Structure and spectral features of H+(H2O)(7): Eigen versus Zundel forms

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)(7). For H+(H2O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)(7) [though nearly isoenergetic to the 3D structure for D+(D2O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments. (c) 2006 American Institute of Physics.open353

Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A

Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER) protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A) protein, which is a critical factor for HCV RNA replication, interacts with the IFN-beta-inducible protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore, the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall flow of autophagy; however, it is a substrate for autophagic degradation. The physical association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation. Altogether, our findings suggest that IFN-beta-induced SCOTIN recruits the HCV NS5A protein to autophagosomes for degradation, thereby restricting HCV replication.1110Ysciescopu

Association between the awareness of osteoporosis and the quality of care for bone health among Korean women with osteoporosis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: The prevalence of osteoporosis is increasing and is a socio-economic burden worldwide. Although screening tests for osteoporosis in Korea are easily accessible, this condition remains undertreated. Evaluating post-diagnostic behavior changes may be helpful for improving the quality of care for bone health in osteoporotic patients. Methods: After reviewing the Fourth Korean National Health and Nutrition Examination Survey 2008–2009, 1,114 women with osteoporosis aged >50 years were included in this cross-sectional study. Factors related to bone health were categorized into the following groups: (1) behavioral health (smoking, alcohol consumption, and physical activity); (2) measured factors (lean body mass [kg], appendicular skeletal muscle mass [kg], and serum vitamin D level [nmol/L]); and (3) nutritional factors (calcium intake, vitamin/mineral supplementation, and healthy supplementary food). Logistic regression analysis and analysis of covariance was conducted after adjusting for age, education, income, residential area, height, weight, and self-perceived health using a weighted method. Results: Doctors diagnosed 39.5% of patients with osteoporosis, and these patients were compared with the control group. The awareness group, who had been diagnosed with osteoporosis by a doctor, had a lower proportion of smokers and higher serum vitamin D level than the control group, who had never been diagnosed with osteoporosis. No other associations were found for quality of bone health care variables. The awareness group had higher odds ratios of vitamin/mineral replacement and healthy supplementary food but no other differences were observed, indicating the patients beliefs in bone health care do not follow the recommended clinical guidelines (e.g. higher physical activity, lower alcohol consumption). Conclusion: To improve the quality of care for bone health in osteoporotic patients, an initial step should be the development of post-diagnostic procedures such as patient counseling and education through a multi-team care approach.Peer Reviewe

Recombinant TAT–gelonin fusion toxin: Synthesis and characterization of heparin/protamine‐regulated cell transduction

Protein toxins, such as gelonin, are highly desirable anti‐cancer drug candidates due to their unparalleled potency and repetitive reaction mechanism in inhibiting protein translation. However, for its potential application in cancer therapy, there remains the cell membrane barrier that allows permeation of only small molecules, which must be overcome. To address this challenge, we conjugated gelonin with a protein transduction domain (PTD), the TAT peptide, via genetic recombination. The chimeric TAT–gelonin fusion protein (TAT‐Gel) retained equipotent N ‐glycosidase activity yet displayed greater cell uptake than unmodified recombinant gelonin (rGel), thereby yielding a significantly augmented cytotoxic activity. Remarkably, TAT‐Gel displayed up to 177‐fold lower IC 50 (avg. 54.3 n M ) than rGel (avg. IC 50 : 3640 n M ) in tested cell lines. This enhanced cytotoxicity, however, also raised potential toxicity concerns due to the non‐selectivity of PTD in its mediated cell transduction. To solve this problem, we investigated the plausibility of regulating the cell transduction of TAT‐Gel via a reversible masking using heparin and protamine. Here, we demonstrated, both in vitro and in vivo , that the cell transduction of TAT‐Gel can be completely curbed with heparin and yet this heparin block can be efficiently reversed by the addition of protamine. This reversible tight regulation of the cell transduction of TAT‐Gel by heparin and protamine sheds light of possible application of TAT‐Gel in achieving a highly effective yet safe drug therapy for the treatment of tumors. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 409–419, 2015.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109572/1/jbma35188.pd

Design of the VISTA-ITL Test Facility for an Integral Type Reactor of SMART and a Post-Test Simulation of a SBLOCA Test

To validate the performance and safety of an integral type reactor of SMART, a thermal-hydraulic integral effect test facility, VISTA-ITL, is introduced with a discussion of its scientific design characteristics. The VISTA-ITL was used extensively to assess the safety and performance of the SMART design, especially for its passive safety system such as a passive residual heat removal system, and to validate various thermal-hydraulic analysis codes. The VISTA-ITL program includes several tests on the SBLOCA, CLOF, and PRHRS performances to support a verification of the SMART design and contribute to the SMART design licensing by providing proper test data for validating the system analysis codes. A typical scenario of SBLOCA was analyzed using the MARS-KS code to assess the thermal-hydraulic similarity between the SMART design and the VISTA-ITL facility, and a posttest simulation on a SBLOCA test for the shutdown cooling system line break has been performed with the MARS-KS code to assess its simulation capability for the SBLOCA scenario of the SMART design. The SBLOCA scenario in the SMART design was well reproduced using the VISTA-ITL facility, and the measured thermal-hydraulic data were properly simulated with the MARS-KS code

Patterns of Using Complementary and Alternative Medicine by Stroke Patients at Two University Hospitals in Korea

This study measured the prevalence of complementary and alternative medicine (CAM) use among Korean stroke patients. Questionnaire-based 20-min interviews were conducted at the hospitals by a trained nurse after an outpatient visit. It included questions on demographic information, clinical information and the utilization of CAM. Of 304 stroke-patient respondents, 164 (54%) had used CAM, of which 66% had started taking CAM products following suggestions from family members and other relatives. Of the 57% of users who felt that CAM was effective, 84% considered that it improved the symptoms of stroke and 16% felt it was effective in achieving psychological relaxation. Of the eight CAM categories used by respondents, 92% used traditional Oriental medical treatments, 36% used plant- and animal-derived over-the-counter health care products, 24% used minerals and vitamins, and 11% used manual therapies. The majority of stroke patients (68%) were trying a new type of CAM, and half of the respondents (45%) relied on the knowledge of their general practitioner about CAMs when deciding whether to use them. Most of the stroke patients in this study used CAM, and a half of them reported beneficial effects. Despite the presence of adverse side effects, they tended to be used without discussion with chief physicians, and hence physicians should be actively involved in the usage of CAM

Effects of education on low-phosphate diet and phosphate binder intake to control serum phosphate among maintenance hemodialysis patients: A randomized controlled trial.

Background:For phosphate control, patient education is essential due to the limited clearance of phosphate by dialysis. However, well-designed randomized controlled trials about dietary and phosphate binder education have been scarce. Methods:We enrolled maintenance hemodialysis patients and randomized them into an education group (n = 48) or a control group (n = 22). We assessed the patients' drug compliance and their knowledge about the phosphate binder using a questionnaire. Results:The primary goal was to increase the number of patients who reached a calcium-phosphorus product of lower than 55. In the education group, 36 (75.0%) patients achieved the primary goal, as compared with 16 (72.7%) in the control group (P = 0.430). The education increased the proportion of patients who properly took the phosphate binder (22.9% vs. 3.5%, P = 0.087), but not to statistical significance. Education did not affect the amount of dietary phosphate intake per body weight (education vs. control: -1.18 ± 3.54 vs. -0.88 ± 2.04 mg/kg, P = 0.851). However, the dietary phosphate-to-protein ratio tended to be lower in the education group (-0.64 ± 2.04 vs. 0.65 ± 3.55, P = 0.193). The education on phosphate restriction affected neither the Patient-Generated Subjective Global Assessment score (0.17 ± 4.58 vs. -0.86 ± 3.86, P = 0.363) nor the level of dietary protein intake (-0.03 ± 0.33 vs. -0.09 ± 0.18, P = 0.569). Conclusion:Education did not affect the calcium-phosphate product. Education on the proper timing of phosphate binder intake and the dietary phosphate-to-protein ratio showed marginal efficacy