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This study identified the key factors of spousal support that influence the outcomes and willingness of female knowledge workers to work from home (WFH). A questionnaire of 59 items was developed, covering basic personal information, spousal support, work perception, work-life balance, and willingness to WFH: 139 valid responses from female participants were collected and analysed. Exploratory factor analysis revealed six distinct factors of spousal support. Regression analysis found that personal-related emotional support, personal-related instrumental support, work-related emotional support, and work-related instrumental support demonstrated positive correlations with work perception and work-life balance, while family-related instrumental support positively correlated with work-life balance. Personal-related emotional support and personal-related instrumental support positively correlated with the willingness to WFH. Notably, personal-related emotional support exhibited the strongest correlation coefficients for willingness and outcomes. The findings could provide information on how a husband could improve his wife's well-being when WFH. Practitioner summary: A survey was conducted among female knowledge workers to examine the influence of different factors of spousal support on the outcomes and willingness of WFH. The results shed light on how husbands can improve their wives' well-being during WFH, offering practical guidance for supporting spouses in this context. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low‐density lipoprotein cholesterol (LDL‐C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL‐C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice. [ABSTRACT FROM AUTHOR]

Aims: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. Methods: Nonlinear mixed‐effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. Results: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non‐complicated methicillin‐resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. Conclusions: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow‐up therapeutic drug monitoring of teicoplanin at least once every week. [ABSTRACT FROM AUTHOR]

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high‐dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy. [ABSTRACT FROM AUTHOR]

This study aims to assess the risk factors for insufficient vancomycin concentrations for its prophylactic use in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to modify the dosing regimen to achieve appropriate plasma concentrations. A total of 27 patients with vancomycin dosing of 1 to 1.5 g based on a weight cutoff of 67 kg were included, of which only 13 (48.15%) had vancomycin plasma concentration >15 mg/L at surgical closure. Risk factors of vancomycin concentration <15 mg/L at surgical‐site closure were confirmed by multivariate logistic regression analysis, which showed that CPB duration was an independent predictor. Patients with CPB duration >4 hours had significantly lower vancomycin concentrations and lower proportion in achieving target vancomycin concentration at the end of CPB and surgical closure. For patients with CPB >4 hours, the modified dosing regimen that a second dose of 0.5 to 0.75 g added at 4 hours since the onset of CPB improved the target achievement of vancomycin concentration at surgical closure. Taken together, CPB duration >4 hours was the risk factor for insufficient vancomycin concentration at surgical closure, while our modified dosing could improve the vancomycin concentrations for its prophylactic use in patients undergoing cardiac surgery with CPB. [ABSTRACT FROM AUTHOR]

Recently, lanthanide-ion-doped luminescent materials have been extensively used as optical thermometry probes due to their fast responses, non-contact, and high sensitivity properties. Based on different responses of two emissions to temperature, the fluorescence intensity ratio (FIR) technique can be used to estimate the sensitivities for assessing the optical thermometry performances. In this study, we introduce different doping concentrations of Eu3+ ions into negative thermal expansion material Sc2W3O12 to increase the thermal-enhanced luminescence from 373 K to 548 K, and investigate the temperature sensing properties in detail. All samples can exhibit their good luminescence behaviors thermally enhanced. The emission intensity of Sc2W3O12:6-mol% Eu3+ phosphor reaches 147.8% of initial intensity at 473 K. As the Eu3+ doping concentration increases, the resistance of the sample to thermal quenching decreases. The FIR technique based on each of the transitions 5D→ 7F1 (592 nm) and 5D→ 7F2 (613 nm) of Eu3+ ions demonstrates a maximum relative temperature sensitivity of 3.063% K−1 at 298 K for Sc2W3O12:6-mol% Eu3+ phosphor. The sensitivity of sample decreases with the increase of Eu3+ concentration. Benefiting from the thermal-enhanced luminescence performance and good temperature sensing properties, the Sc2W3O12:Eu3+ phosphors can be used as optical thermometers. [ABSTRACT FROM AUTHOR]

Background: Pediatric hypertension become an early marker of cardiovascular diseases, but their antihypertensive drug use patterns are rarely known. Purpose: To investigate the epidemiological characteristics of pediatric hypertension and the use of antihypertensive drugs in the real world in China. Methods: In this study, the demographic, diagnosis, and medication prescription data including the antihypertensive drug types and comorbidities, were analyzed. The antihypertensive drugs use were evaluated according to the Chinese guidelines for hypertension. Results: 1301 prescriptions (number of visits) containing 1880 antihypertensive medical orders were collected. The average number of antihypertensive drugs per prescription was 1.45 (± 0.75). The patients aged 16 to 18 (70.18%) accounted for the highest proportion. Kidney diseases (33.28%) were the most common comorbidities. Calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), and β receptor blocker (BB) were the most used antihypertensive drugs. The most frequent monotherapy was CCB, while that of two and three drugs combination were ARB+CCB and ARB+BB+CCB, respectively. Metoprolol (11.44%), nifedipine (10.64%), amlodipine (10.59%), valsartan (6.12%) were the most commonly used antihypertensive drugs. The utilization rate of fixed compound preparations was 7.34%. However, the percentage of recommended antihypertensive drugs was just 14.20%, while the recommended drug combination was 84.93% according to the guidelines. Conclusion: For the first time ever we reported the antihypertensive prescription analysis in children in a large area of China. Our data provided new insights into the epidemiological characteristics and drug use in hypertensive children. We found that the guidelines for medication management in hypertensive children were not routinely followed. The wide use of antihypertensive drugs in children and those with weak clinical evidence raised concerns regarding its rational use. The findings could lead to more effective management of hypertension in children. [ABSTRACT FROM AUTHOR]

Limited therapeutic options exist for multidrug‐resistant/extensively drug‐resistant Acinetobacter baumannii (MDR/XDR‐Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare‐associated MDR/XDR‐Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR‐Ab meningitis/ventriculitis has not been reported. We report on a 66‐year‐old male patient who developed post‐neurosurgical ventriculitis caused by MDR‐Ab. IVT concomitant intravenous colistin sulphate was used as a last‐resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment. [ABSTRACT FROM AUTHOR]

Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28–6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1–1.5 million IU/day, given in 2–3 doses, could attain PTA > 90% for MICs ≤ 0.5 μg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 μg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 μg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 μg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate whether human periodontal ligament (PDL) cells secrete pro-angiogenic factors that induce the vascularization of surrounding bone tissue under tensile stress.Methods: Quantitative real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), Angiopoietin-I (Ang-I), connective tissue growth factor （CTGF）, and macrophage colony-stimulating factor (M-CSF) in PDL cells after tensile force treatments of different durations. Enzyme-linked immunosorbent assay was used to measure the VEGF concentration in the supernatants of cell cultures. Cell viability assay, wound healing assay, and tube formation assay were performed to evaluate the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs).Results: The mRNA expression and protein expression of VEGF, bFGF, Ang-I, and M-CSF was increased in the cells that received 6 to 48 hours of tensile force treatment. And, the VEGF level in the supernatant significantly increased in the human PDL cell cultures stressed for 6 to 48 hours. The abilities of HUVECs to proliferate, migrate, and form tubes were enhanced in media conditioned with tensile-stressed human PDL cells. Hence, tensile force induced human PDL cells to express and release pro-angiogenic factors enhancing the proliferation, migration, and angiogenic capacity of HUVECs.Conclusion: Tensile stress induced human PDL cells to express and release pro-angiogenic factors, including VEGF, bFGF, Ang-I, and M-CSF, thereby enhancing the proliferation, migration, and angiogenic capacity of HUVECs. [ABSTRACT FROM AUTHOR]

Organic–inorganic hybrid ABX3 perovskite (OIHPs) with phase transition have considerable application potential in multifunctional devices for their structural tunability and excellent photo/electric performance. Because the interaction between molecules during the crystallization process is difficult to predict and control, exploring targeted chemical design methods to synthesize phase change materials has been an interesting and challenging problem. As per the synergistic effect of anion and cation, we assemble a cation with high vibrational activity and an inorganic anion with large voids to successfully design a one-dimensional OIHPs phase change material. [FMPD][Cd(SCN)3] (FMPD = 1-fluoroethyl-1-methylpiperidinium) undergoes two reversible phase transitions above room temperature with the substitution of methyl with fluoroethyl increasing the energy barrier of molecular motion. The individual crystal diffraction structures show that, unlike the phase change caused by the reorientation of organic cations in majority of known perovskites, this phase transition is triggered by the order/disorder of cations and anions related to the vibration increase by the introduction of fluoroethyl. The results provide a new design idea for the design and assembly of novel OIHPs-type phase change materials. [ABSTRACT FROM AUTHOR]

Sanghuangporus sanghuang is a well-known pharmacodynamic and economically important edible fungus associated with mulberry (Morus spp.). A distinctly new exopolysaccharide (EPS), designated SHP-2 was obtained from S. sanghuang P0988 broth, and its structure and anti-aging prosperity were characterized. SHP-2 was found to be composed of a back-bone of →4)-β-Manp-(1→4)-α-Araf-(1→3,4)-α-Glcp(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→6)-α-Galp-(1→4)-β-Manp-(1→ and five branches, including four α-D-Glcp-(1→ and one α-D-Manp-(1→SHP-2 was shown to increase antioxidant enzyme activities including catalase (CAT) and superoxide dismutase (SOD) activities, as well as trolox equivalent antioxidant (TEAC) capacity in serum of mice pre-treated with D-Gal, while reducing lipofuscin levels. SHP-2 exerted a favorable influence on immune organ coefficients and ameliorated the histopathological hepatic lesions and apoptosis in hepatocytes of D-galactose-aged mice almost in a dose-dependent manner. Using the same analytical methods, on comparison with previously studied EPS compounds (i.e. SHP-1), SHP-2 was found to have more complex structure, larger molecule weight, and different anti-aging properties. The results presented here suggest that not only does EPS bioactivity vary with respect to molecular structures and molecule weight, but that multiple structures with different activity can be expressed by a single fungal strain. These results may help understanding the anti-aging prosperity of these polysaccharides for use in health foods or dietary supplements. [ABSTRACT FROM AUTHOR]

Background/Aims: This study aimed to investigate the effect of Nell-1 on the osteogenic behaviors of pre-osteoblasts on titanium (Ti) surfaces and to identify the underlying signaling pathway. Methods: Nell-1 at different concentrations was added to culture medium to stimulate MC3T3-E1 subclone 14 on Ti surfaces. A CCK-8 colorimetric assay was used to detect cell proliferation. Alkaline phosphatase activity (ALP) assay and enzyme-linked immunosorbent assay (ELISA) were used to evaluate ALP activity and the osteocalcin (OCN) secretion, respectively. Indicators of osteoblastic differentiation were assessed using real-time polymerase chain reaction analysis (RT-PCR). Western blot (WB) assay was used to analyze the expression changes of the osteogenic proteins and the mitogen-activated protein kinase (MAPK) pathway. Results: Nell-1 significantly increased the osteogenic gene and protein expression levels of ALP, OCN, Runx2, osteoprotegerin (OPG), collagen type I (Col-I), and Osterix (Osx) in pre-osteoblasts on Ti surfaces. The optimal concentration of Nell-1 was 100 ng/ ml. In addition, Nell-1 activated ERK and JNK, but not P38, in MC3T3-E1 cells on the Ti surface. Except for ALP and Col-I, the promotive effects of Nell-1 on the expression of osteogenic markers were suppressed by ERK inhibitor U0126. Conclusion: Certain concentrations of Nell-1 can promote the osteogenic differentiation of pre-osteoblasts on Ti surfaces by activating the MAPK/ERK signaling pathway. [ABSTRACT FROM AUTHOR]

Both the whole cells and protoplasts of Pseudomonas aeruginosa PAO1 and Bacillus cereus , two biofilm-forming bacteria, were disrupted by the lipopeptide 6-2 produced by Bacillus amyloliquefaciens anti-CA. The lipopeptide 6-2 could also effectively inhibit the formation of biofilms and disperse pre-formed biofilms. Live/dead staining of the biofilms grown in the absence or presence of the lipopeptide 6-2 showed that more dead bacterial cells in the presence of the lipopeptide than those in the absence of the lipopeptide and biofilm formation was greatly reduced by the lipopeptide 6-2. Expression of the PslC gene related to exopolysaccharides in P. aeruginosa PAO1 was also inhibited. All these results demonstrated that the lipopeptide 6-2 produced by B. amyloliquefaciens anti-CA had a high activity against biofilm-forming bacteria. The lipopeptide 6-2 also killed the larvae of Balanus amphitrite and inhibit the germination of Laminaria japonica spore and growth of protozoa, all of which were the fouling organisms in marine environments. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the expression patterns of CEACAM5 in prostatic non-neoplastic and neoplastic lesions and further investigate its relationship with tumor microvessel density(MVD) and lymphatic vessel density(LVD). Methods: CEACAM5 expression was detected using immunohistochemical staining in a serial sections of the benign prostatic hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate carcinoma (PCa) lesions. MVD and LVD were quantified in CEACAM5 positive areas by dual-labelling with CD34 and D2-40 respectively. Results: Both PIN and PCa had significantly higher expression for CEACAM5 than BPH which has no positive expression for CEACAM5(P<0.05). In PIN and PCa, CEACAM5 staining showed different expression patterns in terms the of most of membranous staining for PIN, less membranous staining and more cytoplasmic staining for PCa. MVD results showed that PCa and PIN had more angiogenesis than BPH tissue. The value of MVD in PCa tissue was correlated with tumor Gleason grading (P<0.05). LVD results showed that neoplastic lesions had more lymphangiogenesis than non-neoplastic lesion. Conclusion: CEACAM5 had different expression patterns in prostatic non-neoplastic and neoplastic lesions, and these various expression patterns may be correlated with tumor progression through promoting tumorous angiogenesis or lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: This paper investigates the output consensus problem of port-controlled Hamiltonian (PCH) multi-agent systems with both Fixed and switching topologies. Firstly, a distributed group output consensus protocol is designed via the energy shaping method to reach globally stability and group output consensus. Secondly, a new distributed control protocol is proposed by using the structural properties of the PCH systems. The advantage of this protocol is that it can transform the directed graph to the undirected graph by constructing a kind of virtual neighbors. Thirdly, a control protocol is designed with the extended LaSalle0s invariance principle developed for switched systems under the jointly connected topology condition to make all the agents reach output consensus when the topology is switching. Finally, some illustrative examples with simulations are provided to demonstrate the effectiveness of the protocols designed in this paper. [Copyright &y& Elsevier]

Abstract: This paper investigates the stability and estimate of domain of attraction for a class of nonlinear time-varying delay systems, and proposes a number of new results on both the stability and estimate of domain of attraction. Firstly, an equivalent form is obtained for the systems by means of coordinate transformation and orthogonal decomposition of vector fields. Then, based on the equivalent form and the free-weighting matrix method, several sufficient conditions in terms of nonlinear matrix inequalities are derived for the stability analysis by constructing suitable Lyapunov functionals. Finally, the equivalent form and the obtained stability results are applied to the estimate of domain of attraction for this class of nonlinear time-delay systems, and a new approach is presented. Illustrative examples show that the results obtained in this paper are effective in studying the stability and estimation of domain of attraction for the class of nonlinear time-delay systems. [Copyright &y& Elsevier]

Abstract: Using the Hamiltonian function method, we investigate the excitation control of multi-machine multi-load power systems presented by nonlinear diffierential algebraic equations. First, the power system is reformulated as a novel Hamiltonian realization structure via pre-feedback state control. Then, based on the dissipative Hamiltonian realization of the system, a decentralized nonlinear excitation control scheme is constructed. The stability of the closed loop system is analyzed as well. The proposed strategy takes advantage of the intrinsic properties especially including the internal power balance of the power system. Simulation illustrates the effectiveness of the control strategy. [Copyright &y& Elsevier]

An improved tunable coplanar waveguide (CPW) bandstop filter, which exhibits good performance, is proposed in this paper. A novel tunable open stub and a useful formula for frequency shift and impedances are also presented. Further, air bridges and a special method of step compensation in the angle bends are employed to overcome differences in the radiation effects as much as possible. From the measured results, a 33% narrower rejection bandwidth with sharper roll-off was achieved, particularly in comparison to that of the bent filter. An enormous size reduction of 53% was obtained, compared to the conventional open-stub structure. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 198–200, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20091 [ABSTRACT FROM AUTHOR]

In this paper, we propose an improved doubly electromagnetic periodic structure (DEPS) and apply it in a power amplifier for harmonic tuning. The DEPS power amplifier shows an improvement of 0.5 dB and 8% in output power and power-added efficiency (PAE), respectively, compared with the conventional EPS power amplifier. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 342–344, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11209 [ABSTRACT FROM AUTHOR]

Quantification theory (I) provides a kind of multi-ary analysis method for the forecast problem with its criterion variable quantitative and its explanatory variables qualitative. In such a theory, the forecast model is a one-dimensional linear one, which cannot be applied to high-dimension or nonlinear forecast problems. By the matrix semi-tensor product method, this paper improves quantification theory (I) from two aspects: model and dimension. First, based on the algebraic expression of mix-valued logical variables, the forecast problem of one-dimensional criterion variable is investigated, and a new forecast model is presented. Second, we consider the multi-dimension forecast problem, and establish a new multidimension forecast method by using mix-valued logical function vectors. Finally, we give an illustrative example to demonstrate our new results. [ABSTRACT FROM AUTHOR]

Abstract: The changes in the microenvironment of the Trp-3 on the i-face of pig pancreatic IB phospholipase A2 (PLA2) provide a measure of the tight contact (Ramirez and Jain, Protein Sci. 9, 229–239, 1991) with the substrate interface during the processive interfacial turnover. Spectral changes from the single Trp-substituent at position 1, 2, 6, 10, 19, 20, 31, 53, 56 or 87 on the surface of W3F PLA2 are used to probe the Trp-environment. Based on our current understanding only the residue 87 is away from i-face, therefore all other mutants are well suited to report modest differences along the i-face. All Trp-mutants bind tightly to anionic vesicles. Only those with Trp at 1, 2 or 3 near the rim of the active site on the i-face cause significant perturbation of the catalytic functions. Most other Trp-mutants showed < 3-fold change in the interfacial processive turnover rate and the competitive inhibition by MJ33. Binding of calcium to the enzyme in the aqueous phase had modest effect on the Trp-emission intensity. However, on the binding of the enzyme to the interface the fluorescence change is large, and the rate of oxidation of the Trp-substituent with N-bromosuccinimide depends on the location of the Trp-substituent. These results show that the solvation environment of the Trp-substituents on the i-face is shielded in the enzyme bound to the interface. Additional changes are noticeable if the active site of the bound enzyme is also occupied, however, the catalytically inert zymogen of PLA2 (proPLA2) does not show such changes. Significance of these results in relation to the changes in the solvent accessibility and desolvation of the i-face of PLA2 at the interface is discussed. [Copyright &y& Elsevier]

Abstract: Rad51 and Rad54 play crucial roles during homologous recombination. The biochemical activities of human Rad51 (hRad51) and human Rad54 (hRad54) and their interactions with each other are well documented. However, it is not known how these two proteins work together to bypass heterologous sequences; i.e. mismatched base pairs, during homologous recombination. In this study, we used a fluorescence resonance energy transfer assay to monitor homologous recombination processes in real time so that the interactions between hRad54 and hRad51 during DNA strand exchange and branch migration, which are two core steps of homologous recombination, could be characterized. Our results indicate that hRad54 can facilitate hRad51-promoted strand exchange through various degrees of mismatching. We propose that the main roles of hRad51 in homologous recombination is to initiate the homology recognition and strand-exchange steps and those of hRad54 are to promote efficient branch migration, bypass potential mismatches and facilitate long-range strand exchanges through branch migration of Holliday junctions. [Copyright &y& Elsevier]

Nek2A is a cell-cycle-regulated protein kinase that localizes to the centrosome and kinetochore. Our recent studies provide a link between Nek2A and spindle checkpoint signaling [J. Biol. Chem. 279 (2004) 20049]. Extracellular signal-regulated kinase 2 (Erk2) is an important kinase, which belongs to mitogen activating protein (MAP) kinase family. Here we demonstrated that Nek2A binds specifically to Erk2. Erk2 interacts with Nek2A via a conserved Erk2 docking site located to the C-terminus of Nek2A. Our studies indicate this docking site is essential and sufficient for a direct Nek2A-Erk2 interaction. In addition, our immunocytochemical studies show that Nek2A and Erk2 are co-localized to centrosome. Significantly, elimination of Nek2A by RNA interference delocalized Erk2 from its centrosomal location, while inhibition of Erk2 kinase activity did not affect the localization of Nek2A in centrosome. We propose that Erk2 links extracellular signaling to centrosome dynamics by Nek2A. [Copyright &y& Elsevier]

Polyvinylpyrrolidone is a macromolecular polymer with widespread use in industry as well as in medicine for various purposes. Its effect on cells cultured in vitro, however, has not been fully investigated. To elucidate this issue, we studied the influence of PVP K-30 on cultured HeLa cells. PVP K-30 treatment produced a dose- and time-dependent toxicity to HeLa cells. Cells exposed to PVP K-30 exhibited several morphological features of apoptosis. Gel electrophoresis of DNA from PVP K-30-treated cells showed typical apoptotic ladder. And flow cytometric analysis demonstrated that PVP K-30 induced cell cycle arrest at G2/M phase and the subsequent appearance of sub-G1 population. In addition, it was shown that procaspase-3 was activated in response to PVP K-30 treatment. We also found that α-tocopherol efficiently protected HeLa cells from PVP K-30 cytotoxicity. This is the first demonstration that PVP K-30 could induce apoptosis in HeLa cells and cell cycle arrest at G2/M phase, and that PVP K-30 toxicity could be attenuated by α-tocopherol. [Copyright &y& Elsevier]