SNPs in toll-like receptor (TLR) genes as new genetic alterations associated with congenital toxoplasmosis?

Nearly 40 % of pregnant women are infected with Toxoplasma gondii. Primary infections in pregnant women result, in approximately 30–50 % of patients, in transmission of T. gondii through the placenta to the fetus and then in congenital infections with severe, sometimes fatal course. Studies still do not provide sufficient data on the genetic bases of the immunity in fetuses, newborns, and infants with congenital toxoplasmosis. Previous research showed the contribution of toll-like receptors (TLRs) to non-specific immunity against T. gondii invasion, observed in T. gondii-infected animals, especially mice. So far, the activity of TLRs in defense against T. gondii infections was observed particularly for TLR2, TLR4, and TLR9 molecules. Differential TLR activity associates with both cell types, including a variety of placental cells and stage of pregnancy. Several single-nucleotide polymorphisms (SNPs) residing in three genes encoding these receptors were reported as significant genetic modifications of TLRs associated with different pregnancy disorders. Despite those data, genetic alterations of TLRs which have contributed to innate immune response against T. gondii infections are still not precisely described. In this article, we present reasons for the research of the plausible role of SNPs residing in TLR2, TLR4, and TLR9 genes in congenital toxoplasmosis development

A Microelectronic Sensor Device Powered by a Small Implantable Biofuel Cell

Biocatalytic buckypaper electrodes modified with pyrroloquinoline quinone (PQQ)‐dependent glucose dehydrogenase and bilirubin oxidase for glucose oxidation and oxygen reduction, respectively, were prepared for their use in a biofuel cell. A small (millimeter‐scale; 2×3×2 mm3) enzyme‐based biofuel cell was tested in a model glucose‐containing aqueous solution, in human serum, and as an implanted device in a living gray garden slug (Deroceras reticulatum), producing electrical power in the range of 2–10 μW (depending on the glucose source). A microelectronic temperature‐sensing device equipped with a rechargeable supercapacitor, internal data memory and wireless data downloading capability was specifically designed for activation by the biofuel cell. The power management circuit in the device allowed the optimized use of the power provided by the biofuel cell dependent on the sensor operation activity. The whole system (power‐producing biofuel cell and power‐consuming sensor) operated autonomously by extracting electrical energy from the available environmental source, as exemplified by extracting power from the glucose‐containing hemolymph (blood substituting biofluid) in the slug to power the complete temperature sensor system and read out data wirelessly. Other sensor systems operating autonomously in remote locations based on the concept illustrated here are envisaged for monitoring different environmental conditions or can be specially designed for homeland security applications, particularly in detecting bioterrorism threats.Sluggish sensor? A microelectronic sensor device was powered by an enzyme biofuel cell implanted in a slug to operate autonomously.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152860/1/cphc201900700_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152860/2/cphc201900700.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152860/3/cphc201900700-sup-0001-misc_information.pd

Mixed infections with distinct cytomegalovirus glycoprotein B genotypes in Polish pregnant women, fetuses, and newborns

The purpose of this investigation was to describe a distribution of cytomegalovirus (CMV) single and multiple genotypes among infected pregnant women, their fetuses, and newborns coming from Central Poland, as well as congenital cytomegaly outcome. The study involved 278 CMV-seropositive pregnant women, of whom 192 were tested for viral DNAemia. Human cytomegalovirus (HCMV) genotyping was performed for 18 of 34 pregnant women carrying the viral DNA and for 12 of their 15 offspring with confirmed HCMV infections. Anti-HCMV antibodies levels were assessed by chemiluminescence immunoassay (CLIA) and enzyme-linked fluorescence assay (ELFA) tests. Viral DNA loads and genotypes were determined by real-time polymerase chain reaction (PCR) assays for the UL55 gene. In the pregnant women, we identified HCMV gB1, gB2, gB3, and gB4 genotypes. Single gB2, gB3, or gB4 genotypes were observed in 14 (77.8 %) women, while multiple gB1–gB2 or gB2–gB3 genotypes were observed in four (22.2 %). Maternal HCMV genotypes determined the genotypes identified in their fetuses and newborns (p ≤ 0.050). Half of them were infected with single HCMV gB1, gB2, or gB3 genotypes and the other half with multiple gB1–gB2 or gB2–gB3 genotypes. Single and multiple genotypes were observed in both asymptomatic and symptomatic congenital cytomegaly, although no gB3 genotype was identified among asymptomatic cases. In Central Poland, infections with single and multiple HCMV strains occur in pregnant women, as well as in their fetuses and neonates, with both asymptomatic and symptomatic infections. HCMV infections identified in mothers seem to be associated with the viral genotypes in their children

The Role of Dysregulated miRNAs in the Pathogenesis, Diagnosis and Treatment of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is an eye disease causing damage to the macular region of the retina where most of the photoreceptors responsible for central visual acuity are located. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by silent post-transcriptional gene expressions. Previous studies have shown that changes in specific miRNAs are involved in the pathogenesis of eye diseases, including AMD. Altered expressions of miRNAs are related to disturbances of regulating oxidative stress, inflammation, angiogenesis, apoptosis and phagocytosis, which are known factors in the pathogenesis of AMD. Moreover, dysregulation of miRNA is involved in drusen formation. Thus, miRNAs may be used as potential molecular biomarkers for the disease and, furthermore, tailoring therapeutics to particular disturbances in miRNAs may, in the future, offer hope to prevent irreversible vision loss. In this review, we clarify the current state of knowledge about the influence of miRNA on the pathogenesis, diagnosis and treatment of AMD. Our study material consisted of publications, which were found in PubMed, Google Scholar and Embase databases using "Age-related macular degeneration", "miRNA", "AMD biomarkers", "miRNA therapeutics" and "AMD pathogenesis" as keywords. Paper search was limited to articles published from 2011 to date. In the section "Retinal, circulating and vitreous body miRNAs found in human studies", we limited the search to studies with patients published in 2016-2021

Multi-component low and high entropy metallic coatings synthesized by pulsed magnetron sputtering

This paper presents the findings of the synthesis of multicomponent (Al, W, Ni, Ti, Nb) alloy coatings from mosaic targets. For the study, a pulsed magnetron sputtering method was employed under different plasma generation conditions: modulation frequency (10 Hz and 1000 Hz), and power (600 W and 1000 W). The processes achieved two types of alloy coatings, high entropy and classical alloys. After the deposition processes, scanning electron microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy techniques were employed to find the morphology, thickness, and chemical and phase compositions of the coatings. Nanohardness and its related parameters, namely H3.Er2, H.E, and 1.Er2H ratios, were measured. An annealing treatment was performed to estimate the stability range for the selected coatings. The results indicated the formation of as-deposited coatings exhibiting an amorphous structure as a single-phase solid solution. The process parameters had an influence on the resulting morphology-a dense and homogenous as well as a columnar morphology, was obtained. The study compared the properties of high-entropy alloy (HEA) coatings and classical alloy coatings concerning their structure and chemical and phase composition. It was found that the change of frequency modulation and the post-annealing process contributed to the increase in the hardness of the material in the case of HEA coatings

Tryptophan pathway abnormalities in a murine model of hereditary glaucoma

Background: It has been shown that a possible pathogenetic mechanism of neurodegenera-tion in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina. This study aimed to verify the hypothesis that alterations of tryptophan (TRP) metabolism in DBA/2J mice is not limited to the retina. Methods: Samples of the retinal tissue and serum were collected from DBA/2J mice (6 and 10 months old) and control C57Bl/6 mice of the same age. The concentration of TRP, KYNA, kynurenine (KYN), and 3-hydroxykynurenine (3OH-K) was measured by HPLC. The activity of indoleamine 2,3-dioxygenase (IDO) was also determined as a KYN/TRP ratio. Results: TRP, KYNA, L-KYN, and 3OH-K concentration were significantly lower in the retinas of DBA/2J mice than in C57Bl/6 mice. 3OH-K concentration was higher in older mice in both strains. Serum TRP, L-KYN, and KYNA concentrations were lower in DBA/2J than in age-matched controls. However, serum IDO activity did not differ significantly between compared groups and strains. Conclusions: Alterations of the TRP pathway seem not to be limited to the retina in the murine model of hereditary glaucoma

Tryptophan and Kynurenine Pathway Metabolites in Animal Models of Retinal and Optic Nerve Damage: Different Dynamics of Changes

Kynurenines, products of tryptophan (TRP) metabolism, display neurotoxic (e.g., 3-hydroxykynurenine; 3-HK), or neuroprotective (e.g., kynurenic acid; KYNA) properties. Imbalance between the enzymes constituting the kynurenine pathway (KP) plays a role in several disease, including neurodegeneration. In this study, we track changes in concentrations of tryptophan and its selected metabolites after damage to retinal ganglion cells and link this data with expression of KP enzymes. Brown-Norway rats were subjected to intravitreal N-methyl-D-aspartate (NMDA) injection or partial optic nerve crush (PONC). Retinas were collected 2 and 7 days after the completion of PONC or NMDA injection. Concentrations of TRP, kynurenine (KYN), and KYNA were determined by high performance liquid chromatography (HPLC). Data on gene expression in the rat retina were extracted from GEO, public microarray experiments database. Two days after NMDA injection concentration of TRP decreased, while KYN and KYNA increased. At day 7 compared to day 2 decrease of KYN, KYNA and further reduction of TRP concentration were observed, but on day 7 KYN concentration was still elevated when compared to controls. At day 2 and 7 after NMDA injection no statistically significant alterations of 3-HK were observed. TRP and 3-HK concentration was higher in PONC group than in controls. However, both KYN and KYNA were lower. At day seven concentration of TRP, 3-HK, and KYN was higher, whereas concentration of KYNA declined. In vivo experiments showed that retinal damage or optic nerve lesion affect TRP metabolism via KP. However, the pattern of changes in metabolite concentrations was different depending on the model. In particular, in PONC KYNA and KYN levels were decreased and 3-HK elevated. These observations correspond with data on expression of genes encoding KP enzymes assessed after optic nerve crush or transection. After intraorbital optic nerve crush downregulation of KyatI and KyatIII between 24 h and 3 days after procedure was observed. Kmo expression was transiently upregulated (12 h after the procedures). After intraorbital optic nerve transsection (IONT) Kmo expression was upregulated after 48 h and 7 days, KyatI and KyatIII were downregulated after 12, 48 h, 7 days and upregulated after 15 days. Collected data point to the conclusion that development of therapeutic strategies targeting the KP could be beneficial in diseases involving retinal neurodegeneration