Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

Objective: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. Methods: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. Results: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. Conclusion: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development

Indole and 3-indolylacetonitrile inhibit spore maturation in Paenibacillus alvei

<p>Abstract</p> <p>Background</p> <p>Bacteria use diverse signaling molecules to ensure the survival of the species in environmental niches. A variety of both Gram-positive and Gram-negative bacteria produce large quantities of indole that functions as an intercellular signal controlling diverse aspects of bacterial physiology.</p> <p>Results</p> <p>In this study, we sought a novel role of indole in a Gram-positive bacteria <it>Paenibacillus alvei </it>that can produce extracellular indole at a concentration of up to 300 μM in the stationary phase in Luria-Bertani medium. Unlike previous studies, our data show that the production of indole in <it>P. alvei </it>is strictly controlled by catabolite repression since the addition of glucose and glycerol completely turns off the indole production. The addition of exogenous indole markedly inhibits the heat resistance of <it>P. alvei </it>without affecting cell growth. Observation of cell morphology with electron microscopy shows that indole inhibits the development of spore coats and cortex in <it>P. alvei</it>. As a result of the immature spore formation of <it>P. alvei</it>, indole also decreases <it>P. alvei </it>survival when exposed to antibiotics, low pH, and ethanol. Additionally, indole derivatives also influence the heat resistance; for example, a plant auxin, 3-indolylacetonitrile dramatically (2900-fold) decreased the heat resistance of <it>P. alvei</it>, while another auxin 3-indoleacetic acid had a less significant influence on the heat resistance of <it>P. alvei</it>.</p> <p>Conclusions</p> <p>Together, our results demonstrate that indole and plant auxin 3-indolylacetonitrile inhibit spore maturation of <it>P. alvei </it>and that 3-indolylacetonitrile presents an opportunity for the control of heat and antimicrobial resistant spores of Gram-positive bacteria.</p

Surgical anatomy of the uncinate process and transverse foramen determined by computer tomography

Study Design Computed tomography–based cohort study. Objective Although there are publications concerning the relationship between the vertebral artery and uncinate process, there is no practical guide detailing the dimensions of this region to use during decompression of the intervertebral foramen. The purpose of this study is to determine the anatomic parameters that can be used as a guide for thorough decompression of the intervertebral foramen. Methods Fifty-one patients with three-dimensional computed tomography scans of the cervical spine from 2003 to 2012 were included. On axial views, we measured the distance from the midline to the medial and lateral cortices of the pedicle bilaterally from C3 to C7. On coronal reconstructed views, we measured the minimum height of the uncinate process from the cranial cortex of the pedicle adjacent to the posterior cortex of vertebral body and the maximal height of the uncinate process from the cranial cortex of the pedicle at the midportion of the vertebral body bilaterally from C3 to C7. Results The mean distances from midline to the medial and lateral cortices of the pedicle were 10.1 ± 1.3 mm and 13.9 ± 1.5 mm, respectively. The mean minimum height of the uncinate process from the cranial cortex of the pedicle was 4.6 ± 1.6 mm and the mean maximal height was 6.1 ± 1.7 mm. Conclusions Our results suggest that in most cases, one can thoroughly decompress the intervertebral foramen by removing the uncinate out to 13 mm laterally from the midline and 4 mm above the pedicle without violating the transverse foramen

Structural basis for recognition of L-lysine, L-ornithine, and L-2,4-diamino butyric acid by lysine cyclodeaminase

L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes ??-deamination of L-lysine into L-pipecolic acid using ??-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, ??-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with NAD+, (ii) a ternary complex with NAD+ and L-pipecolic acid, (iii) a ternary complex with NAD+ and L-proline, and (iv) a ternary complex with NAD+ and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida. In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that NAD+ is initially converted into NADH and then reverted back into NAD+ at a late stage of the reaction

Simultaneous VLBI Astrometry of H2O and SiO Masers toward the Semiregular Variable R Crateris

We obtained, for the first time, astrometrically registered maps of the 22.2 GHz H2O and 42.8, 43.1, and 86.2 GHz SiO maser emission toward the semiregular b-type variable (SRb) R Crateris, at three epochs (2015 May 21, and 2016 January 7 and 26) using the Korean Very-long-baseline Interferometry Network. The SiO masers show a ring-like spatial structure, while the H2O maser shows a very asymmetric one-side outflow structure, which is located at the southern part of the ring-like SiO maser feature. We also found that the 86.2 GHz SiO maser spots are distributed in an inner region, compared to those of the 43.1 GHz SiO maser, which is different from all previously known distributions of the 86.2 GHz SiO masers in variable stars. The different distribution of the 86.2 GHz SiO maser seems to be related to the complex dynamics caused by the overtone pulsation mode of the SRb R Crateris. Furthermore, we estimated the position of the central star based on the ring fitting of the SiO masers, which is essential for interpreting the morphology and kinematics of a circumstellar envelope. The estimated stellar coordinate corresponds well to the position measured by Gaia

Efficacy of quick Sequential Organ Failure Assessment with lactate concentration for predicting mortality in patients with community-acquired pneumonia in the emergency department

Objective Community-acquired pneumonia (CAP) is a major cause of sepsis, and sepsis-related acute organ dysfunction affects patient mortality. Although the quick Sequential Organ Failure Assessment (qSOFA) is a new screening tool for patients with suspected infection, its predictive value for the mortality of patients with CAP has not been validated. Lactate concentration is a valuable biomarker for critically ill patients. Thus, we investigated the predictive value of qSOFA with lactate concentration for in-hospital mortality in patients with CAP in the emergency department (ED). Methods From January 2015 to June 2015, 443 patients, who were diagnosed with CAP in the ED, were retrospectively analyzed. We defined high qSOFA or lactate concentrations as a qSOFA score ≥2 or a lactate concentration >2 mmol/L upon admission at the ED. The primary outcome was all-cause in-hospital mortality. Results Among the 443 patients, 44 (9.9%) died. Based on the receiver operating characteristic (ROC) analysis, the areas under the curves for the prediction of mortality were 0.720, 0.652, and 0.686 for qSOFA, CURB-65 (confusion, urea, respiratory rate, blood pressure, and age), and Pneumonia Severity Index, respectively. The area under the ROC curve of qSOFA was lower than that of SOFA (0.720 vs. 0.845, P=0.004). However, the area under the ROC curve of qSOFA with lactate concentration was not significantly different from that of SOFA (0.828 vs. 0.845, P=0.509). The sensitivity and specificity of qSOFA with lactate concentration were 71.4% and 83.2%, respectively. Conclusion qSOFA with lactate concentration is a useful and practical tool for the early prediction of in-hospital mortality among patients with CAP in the ED

The discovery and characterization of tungsten insertase in tungsten cofactor biosynthesis

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