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1.
J Lipid Res ; 61(5): 722-733, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32165394

RESUMO

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6-2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Lipase/química , Lipase/metabolismo , Propionibacteriaceae/enzimologia , Sequência de Aminoácidos , Sequência Conservada , Lisofosfatidilcolinas/metabolismo , Modelos Moleculares , Multimerização Proteica , Estrutura Quaternária de Proteína , Especificidade da Espécie
2.
Brain Topogr ; 33(2): 208-220, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32034577

RESUMO

Inhibitory dysfunction is closely associated to post-traumatic stress disorder (PTSD). The present study investigated the neurophysiological evidence for and the brain regions related to inhibitory dysfunction in PTSD. Fifty patients with PTSD and 63 healthy controls (HCs) participated in a Go/Nogo task combined with electroencephalographic recordings. The N2-P3 complexes of event-related potentials (ERPs) elicited during the Nogo condition were compared between groups. Participants underwent structural magnetic resonance imaging to examine cortical volumes and completed questionnaires. Correlations between altered ERPs and cortical volumes of regions of interest as well as psychological symptoms were analysed. Nogo-N2 latencies at five electrode sites (Fz, FCz, Cz, CPz, and Pz) were significantly delayed in patients with PTSD compared to HCs. Nogo-N2 latency had a significant negative correlation with the volume of gyrus in the inferior frontal cortex, orbitofrontal cortex, amygdala, and medial prefrontal cortex. Nogo-N2 latency was significantly and positively correlated with catastrophizing, anxiety, and perceived threat. These findings show inhibitory dysfunction in patients with PTSD, reflected by the delay in Nogo-N2 latencies. They also indicate that Nogo-N2 latencies are associated with smaller cortical volumes responsible for inhibition as well as with major symptoms of PTSD.


Assuntos
Encéfalo/fisiopatologia , Potenciais Evocados , Inibição Psicológica , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Mapeamento Encefálico , Eletroencefalografia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Tempo de Reação/fisiologia
3.
Biochem J ; 473(1): 55-66, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26487697

RESUMO

The DJ-1/ThiJ/PfpI superfamily is a group of proteins found in diverse organisms. This superfamily includes versatile proteins, such as proteases, chaperones, heat-shock proteins and human Parkinson's disease protein. Most members of the DJ-1/ThiJ/PfpI superfamily are oligomers and are classified into subfamilies depending on discriminating quaternary structures (DJ-1, YhbO and Hsp types). SAV1875, a conserved protein from Staphylococcus aureus, is a member of the YhbO-type subfamily. However, its structure and function remain unknown. Thus, to understand the function and activity mechanism of this protein, the crystal structure of SAV1875 from S. aureus was determined. The overall fold of SAV1875 is similar to that observed for the DJ-1/ThiJ/PfpI superfamily. The cysteine residue located in the dimeric interface (Cys(105)) forms a catalytic triad with His(106) and Asp(77), and it is spontaneously oxidized to Cys(105)-SO2H in the crystal structure. To study the oxidative propensity of Cys(105) and the corresponding functional differences with changes in cysteine oxidation state, the crystal structures of SAV1875 variants E17N, E17D and C105D, and over-oxidized SAV1875 were determined. We identified SAV1875 as a novel member of the YhbO-type subfamily exhibiting chaperone function. However, if SAV1875 is over-oxidized further with H2O2, its chaperone activity is eliminated. On the basis of our study, we suggest that SAV1875 functions as a chaperone and the redox state of Cys(105) may play an important role.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Staphylococcus aureus/metabolismo , Cristalografia por Raios X , Oxirredução , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
4.
Sensors (Basel) ; 16(6)2016 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-27271634

RESUMO

This paper proposes a novel method of estimating walking distance based on a precise counting of walking strides using insole sensors. We use an inertial triaxial accelerometer and eight pressure sensors installed in the insole of a shoe to record walkers' movement data. The data is then transmitted to a smartphone to filter out noise and determine stance and swing phases. Based on phase information, we count the number of strides traveled and estimate the movement distance. To evaluate the accuracy of the proposed method, we created two walking databases on seven healthy participants and tested the proposed method. The first database, which is called the short distance database, consists of collected data from all seven healthy subjects walking on a 16 m distance. The second one, named the long distance database, is constructed from walking data of three healthy subjects who have participated in the short database for an 89 m distance. The experimental results show that the proposed method performs walking distance estimation accurately with the mean error rates of 4.8% and 3.1% for the short and long distance databases, respectively. Moreover, the maximum difference of the swing phase determination with respect to time is 0.08 s and 0.06 s for starting and stopping points of swing phases, respectively. Therefore, the stride counting method provides a highly precise result when subjects walk.

5.
J Biol Chem ; 288(8): 6004-13, 2013 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-23297406

RESUMO

Bacterial chromosomal toxin-antitoxin (TA) systems have been proposed not only to play an important role in the stress response, but also to be associated with antibiotic resistance. Here, we identified the chromosomal HP0892-HP0893 TA proteins in the gastric pathogen, Helicobacter pylori, and structurally characterized their protein-protein interaction. Previously, HP0892 protein was suggested to be a putative TA toxin based on its structural similarity to other RelE family TA toxins. In this study, we demonstrated that HP0892 binds to HP0893 strongly with a stoichiometry of 1:1, and HP0892-HP0893 interaction occurs mainly between the N-terminal secondary structure elements of HP0892 and the C-terminal region of HP0893. HP0892 cleaved mRNA in vitro, preferentially at the 5' end of A or G, and the RNase activity of HP0892 was inhibited by HP0893. In addition, heterologous expression of HP0892 in Escherichia coli cells led to cell growth arrest, and the cell toxicity of HP0892 was neutralized by co-expression with HP0893. From these results and a structural comparison with other TA toxins, it is concluded that HP0892 is a toxin with intrinsic RNase activity and HP0893 is an antitoxin against HP0892 from a TA system of H. pylori. It has been known that hp0893 gene and another TA antitoxin gene, hp0895, of H. pylori, are both genomic open reading frames that correspond to genes that are potentially expressed in response to interactions with the human gastric mucosa. Therefore, it is highly probable that TA systems of H. pylori are involved in virulence of H. pylori.


Assuntos
Proteínas de Bactérias/química , Regulação Bacteriana da Expressão Gênica , Helicobacter pylori/metabolismo , Sequência de Aminoácidos , Antitoxinas/química , Sítios de Ligação , Cromatografia em Gel , Clonagem Molecular , Escherichia coli/metabolismo , Regulação da Expressão Gênica , Helicobacter pylori/patogenicidade , Humanos , Espectroscopia de Ressonância Magnética/métodos , Modelos Moleculares , Conformação Molecular , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Ribonucleases/metabolismo , Homologia de Sequência de Aminoácidos , Virulência
6.
Biochim Biophys Acta ; 1834(12): 2579-90, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24060809

RESUMO

The toxin-antitoxin (TA) systems widely spread among bacteria and archaea are important for antibiotic resistance and microorganism virulence. The bacterial kingdom uses TA systems to adjust the global level of gene expression and translation through RNA degradation. In Helicobacter pylori, only two TA systems are known thus far. Our previous studies showed that HP0894-HP0895 acts as a TA system and that HP0894 exhibits intrinsic RNase activity. However, the precise molecular basis for interaction with substrate or antitoxin and the mechanism of mRNA cleavage remain unclear. Therefore, in an attempt to shed some light on the mechanism behind the TA system of HP0894-HP0895, here we present the crystal structures of apo- and metal-bound H. pylori 0894 at 1.28Å and 1.89Å, respectively. Through the combined approach of structural analysis and structural homology search, the amino acids involved in mRNase active site were monitored and the reorientations of different residues were discussed in detail. In the mRNase active site of HP0894 toxin, His84 acts as a catalytic residue and reorients itself to exhibit this type of activity, acting as a general acid in an acid-base catalysis reaction, while His47 and His60 stabilize the transition state. Lys52, Glu58, Asp64 and Arg80 have phosphate binding and specific sequence recognition. Glu58 also acts as a general base, and substrate reorientation is caused by Phe88. Based on experimental findings, a model for antitoxin binding could be suggested.


Assuntos
Proteínas de Bactérias/química , Cobre/química , Helicobacter pylori/enzimologia , Ribonucleases/química , Apoenzimas/química , Apoenzimas/genética , Apoenzimas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Catálise , Domínio Catalítico , Cobre/metabolismo , Cristalografia por Raios X , Helicobacter pylori/genética , Ligação Proteica , Estabilidade de RNA/fisiologia , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleases/genética , Ribonucleases/metabolismo
7.
Nucleic Acids Res ; 40(9): 4216-28, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22241770

RESUMO

VapD-like virulence-associated proteins have been found in many organisms, but little is known about this protein family including the 3D structure of these proteins. Recently, a relationship between the Cas2 family of ribonucleases associated with the CRISPR system of microbial immunity and VapD was suggested. Here, we show for the first time the structure of a member of the VapD family and present a relationship of VapD with Cas2 family and toxin-antitoxin (TA) systems. The crystal structure of HP0315 from Helicobacter pylori was solved at a resolution of 2.8 Å. The structure of HP0315, which has a modified ferredoxin-like fold, is very similar to that of the Cas2 family. Like Cas2 proteins, HP0315 shows endoribonuclease activity. HP0315-cleaved mRNA, mainly before A and G nucleotides preferentially, which means that HP0315 has purine-specific endoribonuclease activity. Mutagenesis studies of HP0315 revealed that D7, L13, S43 and D76 residues are important for RNase activity, in contrast, to the Cas2 family. HP0315 is arranged as an operon with HP0316, which was found to be an antitoxin-related protein. However, HP0315 is not a component of the TA system. Thus, HP0315 may be an evolutionary intermediate which does not belong to either the Cas2 family or TA system.


Assuntos
Proteínas de Bactérias/química , Endorribonucleases/química , Helicobacter pylori/enzimologia , Glicoproteínas de Membrana/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico , Endorribonucleases/genética , Endorribonucleases/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Multimerização Proteica , Estabilidade Proteica , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos
8.
Phytother Res ; 28(12): 1867-72, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25219371

RESUMO

In traditional oriental medicine, apricot (Prunus armeniaca L.) seed has been used to treat skin diseases such as furuncle, acne vulgaris and dandruff, as well as coughing, asthma and constipation. This study describes the phytochemical profile and antimicrobial potential of the essential oil obtained from apricot seeds (Armeniacae Semen). The essential oil isolated by hydrodistillation was analysed by gas chromatography-mass spectroscopy. Benzaldehyde (90.6%), mandelonitrile (5.2%) and benzoic acid (4.1%) were identified. Disc diffusion, agar dilution and gaseous contact methods were performed to determine the antimicrobial activity against 16 bacteria and two yeast species. The minimum inhibitory concentrations ranged from 250 to 4000, 500 to 2000 and 250 to 1000 µg/mL for Gram-positive bacteria, Gram-negative bacteria and yeast strains, respectively. The minimum inhibitory doses by gaseous contact ranged from 12.5 to 50, 12.5 to 50 and 3.13 to 12.5 mg/L air for Gram-positive bacteria, Gram-negative bacteria and yeast strains, respectively. The essential oil exhibited a variable degree of antimicrobial activity against a range of bacteria and yeasts tested.


Assuntos
Anti-Infecciosos/farmacologia , Óleos Voláteis/farmacologia , Prunus/química , Sementes/química , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Leveduras/efeitos dos fármacos
9.
J Microbiol Biotechnol ; 33(1): 28-34, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36457189

RESUMO

Endoribonuclease YbeY is specific to the single-stranded RNA of ribosomal RNAs and small RNAs. This enzyme is essential for the maturation and quality control of ribosomal RNA in a wide range of bacteria and for virulence in some pathogenic bacteria. In this study, we determined the crystal structure of YbeY from Staphylococcus aureus at a resolution of 1.9 Å in the presence of zinc chloride. The structure showed a zinc ion at the active site and two molecules of tricarboxylic acid citrate, which were also derived from the crystallization conditions. Our structure showed the zinc ion-bound local environment at the molecular level for the first time. Molecular comparisons were performed between the carboxylic moieties of citrate and the phosphate moiety of the RNA backbone, and a model of YbeY in complex with a single strand of RNA was subsequently constructed. Our findings provide molecular insights into how the YbeY enzyme recognizes single-stranded RNA in bacteria.


Assuntos
Endorribonucleases , Staphylococcus aureus , Endorribonucleases/genética , Staphylococcus aureus/genética , Virulência , RNA , Zinco
10.
J Biol Chem ; 286(6): 4842-53, 2011 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-21123184

RESUMO

Bacterial toxin-antitoxin (TA) systems are associated with many important cellular processes including antibiotic resistance and microorganism virulence. Here, we identify and structurally characterize TA molecules from the gastric pathogen, Helicobacter pylori. The HP0894 protein had been previously suggested, through our structural genomics approach, to be a putative toxin molecule. In this study, the intrinsic RNase activity and the bacterial cell growth-arresting activity of HP0894 were established. The RNA-binding surface was identified at three residue clusters: (Lys(8) and Ser(9)), (Lys(50)-Lys(54) and Glu(58)), and (Arg(80) and His(84)-Phe(88)). In particular, the -UA- and -CA- sequences in RNA were preferentially cleaved by HP0894, and residues Lys(52), Trp(53), and Ser(85)-Lys(87) were observed to be the main contributors to sequence recognition. The action of HP0894 could be inhibited by the HP0895 protein, and the HP0894-HP0895 complex formed an oligomer with a binding stoichiometry of 1:1. The N and C termini of HP0894 constituted the binding sites to HP0895. In contrast, the unstructured C-terminal region of HP0895 was responsible for binding to HP0894 and underwent a conformational change in the process. Finally, DNA binding activity was observed for both HP0895 and the HP0894-0895 complex but not for HP0894 alone. Taken together, it is concluded that the HP0894-HP0895 protein couple is a TA system in H. pylori, where HP0894 is a toxin with an RNase function, whereas HP0895 is an antitoxin functioning by binding to both the toxin and DNA.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Helicobacter pylori/metabolismo , Complexos Multiproteicos/metabolismo , Multimerização Proteica/fisiologia , Ribonucleases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Helicobacter pylori/genética , Complexos Multiproteicos/genética , Estrutura Terciária de Proteína , Ribonucleases/genética
11.
J Affect Disord ; 306: 167-173, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35314247

RESUMO

OBJECTIVES: Gene-Environment (G × E) interaction is of increasing importance in understanding the pathophysiology of posttraumatic stress disorder (PTSD). This study investigated the interaction effect of childhood traumatic experience and epigenetic methylation of brain-derived neurotrophic factor (BDNF) and a possible moderating effect of oxytocin receptor (OXTR) gene rs53576. METHODS: Ninety-nine patients with PTSD and 81 healthy controls (HCs) were recruited. Clinical assessments, including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. BDNF methylation and OXTR genotyping (A vs. G allele) were conducted through blood sampling. A two-way multivariate analysis and a moderated regression analysis were conducted to investigate the moderating effect of the OXTR gene on the relationship between CTQ and BDNF methylation. RESULTS: As for the HC group, the interaction effect of the CTQ and OXTR genotype was significant on BDNF methylation, and the moderation model showed that CTQ and OXTR group are significant predictors of BDNF methylation. In the G-OXTR type, the high CTQ group showed a greater BDNF methylation level. As for the PTSD group, no interaction or moderation effects were found. LIMITATIONS: The present study did not control the dosage, duration of medications, and different trauma types and the assessment of childhood trauma was based on self-report. CONCLUSIONS: These results suggested that childhood traumatic experience showed a significant impact on BDNF methylation, and OXTR genes have a moderating effect on this epigenetic mechanism in people who have experienced the childhood traumatic episodes.


Assuntos
Experiências Adversas da Infância , Fator Neurotrófico Derivado do Encéfalo , Epigênese Genética , Receptores de Ocitocina , Fator Neurotrófico Derivado do Encéfalo/genética , Metilação de DNA , Humanos , Receptores de Ocitocina/genética
12.
Clin Psychopharmacol Neurosci ; 20(2): 292-299, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35466100

RESUMO

Objective: Patients with post-traumatic stress disorder (PTSD) showed inconsistencies in their cortisol level, an index of the hypothalamic-pituitary-adrenal axis function. This study examined the relationship between dissociation, childhood trauma, and morning cortisol levels in PTSD patients. Methods: This study included 69 (23 males and 46 females) patients and 82 (22 males and 60 females) healthy controls (HCs). Clinical assessments, including the Childhood Trauma Questionnaire (CTQ) and Peri-traumatic Dissociative Experiences Questionnaire scores, and morning cortisol levels were evaluated. The morning cortisol levels were compared between PTSD with high dissociation and low dissociation (PTSD-LD) groups. The effect of CTQ subtype on morning cortisol levels was analyzed. Results: The PTSD with high dissociation group showed significantly lower cortisol levels than that of the PTSD-LD and HC groups. A significant inverse correlation was found between cortisol levels and dissociation. A significant positive correlation was found between dissociation and physical abuse and sexual abuse scores. Morning cortisol levels showed a significant positive correlation with emotional abuse, emotional neglect, and physical neglect, respectively. There was no moderating or mediating effect of CTQ on the relationship between cortisol level and dissociation. Conclusion: These findings suggest that dissociation is a significant factor related to hypocortisolism in PTSD patients. Additionally, basal morning cortisol levels and dissociation scores were closely associated with childhood trauma.

13.
Psychiatry Investig ; 19(10): 857-865, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36327966

RESUMO

OBJECTIVE: This study aimed to explore the relationship between childhood physical abuse and suicidal ideation considering the effects of genetic and environmental factors in patients with post-traumatic stress disorder (PTSD) by focusing on brain-derived neurotrophic factor (BDNF) polymorphism and social support, respectively. METHODS: One-hundred fourteen patients with PTSD and 94 healthy controls (HCs) were genotyped with respect to BDNF Val66Met polymorphism. All participants underwent psychological assessments. The hierarchical regression analysis and the simple slope analysis were conducted. RESULTS: As for patients with PTSD, the moderation effect of BDNF polymorphism was significant but not for social support. Specifically, the BDNF Val/Val genotype worked as a risk factor and strengthens the relationship between childhood physical abuse and suicidal ideation. As for the HCs, the significant moderation effect was found only in social support, but not for BDNF polymorphism. The relationship between childhood physical abuse and suicidal ideation was weakened for the HCs with high social support. CONCLUSION: This study demonstrated a significant BDNF genetic vulnerability for suicide in patients with PTSD who experienced childhood physical abuse. Our results suggested that social support provided a mitigating effect on the relationship between childhood physical abuse and suicidal ideation only in the HCs.

14.
Front Psychiatry ; 12: 613735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841200

RESUMO

Objective: This study examined the relationship of childhood physical abuse, posttraumatic stress disorder (PTSD), depression, and suicide in patients with PTSD through path analysis. Materials and Methods: A total of 114 patients with PTSD (36 men and 78 women) were recruited and completed psychological assessments including the Childhood Trauma Questionnaire, the scale for suicidal ideation, the clinician-administered PTSD scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the PTSD checklist, and the Hospital Anxiety and Depression Scale. Structural equation modeling was used to evaluate the results. We developed a model including childhood physical abuse experience as the causal variable, suicidal ideation as a result variable, and PTSD and depression as mediation variables. PTSD symptoms were divided into four clusters [intrusion, avoidance, negative cognition and mood, and altered arousal and reactivity (hyperarousal)] to determine predictive power for suicide. Results: PTSD symptoms fully mediated the relationship between childhood physical abuse and suicidal ideation. Furthermore, PTSD symptoms fully mediated the relationship between childhood physical abuse and depression. Among the PTSD symptoms, hyperarousal was the only symptom cluster that mediated the relationship between childhood physical abuse and suicidal ideation. The symptom clusters of negative cognition and mood as well as hyperarousal mediated the relationship between childhood physical abuse and depression. Conclusions: This study presents a link between childhood physical abuse and current symptoms in patients with PTSD, and highlights specific PTSD symptom clusters (i.e., hyperarousal, negative cognition and mood) that may increase the risk for psychopathology later in life.

15.
Front Behav Neurosci ; 15: 663052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149370

RESUMO

The present study aimed to investigate the possible influence of childhood trauma and its interaction effect with 10 single-nucleotide polymorphisms (SNPs) of the FK506-binding protein 51 (FKBP5) gene on brain volume in non-clinical individuals. One hundred forty-four non-clinical volunteers (44 men and 100 women) were genotyped with respect to 10 variants (rs9296158, rs3800373, rs1360780, rs9470080, rs4713916, rs4713919, rs6902321, rs56311918, rs3798345, and rs9380528) of FKBP5. Participants underwent magnetic resonance imaging (MRI) scan and psychological assessments such as the childhood Trauma Questionnaire (CTQ), Hospital Anxiety and Depression Scale, rumination response scale, and quality of life assessment instrument. Individuals with the high CTQ score showed enlarged volume of the left orbitofrontal cortex (OFC) if they have childhood trauma-susceptible genotype of FKBP5 rs3800373, rs1360780, rs4713916, rs4713919, rs6902321, and rs3798345 and enlarged volume of the left middle temporal gyrus (MTG) if they have childhood trauma-susceptible genotype of FKBP5 rs3800373, rs1360780, rs4713916, and rs3798345. Among those with the childhood trauma-susceptible genotype, the left OFC and left MTG showed significant negative correlations with positive feelings about life, and the left OFC showed significant positive correlations with negative cognition. This is one of the few studies to identify the volume alteration of the left OFC and the left MTG for the FKBP5 gene-childhood trauma interaction in non-clinical individuals.

16.
J Microbiol ; 59(6): 584-589, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33877576

RESUMO

The SbcCD complex is an essential component of the DNA double-strand break (DSB) repair system in bacteria. The bacterial SbcCD complex recognizes and cleaves the DNA ends in DSBs by ATP-dependent endo- and exonuclease activities as an early step of the DNA repair process. SbcD consists of nuclease, capping, and helix-loop-helix domains. Here, we present the crystal structure of a SbcD fragment from Staphylococcus aureus, which contained nuclease and capping domains, at a resolution of 2.9 Å. This structure shows a dimeric assembly similar to that of the corresponding domains of SbcD from Escherichia coli. The S. aureus SbcD fragment exhibited endonuclease activities on supercoiled DNA and exonuclease activity on linear and nicked DNA. This study contributes to the understanding of the molecular basis for how bacteria can resist sterilizing treatment, causing DNA damage.


Assuntos
Proteínas de Bactérias/química , Desoxirribonucleases/química , Staphylococcus aureus/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico , Cristalização , Quebras de DNA de Cadeia Dupla , Reparo do DNA , DNA Bacteriano/genética , Desoxirribonucleases/genética , Desoxirribonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Conformação Proteica , Domínios Proteicos , Staphylococcus aureus/química , Staphylococcus aureus/genética
17.
Chemotherapy ; 56(2): 153-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20407243

RESUMO

BACKGROUND: This study was performed to determine the extended spectrum of quinolone resistance caused by increased mutations within the target enzymes of quinolones. METHODS: The minimum inhibitory concentrations (MICs) for ciprofloxacin, sparfloxacin, trovafloxacin and DW286 were determined against 98 ciprofloxacin-resistant Staphylococcus aureus strains. Also, PCR-amplified grlA, grlB, gyrA and gyrB DNA fragments were sequenced and amino acid changes were analyzed. RESULTS: The MIC(50) values of quinolones decreased with later-generation compounds, i.e. >or=64 microg/ml for ciprofloxacin, 16 microg/ml for sparfloxacin, 2 microg/ml for trovafloxacin and 0.25 microg/ml for DW286. Combinations of amino acid changes within GrlA (Ser-80, Tyr-83 or Glu-84), GrlB (Pro-451, Pro-585 or Asp-432) and GyrA (Ser-84, Ser-85 or Glu-88) were constructed. The combination of Ser-80-->Phe within GrlA and Ser-84-->Leu within GyrA was the fundamental combination in alterations involved in ciprofloxacin resistance, and additional alterations extended quinolone resistance. CONCLUSION: A larger number of alterations within GrlA and GyrA further extended the spectrum of quinolone resistance.


Assuntos
Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Sequência de Aminoácidos , DNA Girase/genética , DNA Bacteriano , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Testes de Sensibilidade Microbiana , Mutação , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Staphylococcus aureus/enzimologia , Staphylococcus aureus/genética , Transativadores/genética
18.
Mol Cells ; 43(8): 694-704, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32694241

RESUMO

HslUV is a bacterial heat shock protein complex consisting of the AAA+ ATPase component HslU and the protease component HslV. HslV is a threonine (Thr) protease employing the N-terminal Thr residue in the mature protein as the catalytic residue. To date, HslUV from Gram-negative bacteria has been extensively studied. However, the mechanisms of action and activation of HslUV from Gram-positive bacteria, which have an additional N-terminal sequence before the catalytic Thr residue, remain to be revealed. In this study, we determined the crystal structures of HslV from the Gram-positive bacterium Staphylococcus aureus with and without HslU in the crystallization conditions. The structural comparison suggested that a structural transition to the symmetric form of HslV was triggered by ATP-bound HslU. More importantly, the additional N-terminal sequence was cleaved in the presence of HslU and ATP, exposing the Thr9 residue at the N-terminus and activating the ATP-dependent protease activity. Further biochemical studies demonstrated that the exposed N-terminal Thr residue is critical for catalysis with binding to the symmetric HslU hexamer. Since eukaryotic proteasomes have a similar additional N-terminal sequence, our results will improve our understanding of the common molecular mechanisms for the activation of proteasomes.


Assuntos
Proteases Dependentes de ATP/metabolismo , Proteínas de Choque Térmico/metabolismo , Modelos Moleculares , Conformação Proteica , Staphylococcus aureus
19.
Brain Behav ; 10(8): e01733, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618128

RESUMO

INTRODUCTION: Suicidal behavior of post-traumatic stress disorder (PTSD) patients is influenced by genetic and environmental factors. The catechol-O-methyltransferase (COMT) gene has been known to be associated with suicidal ideation. The present study aimed to explore the relationship of COMT polymorphism, childhood trauma, and suicidal ideation in patients with PTSD. METHODS: Fifty patients with PTSD and 62 healthy controls (HCs) were recruited, and COMT variants rs4680 and rs4633 were genotyped through peripheral blood. Psychological assessments such as the childhood trauma questionnaire (CTQ), the scale for suicidal ideation, the clinician-administered PTSD scale for DSM-5, and a PTSD checklist were administered. A regression analysis, the Johnson-Neyman technique, and a two-way analysis of covariance were conducted. RESULTS: Interaction of COMT polymorphism (rs4680, rs4633) and childhood emotional abuse (subscale of CTQ) predicted suicidal ideation in patients with PTSD. Patients with the rs4680 Val/Val genotype, compared to Met carriers genotype, showed higher suicidal ideation when childhood emotional abuse was high. Patients with the rs4633 CC genotype, compared to T carriers genotype, showed higher suicidal ideation when childhood emotional abuse was high. CONCLUSION: Our results suggest that vulnerability to suicide could be increased in the Val/Val genotype of COMT rs4680 and the CC genotype of rs4633 in patients with PTSD. Moreover, PTSD group with high childhood emotional abuse demonstrated a significantly higher suicidal ideation than did those with low childhood emotional abuse.


Assuntos
Catecol O-Metiltransferase , Transtornos de Estresse Pós-Traumáticos , Ideação Suicida , Catecol O-Metiltransferase/genética , Criança , Genótipo , Humanos , Polimorfismo Genético , Transtornos de Estresse Pós-Traumáticos/genética
20.
Psychiatry Investig ; 16(10): 718-727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31587532

RESUMO

OBJECTIVE: The aim of this study is to examine social functioning in patients with schizophrenia and bipolar disorder and explore the psychological and neurophysiological predictors of social functioning. METHODS: Twenty-seven patients with schizophrenia and thirty patients with bipolar disorder, as well as twenty-five healthy controls, completed measures of social functioning (questionnaire of social functioning), neurocognition (Verbal fluency, Korean-Auditory Verbal Learning Test), and social cognition (basic empathy scale and Social Attribution Task-Multiple Choice), and the childhood trauma questionnaire (CTQ). For neurophysiological measurements, mismatch negativity and heart rate variability (HRV) were recorded from all participants. Multiple hierarchical regression was performed to explore the impact of factors on social functioning. RESULTS: The results showed that CTQ-emotional neglect significantly predicted social functioning in schizophrenia group, while HRV-high frequency significantly predicted social functioning in bipolar disorder patients. Furthermore, emotional neglect and HRV-HF still predicted social functioning in all of the subjects after controlling for the diagnostic criteria. CONCLUSION: Our results implicated that even though each group has different predictors of social functioning, early traumatic events and HRV could be important indicators of functional outcome irrespective of what group they are.

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