Comparison of the monomer structure of the FMN-binding protein from <i>Desulfovibrio vulgaris</i> obtained by NMR and molecular dynamics simulation approaches

<div><p>Flavin mononucleotide (FMN)-binding proteins (FBPs) play an important role in the electron transport process in bacteria. In this study, the structures of the FBP from <i>Desulfovibrio vulgaris</i> (<i>Dv</i>FBP) (Miyazaki F) were compared between those obtained experimentally by nuclear magnetic resonance (NMR) spectroscopy and those derived from molecular dynamics simulations (MDSs). A high-residue root of mean square deviation (RMSD) was observed in residues located at both sides of the wings (Gly22, Glu23, Asp24, Ala59, Arg60, Asp61, Glu62, Gly75, Arg76, Asn77, Gly78 and Pro79), while a low-residue RMSD was found in residues located in a hollow of the structure (Asn12, Glu13, Gly14, Val15, Val16, Asn30, Thr31, Trp32, Asn33, Ser34, Gly69, Ser70, Arg71 and Lys72). Inter-planar angles between the Phe7 and Iso and between the Phe7 and Trp106 residues were remarkably different between the MDS- and NMR-derived <i>Dv</i>FBP structures. Distribution of the torsion angles around the covalent bonds in the aliphatic chain of FMN was similar in the MDS- and NMR-derived structures, except for those around the C1′–C2′ and C5′–O5′ bonds. Hydrogen bond formation between IsoO2 and the Gly49 or Gly50 peptide NH was formed in both the NMR- and MDS-derived structures. Overall, the MDS-derived structures were found to be considerably different from the NMR-derived structures, which must be considered when the photoinduced electron transfer in flavoproteins is analysed with MDS-derived structures.</p></div

Relationship among sympathetic nerve activity at 2 min before defecation, symptoms, and quality of life.

Sympathetic nerve activity was evaluated by the sum of Δlow frequency/high frequency (LF/HF). (a) Intensity of abdominal pain, (b) satisfaction levels of defecation, (c) gastrointestinal symptom rating scale (GSRS) diarrhea score, (d) GSRS constipation score, (e) the Japanese version of the 8-item Short-Form Health Survey (SF-8) role physical, and (f) the SF-8 role emotional score were significantly correlated with the sum of ΔLF/HF at 2 min before defecation. Data were analyzed by Spearman test.</p

Autonomic nervous system activity in healthy controls and patients with IBS.

Autonomic nervous system activity in healthy controls and patients with IBS.</p

The graph of obtained data and measuring method of ANS activity.

(a) The real graph of obtained data about autonomic nervous system (ANS) activity and life events. The results of low frequency (LF) (yellow line) and high frequency (HF) (green line) represented in a graph. Life events, such as defecation and eating (the enclosed area with orange line) and period with positive symptoms (the enclosed area with pink line), were recorded. (b) Measuring method of ANS activity. The baseline LF/HF was defined as the value included in the range of the mean ± 2 standard deviations (dashed line) of LF/HF measured in the period with no symptoms. The sum of LF/HF was the area under the curve of LF/HF measured in the period with positive symptoms (upward diagonal). The sum of ΔLF/HF was the sum of variation from the mean value of baseline measured in the period with positive symptoms (dots). The maximum variation of ΔLF/HF indicated the maximum variation from the mean value of baseline measured in the period with positive symptoms (arrow). HF was analyzed in the same way.</p

Background characteristics.

Background characteristics.</p

T-shirt-type wearable device and smartphone application software.

Heart rate variability (HRV) was measured using a T-shirt wearable device attached to a transmitter in front of the T-shirt. The HRV data were transferred and recorded on a smartphone using Bluetooth. At the same time, life events, such as abdominal symptoms, defecation, eating, and awakening or sleep, were recorded in real time using a smartphone application software during HRV recording.</p

Autonomic nervous activities before and after defecation.

(a, b) Changes in sympathetic nerve activities before and after defecation were evaluated by the sum of Δlow frequency/high frequency (LF/HF) and the sum of LF/HF, respectively. (c, d) Changes in parasympathetic nerve activities before and after defecation were evaluated by the sum of ΔHF and the sum of HF, respectively. Data represents the median. Statistical significance was calculated by Mann–Whitney test (*p < 0.05).</p

Hypothesized mechanism of exacerbated symptoms and increased sympathetic nerve activity before defecation.

The stress of abdominal pain activates the amygdala to release corticotrophin-releasing hormone (CRH), resulting in further exacerbation of abdominal pain by increasing colonic motility. These cascades “exacerbate the circle of pain.” Two minutes before defecation, the stress also activates sympathetic nerves as a stress response against abdominal pain. Increased sympathetic nerve activity can decrease colonic motility, which may have a protective role to hold back the defecation. This situation may be under competition between the accelerator of colonic motility caused by CRH and the brake caused by sympathetic nerve activation.</p

Data sheet of study participants.

(CSV)</p

Risk of pancreatitis after pancreatic duct guidewire placement during endoscopic retrograde cholangiopancreatography

<div><p>Background & aims</p><p>Advanced techniques have been developed to overcome difficult cannulation cases in endoscopic retrograde cholangiopancreatography (ERCP). Pancreatic duct guidewire placement method (PGW) is performed in difficult cannulation cases; it is possible that it places patients at risk of post-ERCP pancreatitis (PEP). The mechanism of PEP is still unclear, but pancreatic duct pressure and injury of pancreatic duct are known causes of PEP. Therefore, we hypothesized a relationship between pancreatic duct diameter and PEP and predicted that PGW would increase the risk of PEP in patients with non-dilated pancreatic ducts. This study aimed to investigate whether PGW increased the risk of PEP in patients with pancreatic duct diameter ≤ 3 mm.</p><p>Methods</p><p>We analyzed 332 patients with pancreatic duct ≤ 3 mm who performed first time ERCP session. The primary endpoint was the rate of adverse event of PEP. We evaluated the risk of PEP in patients who had undergone PGW compared to those who had not, using the inverse probability of treatment weighting (IPTW) analysis.</p><p>Results</p><p>PGW was found to be an independent risk factor for PEP by univariate analysis (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.12–5.38; p = 0.03) after IPTW in patients with pancreatic duct diameter ≤ 3 mm. Adjusted for all covariates, PGW remained an independent risk factor for PEP (OR, 3.12; 95% CI, 1.33–7.33; p = 0.01).</p><p>Conclusion</p><p>Our results indicate that PGW in patients with pancreatic duct diameter ≤ 3 mm increases the risk of PEP.</p></div