Search

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG tract expansion in the huntingtin gene (HTT). HD is characterized by involuntary movements, cognitive decline, and behavioral changes. Pathologically, patients with HD show selective striatal neuronal vulnerability at the early disease stage, although the mutant protein is ubiquitously expressed. Activation of the immune system and glial cell-mediated neuroinflammatory responses are early pathological features and have been found in all neurodegenerative diseases (NDDs), including HD. However, the role of inflammation in HD, as well as its therapeutic significance, has been less extensively studied compared to other NDDs. This review highlights the significantly elevated levels of inflammatory proteins and cellular markers observed in various HD animal models and HD patient tissues, emphasizing the critical roles of microglia, astrocytes, and oligodendrocytes in mediating neuroinflammation in HD. Moreover, it expands on recent discoveries related to the peripheral immune system's involvement in HD. Although current immunomodulatory treatments and inflammatory biomarkers for adjunctive diagnosis in HD are limited, targeting inflammation in combination with other therapies, along with comprehensive personalized treatment approaches, shows promising therapeutic potential. [ABSTRACT FROM AUTHOR]

We previously demonstrated that Streptococcus oligofermentans suppressed the growth of Streptococcus mutans, the primary cariogenic pathogen, by producing hydrogen peroxide ([H.sub.2][O.sub.2]) through lactate oxidase activity. In this study, we found that the lox mutant of S. oligofermentans regained the inhibition while growing on peptone-rich plates. Further studies demonstrated that the [H.sub.2][O.sub.2] produced on peptone by S. oligofermentans was mainly derived from seven L-amino acids, i.e., L-aspartic acid, L-tryptophan, L-lysine, L-Asoleucine, L-arginine, L-asparagine, and Lglutamine, indicating the possible existence of L-amino acid oxidase (LAAO) that can produce H2O2 from L-amino acids. Through searching the S. oligofermentans genome for open reading frames with a conserved flavin adenine dinucleotide binding motif that exists in the known LAAOs, including those of snake venom, fungi, and bacteria, a putative LAAO gene, assigned as aaoSo, was cloned and overexpressed in Escherichia coli. The purified protein, SO-LAAO, showed a molecular mass of 43 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and catalyzed H2O2 formation from the seven L-amino acids determined above, thus confirming its LAAO activity. The SO-LAAO identified in S. oligofermentans differed evidently from the known LAAOs in both substrate profile and sequence, suggesting that it could represent a novel LAAO. An aaoSo mutant of S. oligofermentans did lose H2O2 formation from the seven L-amino acids, further verifying its function as an LAAO. Furthermore, the inhibition by S. oligofermentans of S. mutans in a peptone-rich mixed-species biofilm was greatly reduced for the aaoSo mutant, indicating the gene's importance in interspecies competition.

Summary: Natural transformation increases the genetic diversity of bacteria, but is costly and must be strictly controlled. We previously found that deletion of ccpA, a key regulator of carbon catabolite repression (CCR), reduced transformation efficiency of Streptococcus oligofermentans, the current work further investigated the regulatory mechanisms of CcpA. The competence operon comCDE is subjected to basal and autoregulatory transcription. A luciferase reporter detected a transcriptional readthrough (TRT) from the upstream tRNAArg into the comCDE operon, which was induced by L‐arginine. Insertion of the Escherichia coli T1T2 terminator downstream of tRNAArg abolished TRT, and reduced the basal comCDE transcription by 77% and also the transformation efficiency. Deletion of ccpA increased tRNAArg TRT and tRNAArg‐comCDE polycistronic transcript by twofold. An in vitro transcription assay determined that CcpA promoted the transcription termination of tRNAArg TRT, and RNA EMSA and SPR assays detected equal binding affinity of CcpA to both the RNA and DNA of tRNAArg. These results indicate that CcpA controls the basal comCDE transcription by post‐transcriptional actions. Overexpression of comDE or its phospho‐mimicking mutant comDED58E reduced transformation efficiency, indicating that excessive ComE impairs competence development. CCR‐regulated competence was further confirmed by higher tRNAArg TRT but lower transformation efficiency in galactose than in glucose. [ABSTRACT FROM AUTHOR]

Objective To explore whether there was an increased secretion of cystatin C (Cys C) in twin pregnancy. Methods Patients with a total of 281 singleton pregnancies (including 38 patients with preeclampsia) and 72 twin pregnancies, as well as 42 patients who were not pregnant, were included in this study. We tested levels of serum Cys C, creatinine, and uric acid, along with the estimated glomerular filtration rate (eGFR), in different groups. Results The levels of serum Cys C in all 3 trimesters for women with twin pregnancy were much higher than those in the corresponding trimesters for women with singleton pregnancy. However, we observed little change in eGFR in the corresponding trimesters. Cys C/eGFR in the second and third trimester of twin pregnancy increased, compared with the corresponding trimesters of women with singleton pregnancy. Levels of serum Cys C were higher in the third trimester in women with twin pregnancy than that in patients with preeclampsia. Also, Cys C/eGFR in the third trimester of twin pregnancy was close to the level observed in patients with preeclampsia. Conclusions Increased secretion of Cys C could contribute to the elevated serum Cys C levels that we observed in twin pregnancy. [ABSTRACT FROM AUTHOR]

The article presents a case study which focused on the detection of bilirubin crystals in a preterm male infant with sepsis and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Topics discussed include the medical history of the patient's mother, the results of the physical and laboratory tests performed such as blood gas analysis and red blood cell count, and the poor patient outcome recorded despite treatment with acid correction and blood transfusion.

Streptococcus oligofermentans is a newly characterized species belonging to the mitis group of oral streptococci. So far no correlation has been demonstrated between S. oligofermentans and dental caries. Furthermore, a reverse correlation has been observed between the number of S. oligofermentans and the number of Streptococcus mutans, a major cariogenic pathogen, in the oral cavity. These properties suggest that S. oligofermentans may have a potential to be used as a ‘probiotics’ for caries prevention. In this study, we aim to establish a genetic system in S. oligofermentans to further study the biology of this new species. Using homologous regions of the comCDE locus in other streptococci, the comC gene was isolated and sequenced. A synthetic competence-stimulating peptide (CSP) was synthesized and shown to be able to effectively induce competence in S. oligofermentans. This CSP-induced transformation system in S. oligofermentans was used to construct green fluorescent protein ( gfp) and luciferase ( luc) reporter systems, both of which are driven by the lactate dehydrogenase ( ldh) promoter. These reporter systems were further shown to be highly expressed in planktonic and biofilm cells, suggesting that these reporter systems can be used in future ecological studies of S. oligofermentans. [ABSTRACT FROM AUTHOR]

Aquaporins are integral membrane proteins that facilitate the diffusion of water and other small, uncharged solutes across the cellular membrane and are widely distributed in organisms from humans to bacteria. However, the characteristics of prokaryotic aquaporins remain largely unknown. We investigated the distribution and sequence characterization of aquaporins in prokaryotic organisms and summarized the transport characteristics, physiological functions, and regulatory mechanisms of prokaryotic aquaporins. Aquaporin homologues were identified in 3315 prokaryotic genomes retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, but the protein clustering pattern is not completely congruent with the phylogeny of the species that carry them. Moreover, prokaryotic aquaporins display diversified aromatic/arginine constriction region (ar/R) amino acid compositions, implying multiple functions. The typical water and glycerol transport characterization, physiological functions, and regulations have been extensively studied in Escherichia coli AqpZ and GlpF. A Streptococcus aquaporin has recently been verified to facilitate the efflux of endogenous H2O2, which not only contributes to detoxification but also to species competitiveness, improving our understanding of prokaryotic aquaporins. Furthermore, recent studies revealed novel regulatory mechanisms of prokaryotic aquaporins at post-translational level. Thus, we propose that intensive investigation on prokaryotic aquaporins would extend the functional categories and working mechanisms of these ubiquitous, intrinsic membrane proteins. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs) are transmembrane proteins widely distributed in various organisms, and they facilitate bidirectional diffusion of water and uncharged solutes. The catalase-negative bacterium Streptococcus oligofermentans produces the highest H 2 O 2 levels reported to date, which has to be exported to avoid oxidative stress. Here, we report that a S. oligofermentans aquaporin functions as a peroxiporin facilitating bidirectional transmembrane H 2 O 2 transport. Knockout of this aquaporin homolog, So-AqpA, reduced H 2 O 2 export by ∼50% and increased endogenous H 2 O 2 retention, as indicated by the cellular H 2 O 2 reporter HyPer. Heterologous expression of So-aqpA accelerated exogenous H 2 O 2 influx into Saccharomyces cerevisiae and Escherichia coli cells, indicating that So-AqpA acts as an H 2 O 2 -transferring aquaporin. Alanine substitution revealed Phe-40 as a key residue for So-AqpA-mediated H 2 O 2 transport. Northern blotting, qPCR, and luciferase reporter assays disclosed that H 2 O 2 induces a >10-fold expression of So-aqpA Super-resolution imaging showed that H 2 O 2 treatment increases So-AqpA protein molecules per cell by 1.6- to 3-fold. Inactivation of two redox-regulatory transcriptional repressors, PerR and MntR, reduced H 2 O 2 -induced So-aqpA expression to 1.8- and 4-fold, respectively. Electrophoretic mobility shift assays determined that MntR, but not PerR, binds to the So-aqpA promoter, indicating that MntR directly regulates H 2 O 2 -induced So-aqpA expression. Importantly, So-aqpA deletion decreased oxic growth and intraspecies competition and diminished the competitive advantages of S. oligofermentans over the caries pathogen Streptococcus mutans Of note, So-aqpA orthologs with the functionally important Phe-40 are present in all streptococci. Our work has uncovered an intrinsic, H 2 O 2 -inducible bacterial peroxiporin that has a key physiological role in H 2 O 2 detoxification in S. oligofermentans ., (© 2019 Tong et al.)

Commensal oral streptococci play critical roles in oral biofilm formation and promote dental health by competing with, and antagonizing the growth of, pathogenic organisms, such as Streptococcus mutans. Efficient utilization of the spectrum of carbohydrates in the oral cavity by commensal streptococci is essential for their persistence, and yet very little is known about the regulation of carbohydrate catabolism by these organisms. Carbohydrate catabolite repression (CCR) in the abundant oral commensal Streptococcus gordonii strain DL-1 was investigated using the exo-β-D-fructosidase gene (fruA) and a fructose/mannose sugar:phosphotransferase (PTS) enzyme II operon (levDEFG) as model systems. Functional studies confirmed the predicted roles of FruA and LevD in S. gordonii. ManL, the AB domain of a fructose/mannose-type enzyme II PTS permease, contributed to utilization of glucose, mannose, galactose, and fructose and exerted primary control over CCR of the fruA and levD operons. Unlike in S. mutans, ManL-dependent CCR was not sugar specific, and galactose was very effective at eliciting CCR in S. gordonii. Inactivation of the apparent ccpA homologue of S. gordonii actually enhanced CCR of fruA and levD, an effect likely due to its demonstrated role in repression of manL expression. Thus, there are some similarities and fundamental differences in CCR control mechanisms between the oral pathogen S. mutans and the oral commensal S. gordonii that may eventually be exploited to enhance the competitiveness of health-associated commensals in oral biofilms.

Objective: Streptococcus oligofermentans was a newly characterized streptococcal species, which we isolated from dental plaques of carious-free humans. Our previous work indicated that in aerobic environments, it produced, as well as survived high concentration of hydrogen peroxide (4.4 mmol/L). This study analyzed the function of dpr gene in hydrogen peroxide tolerance of Streptococcus oligofermentans., Methods: Cloned and expressed the dpr gene, and characterized Dpr protein. We constructed the dpr mutant strain of S. oligfermentans and detected its susceptivity to hydrogen peroxide. Furthermore, S. oligofermentans dpr gene was cloned into S. mutans, and its susceptivity to hydrogen peroxide was tested., Results: S. oligofermentans dpr mutant strain was much more susceptive to hydrogen peroxide than the wild type, and introduction of its dpr gene into S. mutans could enhance the later' s hydrogen peroxide tolerant ability. Dpr proteins could bind irons, but not to DNA. [Conclusion] dpr gene of S. oligofermentans has significant role in hydrogen peroxide tolerance of the host strain, while Dpr protein may have other oxidant-damage protective mechanisms except for iron-binding.