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1.  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
2.  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(1):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
3.  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
4.  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
5.  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
6.  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
8.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  A SYNDROME OF SEVERE HYPOGLYCEMIA AND ACIDOSIS IN YOUNG IMMUNOSUPPRESSED DIABETIC MONKEYS AND PIGS – ASSOCIATION WITH SEPSIS1 
Transplantation  2012;94(12):1187-1191.
Background
Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes in these animals if islet transplantation is planned.
Methods
We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy +/− islet allotransplantation.
Results
In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment. We do not believe this syndrome has been reported previously by others.
Conclusions
Despite treatment, this syndrome complicated the interpretation of blood glucose readings as a measure of islet graft function, and resulted in death or the need for euthanasia in all 7 animals. We tentatively suggest that the syndrome may be related to the presence of microorganisms that metabolize glucose and produce lactate.
doi:10.1097/TP.0b013e318272210c
PMCID: PMC3529756  PMID: 23128998
Acidosis; metabolic; Hypoglycemia; Infection; Islet transplantationMonkey
16.  Genome Sequence of Dyella ginsengisoli Strain LA-4, an Efficient Degrader of Aromatic Compounds 
Genome Announcements  2013;1(6):e00961-13.
Dyella ginsengisoli strain LA-4 can efficiently degrade environmental pollutants such as biphenyl and azo dyes. Here, we present a 4.55-Mb draft genome sequence of strain LA-4, which may provide further insights into the molecular mechanism in environmental pollution remediation.
doi:10.1128/genomeA.00961-13
PMCID: PMC3837176  PMID: 24265495
17.  Immune-related GTPase M (IRGM1) regulates neuronal autophagy in a mouse model of stroke 
Autophagy  2012;8(11):1621-1627.
Autophagy is an important cellular recycling mechanism through self-digestion in responses to cellular stress such as starvation. Studies have shown that autophagy is involved in maintaining the homeostasis of the neural system during stroke. However, molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. Previously, we and others have shown that immune-related GTPase M (IRGM; termed IRGM1 in the mouse nomenclature) can regulate the survival of immune cells through autophagy in response to infections and autoimmune conditions. Here, using a permanent middle cerebral artery occlusion (pMCAO) mouse model, we found that IRGM1 was upregulated in the ischemic side of the brain, which was accompanied by a significant autophagic response. In contrast, neuronal autophagy was almost complete lost in Irgm1 knockout (KO) mice after pMCAO induction. In addition, the infarct volume in the Irgm1-KO pMCAO mice was significantly increased as compared to wild-type mice. Histological studies suggested that, at the early stage (within 24 h) of ischemia, the IRGM1-dependent autophagic response is associated with a protection of neurons from necrosis in the ischemic core but a promotion of neuronal apoptosis in the penumbra area. These data demonstrate a novel role of IRGM1 in regulating neuronal autophagy and survival during ischemic stroke.
doi:10.4161/auto.21561
PMCID: PMC3494591  PMID: 22874556
autophagy; IRGM1; pMCAO; necrosis and apoptosis
18.  A Protein-Based Hydrogel for In Vitro Expansion of Mesenchymal Stem Cells 
PLoS ONE  2013;8(9):e75727.
Hydrogels are widely used as scaffolds in tissue engineering because they can provide excellent environments for bioactive components including growth factors and cells. We reported in this study on a physical hydrogel formed by a specific protein-peptide interaction, which could be used for the three dimensional (3D) cell culture of murine mesenchymal stem cells (mMSC). The mMSC kept dividing during the 7-day culture period and the metabolic-active cell number at day 7 was 359% more than that at day 1. This kind of physical hydrogel could be converted to a homogeneous solution by firstly adding an equal volume of culture medium and then pipeting for several times. Therefore, mMSC post culture could be easily separated from cell-gel constructs. We believed that the protein-based hydrogel system in this study could be developed into a promising scaffold for in vitro expansion of stem cells and cell therapy. This work would be in the general interests of researchers in the fields of biomaterials and supramolecular chemistry.
doi:10.1371/journal.pone.0075727
PMCID: PMC3777955  PMID: 24069442
19.  Structural insights into Paf1 complex assembly and histone binding 
Nucleic Acids Research  2013;41(22):10619-10629.
The highly conserved Paf1 complex (PAF1C) plays critical roles in RNA polymerase II transcription elongation and in the regulation of histone modifications. It has also been implicated in other diverse cellular activities, including posttranscriptional events, embryonic development and cell survival and maintenance of embryonic stem cell identity. Here, we report the structure of the human Paf1/Leo1 subcomplex within PAF1C. The overall structure reveals that the Paf1 and Leo1 subunits form a tightly associated heterodimer through antiparallel beta-sheet interactions. Detailed biochemical experiments indicate that Leo1 binds to PAF1C through Paf1 and that the Ctr9 subunit is the key scaffold protein in assembling PAF1C. Furthermore, we show that the Paf1/Leo1 heterodimer is necessary for its binding to histone H3, the histone octamer, and nucleosome in vitro. Our results shed light on the PAF1C assembly process and substrate recognition during various PAF1C-coordinated histone modifications.
doi:10.1093/nar/gkt819
PMCID: PMC3905892  PMID: 24038468
20.  A Pre-mRNA-Splicing Factor Is Required for RNA-Directed DNA Methylation in Arabidopsis 
PLoS Genetics  2013;9(9):e1003779.
Cytosine DNA methylation is a stable epigenetic mark that is frequently associated with the silencing of genes and transposable elements (TEs). In Arabidopsis, the establishment of DNA methylation is through the RNA-directed DNA methylation (RdDM) pathway. Here, we report the identification and characterization of RDM16, a new factor in the RdDM pathway. Mutation of RDM16 reduced the DNA methylation levels and partially released the silencing of a reporter gene as well as some endogenous genomic loci in the DNA demethylase ros1-1 mutant background. The rdm16 mutant had morphological defects and was hypersensitive to salt stress and abscisic acid (ABA). Map-based cloning and complementation test led to the identification of RDM16, which encodes a pre-mRNA-splicing factor 3, a component of the U4/U6 snRNP. RNA-seq analysis showed that 308 intron retention events occurred in rdm16, confirming that RDM16 is involved in pre-mRNA splicing in planta. RNA-seq and mRNA expression analysis also revealed that the RDM16 mutation did not affect the pre-mRNA splicing of known RdDM genes, suggesting that RDM16 might be directly involved in RdDM. Small RNA expression analysis on loci showing RDM16-dependent DNA methylation suggested that unlike the previously reported putative splicing factor mutants, rdm16 did not affect small RNA levels; instead, the rdm16 mutation caused a decrease in the levels of Pol V transcripts. ChIP assays revealed that RDM16 was enriched at some Pol V target loci. Our results suggest that RDM16 regulates DNA methylation through influencing Pol V transcript levels. Finally, our genome-wide DNA methylation analysis indicated that RDM16 regulates the overall methylation of TEs and gene-surrounding regions, and preferentially targets Pol IV-dependent DNA methylation loci and the ROS1 target loci. Our work thus contributes to the understanding of RdDM and its interactions with active DNA demethylation.
Author Summary
Both plants and animals utilize cytosine DNA methylation as an important epigenetic mark to suppress transposable elements (TEs), repeat sequences and genes, which is crucial for the genome integrity and development. In plants, de novo DNA methylation can be mediated by the RNA-directed DNA methylation (RdDM) pathway. Plants have also evolved a pathway for active DNA demethylation that is initiated by the ROS1 subfamily of 5-methylcytosine DNA glycosylases, to counteract the RdDM pathway to prevent undesirable silencing. In this study, we identified RDM16, a new factor in the RdDM pathway. We show that RDM16 is a pre-mRNA splicing factor and its function in the regulation of DNA methylation and gene silencing is not through influencing siRNA levels or the expression or splicing of genes encoding known RdDM components, but likely through affecting Pol V transcripts. We also show that RDM16 preferentially affects ROS1 target loci. Together, our findings contribute to the understanding of RdDM and its interactions with ROS1-mediated DNA demethylation.
doi:10.1371/journal.pgen.1003779
PMCID: PMC3772050  PMID: 24068953
21.  PLATELET AGGREGATION IN HUMANS AND NONHUMAN PRIMATES: RELEVANCE TO XENOTRANSPLANTATION 
Xenotransplantation  2012;19(4):233-243.
Introduction
Platelet activation/aggregation plays a key role in the dysregulation of coagulation and the development of thrombotic microangiopathy in nonhuman primate recipients of pig xenografts. As a preliminary to the study of anti-platelet therapy in vitro and in vivo, the present study aimed to compare platelet aggregation in whole blood from humans, baboons, and cynomolgus monkeys.
Methods
Using ‘Chrono-log’ technology (two-sample four-channel Chrono-log Whole Blood Aggregometer), we studied aggregation of platelets in healthy humans (n=8), baboons (n=5), and monkeys (n=8). Whole blood (blood) samples were collected, and platelet aggregation was assessed using three different volumes of blood (1, 0.5, and 0.25 mL). Platelet activation was induced using collagen (at 3 and 5 µg/mL), ristocetin (at 0.5 and 1.0 mg/ml), adenosine diphosphate (ADP; at 10, 20, and 40 µM), or thrombin (at 1 and 5 IU/ml). Inhibition of agonist-induced platelet aggregation by heparin and low molecular weight heparin (LMWH) (at 1, 10, and 100 IU/mL) was evaluated.
Results
Mean platelet counts were 222.1, 263.2, and 276.1 (x103/ul) in humans, baboons, and monkeys, respectively. In all 3 species, platelet aggregation was induced by collagen, ristocetin, ADP, or thrombin in a dose-dependent manner. A blood volume of 0.5mL provided the most consistent results with all agonists in all 3 species. Dilution studies indicated that there was a significant positive correlation between platelet count and percent aggregation of platelets (p<0.05). Collagen (3 and 5µg/mL), ADP (10, 20 and 40 µM) and thrombin (1 and 5 IU/ml) induced significantly greater platelet aggregation in humans than in baboons. ADP (20 and 40 µM) and thrombin (1 and 5 IU/ml) induced significantly greater platelet aggregation in monkeys than in baboons. There was no species difference with ristocetin (0.5 or 1.0 mg/ml). In all species, thrombin (1 or 5 IU) induced greater platelet aggregation than any of the other reagents. Heparin at 1 IU/mL and LMWH at 10 IU/ml in all species almost completely abrogated thrombin-induced platelet aggregation. Heparin at 100 IU/mL effectively inhibited platelet aggregation induced by collagen, but only partially inhibited aggregation induced by ADP or ristocetin. LMWH only partially inhibited aggregation induced by collagen, ristocetin and ADP.
Conclusions
The ‘Chrono-log’ technology proved to be a reliable method of evaluating platelet activation and aggregation in vitro in primates. Species differences may play a role in platelet aggregation, with the monkey being more comparable to the human than the baboon, though overall trends were similar. In all species, thrombin induced greater platelet aggregation than other agonists. Even a concentration of heparin of 1 IU/ml, which is probably the maximal concentration that is clinically-applicable, prevented platelet aggregation induced by thrombin, but were less effective in preventing aggregation induced by collagen, ADP, or, particularly, ristocetin.
doi:10.1111/j.1399-3089.2012.00712.x
PMCID: PMC3425958  PMID: 22909136
Aggregation; Coagulation; Platelets; Primates; Xenotransplantation
22.  Draft Genome Sequences of Two Streptococcus pyogenes Strains Involved in Abnormal Sharp Raised Scarlet Fever in China, 2011 
Journal of Bacteriology  2012;194(21):5983-5984.
A scarlet fever outbreak caused by Streptococcus pyogenes occurred in China in 2011. To determine the genomic features of the outbreak strains, we deciphered genomes of two strains isolated from the regions with the highest incidence rates. The sequences will provide valuable information for comprehensive study of mechanisms related to this outbreak.
doi:10.1128/JB.01474-12
PMCID: PMC3486120  PMID: 23045496
23.  β-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-κB Activation 
Molecular and Cellular Biology  2012;32(19):3990-4000.
Interleukin-1 (IL-1) receptor-associated kinase (IRAK1) is phosphorylated, ubiquitinated, and degraded upon IL-1 stimulation. IRAK1 can be ubiquitinated through both K48- and K63-linked polyubiquitin chains upon IL-1 stimulation. While the Pellino proteins have been shown to meditate K63-linked polyubiquitination on IRAK1, the E3 ligase for K48-linked ubiquitination of IRAK1 has not been identified. In this study, we report that the SCF (Skp1–Cullin1–F-box)–β-TrCP complex functions as the K48-linked ubiquitination E3 ligase for IRAK1. IL-1 stimulation induced the interaction of IRAK1 with Cullin1 and β-TrCP. Knockdown of β-TrCP1 and β-TrCP2 attenuated the K48-linked ubiquitination and degradation of IRAK1. Importantly, β-TrCP deficiency abolished the translocation TAK1-TRAF6 complex from the membrane to the cytosol, resulting in a diminishment of the IL-1-induced TAK1-dependent pathway. Taken together, these results implicate a positive role of β-TrCP-mediated IRAK1 degradation in IL-1-induced TAK1 activation.
doi:10.1128/MCB.00722-12
PMCID: PMC3457527  PMID: 22851693
24.  Genome Sequence of a Novel Indigo-Producing Strain, Pseudomonas monteilii QM 
Journal of Bacteriology  2012;194(16):4459-4460.
Pseudomonas monteilii is a versatile bacterium found in various niches. A newly isolated strain, P. monteilii QM, can effectively produce indigoids from indoles. Here we present a 5.76-Mb assembly of the P. monteilii genome for the first time. It may provide abundant molecular information for the transformation of aromatics.
doi:10.1128/JB.00867-12
PMCID: PMC3416222  PMID: 22843591
25.  Genome Sequence of Sphingomonas xenophaga QYY, an Anthraquinone-Degrading Strain 
Genome Announcements  2013;1(1):e00031-12.
Sphingomonas xenophaga QYY is an efficient anthraquinone-degrading strain. Here, we present a 4.2-Mb assembly of the first genome sequence of S. xenophaga. We have annotated 36 coding sequences (CDSs) encoding aromatic catabolism and 216 CDSs responsible for toxic resistance and stress response, which may provide insights into the degradation of complex aromatics.
doi:10.1128/genomeA.00031-12
PMCID: PMC3569308  PMID: 23405319

Results 1-25 (47)