Modeling of inhibition/excitation firing in olfactory bulb through spiking neurons

Spiking neural systems are based on biologically inspired neural models of computation since they take into account the precise timing of spike events and therefore are suitable to analyze dynamical aspects of neuronal signal transmission. These systems gained increasing interest because they are more sophisticated than simple neuron models found in artificial neural systems; they are closer to biophysical models of neurons, synapses, and related elements and their synchronized firing of neuronal assemblies could serve the brain as a code for feature binding and pattern segmentation. The simulations are designed to exemplify certain properties of the olfactory bulb (OB) dynamics and are based on an extension of the integrate-and-fire (IF) neuron, and the idea of locally coupled excitation and inhibition cells. We introduce the background theory to making an appropriate choice of model parameters. The following two forms of connectivity offering certain computational and analytical advantages, either through symmetry or statistical properties in the study of OB dynamics have been used:

• all-to-all coupling,
• receptive field style coupling.

Our simulations showed that the inter-neuron transmission delay controls the size of spatial variations of the input and also smoothes the network response. Our IF extended model proves to be a useful basis from which we can study more sophisticated features as complex pattern formation, and global stability and chaos of OB dynamics.     

Polymethylmethacrylate/polyethyleneglycol-based partially water soluble binder system for micro ceramic injection moulding

In micro powder injection moulding polyethylene-wax binder systems have been widely established for many years enabling the fabrication of dense ceramic or metal micro structured parts. With respect to complete organic moiety removal a solvent debinding step prior to thermal decomposition using hexane as organic solvent has to be applied dissolving the wax prior to thermal decomposition of the polyethylene. The development of environmentally friendly binder systems must consider the substitution of any organic solvent or even the solvent pre-debinding. In this work a modified process chain, starting with a reactive feedstock mixture consisting of a thermally curable methylmethacrylate/polymethylmethacrylate resin, low molecular mass polyethyleneglycol and submicron-sized zirconia as ceramic filler, followed by feedstock polymerization at elevated temperature, pelletizing, injection moulding, debinding and sintering, will be presented. Prior to replication important feedstock properties like temperature and solid load dependent melt viscosity as well as the real solid load was measured guaranteeing a successful mould filling. Two different debinding strategies—with and without water-assisted predebinding—were pursued and the resulting sinter part densities as well as surface qualities were compared. Zirconia test specimen parts with a density around 99 % of the theoretical density could be obtained successfully.     

Features of low-temperature oxidation of hydrogen in the medium of nitrogen,carbon dioxide,and water vapor at elevated pressures

The article discusses novel research results on combustion features of high-density Н₂/О₂ mixtures (ρ_H2 = 0.70–1.89 mol/dm³, ρ_O2 = 0.32–0.81 mol/dm³) diluted with nitrogen, carbon dioxide, or water vapor (from 46 to 76% mol.) at the uniform heating (1 K/min) of tubular reactor. Based on time dependencies of temperature increment in the reaction mixtures caused by the heat release during oxidation of H₂, it is found that the self-ignition temperature of Н₂/О₂/N₂ and Н₂/О₂/H₂O mixtures is by ≈ 30 K lower than that of the Н₂/О₂/СО₂ mixture. Unlike combustion of H₂ in the N₂ medium, in the CO₂ and H₂O media a chain-thermal explosion is observed at a certain concentration of reagents. The influencing mechanisms of diluents on the H₂ oxidation dynamics, as well as the contribution of homogeneous and heterogeneous reactions in the heat release are revealed. It is established that high heat capacity of H₂/O₂/CO₂ mixture, chemical interaction between its components, and presence of CO₂ molecules adsorbed on the reactor inner surface, are the factors determining the H₂ oxidation dynamics in CO₂ medium. At oxidation of H₂ in the H₂O medium, the process takes place against the background of water evaporation and, as a consequence, is characterized by increased heat capacity and thermal conductivity of the H₂/O₂/H₂O reaction mixture.     

Performance assessment of proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) for analysis of isobaric compounds in food-flavour applications

Characterisation of food-flavour release using quadrupole-based on-line mass spectrometers such as proton-transfer-reaction mass spectrometry (PTR-MS, or PTR-QMS) can be complicated when nominally isobaric aroma compounds are present in complex food matrices. The recent combination of PTR-MS with time-of-flight mass spectrometry (PTR-TOF-MS) offers an analytical tool potentially capable of overcoming this problem because of its enhanced mass resolution. In this context, four pairs of isobaric compounds (cis-3-hexenol and 2,3-pentanedione, benzaldehyde and m-xylene, ethyl butanoate and 2-methylbutanol, and isobutyl isopentanoate and 1-hexanol) were investigated by PTR-TOF-MS to assess its mass-resolving power for food-flavour applications. Headspace analyses of aqueous solutions containing nominally isobaric aroma compounds that are unresolvable by PTR-QMS demonstrated that the PTR-TOF-MS mass-resolving power, which is m/z-dependent, enabled discrimination between isobaric peaks at a centre of mass separation down to at least 0.030 Da. Visual discrimination between these isobaric compound peaks in the headspace of aqueous solutions down to a concentration range of a few tens of ng mL⁻¹ was also possible, enabling an empirical method for determining the limit of quantitation in solution for single compounds. PTR-TOF-MS offers distinct advantages over conventional PTR-MS for certain flavour release applications.     

In Silico Study of piRNA Interactions with the SARS-CoV-2 Genome

A prolonged pandemic with numerous human casualties requires a rapid search for means to control the various strains of SARS-CoV-2. Since only part of the human population is affected by coronaviruses, there are probably endogenous compounds preventing the spread of these viral pathogens. It has been shown that piRNA (PIWI-interacting RNAs) interact with the mRNA of human genes and can block protein synthesis at the stage of translation. Estimated the effects of piRNA on SARS-CoV-2 genomic RNA (gRNA) in silico. A cluster of 13 piRNA binding sites (BS) in the SARS-CoV-2 gRNA region encoding the oligopeptide was identified. The second cluster of BSs 39 piRNAs also encodes the oligopeptide. The third cluster of 24 piRNA BS encodes the oligopeptide. Twelve piRNAs were identified that strongly interact with the gRNA. Based on the identified functionally important endogenous piRNAs, synthetic piRNAs (spiRNAs) are proposed that will suppress the multiplication of the coronavirus even more strongly. These spiRNAs and selected endogenous piRNAs have little effect on human 17494 protein-coding genes, indicating a low probability of side effects. The piRNA and spiRNA selection methodology created for the control of SARS-CoV-2 ({"type":"entrez-nucleotide","attrs":{"text":"NC_045512.2","term_id":"1798174254","term_text":"NC_045512.2"}}NC_045512.2) can be used to control all strains of SARS-CoV-2.     

Identification of a Novel de Novo Variant in the CASZ1 Causing a Rare Type of Dilated Cardiomyopathy

A new de novo frameshift variant has been identified in the CASZ1 gene leading to severe dilated cardiomyopathy. Methods: The proband was analyzed with WES NGS, post-mortem, using dried blood spots on filters. The variant was verified with Sanger sequencing for the proband and her parents. Results: We reported a proband with a new de novo frameshift mutation, c.3781del (p.(Trp1261GlyfsTer29)), in the CASZ1 gene. The clinical presentation was similar to the severe phenotype described in previous studies. Conclusions: In this study, we described a new case with a frameshift mutation in CASZ1 causing a severe phenotype of dilated cardiomyopathy.     

Lowbush blueberries inhibit scavenger receptors CD36 and SR-A expression and attenuate foam cell formation in ApoE-deficient mice

Blueberries have recently been reported to reduce atherosclerotic lesion progression in apoE deficient (apoE(-/-)) mice. However, the underlying mechanisms are not fully understood. The objective of this study was to determine whether lowbush blueberries altered scavenger receptor expression and foam cell formation in apoE(-/-) mice. ApoE(-/-) mice were fed AIN-93 diet (CD) or CD formulated to contain 1% freeze-dried lowbush blueberries (BB) for 20 weeks. Gene expression and protein levels of scavenger receptor CD36 and SR-A in aorta and thioglycollate-elicited peritoneal macrophages (PM) were lower in mice fed BB (P < 0.05). In the second experiment, apoE(-/-) mice were fed CD or BB for 5 weeks. PM were collected and cultured. Gene expression and protein levels of CD36 and SR-A were found to be lower in PM of BB fed mice (P < 0.05). In PM from BB fed mice, fewer oxLDL-induced foam cells were formed compared to those from mice fed CD. Gene expression and protein levels of PPARγ were lower in the PM of BB fed mice (P < 0.05). Detectable isomers of hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acid (HETEs) were also lower in the PM of BB fed mice (P < 0.05 or P < 0.01). In conclusion, BB inhibited expression of the two major scavenger receptors CD36 and SR-A in PM of apoE(-/-) mice, at least in part through down-regulating PPARγ and reducing its endogenous ligands HODEs and HETEs. We proposed that BB mediated reduction of scavenger receptor expression and attenuation of oxLDL-induced foam cell formation in PM of apoE(-/-) mice are important mechanisms of the athero-protective effects of BB.     

Influence of polyols and bulking agents on flavour release from low-viscosity solutions

The release of four volatile flavour compounds (cis-3-hexen-1-ol, benzaldehyde, ethyl butanoate and butyl isovalerate) from pure water and various low-viscosity aqueous solutions (sucrose, maltitol, erythritol, polydextrose and oligofructose, each at 20% (w/w)) was investigated. Dynamic headspace concentrations of the flavour compounds at thermodynamic equilibrium were monitored by proton-transfer-reaction mass spectrometry (PTR-MS). The rheological properties of the solutions were characterised by their viscosity. Flavour release from pure water increased with increasing hydrophobicity and volatility of the flavour compounds. The highly volatile compounds were retained more extensively in the presence of sucrose, polyols and bulking agents, compared to in pure water, whereas an increase in the release of the less volatile cis-3-hexen-1-ol was observed. All aqueous solutions had similar viscosities, although bulking agent solutions tended to have higher viscosities than polyol solutions of the same concentration. A correlation between viscosity and flavour release in the low-viscosity solutions was not evident.     

Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma

Background: The possible involvement of p53 signaling, FGFR3 expression, and FGFR3 mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(−)/CR5/6(−) high-grade and low-grade NMIBC. Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and FGFR3 mutations in codons 248 and 249 were detected by real-time polymerase chain reaction. Results: The expression of p53 protein is an independent factor affecting the animals’ survival time [HR = 0.036, p = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and FGFR3 mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(−)/CR5/6(−)-relapsed noninvasive bladder cancer.