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Background: Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. Twenty newly diagnosed active primary ITP patients who had not been treated with glucocorticosteroids, immune globulin or immunosuppressants prior to sampling were enrolled in this study. Bone marrow blood mononuclear cells were used for whole exome sequencing to further elucidation the variant genes of ITP., Methods: High-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing, and the results were confirmed by Sanger sequencing. The signaling pathways and cellular processes associated with the mutated genes were identified with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses., Results: The results showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including phosphatase and tensin homolog, insulin receptor, and coagulation factor C homology were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B signaling pathways (signal transduction) and platelet activation (immune system)., Conclusion: Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Accident statistics show that more than 80% of car-to-pedestrian collisions (CPC) occur when pedestrians cross the road. It is very important to establish a finite element model with natural walking posture to study the kinematics and injury mechanism of pedestrians. In this study, a finite element model of six-year-old child pedestrian is developed with detailed anatomical characteristics and posture parameters as specified in Euro NCAP Pedestrian Human Model Certification (TB024). The numerical human body model is validated in total twelve simulations in which the pedestrian is impacted against four generic vehicle models at speeds 30, 40, 50 km/h prescribed in TB024. The Head Impact Time (HIT), Contact Force and the Trajectories of HC, T12 and AC of all twelve simulations are compared with the reference corridors provided by Technical Bulletin 024. The results indicate that the numerical human body model of a six-year-old child can be used to demonstrate the suitability of the sensing system for the range of pedestrian sizes; the timing of system deployment, and the bonnet deflection due to body loading. Furthermore, the model could be a good tool for further research on pedestrian injury mechanism and the development of pedestrian protection devices.

Transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) may contribute to tumor metastasis. TGF-β1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1-integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and metastasis in several cancers. However, whether ursolic acid can attenuate TGF-β1-induced EMT in H1975 cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the TGF-β1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolic acid inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion, and activity of matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that ursolic acid could inhibit EMT in NSCLC through TGF-β1 signaling pathway-mediated integrin αVβ5 expression, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude that ursolic acid attenuated TGF-β1-induced EMT in H1975 cells and thus might be a promising therapeutic agent for treating NSCLC.

Lipotoxicity is associated with a high level of fatty acid accumulation in pancreatic β-cells. An overload of free fatty acids contributes to pancreatic β-cell apoptosis and dysfunction. Insulin secretion involves sequential ionic events upon glucose stimulation. ATP sensitive potassium (K ATP ) channels serve as glucose sensors and effectively initiate glucose-stimulated insulin secretion. This study investigated the effects of lipotoxicity on the trafficking of K ATP channels in pancreatic β cells using chronic palmitic acid -injected mice and treated insulinoma cells. The chronic palmitic acid -injected mice displayed type II diabetic characteristics. The pancreatic sections of these mice exhibited a decrease in the expression of K ATP channels. We then tested the time and dose effects of palmitic acid on the cell viability of INS-1 cells. We observed a significant decrease in the surface expression of K ATP channels after 72 h of treatment with 0.4 mM palmitic acid. In addition, this treatment induced pancreatic β-cell apoptosis by increasing cleaved caspase 3 protein level. Our results demonstrated cotreatment with glibenclamide, the sulfonylurea compounds for type II diabetes mellitus, in palmitic acid -treated cells reduces cell death and recovers the glucose stimulated insulin secretion through increasing the surface expression of K ATP channels. Importantly, glibenclamide also improved glucose tolerance, triglyceride concentration, and insulin sensitivity in the palmitic acid-injected mice. In conclusion, an increase in the surface expression of K ATP channels restores insulin secretion, reduces pancreatic β-cell's apoptosis, highlighting correct trafficking of K ATP channels is important in survival of β-cells during lipotoxicity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In recent years, the study of extracellular vesicles has been booming across various industries. Extracellular vesicles are considered one of the most important physiological endogenous carriers for the specific delivery of molecular information (nucleonic acid, cytokines, enzymes, etc.) between cells. It has been discovered that they perform a critical role in promoting tumor cell growth, proliferation, tumor cell invasion, and metastatic ability and regulating the tumor microenvironment to promote tumor cell communication and metastasis. In this review, we will discuss (1) the mechanism of extracellular vesicles generation, (2) their role in tumorigenesis and cancer progression (cell growth and proliferation, tumor microenvironment, epithelial-mesenchymal transition (EMT), invasion, and metastasis), (3) the role of extracellular vesicles in immune therapy, (4) extracellular vesicles targeting in tumor therapy, and (5) the role of extracellular vesicles as biomarkers. It is our hope that better knowledge and understanding of the extracellular vesicles will offer a wider range of effective therapeutic targets for experimental tumor research.

The conductance of K ATP channel activity can be regulated by gating and/or surface expression. Gating analysis is usually performed by electrophysiological recording. Analysis of surface K ATP channel expression levels requires cell fractionation, protein separation, and quantification. Cell fractionation involves time-consuming high-speed centrifugation steps and skilled techniques for taking out specific layers. Moreover, contamination of intracellular membranes can confound results. Although commercial kits have been developed to make it easier for scientists, qualities of these kits vary which can give rise to variable results. Detection of membrane proteins using surface biotinylation technique consists of labeling cell surface proteins with a biotin reagent before lysing the cells, and isolating these tagged proteins by NeutrAvidin pulldown. Then, the samples are subjected to SDS-PAGE separation, transferred to PVDF membranes, and probed with specific antibodies. Quantification of cell surface expression is accomplished by densitometric measurement of the bands corresponding to the protein of interest and subsequent normalization by a membrane protein (as control). This alternative method for detecting expression of surface protein is relatively easy in steps and more economical in comparison to other methods such as cell fractionation.

Background/aims: Intermediate-conductance Ca2+-activated K+ (IKCa; KCa3.1 or KCNN4) channels affect the behaviors of central neurons including motor neurons. The mechanism through which neuronal differentiation is related to the activity of these channels remains largely unclear., Methods: By using various molecular biology tools and electrophysiological measurements, we investigated possible changes in the activity of IKCa channels in a retinoic acid (RA)-induced differentiation process in motor neuron-like NSC-34 cells., Results: The protein and messenger RNA expression of KCa3.1 substantially diminished as NSC-34 cells were differentiated with low serum (1%) and 1 µM RA. In whole-cell current recordings, the density of delayed-rectifier K+ currents obtained from differentiated cells was elevated. However, the density of a ramp pulse-elicited K+ current that was sensitive to blockage by 1-((2-chlorophenyl) (diphenyl)methyl)-1H-pyrazole (TRAM-34)-an inhibitor of IKCa channels-was significantly higher in undifferentiated NSC-34 cells than in differentiated cells. In undifferentiated cells, the activity of IKCa channels was readily detected and the probability of channel openings was resistant to stimulation by diazoxide or suppression by verruculogen. Furthermore, this probability was increased by 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one or 9-phenanthrol and reduced by TRAM-34. The channel-opening probability decreased in RA-induced differentiated cells, whereas the single-channel conductance of IKCa channels did not differ between undifferentiated and differentiated cells. Moreover, the slow component of the mean closed time in these channels was significantly shorter in undifferentiated cells than in differentiated cells; however, the mean open time in the channel remained unchanged as cells were differentiated., Conclusion: RA-induced differentiation in neurons could exert a suppressive effect on the activity of IKCa channels., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Aim: To investigate the impact of polymorphisms in the FPGS, GGH and SLCO1B1 genes on high dose methotrexate (HD-MTX) related toxicity in Chinese patients with non-Hodgkin lymphoma (NHL)., Materials & Methods: We analyzed FPGS (rs10106), GGH (rs719235, rs10464903, rs12681874), SLCO1B1 (rs4149056) genetic polymorphisms in 105 Chinese patients with NHL treated with HD-MTX., Results: There was a statistically significant impact of the SLCO1B1 rs4149056 polymorphism on hepatotoxicity. Patients with TC and CC genotype had more hepatotoxicity than TT genotype (60 vs 32.94%, p = 0.025). After adjusting for disease stage, dosage, infusion time and therapy method, SLCO1B1 rs4149056 genotype remained significantly associated with hepatotoxicity (p = 0.028)., Conclusion: SLCO1B1 rs4149056 genetic variants can affect the HD-MTX-related toxicity in Chinese patients with NHL.

Non-small cell lung carcinoma (NSCLC) is the most common malignancy with the highest morbidity and mortality. Studies have demonstrated that the abnormal expression of cyclin-A2 (CCNA2) is associated with multiple malignancies, yet its functional role in NSCLC metastasis remains to be elucidated. In the present study, we investigated the role of CCNA2 in regulating migration and invasion of NSCLC cells by establishing NSCLC cell strains with constitutively silenced or elevated CCNA2 expression. We demonstrated that ectopic expression of CCNA2 accelerates NSCLC cells migration and invasion in vitro through cell wound scratching and Transwell invasion assays. Conversely, further analysis indicated that suppression of CCNA2 expression via siRNA inhibits metastasis of NSCLC cells. In addition, we studied the correlation between CCNA2 expression and overall survival using the Kaplan-Meier Plotter database in NSCLC cancers. There was correlation between CCNA2 expression levels and patient survival. Finally, our findings demonstrate that CCNA2 promotes invasion and migration of NSCLC cells through integrin αVβ3 signaling pathway. Collectively, this study provides novel insights into that CCNA2 represents a crucial regulator of NSCLC cells metastasis and suggests targeted treatment of CCNA2-expressing cancer serves as a new therapeutic target for NSCLC., Competing Interests: None., (IJCEP Copyright © 2017.)

Epithelial-mesenchymal transition (EMT) can directly contribute to some malignant phenotypes of tumor cells including invasion, metastasis and resistance to chemotherapy. Although EMT is widely demonstrated to play a critical role in chemoresistance and metastasis, the potential signaling network between EMT and drug resistance is still unclear. The distribution of drugs in the internal and external environment of the tumor cells is tightly linked with ATP-binding cassette (ABC) transporters. Recent studies have shown that ABC transporters expression changed continuously during EMT. We believe that EMT is an important regulator of ABC transporters. In this review, we discuss how EMT regulates ABC transporters and their potential linkages. And we hope the knowledge of EMT and ABC transporters will offer more effective targets to experimental research., Competing Interests: Competing Interests: The authors declare no conflicts of interest.

Accumulative evidences have underpinned the nature candidates from Chinese medicine (CM), particularly CM served as blood activating and stasis resolving (BASR, Huoxue Huayu in Chinese) by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that (1) BASR-CM might emphasize on a balanced multi-cytokines network interaction; (2) BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; (3) BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context.

Background: Cytochrome P450 2C19 (CYP2C19) is an important drug-metabolizing enzyme (DME), which is responsible for the biotransformation of several kinds of drugs such as proton pump inhibitors, platelet aggregation inhibitors and antidepressants. Previous studies showed that Buchang NaoXinTong capsules (NXT) increased the CYP2C19 metabolic activity in vitro and enhanced the antiplatelet effect of clopidogrel in vivo. However, the underlying molecular mechanism remained unclear. In the present study, we examined whether Pregnane X receptor (PXR) plays a role in NXT-mediated regulation of CYP2C19 expression., Methods: We applied luciferase assays, real-time quantitative PCR (qPCR), Western blotting and cell-based analysis of metabolic activity experiments to investigate the NXT regulatory effects on the CYP2C19 promoter activity, the mRNA/ protein expression and the metabolic activity., Results: Our results demonstrated that NXT significantly increased the CYP2C19 promoter activity when co-transfected with PXR in HepG2 cells. Mutations in PXR responsive element abolished the NXT inductive effects on the CYP2C19 promoter transcription. Additionally, NXT incubation (150 and 250μg/mL) also markedly up-regulated endogenous CYP2C19 mRNA and protein levels in PXR-transfected HepG2 cells. Correspondingly, NXT leaded to a significant enhancement of the CYP2C19 catalytic activity in PXR-transfected HepG2 cells., Conclusion: In summary, this is the first study to suggest that NXT could induce CYP2C19 expression via PXR activation.

Objective: To study the effect of aqueous extract of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro., Methods: Blood was collected from volunteers. Effects of the prepared water extracts of herbs on platelet aggregation were monitored on a Packs-4 aggregometer. The fluorescence intensity of water extracts of Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae on the expression of P-selectin in human platelets of healthy persons was measured with flow cytometry., Results: Out of several herbs investigated, Flos Carthami and Rhizoma Curcumae potently inhibited platelet aggregation after incubation with platelet-rich plasma (PRP) for 15 min. Caulis Spatholobi Flos Carthami and Rhizoma Curcumae inhibited adenosine-5'-diphosphate (ADP) or platelet activating factor (PAF)-induced platelet aggregation in PRP in a dose-dependent manner. In contrast to Flos Carthami and Rhizoma Curcumae, Caulis Spatholobi could not inhibit thrombin-induced platelet aggregation. Despite its inability to inhibit thrombin-induced platelet aggregation in PRP, Caulis Spatholobi had a greater anti-aggregating activity in PRP induced by ADP or PAF. Caulis Spatholobi and Flos Carthami showed significant inhibitory effects on the expression of P-selectin., Conclusions: Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae have potent anti-platelet properties, and their inhibitory actions are mediated via different mechanisms. Caulis Spatholobi inhibited ADP-induced platelet aggregation but not by thrombin, indicating that its mechanism of action might be independent of the thromboxane pathway. The effect of Caulis Spatholobi and Flos Carthami were associated with suppressing the expression of P-selectin.

The hydrophobicity and hydrophilicity of amino acids play a very important role in protein folding and its interaction with the environment and other molecules, as well as its catalytic mechanism. Based on the two physicochemical indexes, a 2D graphical representation of protein sequences is introduced; meanwhile, a new numerical characteristic has been proposed to compute the distance of different sequences for analysis of sequence similarity/dissimilarity on the basis of this graphical representation. Furthermore, we apply the new distance in the similarities/dissimilarities of ND5 proteins of nine species and predict the four major classes based on the dataset containing 639 domains. The results show that the method is simple and effective.

A novel endophytic actinomycete, designated strain KLBMP 1483(T), was isolated from the stem of the coastal plant Dendranthema indicum (Linn.) Des Moul collected from Nantong, in East China. Phylogenetic analysis showed that strain KLBMP 1483(T) was affiliated with the genus Glycomyces within the family Glycomycetaceae and shared the highest 16S rRNA gene sequence similarities with the type strains of Glycomyces arizonensis NRRL B-16153(T) (96.7%) and Glycomyces tenuis IFO 15904(T) (96.2%), and lower similarities (94.1-95.1%) to the other members of the genus Glycomyces, which distinguished KLBMP 1483(T) from representatives of the genus Glycomyces. The whole-cell hydrolysates contained meso-diaminopimelic acid, glucose, xylose and galactose. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, two unknown aminophospholipids, two phosphoglycolipids, two unknown phospholipids and one unknown lipid. MK-10(H4) was the predominant menaquinone. The major fatty acids were iso-C15:0, anteiso-C15:0, iso-C16:0, iso-C16:1 G and anteiso-C17:0. On the basis of the phenotypic and genotypic characteristics presented in this study, strain KLBMP 1483(T) represents a novel species, for which the name Glycomyces phytohabitans sp. nov. is proposed. The type strain is KLBMP 1483(T) (NBRC 109116(T)=DSM 45766(T)).

A novel actinomycete strain, designated TRM 46012(T), was isolated from sediment of Aiding Lake in Tulufan Basin (42° 64' N 89° 26' E), north-west China. The strain was aerobic and Gram-staining-positive with an optimum NaCl concentration for growth of 0-5% (w/v). The isolate had sparse aerial mycelium and produced bud-shaped spores at the end of the aerial mycelium on ISP medium 4. The isolate contained ll-diaminopimelic acid as the diagnostic diamino acid and ribose as the major whole-cell sugar. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified phospholipid and three unidentified glycolipids. The predominant menaquinones were MK-9(H₆), MK-9(H₈) and MK-9(H₄). The major fatty acids were iso-C(16:0), anteiso-C(17:0) and anteiso-C(15:0). The G+C content of the DNA was 74.4 mol%. Phylogenetic analysis showed that strain TRM 46012(T) had 16S rRNA gene sequence similarity of 95.7% with the most closely related species with a validly published name, Streptomyces cheonanensis, and it could be distinguished from all species in the genus Streptomyces by using the data from this polyphasic taxonomic study. On the basis of these data, strain TRM 46012(T) should be designated as a representative of a novel species of the genus Streptomyces, for which the name Streptomyces aidingensis sp. nov. is proposed. The type strain is TRM 46012(T) ( =CGMCC 4.5739(T) =NBRC 108211(T)).

A novel filamentous actinomycete strain, designated TRM 46004(T), was isolated from sediment of Aiding Lake in Tulufan Basin (42° 64' N 89° 26' E), north-west China. The isolate was characterized using a polyphasic approach. The isolate formed abundant aerial mycelium with few branches and vegetative mycelium, occasionally twisted and coiled; spherical sporangia containing one to several spherical spores developed at the ends of short sporangiophores on aerial mycelium. The G+C content of the DNA was 65.2 mol%. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and xylose, galactose and ribose as the major whole-cell sugars. The diagnostic phospholipids were phosphatidylethanolamine, phosphatidylcholine and phosphatidylglycerol. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H10). The major fatty acids were iso-C16 : 0 and anteiso-C17 : 0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain TRM 46004(T) formed a distinct lineage within the family Pseudonocardiaceae and showed 91.7-96.1 % 16S rRNA gene sequence similarity with members of the family Pseudonocardiaceae. On the basis of the evidence from this polyphasic study, a novel genus and species, Longimycelium tulufanense gen. nov., sp. nov., are proposed. The type strain of Longimycelium tulufanense is TRM 46004(T) (= CGMCC 4.5737(T) = NBRC 107726(T)).

Anti-cancer investigations on Xanthatin mainly focus on in vitro experiments. We herein reported the anti-tumor effects of Xanthatin both in vitro and in vivo. MTS assay results showed that Xanthatin had a remarkable anti-proliferative effect on B16-F10 cells. Moreover, the expression of β-catenin was up-regulated both in vitro and in vivo. Animal studies further revealed that Xanthatin killed the tumor cells around the blood vessels which contributes to reduce microvascular density extremely. All these results indicate that Xanthatin inhibited murine melanoma B16-F10 cell proliferation possibly associated with activation of Wnt/β-catenin pathway and its activity against melanoma tumor might also be relevant to inhibition of angiogenesis., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

The glutamate γ-carboxylation plays a pivotal part in a number of important human diseases. However, traditional protein γ-carboxylation site detection by experimental approaches are often laborious and time-consuming. In this study, we initiated an attempt for the computational prediction of protein γ-carboxylation sites. We developed a new method for predicting the γ-carboxylation sites based on a Random Forest method. As a result, 90.44% accuracy and 0.7739 MCC value were obtained for the training dataset, and 89.83% accuracy and 0.7448 MCC value for the testing dataset. Our method considered several features including sequence conservation, residual disorder, secondary structures, solvent accessibility, physicochemical/biochemical properties and amino acid occurrence frequencies. By means of the feature selection algorithm, an optimal set of 327 features were selected; these features were considered as the ones that contributed significantly to the prediction of protein γ-carboxylation sites. Analysis of the optimal feature set indicated several important factors in determining the γ-carboxylation and a possible consensus sequence of the γ-carboxylation recognition site (γ-CRS) was suggested. These may shed some light on the in-depth understanding of the mechanisms of γ-carboxylation, providing guidelines for experimental validation.

Strain 211020(T) was isolated from rhizosphere soil of Excoecaria agallocha in a mangrove in Hainan, China. The strain produced longitudinal pair spores branching from aerial hyphae. 16S rRNA gene sequence analysis showed that the isolate belonged to the genus Microbispora, exhibiting the highest 16S rRNA gene sequence similarity (98.75 %) to Microbispora corallina JCM 10267(T) with a low DNA-DNA relatedness value (13 ± 0.6 %). The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid but madurose was not detected. The predominant menaquinones were MK-9(H(4)), MK-9(H(2)) and MK-9(H(0)), and the major fatty acids were iso-C(16 : 0), iso-C(15 : 0) and C(17 : 0). The phospholipid profile of strain 211020(T) comprised phosphatidylinositol mannoside, phosphatidylethanolamine, diphosphatidylglycerol and phospholipids of unknown structure containing glucosamine. The DNA G+C content was 70.8 mol%. On the basis of phenotypic and genotypic data, strain 211020(T) can be distinguished as a novel species of the genus Microbispora, for which the name Microbispora hainanensis sp. nov., is proposed. The type strain is 211020(T) ( = CGMCC 4.5595(T) = DSM 45428(T)).

Aim: To investigate whether luteolin, a highly prevalent flavonoid, reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal., Methods: Murine malignant melanoma B16F10 cells were exposed to 1% O(2) for 24 h. Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay, respectively. EMT-related proteins, such as E-cadherin and N-cadherin, were examined using Western blotting. Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1×10(6) cells in 0.2 mL per mouse) via the lateral tail vein. The mice were treated with luteolin (10 or 20 mg/kg, ip) daily for 23 d. On the 23rd day after tumor injection, the mice were sacrificed, and the lungs were collected, and metastatic foci in the lung surfaces were photographed. Tissue sections were analyzed with immunohistochemistry and HE staining., Results: Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips, which was accompanied by increased cellular adhesion and invasion. Luteolin (5-50 μmol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner. Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation), which was reversed by luteolin (5 μmol/L). In B16F10 cells, luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway. In experimental metastasis model mice, treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%. Furthermore, the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues., Conclusion: Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin, suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent.

Special emphasis about cancer metastasis was concentrated on tumor cells themselves, and we usually considered the ability of migration and invasion was the final decider. Recently, bewaring of tumor microenvironment is a fundamental determinant in metastasis has become the most outstanding breakthrough. Considerable "microbes" in the microenvironment are closely linked with tumor metastatic behaviors, and the major proportion of them is tumor-associated macrophages (TAMs). Actually, TAMs conserve immediate "cross-talk" with cancer cells throughout tumor development. It is generally accepted that TAMs have mostly pro-tumoral functions and play an important role in several stages of tumor progression. This progression involves a series of events that leads from the primary site to the metastatic site, including tumor cell growth, angiogenesis, migration, invasion, intravasation and finally extravasation at distant site where the process begins again (metastasis). Thereby, TAMs has attracted substantial attentions in recent years and could become a promising therapeutic strategy. In this review, we focus on the multi-functions of TAMs in cancer and certain drugs targeting TAMs for cancer treatment those are under experimental research procedures or have even been entered human clinical tests.

The next-generation sequencing coupled with chromatin immunoprecipitation (ChIP-seq) is becoming a key technology for the study of transcriptional regulation in the context of functional genomics. Due to the overwhelming amount of data generated from ChIP-seq experiments, the ChIP-seq data processing brings many new challenges in the field of bioinformatics. Considering the development of data processing skills largely behind that of the ChIP-seq experiment techniques, it is urgent to give a review on the ChIP-seq data processing for more and more oncoming researchers to build or improve algorithms. This paper provides a brief overview of the ChIP-seq data processing, highlighting the main prob-lems and methods in detail, to allow scientists to understand rapidly and deeply.

A novel actinomycete strain, designated TRM F103(T), was isolated from a hypersaline habitat of the Tarim basin in Xinjiang province, north-west China. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate belonged to the genus Amycolatopsis and was most closely related to Amycolatopsis halophila YIM 93223(T) (99.3% 16S rRNA gene sequence similarity). However, DNA-DNA relatedness between these two strains, based on triplicate experiments, was only 31.6%. The isolate contained meso-diaminopimelic acid and ribose, glucose and galactose as the major whole-cell sugars. The predominant menaquinone was MK-8(H(4)). The major fatty acids were iso-C(16:0) and C(16:0). The polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine and glucosamine-containing phospholipids. The G+C content of the genomic DNA was 66.4 mol%. The phenotypic data clearly distinguished the isolate from its closest relatives. The combined phylogenetic, chemotaxonomic and phenotypic data indicate that the isolate represents a novel species of the genus Amycolatopsis. The proposed name is Amycolatopsis salitolerans sp. nov., with TRM F103(T) (=JCM 15899(T)=CCTCC AB 208326(T)) as the type strain.

A Gram-reaction-positive, non-motile actinobacterium, designated strain 210121(T), was isolated from rhizosphere soil of the mangrove fern Acrostichum speciosum. 16S rRNA gene sequence analysis showed that the isolate belonged to the genus Asanoa. DNA-DNA relatedness values between strain 210121(T) and the type strains of the three recognized species of the genus Asanoa were below the 70 % threshold recommended for distinguishing bacterial genomic species. The novel isolate contained glutamic acid, glycine, alanine and meso-A(2)pm as cell-wall amino acids, indicating peptidoglycan type A1γ. The characteristic whole-cell sugars were xylose, ribose, glucose and mannose. The predominant menaquinones were MK-9(H(4)), MK-9(H(6)) and MK-9(H(8)). The major fatty acids were iso-C(16 : 0) (30.9 %), C(17 : 0) (23.0 %), anteiso-C(15 : 0) (14.9 %) and iso-C(15 : 0) (12.3 %). The phospholipid profile comprised phosphatidylethanolamine, phosphatidylinositol mannosides and phospholipids of unknown structure containing glucosamine. The G+C content of the DNA was 70.3 mol%. On the basis of the phenotypic and genotypic data, strain 210121(T) ( = CGMCC 4.5593(T)  = DSM 45427(T)) represents a novel species of the genus Asanoa, for which the name Asanoa hainanensis sp. nov., is proposed. An emended description of the genus Asanoa is also proposed.

To further disclose the underlying mechanisms of protein β-sheet formation, studies were made on the rules of β-strands alignment forming β-sheet structure using statistical and machine learning approaches. Firstly, statistical analysis was performed on the sum of β-strands between each β-strand pairs in protein sequences. The results showed a propensity of near-neighbor pairing (or called "first come first pair") in the β-strand pairs. Secondly, based on the same dataset, the pairwise cross-combinations of real β-strand pairs and four pseudo-β-strand contained pairs were classified by support vector machine (SVM). A novel feature extracting approach was designed for classification using the average amino acid pairing encoding matrix (APEM). Analytical results of the classification indicated that a segment of β-strand had the ability to distinguish β-strands from segments of α-helix and coil. However, the result also showed that a β-strand was not strongly conserved to choose its real partner from all the alternative β-strand partners, which was corresponding with the ordination results of the statistical analysis each other. Thus, the rules of "first come first pair" propensity and the non-conservative ability to choose real partner, were possible important factors affecting the β-strands alignment forming β-sheet structures., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Three actinomycetal strains, designated YIM 90479, YIM 90480(T) and YIM 90600(T), were isolated from a salt field in Xinjiang province, North-west China and subjected to polyphasic taxonomic study. All three strains were moderately halophilic and were able to grow on agar at NaCl concentrations of up to 20-25 % (w/v). No growth was observed in the absence of NaCl. Good growth occurred at 37 °C and 15 % (w/v) NaCl. The cell walls of the three strains were of the type IV variety and their phospholipid patterns were type PIII. MK-9 (H(4)) and MK-10 (H(4)) or MK-9 (H(4)) and MK-9 (H(2)) were the predominant menaquinones. iso-C(16 : 0) and anteiso-C(17 : 0) or anteiso-C(15 : 0) and anteiso-C(17 : 0) were the major fatty acids. The G+C contents of the genomic DNA were 66.4-68.3 mol%. Based on differential phenotypic, chemotaxonomic and phylogenetic characteristics and the results of DNA-DNA hybridization tests, the three novel stains represent two novel species, for which the names Actinopolyspora alba sp. nov. and Actinopolyspora erythraea sp. nov. are proposed. The type strains of the species are YIM 90480(T) ( = DSM 45004(T)  = KCTC 19119(T)) and YIM 90600(T) ( = CCTCC M 208247(T)  = KCTC 19372(T)). In addition, we propose that Actinopolyspora iraqiensis (Ruan et al., 1994) be transferred to the genus Saccharomonospora as a heterotypic synonym of Saccharomonospora halophila based on present research results.

A novel strain, 219820(T), whose metabolites were found to be active against tumour cells, was isolated and characterized. The isolate belonged to the genus Streptomyces and had white to grey aerial mycelium and long chains of smooth spores in the aerial mycelium. A phylogenetic tree based on 16S rRNA gene sequences showed that strain 219820(T) had highest similarity to members of the genus Streptomyces and was most closely, albeit loosely, associated with Streptomyces crystallinus NBRC 15401(T) (98.624 % similarity), Streptomyces melanogenes NBRC 12890(T) (98.565 %) and Streptomyces noboritoensis NBRC 13065(T) (98.564 %). However, DNA-DNA relatedness and phenotypic data readily distinguished strain 219820(T) from these phylogenetically related type strains. It is evident from the combination of genotypic and phenotypic data that strain 219820(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces sanyensis sp. nov. is proposed; the type strain is 219820(T) ( = CGMCC 4.5626(T)  = DSM 42014(T)).

Strain 210417(T), which forms highly branched substrate and aerial mycelia, is a Gram-positive, aerobic and non-motile actinomycete isolated from mangrove rhizosphere soil. 16S rRNA gene sequence analysis showed that the strain should be classified in the genus Nonomuraea, being most closely related to the type strains of Nonomuraea coxensis (99.6 %) and Nonomuraea bangladeshensis (99.3 %). Chemotaxonomic properties [madurose as the major sugar in the cell wall; meso-diaminopimelic acid and N-acetylmuramic acid in the peptidoglycan; MK-9(H(4)) as the major menaquinone; iso-C(16 : 0) (24.1 %) as major fatty acid; and phospholipid pattern type IV] are consistent with the assignment of strain 210417(T) to the genus Nonomuraea. Strain 210417(T) could be differentiated from the closely related species N. coxensis and N. bangladeshensis by morphological, physiological, biochemical and chemotaxonomic properties, 16S rRNA gene sequence analysis and DNA-DNA hybridization results. It is therefore proposed that strain 210417(T) represents a novel species of the genus Nonomuraea, for which the name Nonomuraea wenchangensis sp. nov. is given; the type strain is 210417(T) ( = CGMCC 4.5598(T)  = DSM 45477(T)).

A novel actinomycete strain, designated TRM 40133(T), was isolated from a hypersaline habitat of Tarim basin in Xinjiang Province, north-west China. Its taxonomic status was determined using a polyphasic approach. Phylogenetic analysis based on an almost-complete 16S rRNA gene sequence of the strain showed that it formed a well-seperated sub-branch within the radiation of the genus Saccharopolyspora. The highest levels of 16S rRNA gene sequence similarity was found between the strain TRM 40133(T) and Saccharopolyspora qijiaojingensis YIM 91168(T) (96.5%). The chemotaxonomic characteristics of the isolate are typical for the genus Saccharopolyspora. It contained meso-DAP as the diagnostic diamino acid. Whole cell hydrolysate contained arabinose, xylose, ribose and glucose. The diagnostic phospholipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and two unknown phospholipids. The main menaquinone was MK-9(H(6)) and MK-9(H(4)). No mycolic acid was detected. The predominant cellular fatty acids were iso-C(16:0) and anteiso-C(17:0). The G+C content of the genomic DNA was 68.2 mol%. In addition, the strain TRM 40133(T) had a phenotypic profile that readily distinguished it from the recognized representatives of the genus Saccharopolyspora. The strain TRM 40133(T) therefore represents a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora lacisalsi sp. nov. is proposed. The type strain is TRM 40133(T) (=KCTC 19987(T) =CCTCC AA 2010012(T)).

Strain 211018(T) was isolated from mangrove Excocaria agallocha rhizosphere soil. 16S rRNA gene sequence analysis showed the highest similarity to the type strains of Micromonospora olivasterospora DSM 43868(T) (98.6 %) and Micromonospora pattaloongensis TJ2-2(T) (98.4 %). gyrB gene sequence analysis also indicated that strain 211018(T) should be assigned to the genus Micromonospora. The characteristic whole-cell sugars are xylose, mannose and arabinose. The predominant menaquinone is MK-9(H(4)) and the major fatty acids are iso-C(15 : 0) (27.5 %), 10-methyl C(17 : 0) (14.2 %), C(17 : 1)ω8c (12.8 %), iso-C(16 : 0) (12.6 %), anteiso-C(15 : 0) (6.1 %), iso-C(17 : 0) (4.1 %) and anteiso-C(17 : 0) (4.0 %). The phospholipid profile comprises phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. The DNA G+C content is 70.8 mol%. The chemotaxonomic data of the strain coincided with those of the genus Micromonospora. Furthermore, a combination of DNA-DNA hybridization results and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from the closest phylogenetic relatives. On the basis of these phenotypic and genotypic data, strain 211018(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora rhizosphaerae sp. nov. is proposed. The type strain is 211018(T) (=CGMCC 4.5599(T) =DSM 45431(T)).

The present study aimed to investigate the protective effects of injectable caltrop fruit saponin preparation (ICFSP) on ischemia-reperfusion injury in rat brain. Rats were injected with ICFSP and then subjected to cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion. Then the neurological deficit score was evaluated by Bederson's method. The infarct size was assessed by TTC staining. The content of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in rat cerebrum were measured with kits, and the content of 6 K prostaglandin F1α (6-K-PGF 1α), thromboxane B2 (TXB2) and endothelin (ET) in blood plasma was measured by radioimmunoassay. The results demonstrated that ICFSP led to a decrease in infarct size (p < 0.01), neurological deficit score (p < 0.05) and plasma content of TXB2 and ET (p < 0.05), and an increase of the plasma level of 6-K-PGF 1α (p < 0.05) and SOD activity in cerebrum, where the MDA and NO content were decreased. The treatment improved forelimb function. ICFSP showed a similar potency compared to that of Ligustrazine hydrochloride parenteral solution (LHPS) and nimodipine (Nim). We concluded that ICFSP protects the brain damage caused by ischemia-reperfusion injury in rats, and this may be closely related to the regulation of reactive oxygen species (MDA and SOD activity) and NO levels in the rat cerebrum, as well as vasoactive factors in the plasma (6-K-PGF 1α, TXB2 and ET).

The increasing number of people over 65 years old (YO) is an important research topic in the area of impact biomechanics, and finite element (FE) modeling can provide valuable support for related research. There were three objectives of this study: (1) Estimation of the representative age of the previously-documented Ford Human Body Model (FHBM) -- an FE model which approximates the geometry and mass of a mid-sized male, (2) Development of FE models representing two additional ages, and (3) Validation of the resulting three models to the extent possible with respect to available physical tests. Specifically, the geometry of the model was compared to published data relating rib angles to age, and the mechanical properties of different simulated tissues were compared to a number of published aging functions. The FHBM was determined to represent a 53-59 YO mid-sized male. The aforementioned aging functions were used to develop FE models representing two additional ages: 35 and 75 YO. The rib model was validated against human rib specimens and whole rib tests, under different loading conditions, with and without modeled fracture. In addition, the resulting three age-dependent models were validated by simulating cadaveric tests of blunt and sled impacts. The responses of the models, in general, were within the cadaveric response corridors. When compared to peak responses from individual cadavers similar in size and age to the age-dependent models, some responses were within one standard deviation of the test data. All the other responses, but one, were within two standard deviations.

An actinomycete, designated MS426T, the culture broth of which showed potent antimicrobial activity, was isolated from a deep-sea sediment sample of the South China Sea. An almost-complete sequence of the 16S rRNA gene of strain MS426T was determined and aligned with those of representatives of the family Micromonosporaceae available in public databases. Phylogenetic trees were inferred by using three algorithms. Strain MS426T formed a branch adjacent to Verrucosispora lutea YIM 013T in a distinct cluster occupied only by strains of the genus Verrucosispora. Strain MS426T was distinguishable from the type strains of the two described Verrucosispora species by using a combination of chemical and morphological markers and by DNA-DNA relatedness. On the basis of these genotypic and phenotypic differences, the novel antimicrobial strain with pharmaceutical potential represents a novel species, for which the name Verrucosispora sediminis sp. nov. is proposed. The type strain is MS426T (=CGMCC 4.3550T =JCM 15670T).

A novel isolate, designated strain MCCC 1A01535(T), belonging to the genus Streptomyces was isolated from the rhizosphere of the mangrove plant Avicennia mariana from Fujian Province, south China. Characterization of the isolate was based on a polyphasic approach. Pairwise comparison of 16S rRNA gene sequences revealed that strain MCCC 1A01535(T) shared 97.7 and 97.5 % sequence similarities to Streptomyces specialis GW41-1564(T) and Streptomyces hainanensis YIM47672(T), respectively, its most closely related neighbours, whereas the DNA-DNA relatedness value between strains MCCC 1A01535(T) and GW41-1564(T) was 50.2 %. The major fatty acids of strain MCCC 1A01535(T) were iso-C(16 : 0), C(16 : 0) and anteiso-C(15 : 0). These differed from the fatty acid compositions of related strains. Strain MCCC 1A01535(T) exhibited an unusual menaquinone system that comprised MK-10(H(6)) as the predominant component and moderate amounts of MK-9(H(6)), MK-9(H(8)) and MK-10(H(8)); minor amounts of MK-9(H(4)), MK-10(H(4)), MK-9(H(10)) and MK-10(H(10)) were also present. Based on its chemotaxonomic, phenotypic and genotypic characteristics, strain MCCC 1A01535(T) is considered to represent a novel species of the genus Streptomyces, for which the name Streptomyces avicenniae sp. nov. is proposed. The type strain is MCCC 1A01535(T) (=DSM 41943(T)=CGMCC 4.5510(T)).

Computational methods can be used to predict the effects of single amino acid substitutions (single-point mutations). In contrast to previous methods that need many protein sequence and structural features, we applied support vector machines (SVMs) to predict protein function changes associated with amino acid substitutions using only sequence information, and cross-validated them on a large dataset extracted from the Protein Mutant Database (PMD). By three SVM classifiers, we investigated three local sequence features of proteins (residue composition, hydrophobic interaction, and evolutionary property), and examined their effects on the prediction accuracy. As a main result, a novel SVM named substitution-matrix-based kernel SVM was constructed to make speedy and accurate prediction, and its value was shown in an application case. Furthermore, our findings confirmed results from other studies.

Actinomycete strain MCCC 1A01550(T), isolated from the national mangrove reserve in Fujian Province, China, was determined to belong to the genus Streptomyces based on a polyphasic approach. The cell wall of the novel strain contained ll-diaminopimelic acid and galactose. The predominant menaquinones were MK-9(H(4)) and MK-9(H(6)) and the major fatty acids were iso-C(16 : 0), cis9-C(16 : 1) and C(16 : 0). The diagnostic phospholipid was phosphatidylethanolamine. The DNA G+C content of the novel strain was 71.6 mol%. Phylogenetic analysis of 16S rRNA gene sequences confirmed the separation of the novel strain from recognized members of the genus Streptomyces available in public databases. DNA-DNA relatedness values between strain MCCC 1A01550(T) and the type strains of three related species ranged from 21.29 % to 43.38 %. Based on its phenotypic and genotypic characteristics, strain MCCC 1A01550(T) (=DSM 41903(T)=CGMCC 4.3534(T)) represents the type strain of a novel species, for which the name Streptomyces xiamenensis sp. nov. is proposed.

The mangrove ecosystem is a largely unexplored source for actinomycetes with the potential to produce biologically active secondary metabolites. Consequently, we set out to isolate, characterize and screen actinomycetes from soil and plant material collected from eight mangrove sites in China. Over 2,000 actinomycetes were isolated and of these approximately 20%, 5%, and 10% inhibited the growth of Human Colon Tumor 116 cells, Candida albicans and Staphylococcus aureus, respectively, while 3% inhibited protein tyrosine phosphatase 1B (PTP1B), a protein related to diabetes. In addition, nine isolates inhibited aurora kinase A, an anti-cancer related protein, and three inhibited caspase 3, a protein related to neurodegenerative diseases. Representative bioactive isolates were characterized using genotypic and phenotypic procedures and classified to thirteen genera, notably to the genera Micromonospora and Streptomyces. Actinomycetes showing cytotoxic activity were assigned to seven genera whereas only Micromonospora and Streptomyces strains showed anti-PTP1B activity. We conclude that actinomycetes isolated from mangrove habitats are a potentially rich source for the discovery of anti-infection and anti-tumor compounds, and of agents for treating neurodegenerative diseases and diabetes.

Changes in vehicle safety design technology and the increasing use of seat-belts and airbag restraint systems have gradually changed the relative proportion of lower extremity injuries. These changes in real world injuries have renewed interest and the need of further investigation into occupant injury mechanisms and biomechanical impact responses of the knee-thigh-hip complex during frontal impacts. This study uses a detailed finite element model of the human body to simulate occupant knee impacts experienced in frontal crashes. The human body model includes detailed anatomical features of the head, neck, shoulder, chest, thoracic and lumbar spine, abdomen, pelvis, and lower and upper extremities. The material properties used in the model for each anatomic part of the human body were obtained from test data reported in the literature. The human body model used in the current study has been previously validated in frontal and side impacts. It was further validated with cadaver knee-thigh-hip impact tests in the current study. The effects of impactor configuration and flexion angle of the knee on biomechanical impact responses of the knee-thigh-hip complex were studied using the validated human body finite element model. This study showed that the knee flexion angle and the impact direction and shape of the impactors affected the injury outcomes of the knee-thigh-hip complex significantly. The 60 degrees flexed knee impact showed the least impact force, knee pressure, femoral von Mises stress, and pelvic von Mises stress but largest relative displacements of the Posterior Cruciate Ligament (PCL) and Anterior Cruciate Ligament (ACL). The 90 degrees flexed knee impact resulted in a higher impact force, knee pressure, femoral von Mises stress, and pelvic von Mises stress; but smaller PCL and ACL displacements. Stress distributions of the patella, femur, and pelvis were also given for all the simulated conditions.

The biofidelity of the Ford Motor Company human body finite element (FE) model in side impact simulations was analyzed and evaluated following the procedures outlined in ISO technical report TR9790. This FE model, representing a 50th percentile adult male, was used to simulate the biomechanical impact tests described in ISO-TR9790. These laboratory tests were considered as suitable for assessing the lateral impact biofidelity of the head, neck, shoulder, thorax, abdomen, and pelvis of crash test dummies, subcomponent test devices, and math models that are used to represent a 50th percentile adult male. The simulated impact responses of the head, neck, shoulder, thorax, abdomen, and pelvis of the FE model were compared with the PMHS (Post Mortem Human Subject) data upon which the response requirements for side impact surrogates was based. An overall biofidelity rating of the human body FE model was determined using the ISO-TR9790 rating method. The resulting rating for the human body FE model was 8.5 on a 0 to 10 scale with 8.6-10 being excellent biofidelity. In addition, in order to explore whether there is a dependency of the impact responses of the FE model on different analysis codes, three commercially available analysis codes, namely, LS-DYNA, Pamcrash, and Radioss were used to run the human body FE model. Effects of these codes on biofidelity when compared with ISO-TR9790 data are discussed. Model robustness and numerical issues arising with three different code simulations are also discussed.

Human abdominal response and injury in blunt impacts was investigated through finite element simulations of cadaver tests using a full human body model of an average-sized adult male. The model was validated at various impact speeds by comparing model responses with available experimental cadaver test data in pendulum side impacts and frontal rigid bar impacts from various sources. Results of various abdominal impact simulations are presented in this paper. Model-predicted abdominal dynamic responses such as force-time and force-deflection characteristics, and injury severities, measured by organ pressures, for the simulated impact conditions are presented. Quantitative results such as impact forces, abdominal deflections, internal organ stresses have shown that the abdomen responded differently to left and right side impacts, especially in low speed impact. Results also indicated that the model exhibited speed sensitive response characteristics and the compressibility of the abdomen significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated finite element human body model can be useful for abdominal injury assessment. Internal organ injuries, which are difficult to detect in experimental studies with human cadavers due to the difficulty of instrumentation, may be more easily identified with a validated finite element model through stress-strain analysis.

A novel actinomycete was isolated from soil in the tropical rainforest of Singapore. The cells of this actinomycete are highly pleomorphic. In the early stages of growth, most cells are of irregular squarish shape and varied sizes. Cells remain attached after cell division, often forming chains or aggregates of a few cells. Cells at the end of a chain tend to elongate. With prolonged cultivation, cells show different degrees of elongation and enlargement, producing branched hyphae of uneven thickness. At the periphery of the colony, long hyphae form, which are divided into alternating segments of elongated cells and chains of squarish cells. This actinomycete is considerably salt-tolerant, able to grow in the presence of 15% NaCl. Chemotaxonomically, it contains LL-diaminopimelic acid (DAP) in the cell wall, type PI phospholipids and MK-9(H6) as the predominant menaquinone. 16S rDNA sequence analysis assigned this actinomycete to the family Nocardioidaceae, but its 16S rDNA shared no more than 91.2% sequence similarity with other members of the family. Based on phenotypic, chemotaxonomic and phylogenetic evidence, it is proposed that this actinomycete be classified as a new species in a new genus, Actinopolymorpha singaporensis gen. nov., sp. nov.

A skull-brain finite element model of the human head has been coupled with a multilink rigid body model of the Hybrid III dummy. The experimental coupled model is intended to represent anatomically a 50th percentile human to the extent the dummy and the skull-brain model represent a human. It has been verified by simulating several human cadaver head impact tests as well as dummy head 'impacts" during barrier crashes in an automotive environment. Skull-isostress and brain-isostrain response curves were established based on model calibration of experimental human cadaver tolerance data. The skull-isostress response curve agrees with the JARI Human Head Impact Tolerance Curve for skull fracture. The brain-isostrain response curve predicts a higher G level for concussion than does the JARI concussion curve and the Wayne State Tolerance Curve at the longer time duration range. Barrier crash simulations consist of belted dummies impacting an airbag, a hard and soft steering wheel hub, and no head contact with vehicle interior components. Head impact force, intracranial pressures and strains, skull stress, and head center-of-gravity acceleration were investigated as injury parameters. Head injury criterion (HIC) was also calculated along with these parameters. Preliminary results of the model simulations in those impact conditions are discussed.

Biomechanics of cerebral trauma attempts to delineate the dynamic response of the cranial vault contents to a direct or indirect impact to the head. Consequently, brain injury mechanisms and associated tolerance to impact can be deduced by establishing a relationship between neurological deficit and mechanical dosage. The resulting information is invaluable to brain injury prevention and diagnosis. This paper presents an overview of our recent research on head injury focusing on establishing brain injury biomechanics by developing a comprehensive and validated mathematical model. To achieve our goal, we developed a comprehensive three-dimensional finite element human head model, finite element porcine head models, and sensors to monitor head kinematics and brain strains by neutral density accelerometers. The information obtained from this research thus far provided a predictive and somewhat validated mathematical model of the head, which clearly shows a correspondence between brain mechanical response and experimentally observed injuries.

The results of our experiments showed that the 5'-terminal sequences of 23S rRNAs can be used to distinguish different genera of actinomycetes, including the genera Streptomyces, Micromonospora, Amycolatopsis, and Saccharomonospora. There are small differences (< 1%) among the sequences of some strains belonging to the genera Streptomyces (two strains) and Saccharomonospora (seven strains). On the basis of the results of morphological and biochemical analyses, strain 9022 belongs in the genus Saccharomonospora; however, there are distinct differences in the cell wall compositions and the 5' termini of the 23S rRNA sequences of this strain and members of the genus Saccharomonospora. Hence, strain 9022 cannot be classified in the genus Saccharomonospora.

The impact response of the human head has been determined by three-dimensional finite element modeling. This model represents the essential features of a 50th percentile human head. It includes a layered shell closely representing the cranial bones with the interior contents occupied by an inviscid continuum to simulate the brain. A thin fluid layer was included to represent the cerebral-spinal fluid. To validate the model, its response was obtained by applying a sine-squared pulse of 6.8 kN in magnitude and 10 ms in duration. The load was applied to a freely supported head on the frontal bone in the midsagittal plane. The computed pressure-time histories at 5 locations within the brain material compared quite favorably with previously published experimental data from cadaver experiments and provided a reasonable level of confidence in the validation of the model. A parametric study was subsequently conducted to identify the model response when the impact site (frontal, side, occipital) and the material properties of the head were varied. Interestingly, the model predicted higher contre-coup pressure in the frontal lobe (from occipital impact) than that predicted in the occipital region from frontal impact. This finding supports clinical findings of contre-coup injury being more likely to result from occipital impact than from frontal impact.

The dynamic response of the human head to side impact was studied by 2-dimensional finite element modeling. Three models were formulated in this study. Model I is an axisymmetric model. It simulated closed shell impact of the human head, and consisted of a single-layered spherical shell filled wiht an inviscid fluid. The other two models (Model II and III) are plane strain models of a coronal section of the human head. Model II approximated a 50th percentile male head by an outer layer to simulate cranial bone and an inviscid interior core to simulate the intracranial contents. The configuration of Model III is the same as Model II but more detailed anatomical features of the head interior were added, such as, cerebral spinal fluid (CSF); falx cerebri, dura, and tentorium. Linear elastic material properties were assigned to all three models. All three models were loaded by a triangular pulse with a peak pressure of 40 kPa, effectively producing a peak force of 1954 N (440 lb). The purpose of this study was to determine the effects of the membranes and that of the mechanical properties of the skull, brain, and membrane on the dynamic response of the brain during side impact, and to compare the pressure distributions from the plane strain model with the axisymmetric model. A parametric study was conducted on Model II to characterize fully its response to impact under various conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Mycolic acid methanolysates of whole-cell in Mycobacterium and related bacteria were analysed by thin-layer chromatography. The experimental results show that five of twenty-two species, M. tuberculosis, M. bovis, M. kansasii, M. marinum and M. gastri have similar pattern of mycolates, composed of alpha-mycolates, methoxymycolates, ketomycolates and two unknown components. M. gilvum, M. phleri, M. avium, M. intracellulare, M. xenopi and M. nonchromogenicum contain alpha-mycolates, ketomycolates and wax-ester. The patterns of TLC for other tested species were different from each other. Nocardia, Rhodococcus and Corynebacterium show a relatively simple pattern which principally contain alpha-mycolates. The four genus can be differentiated. Spots of mycolic acids of nine strains Mycobacterium sp. isolated from patients in this hospital were similar to M. tuberculosis. These strains were also identified to the same result as above by traditional methods. The method is of value in the classification and identification of Mycobacterium.