Role of GntR family regulatory gene SCO1678 in gluconate metabolism in streptomyces coelicolor M145

Here we report functional characterization of the Streptomyces coelicolor M145 gene SCO1678, which encodes a GntR-like regulator of the FadR subfamily. Bioinformatic analysis suggested that SCO1678 is part of putative operon (gnt) involved in gluconate metabolism. Combining the results of SCO1678 knockout, transcriptional analysis of gnt operon, and Sco1678 protein-DNA electromobility shift assays, we established that Sco1678 protein controls the gluconate operon. It does so via repression of its transcription from a single promoter located between genes SCO1678 and SCO1679. The knockout also influenced, in a medium-dependent manner, the production of secondary metabolites by S. coelicolor. In comparison to the wild type, on gluconate-containing minimal medium, the SCO1678 mutant produced much less actinorhodin and accumulated a yellow-colored pigment, likely to be the cryptic polyketide coelimycin. Possible links between gluconate metabolism and antibiotic production are discussed

Editors' Note

We the editors of Korean Anthropology Review: A journal of Korean anthropology in translation (KAR) are presenting our fourth volume. This time we have selected articles that focus on space and place as anthropological problems. Anthropologists have long recognized space and place as objects of, and participants in, cultural meaning construction, and this volumes contributors explore how spatial phenomena are constructed and contested. The fourth volume also expands the geographical scope of our journal by including pieces that deal not only with South Korea but also present research conducted in another locale, Japan. Our goal is to showcase the geographical diversity of South Korean anthropologists interests, and we intend to continue translating articles that look beyond Korea for future volumes

Glutamate Concentration in the Serum of Patients with Schizophrenia

Glutamate is the major neurotransmitter with multiple functions in the central nervous system. Glutamate-mediated excitotoxicity is involved in the pathophysiological processes in schizophrenia. The purpose of this study was to determine the concentration of glutamate in the serum of patients with paranoid schizophrenia compared with healthy individuals, and depending on the duration of the schizophrenic process and leading clinical symptoms. We investigated the level of glutamate in the serum of 158 patients with paranoid schizophrenia and 94 healthy persons. Higher concentrations of glutamate in schizophrenic patients compared with healthy persons have been found. The maximum concentrations of glutamate were detected in patients with disease duration of more than ten years. Glutamate level in the serum does not depend on the prevailing negative or positive clinical symptoms. The increased concentration of glutamate can hypothetically contribute to dopaminergic and glutamatergic imbalance, leading to the development of psychotic symptoms and cognitive dysfunction

Light-induced sulfur transport inside single-walled carbon nanotubes

This article belongs to the Section 2D and Carbon Nanomaterials.Filling of single-walled carbon nanotubes (SWCNTs) and extraction of the encapsulated species from their cavities are perspective treatments for tuning the functional properties of SWCNT-based materials. Here, we have investigated sulfur-modified SWCNTs synthesized by the ampoule method. The morphology and chemical states of carbon and sulfur were analyzed by transmission electron microscopy, Raman scattering, thermogravimetric analysis, X-ray photoelectron and near-edge X-ray absorption fine structure spectroscopies. Successful encapsulation of sulfur inside SWCNTs cavities was demonstrated. The peculiarities of interactions of SWCNTs with encapsulated and external sulfur species were analyzed in details. In particular, the donor–acceptor interaction between encapsulated sulfur and host SWCNT is experimentally demonstrated. The sulfur-filled SWCNTs were continuously irradiated in situ with polychromatic photon beam of high intensity. Comparison of X-ray spectra of the samples before and after the treatment revealed sulfur transport from the interior to the surface of SWCNTs bundles, in particular extraction of sulfur from the SWCNT cavity. These results show that the moderate heating of filled nanotubes could be used to de-encapsulate the guest species tuning the local composition, and hence, the functional properties of SWCNT-based materials.This work was supported by the Russian Science Foundation (Project 18-72-00017), the bilateral Program “Russian-Germany Laboratory at BESSY II” in the part of XPS and C K-edge NEXAFS measurements, and shared research center SSTRC on the basis of the Novosibirsk VEPP-4 - VEPP-2000 complex at BINP SB RAS, using equipment supported by project RFMEFI62119X0022 in the part of S K-edge NEXAFS measurements. R.A. acknowledges the support from the Spanish Ministerio de Economia y Competitividad (MAT2016-79776-P, AEI/FEDER, EU), from the European Union’s Horizon 2020 programme under the project “ESTEEM3” (823717) and from the Government of Aragon and the European Social Fund under the project “Construyendo Europa desde Aragon” 2014–2020 (grant number E13_17R, FEDER, EU).Peer reviewe

Association of PIP4K2A Polymorphisms with Alcohol Use Disorder

Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. Methods: 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CIIIA). Results: Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. Conclusions: For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula

Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin

Unlike the majority of actinomycete secondary metabolic pathways, the biosynthesis of peptidoglycan glycosyltransferase inhibitor moenomycin in Streptomyces ghanaensis does not involve any cluster-situated regulators (CSRs). This raises questions about the regulatory signals that initiate and sustain moenomycin production. We now show that three pleiotropic regulatory genes for Streptomyces morphogenesis and antibiotic production—bldA, adpA and absB—exert multi-layered control over moenomycin biosynthesis in native and heterologous producers. The bldA gene for tRNALeuUAA is required for the translation of rare UUA codons within two key moenomycin biosynthetic genes (moe), moeO5 and moeE5. It also indirectly influences moenomycin production by controlling the translation of the UUA-containing adpA and, probably, other as-yet-unknown repressor gene(s). AdpA binds key moe promoters and activates them. Furthermore, AdpA interacts with the bldA promoter, thus impacting translation of bldA-dependent mRNAs—that of adpA and several moe genes. Both adpA expression and moenomycin production are increased in an absB-deficient background, most probably because AbsB normally limits adpA mRNA abundance through ribonucleolytic cleavage. Our work highlights an underappreciated strategy for secondary metabolism regulation, in which the interaction between structural genes and pleiotropic regulators is not mediated by CSRs. This strategy might be relevant for a growing number of CSR-free gene clusters unearthed during actinomycete genome mining

Study of early onset schizophrenia:Associations of GRIN2A and GRIN2B polymorphisms

Background: Schizophrenia is a complex mental disorder with a high heritability. Dysfunction of the N-methyl-D-aspartate (NMDA)-type glutamate receptors may be involved in the pathogenesis of schizophrenia. In this study, we examined the contribution of GRIN2A and GRIN2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2A/2B) polymorphisms to the clinical features of schizophrenia, such as the leading symptoms, the type of course, and the age of onset. Methods: A population of 402 Russian patients with schizophrenia from the Siberian region was investigated. Genotyping of seventeen single-nucleotide polymorphisms (SNPs) in GRIN2A and GRIN2B was performed using QuantStudio™ 3D Digital PCR System Life Technologies amplifier using TaqMan Validated SNP Genotyping Assay kits (Applied Biosystems). The results were analyzed using Chi-square and the Fisher’s exact tests. Results: We found an association of GRIN2A rs7206256 and rs11644461 and GRIN2B rs7313149 with the early onset (before the age of 18 years old) schizophrenia. We did not reveal any associations of GRIN2A and GRIN2B polymorphisms with leading (positive vs. negative) symptoms or type of course (continuous vs. episodic) of schizophrenia. Conclusions: In the study, we confirmed the involvement of the GRIN2A and GRIN2B genes in the early onset of schizophrenia in a Russian population of the Siberian region

Genetic polymorphisms of PIP5K2A and course of schizophrenia

BackgroundSchizophrenia is a severe highly heritable mental disorder. The clinical heterogeneity of schizophrenia is expressed in the difference in the leading symptoms and course of the disease. Identifying the genetic variants that affect clinical heterogeneity may ultimately reveal the genetic basis of the features of schizophrenia and suggest novel treatment targets. PIP5K2A (Phosphatidylinositol-4-Phosphate 5-Kinase Type II Alpha) has been investigated as a potential susceptibility gene for schizophrenia.MethodsIn this work, we studied the possible association between eleven polymorphic variants of PIP5K2A and the clinical features of schizophrenia in a population of 384 white Siberian patients with schizophrenia. Genotyping was carried out on QuantStudio 5 Real-Time PCR System with a TaqMan Validate SNP Genotyping Assay (Applied Biosystems, USA).ResultsPIP5K2A rs8341 (chi (2)=6.559, p=0.038) and rs946961 (chi (2)=5.976, p=0.049) showed significant association with course of schizophrenia (continuous or episodic). The rs8341*CT (OR=1.63, 95% CI: 1.04-2.54) and rs946961*CC (OR=5.17, 95% CI: 1.20-22.21) genotypes were associated with a continuous type of course, while the rs8341*TT genotype (OR=0.53, 95% CI: 0.29-0.97) was associated with an episodic type of course of schizophrenia. Therefore rs8341*TT genotype presumably has protective effect against the more severe continuous course of schizophrenia compared to the episodic one.ConclusionsOur experimental data confirm that PIP5K2A is a genetic factor influencing the type of course of schizophrenia in Siberian population. Disturbances in the phosphatidylinositol pathways may be a possible reason for the transition to a more severe continuous course of schizophrenia

Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia

Objective: Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic-induced HPRL. Methods: We recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ2 test. Results: A comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ2 = 3.70; p =.05; odds ratio [OR] = 1.30 [0.99–1.69]). Conclusion: The functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia

5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia

Background Tardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia. Methods A set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4. Results Statistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results. Conclusion We found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor