Structural Properties of CXCL4L1 and Its Recognition of the CXCR3 N-Terminus.

Chemokine CXCL4L1, a homologue of CXCL4, is a more potent antiangiogenic ligand. Its structural property is correlated with the downstream receptor binding. The two chemokines execute their functions by binding the receptors of CXCR3A and CXCR3B. The receptors differ by an extra 51-residue extension in the CXCR3B N-terminus. To understand the binding specificity, a GB1 protein scaffold was used to carry different CXCR3 extracellular elements, and artificial CXCL4 and CXCL4L1 monomers were engineered for the binding assay. We first characterized the molten globule property of CXCL4L1. The structural property causes the CXCL4L1 tetramer to dissociate into monomers in low concentrations, but native CXCL4 adopts a stable tetramer structure in solution. In the titration experiments, the combination of the CXCR3A N-terminus and receptor extracellular loop 2 provided moderate and comparable binding affinities to CXCL4 and CXCL4L1, while sulfation on the CXCR3A N-terminal tyrosine residues provided binding specificity. However, the CXCR3B N-terminal extension did not show significant enhancement in the binding of CXCL4 or CXCL4L1. This result indicates that the tendency to form a chemokine monomer and the binding affinity together contribute the high antiangiogenic activity of CXCL4L1.

Portable lysis apparatus for rapid single-step DNA extraction of Bacillus subtilis.

AIMS: To demonstrate and characterize a portable lysis apparatus for rapid single-step bacterial DNA extraction. METHODS AND RESULTS: Our portable lysis apparatus employed a novel design consisting of an annular piezo-element with perforated diaphragm. Using Bacillus subtilis as target bacteria, our portable lysis apparatus was able to achieve a normalized percent lysis as high as 66% within 30 s. This is comparable to that by microprobe ultrasonication and almost 7 times higher than that by conventional bead beating. The effect from adding glass beads was predictable. However, the results from the addition of sodium dodecyl sulphate (SDS) were counter-intuitive because a further increase from 0·5 to 1% concentration reduced the lysis performance. The portable lysis apparatus is also at least 1·5-5 times more power efficient than microprobe ultrasonication. CONCLUSIONS: Our portable lysis apparatus is capable of rapidly extracting bacterial DNA and is more power efficient than microprobe ultrasonication. The addition of glass beads or SDS concentration (up to 0·5%) improves its performance. SIGNIFICANCE AND IMPACT OF THE STUDY: The portable lysis apparatus provides a standalone, rapid, low cost and power efficient way of obtaining genomic constituents prior to a variety of bioassays used in the field of environmental, biomedical and other applied microbiology.

Frequency of FMR1 premutation carriers and rate of expansion to full mutation in a retrospective diagnostic FMR1 Korean sample.

Detection of female premutation (PM) carriers of fragile X syndrome may be important in that a PM allele from the mother can expand to a full mutation (FM) when transmitted to the fetus. Although the PM carrier frequency might be different in varying populations, there is a little data on the Korean population. Furthermore, the risks of expansion to FM have not been studied in Korean PM carriers. In this retrospective study, we estimated the female PM carrier frequency and the risks of expansion to FM in Korean diagnostic samples collected for FMR1 gene testing. Of 10,241 pre-conceptional or pregnant women, 13 PM [1 in 788; 95% confidence interval (CI), 1/1,250-1/455] and 75 intermediate allele carriers (1 in 137; 95% CI, 1/172-1/110) were identified. In 26 prenatal diagnoses cases, the PM allele was transmitted to the fetus in 13 pregnancies (50%), and five of these expanded to FM. All of the maternal alleles exceeding 70 repeats expanded to FM. In conclusion, the PM frequency in Korean diagnostic samples was lower than that reported in Western populations, while the risk for FM expansion in alleles exceeding 70 repeats might be higher than expected based upon previous reports.

A transverse bunch by bunch feedback system for Pohang Light Source upgrade.

The Pohang Light Source upgrade (PLS-II) project has successfully upgraded the Pohang Light Source (PLS). The main goals of the PLS-II project are to increase the beam energy to 3 GeV, increase the number of insertion devices by a factor of two (20 IDs), increase the beam current to 400 mA, and at the same time reduce the beam emittance to below 10 nm by using the existing PLS tunnel and injection system. Among 20 insertion devices, 10 narrow gap in-vacuum undulators are in operation now and two more in-vacuum undulators are to be installed later. Since these narrow gap in-vacuum undulators are most likely to produce coupled bunch instability by the resistive wall impedance and limit the stored beam current, a bunch by bunch feedback system is implemented to suppress coupled bunch instability in the PLS-II. This paper describes the scheme and performance of the PLS-II bunch by bunch feedback system.

Transplantation is a risk factor for acute kidney injury in patients undergoing total hip replacement arthroplasty for avascular necrosis: an observational study.

BACKGROUND: The increased number of patients undergoing transplantation has increased the number of transplant recipients undergoing total hip replacement arthroplasty (THRA). We have evaluated the association between transplantation and acute kidney injury (AKI) in patients undergoing THRA. METHODS: Patients who underwent THRA from May 2004 to February 2012 were retrospectively assessed. Their demographic and clinical characteristics, the results of perioperative laboratory tests, the amounts of fluids transfused during surgery, and anesthesia time were evaluated. Patients were divided into 2 groups: transplant (n = 222) and nontransplant (n = 2,044) patients. With use of the maximal Acute Kidney Injury Network criteria, AKI was evaluated by changes in creatinine concentration within 48 hours of THRA. Propensity analyses and logistic regression were performed to evaluate the association between transplantation and postoperative AKI. RESULTS: Postoperative AKI was significantly associated with transplantation (P < .0001), and transplantation was an independent factor predictive of postoperative AKI (P < .0001). CONCLUSIONS: Transplant recipients are at risk for AKI following THRA. The mechanism by which organ transplantation enhances postoperative AKI warrants further evaluation.

Clinical evaluation of the computerized chronic urticaria-specific quality of life questionnaire in Korean patients with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is a common skin disorder that affects the well-being and quality of life (QOL) of patients. Recently, we developed and validated a questionnaire for measuring QOL in Korean patients with CU, called the Chronic Urticaria-Specific Quality of Life (CU-QOL) questionnaire. AIM: To evaluate the clinical significance of a computerized version of the CU-QOL, in adult patients with CU. METHODS: This was a cross-sectional observational study that enrolled 249 Korean patients with CU from five university hospitals and measured computerized CU-QOL scores and Urticaria Activity Score (UAS) simultaneously. The internal consistency of the computerized CU-QOL was analysed using Cronbach α. To identify clinical correlations between the CU-QOL and patient characteristics, the atopic status and serum autoantibodies, including antinuclear, antithyroglobulin and antimicrosome antibodies, were measured. Multiple linear regression models were used to identify CU-QOL predictors. RESULTS: Cronbach α was 0.94 for the overall computerized CU-QOL score. The CU-QOL scores correlated significantly with the UAS (r= -0.49, P<0.001). Of the factors aggravating CU, delayed pressure, sunlight exposure and emotional stress significantly influenced the overall CU-QOL scores in the univariate analysis. Multivariate regression models indicated that UAS and emotional stress were significant predictors of the four domains and of the total CU-QOL scores. CONCLUSIONS: The computerized CU-QOL is a convenient and valid tool for measuring QOL in patients with CU. This study suggests that UAS, dermatographism and emotional stress are strong CU-QOL predictors in Korean patients with CU.

A modification of the trans-oesophageal echocardiography protocol can reduce post-operative dysphagia following cardiac surgery.

Use of intra-operative trans-oesophageal echocardiography (TEE) is an independent risk factor for post-operative dysphagia. This study investigated whether modifying the TEE probe-placement protocol could reduce the incidence of post-operative dysphagia. In group I (n = 100), the TEE probe was inserted after anaesthetic induction and remained in place until the completion of surgery. In group II (n = 100), the TEE probe was inserted after anaesthetic induction, the heart was examined, then the probe was removed. The probe was inserted again before weaning from cardiopulmonary bypass and then immediately removed after examination. The incidence of dysphagia was significantly higher in group I than in group II patients (51.1% versus 28.6%). Multivariate regression analysis showed that the length of time that the TEE probe was in the oesophagus was an independent predictor of dysphagia. Modification of the TEE protocol in this way can reduce the incidence of post-operative dysphagia in cardiac surgery patients.

Detection of tuberculosis using artus M. tuberculosis PCR Kit and COBAS AMPLICOR Mycobacterium tuberculosis Test.

SETTING: Nucleic acid amplification tests can detect Mycobacterium tuberculosis complex rapidly and reliably. OBJECTIVE: To compare the diagnostic performance of the artus M. tuberculosis PCR Kit and COBAS AMPLICOR Mycobacterium tuberculosis Test. In the artus assay, an appropriate cycle threshold (Ct) value was determined for positivity. DESIGN: A total of 238 clinical respiratory specimens were analysed using both the artus and COBAS AMPLICOR assays. In 221 specimens, these results were further compared with culture results. RESULTS: The overall agreement between artus and COBAS AMPLICOR was 96.2% (229/238). Among the nine (3.8%) discrepant specimens, three (1.3%) were artus-positive and COBAS AMPLICOR-negative, while the other six (2.5%) were artus-negative and COBAS AMPLICOR-positive. Using culture as a standard, the sensitivity and specificity of the artus assay were 97.8% and 85.1%, and those of COBAS AMPLICOR assay were 100% and 86.2%, respectively. The difference was not statistically significant. In the artus assay, the minimum Ct value for the positivity determination was 38. CONCLUSION: The artus and COBAS AMPLICOR assays showed comparable diagnostic performance and can be confidently used for detection of M. tuberculosis complex. In the artus assay, a Ct value of 38 could be suggested as an appropriate cut-off value.

Impact of intravenous lidocaine on myocardial injury after off-pump coronary artery surgery.

BACKGROUND: Lidocaine has been demonstrated to exert cardioprotective effects against myocardial ischaemia and reperfusion injury. We evaluated whether a continuous i.v. infusion of lidocaine reduced myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). METHODS: In this randomized, double-blinded trial, 99 patients received i.v. lidocaine 2% (i.e. a 1.5 mg kg(-1) bolus at induction of anaesthesia followed by a 2.0 mg kg(-1) h(-1) infusion intraoperatively) or an equal volume of saline. Serum creatine kinase-myocardial band (CK-MB) and troponin I (TnI) concentrations were measured before surgery, upon arrival in the intensive care unit, and at 6, 24, 48, and 72 h after surgery. Cardiac enzymes, other biological markers, and rate of postoperative adverse events were compared between the groups. RESULTS: The median (25-75% inter-quartile range) TnI [0.90 (0.43-1.81) vs 1.71 (0.88-3.02) ng ml(-1), P=0.027] and CK-MB [6.5 (3.9-12.3) vs 9.8 (6.0-18.6) ng ml(-1), P=0.005] concentrations 24 h after surgery were significantly lower in the lidocaine group than in the control group. Moreover, lidocaine infusion reduced the total area under the curve of TnI and CK-MB release after surgery by 42% and 27%, respectively, compared with control. CONCLUSIONS: Continuous i.v. infusion of lidocaine during surgery reduces myocardial injury in patients undergoing OPCAB.

Detection of DNA strand breaks by comet assay in sputum leucocytes of bitumen-exposed workers: a pilot study.

DNA strand breaks were determined in leucocytes of induced sputum (IS) and compared with DNA strand breaks in blood lymphocytes from 42 bitumen-exposed workers pre and post shift. Comet assay results were expressed in arbitrary units based on visual scoring (sputum leucocytes) and Olive tail moment (OTM, blood lymphocytes). DNA damage in IS leucocytes was overall high but did not change during shift. Level of DNA strand breaks in IS samples correlated with total cell count and neutrophil content (Spearman rank correlation coefficient r(s) = 0.47, p = 0.001, r(s)= 0.48, p = 0.001, respectively) and with IL-8 concentration before and after shift (r(s) = 0.31, P = 0.048, and r(s) = 0.43, P = 0.005). DNA damage in IS was not associated with DNA strand breaks in blood lymphocytes (r(s) = -0.04, p = 0.802 before shift, r(s) = 0.27, p = 0.088 after shift). A higher level of DNA strand breaks was measured in blood lymphocytes before shift (median OTM 1.7 before and 1.3 after shift, p = 0.023). A strong correlation was found between the number of neutrophils and IL-8 concentration in IS before and after shift (r(s) = 0.77 and r(s)= 0.75, p < 0.001). This study showed an association between genotoxic and inflammatory effects in the lower airways and compared simultaneously DNA strand breaks in IS and blood of bitumen-exposed workers.

Phenylalkyl 1,2-diamines as sigma-receptor ligands: the discovery of novel antidepressant agents.

This article focuses on the study of phenylalkyl 1,2-diamines as sigma-receptor ligands for the discovery of antidepressant agents. We synthesized N-chain substituted phenylalkyl 1,2-diamine derivatives. Phenylalkyl 1,2-diamines are one of the most important class of therapeutical medicines useful in managing central nervous system diseases and have been used mainly to treat obesity, narcolepsy, minimal brain dysfunction, and mild depression. In the present study, we found that phenylalkyl 1,2-diamine and amide compounds were strongly bound to the sigma-receptors and showed a potent activity of mice forced swimming test. Our article, after briefly outlining the background and nature of sigma-receptor ligands, explores the antidepressant activity of phenylalkyl 1,2-diamines.

FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR regulatory mechanism.

The farAB operon of Neisseria gonorrhoeae encodes an efflux pump which mediates gonococcal resistance to antibacterial fatty acids. It was previously observed that expression of the farAB operon was positively regulated by MtrR, which is a repressor of the mtrCDE-encoded efflux pump system (E.-H. Lee and W. M. Shafer, Mol. Microbiol. 33:839-845, 1999). This regulation was believed to be indirect since MtrR did not bind to the farAB promoter. In this study, computer analysis of the gonococcal genome sequence database, lacZ reporter fusions, and gel mobility shift assays were used to elucidate the regulatory mechanism by which expression of the farAB operon is modulated by MtrR in gonococci. We identified a regulatory protein belonging to the MarR family of transcriptional repressors and found that it negatively controls expression of farAB by directly binding to the farAB promoter. We designated this regulator FarR to signify its role in regulating the farAB operon. We found that MtrR binds to the farR promoter, thereby repressing farR expression. Hence, MtrR regulates farAB in a positive fashion by modulating farR expression. This MtrR regulatory cascade seems to play an important role in adjusting levels of the FarAB and MtrCDE efflux pumps to prevent their excess expression in gonococci.

New sonographic finding for the prenatal diagnosis of bladder exstrophy: a case report.

Bladder exstrophy is a very rare congenital malformation in which the anterior wall of the bladder is absent, and the posterior wall is exposed externally. Although sonographic findings of bladder exstrophy have been documented, we report a case presenting with a solid mass in the lower fetal abdomen with umbilical arteries running alongside the mass. The relationship between umbilical arteries and bladder exstrophy is a new sonographic finding which may be helpful in the prenatal diagnosis of this condition.

Sequential 1,3-dipolar cycloadditions in the synthesis of bis-isoxazolo substituted piperidinones

A strategy for the efficient synthesis of novel bis-isoxazolo substituted piperidinones has been developed. The protocol consists of the Michael addition of an unsaturated alkoxide to beta-nitrostyrene followed by an intramolecular nitrile oxide cycloaddition (INOC) or an intramolecular silyl nitronate olefin cycloaddition (ISOC) to give III. Grignard addition to this isoxazoline intermediate followed by DCC coupling of the resulting isoxazolidine with nitroacetic acid gave II, and a second intramolecular cycloaddition via 1,3-dipoles result in the formation of the targeted novel tetracycles (I). A solid-supported scavenger was employed to increase the efficiency and yield of the Michael addition step.

ENVIRONMENTAL AUDITING: An Approach for Characterizing Tropospheric Ozone Risk to Forests

/ The risk tropospheric ozone poses to forests in the United States is dependent on the variation in ozone exposure across the distribution of the forests in question and the various environmental and climate factors predominant in the region. All these factors have a spatial nature, and consequently an approach to characterization of ozone risk is presented that places ozone exposure-response functions for species as seedlings and model-simulated tree and stand responses in a spatial context using a geographical information systems (GIS). The GIS is used to aggregate factors considered important in a risk characterization, including: (1) estimated ozone exposures over forested regions, (2) measures of ozone effects on species' and stand growth, and (3) spatially distributed environmental, genetic, and exposure influences on species' response to ozone. The GIS-based risk characterization provides an estimation of the extent and magnitude of the potential ozone impact on forests. A preliminary risk characterization demonstrating this approach considered only the eastern United States and only the limited empirical data quantifying the effect of ozone exposures on forest tree species as seedlings. The area-weighted response of the annual seedling biomass loss formed the basis for a sensitivity ranking: sensitive-aspen and black cherry (14%-33% biomass loss over 50% of their distribution); moderately sensitive-tulip popular, loblolly pine, eastern white pine, and sugar maple (5%-13% biomass loss); insensitive-Virginia pine and red maple (0%-1% loss). In the future, the GIS-based risk characterization will include process-based model simulations of the three- to 5-year growth response of individual species as large trees with relevant environmental interactions and model simulated response of mixed stands. The interactive nature of GIS provides a tool to explore consequences of the range of climate conditions across a species' distribution, forest management practices, changing ozone precursors, regulatory control strategies, and other factors influencing the spatial distribution of ozone over time as more information becomes available.KEY WORDS: Ecological risk assessment; GIS; Ozone; Risk characterization; Forests; Trees