Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus

Age-related changes of ocular parameters in Korean subjects

Aims: To evaluate the age-related variations of ocular parameters in Korean subjects. Methods: We recruited 314 normal subjects who visited the department of Ophthalmology between January 2007 and October 2007. Refraction, axial length, corneal curvature, white-to-white distance, anterior chamber depth, corneal endothelial cell density, and retinal nerve fiber layer (RNFL) thickness were measured using auto-refractive keratometer, intraocular lens master, noncontact specular microscope, and optical coherence tomography. Result: In correlation analysis, from 19 to 82 years, hyperopic shift showed a strong positive statistical correlation with age (r = 0.553, P < 0.001). Corneal curvatures increased (r = 0.221, P < 0.001), while axial length (r = -0.506, P < 0.001), anterior chamber depth (r = -0.491, P < 0.001) and white-to-white distance (r = -0.205, P < 0.001) decreased with age. Also, corneal endothelial cell density was lower in older patients than in younger patients (r = -0.409, P < 0.001). Compared to younger patients, RNFL thickness was lower in the older patients as well, in all quadrants (superior, r = -0.283, P < 0.001; inferior, r = -0.230, P < 0.001; nasal, r = 0.025, P = 0.676; and temporal, r = -0.393, P < 0.001). According to multiple regression analysis, out of the six parameters measured, only hyperopic shift, anterior chamber depth and corneal endothelial cell density (P, 0.05) had statistically significant correlation with age. Conclusion: Some of the ocular parameters changed with aging. Hyperopic shift, shallowing anterior chamber depth, and reduction of corneal endothelial cell density were only definitely related to age

Molecular orientation of liquid crystal on polymer blends of coumarin and naphthalenic polyimide

Photo-induced liquid crystal alignment layers were prepared by blending polyimides and photoreactive polymers followed by polarized UV irradiation. Polyimides are selected for the purpose of improving the thermal stability of the molecular orientation of the photoreactive groups. The thermal stability of the LC alignment layer was enhanced regardless of the type of the polyimide while the direction of LC orientation was dependent on the type of polyimide. The photoreactivity of the polyimide governs the LC orientation in the blend alignment layers. © 2008 Springer-Verlag.1

Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin

AbstractMurine norovirus-1 (MNV-1) shares many features with human norovirus (HuNoV) and both are classified within the norovirus genus of Caliciviridae family. MNV-1 is used as the surrogate for HuNoV research since it is the only form that can be grown in cell culture. HuNoV and MNV-1 RNA dependent RNA polymerase (RdRp) proteins with the sequence identity of 59% show essentially identical conformations. Here we report the first structural evidence of 2-thiouridine (2TU) or ribavirin binding to MNV-1 RdRp, based on the crystal structures determined at 2.2Å and 2.5Å resolutions, respectively. Cellular and biochemical studies revealed stronger inhibitory effect of 2TU on the replication of MNV-1 in RAW 264.7 cells, compared to that of ribavirin. Our complex structures highlight the key interactions involved in recognition of the nucleoside analogs which block the active site of the viral RNA polymerase

Predictors of Successful Trial without Catheter for Postoperative Urinary Retention Following Non-Urological Surgery

Purpose To investigate the success rate of trial without catheter (TWOC) for postoperative urinary retention (POUR) after non-urological surgery and to determine predictors of successful TWOC. Methods A total of 104 patients who underwent non-urological surgery and were referred to the department of urology for POUR were included in this retrospective study. All eligible patients underwent indwelling catheterization as an initial treatment and then TWOC was performed 3 to 7 days later. POUR was defined as micturition difficulty with greater than 400 mL of postvoid residual (PVR) urine volume measured by catheterization after non-urological surgery. Successful TWOC was defined as voiding with less than 100 mL of PVR urine volume. Predictive factors were identified by multivariate regression analysis. All definitions corresponded to recommendations of the International Continence Society. Results The mean age of the patients was 65.2 (range, 23 to 92) years. There were 45 male and 59 female patients. Intraoperative indwelling catheterization was performed in 69 (66.3%) patients. Mean duration of indwelling catheterization for POUR was 5.0 (range, 3.0 to 7.0) days and 83 (79.8%) patients received medication with an alpha-blocker. A successful TWOC was observed in 70 (67.4%) patients. The mean age of the patients with failure of TWOC was significantly higher than that of the patients with successful TWOC. The percentages of female patients, spinal surgery, and prone position during surgery in patients with unsuccessful TWOC were higher than in those with successful TWOC. In the multivariate logistic regression analysis, age and location of surgery (spine vs. non-spine) were the independent predictors of successful TWOC for POUR. Conclusions Our data suggest that older age and spinal surgery may be important risk factors for failure of TWOC for POUR after non-urological surgery. Thus, adequate prevention measures may be necessary for POUR after non-urological surgery, especially in patients with these risk factors

Clinicopathological Risk Factors and Biochemical Predictors of Safe Discharge after Total Thyroidectomy and Central Compartment Node Dissection for Thyroid Cancer: A Prospective Study

To determine the clinicopathological risk factors and reliable biochemical predictors of the development of hypocalcemic symptoms after total thyroidectomy on the basis of serum calcium and intact parathyroid hormone (PTH) levels measured 1 hour after surgery, a prospective study was performed on 817 patients who underwent a total thyroidectomy with central compartment node dissection (CCND) due to well-differentiated thyroid cancer. We evaluated the correlations between hypocalcemic symptom development and clinicopathological factors. And the predictability for hypocalcemic symptom development of intact PTH cut-offs (<10 pg/mL and <20 pg/mL, resp.) according to serum calcium level subgroup was analyzed. Female gender (P<0.001) was the only independent risk factor for hypocalcemic symptom development in multivariate regression analysis. The negative predictive value (NPV) of intact PTH, signifying nondevelopment of hypocalcemic symptoms, was higher than the positive predictive value (PPV) which signified development of hypocalcemic symptoms. In addition, when we applied the different adoption of the intact PTH cut-off according to serum calcium level, we could obtain more increased NPVs. A female gender and the application of more specific cut-offs for intact PTH according to the serum calcium levels measured 1 hour after surgery may help the patients to be more safely discharged