Search

Nucleoid-associated proteins play a crucial role in the compaction and regulation of genetic material across organisms. The Sac10b family, also known as Alba, comprises widely distributed and highly conserved nucleoid-associated proteins found in archaea. Sac10b is identified as the first 10 kDa DNA-binding protein in the thermoacidophile Sulfolobus acidocaldarius. Here, we present the crystal structures of two homologous proteins, Sac10b1 and Sac10b2, as well as the Sac10b1 mutant F59A, determined at a resolution of 1.4–2.0 Å. Electron microscopic images reveal the DNA-bridging capabilities of both Sac10b1 and Sac10b2, albeit to varying extents. Analyses of crystal packing and electron microscopic results suggest that Sac10b1 facilitates cooperative DNA binding, forming extensive bridged filaments via the conserved R58 and F59 residues at the dimer-dimer interface. Substitutions at R58 or F59 of Sac10b1 attenuate end-to-end association, resulting in non-cooperative DNA binding, and formation of small, bridged DNA segments in a way similar to Sac10b2. Analytical ultracentrifuge and circular dichroism confirm the presence of thermostable, acid-tolerant dimers in both Sac10b1 and Sac10b2. These findings attest to the functional role of Sac10b in organizing and stabilizing chromosomal DNA through distinct bridging interactions, particularly under extreme growth conditions.

Background: Cognitive-behavioral therapy (CBT) and biofeedback therapy are commonly regarded as effective treatment modalities for panic disorder. The aim of this study was to establish a Taiwanese version of an integrated cognitive-behavioral and biofeedback therapy (ICB) and examine its effects on panic disorder using psychological and physiological indicators. Methods: Thirty patients with panic disorder were enrolled in this study. They were randomly assigned to either the ICB group (n = 15) or the treatment as usual (TAU) group (n = 15). The intervention consisted of six sessions, conducted once a week. Psychological indicators were measured at baseline (prior to intervention), week 3, and week 6, while physiological indicators were measured at baseline and week 6. The psychological indicators included five scales, with the Panic Disorder Severity Scale (PDSS) being the primary measure. The physiological indicators included respiratory sinus arrhythmia (RSA) and skin conductance, which respectively represent parasympathetic and sympathetic activity. Results: Considering all participants, PDSS scores significantly decreased over time, but the difference between the ICB and TAU groups did not reach statistical significance. Among the physiological indicators, resting-state RSA and RSA under relaxation showed significant between-group differences over time, with the ICB group demonstrating a more pronounced improvement in RSA. Conclusion: In the context of existing pharmacological treatments, the benefits of ICB for panic disorder may not be observable through psychological indicators. However, it can lead to enhancement of parasympathetic activity as evidenced by the physiological indicators.

Background/Purpose: Previous studies showed the association between substance use disorders (SUDs) and borderline and antisocial personality disorders. Substance abusers may have emotional, somatic and interpersonal distresses. This study aimed to investigate the associations between substance, personality and psychosocial distresses. Methods: This cross-sectional, questionnaire-based study recruited 39 individuals with heroin use disorder (HUD), 111 with methamphetamine use disorder (MUD) and 101 as the control group in a rural area of Taiwan. The Tridimensional Personality Questionnaire (TPQ) and Opiate Treatment Index were used to assess the association between personality and psychosocial conditions. Deviations of the three personality dimensions of TPQ (novelty seeking, harm avoidance, and reward dependence) could reflect eight personality patterns. Results: We found SUD was associated with high novelty seeking and harm avoidance traits and explosive (borderline) personality pattern, whereas HUD was also linked with sensitive (narcissistic) pattern. Subjects with HUD tended to have more deviant personality traits than subjects with MUD. For subjects with SUDs, all three personality dimensions and sensitive (narcissistic) personality patterns were associated with emotional and somatic distresses, and those with explosive (borderline) and sensitive (narcissistic) patterns had poor social functioning. Conclusion: Our results indicate substance abusers with high novelty seeking and harm avoidance, corresponding to explosive (borderline) or sensitive (narcissistic) patterns, to have a higher tendency to suffer from somatic and psychosocial distresses. Keywords: Heroin, Methamphetamine, Personality, Psychological adjustment

Objectives Composite diagnostic criteria alone are likely to create and introduce biases into diagnoses that subsequently have poor relationships with input symptoms. This study aims to understand the relationships between the diagnoses and the input symptoms, as well as the magnitudes of biases created by diagnostic criteria and introduced into the diagnoses of mental illnesses with large disease burdens (major depressive episodes, dysthymic disorder, and manic episodes).Settings General psychiatric care.Participants Without real-world data available to the public, 100 000 subjects were simulated and the input symptoms were assigned based on the assumed prevalence rates (0.05, 0.1, 0.3, 0.5 and 0.7) and correlations between symptoms (0, 0.1, 0.4, 0.7 and 0.9). The input symptoms were extracted from the diagnostic criteria. The diagnostic criteria were transformed into mathematical equations to demonstrate the sources of biases and convert the input symptoms into diagnoses.Primary and secondary outcomes The relationships between the input symptoms and diagnoses were interpreted using forward stepwise linear regressions. Biases due to data censoring or categorisation introduced into the intermediate variables, and the three diagnoses were measured.Results The prevalence rates of the diagnoses were lower than those of the input symptoms and proportional to the assumed prevalence rates and the correlations between the input symptoms. Certain input or bias variables consistently explained the diagnoses better than the others. Except for 0 correlations and 0.7 prevalence rates of the input symptoms for the diagnosis of dysthymic disorder, the input symptoms could not fully explain the diagnoses.Conclusions There are biases created due to composite diagnostic criteria and introduced into the diagnoses. The design of the diagnostic criteria determines the prevalence of the diagnoses and the relationships between the input symptoms, the diagnoses, and the biases. The importance of the input symptoms has been distorted largely by the diagnostic criteria.

Abstract Previously, we found that Arabidopsis plants transformed with a construct containing the promoter of Oshsp17.3 from rice fused to the β-glucuronidase gene (GUS), Oshsp17.3Pro::GUS (Oshsp17.3p), showed a GUS signal after heat shock (HS) or azetidine-2-carboxylic acid (AZC) treatment. HS and AZC trigger the heat shock response (HSR) and cytosolic protein response (CPR), respectively, in the cytosol by modulating specific heat shock factor (HSF) activity. Here we further identified that AtHSFA2 (At2g26150), AtHSFA7a (At3g51910), AtHSFB2a (At5g62020), and AtHSFB2b (At4g11660) are HS- and AZC-inducible; AtHSFA4a (At4g18880) is AZC-inducible; and AtHSFA5 (At4g13980) is less AZC- and HS-inducible. To investigate the roles of these 6 AtHSFs in the HSR or CPR, we crossed two independent Oshsp17.3p transgenic Arabidopsis plants with the AtHSF-knockout mutants athsfa2 (SALK_008978), athsfa4a (GABI_181H12), athsfa5 (SALK_004385), athsfa7a (SALK_080138), athsfb2a (SALK_137766), and athsfb2b (SALK_047291), respectively. As compared with the wild type, loss-of-function mutation of AtHSFA2, AtHSFA4a, and AtHSFA7a decreased HS and AZC responsiveness, so these 3 AtHSFs are essential for the HSR and CPR. In addition, loss-of-function results indicated that AthsfB2b is involved in regulating the HSR in Arabidopsis. Furthermore, analysis of the relative GUS activity of two double knockout mutants, athsfA2/athsfA4a and athsfA2/athsfA7a, revealed that AtHSFA2, AtHSFA4a, and AtHSFA7a function differentially in the HSR and CPR. Transcription profiling in athsf mutants revealed positive or negative transcriptional regulation among the 6 AtHSFs in Arabidopsis plants under HS and AZC conditions. Tunicamycin treatment demonstrated that these 6 AtHSFs are not involved in the unfolded protein response.

Abstract Ketol-acid reductoisomerase (KARI) is a bifunctional enzyme in the second step of branched-chain amino acids biosynthetic pathway. Most KARIs prefer NADPH as a cofactor. However, KARI with a preference for NADH is desirable in industrial applications including anaerobic fermentation for the production of branched-chain amino acids or biofuels. Here, we characterize a thermoacidophilic archaeal Sac-KARI from Sulfolobus acidocaldarius and present its crystal structure at a 1.75-Å resolution. By comparison with other holo-KARI structures, one sulphate ion is observed in each binding site for the 2′-phosphate of NADPH, implicating its NADPH preference. Sac-KARI has very high affinity for NADPH and NADH, with K M values of 0.4 μM for NADPH and 6.0 μM for NADH, suggesting that both are good cofactors at low concentrations although NADPH is favoured over NADH. Furthermore, Sac-KARI can catalyze 2(S)-acetolactate (2S-AL) with either cofactor from 25 to 60 °C, but the enzyme has higher activity by using NADPH. In addition, the catalytic activity of Sac-KARI increases significantly with elevated temperatures and reaches an optimum at 60 °C. Bi-cofactor utilization and the thermoactivity of Sac-KARI make it a potential candidate for use in metabolic engineering or industrial applications under anaerobic or harsh conditions.

The Sso7c4 from Sulfolobus solfataricus forms a dimer, which is believed to function as a chromosomal protein involved in genomic DNA compaction and gene regulation. Here, we present the crystal structure of wild-type Sso7c4 at a high resolution of 1.63 Å, showing that the two basic C-termini are disordered. Based on the fluorescence polarization (FP) binding assay, two arginine pairs, R11/R22' and R11'/R22, on the top surface participate in binding DNA. As shown in electron microscopy (EM) images, wild-type Sso7c4 compacts DNA through bridging and bending interactions, whereas the binding of C-terminally truncated proteins rigidifies and opens DNA molecules, and no compaction of the DNA occurs. Moreover, the FP, EM and fluorescence resonance energy transfer (FRET) data indicated that the two basic and flexible C-terminal arms of the Sso7c4 dimer play a crucial role in binding and bending DNA. Sso7c4 has been classified as a repressor-like protein because of its similarity to Escherichia coli Ecrep 6.8 and Ecrep 7.3 as well as Agrobacterium tumefaciens ACCR in amino acid sequence. Based on these data, we proposed a model of the Sso7c4-DNA complex using a curved DNA molecule in the catabolite activator protein-DNA complex. The DNA end-to-end distance measured with FRET upon wild-type Sso7c4 binding is almost equal to the distance measured in the model, which supports the fidelity of the proposed model. The FRET data also confirm the EM observation showing that the binding of wild-type Sso7c4 reduces the DNA length while the C-terminal truncation does not. A functional role for Sso7c4 in the organization of chromosomal DNA and/or the regulation of gene expression through bridging and bending interactions is suggested.

Background Restenosis is a common complication after balloon angioplasty. A number of cytokines, chemotactic factors and growth factors may be involved. Several antioxidants have been shown to inhibit intimal thickening after balloon injury in hyperlipidemic animals. Objectives The effects of magnolol on the expression of monocyte chemotactic protein-1 (MCP-1) and intimal response in balloon injured aorta of cholesterol-fed rabbits were investigated. Methods Male New Zealand white rabbits were fed a 2 % high cholesterol (HC) diet together with daily intramuscular injection of either 1 μg/kg B.W. of magnolol (HC-M, n = 10) or vehicle (propylene glycol) as a control (HC-C, n = 10) for a total of 6 weeks. Another 10 rabbits fed a regular diet also served as a control (C) group. A balloon denudation of abdominal aorta was performed in each group at the end of the third week. The aortas were harvested at the end of 6 weeks. Results Magnolol treatment significantly inhibited Cu2+-induced LDL oxidation in cholesterol-fed rabbits and reduced atheroma formation [atheroma area ratio: 0.10 ± 0.03 (HC-M) versus 0.33 ± 0.07 (HC-C), p < 0.05] in thoracic aortas without lowering serum cholesterol. The intimal response was significantly attenuated in the HC-M rabbits when compared to those of the HC-C group [intimal thickness: 88.95 ± 14.91 μm (HC-M) versus 198.02 ± 20.35 μm (HC-C), p < 0.05; intimal area: 278.21 ± 43.16 × 103μm2 (HC-M) versus 642.70 ± 65.01 × 103μm2 (HC-C), p < 0.05]. The MCP-1 mRNA and protein expression were reduced in the HC-M group compared to the HC-C and C groups. Conclusion The inhibitory effects on intimal hyperplasia and MCP-1 expression might be attributed to the antioxidant capacity of magnolol instead of lowering serum cholesterol. Magnolol may offer some protection against postangioplasty restenosis. [ABSTRACT FROM AUTHOR]