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1.  Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway 
Cell Research  2015;25(7):801-817.
The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway kinases Lats1/2 and Mst1/2, as well as the nuclear E3 ubiquitin ligase CRL4DCAF1. Numerous mutations of Merlin have been identified in Neurofibromatosis type 2 and other cancer patients. Despite more than two decades of research, the upstream regulator of Merlin in the Hippo pathway remains unknown. Here we show by high-resolution crystal structures that the Lats1/2-binding site on the Merlin FERM domain is physically blocked by Merlin's auto-inhibitory tail. Angiomotin binding releases the auto-inhibition and promotes Merlin's binding to Lats1/2. Phosphorylation of Ser518 outside the Merlin's auto-inhibitory tail does not obviously alter Merlin's conformation, but instead prevents angiomotin from binding and thus inhibits Hippo pathway kinase activation. Cancer-causing mutations clustered in the angiomotin-binding domain impair angiomotin-mediated Merlin activation. Our findings reveal that angiomotin and Merlin respectively interface cortical actin filaments and core kinases in Hippo signaling, and allow construction of a complete Hippo signaling pathway.
doi:10.1038/cr.2015.69
PMCID: PMC4493278  PMID: 26045165
Merlin; Nf2; angiomotin; Hippo pathway; Lats1/2; phosphorylation; PAK1/2
2.  Sculpting the Immunological Response to Dengue Fever by Polytopic Vaccination 
Vaccine  2005;24(14):2451-2459.
The twin challenges of immunodominance and heterologous immunity have hampered discovery of an effective vaccine against all four dengue viruses. Here we explore how the T cell competition and selection underlying these asymmetrical properties impede effective T cell vaccine design. The theory we develop predicts dengue vaccine clinical trial data well. From the insights that we gain by this theory, we propose two new ideas for design of epitope-based T cell vaccines against dengue: polytopic injection and subdominant epitope priming.
doi:10.1016/j.vaccine.2005.12.031
PMCID: PMC4474404  PMID: 16417956
3.  Bridge- and Solvent-Mediated Intramolecular Electronic Communications in Ubiquinone-Based Biomolecular Wires 
Scientific Reports  2015;5:10352.
Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s.
doi:10.1038/srep10352
PMCID: PMC4440530  PMID: 25996306
4.  Identification, Characterization, and Developmental Expression Pattern of Type III Interferon Receptor Gene in the Chinese Goose 
BioMed Research International  2015;2015:186274.
Interferons, as the first line of defense against the viral infection, play an important role in innate immune responses. Type III interferon (IFN-λ) was a newly identified member of IFN family, which plays IFN-like antiviral activity. Towards a better understanding of the type III interferon system in birds, type III interferon lambda receptor (IFNLR1) was first identified in the Chinese goose. In this paper, we had cloned 1952 bp for goose IFNLR1 (goIFNLR1), including an ORF of 1539 bp, encoding a 512-amino acid protein with a 20 aa predict signal peptide at its N terminal and a 23 aa transmembrane region. The predicted amino acid sequence of goIFNLR1 has 90%, 73%, and 34% identity with duck IFNLR1 (predicted sequence), chicken IFNLR1, and human IFNLR1, respectively. And the age-related tissue distribution of goIFNLR1 was identified by Real Time quantitative PCR (RT-qPCR), we found that the goIFNLR1 has a mainly expression in epithelium-rich tissues similar to other species', such as small intestinal, lung, liver, and stomach. Moreover, a relatively high expression of goIFNLR1 was also observed in the secondary immune tissues (harderian gland and cecal tonsil). The identification and tissue distribution of goIFNLR1 will facilitate further study of the role of IFN-λ in goose antiviral defense.
doi:10.1155/2015/186274
PMCID: PMC4441995  PMID: 26064884
5.  Decreased BMP2 signal in GIT1 knockout mice slows bone healing 
Endochondral ossification, an important stage of fracture healing, is regulated by a variety of signaling pathways. Transforming growth factor b (TGFb) superfamily plays important roles and comprises TGFbs, bone morphogenetic proteins (BMPs), and growth differentiation factors. TGFbs primarily regulate cartilage formation and endochondral ossification. BMP2 shows diverse efficacy, from the formation of skeleton and extraskeletal organs to the osteogenesis and remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1 (GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by promoting bone formation and increasing the secretion of vascular endothelial growth factor. Our study examined whether GIT1 regulates fracture healing through the BMP2 signaling pathway and/or through the TGFb signaling pathway. GIT1 knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8 (pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2 stimulus. We detected no significant change in the pSmad2/3 level after TGFb1 stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on transcription via pSmad2/3 after TGFb1 stimulus. Our results indicate that GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2 expression, thus affecting endochondral ossification at the fracture site.
doi:10.1007/s11010-014-2173-5
PMCID: PMC4418226  PMID: 25138700
GIT1; TGFb; BMP2; Fracture healing
6.  Supramolecular-jack-like guest in ultramicroporous crystal for exceptional thermal expansion behaviour 
Nature Communications  2015;6:6917.
The dynamic behaviours of host frameworks and guest molecules have received much attention for their great relevance with smart materials, but little has been developed to control or understand the host–guest interplay. Here we show that the confined guest can utilize not only molecular static effects but also bulk dynamic properties to control the host dynamics. By virtue of the three-dimensional hinge-like framework and quasi-discrete ultramicropores, a flexible porous coordination polymer exhibits not only drastic guest-modulation effect of the thermal expansion magnitude (up to 422 × 10−6 K−1) and even the anisotropy but also records positive/negative thermal expansion coefficients of +482/−218 × 10−6 K−1. Moreover, single-crystal X-ray diffraction analyses demonstrate that the jack-like motion of the guest supramolecular dimers, being analogous to the anisotropic thermal expansion of bulk van der Waals solids, is crucial for changing the flexibility mode and thermal expansion behaviour of the crystal.
While host–guest interplay has been well studied, there has been less work on utilizing the bulk property of guest. Here, the authors show that the jack-like motion of guest supramolecular aggregations can drastically modulate the thermal expansion properties of a three-dimensional hinge-like framework.
doi:10.1038/ncomms7917
PMCID: PMC4411299  PMID: 25898347
7.  Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells 
Stem Cells International  2015;2015:534758.
Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular endothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further investigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect of the Rho/MRTF-A pathway on the expression of integrins α1β1 and α5β1, which are known to mediate physiological and pathological angiogenesis. Our results showed that increased expression of α1, α5, and β1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A signaling pathway was demonstrated to be involved in regulating the expression of integrins α1, α5, and β1. Luciferase reporter assay and ChIP assay determined that MRTF-A could bind to and transactivate the integrin α1 and α5 promoters. Treatment with the Rho inhibitor C3 transferase, the Rho-associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both the upregulation of α1, α5, and β1 as well as angiogenesis. Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion led to marked reductions in cell migration and vessel network formation compared with the control. These data demonstrate that Rho/MRTF-A signaling is an important mediator that controls integrin gene expression during MSC-mediated angiogenic processes.
doi:10.1155/2015/534758
PMCID: PMC4408638  PMID: 25949242
8.  IKKα negatively regulates ASC-dependent inflammasome activation 
Nature communications  2014;5:4977.
The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IKKα is a critical negative regulator of ASC-dependent inflammasomes. IKKα controls the inflammasome at the level of the adaptor ASC, which interacts with IKKα in the nucleus of resting macrophages in an IKKα kinase-dependent manner. Loss of IKKα kinase activity results in inflammasome hyperactivation. Mechanistically, the downstream nuclear effector IKKi facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation. ASC remains under the control of IKKα in the perinuclear area following translocation of the ASC/IKKα complex. Signal 2 of NLRP3 activation leads to inhibition of IKKα kinase activity through the recruitment of PP2A, allowing ASC to participate in NLRP3 inflammasome assembly. Taken together, these findings reveal a IKKi-IKKα-ASC axis that serves as a common regulatory mechanism for ASC-dependent inflammasomes.
doi:10.1038/ncomms5977
PMCID: PMC4298287  PMID: 25266676
9.  Prognostic role of YB-1 expression in breast cancer: a meta-analysis 
Objective: In published studies, Y-box binding protein-1 (YB-1) correlated with the prognosis of patients with breast cancer (BC), but the specific role of YB-1 is still unclear. Our study aimed to evaluate the prognostic value of YB-1 in BC patients using meta-analysis based on the published studies. Methods: We searched the relevant literatures deadline for June 2014 in databases, including PubMed, Embase, Medline and Cochrane library, and finally 8 studies were included in our study. Our study contained 1094 BC patients with 398 YB-1 positive and 696 YB-1 negative. Results: Our results showed that YB-1 abnormal expression did not correlated with the lymph node status [OR = 1.258, 95% CI = 0.895-1.769, P = 0.186], high histological grade [OR = 2.709, 95% CI = 0.861-8.530, P = 0.089], histological type [OR = 0.837, 95% CI = 0.526-1.331, P = 0.452], P53 status [OR = 2.006, 95% CI 0.686-5.865, P = 0.203] and PR [OR = 0.607, 95% CI = 0.347-1.061, P = 0.080] in BC patients. But YB-1 over-expression was associated with other unfavorable factors: ER negativity [OR = 0.604, 95% CI = 0.388-0.941, P = 0.026], HER2 positivity [OR = 3.841, 95% CI = 2.637-5.594, P = 0.000], and high tumorous T stage [OR = 2.169, 95% CI = 1.295-3.632, P = 0.003]. In addition, our data suggested that high YB-1 expression had an adverse impact on 5-year OS [RR = 2.767, 95% CI = 2.054-3.727, P = 0.000] in BC patients. Conclusions: Our findings implied that YB-1 might a novel biomarker to predict the prognosis of BC, and could be a potential direction for developing diagnostic and therapeutic approaches in BC.
PMCID: PMC4402753  PMID: 25932106
YB-1; breast cancer; prognosis; meta-analysis
10.  Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway 
Molecular Medicine Reports  2015;11(6):4063-4072.
Adipose-derived stem cells (ADSCs) are considered a suitable source of cells for the repair of tissue following acute myocardial infarction (AMI); however, the transplantation efficiency of ADSCs remains low. Therefore, identification of an efficient method to enhance the migration of engrafted cells to the target site is required. The present study used exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, to optimize the migratory capacity of ADSCs. The aim was to determine the effect and mechanisms of Ex-4 on the migration of ADSCs to neonatal rat ventricular cardiomyocyte-derived conditioned medium (NRVC-CM). The ADSCs and cardiomyocytes were cultured in vitro. Following incubation of the ADSCs with Ex-4, cell proliferation was measured using an MTT assay and the expression levels of CXC chemokine receptor 4 (CXCR4) were investigated by reverse transctiption quantitative polymerase chain reaction (RT-qPCR), western blot analysis and flow cytometry. In addition, the expression levels of stromal cell-derived factor-1α (SDF-1α) were evaluated in the NRVC-CM treated with Ex-4 by ELISA, RT-qPCR and western blot analysis. The migration of the ADSCs to the NRVC-CM was examined using a Transwell assay. Changes in the protein expression levels of phosphorylated (p−)Akt were examined in the two types of cell by western blot analysis. The results suggested that Ex-4 promoted the proliferation and expression of CXCR4 in the ADSCs, increased the secretion of SDF-1α in the cardiomyocytes and increased the expression levels of p-Akt in both cells. However, the alterations to the SDF-1α/C XC R4 cascade in the cells were abrogated following pretreatment with LY-294002, a phosphoinositide 3-kinase(PI3K) inhibitor. Furthermore, a Transwell migration assay revealed marked translocation of the ADSCs through the membranes, towards the NRVC-CM, following treatment with Ex-4. However, these effects were reduced significantly by pretreatment of the cells with the SDF-1α/CXCR4 cascade antagonist, AMD3100, and the PI3K inhibitor, LY-294002. These results indicated that Ex-4 augmented the SDF-1α/CXCR4 cascade by activating the PI3K/Akt pathways in the ADSCs and NRVCs. Furthermore, enhancement of the PI3K/Akt-SDF-1α/CXCR4 pathway may be important in the migratory response of ADSCs to NRVC-CM in vitro.
doi:10.3892/mmr.2015.3243
PMCID: PMC4394957  PMID: 25625935
Exendin-4; adipose-derived stem cells; cardiomyocytes; stromal cell-derived factor-1α; CXC chemokine receptor 4; phosphoinositide 3-kinase/Akt pathways; migration
11.  Number of negative lymph nodes can predict survival of breast cancer patients with four or more positive lymph nodes after postmastectomy radiotherapy 
Background
This study was conducted to assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with four or more positive lymph nodes after postmastectomy radiotherapy (PMRT).
Methods
This retrospective study examined 605 breast cancer patients with four or more positive lymph nodes who underwent mastectomy. A total of 371 patients underwent PMRT. The prognostic value of the NLN count in patients with and without PMRT was analyzed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors.
Results
The median follow-up was 54 months, and the overall 8-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 79.8%, 50.0%, 46.8%, and 57.9%, respectively. The optimal cut-off points for NLN count was 12. Univariate analysis showed that the number of NLNs, lymph node ratio (LNR) and pN stage predicted the LRFS of non-PMRT patients (p < 0.05 for all). Multivariate analysis showed that the number of NLNs was an independent prognostic factor affecting the LRFS, patients with a higher number of NLNs had a better LRFS (hazard ratio = 0.132, 95% confidence interval = 0.032-0.547, p =0.005). LNR and pN stage had no effect on LRFS. PMRT improved the LRFS (p < 0.001), DMFS (p = 0.018), DFS (p = 0.001), and OS (p = 0.008) of patients with 12 or fewer NLNs, but it did not any effect on survival of patients with more than 12 NLNs. PMRT improved the regional lymph node recurrence-free survival (p < 0.001) but not the chest wall recurrence-free survival (p = 0.221) in patients with 12 or fewer NLNs.
Conclusions
The number of NLNs can predict the survival of breast cancer patients with four or more positive lymph nodes after PMRT.
Electronic supplementary material
The online version of this article (doi:10.1186/s13014-014-0284-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13014-014-0284-5
PMCID: PMC4278342  PMID: 25511525
Breast cancer; Mastectomy; Negative lymph nodes; Radiotherapy
12.  Relationships between actual and desired workplace characteristics and job satisfaction for community health workers in China: a cross-sectional study 
BMC Family Practice  2014;15:180.
Background
Community health workers are the main providers of community health services in China and have been important in the process of health system reform that has been in place since 2009. Therefore, it is critical that healthcare managers and policy decision makers motivate current staff and improve their job satisfaction. This study examined workplace characteristics and their contribution to job satisfaction in community health workers in Heilongjiang Province, China.
Methods
A cross-sectional survey of 448 community health workers, from three cities in Heilongjiang province, was conducted between October 1, 2012 and December 31, 2012. Multistage sampling procedures were used to measure socioeconomic and demographic status, job satisfaction, and both actual and desired workplace characteristics. Factor analysis was conducted to determine the main factors contributing to workplace characteristics, and multiple linear regression analysis was performed to assess the key determinants of job satisfaction.
Results
Eight groups of factors were identified as the most important workplace characteristics. These comprised system and policy; fringe benefits; work itself; work relationships; professional development; recognition; work environment; and remuneration. In all cases, all desired workplace characteristics were higher than the associated actual workplace characteristics. The main determinants of job satisfaction were occupation, years worked in health service institution, and five subscales representing the gap between desired and actual workplace characteristics, which were system and policy; fringe benefits; working relationship; professional development; and remuneration.
Conclusions
These findings suggested that managers wishing to enhance job satisfaction should assess workplace characteristics comprehensively and design mechanisms that reduce the gap between actual and desired workplace characteristics.
doi:10.1186/s12875-014-0180-y
PMCID: PMC4240823  PMID: 25403924
Actual workplace characteristics; Desired workplace characteristics; Job satisfaction; China
13.  MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases 
MyD88-dependent GM-CSF production by endothelial cells plays a role in the initiation of obesity-associated inflammation by promoting adipose macrophage recruitment and M1-like polarization.
Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor–MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet–induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.
doi:10.1084/jem.20131314
PMCID: PMC4010914  PMID: 24752299
14.  Interferons and Their Receptors in Birds: A Comparison of Gene Structure, Phylogenetic Analysis, and Cross Modulation 
Interferon may be thought of as a key, with the interferon receptor as the signal lock: Crosstalk between them maintains their balance during viral infection. In this review, the protein structure of avian interferon and the interferon receptor are discussed, indicating remarkable similarity between different species. However, the structures of the interferon receptors are more sophisticated than those of the interferons, suggesting that the interferon receptor is a more complicated signal lock system and has considerable diversity in subtypes or structures. Preliminary evolutionary analysis showed that the subunits of the interferon receptor formed a distinct clade, and the orthologs may be derived from the same ancestor. Furthermore, the development of interferons and interferon receptors in birds may be related to an animal’s age and the maintenance of a balanced state. In addition, the equilibrium between interferon and its receptor during pathological and physiological states revealed that the virus and the host influence this equilibrium. Birds could represent an important model for studies on interferon’s antiviral activities and may provide the basis for new antiviral strategies.
doi:10.3390/ijms151121045
PMCID: PMC4264211  PMID: 25405736
interferon; interferon receptor; predicted gene structure; phylogenetic analysis; interplay
15.  Self-assembling choline mimicks with enhanced binding affinities to C-LytA protein 
Scientific Reports  2014;4:6621.
Streptococcus pneumoniae (pneumococcus) causes multiple illnesses in humans. Exploration of effective inhibitors with multivalent attachment sites for choline-binding modules is of great importance to reduce the pneumococcal virulence. In this work, we successfully developed two self-assembling choline mimicks, Ada-GFFYKKK' and Nap-GFFYKKK', which have the abilities to self-assemble into nanoparticles and nanofibers, respectively, yielding multivalent architectures. Additionally, the best characterized choline-binding module, C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) was also produced with high purity. The self-assembling Ada-GFFYKKK' and Nap-GFFYKKK' show strong interactions with C-LytA, which possess much higher association constant values to the choline-binding modules as compared to the individual peptide Fmoc-K'. This study thus provides a self-assembly approach to yield inhibitors that are very promising for reducing the pneumococcal virulence.
doi:10.1038/srep06621
PMCID: PMC4197414  PMID: 25315737
16.  A Genetically Modified Protein-Based Hydrogel for 3D Culture of AD293 Cells 
PLoS ONE  2014;9(9):e107949.
Hydrogels have strong application prospects for drug delivery, tissue engineering and cell therapy because of their excellent biocompatibility and abundant availability as scaffolds for drugs and cells. In this study, we created hybrid hydrogels based on a genetically modified tax interactive protein-1 (TIP1) by introducing two or four cysteine residues in the primary structure of TIP1. The introduced cysteine residues were crosslinked with a four-armed poly (ethylene glycol) having their arm ends capped with maleimide residues (4-armed-PEG-Mal) to form hydrogels. In one form of the genetically modification, we incorporated a peptide sequence ‘GRGDSP’ to introduce bioactivity to the protein, and the resultant hydrogel could provide an excellent environment for a three dimensional cell culture of AD293 cells. The AD293 cells continued to divide and displayed a polyhedron or spindle-shape during the 3-day culture period. Besides, AD293 cells could be easily separated from the cell-gel constructs for future large-scale culture after being cultured for 3 days and treating hydrogel with trypsinase. This work significantly expands the toolbox of recombinant proteins for hydrogel formation, and we believe that our hydrogel will be of considerable interest to those working in cell therapy and controlled drug delivery.
doi:10.1371/journal.pone.0107949
PMCID: PMC4169439  PMID: 25233088
17.  Single-molecule force spectroscopy reveals force-enhanced binding of calcium ions by gelsolin 
Nature Communications  2014;5:4623.
Force is increasingly recognized as an important element in controlling biological processes. Forces can deform native protein conformations leading to protein-specific effects. Protein–protein binding affinities may be decreased, or novel protein–protein interaction sites may be revealed, on mechanically stressing one or more components. Here we demonstrate that the calcium-binding affinity of the sixth domain of the actin-binding protein gelsolin (G6) can be enhanced by mechanical force. Our kinetic model suggests that the calcium-binding affinity of G6 increases exponentially with force, up to the point of G6 unfolding. This implies that gelsolin may be activated at lower calcium ion levels when subjected to tensile forces. The demonstration that cation–protein binding affinities can be force-dependent provides a new understanding of the complex behaviour of cation-regulated proteins in stressful cellular environments, such as those found in the cytoskeleton-rich leading edge and at cell adhesions.
The application of force can influence biological processes such as ligand and protein–protein binding, with mechanical stress typically hindering such interactions. Here, the authors use atomic force microscopy to show that the binding of calcium to gelsolin can be improved under stress.
doi:10.1038/ncomms5623
PMCID: PMC4143929  PMID: 25100107
19.  Work stress, work motivation and their effects on job satisfaction in community health workers: a cross-sectional survey in China 
BMJ Open  2014;4(6):e004897.
Objective
It is well documented that both work stress and work motivation are key determinants of job satisfaction. The aim of this study was to examine levels of work stress and motivation and their contribution to job satisfaction among community health workers in Heilongjiang Province, China.
Design
Cross-sectional survey.
Setting
Heilongjiang Province, China.
Participants
The participants were 930 community health workers from six cities in Heilongjiang Province.
Primary and secondary outcome measures
Multistage sampling procedures were used to measure socioeconomic and demographic status, work stress, work motivation and job satisfaction. Logistic regression analysis was performed to assess key determinants of job satisfaction.
Results
There were significant differences in some subscales of work stress and work motivation by some of the socioeconomic characteristics. Levels of overall stress perception and scores on all five work stress subscales were higher in dissatisfied workers relative to satisfied workers. However, levels of overall motivation perception and scores on the career development, responsibility and recognition motivation subscales were higher in satisfied respondents relative to dissatisfied respondents. The main determinants of job satisfaction were occupation; age; title; income; the career development, and wages and benefits subscales of work stress; and the recognition, responsibility and financial subscales of work motivation.
Conclusions
The findings indicated considerable room for improvement in job satisfaction among community health workers in Heilongjiang Province in China. Healthcare managers and policymakers should take both work stress and motivation into consideration, as two subscales of work stress and one subscale of work motivation negatively influenced job satisfaction and two subscales of work motivation positively influenced job satisfaction.
doi:10.1136/bmjopen-2014-004897
PMCID: PMC4054641  PMID: 24902730
Public Health
21.  Magnetic Field Tunable Small-scale Mechanical Properties of Nickel Single Crystals Measured by Nanoindentation Technique 
Scientific Reports  2014;4:4583.
Nano- and micromagnetic materials have been extensively employed in micro-functional devices. However, measuring small-scale mechanical and magnetomechanical properties is challenging, which restricts the design of new products and the performance of smart devices. A new magnetomechanical nanoindentation technique is developed and tested on a nickel single crystal in the absence and presence of a saturated magnetic field. Small-scale parameters such as Young's modulus, indentation hardness, and plastic index are dependent on the applied magnetic field, which differ greatly from their macroscale counterparts. Possible mechanisms that induced 31% increase in modulus and 7% reduction in hardness (i.e., the flexomagnetic effect and the interaction between dislocations and magnetic field, respectively) are analyzed and discussed. Results could be useful in the microminiaturization of applications, such as tunable mechanical resonators and magnetic field sensors.
doi:10.1038/srep04583
PMCID: PMC3974134  PMID: 24695002
22.  On the mechanisms of the recurvature of super typhoon Megi 
Scientific Reports  2014;4:4451.
Tropical cyclones (TC) are one of the most threatening natural hazards to human beings. Although significant improvements have been made in the track prediction of TCs during the past several decades, considerable uncertainties still exist, especially for recurving tracks. In this study, we explore the physical mechanisms that drove the large recurvature of super typhoon Megi through numerical sensitivity experiments using a regional atmospheric model. The results indicate that the cold air intrusion from the northwest to the southeast of China is the main cause of the sharp turning of Megi. This finding suggests that a cold air intrusion could be taken as an indicator for predicting the recurvature of a tropical cyclone in the future.
doi:10.1038/srep04451
PMCID: PMC3964559  PMID: 24663145
23.  Neural Network Assisted Inverse Dynamic Guidance for Terminally Constrained Entry Flight 
The Scientific World Journal  2014;2014:686040.
This paper presents a neural network assisted entry guidance law that is designed by applying Bézier approximation. It is shown that a fully constrained approximation of a reference trajectory can be made by using the Bézier curve. Applying this approximation, an inverse dynamic system for an entry flight is solved to generate guidance command. The guidance solution thus gotten ensures terminal constraints for position, flight path, and azimuth angle. In order to ensure terminal velocity constraint, a prediction of the terminal velocity is required, based on which, the approximated Bézier curve is adjusted. An artificial neural network is used for this prediction of the terminal velocity. The method enables faster implementation in achieving fully constrained entry flight. Results from simulations indicate improved performance of the neural network assisted method. The scheme is expected to have prospect for further research on automated onboard control of terminal velocity for both reentry and terminal guidance laws.
doi:10.1155/2014/686040
PMCID: PMC3958667  PMID: 24723821
24.  Academic Achievement and Loneliness of Migrant Children in China: School Segregation and Segmented Assimilation1 
Comparative education review  2013;57(1):85-116.
China’s rural-urban migration presents a significant educational challenge. This study uses theories of segmented assimilation and school segregation to measure the assimilation and well-being of migrant children who attend either Beijing’s public schools or its informal migrant schools. Controling for other factors, we find poorer achievement and greater loneliness among migrant children who are isolated in migrant schools than similar migrant students enrolled in regular urban public schools. We show there is little difference in learning outcome or loneliness between urban native children and migrant children who attend public schools. We further discuss similarities and differences between the experiences of migrant children in China and immigrant children in the United States.
doi:10.1086/667790
PMCID: PMC3782113  PMID: 24078743
25.  Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model 
Molecular Vision  2014;20:977-987.
Purpose
Scleral remodeling is an important mechanism underlying the development of myopia. Atropine, an antagonist of G protein-coupled muscarinic receptors, is currently used as an off-label treatment for myopia. Regulator of G-protein signaling 2 (RGS2) functions as an intracellular selective inhibitor of muscarinic receptors. In this study we measured scleral RGS2 expression and scleral remodeling in an animal model of myopia in the presence or absence of atropine treatment.
Methods
Guinea pigs were assigned to four groups: normal (free of form deprivation), form deprivation myopia (FDM) for 4 weeks, FDM treated with saline, and FDM treated with atropine. Biometric measurements were then performed. RGS2 expression levels and scleral remodeling, including scleral thickness and collagen type I expression, were compared among the four groups.
Results
Compared with normal eyes and contralateral control eyes, the FDM eyes had the most prominent changes in refraction, axial length, and scleral remodeling, indicating myopia. There was no significant difference between control and normal eyes. Hematoxylin and eosin staining showed that the scleral thickness was significantly thinner in the posterior pole region of FDM eyes compared to normal eyes. Real-time PCR and western blot analysis showed a significant decrease in posterior scleral collagen type I mRNA and protein expression in the FDM eyes compared to the normal eyes. The FDM eyes also had increased levels of RGS2 mRNA and protein expression in the sclera. Atropine treatment attenuated the FDM-induced changes in refraction, axial length, and scleral remodeling. Interestingly, atropine treatment significantly increased collagen type I mRNA expression but decreased RGS2 mRNA and protein expression in the sclera of the FDM eyes.
Conclusions
We identified a significant RGS2 upregulation and collagen type I downregulation in the sclera of FDM eyes, which could be partially attenuated by atropine treatment. Our data suggest that targeting dysregulated RGS2 may provide a novel strategy for development of therapeutic agents to suppress myopia progression.
PMCID: PMC4087119  PMID: 25018620

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