11/CXCR3 binding induces an immunotolerizing state that is characterized by IL-10^hi (Tr1) and IL-4^hi (Th2) cells, mediated via p70 kinase/mTOR in STAT3- and STAT6-dependent pathways. CXCL11 binds CXCR3 with a higher affinity than CXCL10, suggesting that CXCL11 has the potential to restrain inflammatory autoimmunity. We generated a CXCL11-Ig fusion molecule and evaluated its use in the EAE model of inflammatory autoimmune disease. Administration of CXCL11-Ig during the first episode of relapsing EAE in SJL/J mice not only led to rapid remission, but also prevented subsequent relapse. Using GFP-expressing effector CD4⁺ T cells, we observed that successful therapy was associated with reduced accumulation of these cells at the autoimmune site. Finally, we showed that very low doses of CXCL11 rapidly suppress signs of EAE in C57BL/6 mice lacking functional CXCL11.     

Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population

Background

Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics.

Methods

In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction.

Results

None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043).

Conclusions

The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.     

NMDA receptor-dependent GABAB receptor internalization via CaMKII phosphorylation of serine 867 in GABAB1

GABA_B receptors are the G-protein–coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. GABA_B receptors are abundant on dendritic spines, where they dampen postsynaptic excitability and inhibit Ca²⁺ influx through NMDA receptors when activated by spillover of GABA from neighboring GABAergic terminals. Here, we show that an excitatory signaling cascade enables spines to counteract this GABA_B-mediated inhibition. We found that NMDA application to cultured hippocampal neurons promotes dynamin-dependent endocytosis of GABA_B receptors. NMDA-dependent internalization of GABA_B receptors requires activation of Ca²⁺/Calmodulin-dependent protein kinase II (CaMKII), which associates with GABA_B receptors in vivo and phosphorylates serine 867 (S867) in the intracellular C terminus of the GABA_B1 subunit. Blockade of either CaMKII or phosphorylation of S867 renders GABA_B receptors refractory to NMDA-mediated internalization. Time-lapse two-photon imaging of organotypic hippocampal slices reveals that activation of NMDA receptors removes GABA_B receptors within minutes from the surface of dendritic spines and shafts. NMDA-dependent S867 phosphorylation and internalization is predominantly detectable with the GABA_B1b subunit isoform, which is the isoform that clusters with inhibitory effector K⁺ channels in the spines. Consistent with this, NMDA receptor activation in neurons impairs the ability of GABA_B receptors to activate K⁺ channels. Thus, our data support that NMDA receptor activity endocytoses postsynaptic GABA_B receptors through CaMKII-mediated phosphorylation of S867. This provides a means to spare NMDA receptors at individual glutamatergic synapses from reciprocal inhibition through GABA_B receptors.     

Fenofibrate-induced decrease of expression of CYP2C11 and CYP2C6 in rat

This short communication is aimed to investigate whether the widely used hypolipidemic drug fenofibrate affects CYP2C11 and CYP2C6 in rats, both counterparts of human CYP2C9, known to metabolise many drugs including S-warfarin and largely used non-steroidal antiinflammatory drugs such as ibuprofen, diclofenac and others. The effects of fenofibrate on the expression of rat liver CYP2C11 and CYP2C6 were studied in both healthy Wistar rats and hereditary hypertriglyceridemic rats. Both strains of rats were fed on diet containing fenofibrate (0.1% w/w) for 20 days. Fenofibrate highly significantly suppressed the expression of mRNA of CYP2C11 and less that of CYP2C6 in liver microsomes of both rat strains; this effect was associated with a corresponding decrease in protein levels. The results indicate that the combination of fenofibrate with drugs metabolised by CYP2C9 in humans should be taken with caution as it may lead, for example, to the potentiation of warfarin effects. This type of drug interaction has been observed previously and the results presented here could contribute to the explanation of their mechanism.