Sample records for basal core promoters

  1. Optimization of competitively differentiated polymerase chain reaction in detection of HBV basal core promoter mutation

    Institute of Scientific and Technical Information of China (English)

    Xiao-Mou Peng; Lin Gu; Xue-Juan Chen; Jian-Guo Li; Yang-Su Huang; Zhi-Liang Gao


    AIM: To improve competitively differentiated polymerase chain reaction (CD-PCR) in detection of HBV basal core promoter mutation.METHODS: Recombinant plasmid of double point mutation A1762T/G1764A in basal core promoter of HBV constructed by site-directed mutagenesis was used as mutant control.To reveal the deficiency mechanism of CD-PCR, relationship between the circle number of PCR and the increased speed of products of each competitive primer was comparatively studied. Diversified amount of dNTPs and mutual primer of the competitive primers were tried to optimize CDPCR. Optimized CD-PCR was evaluated by detecting A1762T/G1764A mutation in recombinant plasmids and clinical sera from patients with HBV infection. RESULTS: The deficiency mechanism of CD-PCR was that the products of mismatched competitive primer grew fast when the amplification of matched primer entered into plateau stage, which led to decrease in or disappearance of the difference in the amount of their products. This phenomenon could be eliminated by reducing dNTPs to10 μmol/L and mutual primer to about 100 nmol/L. Optimized CD-PCR could detect both mutant and wild strain indepe ndent of the amount of templates and the number of PCRcycles. Its detection limit was 103 copies/mL, about 50 copies/reaction. About 10% of mutant DNAs among wild type DNAs could be detected. A1762T/G1764A mutant was detected in 41.8% (51/122) of patients with HBV infection, but not detected in controls with negative HBsAg. CONCLUSION: Optimized CD-PCR can detect mutation independent of the amount of initial templates and the number of PCR cycles.

  2. Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

    Institute of Scientific and Technical Information of China (English)

    Andi Utama; Sigit Purwantomo; Marlinang Diarta Siburian; Rama Dhenni; Rino Alvani Gani; Irsan Hasan; Andri Sanityoso; Upik Anderiani Miskad; Fardah Akil; Irawan Yusuf; Wenny Astuti Achwan; Soewignjo Soemohardjo; Syafruddin AR Lelosutan; Ruswhandi Martamala; Benyamin Lukito; Unggul Budihusodo; Laurentius Adrianus Lesmana; Ali Sulaiman; Susan Tai


    AIM:To identify the distribution of hepatitis B virus(HBV) subgenotype and basal core promoter(BCP) mutations among patients with HBV-associated liver disease in Indonesia.METHODS:Patients with chronic hepatitis (CH,n=61),liver cirrhosis (LC,n = 62),and hepatocellular carcinoma (HCC,n = 48) were included in this study.HBV subgenotype was identified based on S or preS gene sequence,and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.RESULTS:HBV genotype B (subgenotypes B2,B3,B4,B5 and B7) the major genotype in the samples,accounted for 75.4%,71.0% and 75.0% of CH,LC and HCC patients,respectively,while the genotype C(subgenotypes C1,C2 and C3) was detected in 24.6%,29.0%,and 25.0% of CH,LC,and HCC patients,respectively.Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C,respectively.Serotype adw2 (84.9%) and adrq+(89.4%) were the most prevalent in HBV genotype B and C,respectively.Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%),suggesting that this mutation was associated with severity of liver disease.The T1753V was also higher in LC (46.8%),but lower in HCC (22.9%) and CH (18.0%),suggesting that this mutation may be an indicator of cirrhosis.CONCLUSION:HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia.Mutations in BCP,such as A1762T/G1764A and T1753V,might have an association with manifestations of liver disease.

  3. Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Myron J Tong; Lawrence M Blatt; Jia-Horng Kao; Jason Tzuying Cheng; William G Corey


    AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma.METHODS: The mean follow-up time was 83.6 ± 39.6mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes,hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development.RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31);P < 0.0001], male sex [odds ratio: 7.61 (2.20-47.95);P = 0.006], and higher log10 HBV DNA [odds ratio:4.69 (1.16-20.43); P < 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47);P = 0.007], presence of precore mutants [odds ratio:4.23 (1.53-19.58); P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P =0.02] were independent predictors for progression to hepatocellular carcinoma.CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with nonhepatocellular carcinoma-related deaths of liver failure,while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.

  4. Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B. (United States)

    Lee, Jong Ho; Hong, Sun Pyo; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook-Hyang


    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations.

  5. Hepatitis B virus genotypes and mutations in the basal core promoter and pre-core/core in chronically infected patients in southern Brazil: a cross-sectional study of HBV genotypes and mutations in chronic carriers

    Directory of Open Access Journals (Sweden)

    Flávia Miryan Martins Almeida de Mello


    Full Text Available Introduction In Brazil, little data exist regarding the distribution of genotypes in relation to basal core promoter (BCP and precore/core mutations among chronic hepatitis B virus (HBV carriers from different regions of the country. The aim of this study was to identify HBV genotypes and the frequency of mutations at the BCP and precore/core region among the prevalent genotypes in chronic carriers from southern Brazil. Methods Nested-polymerase chain reaction (nested-PCR products amplified from the S-polymerase gene, BCP and precore/core region from 54 samples were sequenced and analyzed. Results Phylogenetic analysis of the S-polymerase gene sequences showed that 66.7% (36/54 of the patients were infected with genotype D (D1, D2, D3, 25.9% (14/54 with genotype A (A1, A2, 5.6% (3/54 with subgenotype C2, and 2% (1/54 with genotype E. A comparison of virological characteristics showed significant differences between genotypes A, C and D. The comparison between HBeAg status and the G1896A stop codon mutation in patients with genotype D revealed a relationship between HBV G1896A precore mutants and genotype D and hepatitis B e antigen (HBeAg seroconversion. Genotype D had a higher prevalence of the G1896A mutation and the presence of a thymine at position 1858. Genotype A was associated with a higher prevalence of the G1862T mutation and the presence of a cytosine at position 1858. Conclusions HBV genotype D (D3 is predominant in HBV chronic carriers from southern Brazil. The presence of mutations in the BCP and precore/core region was correlated with the HBV genotype and HBeAg negative status.

  6. Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey. (United States)

    Sunbul, Mustafa; Sugiyama, Masaya; Kurbanov, Fuat; Leblebicioglu, Hakan; Khan, Anis; Elkady, Abeer; Tanaka, Yasuhito; Mizokami, Masashi


    The role of hepatitis B virus (HBV) genetics in the clinical manifestations of infection is being increasingly recognized. Genotype D is one of eight currently recognized major HBV genotypes. The virus is ubiquitous worldwide, but shows different features in different regions. One hundred and ninety-eight patients with chronic HBV infection were enrolled in this study, 38 of whom had been diagnosed with cirrhosis of the liver and/or hepatocellular carcinoma. HBV DNA was isolated from the patients' blood samples and the entire genome and/or the basal core promoter/core promoter region sequenced. Phylogenetic analysis of the complete genomes revealed that subgenotype D1 is the most prevalent subgenotype in Turkey, but there was no definite phylogenetic grouping according to geography for isolates from different regions within Turkey, or for isolates in Turkey relative to other parts of the world. Turkish isolates tended to be genetically similar to European and central Asian isolates. Overall, HBV-infection in Turkey appears to be characterized by early HBeAg seroconversion, a high incidence of the A1896 core promoter mutation and a small viral load. Genotype D characteristic mutations A1757 and T1764/G1766 were found in the BCP region. T1773 was associated with T1764/G1766 and a larger viral load. In conclusion, infection with HBV genotype D in Turkey has a similar clinical outcome to that of Europe and central Asia. Genotypic mutations in genotype D may be linked with disease prognosis in Turkey, but further studies with higher sample numbers and balanced clinical groups are needed to confirm this.

  7. Effects of hepatitis B virus precore and basal core promoter mutations on the expression of viral antigens: genotype B vs C. (United States)

    Liu, C-J; Cheng, H-R; Chen, C-L; Chen, T-C; Tseng, T-C; Wang, Z-L; Chen, P-J; Liu, C-H; Chen, D-S; Kao, J-H


    Hepatitis B virus (HBV) genotypes/mutants are known to affect natural outcomes. The virologic differences among HBV genotype, precore and basal core promoter (BCP) mutations were investigated. HBV strains were isolated from 18 hepatitis B e antigen (HBeAg)-positive patients (nine genotype B and nine genotype C). All had precore and BCP wild-type sequences. After cloning of full-length HBV genome, the effects of viral genotype, precore and BCP mutations singly or additively on the expression of viral DNA and antigens were investigated by mutagenesis and transfection assays in Huh7 cells. Significant findings included the following: (i) expression of intracellular core protein increased when precore or BCP mutation was introduced in genotype C strains; (ii) expression of intracellular surface protein was lower in genotype C precore wild-type strain compared with genotype B; (iii) precore mutation was associated with a lower extracellular expression level of HBV DNA; (iv) secretion of hepatitis B surface antigen in genotype C was lower than that in genotype B; and (v) secretion of HBeAg in genotype B was lower than that in genotype C. No additive effect was observed by combining precore and BCP mutations. Hence, HBV genotype and precore/BCP mutations correlate with intrahepatic expression of viral antigens in vitro.

  8. Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context. (United States)

    Chapel-Fernandes, S; Jordier, F; Lauro, F; Maitland, N; Chiaroni, J; de Micco, P; Mannoni, P; Bagnis, C


    Composite promoters combining the prostate-specific antigen (PSA) enhancer core element with promoter elements derived from gene coding for human prostate-specific transglutaminase gene, prostate-specific membrane antigen gene, prostate-specific antigen, rat probasin or phosphoglycerate kinase were characterized for their ability to specifically express the enhanced green fluorescent protein (EGFP) gene in prostate versus non-prostate cancer cell lines when transferred with a human immunodeficiency virus-1-based lentiviral vector. By themselves minimal proximal promoter elements were found to inefficiently promote relevant tissue-specific expression; in all the vectors tested, addition of the PSA enhancer core element markedly improved EGFP expression in LnCaP, a cancer prostate cell line used as a model for prostate cancer. The composite promoter was inactive in HuH7, a hepatocarcinoma cell line used as a model of neighboring non-prostate cancer cells. Among the promoters tested, the combination of the PSA enhancer and the rat probasin promoter showed both high specificity and a strong EGFP expression. Neither a high viral input nor the presence of the cPPT/CTS sequence affected composite promoter behavior. Our data suggest that composite prostate-specific promoters constructed by combining key elements from various promoters can improve and/or confer tissue specific expression in a lentiviral vector context.

  9. Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection. (United States)

    Zhong, Y W; Di, F L; Liu, C; Zhang, X C; Bi, J F; Li, Y L; Wu, S Q; Dong, H; Liu, L M; He, J; Shi, Y M; Zhang, H F; Zhang, M


    We investigated 168 children and analysed the virological characterization and association with disease progression in children with hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutants. Among 168 patients with HBV infection (aged 0.5-18 years old, mean 10.1), 86 of them had HBV-related liver cirrhosis (LC) and 82 had HBV-related chronic hepatitis B (CHB). A direct sequencing method was employed to determine the HBV genotypes and the mutations in BCP/PC regions. In all, 133 of them were infected with genotype C viruses (79.17%); only 35 patients (20.83%) were infected with genotype B viruses. Both LC patients and CHB patients had significantly higher ratios of genotype C when compared with the ratios of genotype B (83.7%-16.3% versus 74.4%-25.6%). For patients with CHB, the prevalence of BCP/PC wild-type viruses was 52.4%; but this was only 4.7% in patients with LC. The C1653T, T1753C, A1762T/G1764A and G1896A mutations had a significantly higher prevalence in patients with LC. Among all the patients with genotype B viruses, those with LC had lower HBV DNA levels and higher G1899A mutation frequency than patients with CHB. Among all the patients with genotype C viruses, the patients with LC had higher prevalence of C1653T, A1762T/G1764A and G1896A mutation frequency, higher hepatitis B e antigen (HBeAg) -negative rates, lower viral load, lower elevated alanine aminotransferase and lower anti-HBe positive rates than CHB patients. The HBV BCP/PC variants were more common in HBeAg-negative LC patients than in the CHB group (BCP, 53.4% versus 15.6%; PC, 18.6% versus 3.7%, respectively, p viruses, high viral load and C1653T, A1762T/G1764A, G1896A mutant viruses, were more susceptible to developing LC.

  10. Hepatitis B virus basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients. (United States)

    Yan, Chun-Hui; Zhao, Cheng-Yu; Ding, Hai; Peng, Ya-Qin; Jin, Peng-Yuan; Yan, Ling; Zhuang, Hui; Li, Tong


    The present study was aimed to obtain baseline information of basal core promoter A1762T/G1764A and precore G1896A mutations of hepatitis B virus (HBV) in 192 HBeAg-positive chronically-infected Chinese patients, who were potential candidates for antiviral treatment. The detection of these mutations (including minor mutant subpopulations) was achieved by direct sequencing, whose sensitivity for minor mutant subpopulations identification was confirmed by clone sequencing. Patients enrolled were infected with either genotype B (46.35%) or C (53.65%) HBV identified by routine tests in our laboratory. The A1762T/G1764A or G1896A mutations were detected in 125specimens (125/192, 65.10%), in which 77 (77/125, 61.60%) existed as subpopulations. The A1762T/G1764A mutations were found to be more prevalent in genotype C than that in genotype B HBV [62.14% (64/103) vs. 20.22% (18/89), Pgenotypes. The emergence of A1762T/G1764A mutations was also found to be associated with an older age, an elevated ALT/AST level, and a lower HBsAg level in serum [wild-type vs. mutant: 4.57 (3.46-5.42) vs. 3.93 (2.51-5.36), Pgenotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

  11. The core promoter: At the heart of gene expression. (United States)

    Danino, Yehuda M; Even, Dan; Ideses, Diana; Juven-Gershon, Tamar


    The identities of different cells and tissues in multicellular organisms are determined by tightly controlled transcriptional programs that enable accurate gene expression. The mechanisms that regulate gene expression comprise diverse multiplayer molecular circuits of multiple dedicated components. The RNA polymerase II (Pol II) core promoter establishes the center of this spatiotemporally orchestrated molecular machine. Here, we discuss transcription initiation, diversity in core promoter composition, interactions of the basal transcription machinery with the core promoter, enhancer-promoter specificity, core promoter-preferential activation, enhancer RNAs, Pol II pausing, transcription termination, Pol II recycling and translation. We further discuss recent findings indicating that promoters and enhancers share similar features and may not substantially differ from each other, as previously assumed. Taken together, we review a broad spectrum of studies that highlight the importance of the core promoter and its pivotal role in the regulation of metazoan gene expression and suggest future research directions and challenges.

  12. HBV genotypes prevalence, precore and basal core mutants in Morocco. (United States)

    Baha, Warda; Ennaji, My Mustapha; Lazar, Fatiha; Melloul, Marouane; El Fahime, Elmostafa; El Malki, Abdelouahad; Bennani, Abdelouaheb


    The study of hepatitis B virus (HBV) genomic heterogeneity has become a major issue in investigations aimed at understanding the relationship between HBV mutants and the wide spectrum of clinical and pathological conditions associated with HBV infection. The objective of the current study was to find out the pattern of HBV genotypes circulating in Morocco and to investigate the precore (PC) and basal core promoter (BCP) mutants' status in Moroccan chronic hepatitis B patients. Viral genotypes were determined in 221 chronic carriers using INNO-LiPA HBV assay and hemi-nested PCR. Phylogenetic analysis was performed in 70 samples, and multiplex PCR method was used to confirm some genotyping results. PC and CP mutants were determined using Inno-Lipa. All isolates were successfully genotyped. The genotype distribution was D in 90.45% of cases, A (5.9%), E (1 case), and mixed genotypes (5 A/D and 2 D/F) in 3.17% patients. HBV carried in the HBV/D samples could be assigned to D7 (63.3%), D1 (32.7%) and 2% of strains to each D4 and D5, all HBV/A belonged to A2 subgenotype and HBV/E strain could not be sub-genotyped. In 70 studied strains, HBV mutants were detected in 88.6% of cases; PC mutants were detected in (40%) of patients and 21.5% present a mixture of wild type and G1896A mutation. BCP mutants were observed in 65.7% of cases, 22.9% were found to have the T1762/1764A double mutation, 18.6% had A1762/1764T mutation and 22.9% of patients showed the A1762T/G1764A double mutation with either A1762T/G1764T mutation. Co-infection by PC and BCP mutants was detected in 52.9% of cases. Movement from place to place most likely shapes the observed genotype distribution and consequent prevalence of genotypes other than A2 or D7 in this population. High circulation of PC and BCP mutants is common in chronic hepatitis B infection in Morocco.

  13. Proximity of Radiation Desiccation Response Motif to the core promoter is essential for basal repression as well as gamma radiation-induced gyrB gene expression in Deinococcus radiodurans. (United States)

    Anaganti, Narasimha; Basu, Bhakti; Mukhopadhyaya, Rita; Apte, Shree Kumar


    The radioresistant D. radiodurans regulates its DNA damage regulon (DDR) through interaction between a 17bp palindromic cis-regulatory element called the Radiation Desiccation Response Motif (RDRM), the DdrO repressor and a protease IrrE. The role of RDRM in regulation of DDR was dissected by constructing RDRM sequence-, position- or deletion-variants of Deinococcal gyrB gene (DR0906) promoter and by RDRM insertion in the non-RDRM groESL gene (DR0606) promoter, and monitoring the effect of such modifications on the basal as well as gamma radiation inducible promoter activity by quantifying fluorescence of a GFP reporter. RDRM sequence-variants revealed that the conservation of sequence at the 5th and 13th position and the ends of RDRM is essential for basal repression by interaction with DdrO. RDRM position-variants showed that the sequence acts as a negative regulatory element only when located around transcription start site (TSS) and within the span of RNA polymerase (RNAP) binding region. RDRM deletion-variants indicated that the 5' sequence of RDRM possibly possesses an enhancer-like element responsible for higher expression yields upon repressor clearance post-irradiation. The results suggest that RDRM plays both a negative as well as a positive role of in the regulation of DDR in D. radiodurans.

  14. Metacomprehension during Basal Reader Instruction: Do Teachers Promote It? (United States)

    Schmitt, Maribeth Cassidy; Baumann, James F.


    Analyzes elementary teachers' interactions with students during guided reading of basal reader selections to determine the extent to which the interactions promote students' metacomprehension abilities. Finds that teachers assumed most of the responsibility for students' comprehension themselves rather than conducting the lessons in a manner that…

  15. HDAC Activity Is Required for Efficient Core Promoter Function at the Mouse Mammary Tumor Virus Promoter

    Directory of Open Access Journals (Sweden)

    Sang C. Lee


    Full Text Available Histone deacetylases (HDACs have been shown to be required for basal or inducible transcription at a variety of genes by poorly understood mechanisms. We demonstrated previously that HDAC inhibition rapidly repressed transcription from the mouse mammary tumor virus (MMTV promoter by a mechanism that does not require the binding of upstream transcription factors. In the current study, we find that HDACs work through the core promoter sequences of MMTV as well as those of several cellular genes to facilitate transcriptional initiation through deacetylation of nonhistone proteins.

  16. Genome-wide computational prediction and analysis of core promoter elements across plant monocots and dicots (United States)

    Transcription initiation, essential to gene expression regulation, involves recruitment of basal transcription factors to the core promoter elements (CPEs). The distribution of currently known CPEs across plant genomes is largely unknown. This is the first large scale genome-wide report on the compu...

  17. Exome-based Variant Detection in Core Promoters. (United States)

    Kim, Yeong C; Cui, Jian; Luo, Jiangtao; Xiao, Fengxia; Downs, Bradley; Wang, San Ming


    Core promoter controls the initiation of transcription. Core promoter sequence change can disrupt transcriptional regulation, lead to impairment of gene expression and ultimately diseases. Therefore, comprehensive characterization of core promoters is essential to understand normal and abnormal gene expression in biomedical studies. Here we report the development of EVDC (Exome-based Variant Detection in Core promoters) method for genome-scale analysis of core-promoter sequence variation. This method is based on the fact that exome sequences contain the sequences not only from coding exons but also from non-coding region including core promoters generated by random fragmentation in exome sequencing process. Using exome data from three cell types of CD4+ T cells, CD19+ B cells and neutrophils of a single individual, we characterized the features of core promoter-mapped exome sequences, and analysed core-promoter variation in this individual genome. We also compared the core promoters between YRI (Yoruba in Ibadan, Nigeria) and the CEU (Utah residents of European decedent) populations using the exome data generated by the 1000 Genome project, and observed much higher variation in YRI population than in CEU population. Our study demonstrates that the EVDC method provides a simple but powerful means for genome-wile de novo characterization of core promoter sequence variation.

  18. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. (United States)

    Florio, Marta; Albert, Mareike; Taverna, Elena; Namba, Takashi; Brandl, Holger; Lewitus, Eric; Haffner, Christiane; Sykes, Alex; Wong, Fong Kuan; Peters, Jula; Guhr, Elaine; Klemroth, Sylvia; Prüfer, Kay; Kelso, Janet; Naumann, Ronald; Nüsslein, Ina; Dahl, Andreas; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B


    Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

  19. Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells. (United States)

    Ede, Christopher; Chen, Ximin; Lin, Meng-Yin; Chen, Yvonne Y


    Inducible transcription systems play a crucial role in a wide array of synthetic biology circuits. However, the majority of inducible promoters are constructed from a limited set of tried-and-true promoter parts, which are susceptible to common shortcomings such as high basal expression levels (i.e., leakiness). To expand the toolbox for regulated mammalian gene expression and facilitate the construction of mammalian genetic circuits with precise functionality, we quantitatively characterized a panel of eight core promoters, including sequences with mammalian, viral, and synthetic origins. We demonstrate that this selection of core promoters can provide a wide range of basal gene expression levels and achieve a gradient of fold-inductions spanning 2 orders of magnitude. Furthermore, commonly used parts such as minimal CMV and minimal SV40 promoters were shown to achieve robust gene expression upon induction, but also suffer from high levels of leakiness. In contrast, a synthetic promoter, YB_TATA, was shown to combine low basal expression with high transcription rate in the induced state to achieve significantly higher fold-induction ratios compared to all other promoters tested. These behaviors remain consistent when the promoters are coupled to different genetic outputs and different response elements, as well as across different host-cell types and DNA copy numbers. We apply this quantitative understanding of core promoter properties to the successful engineering of human T cells that respond to antigen stimulation via chimeric antigen receptor signaling specifically under hypoxic environments. Results presented in this study can facilitate the design and calibration of future mammalian synthetic biology systems capable of precisely programmed functionality.

  20. The relationship between the hepatitis B virus base core and precore/core promoter mutations and the development of cirrhotic hepatocellular carcinoma and noncirrhotic hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the mutations of basal core promoter(BCP) and precore(PreC) region of hepatitis B virus(HBV) and the association with the development of hepatocellular carcinoma in patients with chronic HBV infection. Methods Totally 381 untreated HBV patients were recruited from the Department of Infectious

  1. A novel method for the determination of basal gene expression of tissue-specific promoters: an analysis of prostate-specific promoters.

    NARCIS (Netherlands)

    Poel, H.G. van der; McCadden, J.; Verhaegh, G.W.C.T.; Kruszewski, M.; Ferrer, F.; Schalken, J.A.; Carducci, M.; Rodriguez, R.


    Because the toxicity of suicide gene therapeutics is directly related to basal promoter activity, we developed an assay to test for promoter "leakiness" using a diphtheria toxin mutant. Sequences of 15 prostate-specific gene promoter constructs were cloned in an expression plasmid (pBK; Stratagene,

  2. Plastome sequences of Lygodium japonicum and Marsilea crenata reveal the genome organization transformation from basal ferns to core leptosporangiates. (United States)

    Gao, Lei; Wang, Bo; Wang, Zhi-Wei; Zhou, Yuan; Su, Ying-Juan; Wang, Ting


    Previous studies have shown that core leptosporangiates, the most species-rich group of extant ferns (monilophytes), have a distinct plastid genome (plastome) organization pattern from basal fern lineages. However, the details of genome structure transformation from ancestral ferns to core leptosporangiates remain unclear because of limited plastome data available. Here, we have determined the complete chloroplast genome sequences of Lygodium japonicum (Lygodiaceae), a member of schizaeoid ferns (Schizaeales), and Marsilea crenata (Marsileaceae), a representative of heterosporous ferns (Salviniales). The two species represent the sister and the basal lineages of core leptosporangiates, respectively, for which the plastome sequences are currently unavailable. Comparative genomic analysis of all sequenced fern plastomes reveals that the gene order of L. japonicum plastome occupies an intermediate position between that of basal ferns and core leptosporangiates. The two exons of the fern ndhB gene have a unique pattern of intragenic copy number variances. Specifically, the substitution rate heterogeneity between the two exons is congruent with their copy number changes, confirming the constraint role that inverted repeats may play on the substitution rate of chloroplast gene sequences.

  3. Core properties and mobility of the basal screw dislocation in wurtzite GaN: a density functional theory study (United States)

    Belabbas, I.; Chen, J.; Heggie, M. I.; Latham, C. D.; Rayson, M. J.; Briddon, P. R.; Nouet, G.


    We have performed first principles simulations, based on density functional theory (DFT), to investigate the core properties of the basal a -type screw dislocation in wurtzite gallium nitride. Our calculations demonstrate that the fully coordinated shuffle core configuration is the most energetically favourable. The calculated electronic structure of the a -type screw dislocation was found to exhibit exclusively shallow gap states which are not associated with any extended metallization. This may explain why a -type screw dislocations are less detrimental to the performance of GaN based electronic devices than c -type screw dislocations.

  4. Dynamic usage of transcription start sites within core promoters

    DEFF Research Database (Denmark)

    Kawaji, Hideya; Frith, Martin C; Katayama, Shintaro


    BACKGROUND: Mammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level......, based on large-scale sequencing of transcript 5' ends. RESULTS: In the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites...

  5. Classification of Promoters Based on the Combination of Core Promoter Elements Exhibits Different Histone Modification Patterns (United States)

    Natsume-Kitatani, Yayoi; Mamitsuka, Hiroshi


    Four different histones (H2A, H2B, H3, and H4; two subunits each) constitute a histone octamer, around which DNA wraps to form histone-DNA complexes called nucleosomes. Amino acid residues in each histone are occasionally modified, resulting in several biological effects, including differential regulation of transcription. Core promoters that encompass the transcription start site have well-conserved DNA motifs, including the initiator (Inr), TATA box, and DPE, which are collectively called the core promoter elements (CPEs). In this study, we systematically studied the associations between the CPEs and histone modifications by integrating the Drosophila Core Promoter Database and time-series ChIP-seq data for histone modifications (H3K4me3, H3K27ac, and H3K27me3) during development in Drosophila melanogaster via the modENCODE project. We classified 96 core promoters into four groups based on the presence or absence of the TATA box or DPE, calculated the histone modification ratio at the core promoter region, and transcribed region for each core promoter. We found that the histone modifications in TATA-less groups were static during development and that the core promoters could be clearly divided into three types: i) core promoters with continuous active marks (H3K4me3 and H3K27ac), ii) core promoters with a continuous inactive mark (H3K27me3) and occasional active marks, and iii) core promoters with occasional histone modifications. Linear regression analysis and non-linear regression by random forest showed that the TATA-containing groups included core promoters without histone modifications, for which the measured RNA expression values were not predictable accurately from the histone modification status. DPE-containing groups had a higher relative frequency of H3K27me3 in both the core promoter region and transcribed region. In summary, our analysis showed that there was a systematic link between the existence of the CPEs and the dynamics, frequency and influence

  6. Classification of Promoters Based on the Combination of Core Promoter Elements Exhibits Different Histone Modification Patterns.

    Directory of Open Access Journals (Sweden)

    Yayoi Natsume-Kitatani

    Full Text Available Four different histones (H2A, H2B, H3, and H4; two subunits each constitute a histone octamer, around which DNA wraps to form histone-DNA complexes called nucleosomes. Amino acid residues in each histone are occasionally modified, resulting in several biological effects, including differential regulation of transcription. Core promoters that encompass the transcription start site have well-conserved DNA motifs, including the initiator (Inr, TATA box, and DPE, which are collectively called the core promoter elements (CPEs. In this study, we systematically studied the associations between the CPEs and histone modifications by integrating the Drosophila Core Promoter Database and time-series ChIP-seq data for histone modifications (H3K4me3, H3K27ac, and H3K27me3 during development in Drosophila melanogaster via the modENCODE project. We classified 96 core promoters into four groups based on the presence or absence of the TATA box or DPE, calculated the histone modification ratio at the core promoter region, and transcribed region for each core promoter. We found that the histone modifications in TATA-less groups were static during development and that the core promoters could be clearly divided into three types: i core promoters with continuous active marks (H3K4me3 and H3K27ac, ii core promoters with a continuous inactive mark (H3K27me3 and occasional active marks, and iii core promoters with occasional histone modifications. Linear regression analysis and non-linear regression by random forest showed that the TATA-containing groups included core promoters without histone modifications, for which the measured RNA expression values were not predictable accurately from the histone modification status. DPE-containing groups had a higher relative frequency of H3K27me3 in both the core promoter region and transcribed region. In summary, our analysis showed that there was a systematic link between the existence of the CPEs and the dynamics, frequency

  7. Characterization of nonconventional hepatitis B viruses lacking the core promoter. (United States)

    Chang, Shau-Feng; Chang, Shih-Hsuan; Li, Bi-Chen; Will, Hans; Netter, Hans Jürgen


    The core gene (C-gene) promoter and regulatory sequences play a central role in the hepatitis B virus (HBV) life cycle. They are essential for the synthesis of the pregenomic and precore mRNA. The pregenomic RNA is the template required for replication and also the template for the synthesis of the core protein and polymerase. Here, we report the in vivo existence and functional characterization of HBV variants that lack the C-gene promoter region and the regulatory sequences located therein. HBV promoter fragments were isolated by PCR from sera of chronic carriers and characterized. Truncated promoter elements were identified, and then tested in the context of wild-type genomes in the HuH-7 cell line. The expression of the recombinant HBV genome resulted in the synthesis of surface proteins, and low level of core protein as well as a transcript pattern similar to, but smaller in size to wild-type virus. The recombinant HBV genome with the truncated promoter region produced pregenomic RNA-like transcripts. These transcripts were encapsidated and reverse transcribed when complemented by sufficient core and polymerase protein. These date provide an explanation as to why such deletion mutants of HBV can be produced at all, they highlight the functional potentials of viral sequences activated by mutations and may be of relevance for viral evolution and persistence.

  8. Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation

    Directory of Open Access Journals (Sweden)

    Caitlin J. Symonette


    Full Text Available Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis.

  9. A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response (United States)

    Chandriani, Sanjay; Frengen, Eirik; Cowling, Victoria H.; Pendergrass, Sarah A.; Perou, Charles M.; Whitfield, Michael L.; Cole, Michael D.


    Background The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear. Methodology/Principal Findings Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNΔMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNΔMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a ‘Core MYC Signature’ and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples. Conclusions/Significance The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes. PMID:19690609

  10. A core MYC gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response.

    Directory of Open Access Journals (Sweden)

    Sanjay Chandriani

    Full Text Available BACKGROUND: The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNDeltaMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNDeltaMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a 'Core MYC Signature' and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples. CONCLUSIONS/SIGNIFICANCE: The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.

  11. Core promoter acetylation is not required for high transcription from the phosphoenolpyruvate carboxylase promoter in maize

    Directory of Open Access Journals (Sweden)

    Horst Ina


    Full Text Available Abstract Background Acetylation of promoter nucleosomes is tightly correlated and mechanistically linked to gene activity. However, transcription is not necessary for promoter acetylation. It seems, therefore, that external and endogenous stimuli control histone acetylation and by this contribute to gene regulation. Photosynthetic genes in plants are excellent models with which to study the connection between stimuli and chromatin modifications because these genes are strongly expressed and regulated by multiple stimuli that are easily manipulated. We have previously shown that acetylation of specific histone lysine residues on the photosynthetic phosphoenolpyruvate carboxylase (Pepc promoter in maize is controlled by light and is independent of other stimuli or gene activity. Acetylation of upstream promoter regions responds to a set of other stimuli which include the nutrient availability of the plant. Here, we have extended these studies by analysing histone acetylation during the diurnal and circadian rhythm of the plant. Results We show that histone acetylation of individual lysine residues is removed from the core promoter before the end of the illumination period which is an indication that light is not the only factor influencing core promoter acetylation. Deacetylation is accompanied by a decrease in gene activity. Pharmacological inhibition of histone deacetylation is not sufficient to prevent transcriptional repression, indicating that deacetylation is not controlling diurnal gene regulation. Variation of the Pepc promoter activity during the day is controlled by the circadian oscillator as it is maintained under constant illumination for at least 3 days. During this period, light-induced changes in histone acetylation are completely removed from the core promoter, although the light stimulus is continuously applied. However, acetylation of most sites on upstream promoter elements follows the circadian rhythm. Conclusion Our results

  12. Informational Text and the Common Core: A Content Analysis of Three Basal Reading Programs (United States)

    Walters, Barbara A.


    The Common Core State Standards for English Language Arts (CCSS-ELA) will have a significant impact on what teachers teach and what primary students are supposed to be able to do (Bomer & Maloch, 2011). By the end of fourth grade, reading instruction should be evenly balanced between literary text and informational text (NGA Center and CCSSO,…

  13. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity. (United States)

    Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun; Wang, Wei; Liu, Jing; Liu, Wei; Pan, Shaokun; Xie, Youhua


    Endogenous viral elements (EVE) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital for viral gene expression and replication. We previously identified in the budgerigar genome two EVEs that contain the full-length genome of an ancient budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2 Cp were active in several human and chicken cell lines. A region from nt -85 to -11 in eBHBV1 Cp was critical for the promoter activity. Bioinformatic analysis revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous transcription factor, at nt -64 to -50 in eBHBV1 Cp. The NF-Y core binding site (ATTGG, nt -58 to -54) was essential for eBHBV1 Cp activity. The same results were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y (NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated the promoter activity. Finally, the NF-Y core binding site is conserved in the Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses. Interestingly, a putative and functionally important NF-Y core binding site is located at nt -21 to -17 in the Cp of human hepatitis B virus. In conclusion, our findings have pinpointed an evolutionary conserved and functionally critical NF-Y binding element in the Cps of avihepadnaviruses.

  14. Mammalian RNA polymerase II core promoters: insights from genome-wide studies

    DEFF Research Database (Denmark)

    Sandelin, Albin; Carninci, Piero; Lenhard, Boris


    The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealin...

  15. Engineering of core promoter regions enables the construction of constitutive and inducible promoters in Halomonas sp. (United States)

    Li, Tingting; Li, Teng; Ji, Weiyue; Wang, Qiuyue; Zhang, Haoqian; Chen, Guo-Qiang; Lou, Chunbo; Ouyang, Qi


    Halomonas strain TD01, a newly identified halophilic bacterium, has proven to be a promising low-cost host for the production of chemicals. However, genetic manipulation in Halomonas sp. is still difficult due to the lack of well-characterized and tunable expression systems. In this study, a systematic, efficient method was exploited to construct both a constitutive promoter library and inducible promoters. Porin, a highly expressed protein in Halomonas TD01, was first identified from the Halomonas TD01 proteome. Subsequent study of the intergenic region upstream of porin led to the identification of a core promoter region, including -10 and -35 elements. By randomizing the sequence between the -35 and -10 elements, a constitutive promoter library was obtained with 310-fold variation in transcriptional activity; an inducible promoter with a >200-fold induction was built by integrating a lac operator into the core promoter region. As two complementary expression systems, the constitutive and inducible promoters were then employed to regulate the biosynthetic pathway of poly-3-hydroxybutyrate (PHB) in Halomonas TD01, demonstrating the usefulness of the expression systems, furthermore, they could be applied in future metabolic engineering of Halomonas TD strains, and the systematic method used in this study can be generalized to other less-characterized bacterial strains.

  16. The co-factor of LIM domains (CLIM/LDB/NLI) maintains basal mammary epithelial stem cells and promotes breast tumorigenesis. (United States)

    Salmans, Michael L; Yu, Zhengquan; Watanabe, Kazuhide; Cam, Eric; Sun, Peng; Smyth, Padhraic; Dai, Xing; Andersen, Bogi


    Mammary gland branching morphogenesis and ductal homeostasis relies on mammary stem cell function for the maintenance of basal and luminal cell compartments. The mechanisms of transcriptional regulation of the basal cell compartment are currently unknown. We explored these mechanisms in the basal cell compartment and identified the Co-factor of LIM domains (CLIM/LDB/NLI) as a transcriptional regulator that maintains these cells. Clims act within the basal cell compartment to promote branching morphogenesis by maintaining the number and proliferative potential of basal mammary epithelial stem cells. Clim2, in a complex with LMO4, supports mammary stem cells by directly targeting the Fgfr2 promoter in basal cells to increase its expression. Strikingly, Clims also coordinate basal-specific transcriptional programs to preserve luminal cell identity. These basal-derived cues inhibit epidermis-like differentiation of the luminal cell compartment and enhance the expression of luminal cell-specific oncogenes ErbB2 and ErbB3. Consistently, basal-expressed Clims promote the initiation and progression of breast cancer in the MMTV-PyMT tumor model, and the Clim-regulated branching morphogenesis gene network is a prognostic indicator of poor breast cancer outcome in humans.

  17. Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. (United States)

    Yang, Chuhu; Bolotin, Eugene; Jiang, Tao; Sladek, Frances M; Martinez, Ernest


    The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that approximately 76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs - M3 (SCGGAAGY) and M22 (TGCGCANK) - that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only approximately 10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, approximately 46% of human core promoters contain the consensus INR (YYANWYY) and approximately 30% are INR-containing TATA-less genes. Significantly, approximately 46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present - and tend to cluster - in the transcription start site (TSS) region of approximately 40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic "housekeeping" processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription.

  18. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis


    Shin, Dong-Hui; Park, Ji-Hye; Lee, Jeong-Yeon; Won, Hee-Young; Jang, Ki-Seok; MIN, KYUENG-WHAN; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu


    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in th...

  19. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis. (United States)

    Shin, Dong-Hui; Park, Ji-Hye; Lee, Jeong-Yeon; Won, Hee-Young; Jang, Ki-Seok; Min, Kyueng-Whan; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu


    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development.

  20. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P;


    The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...... have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes...

  1. Replacing the Promoter of the Murine Gene Encoding P-selectin with the Human Promoter Confers Human-like Basal and Inducible Expression in Mice. (United States)

    Liu, Zhenghui; Zhang, Nan; Shao, Bojing; Panicker, Sumith R; Fu, Jianxin; McEver, Rodger P


    In humans and mice, megakaryocytes/platelets and endothelial cells constitutively synthesize P-selectin and mobilize it to the plasma membrane to mediate leukocyte rolling during inflammation. TNF-α, interleukin 1β, and LPS markedly increase P-selectin mRNA in mice but decrease P-selectin mRNA in humans. Transgenic mice bearing the entire human SELP gene recapitulate basal and inducible expression of human P-selectin and reveal human-specific differences in P-selectin function. Differences in the human SELP and murine Selp promoters account for divergent expression in vitro, but their significance in vivo is not known. Here we generated knockin mice that replace the 1.4-kb proximal Selp promoter with the corresponding SELP sequence (Selp(KI)). Selp(KI) (/) (KI) mice constitutively expressed more P-selectin on platelets and more P-selectin mRNA in tissues but only slightly increased P-selectin mRNA after injection of TNF-α or LPS. Consistent with higher basal expression, leukocytes rolled more slowly on P-selectin in trauma-stimulated venules of Selp(KI) (/) (KI) mice. However, TNF-α did not further reduce P-selectin-dependent rolling velocities. Blunted up-regulation of P-selectin mRNA during contact hypersensitivity reduced P-selectin-dependent inflammation in Selp(KI) (/-) mice. Higher basal P-selectin in Selp(KI) (/) (KI) mice compensated for this defect. Therefore, divergent sequences in a short promoter mediate most of the functionally significant differences in expression of human and murine P-selectin in vivo.

  2. Regulatory Enhancer-Core-Promoter Communication via Transcription Factors and Cofactors. (United States)

    Zabidi, Muhammad A; Stark, Alexander


    Gene expression is regulated by genomic enhancers that recruit transcription factors and cofactors to activate transcription from target core promoters. Over the past years, thousands of enhancers and core promoters in animal genomes have been annotated, and we have learned much about the domain structure in which regulatory genomes are organized in animals. Enhancer-core-promoter targeting occurs at several levels, including regulatory domains, DNA accessibility, and sequence-encoded core-promoter specificities that are likely mediated by different regulatory proteins. We review here current knowledge about enhancer-core-promoter targeting, regulatory communication between enhancers and core promoters, and the protein factors involved. We conclude with an outlook on open questions that we find particularly interesting and that will likely lead to additional insights in the upcoming years.

  3. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion. (United States)

    Mojallal, Mahdi; Zheng, Yujuan; Hultin, Sara; Audebert, Stéphane; van Harn, Tanja; Johnsson, Per; Lenander, Claes; Fritz, Nicolas; Mieth, Christin; Corcoran, Martin; Lembo, Frédérique; Hallström, Marja; Hartman, Johan; Mazure, Nathalie M; Weide, Thomas; Grandér, Dan; Borg, Jean-Paul; Uhlén, Per; Holmgren, Lars


    The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

  4. Pathway for interferon-gamma to promote the differentiation of cholinergic neurons in rat embryonic basal forebrain/septal nuclei

    Institute of Scientific and Technical Information of China (English)


    BACKGROUND: The supernatant of interferon-gamma (IFN γ ) co-cultured with neonatal rat cortical glia can promote the cells in embryonic basal forebrain/septal nuclei to differentiate into cholinergic neurons, but the mechanism is still unclear.OBJECTIVE: To analyze the pathways for IFN γ to promote the differentiation of primarily cultured cholinergic neurons in rat embryonic basal forebrain/septal nuclei through culture in different conditioned medium.DESIGN: A controlled experiment taking cells as the observational target.SETTINGS: Department of Biochemistry and Molecular Biology, Youjiang Medical College for Nationalities; Department of Cell Biology, Beijing University Health Science Center.MATERIALS: Sixty-four pregnant Wistar rats for 16 days (250 - 350 g) and 84 Wistar rats (either male or female, 5 - 7 g) of 0 - 1 day after birth were provided by the experimental animal department of Beijing University Health Science Center. Rat IFN γ were provided by Gibco Company; Glial fibrillary acidic protein by Huamei Company.METHODS: The experiments were carried out in the Department of Cell Biology, Beijing University Health Science Center and Daheng Image Company of Chinese Academy of Science from July 1995 to December 2002. ① Interventions: The nerve cells in the basal forebrain/septal nuclei of the pregnant Wistar rats for 16 days were primarily cultured, and then divided into four groups: Blank control group (not any supernatant and medium was added); Control group (added by mixed glial cell or astrocyte conditioned medium); IFN γ group (added by mixed glial cell or astrocyte conditioned medium+IFN γ ). Antibody group (added by mixed glial cell or astrocyte conditioned medium+IFN γ +Ab-IFN γ ). Mixed glial cell or astrocyte conditioned medium was prepared using cerebral cortex of Wistar rats of 0 - 1 day after birth. ② Evaluation: The immunohistochemical method was used to perform the choline acetyltransferase (ChAT) staining of cholinergic neurons

  5. Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts (United States)

    Ji, C.; Chen, Y.; McCarthy, T. L.; Centrella, M.


    Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

  6. Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription. (United States)

    Xu, Muyu; Gonzalez-Hurtado, Elsie; Martinez, Ernest


    Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human β-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF-regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family.

  7. The CompHP Core Competencies Framework for Health Promotion in Europe (United States)

    Barry, Margaret M.; Battel-Kirk, Barbara; Dempsey, Colette


    Background: The CompHP Project on Developing Competencies and Professional Standards for Health Promotion in Europe was developed in response to the need for new and changing health promotion competencies to address health challenges. This article presents the process of developing the CompHP Core Competencies Framework for Health Promotion across…

  8. Novel SLC19A3 Promoter Deletion and Allelic Silencing in Biotin-Thiamine-Responsive Basal Ganglia Encephalopathy.

    Directory of Open Access Journals (Sweden)

    Irene Flønes

    Full Text Available Biotin-thiamine responsive basal ganglia disease is a severe, but potentially treatable disorder caused by mutations in the SLC19A3 gene. Although the disease is inherited in an autosomal recessive manner, patients with typical phenotypes carrying single heterozygous mutations have been reported. This makes the diagnosis uncertain and may delay treatment.In two siblings with early-onset encephalopathy dystonia and epilepsy, whole-exome sequencing revealed a novel single heterozygous SLC19A3 mutation (c.337T>C. Although Sanger-sequencing and copy-number analysis revealed no other aberrations, RNA-sequencing in brain tissue suggested the second allele was silenced. Whole-genome sequencing resolved the genetic defect by revealing a novel 45,049 bp deletion in the 5'-UTR region of the gene abolishing the promoter. High dose thiamine and biotin therapy was started in the surviving sibling who remains stable. In another patient two novel compound heterozygous SLC19A3 mutations were found. He improved substantially on thiamine and biotin therapy.We show that large genomic deletions occur in the regulatory region of SLC19A3 and should be considered in genetic testing. Moreover, our study highlights the power of whole-genome sequencing as a diagnostic tool for rare genetic disorders across a wide spectrum of mutations including non-coding large genomic rearrangements.

  9. Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression. (United States)

    Saldarriaga, Omar A; Travi, Bruno L; Choudhury, Goutam Ghosh; Melby, Peter C


    IFN-γ/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (-233 to -133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (-153/-142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (-153/-142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-γ/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS.

  10. Predicting Polymerase Ⅱ Core Promoters by Cooperating Transcription Factor Binding Sites in Eukaryotic Genes

    Institute of Scientific and Technical Information of China (English)

    Xiao-Tu MA; Min-Ping QIAN; Hai-Xu TANG


    Several discriminate functions for predicting core promoters that based on the potential cooperation between transcription factor binding sites (TFBSs) are discussed. It is demonstrated that the promoter predicting accuracy is improved when the cooperation among TFBSs is taken into consideration.The core promoter region of a newly discovered gene CKLFSF1 is predicted to locate more than 1.5 kb far away from the 5′ end of the transcript and in the last intron of its upstream gene, which is experimentally confirmed later. The core promoters of 3402 human RefSeq sequences, obtained by extending the mRNAs in human genome sequences, are predicted by our algorithm, and there are about 60% of the predicted core promoters locating within the ± 500 bp region relative to the annotated transcription start site.

  11. Synthetic Core Promoters as Universal Parts for Fine-Tuning Expression in Different Yeast Species. (United States)

    Portela, Rui M C; Vogl, Thomas; Kniely, Claudia; Fischer, Jasmin E; Oliveira, Rui; Glieder, Anton


    Synthetic biology and metabolic engineering experiments frequently require the fine-tuning of gene expression to balance and optimize protein levels of regulators or metabolic enzymes. A key concept of synthetic biology is the development of modular parts that can be used in different contexts. Here, we have applied a computational multifactor design approach to generate de novo synthetic core promoters and 5' untranslated regions (UTRs) for yeast cells. In contrast to upstream cis-regulatory modules (CRMs), core promoters are typically not subject to specific regulation, making them ideal engineering targets for gene expression fine-tuning. 112 synthetic core promoter sequences were designed on the basis of the sequence/function relationship of natural core promoters, nucleosome occupancy and the presence of short motifs. The synthetic core promoters were fused to the Pichia pastoris AOX1 CRM, and the resulting activity spanned more than a 200-fold range (0.3% to 70.6% of the wild type AOX1 level). The top-ten synthetic core promoters with highest activity were fused to six additional CRMs (three in P. pastoris and three in Saccharomyces cerevisiae). Inducible CRM constructs showed significantly higher activity than constitutive CRMs, reaching up to 176% of natural core promoters. Comparing the activity of the same synthetic core promoters fused to different CRMs revealed high correlations only for CRMs within the same organism. These data suggest that modularity is maintained to some extent but only within the same organism. Due to the conserved role of eukaryotic core promoters, this rational design concept may be transferred to other organisms as a generic engineering tool.

  12. Evidence that the Dictyostelium STAT protein Dd-STATa plays a role in the differentiation of inner basal disc cells and identification of a promoter element essential for expression in these cells. (United States)

    Shimada, Nao; Maruo, Toshinari; Maeda, Mineko; Urushihara, Hideko; Kawata, Takefumi


    Dd-STATa, a Dictyostelium homolog of the metazoan STAT (signal transducers and activators of transcription) proteins, is necessary in the slug for correct entry into culmination. Dd-STATa-null mutant fails to culminate and its phenotype correlates with the loss of a funnel-shaped core region, the pstAB core region, which expresses both the ecmA and ecmB genes. To understand how the differentiation of pstAB core cells is regulated, we identified an EST that is expressed in the core cells of normal slugs but down-regulated in the Dd-STATa-null mutant. This EST, SSK348, encodes a close homolog of the Dictyostelium acetyl-CoA synthetase (ACS). A promoter fragment of the cognate gene, aslA (acetyl-CoA synthetase-like A), was fused to a lacZ reporter and the expression pattern determined. As expected from the behavior of the endogenous aslA gene, the aslA::lacZ fusion gene is not expressed in Dd-STATa-null slugs. In parental cells, the aslA promoter is first activated in the funnel-shaped core cells located at the slug anterior, the "pstAB core." During culmination, the pstAB core cells move down, through the prespore cells, to form the inner part of the basal disc. As the spore mass climbs the stalk, the aslA gene comes to be expressed in cells of the upper and lower cups, structures that cradle the spore head. Deletion and point mutation analyses of the promoter identified an AT-rich sequence that is necessary for expression in the pstAB core. This acts in combination with repressor regions that prevent ectopic aslA expression in the pre-stalk regions of slugs and the stalks of culminants. Thus, this study confirms that Dd-STATa is necessary for the differentiation of pstAB core cells, by showing that it is needed for the activation of the aslA gene. It also identifies aslA promoter elements that are likely to be regulated, directly or indirectly, by Dd-STATa.

  13. A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice (United States)

    LIU, J.; KANKI, Y.; OKADA, Y.; JIN, E.; YANO, K.; SHIH, S.-C.; MINAMI, T.; AIRD, W. C.


    Summary Background The von Willebrand factor (VWF) gene is a marker for spatial and temporal heterogeneity of the endothelium. A GATA motif at +220 has been implicated in basal VWF expression in vitro. Other studies have shown that GATA3 and VWF are transcriptionally downregulated in response to inflammatory mediators. Objectives Our goal was to determine the importance of the +220 GATA motif in mediating expression of VWF promoter in vivo, and to elucidate whether the GATA element plays a role in spatial and/or temporal regulation of VWF expression. Methods ChIP and electrophoretic mobility shift assays were carried out in human umbilical vein endothelial cells (HUVEC). Reporter gene constructs containing 3.6 kb of the human VWF promoter with and without amutation of the +220 GATA element were transfected into cultured endothelial cells or targeted to the Hprt locus of mice. The Hprt-targeted mice were subjected to endotoxemia. Results In protein-DNA binding assays, the +220 GATA motif bound GATA-2, -3 and -6. Mutation of the GATA site resulted in reduced basal promoter activity in HUVEC. When targeted to the Hprt locus of mice, the GATA mutation resulted in a significant, proportionate reduction of promoter activity in LacZ expressing vascular beds. Systemic administration of lipopolysaccharide (LPS) resulted in a widespread reduction in VWF mRNA expression and promoter activity. LPS-mediated repression of the VWF promoter was unaffected by the GATA mutation. Conclusions A region of the VWF promoter between −2182 and the end of the first intron contains information for LPS-mediated gene repression. The +220 GATA motif is important for basal, but not LPS-repressible expression of the VWF gene. PMID:19496923

  14. Regulation of gene expression in the protozoan parasite Entamoeba invadens: identification of core promoter elements and promoters with stage-specific expression patterns. (United States)

    Manna, Dipak; Ehrenkaufer, Gretchen M; Singh, Upinder


    Developmental switching between life-cycle stages is a common feature among many pathogenic organisms. Entamoeba histolytica is an important human pathogen and is a leading parasitic cause of death globally. During its life cycle, Entamoeba converts between cysts (essential for disease transmission) and trophozoites (responsible for tissue invasion). Despite being central to its biology, the triggers that are involved in the developmental pathways of this parasite are not well understood. In order to define the transcriptional network associated with stage conversion we used Entamoeba invadens which serves as a model system for Entamoeba developmental biology, and performed RNA sequencing at different developmental time points. In this study RNA-Seq data was utilised to define basal transcriptional control elements as well as to identify promoters which regulate stage-specific gene expression patterns. We discovered that the 5' and 3' untranslated regions of E. invadens genes are short, a median of 20 nucleotides (nt) and 26 nt respectively. Bioinformatics analysis of DNA sequences proximate to the start and stop codons identified two conserved motifs: (i) E. invadens Core Promoter Motif - GAAC-Like (EiCPM-GL) (GAACTACAAA), and (ii) E. invadens 3'-U-Rich Motif (Ei3'-URM) (TTTGTT) in the 5' and 3' flanking regions, respectively. Electrophoretic mobility shift assays demonstrated that both motifs specifically bind nuclear protein(s) from E. invadens trophozoites. Additionally, we identified select genes with stage-specific expression patterns and analysed the ability of each gene promoter to drive a luciferase reporter gene during the developmental cycle. This approach confirmed three trophozoite-specific, four encystation-specific and two excystation-specific promoters. This work lays the framework for use of stage-specific promoters to express proteins of interest in a particular life-cycle stage, adding to the molecular toolbox for genetic manipulation of E

  15. Evolutionary trend of exceptionally long human core promoter short tandem repeats. (United States)

    Ohadi, M; Mohammadparast, S; Darvish, H


    Short tandem repeats (STRs) are variable elements that play a significant role in genome evolution by creating and maintaining quantitative genetic variation. Because of their proximity to the +1 transcription start site (TSS) and polymorphic nature, core promoter STRs may be considered a novel source of variation across species. In a genome-scale analysis of the entire human protein-coding genes annotated in the GeneCards database (19,927), we analyze the prevalence and repeat numbers of different classes of core promoter STRs in the interval between -120 and +1 to the TSS. We also analyze the evolutionary trend of exceptionally long core promoter STRs of ≥6-repeats. 133 genes (~2%) had core promoter STRs of ≥6-repeats. In the majority of those genes, the STR motifs were found to be conserved across evolution. Di-nucleotide repeats had the highest representation in the human core promoter long STRs (72 genes). Tri- (52 genes), tetra-, penta-, and hexa-nucleotide STRs (9 genes) were also present in the descending prevalence. The majority of those genes (84 genes) revealed directional expansion of core promoter STRs from mouse to human. However, in a number of genes, the difference in average allele size across species was sufficiently small that there might be a constraint on the evolution of average allele size. Random drift of STRs from mouse to human was also observed in a minority of genes. Future work on the genes listed in the current study may further our knowledge into the potential importance of core promoter STRs in human evolution.

  16. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

    Directory of Open Access Journals (Sweden)

    Daniel Meier

    Full Text Available The Fanconi anemia (FA gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS. In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs, and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

  17. Characterization and identification of microRNA core promoters in four model species.

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    Xuefeng Zhou


    Full Text Available MicroRNAs are short, noncoding RNAs that play important roles in post-transcriptional gene regulation. Although many functions of microRNAs in plants and animals have been revealed in recent years, the transcriptional mechanism of microRNA genes is not well-understood. To elucidate the transcriptional regulation of microRNA genes, we study and characterize, in a genome scale, the promoters of intergenic microRNA genes in Caenorhabditis elegans, Homo sapiens, Arabidopsis thaliana, and Oryza sativa. We show that most known microRNA genes in these four species have the same type of promoters as protein-coding genes have. To further characterize the promoters of microRNA genes, we developed a novel promoter prediction method, called common query voting (CoVote, which is more effective than available promoter prediction methods. Using this new method, we identify putative core promoters of most known microRNA genes in the four model species. Moreover, we characterize the promoters of microRNA genes in these four species. We discover many significant, characteristic sequence motifs in these core promoters, several of which match or resemble the known cis-acting elements for transcription initiation. Among these motifs, some are conserved across different species while some are specific to microRNA genes of individual species.

  18. Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE

    DEFF Research Database (Denmark)

    Valen, Eivind; Pascarella, Giovanni; Chalk, Alistair;


    in a given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth...... of novel core promoters that are preferentially used in hippocampus: This is the most comprehensive promoter data set for any tissue to date. Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters...

  19. Partnership between CTSI and business schools can promote best practices for core facilities and resources. (United States)

    Reeves, Lilith; Dunn-Jensen, Linda M; Baldwin, Timothy T; Tatikonda, Mohan V; Cornetta, Kenneth


    Biomedical research enterprises require a large number of core facilities and resources to supply the infrastructure necessary for translational research. Maintaining the financial viability and promoting efficiency in an academic environment can be particularly challenging for medical schools and universities. The Indiana Clinical and Translational Sciences Institute sought to improve core and service programs through a partnership with the Indiana University Kelley School of Business. The program paired teams of Masters of Business Administration students with cores and programs that self-identified the need for assistance in project management, financial management, marketing, or resource efficiency. The projects were developed by CTSI project managers and business school faculty using service-learning principles to ensure learning for students who also received course credit for their participation. With three years of experience, the program demonstrates a successful partnership that improves clinical research infrastructure by promoting business best practices and providing a valued learning experience for business students.


    Reeves, Lilith; Dunn-Jensen, Linda M.; Baldwin, Timothy T.; Tatikonda, Mohan V.; Cornetta, Kenneth


    Biomedical research enterprises require a large number of core facilities and resources to supply the infrastructure necessary for translational research. Maintaining the financial viability and promoting efficiency in an academic environment can be particularly challenging for medical schools and universities. The Indiana Clinical and Translational Sciences Institute sought to improve core and service programs through a partnership with the Indiana University Kelley School of Business. The program paired teams of Masters of Business Administration students with cores and programs that self-identified the need for assistance in project management, financial management, marketing, or resource efficiency. The projects were developed by CTSI project managers and business school faculty using service-learning principles to ensure learning for students who also received course credit for their participation. With three years of experience, the program demonstrates a successful partnership that improves clinical research infrastructure by promoting business best practices and providing a valued learning experience for business students. PMID:23919365

  1. Core Promoter Plasticity Between Maize Tissues and Genotypes Contrasts with Predominance of Sharp Transcription Initiation Sites. (United States)

    Mejía-Guerra, María Katherine; Li, Wei; Galeano, Narmer F; Vidal, Mabel; Gray, John; Doseff, Andrea I; Grotewold, Erich


    Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop.

  2. HCV core protein-induced down-regulation of microRNA-152 promoted aberrant proliferation by regulating Wnt1 in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Shifeng Huang

    Full Text Available BACKGROUND: Hepatitis C virus (HCV has been reported to regulate cellular microRNAs (miRNAs. The HCV core protein is considered to be a potential oncoprotein in HCV-related hepatocellular carcinoma (HCV-HCC, but HCV core-regulated miRNAs are largely unknown. Our preliminary experiments revealed significant down-regulation of microRNA-152 (miR-152 by HCV core protein in HepG2 cells. Through target gene prediction softwares, Wnt1 was predicted to be a potential target of miR-152. The present study was initiated to investigate whether miR-152 is aberrantly regulated by the HCV core protein, and involved in the regulation of the aberrant proliferation of HCV-HCC cells. METHODS: MiR-152 levels were examined by stem-loop real-time RT-PCR (SLqRT-PCR. Cell proliferation was analyzed by MTT and colony formation assay. Cell cycle analysis was performed by flow cytometry. Luciferase reporter assay was conducted to confirm miRNA-target association. Wnt1 expression was determined by real-time qPCR and Western blotting. RESULTS: HCV core protein significantly suppressed miR-152 expression, and led to significant Wnt1 up-regulation with a concomitant aberrantly promoted proliferation. Moreover, we validated that miR-152 inhibition promoted, while miR-152 mimics inhibited cell proliferation. Using, qRT-PCR and western blot, Wnt1 was demonstrated to be regulated by miR-152. Luciferase activity assay showed that while miR-152 mimics significantly reduced the luciferase activity by 83.76% (P<0.0001, miR-152 inhibitor showed no effect on luciferase reporter. Most notably, salvage expression of miR-152 after Ad-HCV core infection for 24 h almost totally reversed the proliferation-promoting effect of the HCV core protein, and meanwhile, reduced the expression of both Wnt1 mRNA and protein to basal levels. CONCLUSION: These findings provide important evidence that the reduced miR-152 expression by HCV core protein can indirectly lose an inhibitory effect on Wnt1

  3. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation

    Directory of Open Access Journals (Sweden)

    Ze-Yi Zheng


    Full Text Available Basal-like breast cancers (BLBCs are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  4. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation. (United States)

    Zheng, Ze-Yi; Tian, Lin; Bu, Wen; Fan, Cheng; Gao, Xia; Wang, Hai; Liao, Yi-Hua; Li, Yi; Lewis, Michael T; Edwards, Dean; Zwaka, Thomas P; Hilsenbeck, Susan G; Medina, Daniel; Perou, Charles M; Creighton, Chad J; Zhang, Xiang H-F; Chang, Eric C


    Basal-like breast cancers (BLBCs) are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  5. ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. (United States)

    Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Andres Blanco, Mario; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose-Anne; DeCoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J; Sinha, Satrajit; Kang, Yibin


    Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ΔNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.

  6. Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients. (United States)

    Truong, Bui Xuan; Yano, Yoshihiko; Seo, Yasushi; Phuong, Tran Minh; Tanaka, Yasuhito; Kato, Hirotaka; Miki, Akira; Utsumi, Takako; Azuma, Takeshi; Trach, Nguyen Khanh; Mizokami, Masashi; Hayashi, Yoshitake; Kasuga, Masato


    Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients.

  7. Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy. (United States)

    Lahoz, Carlos; Peña, Rocío; Mostaza, Jose M; Jiménez, Javier; Subirats, Enric; Pintó, Xavier; Taboada, Manuel; López-Pastor, Angela


    Statins decrease cardiovascular morbidity and mortality, essentially, by reducing LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol concentrations. Environmental and genetic factors are known to affect LDL-C response to statins but less is known regarding HDL-C. We have evaluated the lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in relation to the G/A polymorphism in the promoter region of the apo A-I gene in 397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the study population, 61.7% were homozygous for the G allele and 36% were heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis). However, on segregation by gender and smoking status the effect was significant only in non-smoking males. The A allele carriers did not increase their HDL-C concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response between both groups were significant before (P=0.008) and after adjustment for confounding variables such as age and baseline HDL-C concentration (P=0.046). We conclude that the G/A polymorphism of the apo A-I promoter region affects not only baseline HDL-C concentrations but also its response to pravastatin treatment.

  8. Core histone genes of Giardia intestinalis: genomic organization, promoter structure, and expression

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    Adam Rodney D


    Full Text Available Abstract Background Giardia intestinalis is a protist found in freshwaters worldwide, and is the most common cause of parasitic diarrhea in humans. The phylogenetic position of this parasite is still much debated. Histones are small, highly conserved proteins that associate tightly with DNA to form chromatin within the nucleus. There are two classes of core histone genes in higher eukaryotes: DNA replication-independent histones and DNA replication-dependent ones. Results We identified two copies each of the core histone H2a, H2b and H3 genes, and three copies of the H4 gene, at separate locations on chromosomes 3, 4 and 5 within the genome of Giardia intestinalis, but no gene encoding a H1 linker histone could be recognized. The copies of each gene share extensive DNA sequence identities throughout their coding and 5' noncoding regions, which suggests these copies have arisen from relatively recent gene duplications or gene conversions. The transcription start sites are at triplet A sequences 1–27 nucleotides upstream of the translation start codon for each gene. We determined that a 50 bp region upstream from the start of the histone H4 coding region is the minimal promoter, and a highly conserved 15 bp sequence called the histone motif (him is essential for its activity. The Giardia core histone genes are constitutively expressed at approximately equivalent levels and their mRNAs are polyadenylated. Competition gel-shift experiments suggest that a factor within the protein complex that binds him may also be a part of the protein complexes that bind other promoter elements described previously in Giardia. Conclusion In contrast to other eukaryotes, the Giardia genome has only a single class of core histone genes that encode replication-independent histones. Our inability to locate a gene encoding the linker histone H1 leads us to speculate that the H1 protein may not be required for the compaction of Giardia's small and gene-rich genome.

  9. Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma. (United States)

    Kim, Ja Kyung; Chang, Hye Young; Lee, Jung Min; Baatarkhuu, Oidov; Yoon, Young Joon; Park, Jun Yong; Kim, Do Young; Han, Kwang-Hyub; Chon, Chae Yoon; Ahn, Sang Hoon


    Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross-sectional case-control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age-, sex-, and hepatitis B e antigen (HBeAg) status-matched patients without HCC (non- HCC group). Age and sex were also matched between HBeAg-positive and -negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box alpha region, the T1689 [corrected] mutation in between the box alpha and beta regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non-HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P HBV/C2.

  10. Genome-wide identification of human- and primate-specific core promoter short tandem repeats. (United States)

    Bushehri, A; Barez, M R Mashhoudi; Mansouri, S K; Biglarian, A; Ohadi, M


    Recent reports of a link between human- and primate-specific genetic factors and human/primate-specific characteristics and diseases necessitate genome-wide identification of those factors. We have previously reported core promoter short tandem repeats (STRs) of extreme length (≥6-repeats) that have expanded exceptionally in primates vs. non-primates, and may have a function in adaptive evolution. In the study reported here, we extended our study to the human STRs of ≥3-repeats in the category of penta and hexaucleotide STRs, across the entire human protein coding gene core promoters, and analyzed their status in several superorders and orders of vertebrates, using the Ensembl database. The ConSite software was used to identify the transcription factor (TF) sets binding to those STRs. STR specificity was observed at different levels of human and non-human primate (NHP) evolution. 73% of the pentanucleotide STRs and 68% of the hexanucleotide STRs were found to be specific to human and NHPs. AP-2alpha, Sp1, and MZF were the predominantly selected TFs (90%) binding to the human-specific STRs. Furthermore, the number of TF sets binding to a given STR was found to be a selection factor for that STR. Our findings indicate that selected STRs, the cognate binding TFs, and the number of TF set binding to those STRs function as switch codes at different levels of human and NHP evolution and speciation.

  11. Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis. (United States)

    Meyer, Luisa A; Johnson, Michael G; Cullen, Diane M; Vivanco, Juan F; Blank, Robert D; Ploeg, Heidi-Lynn; Smith, Everett L


    Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-1 (big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2×2 factorial trial of daily mechanical loading (-2000με, 120cycles daily, "jump" waveform) and big ET1 (25ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (ΔEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on ΔEapp (p=0.25 and 0.51 for load and big ET1, respectively). The ΔEapp in the "no load + big ET1" (CE, 13±12.2%, p=0.56), "load + no big ET1" (LC, 17±3.9%, p=0.14) and "load + big ET1" (LE, 19±4.2%, p=0.13) treatment groups were not statistically different than the control group (CC, 3.3%±8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (p=0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (p=0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (p=0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (p=0.037, p=0.055 respectively) and MAR (p=0.0040, p=0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (p=0.019) and LC (p=0.074) than CC. The PGE2 levels were elevated at 8days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15

  12. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. (United States)

    Balko, Justin M; Schwarz, Luis J; Bhola, Neil E; Kurupi, Richard; Owens, Phillip; Miller, Todd W; Gómez, Henry; Cook, Rebecca S; Arteaga, Carlos L


    Basal-like breast cancer (BLBC) is an aggressive disease that lacks a clinically approved targeted therapy. Traditional chemotherapy is effective in BLBC, but it spares the cancer stem cell (CSC)-like population, which is likely to contribute to cancer recurrence after the initial treatment. Dual specificity phosphatase-4 (DUSP4) is a negative regulator of the mitogen-activated protein kinase (MAPK) pathway that is deficient in highly aggressive BLBCs treated with chemotherapy, leading to aberrant MAPK activation and resistance to taxane-induced apoptosis. Herein, we investigated how DUSP4 regulates the MAP-ERK kinase (MEK) and c-jun-NH2-kinase (JNK) pathways in modifying CSC-like behavior. DUSP4 loss increased mammosphere formation and the expression of the CSC-promoting cytokines interleukin (IL)-6 and IL-8. These effects were caused in part by loss of control of the MEK and JNK pathways and involved downstream activation of the ETS-1 and c-JUN transcription factors. Enforced expression of DUSP4 reduced the CD44(+)/CD24(-) population in multiple BLBC cell lines in a MEK-dependent manner, limiting tumor formation of claudin-low SUM159PT cells in mice. Our findings support the evaluation of MEK and JNK pathway inhibitors as therapeutic agents in BLBC to eliminate the CSC population.

  13. miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yuan Li


    Full Text Available The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1 and cyclin-dependent kinase inhibit 1B (CDKN1B, by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.

  14. Basal Cell Carcinoma (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  15. CORE

    DEFF Research Database (Denmark)

    Krigslund, Jeppe; Hansen, Jonas; Hundebøll, Martin


    different flows. Instead of maintaining these approaches separate, we propose a protocol (CORE) that brings together these coding mechanisms. Our protocol uses random linear network coding (RLNC) for intra- session coding but allows nodes in the network to setup inter- session coding regions where flows...... intersect. Routes for unicast sessions are agnostic to other sessions and setup beforehand, CORE will then discover and exploit intersecting routes. Our approach allows the inter-session regions to leverage RLNC to compensate for losses or failures in the overhearing or transmitting process. Thus, we...... increase the benefits of XORing by exploiting the underlying RLNC structure of individual flows. This goes beyond providing additional reliability to each individual session and beyond exploiting coding opportunistically. Our numerical results show that CORE outperforms both forwarding and COPE...

  16. ATG12-ATG3 connects basal autophagy and late endosome function. (United States)

    Murrow, Lyndsay; Debnath, Jayanta


    In addition to supporting cell survival in response to starvation or stress, autophagy promotes basal protein and organelle turnover. Compared to our understanding of stress-induced autophagy, little is known about how basal autophagy is regulated and how its activity is coordinated with other cellular processes. We recently identified a novel interaction between the ATG12-ATG3 conjugate and the ESCRT-associated protein PDCD6IP/Alix that promotes basal autophagy and endolysosomal trafficking. Moreover, ATG12-ATG3 is required for diverse PDCD6IP-mediated functions including late endosome distribution, exosome secretion, and viral budding. Our results highlight the importance of late endosomes for basal autophagic flux and reveal distinct roles for the core autophagy proteins ATG12 and ATG3 in controlling late endosome function.

  17. Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells. (United States)

    Pires, Maira M; Hopkins, Benjamin D; Saal, Lao H; Parsons, Ramon E


    Breast cancer can be classified into different molecular subtypes with varying clinical and pathological characteristics. The basal-like breast cancer subtype represents one of the most aggressive and lethal types of breast cancer, and due to poor mechanistic understanding, it lacks targeted therapy. Many basal-like breast cancer patient samples display alterations of established drivers of cancer development, including elevated expression of EGFR, p53 inactivating mutations and loss of expression of the tumor suppressor PTEN; however, their contribution to human basal-like breast cancer pathogenesis remains ill-defined. Using non-transformed human mammary epithelial cells, we set out to determine whether altering EGFR, p53 and PTEN in different combinations could contribute to basal-like breast cancer progression through transformation of cells. Altering PTEN in combination with either p53 or EGFR in contrast to any of the single alterations caused increased growth of transformed colonies in soft agar. Concomitantly modifying all three genes led to the highest rate of cellular proliferation and the greatest degree of anchorage-independent colony formation. Results from our effort to engineer a model of BBC expressing alterations of EGFR, p53 and PTEN suggest that these changes are cooperative and likely play a causal role in basal-like breast cancer pathogenesis. Consideration should be given to targeting EGFR and restoring p53 and PTEN signaling simultaneously as a strategy for treatment of this subtype of breast cancer.

  18. The barley HvNAC6 transcription factor affects ABA accumulation and promotes basal resistance against powdery mildew

    DEFF Research Database (Denmark)

    Chen, Yan-Jun; Perera, Venura; Wagner, Michael


    a transgenic approach to constitutively silence HvNAC6 expression, using RNA interference (RNAi), to investigate the in vivo functions of HvNAC6 in basal resistance responses in barley in relation to the phytohormone ABA. The HvNAC6 RNAi plants displayed reduced HvNAC6 transcript levels and were more...... susceptible to Bgh than wild-type plants. Application of exogenous ABA increased basal resistance against Bgh in wild-type plants, but not in HvNAC6 RNAi plants, suggesting that ABA is a positive regulator of basal resistance which depends on HvNAC6. Silencing of HvNAC6 expression altered the light....../dark rhythm of ABA levels which were, however, not influenced by Bgh inoculation. The expression of the two ABA biosynthetic genes HvNCED1 and HvNCED2 was compromised, and transcript levels of the ABA conjugating HvBG7 enzyme were elevated in the HvNAC6 RNAi lines, but this effect was not clearly associated...

  19. Mutational analysis of the UCP2 core promoter and relationships of variants with obesity

    DEFF Research Database (Denmark)

    Dalgaard, Louise T; Andersen, Gitte; Larsen, Lesli H;


    To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain.......To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain....

  20. Brain-derived neurotrophic factor enhances the basal rate of protein synthesis by increasing active eukaryotic elongation factor 2 levels and promoting translation elongation in cortical neurons. (United States)

    Takei, Nobuyuki; Kawamura, Mihoko; Ishizuka, Yuta; Kakiya, Naomasa; Inamura, Naoko; Namba, Hisaaki; Nawa, Hiroyuki


    The constitutive and activity-dependent components of protein synthesis are both critical for neural function. Although the mechanisms controlling extracellularly induced protein synthesis are becoming clear, less is understood about the molecular networks that regulate the basal translation rate. Here we describe the effects of chronic treatment with various neurotrophic factors and cytokines on the basal rate of protein synthesis in primary cortical neurons. Among the examined factors, brain-derived neurotrophic factor (BDNF) showed the strongest effect. The rate of protein synthesis increased in the cortical tissues of BDNF transgenic mice, whereas it decreased in BDNF knock-out mice. BDNF specifically increased the level of the active, unphosphorylated form of eukaryotic elongation factor 2 (eEF2). The levels of active eEF2 increased and decreased in BDNF transgenic and BDNF knock-out mice, respectively. BDNF decreased kinase activity and increased phosphatase activity against eEF2 in vitro. Additionally, BDNF shortened the ribosomal transit time, an index of translation elongation. In agreement with these results, overexpression of eEF2 enhanced protein synthesis. Taken together, our results demonstrate that the increased level of active eEF2 induced by chronic BDNF stimulation enhances translational elongation processes and increases the total rate of protein synthesis in neurons.

  1. Promoting utilization of Saccharum spp. genetic resources through genetic diversity analysis and core collection construction.

    Directory of Open Access Journals (Sweden)

    Spurthi N Nayak

    Full Text Available Sugarcane (Saccharum spp. and other members of Saccharum spp. are attractive biofuel feedstocks. One of the two World Collections of Sugarcane and Related Grasses (WCSRG is in Miami, FL. This WCSRG has 1002 accessions, presumably with valuable alleles for biomass, other important agronomic traits, and stress resistance. However, the WCSRG has not been fully exploited by breeders due to its lack of characterization and unmanageable population. In order to optimize the use of this genetic resource, we aim to 1 genotypically evaluate all the 1002 accessions to understand its genetic diversity and population structure and 2 form a core collection, which captures most of the genetic diversity in the WCSRG. We screened 36 microsatellite markers on 1002 genotypes and recorded 209 alleles. Genetic diversity of the WCSRG ranged from 0 to 0.5 with an average of 0.304. The population structure analysis and principal coordinate analysis revealed three clusters with all S. spontaneum in one cluster, S. officinarum and S. hybrids in the second cluster and mostly non-Saccharum spp. in the third cluster. A core collection of 300 accessions was identified which captured the maximum genetic diversity of the entire WCSRG which can be further exploited for sugarcane and energy cane breeding. Sugarcane and energy cane breeders can effectively utilize this core collection for cultivar improvement. Further, the core collection can provide resources for forming an association panel to evaluate the traits of agronomic and commercial importance.

  2. Promoting utilization of Saccharum spp. genetic resources through genetic diversity analysis and core collection construction. (United States)

    Nayak, Spurthi N; Song, Jian; Villa, Andrea; Pathak, Bhuvan; Ayala-Silva, Tomas; Yang, Xiping; Todd, James; Glynn, Neil C; Kuhn, David N; Glaz, Barry; Gilbert, Robert A; Comstock, Jack C; Wang, Jianping


    Sugarcane (Saccharum spp.) and other members of Saccharum spp. are attractive biofuel feedstocks. One of the two World Collections of Sugarcane and Related Grasses (WCSRG) is in Miami, FL. This WCSRG has 1002 accessions, presumably with valuable alleles for biomass, other important agronomic traits, and stress resistance. However, the WCSRG has not been fully exploited by breeders due to its lack of characterization and unmanageable population. In order to optimize the use of this genetic resource, we aim to 1) genotypically evaluate all the 1002 accessions to understand its genetic diversity and population structure and 2) form a core collection, which captures most of the genetic diversity in the WCSRG. We screened 36 microsatellite markers on 1002 genotypes and recorded 209 alleles. Genetic diversity of the WCSRG ranged from 0 to 0.5 with an average of 0.304. The population structure analysis and principal coordinate analysis revealed three clusters with all S. spontaneum in one cluster, S. officinarum and S. hybrids in the second cluster and mostly non-Saccharum spp. in the third cluster. A core collection of 300 accessions was identified which captured the maximum genetic diversity of the entire WCSRG which can be further exploited for sugarcane and energy cane breeding. Sugarcane and energy cane breeders can effectively utilize this core collection for cultivar improvement. Further, the core collection can provide resources for forming an association panel to evaluate the traits of agronomic and commercial importance.

  3. Toward a detailed description of the thermally induced dynamics of the core promoter.

    Directory of Open Access Journals (Sweden)

    Boian S Alexandrov


    Full Text Available Establishing the general and promoter-specific mechanistic features of gene transcription initiation requires improved understanding of the sequence-dependent structural/dynamic features of promoter DNA. Experimental data suggest that a spontaneous dsDNA strand separation at the transcriptional start site is likely to be a requirement for transcription initiation in several promoters. Here, we use Langevin molecular dynamic simulations based on the Peyrard-Bishop-Dauxois nonlinear model of DNA (PBD LMD to analyze the strand separation (bubble dynamics of 80-bp-long promoter DNA sequences. We derive three dynamic criteria, bubble probability, bubble lifetime, and average strand separation, to characterize bubble formation at the transcriptional start sites of eight mammalian gene promoters. We observe that the most stable dsDNA openings do not necessarily coincide with the most probable openings and the highest average strand displacement, underscoring the advantages of proper molecular dynamic simulations. The dynamic profiles of the tested mammalian promoters differ significantly in overall profile and bubble probability, but the transcriptional start site is often distinguished by large (longer than 10 bp and long-lived transient openings in the double helix. In support of these results are our experimental transcription data demonstrating that an artificial bubble-containing DNA template is transcribed bidirectionally by human RNA polymerase alone in the absence of any other transcription factors.

  4. Analysis of ultra-deep pyrosequencing and cloning based sequencing of the basic core promoter/precore/core region of hepatitis B virus using newly developed bioinformatics tools.

    Directory of Open Access Journals (Sweden)

    Mukhlid Yousif

    Full Text Available AIMS: The aims of this study were to develop bioinformatics tools to explore ultra-deep pyrosequencing (UDPS data, to test these tools, and to use them to determine the optimum error threshold, and to compare results from UDPS and cloning based sequencing (CBS. METHODS: Four serum samples, infected with either genotype D or E, from HBeAg-positive and HBeAg-negative patients were randomly selected. UDPS and CBS were used to sequence the basic core promoter/precore region of HBV. Two online bioinformatics tools, the "Deep Threshold Tool" and the "Rosetta Tool" (, were built to test and analyze the generated data. RESULTS: A total of 10952 reads were generated by UDPS on the 454 GS Junior platform. In the four samples, substitutions, detected at 0.5% threshold or above, were identified at 39 unique positions, 25 of which were non-synonymous mutations. Sample #2 (HBeAg-negative, genotype D had substitutions in 26 positions, followed by sample #1 (HBeAg-negative, genotype E in 12 positions, sample #3 (HBeAg-positive, genotype D in 7 positions and sample #4 (HBeAg-positive, genotype E in only four positions. The ratio of nucleotide substitutions between isolates from HBeAg-negative and HBeAg-positive patients was 3.5 ∶ 1. Compared to genotype E isolates, genotype D isolates showed greater variation in the X, basic core promoter/precore and core regions. Only 18 of the 39 positions identified by UDPS were detected by CBS, which detected 14 of the 25 non-synonymous mutations detected by UDPS. CONCLUSION: UDPS data should be approached with caution. Appropriate curation of read data is required prior to analysis, in order to clean the data and eliminate artefacts. CBS detected fewer than 50% of the substitutions detected by UDPS. Furthermore it is important that the appropriate consensus (reference sequence is used in order to identify variants correctly.

  5. Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila

    Directory of Open Access Journals (Sweden)

    Lindsay K. Kelly


    Full Text Available Epithelial tissues are polarized along two axes. In addition to apical-basal polarity, they are often polarized within the plane of the epithelium, so-called Planar Cell Polarity (PCP. PCP depends upon Wnt/Frizzled (Fz signaling factors, including Fz itself and Van Gogh (Vang/Vangl. We sought to understand how Vang interaction with other core PCP factors affects Vang function. We find that Fz induces Vang phosphorylation in a cell-autonomous manner. Vang phosphorylation occurs on conserved N-terminal serine/threonine residues, is mediated by CK1ε/Dco, and is critical for polarized membrane localization of Vang and other PCP proteins. This regulatory mechanism does not require Fz signaling through Dishevelled and thus represents a cell-autonomous upstream interaction between Fz and Vang. Furthermore, this signaling event appears to be related to Wnt5a-mediated Vangl2 phosphorylation during mouse limb patterning and may thus be a general mechanism underlying Wnt-regulated PCP establishment.

  6. Low-Affinity Neurotrophin Receptor p75 Promotes the Transduction of Targeted Lentiviral Vectors to Cholinergic Neurons of Rat Basal Forebrain. (United States)

    Antyborzec, Inga; O'Leary, Valerie B; Dolly, James O; Ovsepian, Saak V


    Basal forebrain cholinergic neurons (BFCNs) are one of the most affected neuronal types in Alzheimer's disease (AD), with their extensive loss documented at late stages of the pathology. While discriminatory provision of neuroprotective agents and trophic factors to these cells is thought to be of substantial therapeutic potential, the intricate topography and structure of the forebrain cholinergic system imposes a major challenge. To overcome this, we took advantage of the physiological enrichment of BFCNs with a low-affinity p75 neurotrophin receptor (p75(NTR)) for their targeting by lentiviral vectors within the intact brain of adult rat. Herein, a method is described that affords selective and effective transduction of BFCNs with a green fluorescence protein (GFP) reporter, which combines streptavidin-biotin technology with anti-p75(NTR) antibody-coated lentiviral vectors. Specific GFP expression in cholinergic neurons was attained in the medial septum and nuclei of the diagonal band Broca after a single intraventricular administration of such targeted vectors. Bioelectrical activity of GFP-labeled neurons was proven to be unchanged. Thus, proof of principle is obtained for the utility of the low-affinity p75(NTR) for targeted transduction of vectors to BFCNs in vivo.

  7. Replacement of the human cytomegalovirus promoter with fish enhancer and core elements to control the expression of the G gene of viral haemorrhagic septicemia virus (VHSV). (United States)

    Martinez-Lopez, A; Chinchilla, B; Encinas, P; Gomez-Casado, E; Estepa, A; Coll, J M


    This work explores some of the possibilities to replace human cytomegalovirus (CMV) core and/or enhancer promoter control elements to create new expression vectors for use with fish. The work is relevant to fish vaccination, since DNA vaccines use eukaryotic expression plasmids controlled by the human cytomegalovirus (CMV) promoter to be effective against novirhabdoviruses, such as viral haemorrhagic septicemia virus (VHSV), one of the most devastating fish viral European diseases. To reduce possible homologous recombination with fish genome, core and enhancer sequences from fish origin, such as trout interferon-inducible myxovirus protein (Mx), zebrafish retrovirus long terminal repeat (LTR) and carp β-actin (AE6), were combined with those of CMV to design alternative hybrid promoters. The substitution of CMV core and/or enhancer with the corresponding elements of Mx or the LTR core maintained a similar in vitro protein G expression level than that obtained by using the CMV promoter. Vectors using the dsRNA-inducible Mx enhancer followed either by the LTR or the AE6 cores showed the highest in vitro protein G expression levels. Furthermore, synthetic constructs using the Mx enhancer maintained their polyI:C induction capabilities despite the core used. Some of these hybrid promoters might contribute to the development of all-fish-vectors for DNA vaccines while others might be useful for more basic studies.

  8. Identification of the core promoter of STK11 gene and its transcriptional regulation by p53

    Institute of Scientific and Technical Information of China (English)

    Maojin Yao; Chenjie Li; Yi Chu; Fei Wang; Xiaoliu Shi; Yongjun Wang; Hongwei Shen; Wenfeng Ning; Jianguang Tang; Xiangping Wang; Jie Li; Shiquang Zhou; Xin Yi


    Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps. Most cases of PJS involve the inactivation of germline mutations in the serine/threonine kinase gene STK11 which is also known as LKB1. The function of STK11 was previously linked to the tumor suppressor p53 and was shown to activate the p53 target p21/ WAF1. Recently, STK11 was reported to be interacting with p53 physically in the nucleus and it can directly or indirectly phosphorylate p53. Here we characterized the 5'-flanking region of human STK11 gene and identified a 161-bp fragment with promoter activity. Sequence analysis, mutagenesis and gel shift studies revealed a binding site of Spl and p53, which affects the promoter activity. Mutation analyses showed that this fragment was required for p53-mediated transcriptional activation. This transcriptional activation was further confirmed by real-time quantitative RT-PCR and Western blot analysis. Transient transfection of p53 expression plasmid into fetal liver cell lines increased STK11 mRNA and protein levels. In conclusion, our results reveal a new role for p53 in elevating STK11 gene expression via a positive feedback pattern.

  9. The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis. (United States)

    McGlinchey, Ryan P; Shewmaker, Frank; McPhie, Peter; Monterroso, Begoña; Thurber, Kent; Wickner, Reed B


    Pmel17 is a melanocyte protein necessary for eumelanin deposition 1 in mammals and found in melanosomes in a filamentous form. The luminal part of human Pmel17 includes a region (RPT) with 10 copies of a partial repeat sequence, pt.e.gttp.qv., known to be essential in vivo for filament formation. We show that this RPT region readily forms amyloid in vitro, but only under the mildly acidic conditions typical of the lysosome-like melanosome lumen, and the filaments quickly become soluble at neutral pH. Under the same mildly acidic conditions, the Pmel filaments promote eumelanin formation. Electron diffraction, circular dichroism, and solid-state NMR studies of Pmel17 filaments show that the structure is rich in beta sheet. We suggest that RPT is the amyloid core domain of the Pmel17 filaments so critical for melanin formation.

  10. Relation between hepatitis B virus genotypes and gene mutation of basic core promoter in Li nationality

    Institute of Scientific and Technical Information of China (English)

    Juntao Zeng; Zhengwen Liu; Shiping Zeng; Jing Chen


    Objective:To investigate the relation between hepatitis B virus(HBV) genotypes and the double mutation of A-to-T nucleotide(nt) 1762 and G-to-A nt 1764 in basic core promotev(BCP T1762/A1764) in patients of the Li nationality. Methods:Subjects were 125 HBV DNA positive patients that belong to the Li nationality on Hainan Island. HBV DNA genotype was determined by real time fluorimetrypolymerase chain reaction. BCP T1762/A1764 mutation was performed using the direct sequencing method. Results:The prevalence rates of genotype B, genotype C, genotype D, genotype C and D mixed infection(genotype C+D) and genotype B and D mixed infection (genotype B+C) were 31.20%, 53.60%, 12.00%, 2.40% and 0.80% respectively. Mutation frequencies in patients infected with HBV genotype C(58.21%) were significantly higher than in those infected with other genotypes (P <0.01). The serum viral load of the patients with genotype C(5.74±1.21) was also higher than that of those with genotype B(P <0.01). Conclusion:The major genotypes in the Li nationality were genotype C and genotype B. The infection of genotype D and mixed infection also occurred in the Li nationality. Genotype C HBV has a higher replication rate, and the different degrees of pathogenecity among HBV genotypes may be related to BCP T1762/ A1764 mutation frequency.

  11. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.


    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  12. Green Infrastructure Research Promotes Students' Deeper Interest in Core Courses of a Water Resources Program (United States)

    Yerk, W.; Montalto, F. A.; Foti, R.


    As one of most innovative among low impact development technologies, Green Infrastructure (GI) is a new technology that presents a range of potential research opportunities. Inherently linked to sustainability, urban quality of life, resilience, and other such topics, GI also represents a unique opportunity to highlight the social relevance of practical STEM research to undergraduate students. The nature of research on urban GI, in fact, as well as the accessibility of the GI sites, allows students to combine hands-on experience with theoretical work. Furthermore, the range of scales of the projects is such that they can be managed within a single term, but does not preclude longer engagement. The Sustainable Water Resource Engineering lab at Drexel University is engaged in two types of GI research outside the classroom. One type is a research co-op research internship. The second is a selective university-wide faculty-mentored summer scholarship STAR (Students Tackling Advanced Research) specifically designed for freshmen. The research projects we developed for those curricula can be accomplished by undergraduate students, but also address a larger research need in this emerging field. The research tasks have included identifying and calibrating affordable instruments, designing and building experimental setups, and monitoring and evaluating performance of GI sites. The work also promoted deeper understanding of the hydrological processes and initiated learning beyond the students' current curricula. The practice of the Lab's research being embedded into the educational process receives positive feedback from the students and achieves meaningful and long-lasting learning objectives. The experience helps students to students acquire hands-on experience, improves their metacognition and evidence-based inquiring into real-world problems, and further advances decision-making and communication skills.

  13. Up-regulation effect of hepatitis B virus genome A1846T mutation on viral replication and core promoter activity

    Directory of Open Access Journals (Sweden)

    Ling JIANG


    Full Text Available Objective  To evaluate the influence of hepatitis B virus (HBV genome nucleotide A1846T mutation on the viral replication capacity and the transcription activity of HBV core promoter (CP in vitro. Methods  A total of 385 patients with hepatitis B admitted to the 302 Hospital of PLA were enrolled in the study, including 116 with moderate chronic hepatitis B (CHB-M, 123 with severe chronic hepatitis B (CHB-S, and 146 with acute-on-chronic liver failure (ACLF. Serum HBV DNA was isolated and full-length HBV genome was amplified. The incidence of A1846T was analyzed. Full-length HBV genomes containing 1846T mutation were cloned into pGEM-T easy vector, and the counterpart wild-type 1846A plasmids were obtained by site-directed mutagenesis. The full-length HBV genome was released from recombinant plasmid by BspQ Ⅰ/Sca Ⅰ digestion, and then transfected into HepG2 cells. Secreted HBsAg level and intracellular HBV core particles were measured 72 hours post-transfection to analyze the replication capacity (a 1.0-fold HBV genome model. 1846 mutant and wild-type full-length HBV genomes were extracted to amplify the fragment of HBV CP region, and the dual luciferase reporter of the pGL3-CP was constructed. The luciferase activity was detected 48 hours post-transfection. Results  The incidence of A1846T mutation gradually increased with the severity of hepatitis B, reaching 31.03%, 42.27%, and 55.48% in CHB-M, CHB-S and ACLF patients respectively (P<0.01. The replication capacity of 1846T mutants, level of secreted HBsAg, and transcriptional activity of CP promoter were increased by 320%, 28% and 85% respectively, compared with 1846A wild-type strains. While the more common double mutation A1762T/G1764A in CP region was increased by 67%, 9% and 72% respectively, compared with its counterpart wild-type strains. A1846T had a greater influence on viral replication capacity in vitro. Conclusions A1846T mutation could significantly increase the

  14. Toward core inter-professional health promotion competencies to address the non-communicable diseases and their risk factors through knowledge translation: Curriculum content assessment


    Dean, Elizabeth; Moffat, Marilyn; Skinner, Margot; Dornelas de Andrade, Armele; Myezwa, Hellen; Söderlund, Anne


    Background To increase the global impact of health promotion related to non-communicable diseases, health professionals need evidence-based core competencies in health assessment and lifestyle behavior change. Assessment of health promotion curricula by health professional programs is a first step. Such program assessment is a means of 1. demonstrating collective commitment across health professionals to prevent non-communicable diseases; 2. addressing the knowledge translation gap between wh...

  15. The biology of eukaryotic promoter prediction - a review

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Baldi, Pierre; Chauvin, Yves


    reconsider the biological data that forms the basis of current algorithms, and we here present a review of data that may be useful in this regard. The review covers the following topics: (1) basal transcription and core promoters, (2) activated transcription and transcription factor binding sites, (3) Cp...

  16. CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons. (United States)

    Farina, Margherita; van de Bospoort, Rhea; He, Enqi; Persoon, Claudia M; van Weering, Jan R T; Broeke, Jurjen H; Verhage, Matthijs; Toonen, Ruud F


    Neuropeptides released from dense-core vesicles (DCVs) modulate neuronal activity, but the molecules driving DCV secretion in mammalian neurons are largely unknown. We studied the role of calcium-activator protein for secretion (CAPS) proteins in neuronal DCV secretion at single vesicle resolution. Endogenous CAPS-1 co-localized with synaptic markers but was not enriched at every synapse. Deletion of CAPS-1 and CAPS-2 did not affect DCV biogenesis, loading, transport or docking, but DCV secretion was reduced by 70% in CAPS-1/CAPS-2 double null mutant (DKO) neurons and remaining fusion events required prolonged stimulation. CAPS deletion specifically reduced secretion of stationary DCVs. CAPS-1-EYFP expression in DKO neurons restored DCV secretion, but CAPS-1-EYFP and DCVs rarely traveled together. Synaptic localization of CAPS-1-EYFP in DKO neurons was calcium dependent and DCV fusion probability correlated with synaptic CAPS-1-EYFP expression. These data indicate that CAPS-1 promotes fusion competence of immobile (tethered) DCVs in presynaptic terminals and that CAPS-1 localization to DCVs is probably not essential for this role.

  17. The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells. (United States)

    Itou, Junji; Tanaka, Sunao; Li, Wenzhao; Iida, Atsuo; Sehara-Fujisawa, Atsuko; Sato, Fumiaki; Toi, Masakazu


    During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1. In addition, we clarified that integrin α6 and β1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6β1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6β1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6β1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration.

  18. Dimer-dependent intrinsic/basal activity of the class B G protein-coupled receptor PAC1 promotes cellular anti-apoptotic activity through Wnt/β-catenin pathways that are associated with dimer endocytosis.

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    Rongjie Yu

    is associated with the endocytosis of PAC1 dimers. The discovery and study of the dimer-dependent basal activity of PAC1 not only help us understand the physiological and pathological role of PAC1 but also promote the development of drugs targeting PAC1.

  19. Variability in the precore and core promoter regions of HBV strains in Morocco: characterization and impact on liver disease progression.

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    Bouchra Kitab

    Full Text Available BACKGROUND: Hepatitis B virus (HBV is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD, including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg has been frequently associated with mutations in the pre-core (pre-C and core promoter (CP regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco. METHODS/PRINCIPAL FINDINGS: A cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD. Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9% and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15-1.04; p = 0.04. HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p = 0.84. CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (≥ 40 years, male sex, high viral load (>4.3 log(10 IU/mL and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8-8; p<0.0001. CONCLUSIONS: This study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.

  20. Hepatitis B virus genotype C isolates with wild-type core promoter sequence replicate less efficiently than genotype B isolates but possess higher virion secretion capacity. (United States)

    Qin, Yanli; Tang, Xiaoli; Garcia, Tamako; Hussain, Munira; Zhang, Jiming; Lok, Anna; Wands, Jack; Li, Jisu; Tong, Shuping


    Infection by hepatitis B virus (HBV) genotype C is associated with a prolonged viremic phase, delayed hepatitis B e antigen (HBeAg) seroconversion, and an increased incidence of liver cirrhosis and hepatocellular carcinoma compared with genotype B infection. Genotype C is also associated with the more frequent emergence of core promoter mutations, which increase genome replication and are independently associated with poor clinical outcomes. We amplified full-length HBV genomes from serum samples from Chinese and U. S. patients with chronic HBV infection and transfected circularized genome pools or dimeric constructs of individual clones into Huh7 cells. The two genotypes could be differentiated by Western blot analysis due to the reactivities of M and L proteins toward a monoclonal pre-S2 antibody and slightly different S-protein mobilities. Great variability in replication capacity was observed for both genotypes. The A1762T/G1764A core promoter mutations were prevalent in genotype C isolates and correlated with increased replication capacity, while the A1752G/T mutation frequently found in genotype B isolates correlated with a low replication capacity. Importantly, most genotype C isolates with wild-type core promoter sequence replicated less efficiently than the corresponding genotype B isolates due to less efficient transcription of the 3.5-kb RNA. However, genotype C isolates often displayed more efficient virion secretion. We propose that the low intracellular levels of viral DNA and core protein of wild-type genotype C delay immune clearance and trigger the subsequent emergence of A1762T/G1764A core promoter mutations to upregulate replication; efficient virion secretion compensates for the low replication capacity to ensure the establishment of persistent infection by genotype C.

  1. Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype


    Yanli Qin; Xueshi Zhou; Haodi Jia; Chaoyang Chen; Weifeng Zhao; Jiming Zhang; Shuping Tong


    Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter ...

  2. Neuropsychiatry of the basal ganglia


    Ring, H.; Serra-Mestres, J


    This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are import...

  3. HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1. (United States)

    Shin, Ju Yeop; Hur, Wonhee; Wang, Jin Sang; Jang, Jeong Won; Kim, Chang Wook; Bae, Si Hyun; Jang, Sung Key; Yang, Se-Hwan; Sung, Young Chul; Kwon, Oh-Joo; Yoon, Seung Kew


    Liver cirrhosis is one of the major complications of hepatitis C virus (HCV) infection, but the mechanisms underlying HCV-related fibrogenesis are still not clear. Although the roles of HCV core protein remain poorly understood, it is supposed to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to examine the role of HCV core protein on the hepatic fibrogenesis. We established an in vitro co-culture system with primary hepatic stellate cell (HSC) isolated from rats, and a stable HepG2-HCV core cell line which had been transfected with HCV core gene. The expressions of fibrosis-related molecules transforming growth factor beta1 (TGF-beta1), transforming growth factor beta receptor II (TGFbetaRII), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were analyzed via histological or molecular methods. In addition, the expression levels of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) from the co-cultured media were measured by zymogram and ELISA, respectively. The expressions of alpha-SMA, TGF-beta1, Col I, TGFbetaRII and MMP-2 were significantly increased in the co-culture of stable HepG2-HCV core with HSC. Moreover, the significant increases of CTGF and TGF-beta1 in the HCV core-expressing cells were observed by either Northern or Western blot analysis. These results suggest that HCV core protein may contribute to the hepatic fibrogenesis via up-regulation of CTGF and TGF-beta1.

  4. Insertion of core CpG island element into human CMV promoter for enhancing recombinant protein expression stability in CHO cells. (United States)

    Mariati; Yeo, Jessna H M; Koh, Esther Y C; Ho, Steven C L; Yang, Yuansheng


    The human cytomegalovirus promoter (hCMV) is susceptible to gene silencing in CHO cells, most likely due to epigenetic events, such as DNA methylation and histone modifications. The core CpG island element (IE) from the hamster adenine phosphoribosyltransferase gene has been shown to prevent DNA methylation. A set of modified hCMV promoters was developed by inserting one or two copies of IE in either forward or reverse orientations either upstream of the hCMV enhancer, between the enhancer and core promoter (CP), or downstream of the CP. The modified hCMV with one copy of IE inserted between the enhancer and core promoter in reverse orientation (MR1) was most effective at enhancing expression stability without compromising expression level when compared with the wild-type (WT) hCMV. A third of 18 EGFP expressing clones generated using MR1 retained 70% of their starting expression level after 8 weeks of culture in the absence of selection pressure, while none of 18 WT hCMV generated clones had expression above 50%. MR1 also improved antibody expression stability of methotrexate (MTX) amplified CHO cell lines. Stably transfected pools generated using MR1 maintained 62% of their original monoclonal antibody titer after 8 weeks of culture in the absence of MTX, compared to only 37% for WT hCMV pools. Low levels of CpG methylation within both WT hCMV and MR1 were observed in all the analyzed cell lines and the methylation levels did not correlate to the expression stability, suggesting IE enhances expression stability by other mechanisms other than preventing methylation.

  5. Expression pattern and core region analysis of AtMPK3 promoter in response to environmental stresses

    Institute of Scientific and Technical Information of China (English)


    The protein kinase AtMPK3,a component of the MAP kinase cascade,plays an important role in stress signal transduction in plant cells. To clarify how AtMPK3 is regulated at the transcriptional level in response to various environmental factors, the 1016-bp promoter sequence upstream of the transcription start site of the AtMPK3 gene was isolated. Analyses of the promoter sequence using plant promoter databases revealed that the AtMPK3 promoter contains many potential cis-acting elements involved in environmental stress responses. We constructed four deletion mutants of the AtMPK3 promoter, and introduced the intact and truncated promoter sequences fused to the β-glucuronidase (GUS) gene into Arabidopsis. GUS histochemical staining and quantitative fluorometric GUS assays were performed to visualize and compare the expression patterns in response to different environmental stimuli. The region between-188 and-62 upstream of the transcription start site was identified as the essential DNA sequence of the AtMPK3 promoter for responses to drought, high salinity, low temperature, and wounding. These results advance our understanding of the molecular mechanisms controlling AtMPK3 expression in response to different environmental stimuli.

  6. Interaction of the transcription start site core region and transcription factor YY1 determine ascorbate transporter SVCT2 exon 1a promoter activity.

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    Huan Qiao

    Full Text Available Transcription of the ascorbate transporter, SVCT2, is driven by two distinct promoters in exon 1 of the transporter sequence. The exon 1a promoter lacks a classical transcription start site and little is known about regulation of promoter activity in the transcription start site core (TSSC region. Here we present evidence that the TSSC binds the multifunctional initiator-binding protein YY1. Electrophoresis shift assays using YY1 antibody showed that YY1 is present as one of two major complexes that specifically bind to the TSSC. The other complex contains the transcription factor NF-Y. Mutations in the TSSC that decreased YY1 binding also impaired the exon 1a promoter activity despite the presence of an upstream activating NF-Y/USF complex, suggesting that YY1 is involved in the regulation of the exon 1a transcription. Furthermore, YY1 interaction with NF-Y and/or USF synergistically enhanced the exon 1a promoter activity in transient transfections and co-activator p300 enhanced their synergistic activation. We propose that the TSSC plays a vital role in the exon 1a transcription and that this function is partially carried out by the transcription factor YY1. Moreover, co-activator p300 might be able to synergistically enhance the TSSC function via a "bridge" mechanism with upstream sequences.

  7. Detailed analysis of Helicobacter pylori Fur-regulated promoters reveals a Fur box core sequence and novel Fur-regulated genes. (United States)

    Pich, Oscar Q; Carpenter, Beth M; Gilbreath, Jeremy J; Merrell, D Scott


    In Helicobacter pylori, iron balance is controlled by the Ferric uptake regulator (Fur), an iron-sensing repressor protein that typically regulates expression of genes implicated in iron transport and storage. Herein, we carried out extensive analysis of Fur-regulated promoters and identified a 7-1-7 motif with dyad symmetry (5'-TAATAATnATTATTA-3'), which functions as the Fur box core sequence of H. pylori. Addition of this sequence to the promoter region of a typically non-Fur regulated gene was sufficient to impose Fur-dependent regulation in vivo. Moreover, mutation of this sequence within Fur-controlled promoters negated regulation. Analysis of the H. pylori chromosome for the occurrence of the Fur box established the existence of well-conserved Fur boxes in the promoters of numerous known Fur-regulated genes, and revealed novel putative Fur targets. Transcriptional analysis of the new candidate genes demonstrated Fur-dependent repression of HPG27_51, HPG27_52, HPG27_199, HPG27_445, HPG27_825 and HPG27_1063, as well as Fur-mediated activation of the cytotoxin associated gene A, cagA (HPG27_507). Furthermore, electrophoretic mobility shift assays confirmed specific binding of Fur to the promoters of each of these genes. Future experiments will determine whether loss of Fur regulation of any of these particular genes contributes to the defects in colonization exhibited by the H. pylori fur mutant.

  8. Low frequency of mutations in the core promoter and precore regions of hepatitis B virus in anti-HBe positive Brazilian carriers

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    Niel Christian


    Full Text Available Abstract Background Mutations in the core promoter and precore regions of the hepatitis B virus (HBV genome, notably the double substitution (AGG to TGA at nt positions 1762-1764 in the core promoter, and the precore stop codon mutation G to A at nt 1896, can often explain the anti-HBe phenotype in chronic carriers. However, the A1896 mutation is restricted to HBV isolates that have T at nt 1858. The double substitution at positions 1762-1764 has been described to occur preferentially in patients infected with strains showing C instead of T at nt 1858. Results HBV DNAs from 29 anti-HBe Brazilian samples were characterized by nucleotide sequencing of PCR products from precore region. Among them, 18 isolates presented C at nt 1858 (mostly genotype A strains. The 11 remaining isolates (genotypes D and F had T1858. The stop codon mutation at nt 1896 was found in seven isolates (24% of the total and 63% of the isolates that had T1858. The frequency of the double substitution at positions 1762-1764 was surprisingly low (20% among C1858 isolates. An association between A1896 and TGA 1762-1764 mutations was observed among genotype D isolates: these showed either none of the two mutations or both. Furthermore, strains mutated at positions 1896 and/or 1762-1764 also presented an elevated number of other, less common substitutions in the core promoter and precore regions. Conclusions The data reported here are not in accordance with some reports from other parts of the world. In half of the isolates, none of the mutations previously described could explain the anti-HBe phenotype.

  9. The core planar cell polarity gene prickle interacts with flamingo to promote sensory axon advance in the Drosophila embryo. (United States)

    Mrkusich, Eli M; Flanagan, Dustin J; Whitington, Paul M


    The atypical cadherin Drosophila protein Flamingo and its vertebrate homologues play widespread roles in the regulation of both dendrite and axon growth. However, little is understood about the molecular mechanisms that underpin these functions. Whereas flamingo interacts with a well-defined group of genes in regulating planar cell polarity, previous studies have uncovered little evidence that the other core planar cell polarity genes are involved in regulation of neurite growth. We present data in this study showing that the planar cell polarity gene prickle interacts with flamingo in regulating sensory axon advance at a key choice point - the transition between the peripheral nervous system and the central nervous system. The cytoplasmic tail of the Flamingo protein is not required for this interaction. Overexpression of another core planar cell polarity gene dishevelled produces a similar phenotype to prickle mutants, suggesting that this gene may also play a role in regulation of sensory axon advance.

  10. Vismodegib in basal cell carcinoma. (United States)

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A


    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  11. Metacognitive Theory Applied: Strategic Reading Instruction in the Current Generation of Basal Readers. (United States)

    Schmitt, Maribeth Cassidy; Hopkins, Carol J.


    Examines the content of eight basal reading series (published in 1989) to determine how and the extent to which lessons and activities that promote metacomprehension behaviors necessary for independent reading were included. Finds that basal authors made considerable efforts to incorporate activities and lessons that promote or foster strategic…

  12. Functional Analysis of the Dioxin Response Elements (DREs of the Murine CYP1A1 Gene Promoter: Beyond the Core DRE Sequence

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    Shuaizhang Li


    Full Text Available The aryl hydrocarbon receptor (AhR is a ligand-dependent transcription factor that mediates the biological and toxicological effects of halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. When activated by dioxin, the cytosolic AhR protein complex translocates into the nucleus and dimerizes with the ARNT (Ah receptor nuclear translocator protein. The heteromeric ligand:AhR/Arnt complex then recognizes and binds to its specific DNA recognition site, the dioxin response element (DRE. DREs are located upstream of cytochrome P4501A1 (CYP1A1 and other AhR-responsive genes, and binding of the AhR complex stimulates their transcription. Although CYP1A1 expression has been used as the model system to define the biochemical and molecular mechanism of AhR action, there is still limited knowledge about the roles of each of the seven DREs located in the CYP1A1 promoter. These seven DREs are conserved in mouse, human and rat. Deletion analysis showed that a single DRE at -488 was enough to activate the transcription. Truncation analysis demonstrated that the DRE at site -981 has the highest transcriptional efficiency in response to TCDD. This result was verified by mutation analysis, suggesting that the conserved DRE at site -981 could represent a significant and universal AhR regulatory element for CYP1A1. The reversed substituted intolerant core sequence (5'-GCGTG-3' or 5'-CACGC-3' of seven DREs reduced the transcriptional efficiency, which illustrated that the adjacent sequences of DRE played a vital role in activating transcription. The core DRE sequence (5'-TNGCGTG-3' tends to show a higher transcriptional level than that of the core DRE sequence (5'-CACGCNA-3' triggered by TCDD. Furthermore, in the core DRE (5'-TNGCGTG-3' sequence, when “N” is thymine or cytosine (T or C, the transcription efficiency was stronger compared with that of the other nucleotides. The effects of DRE orientation, DRE adjacent sequences and

  13. Basal hydraulic conditions of Ice Stream B (United States)

    Engelhardt, Hermann; Kamb, Barclay


    Fifteen boreholes have been drilled to the base of Ice Stream B in the vicinity of UpB Camp. The boreholes are spread over an area of about 500 x 1000 m. Several till cores were retrieved from the bottom of the 1000-m-deep holes. Laboratory tests using a simple shear box revealed a yield strength of basal till of 2 kPa. This agrees well with in-situ measurements using a shear vane. Since the average basal shear stress of Ice Stream B with a surface slope of 0.1 degree is about 20 kPa, the ice stream cannot be supported by till that weak. Additional support for this conclusion comes from the basal water pressure that has been measured in all boreholes as soon as the hot water drill reached bottom. In several boreholes, the water pressure has been continuously monitored; in two of them, over several years. The water pressure varies but stays within 1 bar of flotation where ice overburden pressure and water pressure are equal. The ratio of water and overburden pressure lies between 0.986 and 1.002. This is an extremely high value as compared to other fast-moving ice masses; e.g., Variegated Glacier in surge has a ratio of 0.8, and Columbia Glacier - a fast-moving tidewater glacier - has a ratio of 0.9. It implies that water flow under the glacier occurs in a thin film and not in conduits that would drain away water too rapidly. It also implies that basal sliding must be very effective. Water flow under the glacier was measured in a salt-injection experiment where a salt pulse was released at the bottom of a borehole while 60 m down-glacier, the electrical resistance was measured between two other boreholes. A flow velocity of 7 mm/s was obtained.

  14. The G1613A mutation in the HBV genome affects HBeAg expression and viral replication through altered core promoter activity.

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    Man-Shan Li

    Full Text Available Infection of hepatitis B virus (HBV causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC. Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC.

  15. Movable magnetic porous cores enclosed within carbon microcapsules: structure-controlled synthesis and promoted carbon-based applications. (United States)

    You, Lijun; Zhang, Yuting; Xu, Shuai; Guo, Jia; Wang, Changchun


    Rattle-type porous carbon microcapsules (RPCMs) were deliberately designed to combine multiple functions with the aim of improving the applicability of amorphous carbon in a synergistic fashion. A movable Fe3O4 nanocluster coated with porous carbon is encapsulated in the cavity of a carbon microcapsule with an eggshell-like characteristic, allowing for storage, adsorption, and exchange of matters through the mesoporous channels of the carbon layer. The synthetic strategy of RPCMs is flexible and universal, involving the constitution and carbonization of Fe3O4@PF@PS@PF template particles. This results in a double carbon shell and a sandwiched hollow cavity with a movable magnetic core. There is evidence that RPCMs possess large surface areas, hierarchical pore sizes, hydrophobicity, and magnetic responsiveness. Hence, diverse applications have been investigated. It is proved that RPCMs exhibit excellent performance in the effective enrichment of peptides/proteins. The detection limit toward peptides could reach as low as 10 nM, and the enrichment capacity toward MYO protein is as high as 410 mg/g (protein/beads). Furthermore, RPCMs are able to harvest proteins in complex real samples such as fetal bovine serum and rabbit blood. In addition, RPCMs could be fabricated in a supercapacitor electrode and display outstanding energy-storage performance. The electrochemical measurements demonstrate that RPCM-based electrodes have a specific capacitance of as high as 216 F/g (0.1 A/g), long-term cycling stability with a capacitance retention of 92.4% over 1000 cycles (0.2 A/g), and good electronic conductivity.

  16. Choosing the Right Basal Reader. (United States)

    Robbins, Ruth H.


    Looks at factors in the textbook publishing industry, especially costs and censorship, which affect the quality of available reading series. Notes the problem of readability and content bias. Finally, presents a checklist of basal reader evaluation criteria. (SJL)

  17. Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.

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    So Yeon Kwon


    Full Text Available NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions.

  18. Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia. (United States)

    Khan, Anis; Al Balwi, Mohammed A; Tanaka, Yasuhito; Hajeer, Ali; Sanai, Faisal M; Al Abdulkarim, Ibrahim; Al Ayyar, Latifah; Badri, Motasim; Saudi, Dib; Tamimi, Waleed; Mizokami, Masashi; Al Knawy, Bandar


    In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non-HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme-linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non-HCC and 45 HCC patients infected with HBV/D, followed by age-matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti-HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non-HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age- and gender-adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8-118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3-17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3-84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high-risk patients and improving diagnostic and treatment strategies for HBV/D1.

  19. Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY1) residents' ACGME six core competencies: a 2-year study. (United States)

    Lee, Fa-Yauh; Yang, Ying-Ying; Hsu, Hui-Chi; Chuang, Chiao-Lin; Lee, Wei-Shin; Chang, Ching-Chih; Huang, Chia-Chang; Chen, Jaw-Wen; Cheng, Hao-Min; Jap, Tjin-Shing


    Objective The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the 'faculty development programme for teaching ACGME competencies.' Methods During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. Results The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of 'how to teach ACGME competencies.' Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. Conclusions According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical

  20. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga


    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  1. Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype. (United States)

    Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping


    Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development.

  2. Cryotherapy in basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sandra A


    Full Text Available Cryotherapy has proved to be an effective tool in the management of various dermatoses. We report 6 patients with histopathologically proven basal cell carcinoma of variable sizes treated with liquid nitrogen cryotherapy by the open spray technique. Lesions tended to heal with depigmentation and scar formation. However depigmented areas often repigmented over a period of time.

  3. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    DEFF Research Database (Denmark)

    Su, Ying; Subedee, Ashim; Bloushtain-Qimron, Noga;


    genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree......Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated...... of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required...

  4. Deformation Studies of NEEM, Greenland Basal Folded Ice (United States)

    Keegan, K.; Dahl-Jensen, D.; Montagnat, M.; Weikusat, I.


    Deep Greenland ice cores and airborne radio echo sounding (RES) images have recently revealed that basal ice flow of the Greenland Ice Sheet is very unstable. In many locations, a basal layer of disturbed ice is observed. At the NEEM, Greenland site this folding occurs at the boundary between the Eemian and glacial ice regimes, indicating that differences in physical properties of the ice play a role in the disturbance. Past work in metallurgy and ice suggests that impurity content controls grain evolution and therefore deformation. We hypothesize that the differences in ice flow seen deep in the NEEM ice core are controlled by differences in the impurity content of the ice layers. Here we present results of fabric, grain size, impurity content, and deformation studies from samples above and below this unstable boundary in the ice sheet.

  5. The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues

    Energy Technology Data Exchange (ETDEWEB)

    Starska, Katarzyna, E-mail: [I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź (Poland); Bryś, Magdalena; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland); Olszewski, Jurek; Pietkiewicz, Piotr [II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź (Poland); Lewy-Trenda, Iwona; Danilewicz, Marian [Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź (Poland); Krześlak, Anna [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland)


    Metallothioneins (MTs) are intracellular thiol-rich heavy metal-binding proteins which join trace metal ions protecting cells against heavy metal toxicity and regulate metal distribution and donation to various enzymes and transcription factors. The goal of this study was to identify the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene, and to investigate its effect on allele-specific gene expression and Cd, Zn, Cu and Ni content in sinonasal inverted papilloma tissue (IP), with non-cancerous sinonasal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was identified by restriction fragment length polymorphism using 117 IP and 132 NCM. MT2A gene analysis was performed by quantitative real-time PCR. Metal levels were analyzed by flame atomic absorption spectrometry. The frequency of A allele carriage was 99.2% and 100% in IP and NCM, respectively. The G allele carriage was detected in 23.9% of IP and in 12.1% of the NCM samples. As a result, a significant association of − 5 A/G SNP in MT2A gene with mRNA expression in both groups was determined. A significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. A highly significant association was detected between the rs28366003 genotype and Cd and Zn content in IP. Furthermore, significant differences were identified between A/A and A/G genotype with regard to the type of metal contaminant. The Spearman rank correlation results showed the MT2A gene expression and both Cd and Cu levels were negatively correlated. The results obtained in this study suggest that the − 5 A/G SNP in the MT2A gene may have an effect on allele-specific gene expression and toxic metal accumulation in sinonasal inverted papilloma. - Highlights: • MT2A gene expression and metal content in sinonasal inverted papilloma tissues • Association between SNP (rs28366003) and expression of MT2A • Significant

  6. 提升焊管企业核心竞争力的有效途径%Effective Way to Promoting Core Competitiveness of Welded Pipe Enterprise

    Institute of Scientific and Technical Information of China (English)



    针对目前国内外焊管产品市场供大于求的局面,以及我国焊管产品出口面临的严峻形势,分析了我国焊管生产技术、机组装备水平及高端焊管产品的研发状况,探讨了提升我国焊管企业核心竞争力的几种有效途径,包括企业集团战略的实施、生产技术和装备水平的不断改进、企业科技创新和产品结构的调整以及品牌战略和人才战略的实施.最后对焊管企业的管理和发展提出了建议.%Aimaing at oversupply situation of welded pipe products in domestic and overseas market, and the severe situation for China welded pipe products export, it analyzed welded pipe production technology, unit equipment level and development status of high-end welded pipe products in China domestic, disscussed several effective ways to promoting core competitiveness of welded pipe enterprise, including implementating corporate group strategy, updating technology and equipment level, technological innovation, adjusting product structure, and carrying out brand strategy and talent strategy. In the end, it put forward proposals to management and development for welded pipe enterprise.

  7. Promotion of Human Civilization by Socialism: From the Core Values Perspective of "Harmony"%从“和谐”核心价值观看社会主义对人类文明的进步

    Institute of Scientific and Technical Information of China (English)



    在社会主义核心价值观的基本范畴中,“和谐”应该是一个最高的范畴。从“和谐”这一社会主义核心价值观的基本范畴看,社会主义对人类文明有着巨大的进步。这些进步在总体上可以归纳为:物质文明、政治文明与精神文明的和谐发展对人类文明的全面进步,个体与群体(社会)的和谐发展对人类文明的全面进步以及人与自然的和谐发展对人类文明的全面进步等。%Among the basic concepts of socialist core values, "harmony" should be the ultimate concept. From the perspective of such basic concept of socialist core values as "harmony," socialism has exerted great promotions for human civilization. These promotions can generally be categorized as the following: the harmonious development of material civilization, political civilization and spiritual civilization comprehensively promotes human civilization; the harmonious development of individuals and collectives (societies) comprehensively promotes human civilization, and the harmonious development of human beings and nature comprehensively promotes human civilization.

  8. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  9. The basal ganglia and apraxia. (United States)

    Pramstaller, P P; Marsden, C D


    Ever since Liepmann's original descriptions at the beginning of the century apraxia has usually been attributed to damage confined to the cerebral cortex and/or cortico-cortical connecting pathways. However, there have been suggestions that apraxia can be due to deep subcortical lesions, which raises the question as to whether damage to the basal ganglia or thalamus can cause apraxia. We therefore analysed 82 cases of such 'deep' apraxias reported in the literature. These reports consisted of a small number (n=9) of cases studied neuropathologically, and a much larger group (n=73) in which CT or MRI was used to identify the size and extent of the lesion. The reports were subdivided into (i) those with small isolated lesions which involved nuclei of the basal ganglia or thalamus only, and not extending to involve periventricular or peristriatal white matter; (ii) those with large lesions which involved two or more of the nuclei, or one or more of these deep structures plus damage to closely adjacent areas including the internal capsule, periventricular or peristriatal white matter; and (iii) lesions sparing basal ganglia and thalamus but involving adjacent white matter. The main conclusions to be drawn from this meta-analysis are that lesions confined to the basal ganglia (putamen, caudate nucleus and globus pallidus) rarely, if ever, cause apraxia. Lesions affecting the lenticular nucleus or putamen nearly always intruded into the adjacent lateral white matter to involve association fibres, in particular those of the superior longitudinal fasciculus and frontostriatal connections. Apraxia occurred with deep lesions of the basal ganglia apparently sparing white matter in only eight out of the 82 cases. Apraxia was most commonly seen when there were lesions in the lenticular nucleus or putamen (58 out of 72 cases) with additional involvement of capsular, and particularly of periventricular or peristriatal, white matter. Lesions of the globus pallidus (no cases) or

  10. Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

    Institute of Scientific and Technical Information of China (English)

    Andi Utama; Benyamin Lukito; Tantoro Harmono; Nasrul Zubir; Julius; Soewignjo Soemohardjo; Laurentius Adrianus Lesmana; Ali Sulaiman; Susan Tai; Marlinang Diarta Siburian; Sigit Purwantomo; Mariana Destila Bayu Intan; Tri Shinta Kurniasih; Rino Alvani Gani; Wenny Astuti Achwan; Arnelis; Syafruddin AR Lelosutan


    AIM: To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS: Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.RESULTS: Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however,the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+)patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-)patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION: The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.

  11. Transient expression in tobacco Bright Yellow 2 cells and pollen grains: A fast, efficient and reliable system for functional promoter analysis of plant genes

    Directory of Open Access Journals (Sweden)

    Bratić Ana M.


    Full Text Available Gene expression is mediated by DNA sequences directly upstream from the coding sequences, recruited transcription factors and RNA polymerase in a spatially-defined manner. Understanding promoter strength and regulation would enhance our understanding of gene expression. The goal of this study was to develop a fast, efficient and reliable method for testing basal promoter activity and identifying core sequences within its pollen specific elements. In this paper we examined the functionality of buckwheat metallothionein promoter by a histochemical GUS assay in two transient expression systems: BY2 cells and pollen grains. Strong promoter activity was observed in both systems.

  12. Migraine attacks the Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Bigal Marcelo


    Full Text Available Abstract Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month. The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF to a matched (gender, age, age of onset and type of medication group of patients whose migraine episodes progressed (HF. Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

  13. Mephedrone alters basal ganglia and limbic neurotensin systems. (United States)

    German, Christopher L; Hoonakker, Amanda H; Fleckenstein, Annette E; Hanson, Glen R


    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters pre-synaptic dopamine (DA) activity like many psychostimulants. However, little is known about the post-synaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1 -like receptors in the striatum and the substantia nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.

  14. Characterization of a Crabs Claw Gene in Basal Eudicot Species Epimedium sagittatum (Berberidaceae)


    Wei Sun; Wenjun Huang; Zhineng Li; Haiyan Lv; Hongwen Huang; Ying Wang


    The Crabs Claw (CRC) YABBY gene is required for regulating carpel development in angiosperms and has played an important role in nectary evolution during core eudicot speciation. The function or expression of CRC-like genes has been explored in two basal eudicots, Eschscholzia californica and Aquilegia formosa. To further investigate the function of CRC orthologous genes related to evolution of carpel and nectary development in basal eudicots, a CRC ortholog, EsCRC, was isolated and character...

  15. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying Su


    Full Text Available Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and we identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of the luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.

  16. The Basal Ganglia and Motor Control


    Groenewegen, Henk J.


    This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the mos...

  17. Functional Neuroanatomy of the Basal Ganglia


    Lanciego, José L.; Luquin, Natasha; Obeso, José A.


    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amp...

  18. Mediator is an intrinsic component of the basal RNA polymerase II machinery in vivo. (United States)

    Lacombe, Thierry; Poh, Siew Lay; Barbey, Régine; Kuras, Laurent


    Mediator is a prominent multisubunit coactivator that functions as a bridge between gene-specific activators and the basal RNA polymerase (Pol) II initiation machinery. Here, we study the poorly documented role of Mediator in basal, or activator-independent, transcription in vivo. We show that Mediator is still present at the promoter when the Pol II machinery is recruited in the absence of an activator, in this case through a direct fusion between a basal transcription factor and a heterologous DNA binding protein bound to the promoter. Moreover, transcription resulting from activator-independent recruitment of the Pol II machinery is impaired by inactivation of the essential Mediator subunit Med17 due to the loss of Pol II from the promoter. Our results strongly support that Mediator is an integral component of the minimal machinery essential in vivo for stable Pol II association with the promoter.

  19. Moving beyond Compliance: Promoting Research-Based Professional Discretion in the Implementation of the Common Core State Standards in English Language Arts (United States)

    Woodard, Rebecca; Kline, Sonia


    State- and local-level mandates are currently being implemented to ensure strict compliance to the new national Common Core State Standards for English Language Arts (CCSS for ELA) and related assessments. These standards provide many potential opportunities to improve literacy education nationally and locally. However, the CCSS for ELA will…

  20. Persistent and Pervasive Basal Freeze-on: Implications for the Preservation of the Oldest Ice (United States)

    Bell, R. E.; Ferraccioli, F.; Braaten, D. A.; Corr, H. F.; Creyts, T. T.; Das, I.; Frearson, N.; Jordan, T. A.; Studinger, M.; Wolovick, M.


    Paleoclimate records from ice cores are based on the assumption that the stratigraphy is relatively simple and that the ice at the bottom of the ice sheet is undisturbed. The search for the oldest ice has targeted low accumulation areas such as Dome A and deep basins such as the Aurora Basin. The preservation of old ice will be significantly altered if there is widespread freeze-on at the base of the ice sheet. Previous evidence for basal freeze-on from the interior of major ice sheets has been limited to the thin layers of sediment-laden ice at the base of deep ice cores and the accretion ice from Lake Vostok. Here we present the first evidence for widespread freeze-on to the base of the East Antarctic ice sheet from data collected by a seven nation International Polar Year Expedition to Dome A. In the extensive radar data over the Gamburtsev Subglacial Mountains, we have identified distinct near-bed reflectors in the generally homogenous basal ice. The near-bed reflectors originate at the ice sheet bed coincident with flat, bright reflectors, sites associated with basal water. We interpret these near-bed reflectors as the interface between meteoric ice and ice frozen onto the base of the ice sheet. These frozen-on reflectors can be traced up to 100 km along flow. The thickness of the frozen-on basal ice reaches a maximum of 1100m that, in this case, represents 10-20% of the ice thickness along flowlines. In some sites, the frozen-on ice deflects the overlying meteoric ice upward 100's of meters indicating the ice accretion process influences the entire overlying ice sheet. The process of basal freeze-on beneath large ice sheets is likely persistent and pervasive. We infer that a significant fraction of the base of the East Antarctic ice sheet contains frozen-on ice and the process of widespread accretion must be considered in the search for the oldest ice. For example, the upper 70m thick accretion ice (accretion ice 1) from the Vostok ice core may be the result

  1. Proteomics Core (United States)

    Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in a...

  2. Proteomics Core (United States)

    Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in...

  3. A Novel Basal Body Protein That Is a Polo-like Kinase Substrate Is Required for Basal Body Segregation and Flagellum Adhesion in Trypanosoma brucei. (United States)

    Hu, Huiqing; Zhou, Qing; Li, Ziyin


    The Polo-like kinase (PLK) in Trypanosoma brucei plays multiple roles in basal body segregation, flagellum attachment, and cytokinesis. However, the mechanistic role of TbPLK remains elusive, mainly because most of its substrates are not known. Here, we report a new substrate of TbPLK, SPBB1, and its essential roles in T. brucei. SPBB1 was identified through yeast two-hybrid screening with the kinase-dead TbPLK as the bait. It interacts with TbPLK in vitro and in vivo, and is phosphorylated by TbPLK in vitro. SPBB1 localizes to both the mature basal body and the probasal body throughout the cell cycle, and co-localizes with TbPLK at the basal body during early cell cycle stages. RNAi against SPBB1 in procyclic trypanosomes inhibited basal body segregation, disrupted the new flagellum attachment zone filament, detached the new flagellum, and caused defective cytokinesis. Moreover, RNAi of SPBB1 confined TbPLK at the basal body and the bilobe structure, resulting in constitutive phosphorylation of TbCentrin2 at the bilobe. Altogether, these results identified a basal body protein as a TbPLK substrate and its essential role in promoting basal body segregation and flagellum attachment zone filament assembly for flagellum adhesion and cytokinesis initiation.

  4. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM


    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  5. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome). (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R


    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  6. Role of core promoter sequences in the mechanism of swarmer cell-specific silencing of gyrB transcription in Caulobacter crescentus

    Directory of Open Access Journals (Sweden)

    Gober James W


    Full Text Available Abstract Background Each Caulobacter crescentus cell division yields two distinct cell types: a flagellated swarmer cell and a non-motile stalked cell. The swarmer cell is further distinguished from the stalked cell by an inability to reinitiate DNA replication, by the physical properties of its nucleoid, and its discrete program of gene expression. Specifically, with regard to the latter feature, many of the genes involved in DNA replication are not transcribed in swarmer cells. Results We show that for one of these genes involved in DNA replication, gyrB, its pattern of temporal expression depends upon an 80 base pair promoter region with strong resemblance to the Caulobacter crescentus σ73 consensus promoter sequence; regulation does not appear to be affected by the general strength of the promoter activity, as mutations that increased its conformity with the consensus did not affect its cell-cycle expression pattern. Transcription from the gyrB promoter in vitro required only the presence of the σ73 RNA polymerase (from E. coli and the requisite nucleoside triphosphates, although a distinct binding activity, present in crude whole-cell extracts, formed a complex gyrB promoter DNA. We also assayed the effect on gyrB expression in strains containing mutations in either smc or dps, two genes encoding proteins that condense DNA. However we found there was no change in the temporal pattern of gyrB transcription in strains containing deletions in either of these genes. Conclusion These experiments demonstrate that gyrB transcription does not require any auxiliary factors, suggesting that temporal regulation is not dependent upon an activator protein. Swarmer-specific silencing may not be attributable to the observed physical difference in the swarmer cell nucleoid, since mutations in either smc or dps, two genes encoding proteins that condense DNA, did not alter the temporal pattern of gyrB transcription in strains containing deletions in either

  7. Basal physiological parameters in domesticated tree shrews (Tupaia belangeri chinensis). (United States)

    Wang, Jing; Xu, Xin-Li; Ding, Ze-Yang; Mao, Rong-Rong; Zhou, Qi-Xin; Lü, Long-Bao; Wang, Li-Ping; Wang, Shuang; Zhang, Chen; Xu, Lin; Yang, Yue-Xiong


    Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 ℃, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.

  8. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir


    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  9. Metastatic Basal cell carcinoma accompanying gorlin syndrome. (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel


    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  10. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)



    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  11. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;


    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  12. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD


    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  13. Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention (United States)

    Villano, Ines; Messina, Antonietta; Valenzano, Anna; Moscatelli, Fiorenzo; Esposito, Teresa; Monda, Vincenzo; Esposito, Maria; Precenzano, Francesco; Carotenuto, Marco; Viggiano, Andrea; Chieffi, Sergio; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni


    The basal forebrain (BF) cholinergic system has an important role in attentive functions. The cholinergic system can be activated by different inputs, and in particular, by orexin neurons, whose cell bodies are located within the postero-lateral hypothalamus. Recently the orexin-producing neurons have been proved to promote arousal and attention through their projections to the BF. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity. PMID:28197081

  14. 构建由OSE2修饰hTERT核心启动子在骨肉瘤转录靶向基因治疗前景中的研究%Study of construction hTERT core promoter modified by OSE2 in osteosarcoma transcription target gene therapy

    Institute of Scientific and Technical Information of China (English)

    李立文; 王臻; 苏明权; 马越云; 杨旻; 李哲


    Objective Constructing replication defect type virus vector of yeast cytosine deaminase gene expression guided by hTERT core promoter modified by OSE2 tandem replicator.Methods Multimer of OSE2 was designed and cloned into the upstream site of hTERT core promoter,then confirmed by sequencing.Shuttle plasmids were constructed using modified hTERT promoter and Fcy1 and cotransfected HEK 293 cells.Recombination yields replication defect type adenovirus.Result HEK 293 cells cotransfected by shuttle plasmid and assisted plasmid appeared typical cytopathic effect 7~ 10 days later.122bp objective fragment was confirmed by PCR evaluation.Conclusion We successfully constructed the replication defective adenovirus of Fcy1 gene expression guided by hTERT core promoter modified by 3 or 6 copys OSE2.

  15. Positive and negative regulation of basal expression of a yeast HSP70 gene.


    Park, H O; Craig, E A


    The SSA1 gene, one of the heat-inducible HSP70 genes in the yeast Saccharomyces cerevisiae, also displays a basal level of expression during logarithmic growth. Multiple sites related to the heat shock element (HSE) consensus sequence are present in the SSA1 promoter region (Slater and Craig, Mol. Cell. Biol. 7:1906-1916, 1987). One of the HSEs, HSE2, is important in the basal expression of SSA1 as well as in heat-inducible expression. A promoter containing a mutant HSE2 showed a fivefold-low...

  16. Lacustrine Basal Ages Constrain the Last Deglaciation in the Uinta Mountains, Utah, USA (United States)

    Munroe, Jeffrey; Laabs, Benjamin


    Basal radiocarbon ages from 21 high-elevation lakes limit the timing of final Pleistocene deglaciation in the Uinta Mountains of northeastern Utah, USA. The lakes are located in glacial valleys and cirques 5 to 20 km upstream from LGM terminal moraines at elevations from 2830 to 3475 m. Many are impounded behind recessional moraines. Cores were retrieved from a floating platform with a percussion corer driven to the point of refusal. All penetrated inorganic silty clay beneath gyttja. AMS radiocarbon analyses were made on terrestrial macrofossils, daphnia ephippia, pollen concentrates, and bulk sediment retrieved from the base of each core. No radiocarbon reservoir effect was observed when bulk dates were checked against terrestrial material. Radiocarbon results were converted to calendar years using the IntCal09 calibration curve in OxCal 4.1. Given the stratigraphy observed in the cores, these calibrated basal ages are considered close limits on the timing of the local deglaciation and lake formation. The oldest three lakes have basal radiocarbon ages that calibrate to a few centuries after the Bölling/Alleröd warming, indicating that the landscape was becoming ice free at this time. These are followed by an overlapping group of five lakes with basal ages between 13.5 and 13.0 ka BP. Five more cores, from four separate lakes, have basal ages tightly clustered between 13.0 and 12.5 ka BP. Three of these lakes are dammed by moraines, suggesting glacial activity during the early part of the Younger Dryas interval. The lone kettle lake in the study yielded a basal age of 12.3 ka BP, considerably younger than the basal age of 13.9 ka BP from a nearby lake filling a bedrock basin, indicating that buried ice may have been locally stable for more than a millennium after deglaciation. The remaining seven lakes have basal ages between 12.0 and 11.0 ka BP. Four of these lakes are also dammed by moraines. These two non-overlapping clusters of basal ages for moraine

  17. Ice cores

    DEFF Research Database (Denmark)

    Svensson, Anders


    Ice cores from Antarctica, from Greenland, and from a number of smaller glaciers around the world yield a wealth of information on past climates and environments. Ice cores offer unique records on past temperatures, atmospheric composition (including greenhouse gases), volcanism, solar activity......, dustiness, and biomass burning, among others. In Antarctica, ice cores extend back more than 800,000 years before present (Jouzel et al. 2007), whereas. Greenland ice cores cover the last 130,000 years...

  18. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam


    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  19. Automatic basal slice detection for cardiac analysis (United States)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.


    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  20. Biomarkers for Basal-like Breast Cancer


    Choo, Jennifer R.; Torsten O. Nielsen


    Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal...

  1. Promoting marketing management level to the development assistance for the core of grid enterprises%提升营销管理水平的探讨

    Institute of Scientific and Technical Information of China (English)



    New power marketing method to meet the market needs should be established, taking natural resources as premise, based on demand forecasting management, for the purpose of quality services, centered in meet user needs and guide the consumer. Grid enterprises is always ready to offer quality and cheap cleaner energy, is adapted to commercializes operation and legalized management, have layered efficient operating and full - featured, which is the fierce urgency of its core business--the marketing management work.%建立适应市场需要的新型电力营销理念,以可持续发展为前提,以需求预测管理为基础,以用户需求为导向,以优质服务为宗旨,以满足用户需求、引导用户消费为中心,随时随地为用户提供质优、价廉的清洁能源,适应商业化运营、法制化管理,分层高效运作,功能齐备,是电网企业核心业务---营销管理工作的当前之急。

  2. Clinical utility of complex mutations in the core promoterand proximal precore regions of the hepatitis B virusgenome

    Institute of Scientific and Technical Information of China (English)

    Young Min Park


    The core promoter and proximal precore regions arethe most complex portions of the hepatitis B virus(HBV) genome. These regions cooperatively regulateviral replication and differentially regulate the synthesisof the viral proteins E, core, and X. Multiple mutationsin these regions are associated with the persistencyof viral infection and the development of cirrhosis andhepatocellular carcinoma (HCC). In South Korea, nearlyall HBVs are classified as HBV genotype C2; the majorityof these viruses have the basal core promoter doublemutation, a precore stop mutation, or both. Thesemutations may play a role in the alteration of viral andclinical features, and abundant and complex mutationsare particularly prevalent in the core promoter andproximal precore regions. We previously demonstratedthat the accumulation of ≥ 6 mutations at eight keynucleotides located in these regions (G1613A, C1653T,T1753V, A1762T, G1764A, A1846T, G1896A, andG1899A) is a useful marker to predict the developmentof HCC regardless of advanced liver disease. In addition,certain mutation combinations were predominant incases with ≥ 4 mutations. In cases with ≤ 5 mutations,a low Hepatitis B e antigen titer (〈 35 signal to noiseratio) was indicative of HCC risk. Viral mutation data ofthe single HBV genotype C2 suggest that the combinedeffect of the number and pattern of mutations in thecore promoter and proximal precore regions is helpful inpredicting HCC risk.

  3. 基于“微笑曲线”理论下提升民营企业核心竞争力的研究%Study on Core Competence Promotion of Private Enterprises Based on"Smiling Curve Theory"

    Institute of Scientific and Technical Information of China (English)



    After international financial crisis,private enterprises in China face unprecedented opportunities and challenges.How to promote core competence is crucial to sustainable development of our private enterprises.Based on "Smiling Curve Theory",this article not only analyzes the status and action of our private enterprises in national economy and social develop-ment,but also problems and difficulties they are facing.Meanwhile,this article expounds the necessity of transferring their development to the two ends of "Smiling Curve" in global industry chain,putting forward specific strategies and measures of promoting core competence of our private enterprises based on that.%国际金融危机以来,我国民营企业面临着前所未有的机遇与挑战,提升核心竞争力是我国民营企业未来可持续发展的关键。本文基于"微笑曲线"理论分析了我国民营企业在国民经济和社会发展中的重要作用及面临的问题和困境,提出向全球产业链"微笑曲线"两端转移发展的必要性以及在此基础上提升我国民营企业核心竞争力的具体对策和措施。

  4. 5meCpG epigenetic marks neighboring a primate-conserved core promoter short tandem repeat indicate X-chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Filipe Brum Machado

    Full Text Available X-chromosome inactivation (XCI is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX and males (XY. DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG in promoter regions is a key epigenetic marker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa from inactive (Xi X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8 and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2 and Xq (AR chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic

  5. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)


    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  6. Somatotopic organization of the primate basal ganglia

    Directory of Open Access Journals (Sweden)

    Atsushi eNambu


    Full Text Available Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson’s disease and dystonia.

  7. Identification of triple-negative and basal-like canine mammary carcinomas using four basal markers. (United States)

    Kim, N H; Lim, H Y; Im, K S; Kim, J H; Sur, J-H


    Molecular-based classification of canine mammary carcinomas (CMCs) has been a recent research focus. In human breast cancer, triple-negative and basal-like phenotypes are distinct molecular subgroups that are known for their poor prognosis, but these tumours are not yet well defined in the dog. The aim of this study was to determine whether CMCs include triple-negative and basal-like phenotypes by immunohistochemical assessment of expression of the oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and four basal markers, cytokeratin (CK) 14, CK5/6, p63 and the epidermal growth factor receptor (EGFR). In this study of 241 CMCs, 45 triple-negative tumours (OR(-), PR(-) and HER2(-)) were identified and this phenotype was associated with an unfavourable prognosis. In these tumours, the expression of CK14, CK5/6 and EGFR was related to clinicopathological parameters, while the expression of p63 was not relevant. The majority of the triple-negative tumours were of the basal-like phenotype, given that 75.6% of them expressed more than two basal markers. However, three of the basal markers were not uniformly expressed; therefore, the proportion of the basal-like phenotype was altered on the basis of the selection of the markers. Although both triple-negative and basal-like phenotypes are distinct entities in CMC, further study is needed to differentiate one from the other.

  8. Radiologic study of basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)


    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  9. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)


    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  10. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R;


    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed...

  11. Parallel basal ganglia circuits for decision making. (United States)

    Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi


    The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

  12. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser


    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  13. On the Dimensions of Promoting Popularization Media Direction of the Socialist Core Value System%论推进社会主义核心价值体系大众化的媒体引导向度

    Institute of Scientific and Technical Information of China (English)



    Media is a important carrier to spread ideological culture.It is a main channel to popularize mainstream values.It can play an important role in organizing and directing public opinion.We must play fully respective advantage of traditional and new media in the course of promoting popularization of the socialist core value system.We should not only consolidate position of traditional media direction,but also exploit channel of new media direction.The traditional media must cooperate with new media to build strong vigor of public opinion.It can boost up charm,inspire force and influence maximally in order to cause people to identify with the socialist core value system.%媒体是思想文化传播的重要载体,是推广主流价值观的主渠道,在组织和引导社会舆论方面发挥着重要作用。在推进社会主义核心价值体系大众化进程中,要充分发挥传统媒体和新兴媒体的各自优势,不断巩固传统媒体引导阵地,积极开拓新兴媒体引导渠道,实现传统媒体和新兴媒体的联动,努力营造舆论强势,最大限度地增强理论宣传的吸引力、感染力和影响力,从而使社会主义核心价值体系更好地在广大人民群众中入耳、入脑、入心。

  14. Core bioactive components promoting blood circulation in the traditional Chinese medicine compound xueshuantong capsule (CXC) based on the relevance analysis between chemical HPLC fingerprint and in vivo biological effects. (United States)

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei


    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  15. Basal melting and Eemian ice along the main ice ridge in northern Greenland

    DEFF Research Database (Denmark)

    Buchardt, Susanne Lilja

    The variation of the basal melt rate and the location of the Eemian layer in the ice column are investigated along the ice divide between the NorthGRIP and NEEM ice core drill sites in northern Greenland. At NorthGRIP an ice core was drilled in the period 1996-2004, and the stable isotope record (d...... the line. A Dansgaard-Johnsen model is then used to simulate the ice flow along the flow line from NorthGRIP to NEEM. One- as well as two-dimensional approaches are taken. The basal melt rates and other unknown flow parameters are determined using a Monte Carlo method. The Monte Carlo solution...... is constrained by isochrones revealed in radio-echo sounding images of the ice. The obtained results indicate a high spatial variability in the basal melt rate in the area, and values between zero and 25 mm/yr are found. The results indicate that there is little or no basal melting at NEEM. The location...

  16. Ice Cores (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Records of past temperature, precipitation, atmospheric trace gases, and other aspects of climate and environment derived from ice cores drilled on glaciers and ice...

  17. Core BPEL

    DEFF Research Database (Denmark)

    Hallwyl, Tim; Højsgaard, Espen

    extensions. Combined with the fact that the language definition does not provide a formal semantics, it is an arduous task to work formally with the language (e.g. to give an implementation). In this paper we identify a core subset of the language, called Core BPEL, which has fewer and simpler constructs......, does not allow omissions, and does not contain ignorable elements. We do so by identifying syntactic sugar, including default values, and ignorable elements in WS-BPEL. The analysis results in a translation from the full language to the core subset. Thus, we reduce the effort needed for working...... formally with WS-BPEL, as one, without loss of generality, need only consider the much simpler Core BPEL. This report may also be viewed as an addendum to the WS-BPEL standard specification, which clarifies the WS-BPEL syntax and presents the essential elements of the language in a more concise way...

  18. The rcsA Promoter of Pantoea stewartii subsp. stewartii Features a Low-Level Constitutive Promoter and an EsaR Quorum-Sensing-Regulated Promoter


    Carlier, Aurelien L.; von Bodman, S B


    The upstream region of the Pantoea stewartii rcsA gene features two promoters, one for constitutive basal-level expression and a second autoregulated promoter for induced expression. The EsaR quorum-sensing repressor binds to a site centered between the two promoters, blocking transcription elongation from the regulated promoter under noninducing conditions.

  19. Bilateral germinoma of the basal ganglia. (United States)

    Rossi, Andrea; Garrè, Maria Luisa; Ravegnani, Marcello; Nozza, Paolo; Abbruzzese, Arturo; Giangaspero, Felice; Tortori-Donati, Paolo


    Germinoma arising in the bilateral basal ganglia is exceedingly rare, with only five cases reported to date. Owing to non-specific clinical findings and the frequent presence of ill-defined abnormalities without a definite tumor mass on neuroimaging, the diagnosis can be difficult. We describe a case in which magnetic resonance spectroscopy (MRS) findings suggested a tumor and supported the decision to perform biopsy of the lesion.

  20. Basal ganglia lesions in children and adults

    Energy Technology Data Exchange (ETDEWEB)

    Bekiesinska-Figatowska, Monika, E-mail: [Department of Diagnostic Imaging, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Mierzewska, Hanna, E-mail: [Department of Neurology of Children and Adolescents, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Jurkiewicz, Elżbieta, E-mail: [Department of Diagnostic Imaging, Children' s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw (Poland)


    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive.

  1. 构建MYC反应元件修饰hTERT核心启动子引导荧光素酶表达的腺病毒载体%Construction of adenoviral vector for luciferase driven by hTERT core promoter modified with MYC-responsive elements

    Institute of Scientific and Technical Information of China (English)

    杨旻; 王臻; 李立文; 苏明权; 于文彬


    AIM:To construct adenoviral vectors for luciferase driven by human telomerase reverse transcriptase(hTERT) core promoter with multimer of MYC responsive elements.METHODS:Multimer of MYC responsive elements was cloned into the upstream site of hTERT core promoter and the modified hTERT promoter and luciferase were cloned into the plasmid pDC316 to construct shuttle plasmids which cotransfected HEK 293 cells with rescue plasmid pBHGlox(delta)E1,3Cre to achieve recombinant adenoviral vectors.The cytopathic effects and PCR using primers specific for luciferase were used to identify the recombinant adenoviral vectors.RESULTS:Adenoviral vectors with luciferase driven by hTERT core promoter with none or positive and negative six copies of MYC responsive elements were constructed and amplified.The titer of the adenovirus were 3.5× 106 pfu/ml,2.5× 106 pfu/ml and 1.5× 106 pfu/ml respectively determined by plaque assay.CONCLUSION:The further research on transciriptional targeting in osteosarcoma gene therapy can be done using adenoviral vectors with luciferase driven by hTERT promoter with MYC responsive elements.

  2. A comprehensive interpretation of the NEEM basal ice build-up using a multi parametric approach (United States)

    Goossens, T.; Sapart, C. J.; Dahl-Jensen, D.; Popp, T.; El Amri, S.; Tison, J. L.


    Basal ice is a common expression to describe debris-laden ice layers found close to the ice-bedrock interface under glaciers and ice sheets. The study of basal ice properties provides a unique opportunity to improve our understanding of subglacial environments and processes and to refine ice sheet behaviour modelling. Here, we present and discuss the results of water stable isotopes (δ18O and δD), ice fabrics, debris weight and gas content of the basal part of the NEEM (North Greenland Eemian Ice Drilling Project) ice core. Below a depth of 2533.85 m, almost 10 m of basal debris-rich material were retrieved from the borehole. The sequence is composed of an alternation of three visually contrasting types of ice: clear ice with specks of particulate inclusions, stratified debris-rich layers, and ice containing dispersed debris. The use of water stable isotope signatures (δ18O and δD) together with other parameters, allows to discriminate between the different types of ice and to unravel the processes involved in their formation and transformation. The basal debris-rich material presents δ18O values [-39.9 ‰; -34.4 ‰] within the range of the above last 300 m of unaltered meteoric ice [-44.9 ‰; -30.6 ‰] spanning a glacial-interglacial range of values. This rules out the hypothesis of a basal ice layer originating from pre-ice sheet ice overridden by the growing ice sheet (as previously suggested e.g. in the case of the GRIP ice core), since the latter would result in an heavier isotopic signature for ice formed at a much lower altitude. We show that clear basal ice with specks corresponds to altered meteoric glacial ice where a climatic signal is preserved. On the other hand, both stratified debris-rich layers and ice containing dispersed debris layers express an "open" or "closed" system melting/refreezing signature, somewhat blurred by mixing processes. Climatic reconstruction is therefore prohibited from these ice types. We propose a first

  3. A comprehensive interpretation of the NEEM basal ice build-up using a multi parametric approach

    Directory of Open Access Journals (Sweden)

    T. Goossens


    Full Text Available Basal ice is a common expression to describe debris-laden ice layers found close to the ice–bedrock interface under glaciers and ice sheets. The study of basal ice properties provides a unique opportunity to improve our understanding of subglacial environments and processes and to refine ice sheet behaviour modelling. Here, we present and discuss the results of water stable isotopes (δ18O and δD, ice fabrics, debris weight and gas content of the basal part of the NEEM (North Greenland Eemian Ice Drilling Project ice core. Below a depth of 2533.85 m, almost 10 m of basal debris-rich material were retrieved from the borehole. The sequence is composed of an alternation of three visually contrasting types of ice: clear ice with specks of particulate inclusions, stratified debris-rich layers, and ice containing dispersed debris. The use of water stable isotope signatures (δ18O and δD together with other parameters, allows to discriminate between the different types of ice and to unravel the processes involved in their formation and transformation. The basal debris-rich material presents δ18O values [−39.9 ‰; −34.4 ‰] within the range of the above last 300 m of unaltered meteoric ice [−44.9 ‰; −30.6 ‰] spanning a glacial–interglacial range of values. This rules out the hypothesis of a basal ice layer originating from pre-ice sheet ice overridden by the growing ice sheet (as previously suggested e.g. in the case of the GRIP ice core, since the latter would result in an heavier isotopic signature for ice formed at a much lower altitude. We show that clear basal ice with specks corresponds to altered meteoric glacial ice where a climatic signal is preserved. On the other hand, both stratified debris-rich layers and ice containing dispersed debris layers express an "open" or "closed" system melting/refreezing signature, somewhat blurred by mixing processes. Climatic reconstruction is therefore prohibited from these ice types. We

  4. Genetics Home Reference: familial idiopathic basal ganglia calcification (United States)

    ... idiopathic basal ganglia calcification ( FIBGC , formerly known as Fahr disease) is a condition characterized by abnormal deposits of ... on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet. 1999 Sep;65(3): ...

  5. The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Starska, Katarzyna, E-mail: [I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź (Poland); Krześlak, Anna; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland); Olszewski, Jurek [II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź (Poland); Morawiec-Sztandera, Alina [Department of Head and Neck Surgery, Medical University of Łódź, Paderewskiego 4, 93-509 Łódź (Poland); Aleksandrowicz, Paweł [Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin (Poland); Lewy-Trenda, Iwona [Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź (Poland); and others


    Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. - Highlights: • MT2A gene expression and metal content in laryngeal cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn and Cu levels • Negative correlation between MT2A gene expression and Cd, Zn and Cu levels.

  6. Integrated profiling of basal and luminal breast cancers.

    NARCIS (Netherlands)

    Adelaide, J.; Finetti, P.; Bekhouche, I.; Repellini, L.; Geneix, J.; Sircoulomb, F.; Charafe-Jauffret, E.; Cervera, N.; Desplans, J.; Parzy, D.; Schoenmakers, E.F.P.M.; Viens, P.; Jacquemier, J.; Birnbaum, D.; Bertucci, F.; Chaffanet, M.


    Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal

  7. Adenoid basal cell carcinoma and its mimics

    Directory of Open Access Journals (Sweden)

    Sujata Jetley


    Full Text Available Basal cell carcinoma (BCC is the most common malignant tumor of skin. The most common site (80% is head and neck. BCC exhibits a varied morphology such as adenoid, keratotic, sebaceous, basosquamous, apocrine, eccrine or fibroepithelial. Tumors with a similar histopathological picture are cutaneous adenoid cystic carcinoma and primary cutaneous cribriform apocrine carcinoma. Immunohistochemistry, along with clinical findings, acts as an adjunct in reaching an accurate diagnosis. Here, we present an interesting case of adenoid BCC in a 55-year-old man.

  8. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien


    Full Text Available Basal cell carcinoma (BCC remains the most common form of nonmelanoma skin cancer (NMSC in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT, will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  9. Mössbauer spectroscopy of Basal Ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Miglierini, Marcel, E-mail: [Institute of Nuclear and Physical Engineering, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovičova 3, 812 19 Bratislava, Slovakia and Regional Centre of Advanced Technologies and Materials (Czech Republic); Lančok, Adriana [Institute of Inorganic Chemistry AS CR, v. v. i., 250 68 Husinec-Řež 1001 (Czech Republic); Kopáni, Martin [Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Sasinkova 2, 811 08 Bratislava (Slovakia); Boča, Roman [Department of Chemistry, Faculty of Natural Sciences, University of SS. Cyril and Methodius, 917 01 Trnava (Slovakia)


    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  10. Archaefructaceae, a new basal angiosperm family. (United States)

    Sun, Ge; Ji, Qiang; Dilcher, David L; Zheng, Shaolin; Nixon, Kevin C; Wang, Xinfu


    Archaefructaceae is proposed as a new basal angiosperm family of herbaceous aquatic plants. This family consists of the fossils Archaefructus liaoningensis and A. sinensis sp. nov. Complete plants from roots to fertile shoots are known. Their age is a minimum of 124.6 million years from the Yixian Formation, Liaoning, China. They are a sister clade to all angiosperms when their characters are included in a combined three-gene molecular and morphological analysis. Their reproductive axes lack petals and sepals and bear stamens in pairs below conduplicate carpels.

  11. AIDA-1 Moves out of the Postsynaptic Density Core under Excitatory Conditions.

    Directory of Open Access Journals (Sweden)

    Ayse Dosemeci

    Full Text Available AIDA-1 is highly enriched in postsynaptic density (PSD fractions and is considered a major component of the PSD complex. In the present study, immunogold electron microscopy was applied to determine localization as well as the activity-induced redistribution of AIDA-1 at the PSD using two antibodies that recognize two different epitopes. In cultured rat hippocampal neurons under basal conditions, immunogold label for AIDA-1 is mostly located within the dense core of the PSD, with a median distance of ~30 nm from the postsynaptic membrane. Under excitatory conditions, such as depolarization with high K+ (90 mM, 2 min or application of NMDA (50 μM, 2 min, AIDA-1 label density at the PSD core is reduced to 40% of controls and the median distance of label from the postsynaptic membrane increases to ~55 nm. The effect of excitatory conditions on the postsynaptic distribution of AIDA-1 is reversed within 30 minutes after returning to control conditions. The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95. Activity-induced transient translocation of these abundant proteins from the PSD core could promote structural flexibility, vacate sites on PSD-95 for the insertion of other components and thus may create a window for synaptic modification.

  12. Cloning and functional analysis of SEL1L promoter region, a pancreas-specific gene. (United States)

    Cattaneo, M; Sorio, C; Malferrari, G; Rogozin, I B; Bernard, L; Scarpa, A; Zollo, M; Biunno, I


    We examined the promoter activity of SEL1L, the human ortholog of the C. elegans gene sel-1, a negative regulator of LIN-12/NOTCH receptor proteins. To understand the relation in SEL1L transcription pattern observed in different epithelial cells, we determined the transcription start site and sequenced the 5' flanking region. Sequence analysis revealed the presence of consensus promoter elements--GC boxes and a CAAT box--but the absence of a TATA motif. Potential binding sites for transcription factors that are involved in tissue-specific gene expression were identified, including: activator protein-2 (AP-2), hepatocyte nuclear factor-3 (HNF3 beta), homeobox Nkx2-5 and GATA-1. Transcription activity of the TATA-less SEL1L promoter was analyzed by transient transfection using luciferase reporter gene constructs. A core basal promoter of 302 bp was sufficient for constitutive promoter activity in all the cell types studied. This genomic fragment contains a CAAT and several GC boxes. The activity of the SEL1L promoter was considerably higher in mouse pancreatic beta cells (beta TC3) than in several human pancreatic neoplastic cell lines; an even greater reduction of its activity was observed in cells of nonpancreatic origin. These results suggest that SEL1L promoter may be a useful tool in gene therapy applications for pancreatic pathologies.

  13. BRCA1 transcriptionally regulates genes associated with the basal-like phenotype in breast cancer. (United States)

    Gorski, Julia J; James, Colin R; Quinn, Jennifer E; Stewart, Gail E; Staunton, Kieran Crosbie; Buckley, Niamh E; McDyer, Fionnuala A; Kennedy, Richard D; Wilson, Richard H; Mullan, Paul B; Harkin, D Paul


    Expression profiling of BRCA1-deficient tumours has identified a pattern of gene expression similar to basal-like breast tumours. In this study, we examine whether a BRCA1-dependent transcriptional mechanism may underpin the link between BRCA1 and basal-like phenotype. In methods section, the mRNA and protein were harvested from a number of BRCA1 mutant and wild-type breast cancer cell lines and from matched isogenic controls. Microarray-based expression profiling was used to identify potential BRCA1-regulated transcripts. These gene targets were then validated (by in silico analysis of tumour samples) by real-time PCR and Western blot analysis. Chromatin immunoprecipitation (ChIP) assays were used to confirm recruitment of BRCA1 to specific promoters. In results, we demonstrate that functional BRCA1 represses the expression of cytokeratins 5(KRT5) and 17(KRT17) and p-Cadherin (CDH3) in HCC1937 and T47D breast cancer cell lines at both mRNA and protein level. ChIP assays demonstrate that BRCA1 is recruited to the promoters of KRT5, KRT17 and CDH3, and re-ChIP assays confirm that BRCA1 is recruited independently to form c-Myc and Sp1 complexes on the CDH3 promoter. We show that siRNA-mediated inhibition of endogenous c-Myc (and not Sp1) results in a marked increase in CDH3 expression analogous to that observed following the inhibition of endogenous BRCA1. The data provided suggest a model whereby BRCA1 and c-Myc form a repressor complex on the promoters of specific basal genes and represent a potential mechanism to explain the observed overexpression of key basal markers in BRCA1-deficient tumours.

  14. Activation of the Basal Forebrain by the Orexin/Hypocretin Neurons: Orexin International Symposium


    Arrigoni, Elda; Mochizuki, Takatoshi; Scammell, Thomas E.


    The orexin neurons play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurons promote arousal. Here we review anatomical, pharmacological and electrophysiologic...

  15. Basal cell nevus syndrome or Gorlin syndrome. (United States)

    Thalakoti, Srikanth; Geller, Thomas


    Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

  16. Characterization of a Crabs Claw Gene in Basal Eudicot Species Epimedium sagittatum (Berberidaceae

    Directory of Open Access Journals (Sweden)

    Wei Sun


    Full Text Available The Crabs Claw (CRC YABBY gene is required for regulating carpel development in angiosperms and has played an important role in nectary evolution during core eudicot speciation. The function or expression of CRC-like genes has been explored in two basal eudicots, Eschscholzia californica and Aquilegia formosa. To further investigate the function of CRC orthologous genes related to evolution of carpel and nectary development in basal eudicots, a CRC ortholog, EsCRC, was isolated and characterized from Epimedium sagittatum (Sieb. and Zucc. Maxim. A phylogenetic analysis of EsCRC and previously identified CRC-like genes placed EsCRC within the basal eudicot lineage. Gene expression results suggest that EsCRC is involved in the development of sepals and carpels, but not nectaries. Phenotypic complementation of the Arabidopsis mutant crc-1 was achieved by constitutive expression of EsCRC. In addition, over-expression of EsCRC in Arabidopsis and tobacco gave rise to abaxially curled leaves. Transgenic results together with the gene expression analysis suggest that EsCRC may maintain a conserved function in carpel development and also play a novel role related to sepal formation. Absence of EsCRC and ElCRC expression in nectaries further indicates that nectary development in non-core eudicots is unrelated to expression of CRC-like genes.

  17. Identification of a novel temperature sensitive promoter in cho cells

    Directory of Open Access Journals (Sweden)

    Hesse Friedemann


    Full Text Available Abstract Background The Chinese hamster ovary (CHO expression system is the leading production platform for manufacturing biopharmaceuticals for the treatment of numerous human diseases. Efforts to optimize the production process also include the genetic construct encoding the therapeutic gene. Here we report about the successful identification of an endogenous highly active gene promoter obtained from CHO cells which shows conditionally inducible gene expression at reduced temperature. Results Based on CHO microarray expression data abundantly transcribed genes were selected as potential promoter candidates. The S100a6 (calcyclin and its flanking regions were identified from a genomic CHO-K1 lambda-phage library. Computational analyses showed a predicted TSS, a TATA-box and several TFBSs within the 1.5 kb region upstream the ATG start signal. Various constructs were investigated for promoter activity at 37°C and 33°C in transient luciferase reporter gene assays. Most constructs showed expression levels even higher than the SV40 control and on average a more than two-fold increase at lower temperature. We identified the core promoter sequence (222 bp comprising two SP1 sites and could show a further increase in activity by duplication of this minimal sequence. Conclusions This novel CHO promoter permits conditionally high-level gene expression. Upon a shift to 33°C, a two to three-fold increase of basal productivity (already higher than SV40 promoter is achieved. This property is of particular advantage for a process with reduced expression during initial cell growth followed by the production phase at low temperature with a boost in expression. Additionally, production of toxic proteins becomes feasible, since cell metabolism and gene expression do not directly interfere. The CHO S100a6 promoter can be characterized as cold-shock responsive with the potential for improving process performance of mammalian expression systems.

  18. Basal Cell Nevus Syndrome. A Case Presentation

    Directory of Open Access Journals (Sweden)

    Ángel Luis Cruz Leiva


    Full Text Available Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

  19. Basal body temperature recordings in spontaneous abortion. (United States)

    Cohen, J; Iffy, L; Keyser, H H


    Basal body temperature (BBT) charts taken during the cycle of conception in cases that resulted in spontaneous abortion appear to provide the best available information concerning events associated with time of fertilization in doomed gestations. This study is based on a series of 227 patients who had early spontaneous abortion occurring between January 1967 and December 1974. A diagnosis of pregnancy initiated regular assays of urinary estrogen and pregnanediol excretion. Patients were instructed to report any bleeding episode which might occur, and to preserve all tissues that might be expelled. A total of 11 basal body temperature charts were obtained from patients who had subsequent early spontaneous abortion. Chromosome studies and histologic investigations were conducted. Another group of 11 consecutive BBT records were obtained from patients who had normal deliveries. The study shows that women with normal cycles experience a midcycle temperature rise requiring 1 to 3 days. In subsequent patients, this time limit was exceeded in 7 out of 11 cases of early abortion, and in 4 of 11 fertilization that resulted in an apparently normal gestation and infant. As temperature rise resulted from vigorous progesterone secretion by the corpus luteum, subnormal levels indicate inadequate steroidogenesis in the early luteal phase, and falling estrogen and progesterone levels predicted fetal demise in all cases. These findings are useful in the management of early pregnancy that follows repeated spontaneous first trimester abortions or a prolonged period of infertility. They also confirm experimental and clinical evidence regarding the role of ovulation defects in the occurrence of various types of reproductive wastage, including early abortion, anatomic and chromosome defects of the embryo and others. Prospective studies of cycles of conception through BBT recordings/hormone assays may shed light in the understanding of defects of human reproduction.

  20. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM


    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  1. [A Role of the Basal Ganglia in Processing of Complex Sounds and Auditory Attention]. (United States)

    Silkis, I G


    A hypothetical mechanism is suggested for processing of complex sounds and auditory attention in parallel neuronal loops including various auditory cortical areas connected with parts of the medial geniculate body, inferior colliculus and basal ganglia. Release of dopamine in the striatum promotes bidirectional modulation of strong and weak inputs from the neocortex to striatal neurons giving rise to direct and indirect pathways through the basal ganglia. Subsequent synergistic disinhibition of one and inhibition of other groups of thalamic neurons by the basal ganglia result in the creation of contrasted neuronal representations of properties of auditory stimuli in related cortical areas. Contrasting is strengthened due to a simultaneous disinhibition of pedunculopontine nucleus and action at muscarine receptors on neurons in the medial geniculate body. It follows from this mechanism that involuntary attention to sound tone can enhance an early component of the responses of neurons in the primary auditory cortical area (50 msec) in the absence of dopamine due to a disinhibition of thalamic neurons via the direct pathway through the basal ganglia, whereas voluntary attention to complex sounds can enhance only those components of responses of neurones in secondary auditory cortical areas which latencies exceeds latencies of dopaminergic cells (i.e. after 100 msec). Various consequences of proposed mechanism are in agreement with known experimental data.

  2. Abnormal Basal Ganglia Functional Connectivity in Idiopathic Generalized Epilepsy

    Institute of Scientific and Technical Information of China (English)

    Cheng Luo; Yang Xia; Zhi-Wei Guo; Dong Zhou


    The basal ganglia have been implicated in a modulation role in idiopathic generalized epilepsy (IGE) by an invasive electrophysioigic means.This paper investigates the basal ganglia functional connectivity by using the region-wise functional connection analysis in resting-state functional magnetic resonance imaging (fMRi) in IGE.The increased functional connectivity within basal ganglia,and between the basal ganglia and the thalamus,and decreased functional connectivity between basal ganglia and motor cortex are found in IGE compared with the controls. These findings not only implicate dysfunctional integration in the motor loop in IGE and the enhanced interaction in the modulated loop,but also suggest that the basal ganglia modulate the generalized epileptic discharges with the influence over thalamus in the corticothalamus network.

  3. Basal Lamina Mimetic Nanofibrous Peptide Networks for Skeletal Myogenesis (United States)

    Yasa, I. Ceren; Gunduz, Nuray; Kilinc, Murat; Guler, Mustafa O.; Tekinay, Ayse B.


    Extracellular matrix (ECM) is crucial for the coordination and regulation of cell adhesion, recruitment, differentiation and death. Therefore, equilibrium between cell-cell and cell-matrix interactions and matrix-associated signals are important for the normal functioning of cells, as well as for regeneration. In this work, we describe importance of adhesive signals for myoblast cells’ growth and differentiation by generating a novel ECM mimetic peptide nanofiber scaffold system. We show that not only structure but also composition of bioactive signals are important for cell adhesion, growth and differentiation by mimicking the compositional and structural properties of native skeletal muscle basal lamina. We conjugated laminin-derived integrin binding peptide sequence, “IKVAV”, and fibronectin-derived well known adhesive sequence, “RGD”, into peptide nanostructures to provide adhesive and myogenic cues on a nanofibrous morphology. The myogenic and adhesive signals exhibited a synergistic effect on model myoblasts, C2C12 cells. Our results showed that self-assembled peptide nanofibers presenting laminin derived epitopes support adhesion, growth and proliferation of the cells and significantly promote the expression of skeletal muscle-specific marker genes. The functional peptide nanofibers used in this study present a biocompatible and biodegradable microenvironment, which is capable of supporting the growth and differentiation of C2C12 myoblasts into myotubes.

  4. Basal cell carcinoma in oculo-cutaneous albinism

    Directory of Open Access Journals (Sweden)

    Ajay Kumar


    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

  5. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    Lo Muzio Lorenzo


    Full Text Available Abstract Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs, odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies. Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling. Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome. Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser

  6. A comprehensive interpretation of the NEEM basal ice build-up using a multi-parametric approach (United States)

    Goossens, Thomas; Sapart, Célia J.; Dahl-Jensen, Dorthe; Popp, Trevor; El Amri, Saïda; Tison, Jean-Louis


    Basal ice is a common expression to describe bottom ice layers of glaciers, ice caps and ice sheets in which the ice is primarily conditioned by processes operating at the bed. It is chemically and/or physically distinct from the ice above and can be characterized by a component of basally derived sediments. The study of basal ice properties provides a rare opportunity to improve our understanding of subglacial environments and processes and to refine ice sheet behaviour modelling. Here, we present and discuss the results of water stable isotopes (δ18O and δD), ice fabrics, debris weight/size distribution and gas content of the basal part of the NEEM (North Greenland Eemian Ice Drilling Project) ice core. Below a depth of 2533.85 m, almost 10 m of basal debris-rich material was retrieved from the borehole, and regular occurrence of frozen sediments with only interstitial ice lenses in the bottom 5 m suggest that the ice-bedrock interface was reached. The sequence is composed of an alternation of three visually contrasting types of ice: clear ice with specks (very small amounts) of particulate inclusions, stratified debris-rich layers and ice containing dispersed debris. The use of water stable isotope signatures (δ18O and δD), together with other parameters, allows discrimination between the different types of ice and to unravel the processes involved in their formation and transformation. The basal debris-rich material presents δ18O values [-39.9 ‰; -34.4 ‰] within the range of the above last 300 m of unaltered meteoric ice [-44.9 ‰; -30.6 ‰] spanning a glacial-interglacial range of values. This rules out the hypothesis of a basal ice layer originating from pre-ice sheet ice overridden by the growing ice sheet, as previously suggested e.g. in the case of GRIP (Greenland Ice Core Project). We show that clear basal ice with specks corresponds to altered meteoric glacial ice where some of the climatic signal could have been preserved. However, the

  7. [Vismodegib Therapy for Periocular Basal Cell Carcinoma]. (United States)

    Keserü, M; Green, S; Dulz, S


    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason.

  8. How Basal Ganglia Outputs Generate Behavior

    Directory of Open Access Journals (Sweden)

    Henry H. Yin


    Full Text Available The basal ganglia (BG are a collection of subcortical nuclei critical for voluntary behavior. According to the standard model, the output projections from the BG tonically inhibit downstream motor centers and prevent behavior. A pause in the BG output opens the gate for behavior, allowing the initiation of actions. Hypokinetic neurological symptoms, such as inability to initiate actions in Parkinson’s disease, are explained by excessively high firing rates of the BG output neurons. This model, widely taught in textbooks, is contradicted by recent electrophysiological results, which are reviewed here. In addition, I also introduce a new model, based on the insight that behavior is a product of closed loop negative feedback control using internal reference signals rather than sensorimotor transformations. The nervous system is shown to be a functional hierarchy comprising independent controllers occupying different levels, each level controlling specific variables derived from its perceptual inputs. The BG represent the level of transition control in this hierarchy, sending reference signals specifying the succession of body orientations and configurations. This new model not only explains the major symptoms in movement disorders but also generates a number of testable predictions.

  9. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion (United States)

    Niumsawatt, Vachara; Castley, Andrew


    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  10. Mineralizing angiopathy with basal ganglia stroke in an infant

    Directory of Open Access Journals (Sweden)

    Puneet Jain


    Full Text Available Basal ganglia stroke is known following trivial head trauma. Recently a distinct clinic-radiological entity termed ′mineralizing angiopathy′ was described. We report an infant who developed basal ganglia stroke following trivial fall. His clinic-radiological features are described.

  11. Vismodegib resistance in basal cell carcinoma: not a smooth fit. (United States)

    Ridky, Todd W; Cotsarelis, George


    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  12. Evolution and diversification of the basal transcription machinery. (United States)

    Duttke, Sascha H C


    Transcription initiation was once thought to be regulated primarily by sequence-specific transcription factors with the basal transcription machinery being largely invariant. Gradually it became apparent that the basal transcription machinery greatly diversified during evolution and new studies now demonstrate that diversification of the TATA-binding protein (TBP) family yielded specialized and largely independent transcription systems.

  13. Archaeal promoter architecture and mechanism of gene activation

    DEFF Research Database (Denmark)

    Peng, Nan; Ao, Xiang; Liang, Yun Xiang;


    Sulfolobus solfataricus and Sulfolobus islandicus contain several genes exhibiting D-arabinose-inducible expression and these systems are ideal for studying mechanisms of archaeal gene expression. At sequence level, only two highly conserved cis elements are present on the promoters: a regulatory...... element named ara box directing arabinose-inducible expression and the basal promoter element TATA, serving as the binding site for the TATA-binding protein. Strikingly, these promoters possess a modular structure that allows an essentially inactive basal promoter to be strongly activated. The invoked...

  14. Basal ganglia - thalamus and the crowning enigma

    Directory of Open Access Journals (Sweden)

    Marianela eGarcia-Munoz


    Full Text Available When Hubel (1982 referred to layer 1 of primary visual cortex as …a ‘crowning mystery’ to keep area-17 physiologists busy for years to come... he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1, the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory cortex before focusing on motor cortex.

  15. Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System. (United States)

    Brodal, Hans P; Osnes, Berge; Specht, Karsten


    Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music.

  16. Using health promotion competencies for curriculum development in higher education. (United States)

    Madsen, Wendy; Bell, Tanya


    Health promotion core competencies are used for a variety of reasons. Recently there have been moves to gain international consensus regarding core competencies within health promotion. One of the main reasons put forward for having core competencies is to guide curriculum development within higher education institutions. This article outlines the endeavours of one institution to develop undergraduate and postgraduate curricula around the Australian core competencies for health promotion practitioners. It argues that until core competencies have been agreed upon internationally, basing curricula on these carries a risk associated with change. However, delaying curricula until such risks are ameliorated decreases opportunities to deliver dynamic and current health promotion education within higher institutions.

  17. Dual-core antiresonant hollow core fibers. (United States)

    Liu, Xuesong; Fan, Zhongwei; Shi, Zhaohui; Ma, Yunfeng; Yu, Jin; Zhang, Jing


    In this work, dual-core antiresonant hollow core fibers (AR-HCFs) are numerically demonstrated, based on our knowledge, for the first time. Two fiber structures are proposed. One is a composite of two single-core nested nodeless AR-HCFs, exhibiting low confinement loss and a circular mode profile in each core. The other has a relatively simple structure, with a whole elliptical outer jacket, presenting a uniform and wide transmission band. The modal couplings of the dual-core AR-HCFs rely on a unique mechanism that transfers power through the air. The core separation and the gap between the two cores influence the modal coupling strength. With proper designs, both of the dual-core fibers can have low phase birefringence and short modal coupling lengths of several centimeters.

  18. Basal physiological parameters in domesticated tree shrews(Tupaia belangeri chinensis)

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Xin-Li XU; Ze-Yang DING; Rong-Rong MAO; Qi-Xin ZHOU; Long-Bao LV; Li-Ping WANG; Shuang WANG; Chen ZHANG


    Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1) body weight,(2) core body temperature and rhythm,(3) diet metabolism,(4) locomotor rhythm,(5) electroencephalogram,(6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 ℃,which was higher than that of rats and macaques; (b) Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats,tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.

  19. Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons. (United States)

    Unal, Cagri T; Pare, Denis; Zaborszky, Laszlo


    In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.

  20. Cholesterol-mediated activation of P-glycoprotein: distinct effects on basal and drug-induced ATPase activities. (United States)

    Belli, Sara; Elsener, Priska M; Wunderli-Allenspach, Heidi; Krämer, Stefanie D


    Cholesterol promotes basal and verapamil-induced ATPase activity of P-glycoprotein (P-gp). We investigated whether these effects are related to each other and to the impact of the sterol on bilayer fluidity and verapamil membrane affinity. P-gp was reconstituted in egg-phosphatidylcholine (PhC) liposomes with or without cholesterol, 1,2-dipalmitoyl-phosphatidylcholine (DPPC), alpha-tocopherol (alpha-Toc) or 2,2,5,7,8-pentamethyl-6-chromanol (PMC). Basal and verapamil-induced ATPase activities were studied with an enzymatic assay. Membrane fluidity was characterized with diphenyl-hexatriene anisotropy measurements and membrane affinity by equilibrium dialysis. DPPC (70% mol/mol) decreased the fluidity of PhC bilayers to the same level as 20% cholesterol. PMC (20%) and alpha-Toc (20%) decreased the fluidity to lesser extents. alpha-Toc and PMC, but not DPPC increased the verapamil membrane affinity. While 20% cholesterol strikingly enhanced the basal ATPase activity, none of the other constituents had a similar effect. In contrast, verapamil stimulation of P-gp ATPase activity was not only enabled by cholesterol but also by alpha-Toc and DPPC. PMC had no effect. In conclusion, cholesterol exerts distinct effects on basal and verapamil-induced ATPase activity. The influence on basal ATPase activity is sterol-specific while its effect on verapamil-induced ATPase activity is unspecific and not related to its influence on membrane fluidity and on verapamil membrane affinity.

  1. GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells. (United States)

    Gao, Xia; Bali, Aman S; Randell, Scott H; Hogan, Brigid L M


    Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical-basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2.

  2. 英语翻转课堂促进幼师职业核心能力培养刍议%On the promotion of English flipped classroom in preschool educators’vocational core competences cultivation

    Institute of Scientific and Technical Information of China (English)



    With the high-speed development of information technology and the advent of knowledge-based economy sci-oety,the cultivation of students'vocational core competences in higher vocational colleges is of greater importance. The college English training goals are highly unified to the demands of vocational core competences.With the combination of microlecture re-sources and flipped classroom to establish a new English teaching mode-microlecture based “English flipped classroom”,has positive effects on cultivating higher vocational preschool educators’vocational core competences.%高职院校对学生职业核心能力的培养随着信息技术的高速发展以及知识经济社会的到来而愈发重要。大学英语培养目标与职业核心能力的培养需求高度统一。文章结合微课资源和翻转课堂模式建立起的新型英语教学模式———基于微课的英语翻转课堂,对高职幼师职业核心能力的培养有着积极作用。

  3. Animal MRI Core (United States)

    Federal Laboratory Consortium — The Animal Magnetic Resonance Imaging (MRI) Core develops and optimizes MRI methods for cardiovascular imaging of mice and rats. The Core provides imaging expertise,...

  4. Metazoan promoters

    DEFF Research Database (Denmark)

    Lenhard, Boris; Sandelin, Albin Gustav; Carninci, Piero


    Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters...... and their features, helping researchers who are investigating functional categories of promoters and their modes of regulation. Additional features of promoters that are being characterized include types of histone modifications, nucleosome positioning, RNA polymerase pausing and novel small RNAs. In this Review, we...... discuss recent findings relating to metazoan promoters and how these findings are leading to a revised picture of what a gene promoter is and how it works....

  5. Basal ganglia calcification on computed tomography in systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki and others


    The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis.

  6. Multiple superficial basal cell carcinomas (basalomatosis) following cobalt irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wollenberg, A.; Przybilla, B. [Muenchen Univ. (Germany). Dermatologische Klinik und Poliklinik; Peter, R.U. [Federal Armed Forces Medical Academy, Munich (Germany). Inst. of Radiobiology


    Basalomatosis is an uncommon skin condition characterized by the occurrence of multiple basal cell carcinomas. Many cases reported in the literature have been attributed to arsenic treatment in psoriasis patients. We report a patient with basalomatosis caused by cobalt-60 ({sup 60}Co) irradiation. A 55-year-old farmer developed 43 basal cell carcinomas 20 years after treatment of an immuno-blastoma with {sup 60}Co irradiation. All the tumours were located within the radiation fields. Other possible causes of basalomatosis, such as arsenic intoxication and basal cell naevus syndrome, were excluded. The patient`s multiple superficial basal cell carcinomas probably represent a late adverse effect of the {sup 60}Co irradiation. (Author).

  7. Ki-67核心启动子在胃癌SCG-991细胞中的转录活性%Identification of proximal core promoter sequences of Ki-67 gene essential for transcriptional acti vation in human gastric cancer SCG-991 cells

    Institute of Scientific and Technical Information of China (English)

    徐为; 李望; 裴冬生; 郑骏年; 宋文哲; 李圆; 张宝福; 刘俊杰; 顾玉明; 高超; 章龙珍


    目的 观察Ki-67核心启动子在人胃癌细胞中的转录活性.方法 使用缺失分析法分别从5'端和3'端对Ki-67基因启动子逐段缺失,得到不同长度的8个和3个截短DNA片段.分别插入pGL3-Basic载体后转染人胃癌SCG-991细胞,使用双荧光素酶检测系统鉴定转录活性,确定Ki-67基因核心启动子.比较Ki-67核心启动子与另2种肿瘤启动子hTERT和Survivin的转录活性.结果 自5'端缺失得到的-223~+771截短片段在SCG-991细胞内转录活性达到病毒SV40启动子活性的56.5%;自3'端缺失的-223~+30截短片段转录活性更强,为-223~+771片段活性的2.1倍,是hTERT启动子的1.7及Survivin启动子和15.3倍.结论 Ki-67核心启动子区域为-223~+30,在胃癌SCG-991细胞中的转录活性超过SV40启动子,以及hTERT启动子及Survivin启动子.%Objective To identify the proximal core promoter of Ki-67 gene and its transcriptional activities in human gastric cancer SCG-991 cells. Methods Various lengths of DNA fragments,8 of which were 5' truncations including the initiating ATG codon and 3 of which were 3' truncations encompassing the transcription initiation,were amplified by PCR from the 5' flanking sequence of Ki-67 gene and inserted into luciferase reporter vector pGL3-Basie,and tested by dual-luciferase reporter assay system to identify the core promoter essential for transcriptional activation. Then transcriptional activity of Ki-67 core promoter was compared with that of hTERT and Survivin promoter,respectively. Results The transcriptional activity of the proximal -223 ~ + 771 fragment in gastric cancer SCG-991 cells was equivalent to 56.5% of SV40 promoter/enhancer. The transcriptional activity of 3' truncations of -223~+30 fragments in SCG-991 cells was approximately 2.1-fold activity of -223~+ 771 fragments. In contrast,in normal umbilical vein epithelial cells,no significant transcriptional activity was observed in either 5' -truncated -320~+771

  8. Familial idiopathic basal ganglia calcification (Fahr’s disease)


    Mufaddel, Amir A.; Al-Hassani, Ghanem A.


    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsych...

  9. Basal Dynamics and Internal Structure of Ice Sheets (United States)

    Wolovick, Michael J.

    The internal structure of ice sheets reflects the history of flow and deformation experienced by the ice mass. Flow and deformation are controlled by processes occurring within the ice mass and at its boundaries, including surface accumulation or ablation, ice rheology, basal topography, basal sliding, and basal melting or freezing. The internal structure and basal environment of ice sheets is studied with ice-penetrating radar. Recently, radar observations in Greenland and Antarctica have imaged large englacial structures rising from near the bed that deform the overlying stratigraphy into anticlines, synclines, and overturned folds. The mechanisms that may produce these structures include basal freeze-on, travelling slippery patches at the ice base, and rheological contrasts within the ice column. In this thesis, I explore the setting and mechanisms that produce large basal stratigraphic structures inside ice sheets. First, I use radar data to map subglacial hydrologic networks that deliver meltwater uphill towards freeze-on structures in East Antarctica. Next, I use a thermomechanical flowline model to demonstrate that trains of alternating slippery and sticky patches can form underneath ice sheets and travel downstream over time. The disturbances to the ice flow field produced by these travelling patches produce stratigraphic folds resembling the observations. I then examine the overturned folds produced by a single travelling sticky patch using a kinematic flowline model. This model is used to interpret stratigraphic measurements in terms of the dynamic properties of basal slip. Finally, I use a simple local one-dimensional model to estimate the thickness of basal freeze-on that can be produced based on the supply of available meltwater, the thermal boundary conditions, ice sheet geometry, and the ice flow regime.

  10. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma. (United States)

    Torres, T; Fernandes, I; Costa, V; Selores, M


    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  11. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma


    Torres, T.; I. Fernandes; Costa, V.; Selores, M


    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  12. Reassessing Models of Basal Ganglia Function and Dysfunction


    Nelson, Alexandra B.; Kreitzer, Anatol C.


    The basal ganglia are a series of interconnected subcortical nuclei. The function and dysfunction of these nuclei has been studied intensively as it pertains to motor control, but more recently our knowledge of these functions has broadened to include prominent roles in cognition and affective control. This review will summarize historical models of basal ganglia function, findings which have supported or conflicted with these models, and emphasize recent work in animals and humans directly t...

  13. Cognitive-motor interactions of the basal ganglia in development


    Gerry eLeisman; Orit eBraun-Benjamin; Robert eMelillo


    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-bas...

  14. Basal cell carcinomas in elderly patients treated by cryotherapy. (United States)

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius


    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases.

  15. An MRI atlas of the mouse basal ganglia. (United States)

    Ullmann, Jeremy F P; Watson, Charles; Janke, Andrew L; Kurniawan, Nyoman D; Paxinos, George; Reutens, David C


    The basal ganglia are a group of subpallial nuclei that play an important role in motor, emotional, and cognitive functions. Morphological changes and disrupted afferent/efferent connections in the basal ganglia have been associated with a variety of neurological disorders including psychiatric and movement disorders. While high-resolution magnetic resonance imaging has been used to characterize changes in brain structure in mouse models of these disorders, no systematic method for segmentation of the C57BL/6 J mouse basal ganglia exists. In this study we have used high-resolution MR images of ex vivo C57BL/6 J mouse brain to create a detailed protocol for segmenting the basal ganglia. We created a three-dimensional minimum deformation atlas, which includes the segmentation of 35 striatal, pallidal, and basal ganglia-related structures. In addition, we provide mean volumes, mean T2 contrast intensities and mean FA and ADC values for each structure. This MR atlas is available for download, and enables researchers to perform automated segmentation in genetic models of basal ganglia disorders.

  16. Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

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    Mitrugno Valentina


    Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.

  17. Stratified basal diamicts and their implications for subglacial conditions in deeply incised bedrock troughs (United States)

    Buechi, Marius W.; Menzies, John; Anselmetti, Flavio S.


    Deep bedrock troughs ("tunnel valleys"), formed below Pleistocene piedmont glaciers, serve as valuable archives of the Quaternary landscape evolution of the Northern Alpine foreland basin. The sedimentary infill of these troughs is often dominated by glacier retreat deposits (e.g. glacio-lacustrine silts), while the context of diamicts and gravels at the base, i.e. directly overlying bedrock, remain controversial with regard to their deposition in a subglacial or proglacial environment. We present results from a set of drill cores that recovered such coarse-grained basal units in a major buried bedrock-trough system in the Lower Glatt Valley, Northern Switzerland. The excellent core recovery has allowed a detailed lithological study combining macroscopic, microscopic and geochemical methods. The macroscopic analysis revealed that the basal infill comprises diamicts segmented into ~1-3 m thick layers by sorted interbeds. These interbeds consist either of i) clast-supported gravels interpreted as bedload or lag deposits, or ii) laminated sands and silts representing deposition dominated by low-energy settling. The thinly spaced stacking of sorted and stratified sediments results in a high vertical facies variability. The distinct changes in the energy levels at which the sorted interbeds were transported and deposited are interpreted to indicate alternating phases of a decoupled and coupled ice-bed-interface at the base of the overdeepening. This interpretation is supported by the microstructural analysis performed on thin-sections from diamictons of the basal unit, which reveal a polyphase (brittle and ductile) deformation of the diamicts. A primary indication for a subglacial origin of the deformation comes from an abundance of crushed grains, interpreted as resulting from in-situ fracturing of grains under high tensile stresses, typically attained at grain-to-grain contacts during subglacial deformation. Such a signature is unlikely to occur in a proglacial

  18. Transcriptional directionality of the human insulin-degrading enzyme promoter. (United States)

    Zhang, Lang; Wang, Pan; Ding, Qingyang; Wang, Zhao


    Unidirectional promoters dominate among mammalian genomes. However, the mechanism through which the transcriptional directionality of promoters is accomplished remains to be clarified. Insulin-degrading enzyme (IDE) is a ubiquitously expressed zinc metalloprotease, whose promoter contains a CpG island. We previously showed that the basal promoter region of mouse IDE has bidirectional transcriptional activity, but an upstream promoter element blocks its antisense transcription. Therefore, we wonder whether the human IDE promoter contains an analogous element. Similarly, the basal promoter region of human IDE (-102 ~ +173 and -196 ~ +173 relative to the transcription start site) showed bidirectional transcriptional activity. However, the region from -348 to +173 could only be transcribed from the normal orientation, implying that an upstream promoter element between -348 and -196 blocks the antisense transcription of the human IDE promoter. Through promoter deletion and mutagenesis analysis, we mapped this element precisely and found that the upstream promoter element locates between -318 and -304. Furthermore, the transcription-blocking elements in the mouse and human IDE promoters inhibited the transcription of the SV40 promoter when put downstream of it. In conclusion, we identify an upstream promoter element which blocks the antisense transcription of the human IDE promoter. Our studies are helpful to clarify the transcriptional directionality of promoters.

  19. hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis

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    Snijders Peter JF


    Full Text Available Abstract Background Activation of telomerase resulting from deregulated hTERT expression is a key event during high-risk human papillomavirus (hrHPV-induced cervical carcinogenesis. In the present study we examined hTERT promoter activity and its relation to DNA methylation as one of the potential mechanisms underlying deregulated hTERT transcription in hrHPV-transformed cells. Methods Using luciferase reporter assays we analyzed hTERT promoter activity in primary keratinocytes, HPV16- and HPV18-immortalized keratinocyte cell lines and cervical cancer cell lines. In the same cells as well as cervical specimens we determined hTERT methylation by bisulfite sequencing analysis of the region spanning -442 to +566 (relative to the ATG and quantitative methylation specific PCR (qMSP analysis of two regions flanking the hTERT core promoter. Results We found that in most telomerase positive cells increased hTERT core promoter activity coincided with increased hTERT mRNA expression. On the other hand basal hTERT promoter activity was also detected in telomerase negative cells with no or strongly reduced hTERT mRNA expression levels. In both telomerase positive and negative cells regulatory sequences flanking both ends of the core promoter markedly repressed exogenous promoter activity. By extensive bisulfite sequencing a strong increase in CpG methylation was detected in hTERT positive cells compared to cells with no or strongly reduced hTERT expression. Subsequent qMSP analysis of a larger set of cervical tissue specimens revealed methylation of both regions analyzed in 100% of cervical carcinomas and 38% of the high-grade precursor lesions, compared to 9% of low grade precursor lesions and 5% of normal controls. Conclusions Methylation of transcriptionally repressive sequences in the hTERT promoter and proximal exonic sequences is correlated to deregulated hTERT transcription in HPV-immortalized cells and cervical cancer cells. The detection of DNA

  20. Phylogenetic distribution of microRNAs supports the basal position of acoel flatworms and the polyphyly of Platyhelminthes. (United States)

    Sempere, Lorenzo F; Martinez, Pedro; Cole, Charles; Baguñà, Jaume; Peterson, Kevin J


    Phylogenetic analyses based on gene sequences suggest that acoel flatworms are not members of the phylum Platyhelminthes, but instead are the most basal branch of triploblastic bilaterians. Nonetheless, this result has been called into question. An alternative test is to use qualitative molecular markers that should, in principle, exclude the possibility of convergent (homoplastic) evolution in unrelated groups. microRNAs (miRNAs), noncoding regulatory RNA molecules that are under intense stabilizing selection, are a newly discovered set of phylogenetic markers that can resolve such taxonomic disputes. The acoel Childia sp. has recently been shown to possess a subset of the conserved core of miRNAs found across deuterostomes and protostomes, whereas a polyclad flatworm-in addition to this core subset-possesses miRNAs restricted to just protostomes. Here, we examine another acoel, Symsagittifera roscoffensis, and three other platyhelminths. Our results show that the distribution of miRNAs in S. roscoffensis parallels that of Childia. In addition, two of 13 new miRNAs cloned from a triclad flatworm are also found in other lophotrochozoan protostomes, but not in ecdysozoans, deuterostomes, or in basal metazoans including acoels. The limited set of miRNAs found in acoels, intermediate between the even more reduced set in cnidarians and the larger and expanding set in the rest of bilaterians, is compelling evidence for the basal position of acoel flatworms and the polyphyly of Platyhelminthes.

  1. Cognitive-Motor Interactions of the Basal Ganglia in Development

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    Gerry eLeisman


    Full Text Available Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia are also crucial elements in the circuits that confer human reasoning and adaptive function and are key elements in the control of reward-based learning, sequencing, discrete elements that constitute complete motor acts, and cognitive function. Imaging studies of intact humans and electrophysiologic studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to ADHD with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition.

  2. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns. (United States)


    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  3. Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation (United States)

    Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.


    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  4. k-core covers and the core

    NARCIS (Netherlands)

    Sanchez-Rodriguez, E.; Borm, Peter; Estevez-Fernandez, A.; Fiestras-Janeiro, G.; Mosquera, M.A.


    This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

  5. Academic Rigor: The Core of the Core (United States)

    Brunner, Judy


    Some educators see the Common Core State Standards as reason for stress, most recognize the positive possibilities associated with them and are willing to make the professional commitment to implementing them so that academic rigor for all students will increase. But business leaders, parents, and the authors of the Common Core are not the only…

  6. Activation of BmGSTd1 promoter and regulation by transcription factor Krüppel (Kr) in silkworm, Bombyx mori. (United States)

    Zhao, Guodong; Wang, Binbin; Liu, Yunlei; Du, Jie; Li, Bing; Chen, Yuhua; Xu, Yaxiang; Shen, Weide; Xia, Qingyou; Wei, Zhengguo


    The Glutathione S-transferases (GSTs) are a large family of multifunctional enzymes, many of which play an important role in the detoxification of endogenous and exogenous toxic substances. In this research, firstly, we measured the rutin-induced transcriptional level of BmGSTd1 gene by using real-time quantitative RT-PCR method and dual spike-in strategy. The activities of the BmGSTd1 promoter in various tissues of silkworm were measured by firefly luciferase activity and normalized by the Renilla luciferase activity. Results showed that the activity of the BmGSTd1 promoter were highest in Malpighian tubule, followed by fat body, silk gland, hemocyte, epidermis, and midgut. The essential region for basal and rutin-induced transcriptional activity was -1573 to -931bp in Malpighian tubule and fat body of silkworm. Promoter truncation analysis using a dual-luciferase reporter assay in BmN cells showed that the region -1288 to -1202bp for BmGSTd1 gene was essential for basal and rutin-induced transcriptional activity. Sequence analysis of this region revealed several potential transcriptional regulatory elements such as Bcd and Kr. The mutation of core base of Kr site demonstrated that Kr functioned positively in rutin-mediated BmGSTd1 transcription.

  7. Evaluating Community Health Advisor (CHA) Core Competencies: The CHA Core Competency Retrospective Pretest/Posttest (CCCRP). (United States)

    Story, Lachel; To, Yen M


    Health care and academic systems are increasingly collaborating with community health advisors (CHAs) to provide culturally relevant health interventions that promote sustained community transformation. Little attention has been placed on CHA training evaluation, including core competency attainment. This study identified common CHA core competencies, generated a theoretically based measure of those competencies, and explored psychometric properties of that measure. A concept synthesis revealed five CHA core competencies (leadership, translation, guidance, advocacy, and caring). The CHA Core Competency Retrospective Pretest/Posttest (CCCRP) resulted from that synthesis, which was administered using multiple approaches to individuals who previously received CHA training (N= 142). Exploratory factor analyses revealed a two-factor structure underlying the posttraining data, and Cronbach's alpha indicated high internal consistency. This study suggested some CHA core competencies might be more interrelated than previously thought, and two major competencies exist rather than five and supported the CCCRP's use to evaluate core competency attainment resulting from training.

  8. Basal cell carcinomas in elderly patients treated by cryotherapy

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    Chiriac A


    Full Text Available Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain can be applied and resolve such cases. Keywords: basal cell carcinoma, cryotherapy

  9. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

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    Birgül Tepe


    Full Text Available Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic factor except for chronic sunlight exposure. The aim of our report is to show that this prevalant cutaneous malignancy can be encountered in rare/unusual areas. (Turk J Dermatol 2012; 6: 51-4

  10. Multiple jaw cysts not associated with basal cell nevus syndrome

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    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)


    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  11. Computed tomography of granulomatous basal meningitis caused by pneumococcus

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    Sonobe, Makoto; Takahashi, Shinichiro (Mito National Hospital, Ibaraki (Japan)); Ohara, Kazuo


    A case of 3-month-old female with ''granulomatous basal meningitis'' caused by pneumococcus was described. She suffered from high fever, vomiting, convulsion and loss of consciousness on January 28th, 1982. On admission the protein content of the spinal fluid was 280 mg/100 ml, the glucose 4 mg/100 ml and the cell count was 1206/3(L : 845, N : 361). Her symptoms and signs were deteriorated in spite of antibiotics and anticonvulsants. CT scan on the 10th day showed the enhanced basal cistern. She died on the 11th day but autopsy was not carried out. In this case, pneumococcus was cultured in CSF. This seemed to be the first case of ''granulomatous basal meningitis'' due to purulent meningitis in Japan.

  12. A population level computational model of the basal ganglia that generates parkinsonian Local Field Potential activity. (United States)

    Tsirogiannis, George L; Tagaris, George A; Sakas, Damianos; Nikita, Konstantina S


    Recordings from the basal ganglia's subthalamic nucleus are acquired via microelectrodes immediately prior to the application of Deep Brain Stimulation (DBS) treatment for Parkinson's Disease (PD) to assist in the selection of the final point for the implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality-effect relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest a pivotal role of both of these parameters to the pathophysiology of PD.

  13. Kinome expression profiling and prognosis of basal breast cancers

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    Jacquemier Jocelyne


    Full Text Available Abstract Background Basal breast cancers (BCs represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES. Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling. Methods DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set. Results A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73. This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518 sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test. Conclusions Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.

  14. Molecular characterization of Italian nevoid basal cell carcinoma syndrome patients. (United States)

    Pastorino, L; Cusano, R; Nasti, S; Faravelli, F; Forzano, F; Baldo, C; Barile, M; Gliori, S; Muggianu, M; Ghigliotti, G; Lacaita, M G; Lo Muzio, L; Bianchi-Scarra, G


    Mutations in the PTCH gene, the human homolog of the Drosophila patched gene, have been found to lead to the autosomal dominant disorder termed Nevoid Basal Cell Carcinoma Syndrome (NBCCS, also called Gorlin Syndrome). Patients display an array of developmental anomalies and are prone to develop a variety of tumors, with multiple Basal Cell Carcinomas occurring frequently. We provide here the results of molecular testing of a set of Italian Nevoid Basal Cell Carcinoma Syndrome patients. Twelve familial patients belonging to 7 kindreds and 5 unaffected family members, 6 non-familial patients and an additional set of 7 patients with multiple Basal Cell Carcinoma but no other criteria for the disease were examined for mutations in the PTCH gene. All of the Nevoid Basal Cell Carcinoma Syndrome patients were found to carry variants of the PTCH gene. We detected nine novel mutations (1 of which occurring twice): 1 missense mutation (c.1436T>G [p.L479R]), 1 nonsense mutation (c.1138G>T [p.E380X]), 6 frameshift mutations (c.323_324ins2, c.2011_2012dup, c.2535_2536dup, c.2577_2583del, c.3000_3005del, c.3050_3051del), 1 novel splicing variant (c.6552A>T) and 3 mutations that have been previously reported (c.3168+5G>A, c.1526G>T [p.G509V], and c.3499G>A [p.G1167R]). None of the patients with multiple Basal Cell Carcinoma but no other criteria for the syndrome, carried germline coding region mutations.

  15. A review of stand basal area growth models

    Institute of Scientific and Technical Information of China (English)

    Sun Hong-gang; Zhang Jian-guo; Duan Ai-guo; He Cai-yun


    Growth and yield modeling has a long history in forestry. The methods of measuring the growth of stand basal area have evolved from those developed in the U.S.A. and Germany during the last century. Stand basal area modeling has progressed rapidly since the first widely used model was published by the U.S. Forest Service. Over the years, a variety of models have been developed for predicting the growth and yield of uneven/even-aged stands using stand-level approaches. The modeling methodology has not only moved from an empirical approach to a more ecological process-based approach but also accommodated a variety of techniques such as: 1) simultaneous equation methods, 2) difference models, 3) artificial neural network techniques, 4) linear/nonlinear regression models, and 5) matrix models. Empirical models using statistical methods were developed to reproduce accurately and precisely field observations. In contrast, process models have a shorter history, developed originally as research and education tools with the aim of increasing the understanding of cause and effect relationships. Empirical and process models can be married into hybrid models in which the shortcomings of both component approaches can, to some extent, be overcome. Algebraic difference forms of stand basal area models which consist of stand age, stand density and site quality can fully describe stand growth dynamics. This paper reviews the current literature regarding stand basal area models, discusses the basic types of models and their merits and outlines recent progress in modeling growth and dynamics of stand basal area. Future trends involving algebraic difference forms, good fitting variables and model types into stand basal area modeling strategies are discussed.

  16. Promoter analysis and RNA interference of CYP6ab4 in the silkworm Bombyx mori. (United States)

    Zhao, Guo-Dong; Zhang, Yi-Ling; Liu, Yun-Lei; Li, Bing; Chen, Yu-Hua; Xu, Ya-Xiang; Xia, Qing-You; Shen, Wei-De; Wei, Zheng-Guo


    In insects, cytochrome P450 monooxygenases (P450s) are involved in the metabolism of endogenous compounds such as steroid hormones and lipids. In this study, we measured the 20-hydroxyecdysone (20E)-induced transcriptional level of the CYP6ab4 gene using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) with a dual spike-in strategy. We then probed possible physiological functions using RNAi experiments in the silkworm Bombyx mori. The activity of the CYP6ab4 promoter in various silkworm tissues was measured by firefly luciferase activity and normalized by Renilla luciferase activity. Our results showed that the activity of the CYP6ab4 promoter was highest in the malpighian tubule, followed by the fat body, the silk gland, the midgut, the epidermis, and the hemocyte. The essential region for basal and 20E-induced transcriptional activity was between -908 and -456 bp from the transcription start site. Through promoter truncation analysis using a dual-luciferase reporter assay in B. mori ovary cells (BmN), we showed that the region between -827 and -722 bp was essential for basal and 20E-induced transcriptional activity. Sequence analysis of this region revealed several potential transcriptional regulatory elements such as Hunchback (Hb) and BR-C Z. Mutation of the core bases of the BR-C Z binding site demonstrated that BR-C Z induces 20E-mediated CYP6ab4 transcription. Further identification of cis- and trans-elements and their roles in the upregulation of CYP6ab4 may be useful for elucidating the contribution of P450 to the response mechanism to 20E.

  17. Nevoid Basal Cell Carcinoma Syndrome : A Case Report

    Directory of Open Access Journals (Sweden)

    K Rajanikanth


    Full Text Available The nevoid basal cell carcinoma syndrome (NBCCS or Gorlin - Goltz syndrome is an autosomal disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The major organ systems involved are skin, bones, central nervous system, eyes, gonads and endocrine. This particular syndrome is extensively described in the literature under different names. However, there are only few cases reported in the Indian literature. An unusual case of a 33-year old male with large odontogenic keratocyst involving impacted canine in the mandible, along with multiple cysts and impacted teeth in the maxilla; bifid rib and vertebral anomalies has been described.

  18. Professional Preparation in Health Promotion. (United States)

    Hill, Charles E.; Fisher, Shirley P.


    Colleges and universities must develop curricula to prepare health promotion specialists to work with persons of all ages. Program core should include self-care, consumer awareness, nutrition, weight control, stress management, and substance abuse. Health and physical educators should learn to facilitate change of negative health behaviors into…

  19. On Promoting the Core Competence of Cultural Tourism Industry in Hebei Province%提升河北省文化旅游产业核心竞争力的思考

    Institute of Scientific and Technical Information of China (English)

    苏晓丽; 蒋再松; 杜立文; 王登才


    新兴文化旅游业是河北省发展绿色经济,实现“绿色崛起”的重要途径。梳理了河北省内各地区文化旅游资源,在分析文化旅游产业发展的基础上,提出提升河北省文化旅游业竞争力要关注旅游者消费理念和方式的转变,有针对性地开拓市场;以现代营销理念宣传特色文化旅游品牌,建立消费者对旅游品牌的忠诚度;实施差异化战略,统筹发展,加强各行业和地区的联动;利用现代信息技术打造立体化旅游渠道,开发“情境旅游”;发挥旅游地高校文化传播力和影响力的措施。%Emerging cultural tourism is an important way for the development of green economy in Hebei Province. On the basis of analyzing cultural tourism resources in HeBei Province, the paper came up with the following sugges- tions on promoting cultural tourism competitiveness in Hebei province: paying attention to the transformation of tourist consumption concept and means and developing targeted market; promoting feature tourism through modem marketing and establish consumer' s loyalty; Implementing differentiation Strategy to coordinate the tourism development with other industries in different areas ; developing three-dimensional "situational tourism" via modem information technol- nov. develonin~ the roles of the colleges and universities in tourism destinations.

  20. "Meng Wa" Non-commercial Advertising:The Designing Strategy to Promote Socialist Core Values%“梦娃”公益广告传播社会主义核心价值观的创作策略

    Institute of Scientific and Technical Information of China (English)



    “梦娃”公益广告传播效果好,社会主义核心价值理念随“梦娃”萌动可爱的形象植入受众心中。从创作视角来看,“梦娃”系列公益广告体现出情节故事化、元素民族化、哲理通俗化、形式动画化等典型特点,为公益广告的创作提供了值得借鉴的经验。%The"Meng Wa" ( a baby symbolizing the Chinese Dream) series non-commercial advertising has produced favorable effects, as the socialist core values, along with the cute"Meng Wa", have found their way ever deeper into the hearts of the people. From the perspective of advertising design, the Meng Wa series have the characteristics of story-telling plots, ethnic elements, easy-to-understand philosophy, and animated forms, which is a good example of a successful non-commercial advertisement.

  1. Health Promotion

    DEFF Research Database (Denmark)

    Povlsen, Lene; Borup, I.


    In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...... - an associate professorship was established with a focus on health promotion. Nevertheless, the concept of health promotion had been integrated with or mentioned in courses run prior to the new post. Subsequently, a wide spectrum of courses in health promotion was introduced, such as Empowerment for Child...

  2. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P


    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  3. Experience on research and development of core information and public education materials for promotion of HIV testing among MSM%促进MSM艾滋病检测核心信息及宣传教育材料研制体会

    Institute of Scientific and Technical Information of China (English)

    马瞧勤; 周欣; 蔡高峰; 潘晓红; 姚丹


    目的 开发促进男男性行为人群(MSM)艾滋病检测核心信息及宣传材料,促使更多的MSM接受检测.方法 通过文献及相关调查数据阅读,MSM个人访谈和小组访谈,Delphi法专家咨询,研发促进MSM艾滋病检测的核心信息.在宣传材料设计和制作过程中,专业人员和目标人群始终参与,并通过咨询访谈,充分考虑目标人群的意见.在专家和MSM中开展对开发过程科学性的论证及对研发的小册子和海报宣传效果的评估.结果 专家们认为开发过程科学合理,专家与MSM对开发的宣传材料评价普遍较好,在插图与文字内容一致性、吸引力、艺术性与美感、实效性方面,小册子14条信息及插图、海报等专家评价平均分值为4.3~4.6分,MSM评价平均分值为4.3~4.5分.结论 艾滋病核心信息及宣传教育材料开发制作需遵循一定的科学流程,并需对开发的宣传材料的宣传效果开展评价.%Objective To develop core information and publicity materials to promote HIV testing among men who have sex with men (MSM).Methods The core information for promotion of HIV testing among MSM was developed through reviews of literature and surveillance data,individual interview,group interview and Delphi interview.Professional staff and MSM participated in the whole process of design.Counseling and interviews were conducted to listen to the opinions of MSM on the designed publicity materials.Scientific evaluation on the development process of the core information and publicity material,and the education effects of the developed pamphlet and poster were conducted among experts and MSM.Results The experts believed that the processes of the development for core information and publicity were scientific and reasonable.Both experts and MSM spoke highly of the effects of developed education materials.With respects to the consistency of information with illustration,attraction,aesthetic perception and arts,actual effects

  4. Comodules over semiperfect corings

    CERN Document Server

    Caenepeel, S


    We discuss when the Rat functor associated to a coring satisfying the left $\\alpha$-condition is exact. We study the category of comodules over a semiperfect coring. We characterize semiperfect corings over artinian rings and over qF-rings.

  5. Coring Sample Acquisition Tool (United States)

    Haddad, Nicolas E.; Murray, Saben D.; Walkemeyer, Phillip E.; Badescu, Mircea; Sherrit, Stewart; Bao, Xiaoqi; Kriechbaum, Kristopher L.; Richardson, Megan; Klein, Kerry J.


    A sample acquisition tool (SAT) has been developed that can be used autonomously to sample drill and capture rock cores. The tool is designed to accommodate core transfer using a sample tube to the IMSAH (integrated Mars sample acquisition and handling) SHEC (sample handling, encapsulation, and containerization) without ever touching the pristine core sample in the transfer process.

  6. On the nature of the dirty ice at the bottom of the GISP2 ice core (United States)

    Bender, Michael L.; Burgess, Edward; Alley, Richard B.; Barnett, Bruce; Clow, Gary D.


    We present data on the triple Ar isotope composition in trapped gas from clean, stratigraphically disturbed ice between 2800 and 3040m depth in the GISP2 ice core, and from basal dirty ice from 3040 to 3053m depth. We also present data for the abundance and isotopic composition of O2 and N2, and abundance of Ar, in the basal dirty ice. The Ar/N2 ratio of dirty basal ice, the heavy isotope enrichment (reflecting gravitational fractionation), and the total gas content all indicate that the gases in basal dirty ice originate from the assimilation of clean ice of the overlying glacier, which comprises most of the ice in the dirty bottom layer. O2 is partly to completely depleted in basal ice, reflecting active metabolism. The gravitationally corrected ratio of 40Ar/38Ar, which decreases with age in the global atmosphere, is compatible with an age of 100-250ka for clean disturbed ice. In basal ice, 40Ar is present in excess due to injection of radiogenic 40Ar produced in the underlying continental crust. The weak depth gradient of 40Ar in the dirty basal ice, and the distribution of dirt, indicate mixing within the basal ice, while various published lines of evidence indicate mixing within the overlying clean, disturbed ice. Excess CH4, which reaches thousands of ppm in basal dirty ice at GRIP, is virtually absent in overlying clean disturbed ice, demonstrating that mixing of dirty basal ice into the overlying clean ice, if it occurs at all, is very slow. Order-of-magnitude estimates indicate that the mixing rate of clean ice into dirty ice is sufficient to maintain a steady thickness of dirty ice against thinning from the mean ice flow. The dirty ice appears to consist of two or more basal components in addition to clean glacial ice. A small amount of soil or permafrost, plus preglacial snow, lake or ground ice could explain the observations.

  7. On the nature of the dirty ice at the bottom of the GISP2 ice core (United States)

    Bender, Michael L.; Burgess, Edward; Alley, Richard B.; Barnett, Bruce; Clow, Gary D.


    We present data on the triple Ar isotope composition in trapped gas from clean, stratigraphically disturbed ice between 2800 and 3040 m depth in the GISP2 ice core, and from basal dirty ice from 3040 to 3053 m depth. We also present data for the abundance and isotopic composition of O 2 and N 2, and abundance of Ar, in the basal dirty ice. The Ar/N 2 ratio of dirty basal ice, the heavy isotope enrichment (reflecting gravitational fractionation), and the total gas content all indicate that the gases in basal dirty ice originate from the assimilation of clean ice of the overlying glacier, which comprises most of the ice in the dirty bottom layer. O 2 is partly to completely depleted in basal ice, reflecting active metabolism. The gravitationally corrected ratio of 40Ar/ 38Ar, which decreases with age in the global atmosphere, is compatible with an age of 100-250 ka for clean disturbed ice. In basal ice, 40Ar is present in excess due to injection of radiogenic 40Ar produced in the underlying continental crust. The weak depth gradient of 40Ar in the dirty basal ice, and the distribution of dirt, indicate mixing within the basal ice, while various published lines of evidence indicate mixing within the overlying clean, disturbed ice. Excess CH 4, which reaches thousands of ppm in basal dirty ice at GRIP, is virtually absent in overlying clean disturbed ice, demonstrating that mixing of dirty basal ice into the overlying clean ice, if it occurs at all, is very slow. Order-of-magnitude estimates indicate that the mixing rate of clean ice into dirty ice is sufficient to maintain a steady thickness of dirty ice against thinning from the mean ice flow. The dirty ice appears to consist of two or more basal components in addition to clean glacial ice. A small amount of soil or permafrost, plus preglacial snow, lake or ground ice could explain the observations.

  8. 对标外资银行,提升中资银行交易银行业务的核心竞争力%Foreign BanksBenchmarked in Promoting Chinese- Funded Banks' Core Competencein Transactional Banking Businesses

    Institute of Scientific and Technical Information of China (English)



    做大做强现金管理和贸易融资等交易银行业务,转变经营模式,已成为国内很多商业银行应对利率市场化的共同选择。然而与外资银行的领先实践相比,中资银行在全球服务能力、服务质量和专业化水平等方面差距明显。本文通过对标外资银行,阐述了打造中资银行交易银行业务核心竞争力的路径,并提出明确战略核心定位、做好顶层设计、加强客户管理、完善产品创新机制、加强队伍建设等方面的建议。%Strengthening cash management and trade finance and other transactional banking businesses, along with changing management mode have become many domestic commercial banks' common choices in response to interest rate's marketization. However, compared with foreign Banks' leading practice, Chinese banks still have a long way to go in aspects like global service ability, service quality, professional level and etc. . With foreign banks as the benchmark,this paper expounds how to build the core competitiveness of Chinese banks in their transactional banking businesses and gives suggestions on how to clarify the strategic positioning, complete the top-level design, strengthen the customer man⁃agement, improve product innovation mechanism, and strengthen the team construction and etc.

  9. Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review (United States)

    Cohen, Philip R


    Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer. PMID:27738570

  10. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases (United States)

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama


    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936


    DEFF Research Database (Denmark)

    Buzgo, Matyas; Soltis, Douglas E.; Soltis, Pamela S.;


    Basal monocots exhibit considerable variation in inflorescence and floral structure. In some cases, such as Triglochin maritima, it is not clear whether the lateral and terminal structures of the inflores- cence are flowers or pseudanthia, or where the limits between flowers and inflorescence lie...

  12. Utilizing Psycholinguistic Insights in Teaching via the Basal Reader. (United States)

    Newman, Harold

    Ideas of educational psycholinguists Frank Smith and Kenneth Goodman can be combined with the ideas presented in current basal reader manuals to help teachers teach reading more effectively. Since reading and speaking are parallel processes, teachers may invite children to "read" with them, hearing the melody of language as they point to…

  13. Saccade learning with concurrent cortical and subcortical basal ganglia loops

    Directory of Open Access Journals (Sweden)

    Steve eN'guyen


    Full Text Available The Basal Ganglia is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks.We propose a model of saccade generation with reinforcement learning capabilities based onour previous basal ganglia and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of thesaccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks.The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not. Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate.

  14. Basal ganglia play a crucial role in decision making


    Thibaut, Florence


    Many studies have suggested that the striatum, located at the interface of the cortico-basal ganglia-thalamic circuit, consists of separate circuits that serve distinct functions It plays an important role in motor planning, value processing, and decision making.

  15. Normal sexual dimorphism in the human basal ganglia.

    NARCIS (Netherlands)

    Rijpkema, M.J.P.; Everaerd, D.S.; Pol, C.; Franke, B.; Tendolkar, I.; Fernandez, G.S.E.


    Male and female brains differ in both structure and function. Investigating this sexual dimorphism in healthy subjects is an important first step to ultimately gain insight into sex-specific differences in behavior and risk for neuropsychiatric disorders. The basal ganglia are among the main regions

  16. [Successful therapy of metastatic basal cell carcinoma with vismodegib]. (United States)

    Zutt, M; Mazur, F; Bergmann, M; Lemke, A J; Kaune, K M


    A 71-year-old man presented with giant basal cell carcinoma on the abdomen which had metastasized. He was treated with oral vismodegib. Both the primary ulcerated tumor on the abdomen and the metastases responded. Vismodegib was well tolerated without significant side effects. The tumor recurred promptly after vismodegib was discontinued, and then was resistant to therapy when vismodegib was re-administered.

  17. Soil CO2 efflux in a sand grassland: contribution by root, mycorrhizal and basal respiration components (United States)

    Papp, Marianna; Balogh, János; Pintér, Krisztina; Cserhalmi, Dóra; Nagy, Zoltán


    Grasslands play an important role in global carbon cycle because of their remarkable extension and carbon storage capacity. Soil respiration takes a major part in the carbon cycle of the ecosystems; ratio of its autotrophic and heterotrophic components is important also when considering their sensitivity to environmental drivers. The aim of the study was to estimate the contribution by root, mycorrhizal and basal components to total soil CO2 efflux. The study was carried out in the semi-arid sandy grassland dominated by Festuca pseudovina at the Kiskunság National Park in Hungary (Bugac site) where C-flux measurements have been going on since 2002. The soil CO2 effluxes were measured in the following treatments: a./ control, b./ root-exclusion, c./ root and mycorrhiza exclusion by using 80 cm long 15 cm inner diameter PVC tubes and micro-pore inox meshes. Inox mesh was used to exclude roots, but let the mycorrhiza filaments to grow into the tubes. 10 soil cores were excavated, sieved, then root-free soil was packed back layer by layer into the cores giving 6 and 4 repetitions in b and c treatments respectively. Basal respiration is referred to as the heterotrophic respiration without influence of roots or mycorrhiza. Difference between root-exclusion and root and mycorrhiza exclusion treatment gave the value of mycorrhizal respiration and control (non-disturbed) plots the total soil CO2 efflux. The contribution by the above components was evaluated. Soil CO2 efflux was measured continuously by using an automated open system of 10 soil respiration chambers. Data was collected in every two hours from each treatment (one of the chambers recorded basal respiration, 3 chambers were settled on root-excluded treatments and 6 chambers measured control plots). Chambers were moved in every 2 weeks between the repetitions of the treatments. Soil CO2 efflux (mycorrhiza-free, root free, control) data were fitted using a soil respiration model, where soil temperature, soil

  18. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells. (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas


    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.

  19. 以育人、用人为核心,推进科学人才观制度建设%Promoting the Construction of Scientific Outlook on Tal-ents with Talent Cultivation and Employment as the Core

    Institute of Scientific and Technical Information of China (English)


    Good talent cultivation and employment is the funda-mental approach to realize the strategy of reinvigorating China through human resource development. In the current phase, some phenomena of disharmony to economic and social development still exist in talent cultivation and employment. Commanding tal-ent work with scientific outlook on talents, reforming the system of college entrance examination from two aspects—talent cultivation and employment, promoting the reform of talent work system, in-novating talent selection, evaluation and flow systems and creat-ing a fair and harmonious talent employment environment have great significance for realizing economic transition and sustain-able development of the nation.%  育好人才,用好人才,是实现人才强国战略的根本途径。现阶段,在育人、用人方面仍存在一些与经济社会发展不相适应的现象,以科学人才观统领人才工作,从育人、用人两方面着手,改革高考制度,推进人才工作制度改革,创新人才选拔、评价、流动制度,营造公平和谐的用人环境,对实现经济转型、国家持续发展意义重大。

  20. Promoting university laboratory connotation development by the core of team construction%以队伍建设为抓手 促进高校实验室内涵发展

    Institute of Scientific and Technical Information of China (English)



    在论述实验队伍建设与实验室内涵发展关系的基础上,强调了实验队伍建设的重要性,并提出了改善实验工作环境,提升实验教学岗位的吸引力;改善管理,调动实验队伍的积极性,挖掘他们的创造力;把实验队伍建设纳入学校建设与发展的整体规划;把实验室的发展作为校长业绩考核的一项重要指标等措施。%To begin with,based on the relation between laboratory team construction and laboratory connotation development,the significances of laboratory team construction are emphasized,and advices that experimental work environment and laboratory education post attraction should be promoted are pointed out.Then relative recommendations are described.Management should be modified,and the initiative and creativity of laboratory team should be stimulated.Moreover,referring to university construction and development of overall planning,laboratory team construction should be noticed.Last but not least,the status of laboratory connotation development should be taken as the indicator of the principal performance evaluation.

  1. Basal jawed vertebrate phylogenomics using transcriptomic data from Solexa sequencing.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available The traditionally accepted relationships among basal jawed vertebrates have been challenged by some molecular phylogenetic analyses based on mitochondrial sequences. Those studies split extant gnathostomes into two monophyletic groups: tetrapods and piscine branch, including Chondrichthyes, Actinopterygii and sarcopterygian fishes. Lungfish and bichir are found in a basal position on the piscine branch. Based on transcriptomes of an armored bichir (Polypterus delhezi and an African lungfish (Protopterus sp. we generated, expressed sequences and whole genome sequences available from public databases, we obtained 111 genes to reconstruct the phylogenetic tree of basal jawed vertebrates and estimated their times of divergence. Our phylogenomic study supports the traditional relationship. We found that gnathostomes are divided into Chondrichthyes and the Osteichthyes, both with 100% support values (posterior probabilities and bootstrap values. Chimaeras were found to have a basal position among cartilaginous fishes with a 100% support value. Osteichthyes were divided into Actinopterygii and Sarcopterygii with 100% support value. Lungfish and tetrapods form a monophyletic group with 100% posterior probability. Bichir and two teleost species form a monophyletic group with 100% support value. The previous tree, based on mitochondrial data, was significantly rejected by an approximately unbiased test (AU test, p = 0. The time of divergence between lungfish and tetrapods was estimated to be 391.8 Ma and the divergence of bichir from pufferfish and medaka was estimated to be 330.6 Ma. These estimates closely match the fossil record. In conclusion, our phylogenomic study successfully resolved the relationship of basal jawed vertebrates based on transtriptomes, EST and whole genome sequences.

  2. Calving fluxes and basal melt rates of Antarctic ice shelves. (United States)

    Depoorter, M A; Bamber, J L; Griggs, J A; Lenaerts, J T M; Ligtenberg, S R M; van den Broeke, M R; Moholdt, G


    Iceberg calving has been assumed to be the dominant cause of mass loss for the Antarctic ice sheet, with previous estimates of the calving flux exceeding 2,000 gigatonnes per year. More recently, the importance of melting by the ocean has been demonstrated close to the grounding line and near the calving front. So far, however, no study has reliably quantified the calving flux and the basal mass balance (the balance between accretion and ablation at the ice-shelf base) for the whole of Antarctica. The distribution of fresh water in the Southern Ocean and its partitioning between the liquid and solid phases is therefore poorly constrained. Here we estimate the mass balance components for all ice shelves in Antarctica, using satellite measurements of calving flux and grounding-line flux, modelled ice-shelf snow accumulation rates and a regional scaling that accounts for unsurveyed areas. We obtain a total calving flux of 1,321 ± 144 gigatonnes per year and a total basal mass balance of -1,454 ± 174 gigatonnes per year. This means that about half of the ice-sheet surface mass gain is lost through oceanic erosion before reaching the ice front, and the calving flux is about 34 per cent less than previous estimates derived from iceberg tracking. In addition, the fraction of mass loss due to basal processes varies from about 10 to 90 per cent between ice shelves. We find a significant positive correlation between basal mass loss and surface elevation change for ice shelves experiencing surface lowering and enhanced discharge. We suggest that basal mass loss is a valuable metric for predicting future ice-shelf vulnerability to oceanic forcing.

  3. The non-active stellar chromosphere: Ca II basal flux (United States)

    Pérez Martínez, M. I.; Schröder, K.-P.; Hauschildt, P.


    We analyse high-resolution, high-s/n European Southern Observatories (ESO)-archive spectra (from UVES, the UV echelle spectrograph) of 76 inactive or modestly active stars of spectral type G to M, main sequence and giants. Using PHOENIX model photospheres with Ca II K lines that match the observed line profiles, we (i) revise the effective temperatures, (ii) obtain a precise surface flux scale for each star and (iii) directly determine the exact surface fluxes of each Ca II K chromospheric emission with respect to the photospheric line profile. We find that our stellar sample exhibits a lower boundary to its chromospheric surface flux distribution with an unprecedented definition. From a subsample of the 25 least active stars, we obtain a simple empirical formula for the basal Ca II flux as a function of effective temperature: log {F^basal_{Ca II(H+K)}} = 7.05(± 0.31) log {T_eff} - 20.86(± 1.15). This is in good agreement with the Mg II basal flux. In a direct comparison with the large body of Mt Wilson S-measurements of the chromospheric Ca II emission and its well-defined cut-off, excellent agreement is achieved as well. A new result, however, is the small scatter of the least active star's fluxes about the basal flux. It is about 25 per cent and equals the residual uncertainties of our approach. At the same time, we do not find any evidence for a gravity dependence within these limits. This strongly confirms the basal flux as a well-defined and universal phenomenon, which characterizes every inactive chromosphere.

  4. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats. (United States)

    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O


    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  5. Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex. (United States)

    Wong, Fong Kuan; Fei, Ji-Feng; Mora-Bermúdez, Felipe; Taverna, Elena; Haffner, Christiane; Fu, Jun; Anastassiadis, Konstantinos; Stewart, A Francis; Huttner, Wieland B


    The evolutionary expansion of the neocortex in mammals has been linked to enlargement of the subventricular zone (SVZ) and increased proliferative capacity of basal progenitors (BPs), notably basal radial glia (bRG). The transcription factor Pax6 is known to be highly expressed in primate, but not mouse, BPs. Here, we demonstrate that sustaining Pax6 expression selectively in BP-genic apical radial glia (aRG) and their BP progeny of embryonic mouse neocortex suffices to induce primate-like progenitor behaviour. Specifically, we conditionally expressed Pax6 by in utero electroporation using a novel, Tis21-CreERT2 mouse line. This expression altered aRG cleavage plane orientation to promote bRG generation, increased cell-cycle re-entry of BPs, and ultimately increased upper-layer neuron production. Upper-layer neuron production was also increased in double-transgenic mouse embryos with sustained Pax6 expression in the neurogenic lineage. Strikingly, increased BPs existed not only in the SVZ but also in the intermediate zone of the neocortex of these double-transgenic mouse embryos. In mutant mouse embryos lacking functional Pax6, the proportion of bRG among BPs was reduced. Our data identify specific Pax6 effects in BPs and imply that sustaining this Pax6 function in BPs could be a key aspect of SVZ enlargement and, consequently, the evolutionary expansion of the neocortex.

  6. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Jain S


    Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

  7. How Rhetorical Theories of Genre Address Common Core Writing Standards (United States)

    Collin, Ross


    This article begins with a review of the forms of writing promoted in the Common Core State Standards. Across content areas, Common Core encourages teachers to attune students' writing to rhetorical concerns of audience, purpose, task, and disciplinary thinking. To address these concerns, teachers might take a rhetorical approach to the study…

  8. Basal Cell Carcinoma: From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease

    Directory of Open Access Journals (Sweden)

    Daniela Göppner


    Full Text Available Due to intensified research over the past decade, the Hedgehog (HH pathway has been identified as a pivotal defect implicated in roughly 25% of all cancers. As one of the most frequent cancer worldwide, the development of Basal cell carcinoma (BCC due to activation of the HH pathway has been convincingly demonstrated. Thus the discovery of this central tumor-promoting signalling pathway has not only revolutionized the understanding of BCC carcinogenesis but has also enabled the development of a completely novel therapeutic approach. Targeting just a few of several potential mutations, HH inhibitors such as GDC-0449 achieved already the first promising results in metastatic or locally advanced BCC. This paper summarizes the current understanding of BCC carcinogenesis and describes the current “mechanism-based” therapeutic strategies.

  9. Effects of the Basal Boundary on Debris-flow Dynamics (United States)

    Iverson, R. M.; Logan, M.; Lahusen, R. G.; Berti, M.


    Data aggregated from 37 large-scale experiments reveal some counterintuitive effects of bed roughness on debris-flow dynamics. In each experiment 10 m3 of water-saturated sand and gravel, mixed with 1 to 12% silt and clay by dry weight, was abruptly released from a gate at the head of a 2-m wide, 1.2-m deep, 82.5-m long rectangular flume inclined 31° throughout most of its length and adjoined to a gently sloping, planar runout surface at its toe. The flume's basal boundary consisted of either a smooth, planar concrete surface or a concrete surface roughened with a grid of conical bumps. Tilt-table tests with dry debris-flow sediment showed that this roughness imparted a basal friction angle of 38°, comparable to the sediment's internal friction angle of 38-42°, whereas the smooth-bed friction angle was 28°. About 20 electronic sensors installed in the flume yielded data on flow speeds and depths as well as basal stresses and pore pressures. Behavior observed in all experiments included development of steep, unsaturated, coarse-grained debris-flow snouts and tapering, liquefied, fine-grained tails. Flows on the rough bed were typically about 50% thicker and 20% slower than flows on the smooth bed, although the rough bed caused snout steepening that enabled flow fronts to move faster than expected, given the increased bed friction. Moreover, flows on rough beds ran out further than flows on smooth beds owing to enhanced grain-size segregation and lateral levee formation. With the rough bed, measured basal stresses and pore pressures differed little from values expected from static gravitational loading of partially liquefied debris. With the smooth bed, however, measured basal stresses and pore pressures were nearly twice as large as expected values. This anomaly resulted from flow disturbance at the upstream lips of steel plates in which sensors were mounted. The lips produced barely visible ripples in otherwise smooth flow surfaces, yet sufficed to generate

  10. The bacterial microbiota of Stolotermes ruficeps (Stolotermitidae), a phylogenetically basal termite endemic to New Zealand. (United States)

    Reid, Nicola M; Addison, Sarah L; West, Mark A; Lloyd-Jones, Gareth


    Stolotermes ruficeps is a widespread, primitive, lower termite occupying dead and decaying wood of many tree species in New Zealand's temperate forests. We identified core bacterial taxa involved in gut processes through combined DNA- and RNA (cDNA)-based pyrosequencing analysis of the 16S nucleotide sequence from five S. ruficeps colonies. Most family and many genus-level taxa were common to S. ruficeps colonies despite being sampled from different tree species. Major taxa identified were Spirochaetaceae, Elusimicrobiaceae and Porphyromonadaceae. Others less well known in termite guts were Synergistaceae, Desulfobacteraceae, Rhodocyclaceae, Lachnospiraceae and Ruminococcaceae. Synergistaceae, Lachnospiraceae and Spirochaetaceae were well represented in the RNA data set, indicating a high-protein synthesis potential. Using 130,800 sequences from nine S. ruficeps DNA and RNA data sets, we estimated a high level of bacterial richness (4024 phylotypes at 3% genetic distance). Very few abundant phylotypes were site-specific; almost all (95%) abundant phylotypes, representing 97% of data set sequences, were detected in at least two S. ruficeps colonies. This study of a little-researched phylogenetically basal termite identifies core bacteria taxa. These findings will extend inventories of termite gut microbiota and contribute to the understanding of the specificity of termite gut microbiota.

  11. Sp1 and KLF15 regulate basal transcription of the human LRP5 gene

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    Zou Yongxin


    Full Text Available Abstract Background LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear. Results In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs. Conclusions Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.

  12. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb. (United States)

    Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang


    The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

  13. Expression studies and promoter analysis of the nuclear gene for mitochondrial transcription factor 1 (MTF1) in yeast. (United States)

    Jan, P S; Stein, T; Hehl, S; Lisowsky, T


    The basal mitochondrial transcription apparatus of Saccharomyces cerevisiae consists of the core enzyme for mitochondrial RNA polymerase and the specificity factor. The core enzyme is homologous to those of bacteriophages T3, T7 and SP6 whereas the specificity factor shows similarities with bacterial sigma factors. Recently it was shown that the bacteriophage-type core enzyme is widespread among the eukaryotic lineage and a common picture for the mitochondrial transcription apparatus in eukaryotic cells is now emerging. In contrast to the situation for the core enzyme, the gene for the specificity factor has only been identified from S. cerevisiae and more recently from two other yeast species. As the specificity factor is the key component for initiation of transcription at the mitochondrial promoter we wanted to study in more detail gene expression, regulation, and the function of the promoter of the nuclear MTF1 gene. For this purpose the messenger RNA level for scMTF1 was investigated under a large number of different growth conditions and thereby exhibited a very low, but regulated and carbon source-dependent, expression. Deletion experiments identify the minimal promoter for functional complementation in yeast. To evaluate the functional conservation of the promoter elements the homologous MTF1 gene from the closely related yeast Saccharomyces douglasii was isolated and tested in heterologous complementation experiments. In spite of a highly conserved protein sequence these studies demonstrate that at low-copy number sdMTF1 is not able to substitute for scMTF1 in S. cerevisiae. Promoter exchange experiments with MTF1 from S. cerevisiae and S. douglasii demonstrate that differences in gene expression are responsible for the failure in heterologous complementation. This finding prompted us to compare the promoter regions of MTF1 from four different yeast species. For this purpose the sequences of the 5' regions from S. douglasii, S. kluyveri and Kluyveromyces

  14. MRI of germinomas arising from the basal ganglia and thalamus

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    Kim, D.I.; Yoon, P.H.; Ryu, Y.H.; Jeon, P.; Hwang, G.J. [Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)


    We reviewed the MRI findings of germinomas originating from the basal ganglia, thalamus or deep white matter in 13 patients with 14 germinomas, excluding those in the suprasellar or pineal regions. Ten cases were confirmed as germinomas by stereotaxic biopsy, three by partial and one by total removal of the tumour. Analysis was focussed on the location and the signal characteristic of the tumour, haemorrhage, cysts within the tumour and any other associated findings. Thirteen of the tumours were in the basal ganglia and one in the thalamus. Haemorrhage was observed in seven patients, while twelve showed multiple cysts. Associated ipsilateral cerebral hemiatrophy was seen in three patients. The signal intensity of the parenchymal germinomas was heterogeneous on T1- and T2-weighted images due to haemorrhage, cysts and solid portions. We also report the MRI findings of germinomas in an early stage in two patients. (orig.) With 5 figs., 1 tab., 17 refs.

  15. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    N K Kiran


    Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  16. 基底节性失语%Basal Ganglia Aphasia

    Institute of Scientific and Technical Information of China (English)

    隆昱洲; 柳华; 艾青龙


    基底节病变常导致语言功能障碍,其表现彤式复杂,既可出现口语语言障碍,也可出现书面语语言障碍,几乎包括所有失语类型.文章就基底节解剖、基底节失语的定义、特点、机制以及病变部位对语言的影响做了综述.%Basal ganglion lesions often result in language impairment. Its patterns of manifestation are complicated. Patients may either have oral language disorders or written language disorders, which almost includes all types of aphasia, The article reviews the anatomy, definition, feature and mechanisms of basal ganglia aphasia as well as the effect of lesion sites on language.

  17. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder (United States)

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu


    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr's disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly presents with mental damage, convulsion, parkinson-like clinical picture, and neuropsychiatric behavior disorders; however, presentation with impulse control disorder is not a frequent presentation. In the current report, a 43-year-old male patient who has been admitted to psychiatry policlinic with the complaints of aggressive behavior episodes and who has been diagnosed with impulse control disorder and IBGC was evaluated in the light of the literature. PMID:26246920

  18. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros


    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  19. Basal autophagy is required for the efficient catabolism of sialyloligosaccharides. (United States)

    Seino, Junichi; Wang, Li; Harada, Yoichiro; Huang, Chengcheng; Ishii, Kumiko; Mizushima, Noboru; Suzuki, Tadashi


    Macroautophagy is an essential, homeostatic process involving degradation of a cell's own components; it plays a role in catabolizing cellular components, such as protein or lipids, and damaged or excess organelles. Here, we show that in Atg5(-/-) cells, sialyloligosaccharides specifically accumulated in the cytosol. Accumulation of these glycans was observed under non-starved conditions, suggesting that non-induced, basal autophagy is essential for their catabolism. Interestingly, once accumulated in the cytosol, sialylglycans cannot be efficiently catabolized by resumption of the autophagic process, suggesting that functional autophagy is important for preventing sialyloligosaccharides from accumulating in the cytosol. Moreover, knockdown of sialin, a lysosomal transporter of sialic acids, resulted in a significant reduction of sialyloligosaccharides, implying that autophagy affects the substrate specificity of this transporter. This study thus provides a surprising link between basal autophagy and catabolism of N-linked glycans.

  20. Promoting Models (United States)

    Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si

    There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.

  1. Sediment Core Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Provides instrumentation and expertise for physical and geoacoustic characterization of marine sediments.DESCRIPTION: The multisensor core logger measures...

  2. Sediment Core Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Provides instrumentation and expertise for physical and geoacoustic characterization of marine sediments. DESCRIPTION: The multisensor core logger measures...

  3. A Critical Review of Habit Learning and the Basal Ganglia


    Seger, Carol A.; Spiering, Brian J.


    The current paper briefly outlines the historical development of the concept of habit learning and discusses its relationship to the basal ganglia. Habit learning has been studied in many different fields of neuroscience using different species, tasks, and methodologies, and as a result it has taken on a wide range of definitions from these various perspectives. We identify five common but not universal, definitional features of habit learning: that it is inflexible, slow or incremental, unco...

  4. Prospects for cannabinoid therapies in basal ganglia disorders


    Fernández-Ruiz, Javier; Moreno-Martet, Miguel; Rodríguez-Cueto, Carmen; Palomo-Garo, Cristina; Gómez-Cañas, María; Valdeolivas, Sara; Guaza, Carmen; Romero, Julián; Guzmán, Manuel; Mechoulam, Raphael; Ramos, José A


    Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ9-tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxid...

  5. The proprioception and neuromuscular stability of the basal thumb joint


    Mobargha, Nathalie


    OBJECTIVES The basal thumb joint, or the first carpometacarpal joint (CMC1) is an enigmatic construction. The concavo-convex shape of the CMC1 and wide range of movement, allows for both precision and power grips and is particularly susceptible to the development of osteoarthritis. Previous theories regarding the development of CMC1 osteoarthritis have focused on the role of gender, excessive joint load and ligament laxity as causative factors. An emerging theory is the role o...

  6. Translating structure to clinical properties of an ideal basal insulin. (United States)

    Unnikrishnan, A G; Bantwal, Ganapathi; Sahay, R K


    There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

  7. Youth hypertension cerebral hemorrhage in basal ganglia surgery operation analysis

    Institute of Scientific and Technical Information of China (English)

    Qi-Hua Wang; Da-Shuang Lu; Jie Cui; Bo-Lin Qiao; Jing-Chun Wang


    Objective:Discuss surgical treatment of youth hypertension cerebral hemorrhage in basal ganglia.Methods:Retrospective analysis from January 2012 to April 2015 were adopted to bone flap craniotomy decompression for removal of hematoma and drainage drilling two kinds of surgical treatment of 46 cases of young patients with hypertension cerebral hemorrhage in basal ganglia.Results:Surgical operation, 28 patients postoperative review head CT, no further hemorrhage cases, residual hematoma volume 2-6 mL. Drilling drainage in the treatment of 18 patients, 1 case was bleeding again given surgical operation to remove the hematoma and the rest of the 17 cases without bleeding again, after 3 d, 17 cases of patients of postoperative hematoma drainage thoroughly. After 6 months, 46 cases of patients with postoperative review, GOS score light disability 9 cases, moderate disability 33 cases, 4 cases were severely disabled, curative effect is satisfied.Conclusions:Two kinds of operative methods each have advantages and disadvantages, young patients with hypertension cerebral hemorrhage in basal ganglia should according to patients' disease progression after speed, on admission patient's state of consciousness and head CT measured on admission hematoma volume, respectively.

  8. Movement Disorders Following Cerebrovascular Lesion in the Basal Ganglia Circuit. (United States)

    Park, Jinse


    Movement disorders are primarily associated with the basal ganglia and the thalamus; therefore, movement disorders are more frequently manifest after stroke compared with neurological injuries associated with other structures of the brain. Overall clinical features, such as types of movement disorder, the time of onset and prognosis, are similar with movement disorders after stroke in other structures. Dystonia and chorea are commonly occurring post-stroke movement disorders in basal ganglia circuit, and these disorders rarely present with tremor. Rarer movement disorders, including tic, restless leg syndrome, and blepharospasm, can also develop following a stroke. Although the precise mechanisms underlying the pathogenesis of these conditions have not been fully characterized, disruptions in the crosstalk between the inhibitory and excitatory circuits resulting from vascular insult are proposed to be the underlying cause. The GABA (gamma-aminobutyric acid)ergic and dopaminergic systems play key roles in post-stroke movement disorders. This review summarizes movement disorders induced by basal ganglia and thalamic stroke according to the anatomical regions in which they manifest.

  9. Effects of aging on basal fat oxidation in obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K


    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2......)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P...... = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44...

  10. Photodynamic therapy for basal cell skin cancer ENT-organs

    Directory of Open Access Journals (Sweden)

    V. N. Volgin


    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  11. Bacterial diversity of oil palm Elaeis guineensis basal stems (United States)

    Amran, Afzufira; Jangi, Mohd Sanusi; Aqma, Wan Syaidatul; Yusof, Nurul Yuziana Mohd; Bakar, Mohd Faizal Abu; Isa, Mohd Noor Mat


    Oil palm, Elaeis guineensis is one of the major industrial production crops in Malaysia. Basal stem rot, caused by the white fungus, Ganoderma boninense, is a disease that reduces oil palm yields in most production areas of the world. Understanding of bacterial community that is associated with Ganoderma infection will shed light on how this bacterial community contributes toward the severity of the infection. In this preliminary study, we assessed the bacterial community that inhabit the basal stems of E. guineensis based on 16S rRNA gene as a marker using next generation sequencing platform. This result showed that a total of 84,372 operational taxonomic-units (OTUs) were identified within six samples analyzed. A total 55,049 OTUs were assigned to known taxonomy whereas 29,323 were unassigned. Cyanobacteria, Bacteroidetes, Firmicutes and Proteobacteria were the most abundant phyla found in all six samples and the unique taxonomy assigned for each infected and healthy samples were also identified. The findings from this study will further enhance our knowledge in the interaction of bacterial communities against Ganoderma infection within the oil palm host plant and for a better management of the basal stems rot disease.

  12. Proactive selective response suppression is implemented via the basal ganglia. (United States)

    Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody; Aron, Adam R


    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.

  13. Pigmented basal cell carcinoma of the eyelid in Hispanics

    Directory of Open Access Journals (Sweden)

    Lily Koo Lin


    Full Text Available Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

  14. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX


    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  15. A Case of Basal Cell Adenoma of the Upper Lip

    Directory of Open Access Journals (Sweden)

    Masanori Kudoh


    Full Text Available Basal cell adenoma is a rare type of benign salivary gland tumor found most commonly in the parotid gland. We present a rare case of basal cell adenoma arising in the minor salivary gland of the upper lip. The patient was a 59-year-old Japanese man who visited our department in December 2012 with a chief complaint of a mass in the upper lip, which had increased in size over several years. A mobile, elastic, and relatively soft mass without tenderness was palpable in the upper lip region. The mucosa of the upper lip covering the mass was normal. Tumor extirpation was performed under local anesthesia. Histologically, the tumor had a capsule and was composed of islands of relatively uniform, monotonous cells. Immunohistochemically, the inner tumor comprised tubuloductal structures that showed strong staining for CK7, while the outer tumor showed weak staining for CK7. The outer tumor cells also stained positively for CD10 and p63. The MIB-1 (Ki-67 labeling index was extremely low. Basal cell adenoma was diagnosed based on these results. The postoperative course was uneventful 12 months after surgery and there has been no recurrence.

  16. Field measurement of basal forces generated by erosive debris flows (United States)

    McCoy, S.W.; Tucker, G.E.; Kean, J.W.; Coe, J.A.


    It has been proposed that debris flows cut bedrock valleys in steeplands worldwide, but field measurements needed to constrain mechanistic models of this process remain sparse due to the difficulty of instrumenting natural flows. Here we present and analyze measurements made using an automated sensor network, erosion bolts, and a 15.24 cm by 15.24 cm force plate installed in the bedrock channel floor of a steep catchment. These measurements allow us to quantify the distribution of basal forces from natural debris‒flow events that incised bedrock. Over the 4 year monitoring period, 11 debris‒flow events scoured the bedrock channel floor. No clear water flows were observed. Measurements of erosion bolts at the beginning and end of the study indicated that the bedrock channel floor was lowered by 36 to 64 mm. The basal force during these erosive debris‒flow events had a large‒magnitude (up to 21 kN, which was approximately 50 times larger than the concurrent time‒averaged mean force), high‒frequency (greater than 1 Hz) fluctuating component. We interpret these fluctuations as flow particles impacting the bed. The resulting variability in force magnitude increased linearly with the time‒averaged mean basal force. Probability density functions of basal normal forces were consistent with a generalized Pareto distribution, rather than the exponential distribution that is commonly found in experimental and simulated monodispersed granular flows and which has a lower probability of large forces. When the bed sediment thickness covering the force plate was greater than ~ 20 times the median bed sediment grain size, no significant fluctuations about the time‒averaged mean force were measured, indicating that a thin layer of sediment (~ 5 cm in the monitored cases) can effectively shield the subjacent bed from erosive impacts. Coarse‒grained granular surges and water‒rich, intersurge flow had very similar basal force distributions despite

  17. Orexin-A facilitates emergence of the rat from isoflurane anesthesia via mediation of the basal forebrain. (United States)

    Zhang, Li-Na; Yang, Cen; Ouyang, Peng-Rong; Zhang, Zhi-Chao; Ran, Ming-Zi; Tong, Li; Dong, Hai-Long; Liu, Yong


    Previous studies have demonstrated that orexinergic neurons involve in promoting emergence from anesthesia of propofol, an intravenous anesthetics, while whether both of orexin-A and orexin-B have promotive action on emergence via mediation of basal forebrain (BF) in isoflurane anesthesia has not been elucidated. In this study, we observed c-Fos expressions in orexinergic neurons following isoflurane inhalation (for 0, 30, 60, and 120min) and at the time when the righting reflex returned after the cessation of anesthesia. The plasma concentrations of orexin-A and -B in anesthesia-arousal process were measured by radioimmunoassay. Orexin-A and -B (30 or 100pmol) or the orexin receptor-1 and -2 antagonist SB-334867A and TCS-OX2-29 (5 or 20μg) were microinjected into the basal forebrain respectively. The effects of them on the induction (loss of the righting reflex) and the emergence time (return of the righting reflex) under isoflurane anesthesia were observed. The results showed that the numbers of c-Fos-immunoreactive orexinergic neurons in the hypothalamus decreased over time with continued isoflurane inhalation, but restored at emergence. Similar alterations were observed in changes of plasma orexin-A concentrations but not in orexin-B during emergence. Administration of orexins had no effect on the induction time, but orexin-A facilitated the emergence of rats from isoflurane anesthesia while orexin-B didn't. Conversely, microinjection of the orexin receptor-1 antagonist SB-334867A delayed emergence from isoflurane anesthesia. The results indicate that orexin-A plays a promotive role in the emergence of isoflurane anesthesia and this effect is mediated by the basal forebrain.

  18. EEA core set of indicators. Guide

    Energy Technology Data Exchange (ETDEWEB)



    This guide provides information on the quality of the 37 indicators in the EEA core set. Its primary role is to support improved implementation of the core set in the EEA, European topic centres and the European environment information and observation network (Eionet). In parallel, it is aimed at helping users outside the EEA/Eionet system make best use of the indicators in their own work. It is hoped that the guide will promote cooperation on improving indicator methodologies and data quality as part of the wider process to streamline and improve environmental reporting in the European Union and beyond. (au)

  19. Basal transcription machinery: role in regulation of stress response in eukaryotes

    Indian Academy of Sciences (India)

    Parag Sadhale; Jiyoti Verma; Aruna Naorem


    The holoenzyme of prokaryotic RNA polymerase consists of the core enzyme, made of two , , ’ and subunits, which lacks promoter selectivity and a sigma () subunit which enables the core enzyme to initiate transcription in a promoter dependent fashion. A stress sigma factor s, in prokaryotes seems to regulate several stress response genes in conjunction with other stress specific regulators. Since the basic principles of transcription are conserved from simple bacteria to multicellular complex organisms, an obvious question is: what is the identity of a counterpart of s, that is closest to the core polymerase and that dictates transcription of stress regulated genes in general? In this review, we discuss the logic behind the suggestion that like in prokaryotes, eukaryotes also have a common functional unit in the transcription machinery through which the stress specific transcription factors regulate rapid and highly controlled induction of gene expression associated with generalized stress response and point to some candidates that would fit the bill of the eukaryotic s.

  20. Making an Ice Core. (United States)

    Kopaska-Merkel, David C.


    Explains an activity in which students construct a simulated ice core. Materials required include only a freezer, food coloring, a bottle, and water. This hands-on exercise demonstrates how a glacier is formed, how ice cores are studied, and the nature of precision and accuracy in measurement. Suitable for grades three through eight. (Author/PVD)

  1. Ice Core Investigations (United States)

    Krim, Jessica; Brody, Michael


    What can glaciers tell us about volcanoes and atmospheric conditions? How does this information relate to our understanding of climate change? Ice Core Investigations is an original and innovative activity that explores these types of questions. It brings together popular science issues such as research, climate change, ice core drilling, and air…

  2. Iowa Core Annual Report (United States)

    Iowa Department of Education, 2015


    One central component of a great school system is a clear set of expectations, or standards, that educators help all students reach. In Iowa, that effort is known as the Iowa Core. The Iowa Core represents the statewide academic standards, which describe what students should know and be able to do in math, science, English language arts, and…

  3. Mercury's core evolution (United States)

    Deproost, Marie-Hélène; Rivoldini, Attilio; Van Hoolst, Tim


    Remote sensing data of Mercury's surface by MESSENGER indicate that Mercury formed under reducing conditions. As a consequence, silicon is likely the main light element in the core together with a possible small fraction of sulfur. Compared to sulfur, which does almost not partition into solid iron at Mercury's core conditions and strongly decreases the melting temperature, silicon partitions almost equally well between solid and liquid iron and is not very effective at reducing the melting temperature of iron. Silicon as the major light element constituent instead of sulfur therefore implies a significantly higher core liquidus temperature and a decrease in the vigor of compositional convection generated by the release of light elements upon inner core formation.Due to the immiscibility in liquid Fe-Si-S at low pressure (below 15 GPa), the core might also not be homogeneous and consist of an inner S-poor Fe-Si core below a thinner Si-poor Fe-S layer. Here, we study the consequences of a silicon-rich core and the effect of the blanketing Fe-S layer on the thermal evolution of Mercury's core and on the generation of a magnetic field.

  4. Initial basal cell carcinomas diagnosed in the National Campaign for Skin Cancer Prevention are smaller than those identified by the conventional medical referral system* (United States)

    Wakiyama, Thweicyka Pinheiro; França, Maria Laura Marconi; Carvalho, Larissa Pierri; Marques, Mariangela Esther Alencar; Miot, Hélio Amante; Schmitt, Juliano Vilaverde


    BACKGROUND Basal cell carcinoma is the malignant tumor most often diagnosed in the National Campaign for Skin Cancer Prevention (NCSCP). Little is known about the profile of these lesions compared to the profile of lesions diagnosed by conventional routes of public dermatological care. OBJECTIVE To identify if basal cell carcinomas identified in prevention campaigns and referred to surgery are smaller than those routinely removed in a same medical institution. METHODS Cross-sectional study including tumors routed from 2011-2014 campaigns and 84 anatomopathological reports of outpatients. RESULTS The campaigns identified 223 individuals with suspicious lesions among 2,531 examinations (9%), with 116 basal cell carcinomas removed. Anatomopathological examinations revealed that the primary lesions identified in the national campaigns were smaller than those referred to surgery by the conventional routes of public health care (28 [13-50] x 38 [20-113] mm2, p <0.01). On the other hand, after a mean follow-up of 15.6 ± 10.3 months, 31% of cases identified in campaigns showed new basal cell carcinoma lesions. STUDY LIMITATIONS Retrospective study and inaccuracies in the measurements of the lesions. CONCLUSIONS The NCSCP promotes an earlier treatment of basal cell carcinomas compared to patients referred to surgery by the conventional routes of public health care, which can result in lower morbidity rates and better prognosis. PMID:28225952

  5. Multiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/triple negative breast cancer. (United States)

    Kochel, Tyler J; Reader, Jocelyn C; Ma, Xinrong; Kundu, Namita; Fulton, Amy M


    Cyclooxygenase-2 (COX-2) and its primary enzymatic product, prostaglandin E2 (PGE2), are associated with a poor prognosis in breast cancer. In order to elucidate the factors contributing to intratumoral PGE2 levels, we evaluated the expression of COX-2/PGE2 pathway members MRP4, the prostaglandin transporter PGT, 15-PGDH (PGE2 metabolism), the prostaglandin E receptor EP4, COX-1, and COX-2 in normal, luminal, and basal breast cancer cell lines. The pattern of protein expression varied by cell line reflecting breast cancer heterogeneity. Overall, basal cell lines expressed higher COX-2, higher MRP4, lower PGT, and lower 15-PGDH than luminal cell lines resulting in higher PGE2 in the extracellular environment. Genetic or pharmacologic suppression of MRP4 expression or activity in basal cell lines led to less extracellular PGE2. The key finding is that xenografts derived from a basal breast cancer cell line with stably suppressed MRP4 expression showed a marked decrease in spontaneous metastasis compared to cells with unaltered MRP4 expression. Growth properties of primary tumors were not altered by MRP4 manipulation. In addition to the well-established role of high COX-2 in promoting metastasis, these data identify an additional mechanism to achieve high PGE2 in the tumor microenvironment; high MRP4, low PGT, and low 15-PGDH. MRP4 should be examined further as a potential therapeutic target in basal breast cancer.

  6. Mars' core and magnetism. (United States)

    Stevenson, D J


    The detection of strongly magnetized ancient crust on Mars is one of the most surprising outcomes of recent Mars exploration, and provides important insight about the history and nature of the martian core. The iron-rich core probably formed during the hot accretion of Mars approximately 4.5 billion years ago and subsequently cooled at a rate dictated by the overlying mantle. A core dynamo operated much like Earth's current dynamo, but was probably limited in duration to several hundred million years. The early demise of the dynamo could have arisen through a change in the cooling rate of the mantle, or even a switch in convective style that led to mantle heating. Presently, Mars probably has a liquid, conductive outer core and might have a solid inner core like Earth.

  7. Trypanosoma brucei: a putative RNA polymerase II promoter. (United States)

    Bayele, Henry K


    RNA polymerase II (pol II) promoters are rare in the African trypanosome Trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. Here, we describe a putative pol II promoter and its structure-function relationship. The promoter has features of an archetypal eukaryotic pol II promoter including putative canonical CCAAT and TATA boxes, and an initiator element. However, the spatial arrangement of these elements is only similar to yeast pol II promoters. Deletion mapping and transcription assays enabled delineation of a minimal promoter that could drive orientation-independent reporter gene expression suggesting that it may be a bidirectional promoter. In vitro transcription in a heterologous nuclear extract revealed that the promoter can be recognized by the basal eukaryotic transcription complex. This suggests that the transcription machinery in the parasite may be very similar to those of other eukaryotes.

  8. Adenosine Inhibits the Excitatory Synaptic Inputs to Basal Forebrain Cholinergic, GABAergic and Parvalbumin Neurons in mice

    Directory of Open Access Journals (Sweden)

    Chun eYang


    Full Text Available Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV neurons to determine the effect of adenosine. Whole-cell recordings were made BF cholinergic neurons and from BF GABAergic & PV neurons with the size (>20 µm and intrinsic membrane properties (prominent H-currents corresponding to cortically projecting neurons. A brief (2 min bath application of adenosine (100 μM decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents in all groups of BF cholinergic, GABAergic and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 μM. Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1-receptor mediated inhibition of glutamatergic inputs to cortically-projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for

  9. Chronic hypoxia increases TRPC6 expression and basal intracellular Ca2+ concentration in rat distal pulmonary venous smooth muscle.

    Directory of Open Access Journals (Sweden)

    Lei Xu

    Full Text Available Hypoxia causes remodeling and contractile responses in both pulmonary artery (PA and pulmonary vein (PV. Here we explore the effect of hypoxia on PV and pulmonary venous smooth muscle cells (PVSMCs.Chronic hypoxic pulmonary hypertension (CHPH model was established by exposing rats to 10% O2 for 21 days. Rat distal PVSMCs were isolated and cultured for in vitro experiments. The fura-2 based fluorescence calcium imaging was used to measure the basal intracellular Ca2+ concentration ([Ca2+]i and store-operated Ca2+ entry (SOCE. Quantitative RT-PCR and western blotting were performed to measure the expression of mRNA and levels of canonical transient receptor potential (TRPC protein respectively.Hypoxia increased the basal [Ca2+]i and SOCE in both freshly dissociated and serum cultured distal PVSMCs. Moreover, hypoxia increased TRPC6 expression at mRNA and protein levels in both cultured PVSMCs exposed to prolonged hypoxia (4% O2, 60 h and distal PV isolated from CHPH rats. Hypoxia also enhanced proliferation and migration of rat distal PVSMCs.Hypoxia induces elevation of SOCE in distal PVSMCs, leading to enhancement of basal [Ca2+]i in PVSMCs. This enhancement is potentially correlated with the increased expression of TRPC6. Hypoxia triggered intracellular calcium contributes to promoted proliferation and migration of PVSMCs.

  10. FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma. (United States)

    Perez-Balaguer, Ariadna; Ortiz-Martínez, Fernando; García-Martínez, Araceli; Pomares-Navarro, Critina; Lerma, Enrique; Peiró, Gloria


    The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10% (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p Triple-Negative/Basal-like tumors, and is associated with increase relapses.

  11. The t-core of an s-core


    Fayers, Matthew


    We consider the $t$-core of an $s$-core partition, when $s$ and $t$ are coprime positive integers. Olsson has shown that the $t$-core of an $s$-core is again an $s$-core, and we examine certain actions of the affine symmetric group on $s$-cores which preserve the $t$-core of an $s$-core. Along the way, we give a new proof of Olsson's result. We also give a new proof of a result of Vandehey, showing that there is a simultaneous $s$- and $t$-core which contains all others.

  12. Earth's inner core: Innermost inner core or hemispherical variations?

    NARCIS (Netherlands)

    Lythgoe, K. H.; Deuss, A.; Rudge, J. F.; Neufeld, J. A.


    The structure of Earth's deep inner core has important implications for core evolution, since it is thought to be related to the early stages of core formation. Previous studies have suggested that there exists an innermost inner core with distinct anisotropy relative to the rest of the inner core.

  13. Korrelasjon mellom core styrke, core stabilitet og utholdende styrke i core


    Berg-Olsen, Andrea Marie; Fugelsøy, Eivor; Maurstad, Ann-Louise


    Formålet med studien var å se hvilke korrelasjon det er mellom core styrke, core stabilitet og utholdende styrke i core. Testingen bestod av tre hoveddeler hvor vi testet core styrke, core stabilitet og utholdende styrke i core. Innenfor core styrke og utholdende styrke i core ble tre ulike tester utført. Ved måling av core stabilitet ble det gjennomført kun en test. I core styrke ble isometrisk abdominal fleksjon, isometrisk rygg ekstensjon og isometrisk lateral fleksjon testet. Sit-ups p...

  14. Expression of stromelysin 3 in basal cell carcinomas. (United States)

    Cribier, B; Noacco, G; Peltre, B; Grosshans, E


    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  15. Basal salivary cortisol secretion and susceptibility to upper respiratory infection. (United States)

    Janicki-Deverts, Denise; Cohen, Sheldon; Turner, Ronald B; Doyle, William J


    The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal salivary cortisol production are associated with increased risk and severity of infection and subsequent illness following experimental exposure to a virus that causes the common cold. The present analyses combine archival data from three viral-challenge studies. Participants were 608 healthy adults, aged 18 to 55 years (49.2% female; 65.8% white), who each completed a three-day saliva collection protocol; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for objective signs of infection (presence of challenge virus in nasal secretions) and clinical illness (mucus weight, mucociliary clearance time). Basal cortisol production (operationalized as the calculated area-under-the-curve averaged across the 3 days) showed a graded association with infection risk, with those producing higher levels of cortisol being at greater risk. Cortisol also showed a continuous association with duration of viral shedding, an indicator of viral replication and continuing infection, such that higher cortisol concentrations predicted more days of shedding. Cortisol was not, however, related to severity of objective illness. These findings are the first to demonstrate in healthy adults an association between basal cortisol production and an objectively measured and clinically relevant infectious disease outcome.

  16. A phylogenomic approach to resolve the basal pterygote divergence. (United States)

    Simon, Sabrina; Strauss, Sascha; von Haeseler, Arndt; Hadrys, Heike


    One of the most fascinating Bauplan transitions in the animal kingdom was the invention of insect wings, a change that also contributed to the success and enormous diversity of this animal group. However, the origin of insect flight and the relationships of basal winged insect orders are still controversial. Three hypotheses have been proposed to explain the phylogeny of winged insects: 1) the traditional Palaeoptera hypothesis (Ephemeroptera + Odonata, Neoptera), 2) the Metapterygota hypothesis (Ephemeroptera, Odonata + Neoptera), and 3) the Chiastomyaria hypothesis (Odonata, Ephemeroptera + Neoptera). Neither phylogenetic analyses of single genes nor even multiple marker systems (e.g., molecular markers + morphological characters) have yet been able to conclusively resolve basal pterygote divergences. A possible explanation for the lack of resolution is that the divergences took place in the mid-Devonian within a short period of time and attempts to solve this problem have been confounded by the major challenge of finding molecular markers to accurately track these short ancient internodes. Although phylogenomic data are available for Neoptera and some wingless (apterygote) orders, they are lacking for the crucial Odonata and Ephemeroptera orders. We adopt a multigene approach including data from two new expressed sequence tag projects-from the orders Ephemeroptera (Baetis sp.) and Odonata (Ischnura elegans)-to evaluate the potential of phylogenomic analyses in clarifying this unresolved issue. We analyzed two data sets that differed in represented taxa, genes, and overall sequence lengths: maxspe (15 taxa, 125 genes, and 31,643 amino acid positions) and maxgen (8 taxa, 150 genes, and 42,541 amino acid positions). Maximum likelihood and Bayesian inference analyses both place the Odonata at the base of the winged insects. Furthermore, statistical hypotheses testing rejected both the Palaeoptera and the Metapterygota hypotheses. The comprehensive molecular data set

  17. Correlation transfer from basal ganglia to thalamus in Parkinson's disease. (United States)

    Reitsma, Pamela; Doiron, Brent; Rubin, Jonathan


    Spike trains from neurons in the basal ganglia of parkinsonian primates show increased pairwise correlations, oscillatory activity, and burst rate compared to those from neurons recorded during normal brain activity. However, it is not known how these changes affect the behavior of downstream thalamic neurons. To understand how patterns of basal ganglia population activity may affect thalamic spike statistics, we study pairs of model thalamocortical (TC) relay neurons receiving correlated inhibitory input from the internal segment of the globus pallidus (GPi), a primary output nucleus of the basal ganglia. We observe that the strength of correlations of TC neuron spike trains increases with the GPi correlation level, and bursty firing patterns such as those seen in the parkinsonian GPi allow for stronger transfer of correlations than do firing patterns found under normal conditions. We also show that the T-current in the TC neurons does not significantly affect correlation transfer, despite its pronounced effects on spiking. Oscillatory firing patterns in GPi are shown to affect the timescale at which correlations are best transferred through the system. To explain this last result, we analytically compute the spike count correlation coefficient for oscillatory cases in a reduced point process model. Our analysis indicates that the dependence of the timescale of correlation transfer is robust to different levels of input spike and rate correlations and arises due to differences in instantaneous spike correlations, even when the long timescale rhythmic modulations of neurons are identical. Overall, these results show that parkinsonian firing patterns in GPi do affect the transfer of correlations to the thalamus.

  18. IGCSE core mathematics

    CERN Document Server

    Wall, Terry


    Give your core level students the support and framework they require to get their best grades with this book dedicated to the core level content of the revised syllabus and written specifically to ensure a more appropriate pace. This title has been written for Core content of the revised Cambridge IGCSE Mathematics (0580) syllabus for first teaching from 2013. ? Gives students the practice they require to deepen their understanding through plenty of practice questions. ? Consolidates learning with unique digital resources on the CD, included free with every book. We are working with Cambridge

  19. Core shroud corner joints (United States)

    Gilmore, Charles B.; Forsyth, David R.


    A core shroud is provided, which includes a number of planar members, a number of unitary corners, and a number of subassemblies each comprising a combination of the planar members and the unitary corners. Each unitary corner comprises a unitary extrusion including a first planar portion and a second planar portion disposed perpendicularly with respect to the first planar portion. At least one of the subassemblies comprises a plurality of the unitary corners disposed side-by-side in an alternating opposing relationship. A plurality of the subassemblies can be combined to form a quarter perimeter segment of the core shroud. Four quarter perimeter segments join together to form the core shroud.

  20. Isolation of Alcohol Dehydrogenase cDNA and Basal Regulatory Region from Metroxylon sagu. (United States)

    Wee, Ching Ching; Roslan, Hairul Azman


    Alcohol dehydrogenase (Adh) is a versatile enzyme involved in many biochemical pathways in plants such as in germination and stress tolerance. Sago palm is plant with much importance to the state of Sarawak as one of the most important crops that bring revenue with the advantage of being able to withstand various biotic and abiotic stresses such as heat, pathogens, and water logging. Here we report the isolation of sago palm Adh cDNA and its putative promoter region via the use of rapid amplification of cDNA ends (RACE) and genomic walking. The isolated cDNA was characterized and determined to be 1464 bp long encoding for 380 amino acids. BLAST analysis showed that the Adh is similar to the Adh1 group with 91% and 85% homology with Elaeis guineensis and Washingtonia robusta, respectively. The putative basal msAdh1 regulatory region was further determined to contain promoter signals of TATA and AGGA boxes and predicted amino acids analyses showed several Adh-specific motifs such as the two zinc-binding domains that bind to the adenosine ribose of the coenzyme and binding to alcohol substrate. A phylogenetic tree was also constructed using the predicted amino acid showed clear separation of Adh from bacteria and clustered within the plant Adh group.

  1. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia;


    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... defects than standard excisions with 4 or 6 mm margins. Closure of skin defects was achieved by side-to-side closure in 49% and by local flaps in 40%. There were no relapses during the observation time. The safety, cosmetic and functional outcome were excellent. CONCLUSIONS: We recommend that MMS...

  2. Delayed Diagnosis: Giant Basal Cell Carcinoma of Scalp

    Directory of Open Access Journals (Sweden)

    Didem Didar Balcı,


    Full Text Available Although basal cell carcinoma (BCC is the most common form of skin cancer, the scalp lesions of BCC have been rarely reported. Giant BCC is defined as a tumor larger than 5 cm in diameter and only 0.5-1 % of all BCCs achieve this size. We report a case of giant BCC on the scalp that was treated with topical coticosteroids and antifungal shampoo for five years. BCC should be considered in the differential diagnosis in erythematous plaque type lesions resistant to therapy with long duration localized on the scalp.

  3. The basal ganglia: an overview of circuits and function. (United States)

    Utter, Amy A; Basso, Michele A


    The technique of electrical stimulation of brain tissue-known clinically as deep brain stimulation (DBS)-is at the fore of treatment of human neurological disease. Here we provide a general overview highlighting the anatomy and circuitry of the basal ganglia (BG). We introduce common disease states associated with BG dysfunction and current hypotheses of BG function. Throughout this introductory review we direct the reader to other reviews in this special issue of Neuroscience and Biobehavioral Reviews highlighting the interaction between basic science and clinical investigation to more fully understand the BG in both health and disease.

  4. Basal cell carcinomas in elderly patients treated by cryotherapy


    Chiriac A.; Mihaila D.; Foia L; Solovan C


    Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in ...

  5. iPSC Core (United States)

    Federal Laboratory Consortium — The induced Pluripotent Stem Cells (iPSC) Core was created in 2011 to accelerate stem cell research in the NHLBI by providing investigators consultation, technical...

  6. Reference: -300CORE [PLACE

    Lifescience Database Archive (English)

    Full Text Available -300CORE Forde BG, Heyworth A, Pywell J, Kreis M Nucleotide sequence of a B1 hordein gene and the identifica...tion of possible upstream regulatory elements in endosperm storage protein genes fr

  7. Biospecimen Core Resource - TCGA (United States)

    The Cancer Genome Atlas (TCGA) Biospecimen Core Resource centralized laboratory reviews and processes blood and tissue samples and their associated data using optimized standard operating procedures for the entire TCGA Research Network.

  8. NICHD Zebrafish Core (United States)

    Federal Laboratory Consortium — The core[HTML_REMOVED]s goal is to help researchers of any expertise perform zebrafish experiments aimed at illuminating basic biology and human disease mechanisms,...

  9. Focusing on Core Business

    Institute of Scientific and Technical Information of China (English)


    China is regulating state-owned enterprises that are investing outside of their core business realms, concerned that poor investment decisions could lead to loss of state-owned assets, but some doubt the effect of the new regulation

  10. Organizing Core Tasks

    DEFF Research Database (Denmark)

    Boll, Karen

    Civil servants conduct the work which makes welfare states functions on an everyday bases: Police men police, school teachers teach, and tax inspectors inspect. Focus in this paper is on the core tasks of tax inspectors. The paper argues that their core task of securing the collection of revenue...... has remained much the same within the last 10 years. However, how the core task has been organized has changed considerable under the influence of various “organizing devices”. The paper focusses on how organizing devices such as risk assessment, output-focus, effect orientation, and treatment...... projects influence the organization of core tasks within the tax administration. The paper shows that the organizational transformations based on the use of these devices have had consequences both for the overall collection of revenue and for the employees’ feeling of “making a difference”. All in all...

  11. Glass-clad semiconductor core optical fibers (United States)

    Morris, Stephanie Lynn

    ; experimental results show a decrease in fiber core oxygen content in the fibers drawn with the tailored glass composition. In a further attempt to reduce the presence of oxide species in the core, a reactive molten core approach to semiconductor optical fibers are developed. Specifically, the addition of silicon carbide (SiC) into a silicon (Si) core provides an in-situ reactive getter of oxygen during the draw process to achieve oxygen-free silicon optical fibers. Elemental analysis and x-ray diffraction of fibers drawn using this reactive chemistry approach show negligible oxygen concentration in the highly crystalline silicon core, a significant departure from the nearly 18 atom percent oxygen in previous fibers. Scattering of light out of the core is shown qualitatively to have been reduced in the process. The role of the cross-sectional geometry on the resultant core crystallography with respect to the fiber axis is explored in a continued effort to better understand the nature of the crystal formation and structural properties in these semiconductor core optical fibers. A square cross-sectional geometry was explored to determine if core non-circularity can enhance or promote single crystallinity, as the semiconductors studied have a preference to form cubic crystals. Resultant crystallography of the non-circular core showed a significant improvement in maintaining a preferred crystallographic orientation, with the square core fibers exhibiting a 90% preference for the family of directions occurring closest to the longitudinal direction of the fiber. The ability to orient the crystallography with respect to the fiber axis could be of great value to future nonlinear optical fiber-based devices. In summary, this dissertation begins to elucidate some of the microstructural features, not present in conventional glass optical fibers, which could be important for future low-loss single crystalline semiconductor optical fibers. Additionally, this dissertation offers novel

  12. Influence of damage and basal friction on the grounding line dynamics (United States)

    Brondex, Julien; Gagliardini, Olivier; Gillet-Chaulet, Fabien; Durand, Gael


    The understanding of grounding line dynamics is a major issue in the prediction of future sea level rise due to ice released from polar ice sheets into the ocean. This dynamics is complex and significantly affected by several physical processes not always adequately accounted for in current ice flow models. Among those processes, our study focuses on ice damage and evolving basal friction conditions. Softening of the ice due to damaging processes is known to have a strong impact on its rheology by reducing its viscosity and therefore promoting flow acceleration. Damage creates where shear stresses are high enough which is usually the case at shear margins and in the vicinity of pinning points in contact with ice-shelves. Those areas are known to have a buttressing effect on ice shelves contributing to stabilize the grounding line. We aim at evaluating the extent to which this stabilizing effect is hampered by damaging processes. Several friction laws have been proposed by various author to model the contact between grounded-ice and bedrock. Among them, Coulomb-type friction laws enable to account for reduced friction related to low effective pressure (the ice pressure minus the water pressure). Combining such a friction law to a parametrization of the effective pressure accounting for the fact that the area upstream the grounded line is connected to the ocean, is expected to have a significant impact on the grounding line dynamics. Using the finite-element code Elmer/Ice within which both the Coulomb-type friction law, the effective pressure parametrization and the damage model have been implemented, the goal of this study is to investigate the sensitivity of the grounding line dynamics to damage and to an evolving basal friction. The relative importance between those two processes on the grounding line dynamics is addressed as well.

  13. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

    Directory of Open Access Journals (Sweden)

    Ermelinda Porpiglia


    Full Text Available Erythropoietin (Epo-induced Stat5 phosphorylation (p-Stat5 is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the

  14. Basal Complex and Basal Venation of Odonata Wings: Structural Diversity and Potential Role in the Wing Deformation (United States)

    Rajabi, H.; Ghoroubi, N.; Malaki, M.; Darvizeh, A.; Gorb, S. N.


    Dragonflies and damselflies, belonging to the order Odonata, are known to be excellent fliers with versatile flight capabilities. The ability to fly over a wide range of speeds, high manoeuvrability and great agility are a few characteristics of their flight. The architecture of the wings and their structural elements have been found to play a major role in this regard. However, the precise influence of individual wing components on the flight performance of these insects remains unknown. The design of the wing basis (so called basal complex) and the venation of this part are responsible for particular deformability and specific shape of the wing blade. However, the wing bases are rather different in representatives of different odonate groups. This presumably reflects the dimensions of the wings on one hand, and different flight characteristics on the other hand. In this article, we develop the first three-dimensional (3D) finite element (FE) models of the proximal part of the wings of typical representatives of five dragonflies and damselflies families. Using a combination of the basic material properties of insect cuticle, a linear elastic material model and a nonlinear geometric analysis, we simulate the mechanical behaviour of the wing bases. The results reveal that although both the basal venation and the basal complex influence the structural stiffness of the wings, it is only the latter which significantly affects their deformation patterns. The use of numerical simulations enabled us to address the role of various wing components such as the arculus, discoidal cell and triangle on the camber formation in flight. Our study further provides a detailed representation of the stress concentration in the models. The numerical analysis presented in this study is not only of importance for understanding structure-function relationship of insect wings, but also might help to improve the design of the wings for biomimetic micro-air vehicles (MAVs). PMID:27513753

  15. Clinical variants, stages, and management of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lyubomir A Dourmishev


    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  16. Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity. (United States)

    Pizarro, Marcela; Troncoso, Rodrigo; Martínez, Gonzalo J; Chiong, Mario; Castro, Pablo F; Lavandero, Sergio


    Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxo-induced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability. Here we investigated the effect of Doxo 1uM for 24h of stimulation on cultured neonatal rat cardiomyocytes. We showed that Doxo inhibits basal autophagy. This inhibition is due to both Akt/mTOR signaling pathway activation and Beclin 1 level decrease. To assess the role of autophagy on Doxo-induced cardiomyocyte death, we evaluated the effects 3-methyladenine (3-MA), bafilomycin A1 (BafA), siRNA Beclin 1 (siBeclin 1) and rapamycin (Rapa) on cell viability. Inhibition of autophagy with 3-MA, BafA and siBeclin 1 increased lactate dehydrogenase (LDH) release but, when autophagy was induced by Rapa, Doxo-induced cardiomyocyte death was decreased. These results suggest that Doxo inhibits basal autophagy and contributes to cardiomyocyte death. Activation of autophagy could be used as a strategy to protect the heart against Doxo toxicity.

  17. The evolution of floral biology in basal angiosperms. (United States)

    Endress, Peter K


    In basal angiosperms (including ANITA grade, magnoliids, Choranthaceae, Ceratophyllaceae) almost all bisexual flowers are dichogamous (with male and female functions more or less separated in time), and nearly 100 per cent of those are protogynous (with female function before male function). Movements of floral parts and differential early abscission of stamens in the male phase are variously associated with protogyny. Evolution of synchronous dichogamy based on the day/night rhythm and anthesis lasting 2 days is common. In a few clades in Magnoliales and Laurales heterodichogamy has also evolved. Beetles, flies and thrips are the major pollinators, with various degrees of specialization up to large beetles and special flies in some large-flowered Nymphaeaceae, Magnoliaceae, Annonaceae and Aristolochiaceae. Unusual structural specializations are involved in floral biological adaptations (calyptras, inner staminodes, synandria and food bodies, and secretory structures on tepals, stamens and staminodes). Numerous specializations that are common in monocots and eudicots are absent in basal angiosperms. Several families are poorly known in their floral biology.

  18. Morphological elucidation of basal ganglia circuits contributing reward prediction

    Directory of Open Access Journals (Sweden)

    Fumino eFujiyama


    Full Text Available Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits.The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments.

  19. Coordinated Beating of Algal Flagella is Mediated by Basal Coupling (United States)

    Wan, Kirsty; Goldstein, Raymond

    Cilia or flagella often exhibit synchronized behavior. This includes phase-locking, as seen in Chlamydomonas, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga Volvox has shown that hydrodynamic coupling alone is sufficient for synchrony. However, the situation is more complex when considering multiple flagella on a single cell. We suggest that a mechanism, internal to the cell, provides an additional flagellar coupling. For instance, flagella of Chlamydomonas mutants deficient in filamentary connections between basal bodies are found to display markedly different synchronization from the wildtype. Diverse flagellar coordination strategies found in quadri-, octo- and hexadecaflagellates reveal further evidence that intracellular couplings between flagellar basal bodies compete with hydrodynamic interactions to determine the precise form of flagellar synchronization in unicellular algae.

  20. Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms. (United States)

    Lacour, J P


    Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.

  1. Treatment of nevoid basal cell carcinoma syndrome: a case report (United States)


    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is characterized by various embryological deformities and carcinoma formation. It is caused by PTCHI gene mutations and is autosomal dominantly inherited. Some of the main symptoms of NBCCS are multiple basal cell carcinomas, multiple keratocystic odontogenic tumors (KCOTs) of the mandible, hyperkeratosis of the palmar and plantar, skeletal deformity, calcification of the falx cerebri, and facial defomity. Recurrent KCOT is the main symptom of NBCCS and is present in approximately 90% of patients. In NBCCS, KCOTs typically occur in multiples. KCOTs can be detected in patients under the age of 10, and new and recurring cysts develop until approximately the age of 30. The postoperation recurrence rate is approximately 60%. This case report presents a 14-year-old female patient with a chief complaint of a cyst found in the maxilla and mandible. The patient was diagnosed with NBCCS, and following treatment of marsupialization and enucleation, the clinical results were satisfactory. PMID:27847737

  2. Mephedrone alters basal ganglia and limbic dynorphin systems. (United States)

    German, Christopher L; Alburges, Mario E; Hoonakker, Amanda J; Fleckenstein, Annette E; Hanson, Glen R


    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D1 -like (SCH-23380) or D2 -like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  3. Familial idiopathic basal ganglia calcification (Fahr’s disease) (United States)

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.


    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr’s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr’s disease. PMID:24983277

  4. Familial idiopathic basal ganglia calcification (Fahr`s disease). (United States)

    Mufaddel, Amir A; Al-Hassani, Ghanem A


    Familial idiopathic basal ganglia calcification (Fahr`s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr`s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr`s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr`s disease.

  5. Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter

    Directory of Open Access Journals (Sweden)

    Rivero Samuel


    Full Text Available Abstract Background DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene Dlk2 is coordinated with that of Dlk1 in several tissues and cell lines. Unlike Dlk1, the mouse Dlk2 gene and its locus at chromosome 17 are not fully characterized. Results The goal of this work was the characterization of Dlk2 mRNA, as well as the analysis of the mechanisms that control its basal transcription. First, we analyzed the Dlk2 transcripts expressed by several mouse cells lines and tissues, and mapped the transcription start site by 5' Rapid Amplification of cDNA Ends. In silico analysis revealed that Dlk2 possesses a TATA-less promoter containing minimal promoter elements associated with a CpG island, and sequences for Inr and DPE elements. Besides, it possesses six GC-boxes, considered as consensus sites for the transcription factor Sp1. Indeed, we report that Sp1 directly binds to the Dlk2 promoter, activates its transcription, and regulates its level of expression. Conclusions Our results provide the first characterization of Dlk2 transcripts, map the location of the Dlk2 core promoter, and show the role of Sp1 as a key regulator of Dlk2 transcription, providing new insights into the molecular mechanisms that contribute to the expression of the Dlk2 gene.

  6. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    Energy Technology Data Exchange (ETDEWEB)

    Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))


    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  7. Inducible and constitutive promoters for genetic systems in Sulfolobus acidocaldarius. (United States)

    Berkner, Silvia; Wlodkowski, Alexander; Albers, Sonja-Verena; Lipps, Georg


    Central to genetic work in any organism are the availability of a range of inducible and constitutive promoters. In this work we studied several promoters for use in the hyperthermophilic archaeon Sulfolobus acidocaldarius. The promoters were tested with the aid of an E. coli-Sulfolobus shuttle vector in reporter gene experiments. As the most suitable inducible promoter a maltose inducible promoter was identified. It comprises 266 bp of the sequence upstream of the gene coding for the maltose/maltotriose binding protein (mbp, Saci_1165). Induction is feasible with either maltose or dextrin at concentrations of 0.2-0.4%. The highest increase in expression (up to 17-fold) was observed in late exponential and stationary phase around 30-50 h after addition of dextrin. Whereas in the presence of glucose and xylose higher basal activity and reduced inducibility with maltose is observed, sucrose can be used in the growth medium additionally without affecting the basal activity or the inducibility. The minimal promoter region necessary could be narrowed down to 169 bp of the upstream sequence. The ABCE1 protein from S. solfataricus was successfully expressed under control of the inducible promoter with the shuttle vector pC and purified from the S. acidocaldarius culture with a yield of about 1 mg L(-1) culture. In addition we also determined the promoter strength of several constitutive promoters.

  8. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)


    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive t

  9. Ice-sheet flow conditions deduced from mechanical tests of ice core

    DEFF Research Database (Denmark)

    Miyamoto, Atsushi; Narita, Hideki; Hondoh, Takeo;


    Uniaxial compression tests were performed on samples of the Greenland Ice Core Project (GRIP) deep ice core, both in the field and later in a cold-room laboratory, in order to understand the ice-flow behavior of large ice sheets. Experiments were conducted under conditions of constant strain rate......-core samples with basal planes parallel to the horizontal plane of the ice sheet. The ice-flow enhancement factors show a gradual increase with depth down to approximately 2000 m. These results can be interpreted in terms of an increase in the fourth-order Schmid factor. Below 2000 m depth, the flow...

  10. Mathematical modelling of p53 basal dynamics and DNA damage response. (United States)

    Chong, Ket Hing; Samarasinghe, Sandhya; Kulasiri, Don


    The p53 tumour suppressor protein is a transcription factor that activates genes that result in cell cycle arrest, DNA damage repair, senescence or apoptosis. Recent individual cell studies have indicated that p53 activation is highly regulated in response to stressed conditions and non-stressed (normal proliferating) conditions in cells. The aim of this research is to investigate the design principles behind the precise regulation of p53 activation, under normal and stressed conditions. We extended the Sun et al. (2011) mathematical model of delay differential equations by incorporating the most recently found molecular interactions and hypotheses. In particular, we found that the core regulatory network consists of ATM, Mdm2, MdmX, Wip1 and p53. Our model of the p53 core regulatory feedback mechanisms can reproduce a series of repeated pulses in stressed conditions with appropriate induction of cell cycle arrest, and one or two spontaneous pulses (basal dynamics) in non-stressed conditions and these are consistent with the recent experimental findings. Our results show that the p53 spontaneous pulses are due to intrinsic DNA double strand breaks in normal proliferating cells, and p53 auto-regulation (positive feedback loop) allows threshold activation of p53 in generating these pulses. It also shows that the p53 dynamics are excitable; bifurcation analysis revealed a spectrum of p53 behaviour under stressed and non-stressed (normal) conditions on the basis of stress signal activation rate, and characterised p53 dynamics as Type II excitability. Additionally, the model makes testable predictions on pharmacological intervention to reactivate p53. Importantly, we reveal novel findings on the mechanism of threshold activation of p53 pulsatile and oscillatory dynamics that are important for its physiological function as the guardian of the genome.

  11. Marine ice sheet model performance depends on basal sliding physics and sub-shelf melting (United States)

    Gladstone, Rupert Michael; Warner, Roland Charles; Galton-Fenzi, Benjamin Keith; Gagliardini, Olivier; Zwinger, Thomas; Greve, Ralf


    Computer models are necessary for understanding and predicting marine ice sheet behaviour. However, there is uncertainty over implementation of physical processes at the ice base, both for grounded and floating glacial ice. Here we implement several sliding relations in a marine ice sheet flow-line model accounting for all stress components and demonstrate that model resolution requirements are strongly dependent on both the choice of basal sliding relation and the spatial distribution of ice shelf basal melting.Sliding relations that reduce the magnitude of the step change in basal drag from grounded ice to floating ice (where basal drag is set to zero) show reduced dependence on resolution compared to a commonly used relation, in which basal drag is purely a power law function of basal ice velocity. Sliding relations in which basal drag goes smoothly to zero as the grounding line is approached from inland (due to a physically motivated incorporation of effective pressure at the bed) provide further reduction in resolution dependence.A similar issue is found with the imposition of basal melt under the floating part of the ice shelf: melt parameterisations that reduce the abruptness of change in basal melting from grounded ice (where basal melt is set to zero) to floating ice provide improved convergence with resolution compared to parameterisations in which high melt occurs adjacent to the grounding line.Thus physical processes, such as sub-glacial outflow (which could cause high melt near the grounding line), impact on capability to simulate marine ice sheets. If there exists an abrupt change across the grounding line in either basal drag or basal melting, then high resolution will be required to solve the problem. However, the plausible combination of a physical dependency of basal drag on effective pressure, and the possibility of low ice shelf basal melt rates next to the grounding line, may mean that some marine ice sheet systems can be reliably simulated at

  12. LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.

    Directory of Open Access Journals (Sweden)

    Yan Liu


    Full Text Available Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT. For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1 is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.

  13. Cost-efficient FPGA implementation of basal ganglia and their Parkinsonian analysis. (United States)

    Yang, Shuangming; Wang, Jiang; Li, Shunan; Deng, Bin; Wei, Xile; Yu, Haitao; Li, Huiyan


    The basal ganglia (BG) comprise multiple subcortical nuclei, which are responsible for cognition and other functions. Developing a brain-machine interface (BMI) demands a suitable solution for the real-time implementation of a portable BG. In this study, we used a digital hardware implementation of a BG network containing 256 modified Izhikevich neurons and 2048 synapses to reliably reproduce the biological characteristics of BG on a single field programmable gate array (FPGA) core. We also highlighted the role of Parkinsonian analysis by considering neural dynamics in the design of the hardware-based architecture. Thus, we developed a multi-precision architecture based on a precise analysis using the FPGA-based platform with fixed-point arithmetic. The proposed embedding BG network can be applied to intelligent agents and neurorobotics, as well as in BMI projects with clinical applications. Although we only characterized the BG network with Izhikevich models, the proposed approach can also be extended to more complex neuron models and other types of functional networks.

  14. Assessing Core Competencies (United States)

    Narayanan, M.


    Catherine Palomba and Trudy Banta offer the following definition of assessment, adapted from one provided by Marches in 1987. Assessment in the systematic collection, review, and use of information about educational programs undertaken for the purpose of improving student learning and development. (Palomba and Banta 1999). It is widely recognized that sophisticated computing technologies are becoming a key element in today's classroom instructional techniques. Regardless, the Professor must be held responsible for creating an instructional environment in which the technology actually supplements learning outcomes of the students. Almost all academic disciplines have found a niche for computer-based instruction in their respective professional domain. In many cases, it is viewed as an essential and integral part of the educational process. Educational institutions are committing substantial resources to the establishment of dedicated technology-based laboratories, so that they will be able to accommodate and fulfill students' desire to master certain of these specific skills. This type of technology-based instruction may raise some fundamental questions about the core competencies of the student learner. Some of the most important questions are : 1. Is the utilization of these fast high-powered computers and user-friendly software programs creating a totally non-challenging instructional environment for the student learner ? 2. Can technology itself all too easily overshadow the learning outcomes intended ? 3. Are the educational institutions simply training students how to use technology rather than educating them in the appropriate field ? 4. Are we still teaching content-driven courses and analysis oriented subject matter ? 5. Are these sophisticated modern era technologies contributing to a decline in the Critical Thinking Capabilities of the 21st century technology-savvy students ? The author tries to focus on technology as a tool and not on the technology

  15. Influence of interferon-gamma on the differentiation of cholinergic neurons in rat embryonic basal forebrain and septal nuclei

    Institute of Scientific and Technical Information of China (English)

    Yanhong Luo; Lin An


    nerve cells. Nerve cells were marked with MAP2 and counted to evaluate the neuronal proliferation in basal forebrain and septal nuclei.MAIN OUTCOME MEASURES: Effect of interferon-γ on the number and activity of choline acetyl transferase-positive cells in basal forebrain and septal nuclei as well as the effect on neuronal proliferation.RESULTS: ① Nerve cells in the basal forebrain and septal nuclei of IFN-γ group grew well compared with control group. ② The differentiation of cholinergic neurons: The number and activity of choline acetyl transferase positive cells in IFN-γ group were significantly higher than those in the control group [(49.30±4.92) /100 cells vs (7.50±1.58) /100 cells; (2 049.00±12.30) min-1 vs (1 227.30±12.59) min 1, P < 0.01],while there was no significant difference in the number and activity of choline acetyl transferase positive cells between IFN-γ + IFN-γ antibody group and control group(P > 0.05). ③ The proliferation of cholinergic neurons: Cell percentage was 17.2% and 19.8% at S-stage, 6.2% and 6.1% at G2+M stage in the control group and IFN-γ group respectively, without significant difference (P > 0.05).CONCLUSION: IFN-γ does not promote the neuronal proliferation in basal forebrain and septal nuclei, and the increased expression of cholinergic neurons is not resulted by the increase in the number of neurons, but its differentiation.

  16. Pressure Core Characterization (United States)

    Santamarina, J. C.


    Natural gas hydrates form under high fluid pressure and low temperature, and are found in permafrost, deep lakes or ocean sediments. Hydrate dissociation by depressurization and/or heating is accompanied by a multifold hydrate volume expansion and host sediments with low permeability experience massive destructuration. Proper characterization requires coring, recovery, manipulation and testing under P-T conditions within the stability field. Pressure core technology allows for the reliable characterization of hydrate bearing sediments within the stability field in order to address scientific and engineering needs, including the measurement of parameters used in hydro-thermo-mechanical analyses, and the monitoring of hydrate dissociation under controlled pressure, temperature, effective stress and chemical conditions. Inherent sampling effects remain and need to be addressed in test protocols and data interpretation. Pressure core technology has been deployed to study hydrate bearing sediments at several locations around the world. In addition to pressure core testing, a comprehensive characterization program should include sediment analysis, testing of reconstituted specimens (with and without synthetic hydrate), and in situ testing. Pressure core characterization technology can be used to study other gas-charged formations such as deep sea sediments, coal bed methane and gas shales.

  17. Inner core structure behind the PKP core phase triplication

    NARCIS (Netherlands)

    Blom, Nienke A.; Deuss, Arwen; Paulssen, Hanneke; Waszek, Lauren


    The structure of the Earth's inner core is not well known between depths of ∼100–200 km beneath the inner core boundary. This is a result of the PKP core phase triplication and the existence of strong precursors to PKP phases, which hinder the measurement of inner core compressional PKIKP waves at e

  18. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Directory of Open Access Journals (Sweden)

    Lynne Robertson


    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  19. Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. (United States)

    Sharpe, Hayley J; Pau, Gregoire; Dijkgraaf, Gerrit J; Basset-Seguin, Nicole; Modrusan, Zora; Januario, Thomas; Tsui, Vickie; Durham, Alison B; Dlugosz, Andrzej A; Haverty, Peter M; Bourgon, Richard; Tang, Jean Y; Sarin, Kavita Y; Dirix, Luc; Fisher, David C; Rudin, Charles M; Sofen, Howard; Migden, Michael R; Yauch, Robert L; de Sauvage, Frederic J


    Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

  20. Basal Secretion of Lysozyme from Human Airways in Vitro

    Directory of Open Access Journals (Sweden)

    Patricia Roger


    Full Text Available The aim of this study was to examine the basal release of lysozyme from isolated human lung tissues. Measurements of lysozyme in the fluids derived from lung preparations were performed using a rate-of-lysis assay subsequent to acidification of the biological samples. Lysozyme released from bronchial preparations into fluids was greater than that observed for parenchymal tissues. The lysozyme quantities detected in bronchial fluids were not modified by removal of the surface epithelium. Furthermore, the quantities of lysozyme in bronchial fluids was correlated with the size of the bronchial preparations. These results suggest that the lysozyme was principally secreted by the human bronchi (submucosal layer rather than by parenchyma tissues and that a greater release was observed in the proximal airways.

  1. Petrophysical evaluation methods: basal quartz formation, Manyberries Area , Alberta

    Energy Technology Data Exchange (ETDEWEB)

    Davis, B.W.


    Hydrocarbons, both oil and gas, have been discovered in the basal quartz formation in the Manyberries area of SE Alberta. Estimation of producible fluids and hydrocarbons in place has been difficult due to the very shaly nature of the reservoir rock. Calculations of water saturation with no corrections for clay conductivity underestimates the hydrocarbons in place. The Waxman-Smits evaluation technique, which provides a method to account for clay conductivities, was used to estimate water saturation based on total porosity. Work of other authors provides a technique to correlate total and effective porosities. This was used to estimate effective porosity and subsequently water saturation based on the effective porosity. Error analysis was undertaken to estimate the uncertainty in the calculated water saturations.

  2. Desalination of Basal Water by Mesoporous Carbons Nanocomposite Membrane. (United States)

    Choi, Jeongdong; Ahn, Youngho; Gamal El-Din, Mohamed; Kim, Eun-Sik


    The hydro-transportation process used to obtain bitumen from the Alberta oil sands produces large volume of basal depressurization water (BDW), which contains high salt concentrations. In this research, thin-film nanocomposite (TFN) membrane technology applied to treat BDW in lab-scale, and evaluated water properties before and after the treatment. The average rejection ratios of ionic species were 95.2% and 92.8% by TFN membrane (with ordered mesoporous carbons (OMCs)) and thin-film composite (TFC) (without OMCs) membrane, respectively. The turbidity and total dissolved solids (TDS) were completely rejected in all treatment conditions. Interestingly, the water flux of TFN membrane was dramatically increased compared to TFC membrane. The increase of water flux was believed to be caused by the increased membrane surface hydrophilicity and nano-pore effects by the OMCs.

  3. Redefinition and global estimation of basal ecosystem respiration rate

    DEFF Research Database (Denmark)

    Yuan, Wenping; Luo, Yiqi; Li, Xianglan;


    Basal ecosystem respiration rate (BR), the ecosystem respiration rate at a given temperature, is a common and important parameter in empirical models for quantifying ecosystem respiration (ER) globally. Numerous studies have indicated that BR varies in space. However, many empirical ER models still...... use a global constant BR largely due to the lack of a functional description for BR. In this study, we redefined BR to be ecosystem respiration rate at the mean annual temperature. To test the validity of this concept, we conducted a synthesis analysis using 276 site-years of eddy covariance data...... use efficiency GPP model (i.e., EC-LUE) was applied to estimate global GPP, BR and ER with input data from MERRA (Modern Era Retrospective-Analysis for Research and Applications) and MODIS (Moderate resolution Imaging Spectroradiometer). The global ER was 103 Pg C yr −1, with the highest respiration...

  4. Basal ganglia calcification as a putative cause for cognitive decline

    Directory of Open Access Journals (Sweden)

    João Ricardo Mendes de Oliveira

    Full Text Available ABSTRACT Basal ganglia calcifications (BGC may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients

  5. A basal tyrannosauroid dinosaur from the Late Jurassic of China. (United States)

    Xu, Xing; Clark, James M; Forster, Catherine A; Norell, Mark A; Erickson, Gregory M; Eberth, David A; Jia, Chengkai; Zhao, Qi


    The tyrannosauroid fossil record is mainly restricted to Cretaceous sediments of Laurasia, although some very fragmentary Jurassic specimens have been referred to this group. Here we report a new basal tyrannosauroid, Guanlong wucaii gen. et sp. nov., from the lower Upper Jurassic of the Junggar Basin, northwestern China. G. wucaii is the oldest known tyrannosauroid and shows several unexpectedly primitive pelvic features. Nevertheless, the limbs of G. wucaii share several features with derived coelurosaurs, and it possesses features shared by other coelurosaurian clades. This unusual combination of character states provides an insight into the poorly known early radiation of the Coelurosauria. Notably, the presumed predatory Guanlong has a large, fragile and highly pneumatic cranial crest that is among the most elaborate known in any non-avian dinosaur and could be comparable to some classical exaggerated ornamental traits among vertebrates.

  6. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia


    was 66.1 years. The most common localisations were the forehead (31.3%), the nose (31.0%) and the cheek (14.7%). Primary BCC comprised 54.0%; the remaining cases were relapses, most frequently after curettage (36.9%), radiotherapy (18.9%) and photodynamic therapy (11.7%). MMS leads to 40% smaller skin......INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... of the surrounding healthy skin, and it also offers higher cure rates than standard tumour excision with a predefined margin of healthy skin. The superiority of MMS relies on the fact that the entire (100%) margin of the excised tissue is examined microscopically for residual tumour in contrast to the traditional...

  7. Does Lactation Mitigate Triple Negative/Basal Breast Cancer Progression? (United States)


    Jennifer Richer (Department of Pathology) for critical manuscript review; Dr. Marileila Garcia (University of Colorado Cancer Center Cytogenetics Core...Res 2008, 68(18):7278-7282. 48. Sleeman KE, Kendrick H, Robertson D, Isacke CM, Ashworth A, Smalley MJ: Dissociation of estrogen receptor expression

  8. Basal lamina structural alterations in human asymmetric aneurismatic aorta

    Directory of Open Access Journals (Sweden)

    M Cotrufo


    Full Text Available Basal lamina (BL is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation.We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens.We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study.We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RTPCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin a2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type

  9. Auditory cortex basal activity modulates cochlear responses in chinchillas.

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    Alex León

    Full Text Available BACKGROUND: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. METHODOLOGY/PRINCIPAL FINDINGS: Cochlear microphonics (CM, auditory-nerve compound action potentials (CAP and auditory cortex evoked potentials (ACEP were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments and a permanent reduction in five chinchillas (lesion experiments. We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. CONCLUSIONS/SIGNIFICANCE: These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the

  10. The nervous systems of basally branching nemertea (palaeonemertea.

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    Patrick Beckers

    Full Text Available In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

  11. The nervous systems of basally branching nemertea (palaeonemertea). (United States)

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas


    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.


    Directory of Open Access Journals (Sweden)



    Full Text Available The studies aimed to describe the nervous formations from the base of the cranium in the hen and domestic duck. These clarifications are necessary in order to disclose some unknown facts regarding this region in the poultry species used preponderantly in laboratory studies of the aviary flu. The vegetative connections from the base of the skull have been studied on 10 poultry specimens, 5 hens and 5 ducks. The animals have been euthanatized using chloroform and a special dye has been injected through the heart in order to achieve a better differentiation of the nervous formations. Dissection was performed under a magnifying glass using instruments adequate to highly fine dissections. Photos and sketches of the dissected pieces have been taken. Nomina Anatomica (2003 was used to describe the observed formations.The studies showed that the cranial cervical ganglia around which is the sub-basal nervous tissue, is located on the border of the occipital hole, at the basis of the temporal pyramid, much deeper than in mammalians; it is better developed in the duck (3-4 mm than in the hen (1-2 mm; the cranial cervical ganglia has the shape of a globe in gallinaceans and it is long in shape in the ducks. A multitude of connecting branches were observed around the lymph node, linking it to the vague nerve, to the hypoglossal nerve, to the glossopharyngeal nerve and to the transversal paravertebral chain which is specific to poultry; an obvious branch detaches from the cranial pole, which is the sub-basal connective, while the cervical connective detaches from the caudal pole, connecting it to the cervical-thoracic lymph node.

  13. Vector promoters used in Klebsiella pneumoniae. (United States)

    Jiang, Xiao; Zhu, Chengqian; Lin, Jie; Li, Jingkang; Fu, Shuilin; Gong, Heng


    Much effort has been devoted to the metabolic engineering of Klebsiella pneumoniae; however, our knowledge of the actual expression level of promoters used in K. pneumoniae is limited. In this study, the expression levels of three promoters were compared systematically by using the lacZ reporter gene with different carbon sources in K. pneumoniae. The results showed that, although promoters PT5 and Ptac designed for Escherichia coli were functional, PT5 appeared more efficient and the induction/repression ratio of Ptac was decreased extremely in K. pneumoniae. The basal level of Ptac for lacZ expression reached 396.5 U/mg, which was 9.5-fold higher compared with PT5 in LB medium, indicating Ptac can be used as an efficient "constitutive" promoter as well as an efficient induced promoter in K. pneumoniae. In different carbon sources medium, a newly constructed endogenous constitutive Pbud proved to be a stable and weak promoter. On the basis of our data, a set of Pbud and Ptac promoters could meet the broad range (about 1,000 orders of magnitude) of gene expression needed for engineered K. pneumoniae in glycerol-based medium.

  14. 面向农民的农业技术推广问题分析--以交易成本理论为视域%Analysis of the Problem of Taking Farmers as the Core of Agricultural Technology Promotion Channel---Form the Perspective of the Transaction Costs Theory

    Institute of Scientific and Technical Information of China (English)



      在计划经济体制下建立的传统农业技术推广体系曾经发挥过重要历史性作用,但是难以适应市场经济条件下农业与农村发展对多样化、多层次农业技术的需求。首先概述交易成本的概念;其次解释了农业技术推广中农民的交易成本过大,这样打击了农民参与应用农业技术、产品的积极性;最后,通过以农民为核心的创新农技推广渠道,以此来实现减少农民为获得农业技术、产品的交易成本的目标。%In the planned economic system , the traditional agricultural technology popularization system played an important historical role , but it is difficult to adapt to the market economy in the condition of development demand for diversified and multi -level agricultural technology . This paper first outlines the concept of transaction costs and then explains the heavy transaction costs of the farmers in agricultural technology popularization , which influences the enthusiasm of farmers to participate in the application of agricultural technology and products . Finally , by treating farmers as the core of innovation in agricultural technology promotion channels , we aim to reduce the transaction costs of agricultural technology and products .

  15. Birefringent hollow core fibers

    DEFF Research Database (Denmark)

    Roberts, John


    Hollow core photonic crystal fiber (HC-PCF), fabricated according to a nominally non-birefringent design, shows a degree of un-controlled birefringence or polarization mode dispersion far in excess of conventional non polarization maintaining fibers. This can degrade the output pulse in many...... and an increased overlap between the polarization modes at the glass interfaces. The interplay between these effects leads to a wavelength for optimum polarization maintenance, lambda(PM), which is detuned from the wavelength of highest birefringence. By a suitable fiber design involving antiresonance of the core...

  16. Cloning and characterization of the Mx1, Mx2 and Mx3 promoters from gilthead seabream (Sparus aurata). (United States)

    González-Mariscal, J A; Gallardo-Gálvez, J B; Méndez, T; Álvarez, M C; Béjar, J


    Mx proteins are main effectors of the antiviral innate immune response mediated by type I interferon (IFN I). Actually, diverse Mx proteins from fish proved highly active against fish viruses, standing out among them the Mx1, Mx2 and Mx3 from gilthead seabream (Sparus aurata), a species exhibiting a natural resistance to viral diseases. In this study, the structure and functional activity of their corresponding promoters (pMx1, pMx2 and pMx3) have been assessed. The three promoters present an identical 3' region of 157 bp, exhibiting a single canonical interferon-stimulated response element (ISRE), which is indispensible for the poli:IC induction of pMx1 and pMx3, while not for that of pMx2. In the remaining part of the three promoters other regulatory motifs were identified, as gamma IFN activated sites in variable number (1, 4 and 2 in pMx1, pMx2 and pMx3, respectively), as well as several independent GAAA elements or ISRE core sequences (13, 15 and 12 in pMx1, pMx2 and pMx3, respectively). The structural dissimilarities shown by the three promoters parallels with the differences observed in their response profiles, in terms of the time course of the induction, and basal and induced expression levels of each promoter. Altogether, these findings indicate that the expression of Mx1, Mx2 and Mx3 genes from the gilthead seabream might be specifically regulated, in accordance with the functional role of each Mx protein in the successful antiviral response shown by this species.

  17. Nuclear 28S rDNA phylogeny supports the basal placement of Noctiluca scintillans (Dinophyceae; Noctilucales) in dinoflagellates. (United States)

    Ki, Jang-Seu


    Noctiluca scintillans (Macartney) Kofoid et Swezy, 1921 is an unarmoured heterotrophic dinoflagellate with a global distribution, and has been considered as one of the ancestral taxa among dinoflagellates. Recently, 18S rDNA, actin, alpha-, beta-tubulin, and Hsp90-based phylogenies have shown the basal position of the noctilucids. However, the relationships of dinoflagellates in the basal lineages are still controversial. Although the nuclear rDNA (e.g. 18S, ITS-5.8S, and 28S) contains much genetic information, DNA sequences of N. scintillans rDNA molecules were insufficiently characterized as yet. Here the author sequenced a long-range nuclear rDNA, spanning from the 18S to the D5 region of the 28S rDNA, of N. scintillans. The present N. scintillans had a nearly identical genotype (>99.0% similarity) compared to other Noctiluca sequences from different geographic origins. Nucleotide divergence in the partial 28S rDNA was significantly high (pdinoflagellates, two perkinsids, and two apicomplexans as outgroups showed that N. scintillans and Oxyrrhis marina formed a clade that diverged separately from core dinoflagellates.

  18. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Arpandev Bhattacharyya


    Full Text Available Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30 therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A 1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216 switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6% to week 24 (1.0% in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001, while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.

  19. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study (United States)

    Bhattacharyya, Arpandev; Shetty, Raman; Rajkumar, C; Bantwal, Ganapathi


    Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH) insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216) switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6%) to week 24 (1.0%) in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001), while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort. PMID:25143902

  20. Languages for Dublin Core. (United States)

    Baker, Thomas


    Focusing on languages for the Dublin Core, examines the experience of some related ways to seek semantic interoperability through simplicity: planned languages, interlingua constructs, and pidgins. Also defines the conceptual and organizational problem of maintaining a metadata standard in multiple languages. (AEF)

  1. Modeling Core Collapse Supernovae (United States)

    Mezzacappa, Anthony


    Core collapse supernovae, or the death throes of massive stars, are general relativistic, neutrino-magneto-hydrodynamic events. The core collapse supernova mechanism is still not in hand, though key components have been illuminated, and the potential for multiple mechanisms for different progenitors exists. Core collapse supernovae are the single most important source of elements in the Universe, and serve other critical roles in galactic chemical and thermal evolution, the birth of neutron stars, pulsars, and stellar mass black holes, the production of a subclass of gamma-ray bursts, and as potential cosmic laboratories for fundamental nuclear and particle physics. Given this, the so called ``supernova problem'' is one of the most important unsolved problems in astrophysics. It has been fifty years since the first numerical simulations of core collapse supernovae were performed. Progress in the past decade, and especially within the past five years, has been exponential, yet much work remains. Spherically symmetric simulations over nearly four decades laid the foundation for this progress. Two-dimensional modeling that assumes axial symmetry is maturing. And three-dimensional modeling, while in its infancy, has begun in earnest. I will present some of the recent work from the ``Oak Ridge'' group, and will discuss this work in the context of the broader work by other researchers in the field. I will then point to future requirements and challenges. Connections with other experimental, observational, and theoretical efforts will be discussed, as well.

  2. Core calculations of JMTR

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, Yoshiharu [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment


    In material testing reactors like the JMTR (Japan Material Testing Reactor) of 50 MW in Japan Atomic Energy Research Institute, the neutron flux and neutron energy spectra of irradiated samples show complex distributions. It is necessary to assess the neutron flux and neutron energy spectra of an irradiation field by carrying out the nuclear calculation of the core for every operation cycle. In order to advance core calculation, in the JMTR, the application of MCNP to the assessment of core reactivity and neutron flux and spectra has been investigated. In this study, in order to reduce the time for calculation and variance, the comparison of the results of the calculations by the use of K code and fixed source and the use of Weight Window were investigated. As to the calculation method, the modeling of the total JMTR core, the conditions for calculation and the adopted variance reduction technique are explained. The results of calculation are shown. Significant difference was not observed in the results of neutron flux calculations according to the difference of the modeling of fuel region in the calculations by K code and fixed source. The method of assessing the results of neutron flux calculation is described. (K.I.)

  3. Some Core Contested Concepts (United States)

    Chomsky, Noam


    Core concepts of language are highly contested. In some cases this is legitimate: real empirical and conceptual issues arise. In other cases, it seems that controversies are based on misunderstanding. A number of crucial cases are reviewed, and an approach to language is outlined that appears to have strong conceptual and empirical motivation, and…

  4. The core and cosmopolitans

    DEFF Research Database (Denmark)

    Dahlander, Linus; Frederiksen, Lars


    Users often interact and help each other solve problems in communities, but few scholars have explored how these relationships provide opportunities to innovate. We analyze the extent to which people positioned within the core of a community as well as people that are cosmopolitans positioned...

  5. Schumpeter's core works revisited

    DEFF Research Database (Denmark)

    Andersen, Esben Sloth


    This paper organises Schumpeter’s core books in three groups: the programmatic duology,the evolutionaryeconomic duology,and the socioeconomic synthesis. By analysing these groups and their interconnections from the viewpoint of modern evolutionaryeconomics,the paper summarises resolved problems...

  6. Adult educators' core competences

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne


    environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or “core...

  7. Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology


    Schmitz, Taylor W.; Nathan Spreng, R.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q.; Toga, Arthur W; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Leslie M Shaw; Khachaturian, Zaven


    There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received ne...

  8. Controlling promoter strength and regulation in Saccharomyces cerevisiae using synthetic hybrid promoters. (United States)

    Blazeck, John; Garg, Rishi; Reed, Ben; Alper, Hal S


    A dynamic range of well-controlled constitutive and tunable promoters are essential for metabolic engineering and synthetic biology applications in all host organisms. Here, we apply a synthetic hybrid promoter approach for the creation of strong promoter libraries in the model yeast, Saccharomyces cerevisiae. Synthetic hybrid promoters are composed of two modular components-the enhancer element, consisting of tandem repeats or combinations of upstream activation sequences (UAS), and the core promoter element. We demonstrate the utility of this approach with three main case studies. First, we establish a dynamic range of constitutive promoters and in doing so expand transcriptional capacity of the strongest constitutive yeast promoter, P(GPD) , by 2.5-fold in terms of mRNA levels. Second, we demonstrate the capacity to impart synthetic regulation through a hybrid promoter approach by adding galactose activation and removing glucose repression. Third, we establish a collection of galactose-inducible hybrid promoters that span a nearly 50-fold dynamic range of galactose-induced expression levels and increase the transcriptional capacity of the Gal1 promoter by 15%. These results demonstrate that promoters in S. cerevisiae, and potentially all yeast, are enhancer limited and a synthetic hybrid promoter approach can expand, enhance, and control promoter activity.

  9. Science Signaling Podcast for 21 February 2017: Pentraxin-3 in basal-like breast cancer. (United States)

    Karnoub, Antoine E; VanHook, Annalisa M


    This Podcast features an interview with Antoine Karnoub, senior author of a Research Article that appears in the 21 February 2017 issue of Science Signaling, about how pentraxin-3 (PTX3) links increased phosphoinositide 3-kinase (PI3K) signaling to stem cell properties in basal-like breast cancer (BLBC). BLBC is an aggressive type of breast cancer in which the tumor cells exhibit increased PI3K signaling and have stem cell-like properties. Thomas et al found that aberrant PI3K signaling in BLBCs stimulated the expression of PTX3, which encodes a protein that functions in innate immunity. PTX3 promoted stem cell-like traits in mammary epithelial cells and stimulated the growth of breast cancer cells. Conversely, decreasing the abundance of PTX3 in breast cancer cells reduced both the growth of these cells and their expression of stem cell markers. The abundance of PTX3 transcripts in breast tumors negatively correlated with patient survival, suggesting that PTX3 may be a useful biomarker for stratifying BLBC patients and that targeting PTX3 may suppress tumor growth in some BLBC patients.Listen to Podcast.

  10. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem


    Full Text Available O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambiental associado a sua gênese. Entretanto, descrevem-se outros elementos de risco: fotótipos claros, idade avançada, história familiar de carcinomas de pele, olhos e cabelos claros, sardas na infância e imunossupressão, além de aspectos comportamentais, como exercício profissional exposto ao sol, atividade rural e queimaduras solares na juventude. Entre 30% e 75% dos casos esporádicos estão associados à mutação do gene patched hedgehog, mas outras alterações genéticas são ainda descritas. A neoplasia é comumente encontrada concomitantemente com lesões cutâneas relacionadas à exposição solar crônica, tais como: queratoses actínicas, lentigos solares e telangiectasias faciais. A prevenção do carcinoma basocelular se baseia no conhecimento de fatores de risco, no diagnóstico e tratamento precoces e na adoção de medidas específicas, principalmente, nas populações susceptíveis. Os autores apresentam uma revisão da epidemiologia do carcinoma basocelular.Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor

  11. Traumatic bilateral basal ganglia bleed: A report of rare two cases and review of the literature (United States)

    Kankane, Vivek Kumar; Gupta, Tarun Kumar; Jaiswal, Gaurav


    Traumatic basal ganglia hemorrhage (TBGH) is relatively uncommon. Bilateral basal ganglia hematoma after trauma is extremely rare and is limited to case reports. We report two cases of traumatic bilateral basal ganglia hemorrhage and review the literature in brief. Both cases were managed conservatively. The general incidence of TBGH is reported between 2.4% and 3% of closed head injury. However, the incidence is higher in postmortem studies (9.8%). Bilateral traumatic basal ganglia hematoma is extremely rare. Descriptions are limited to case reports.

  12. NLRC5 controls basal MHC class I gene expression in an MHC enhanceosome-dependent manner. (United States)

    Neerincx, Andreas; Rodriguez, Galaxia M; Steimle, Viktor; Kufer, Thomas A


    Nucleotide-binding domain and leucine-rich repeat (NLR) proteins play important roles in innate immune responses as pattern-recognition receptors. Although most NLR proteins act in cell autonomous immune pathways, some do not function as classical pattern-recognition receptors. One such NLR protein is the MHC class II transactivator, the master regulator of MHC class II gene transcription. In this article, we report that human NLRC5, which we recently showed to be involved in viral-mediated type I IFN responses, shuttles to the nucleus and activates MHC class I gene expression. Knockdown of NLRC5 in different human cell lines and primary dermal fibroblasts leads to reduced MHC class I expression, whereas introduction of NLRC5 into cell types with very low expression of MHC class I augments MHC class I expression to levels comparable to those found in lymphocytes. Expression of NLRC5 positively correlates with MHC class I expression in human tissues. Functionally, we show that both the N-terminal effector domain of NLRC5 and its C-terminal leucine-rich repeat domain are needed for activation of MHC class I expression. Moreover, nuclear shuttling and function depend on a functional Walker A motif. Finally, we identified a promoter sequence in the MHC class I promoter, the X1 box, to be involved in NLRC5-mediated MHC class I gene activation. Taken together, this suggested that NLRC5 acts in a manner similar to class II transactivator to drive MHC expression and revealed NLRC5 as an important regulator of basal MHC class I expression.

  13. Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain. (United States)

    Vazquez-DeRose, Jacqueline; Schwartz, Michael D; Nguyen, Alexander T; Warrier, Deepti R; Gulati, Srishti; Mathew, Thomas K; Neylan, Thomas C; Kilduff, Thomas S


    Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. We hypothesized that HCRT antagonists induce sleep, in part, through disfacilitation of BF neurons; consequently, ALM should have reduced efficacy in BF-lesioned (BFx) animals. To test this hypothesis, rats were given bilateral IgG-192-saporin injections, which predominantly targets cholinergic BF neurons. BFx and intact rats were then given oral ALM, the benzodiazepine agonist zolpidem (ZOL) or vehicle (VEH) at lights-out. ALM was less effective than ZOL at inducing sleep in BFx rats compared to controls. BF adenosine (ADO), γ-amino-butyric acid (GABA), and glutamate levels were then determined via microdialysis from intact, freely behaving rats following oral ALM, ZOL or VEH. ALM increased BF ADO and GABA levels during waking and mixed vigilance states, and preserved sleep-associated increases in GABA under low and high sleep pressure conditions. ALM infusion into the BF also enhanced cortical ADO release, demonstrating that HCRT input is critical for ADO signaling in the BF. In contrast, oral ZOL and BF-infused ZOL had no effect on ADO levels in either BF or cortex. ALM increased BF ADO (an endogenous sleep-promoting substance) and GABA (which is increased during normal sleep), and required an intact BF for maximal efficacy, whereas ZOL blocked sleep-associated BF GABA release, and required no functional contribution from the BF to induce sleep. ALM thus induces sleep by facilitating the neural mechanisms underlying the normal transition to sleep.

  14. The Chemistry of Curcumin, the Health Promoting Ingredient in Turmeric (United States)

    Dewprashad, Brahmadeo


    Case studies pertaining to the health benefits of foods can be particularly effective in engaging students and in teaching core concepts in science (Heidemann and Urquart 2005). This case study focuses on the chemistry of curcumin, the health-promoting ingredient in turmeric. The case was developed to review core concepts in organic chemistry and…

  15. Study on core design for reduced-moderation water reactors

    Energy Technology Data Exchange (ETDEWEB)

    Okubo, Tsutomu [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment


    The Reduced-Moderation Water Reactor (RMWR) is a water-cooled reactor with the harder neutron spectrum comparing with the LWR, resulting from low neutron moderation due to reduced water volume fraction. Based on the difference from the spectrum from the LWR, the conversion from U-238 to Pu-239 is promoted and the new cores preferable to effective utilization of uranium resource can be possible Design study of the RMWR core started in 1997 and new four core concepts (three BWR cores and one PWR core) are recently evaluated in terms of control rod worths, plutonium multiple recycle, high burnup and void coefficient. Comparative evaluations show needed incorporation of control rod programming and simplified PUREX process as well as development of new fuel cans for high burnup of 100 GW-d/t. Final choice of design specifications will be made at the next step aiming at realization of the RMWR. (T. Tanaka)

  16. Setting a chronology for the basal ice at Dye-3 and GRIP: Implications for the long-term stability of the Greenland Ice Sheet (United States)

    Yau, Audrey M.; Bender, Michael L.; Blunier, Thomas; Jouzel, Jean


    The long-term stability of the Greenland Ice Sheet (GIS) is an important issue in our understanding of the climate system. Limited data suggest that the northern and southern sections extend well back into the Pleistocene, but most age constraints do not definitively date the ice. Here, we re-examine the GRIP and Dye-3 ice cores to provide direct ice core observations as to whether the GIS survived previous interglacials known to be warmer (˜130 ka) or longer (˜430 ka) than the present interglacial. We present geochemical analyses of the basal ice from Dye-3 (1991-2035 m) and GRIP (3020-3026 m) that characterize and date the ice. We analyzed the elemental and isotopic composition of O2, N2, and Ar, of trapped air in these two cores to assess the origin of trapped gases in silty ice. Dating of the trapped air was then achieved by measuring the paleoatmospheric δ40Ar/38Ar and the 17O anomaly (17Δ) of O2. The resulting age is a lower limit because the trapped air may be contaminated with crustal radiogenic 40Ar. The oldest average age of replicates measured at various depths is 970 ± 140 ka for the GRIP ice core and 400 ka ± 170 ka for Dye-3. 17Δ data from Dye-3 also argue strongly that basal ice in this core predates the Eemian. This confirms that the Greenland Ice Sheet did not completely melt at Southern Greenland during the last interglacial, nor did it completely melt at Summit Greenland during the unusually long interglacial ˜430 kyr before present.

  17. DNA immunization with fusion genes containing HCV core region and HBV core region

    Institute of Scientific and Technical Information of China (English)

    杨莉; 刘晶; 孔玉英; 汪垣; 李光地


    The eucaryotic expression plasmids were constructed to express the complete (HCc191) or the truncated (HCc69 and HCc40) HCV core genes, solely or fused with the HBV core gene (HBc144). These constructions were transiently expressed in COS cells under the control of the CMV promoter. The antigenicity of HBc and HCc could be detected in the expression products by ELISA and Western blot. The mice immunized with these expression plasmids efficiently produced the anti-HCc antibodies, and also anti-HBc antibodies when the plasmids contained the fusion genes. In addition, the antibodies induced by the fusion genes were more persistent than those induced by the non-fusion HCV core genes. These indicate that the fusion of HCc genes to HBc gene is in favor of the immunogenicity of HCc, while the immunogenicity of HBc is not affected.

  18. Application of Core Dynamics Modeling to Core-Mantle Interactions (United States)

    Kuang, Weijia


    Observations have demonstrated that length of day (LOD) variation on decadal time scales results from exchange of axial angular momentum between the solid mantle and the core. There are in general four core-mantle interaction mechanisms that couple the core and the mantle. Of which, three have been suggested likely the dominant coupling mechanism for the decadal core-mantle angular momentum exchange, namely, gravitational core-mantle coupling arising from density anomalies in the mantle and in the core (including the inner core), the electromagnetic coupling arising from Lorentz force in the electrically conducting lower mantle (e.g. D-layer), and the topographic coupling arising from non-hydrostatic pressure acting on the core-mantle boundary (CMB) topography. In the past decades, most effort has been on estimating the coupling torques from surface geomagnetic observations (kinematic approach), which has provided insights on the core dynamical processes. In the meantime, it also creates questions and concerns on approximations in the studies that may invalidate the corresponding conclusions. The most serious problem is perhaps the approximations that are inconsistent with dynamical processes in the core, such as inconsistencies between the core surface flow beneath the CMB and the CMB topography, and that between the D-layer electric conductivity and the approximations on toroidal field at the CMB. These inconsistencies can only be addressed with numerical core dynamics modeling. In the past few years, we applied our MoSST (Modular, Scalable, Self-consistent and Three-dimensional) core dynamics model to study core-mantle interactions together with geodynamo simulation, aiming at assessing the effect of the dynamical inconsistencies in the kinematic studies on core-mantle coupling torques. We focus on topographic and electromagnetic core-mantle couplings and find that, for the topographic coupling, the consistency between the core flow and the CMB topography is

  19. Exploring the cognitive and motor functions of the basal ganglia: an integrative review of computational cognitive neuroscience models


    Sebastien eHelie; Srinivasa eChakravarthy; Ahmed A. Moustafa


    Many computational models of the basal ganglia have been proposed over the past twenty-five years. While computational neuroscience models have focused on closely matching the neurobiology of the basal ganglia, computational cognitive neuroscience models have focused on how the basal ganglia can be used to implement cognitive and motor functions. This review article focuses on computational cognitive neuroscience models of the basal ganglia and how they use the neuroanatomy of the basal gangl...

  20. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas. (United States)

    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah


    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  1. Thresholds in the sliding resistance of simulated basal ice

    Directory of Open Access Journals (Sweden)

    L. F. Emerson


    Full Text Available We report laboratory determinations of the shear resistance to sliding melting ice with entrained particles over a hard, impermeable surface. With higher particle concentrations and larger particle sizes, Coulomb friction at particle-bed contacts dominates and the shear stress increases linearly with normal load. We term this the sandy regime. When either particle concentration or particle size is reduced below a threshold, the dependence of shear resistance on normal load is no longer statistically significant. We term this regime slippery. We use force and mass balance considerations to examine the flow of melt water beneath the simulated basal ice. At high particle concentrations, the transition from sandy to slippery behavior occurs when the particle size is comparable to the thickness of the melt film that separates the sliding ice from its bed. For larger particle sizes, a transition from sandy to slippery behavior occurs when the particle concentration drops sufficiently that the normal load is no longer transferred completely to the particle-bed contacts. We estimate that the melt films separating the particles from the ice are approximately 0.1 µm thick at this transition. Our laboratory results suggest the potential for abrupt transitions in the shear resistance beneath hard-bedded glaciers with changes in either the thickness of melt layers or the particle loading.

  2. Effects of aging on nitrergic system in human basal nuclei

    Directory of Open Access Journals (Sweden)

    Bruno Lopes dos Santos


    Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

  3. Everolimus for Compassionate Use in Multiple Basal Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Laura Eibenschutz


    Full Text Available Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR and has been shown to have antineoplastic activity in addition to its use as an immunosuppressive agent for the prevention of organ transplant rejection. We report the use of everolimus for the compassionate treatment of four elderly, nontransplant patients presenting with multiple basal cell carcinomas (BCC. All patients had a long history of BCC, had refused surgery as a current treatment option, and did not respond to alternative treatments (including topical 5-fluorouracil and imiquimod. Patients were treated with oral everolimus (1.5–3.0 mg daily for 12 months or longer: a complete and sustained response was seen in one case, and partial responses were seen in two other cases. Everolimus was well tolerated in these elderly patients. These promising preliminary data suggest that further dose-finding, controlled clinical studies are warranted to evaluate the antineoplastic effects of everolimus in patients affected by BCC who cannot or will not undergo surgery.

  4. Neglected Basal Cell Carcinomas in the 21st Century

    Directory of Open Access Journals (Sweden)

    Erika Varga


    Full Text Available Although tumors on the surface of the skin are considered to be easily recognizable, neglected advanced skin neoplasms are encountered even in the 21st century. There can be numerous causes of the delay in the diagnosis: fear of the diagnosis and the treatment, becoming accustomed to a slowly growing tumor, old age, a low social milieu, and an inadequate hygienic culture are among the factors leading some people not to seek medical advice. The treatment of such advanced neoplasms is usually challenging. The therapy of neglected cases demands an individual multidisciplinary approach and teamwork. Basal cell carcinoma (BCC, the most common cutaneous tumor, usually develops in the elderly, grows slowly, and has an extremely low metastatic potential; these factors are suggesting that BCCs might well be the “ideal candidates” for neglected tumors. Five neglected advanced cases of BCC were diagnosed in our dermatological institute between 2000 and 2009. The clinical characteristics and treatment modalities of these neoplasms are discussed, together with the possible causes of the neglect.

  5. Basal ganglia outputs map instantaneous position coordinates during behavior. (United States)

    Barter, Joseph W; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A; Bartholomew, Ryan A; Yin, Henry H


    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions.

  6. Vismodegib: in locally advanced or metastatic basal cell carcinoma. (United States)

    Keating, Gillian M


    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. Oral vismodegib was effective in the treatment of patients with locally advanced (n = 63) or metastatic (n = 33) BCC, according to the results of an ongoing, noncomparative, multinational, pivotal, phase II trial (ERIVANCE BCC). In this trial (using a clinical cutoff date of 26 November 2010), the independent review facility overall response rate was 42.9% in patients with locally advanced BCC and 30.3% in patients with metastatic BCC. In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.

  7. Basal magnetic flux and the local solar dynamo

    CERN Document Server

    Stenflo, J O


    The average unsigned magnetic flux density in magnetograms of the quiet Sun is generally dominated by instrumental noise. Due to the entirely different scaling behavior of the noise and the solar magnetic pattern it has been possible to determine the standard deviation of the Gaussian noise distribution and remove the noise contribution from the average unsigned flux density for the whole 15-yr SOHO/MDI data set and for a selection of SDO/HMI magnetograms. There is a very close correlation between the MDI disk-averaged unsigned vertical flux density and the sunspot number, and regression analysis gives a residual level of 2.7 G when the sunspot number is zero. The selected set of HMI magnetograms, which spans the most quiet phase of solar activity, has a lower limit of 3.0 G to the noise-corrected average flux density. These apparently cycle-independent levels may be identified as a basal flux density, which represents an upper limit to the possible flux contribution from a local dynamo, but not evidence for ...

  8. Geomagnetism of earth's core (United States)

    Benton, E. R.


    Instrumentation, analytical methods, and research goals for understanding the behavior and source of geophysical magnetism are reviewed. Magsat, launched in 1979, collected global magnetometer data and identified the main terrestrial magnetic fields. The data has been treated by representing the curl-free field in terms of a scalar potential which is decomposed into a truncated series of spherical harmonics. Solutions to the Laplace equation then extend the field upward or downward from the measurement level through intervening spaces with no source. Further research is necessary on the interaction between harmonics of various spatial scales. Attempts are also being made to analytically model the main field and its secular variation at the core-mantle boundary. Work is also being done on characterizing the core structure, composition, thermodynamics, energetics, and formation, as well as designing a new Magsat or a tethered satellite to be flown on the Shuttle.

  9. USGS Core Research Center (CRC) Collection of Core (United States)

    U.S. Geological Survey, Department of the Interior — The Core Research Center (CRC) was established in 1974 by the U.S. Geological Survey (USGS) to preserve valuable rock cores for use by scientists and educators from...

  10. Ice Cores of the National Ice Core Laboratory (United States)

    U.S. Geological Survey, Department of the Interior — The U.S. National Ice Core Laboratory (NICL) is a facility for storing, curating, and studying ice cores recovered from the polar regions of the world. It provides...

  11. Some core contested concepts. (United States)

    Chomsky, Noam


    Core concepts of language are highly contested. In some cases this is legitimate: real empirical and conceptual issues arise. In other cases, it seems that controversies are based on misunderstanding. A number of crucial cases are reviewed, and an approach to language is outlined that appears to have strong conceptual and empirical motivation, and to lead to conclusions about a number of significant issues that differ from some conventional beliefs.

  12. Central core disease

    Directory of Open Access Journals (Sweden)

    Jungbluth Heinz


    Full Text Available Abstract Central core disease (CCD is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown but the condition is probably more common than other congenital myopathies. CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle; orthopaedic complications are common and malignant hyperthermia susceptibility (MHS is a frequent complication. CCD and MHS are allelic conditions both due to (predominantly dominant mutations in the skeletal muscle ryanodine receptor (RYR1 gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1. Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanism(s. The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy; muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment. In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.

  13. Minimal Role of Basal Shear Tractions in Driving Nubia-Somalia Divergence Across the East African Rift System (United States)

    Stamps, D. S.; Calais, E.; Iaffaldano, G.; Flesch, L. M.


    The Nubian and Somalian plates actively diverge along the topographically high, ~5000 km long East African Rift System (EARS). As no major subduction zones bound Africa, one can assume that the forces driving the Nubia-Somalia plate system result primarily from mantle buoyancies and lateral variation in lithospheric gravitational potential energy. Images from seismic tomography and convection models suggest active mantle flow beneath Africa. However, the contribution from large-scale convection to the force balance driving plate divergence across the EARS remains in question. In this work we investigate the impact of mantle shear tractions on the dynamics of Nubia-Somalia divergence across the EARS. We compare surface motions inferred from GPS observations with strain rates and velocities predicted from dynamic models where basal shear stresses are (1) derived from forward mantle circulation models and (2) inferred from stress field boundary conditions that balance buoyancy forces in the African lithosphere. Upper mantle anisotropy derived from seismic observations beneath Africa provide independent constraints for the latter. Preliminary results suggest that basal shear tractions play a minor role in the dynamics of Nubia-Somalia divergence along the EARS. This result implies mantle-lithosphere decoupling, possibly promoted by a low viscosity asthenosphere. We corroborate the robustness of our results with estimates of upper mantle viscosity based on local upper mantle temperature estimates and rheological parameters obtained from laboratory experiments.

  14. Tetracycline-controlled transcriptional regulation systems:countermeasures to eliminate basal transgene leaks in Tet-based systems

    Institute of Scientific and Technical Information of China (English)

    XIAO Dong; SUN Yan; GU Weiwang; CHEN Xigu


    To analyze the function of any given transgene(s) accurately in transgenic mice, and to produce credible transgenic animal models of various human diseases (precisely and realistically mimicking disease states), it is critical to be able to control gene expression in the animals conditionally. The ability to switch gene expression "on" or "off" in the restricted cells or tissue(s) at specific time(s)allows unprecedented flexibility for exploring gene function(s) in both the health and the disease. Pioneering work on inducible transgene expression has led to the development of a wide variety of controlled gene expression systems that meet this criterion. Among them, the tetracycline-inducible systems (e. g. Tet-off and Tet-on) have been widely, frequently and successfully employed in vitro and in vivo.These systems, however, are not always tight but leaky; sometimes the leakage is significant. In some circumstances, the resulting leak is acceptable, but in others, it is more problematic. Though these systems face this disadvantage, i.e. basal transgene leakage in vitro and in vivo, several approaches, including using improved versions (e. g. rtTA2S-M2 and rtTA2S-S2) of rtTA, tetracycline-controlled transcriptional silencer (tTS), an "ideal" minimal promoter in responsive components or combinations thereof, have been developed to avoid this limitation effectively. In this review we discuss the countermeasures available to eliminate basal transgene leakage from Tet-based systems.

  15. Studies on the Mechanism of Single Basal Application of Controlled-Release Fertilizers for Increasing Yield of Rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    TANG Shuan-hu; YANG Shao-hai; CHEN Jian-sheng; XU Pei-zhi; ZHANG Fa-bao; AI Shao-ying; HUANG Xu


    This paper was to explore the mechanism of single basal application of controlled-release fertilizers for increasing yield of rice (Oryza sativa L.). Pot trials and cylinder trials were carried out from 2002 to 2005 to study the influences of single basal application of 3 controlled-release fertilizers on the changes of soil available N, root development, senescence and lodging resistance at late growth stages. Results showed that at 30 days after fertilization, single basal application of controlled-release fertilizers coated with vegetal-substance (CRF1) and polymer materials (CRF3) increased soil available N to 12.0 and 147.9%, respectively, in comparison to split fertilization of rice-specific fertilizer (RSF1). Treatments of the two CRFs obviously benefited the development of root system, resulting in greater rice root weights with extensive distribution and higher root activity. In addition, the two CRF treatments, in comparison to RSF1, enhanced chlorophyll consents of the flag leaves to 9.5 and 15.5%, and soluble protein up to 89.7 and 108.0% respectively. Application of the two CRFs also made the base of rice stems strong and large, declined the proportion of shoot and root, increased root depth index. Though relatively low K rate, single basal application of the CRF3 coated with NH4MgPO4 could also promote the development of root system, enhance root activity and some physiological functions of flag leaves. Based on these results, it was concluded that major mechanisms for increasing rice yield by single basal application of the CRFs should be attributed to grater soil available N supply, superior development of root systems, better nutrient absorption capacity, slower senescence and enhancement of lodging resistance at late stages.

  16. Comparative transcriptional profiling analysis of the two daughter cells from tobacco zygote reveals the transcriptome differences in the apical and basal cells

    Directory of Open Access Journals (Sweden)

    Hu Tian-Xiang


    Full Text Available Abstract Background In angiosperm, after the first asymmetric zygotic cell division, the apical and basal daughter cells follow distinct development pathways. Global transcriptome analysis of these two cells is essential in understanding their developmental differences. However, because of the difficulty to isolate the in vivo apical and basal cells of two-celled proembryo from ovule and ovary in higher plants, the transcriptome analysis of them hasn't been reported. Results In this study, we developed a procedure for isolating the in vivo apical and basal cells of the two-celled proembryo from tobacco (Nicotiana tabacum, and then performed a comparative transcriptome analysis of the two cells by suppression subtractive hybridization (SSH combined with macroarray screening. After sequencing, we identified 797 differentially expressed ESTs corresponding to 299 unigenes. Library sequence analysis successfully identified tobacco homologies of genes involved in embryogenesis and seed development. By quantitative real-time PCR, we validated the differential expression of 40 genes, with 6 transcripts of them specifically expressed in the apical or basal cell. Expression analysis also revealed some transcripts displayed cell specific activation in one of the daughter cells after zygote division. These differential expressions were further validated by in situ hybridization (ISH. Tissue expression pattern analysis also revealed some potential roles of these candidate genes in development. Conclusions The results show that some differential or specific transcripts in the apical and basal cells of two-celled proembryo were successfully isolated, and the identification of these transcripts reveals that these two daughter cells possess distinct transcriptional profiles after zygote division. Further functional work on these differentially or specifically expressed genes will promote the elucidation of molecular mechanism controlling early embryogenesis.

  17. Basal metabolic rate of endotherms can be modeled using heat-transfer principles and physiological concepts: reply to "can the basal metabolic rate of endotherms be explained by biophysical modeling?". (United States)

    Roberts, Michael F; Lightfoot, Edwin N; Porter, Warren P


    Our recent article (Roberts et al. 2010 ) proposes a mechanistic model for the relation between basal metabolic rate (BMR) and body mass (M) in mammals. The model is based on heat-transfer principles in the form of an equation for distributed heat generation within the body. The model can also be written in the form of the allometric equation BMR = aM(b), in which a is the coefficient of the mass term and b is the allometric exponent. The model generates two interesting results: it predicts that b takes the value 2/3, indicating that BMR is proportional to surface area in endotherms. It also provides an explanation of the physiological components that make up a, that is, respiratory heat loss, core-skin thermal conductance, and core-skin thermal gradient. Some of the ideas in our article have been questioned (Seymour and White 2011 ), and this is our response to those questions. We specifically address the following points: whether a heat-transfer model can explain the level of BMR in mammals, whether our test of the model is inadequate because it uses the same literature data that generated the values of the physiological variables, and whether geometry and empirical values combine to make a "coincidence" that makes the model only appear to conform to real processes.

  18. On the Enlightenment of the Thought of Rites and Music to the Promotion of Core Socialist Values in Colleges and Universities%论礼乐思想对高校弘扬社会主义核心价值观的启示

    Institute of Scientific and Technical Information of China (English)

    倪丽萍; 梁春节


    The thought of rites and music began in the Western Zhou Dynasty and formed in the period of Spring and Autumn and Warring States. As an important component of Chinese tradi-tional Confucian culture, it embodies the idea of education, the method of cultivation and the essence of governing a country based on the combination of rites and music. Rite emphasizes on the constraint by etiquette and system and the regulation of daily behaviors, while music focuses on the edification of inner spirit and the recognition of values. The thought of rites and music merges moral cognition, emotional experience and value recogni-tion together, making values internalize in mind and externalize in behavior, and organically unifying knowledge, emotion, sense and action, thus cultivating perfect personality. Therefore, it is of important referential significance for the promotion of core social-ist values in contemporary colleges and universities combined with Chinese excellent cultural traditions.%礼乐思想发轫于西周,形成于春秋战国,是中国传统儒家文化的重要组成部分,其中蕴含着礼乐结合的育人之道、教化之方、治国之要."乐由中出,礼自外作",礼教侧重外在礼仪制度的约束、日常行为的规范,乐教强调内在精神的熏陶、价值理念的体认.礼乐思想将道德认知、情感体验与价值认同相互渗透,使价值理念内化于心、外化于行,知、情、意、行有机统一,从而培育健全人格,对当代高校结合中国优秀文化传统弘扬社会主义核心价值观有着重要的借鉴意义.

  19. China Has Successfully Promote the Sustainable Development as the Core Issues of the G20 Summit in Hangzhou for the First Time%中国成功推动可持续发展首次作为G20领导人杭州峰会核心议题

    Institute of Scientific and Technical Information of China (English)

    周世骐; 周世镕; 刘洋


    二十国集团( G20)领导人第十一次峰会即杭州峰会于2016年9月5日闭幕,会议取得圆满成功,取得了一系列重要成果。中国作为二十国集团( G20)领导人杭州峰会轮值主席国发挥其卓越领导力,成功将可持续发展引入二十国集团( G20)领导人峰会议程,并推动其首次成为二十国集团( G20)杭州峰会核心议题,制定了《二十国集团落实2030年可持续发展议程行动计划》。中国已经全面启动落实2030年可持续发展议程工作,分享中国发展理念和经验,以切实行动充分发挥对全球落实可持续发展议程的重要引领作用。%The G20 Summit in Hangzhou successfully concluded on September 5, 2016, and a series of important results were obtained� China as the president the G20 Summit in Hangzhou, has played its outstanding leadership, has successfully introduced the sustainable development into the G20 Summit in Hangzhou agenda, and promoted it first to become core issues of the G20 Summit� The G20 Summit in Hangzhou at last formalized the G20 Action Plan on the 2030 Agenda for Sustainable Development� China has started to carry out the sustainable development agenda in 2030, shared the development idea and experience, and played the important leading role to implement global sustainable development agenda with concrete actions.

  20. Core-seis: a code for LMFBR core seismic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chellapandi, P.; Ravi, R.; Chetal, S.C.; Bhoje, S.B. [Indira Gandhi Centre for Atomic Research, Kalpakkam (India). Reactor Group


    This paper deals with a computer code CORE-SEIS specially developed for seismic analysis of LMFBR core configurations. For demonstrating the prediction capability of the code, results are presented for one of the MONJU reactor core mock ups which deals with a cluster of 37 subassemblies kept in water. (author). 3 refs., 7 figs., 2 tabs.

  1. Core Exercises: Why You Should Strengthen Your Core Muscles (United States)

    Healthy Lifestyle Fitness You know core exercises are good for you — but do you include core exercises in your fitness routine? Here's why ... 18, 2014 Original article: . Mayo Clinic Footer Legal Conditions and ...

  2. Engineering Promoter Architecture in Oleaginous Yeast Yarrowia lipolytica. (United States)

    Shabbir Hussain, Murtaza; Gambill, Lauren; Smith, Spencer; Blenner, Mark A


    Eukaryotic promoters have a complex architecture to control both the strength and timing of gene transcription spanning up to thousands of bases from the initiation site. This complexity makes rational fine-tuning of promoters in fungi difficult to predict; however, this very same complexity enables multiple possible strategies for engineering promoter strength. Here, we studied promoter architecture in the oleaginous yeast, Yarrowia lipolytica. While recent studies have focused on upstream activating sequences, we systematically examined various components common in fungal promoters. Here, we examine several promoter components including upstream activating sequences, proximal promoter sequences, core promoters, and the TATA box in autonomously replicating expression plasmids and integrated into the genome. Our findings show that promoter strength can be fine-tuned through the engineering of the TATA box sequence, core promoter, and upstream activating sequences. Additionally, we identified a previously unreported oleic acid responsive transcription enhancement in the XPR2 upstream activating sequences, which illustrates the complexity of fungal promoters. The promoters engineered here provide new genetic tools for metabolic engineering in Y. lipolytica and provide promoter engineering strategies that may be useful in engineering other non-model fungal systems.

  3. Fissura palatina reparada: fechamento velofaríngeo antes e durante o som basal Cleft palate repair: velopharyngeal closure before and during the basal tone

    Directory of Open Access Journals (Sweden)

    Giseane Conterno


    Full Text Available Portadores de fissura palatina apresentam inadequado fechamento velofaríngeo (FVF, com consequente hipernasalidade vocal que pode ser diminuída com o som basal. OBJETIVO: Comparar o FVF durante a realização do som basal com a emissão em registro modal, em pacientes com fissura palatina pós-forame reparada. MATERIAIS E MÉTODOS: Estudo de Casos com quatro homens adultos, portadores de fissura palatina pós-forame reparada. Imagens do FVF por nasofaringoscopia, durante a emissão da vogal [a] em registro modal e basal. Julgamento das imagens realizado por quatro otorrinolaringologistas. RESULTADOS: Em três sujeitos, não houve mudança no tipo de FVF entre os registros analisados; as modificações que ocorreram na maioria dos sujeitos referem-se apenas ao grau de movimentação das estruturas envolvidas, pois, em registro basal, o movimento das paredes laterais da faringe se manteve, o movimento da parede posterior da faringe estabilizou, o movimento do véu palatino diminuiu discretamente, e a Prega de Passavant se evidenciou. CONCLUSÕES: O tipo de FVF se manteve em três dos quatro sujeitos analisados, quando comparado o registro modal com o basal, havendo modificações no grau da movimentação das estruturas envolvidas, evidenciando a Prega de Passavant.Patients with palatine fissure have inadequate velopharyngeal closure (VPC, with consequent vocal hypernasality which can be reduced by a basal tone. AIM: to compare VPC during a basal tone with the emission of a modal recording, in patients with repaired post-foramen palatine fissure. MATERIALS AND METHODS: case study with four adult men, all with repaired post-foramen palatine fissure. VPC images through nasal-pharyngoscopy during the emission o f the [a] vowel in a modal and basal recording. The images were studied by four ENTs. RESULTS: in three subjects there was no change in the type of VPC considering the recordings analyzed; the changes which happened to most of the subjects

  4. Sustained high basal motion of the Greenland ice sheet revealed by borehole deformation

    DEFF Research Database (Denmark)

    Ryser, Claudia; Luethi, Martin P.; Andrews, Lauren C.;


    Ice deformation and basal motion characterize the dynamical behavior of the Greenland ice sheet (GrIS). We evaluate the contribution of basal motion from ice deformation measurements in boreholes drilled to the bed at two sites in the western marginal zone of the GrIS. We find a sustained high am...

  5. [Neurobiology of parkinsonism. I. Neural substrates an neurochemistry of the basal ganglia]. (United States)

    Ponzoni, S; Garcia-Cairasco, N


    Movement disorders, in general, are characterized by a breakdown in the integrated coordination of posture and motion by multiple brain and muscular systems. In the expression of parkinsonism, in particular, critical and altered structures such as substantia nigra, appear to be related to the cortex-basal ganglia and thalamus-basal ganglia sub-circuits.

  6. Left common basal pyramid torsion following left upper lobectomy/segmentectomy. (United States)

    Wang, Wei-Li; Cheng, Yen-Po; Cheng, Ching-Yuan; Wang, Bing-Yen


    Lobar or segmental lung torsion is a severe complication of lung resection. To the best of our knowledge, common basal pyramid torsion has never been reported. We describe a case of left basal pyramid torsion after left upper lobectomy and superior segmentectomy, which was successfully treated by thoracoscopic surgery.

  7. Expression of basal cell keratins in human prostate cancer metastases and cell lines.

    NARCIS (Netherlands)

    Leenders, G.J.L.H. van; Aalders, M.W.; Hulsbergen-van de Kaa, C.A.; Ruiter, D.J.; Schalken, J.A.


    Within normal human prostate epithelium, basal and luminal cells can be discriminated by their expression of keratins (K). While basal cells express K5/14, luminal cells show expression of K8/18 and an intermediate cell population can be identified by co-expression of K5/18. Prostate cancer is predo

  8. Does Lactation Mitigate Triple Negative/Basal Breast Cancer Progression (United States)


    Progression. March 6, 2012, Postdoctoral Seminar Series, University of Colorado Denver. 3. Tanya D. Russell. Pregnancy and Involution Promote...are DCIS, and standard treatment typically involves surgery and radiation. A better understanding of the role of the myoepithelium in early stage...Aurora, CO, USA 80045. 2 School of Medicine, Department of Pediatrics , B119, Bldg 406, Room 105 3University of Colorado Cancer Center, Bldg 500

  9. Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice. (United States)

    Giulivi, Cecilia; Ross-Inta, Catherine; Omanska-Klusek, Alicja; Napoli, Eleonora; Sakaguchi, Danielle; Barrientos, Genaro; Allen, Paul D; Pessah, Isaac N


    Malignant hyperthermia (MH) and central core disease in humans have been associated with mutations in the skeletal ryanodine receptor (RyR1). Heterozygous mice expressing the human MH/central core disease RyR1 R163C mutation exhibit MH when exposed to halothane or heat stress. Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca(2+) concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions. R163C skeletal muscle exhibited a significant increase in matrix Ca(2+), increased reactive oxygen species production, lower expression of mitochondrial proteins, and higher mtDNA copy number. These changes, in conjunction with lower myoglobin and glycogen contents, Myh4 and GAPDH transcript levels, GAPDH activity, and lower glucose utilization suggested a switch to a compromised bioenergetic state characterized by both low oxidative phosphorylation and glycolysis. The shift in bioenergetic state was accompanied by a dysregulation of Ca(2+)-responsive signaling pathways regulated by calcineurin and ERK1/2. Chronically elevated resting Ca(2+) in R163C skeletal muscle elicited the maintenance of a fast-twitch fiber program and the development of insulin resistance-like phenotype as part of a metabolic adaptation to the R163C RyR1 mutation.

  10. Refractory epilepsy and basal ganglia: the role of seizure frequency

    Energy Technology Data Exchange (ETDEWEB)

    Bouilleret, V.; Trebossen, R.; Mantzerides, M.; Semah, F.; Ribeiro, M.J. [Service Hospitalier Frederic Joliot, I2BM/DSV, CEA, 91 - Orsay (France); Bouilleret, V. [CHU Bicetre, Unite de Neurophysiologie et d' Epileptologie, AP-HP, 75 - Paris (France); Chassoux, F. [Hopital Saint Anne, Service de Neurochirurgie, 75 - Paris (France); Biraben, A. [CHU, Service de Neurologie, Hopital Pontchaillou, 35 - Rennes (France)


    Objectives. - A decrease of [{sup 18}F]Fluoro-L-DOPA uptake in basal ganglia (B.G.) was recently reported in medically refractory epilepsy. The purpose of this study was to assess the involvement of dopaminergic neurotransmission in refractory Temporal Lobe Epilepsy (T.L.E.) and its relationship to glucose metabolism and morphological changes. Methods. - Twelve T.L.E. patients were studied using [{sup 18}F]FDG PET, [{sup 18}F]Fluoro-L-DOPA PET and MRI and compared with healthy control volunteers. Morphological cerebral changes were assessed using Voxel-Based Morphometry (V.B.M.). Student t test statistical maps of functional and morphological differences between patients and controls were obtained using a general linear model. Results. - In T.L.E. patients, [{sup 18}F]Fluoro-L-DOPA uptake was reduced to the same extent in caudate and putamen in both cerebral hemispheres as well as in the substantia nigra (S.N.). These dopaminergic functional alterations occurred without any glucose metabolism changes in these areas. The only mild morphological abnormality was found in striatal regions without any changes in the S.N.. Conclusion. - The present study provides support for dopaminergic neurotransmission involvement in T.L.E.. The discrepancies between G.M.V. atrophy and the pattern of [{sup 18}F]Fluoro-L-DOPA suggest that B.G. involvement is not related to structural subcortical abnormalities. A functional decrease can be ruled out as there was no change of the glycolytic pathway metabolism in these areas. (authors)

  11. Association of basal forebrain volumes and cognition in normal aging. (United States)

    Wolf, D; Grothe, M; Fischer, F U; Heinsen, H; Kilimann, I; Teipel, S; Fellgiebel, A


    The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years. Most notably, we found significant associations between general intelligence and BFCS volumes, specifically within areas corresponding to posterior nuclei of the nucleus basalis of Meynert (Ch4p) and the nucleus subputaminalis (NSP). Associations between specific cognitive domains and BFCS volumes were less pronounced. Supplementary analyses demonstrated that especially the volume of NSP but also the volume of Ch4p was related to the volume of widespread temporal, frontal, and parietal gray and white matter regions. Volumes of these gray and white matter regions were also related to general intelligence. Higher volumes of Ch4p and NSP may enhance the effectiveness of acetylcholine supply in related gray and white matter regions underlying general intelligence and hence explain the observed association between the volume of Ch4p as well as NSP and general intelligence. Since general intelligence is known to attenuate the degree of age-associated cognitive decline and the risk of developing late-onset AD, the BFCS might, besides the specific contribution to the pathophysiology in AD, constitute a mechanism of brain resilience in normal aging.

  12. Erosion and basal forces in granular flow experiments (United States)

    Sanvitale, Nicoletta; Bowman, Elisabeth


    Extreme mass wasting avalanche events such as rock, snow and ice avalanches, debris flows, and pyroclastic flows are among the most hazardous geological phenomena. These events driven by gravity, can travel for long distance and high speed, increasing their volumes as they can entertain material along their path. The erosion of material and its entrainment can greatly affect the overall dynamics of transportation, either enhancing or impeding the avalanche mobility depending on flow dynamics and characteristics of the substrate. However, the mechanisms and processes acting at the base as they travel over deformable or erodible substrates are still poor understood. Experiments, simulations and field measurements indicate that large fluctuations can occur in basal forces and stresses, which may be the result of non-uniform load transfer within the mass, and rolling, bouncing and sliding of the particles along the bed. In dense granular materials, force distributions can propagate through filamentary chain structures that carry a large fraction of the forces within the system. Photoelastic experiments on two-dimensional, monodisperse, gravity-driven flows have shown that force chains can transmit high localized forces to the boundary of dense granular flows. Here we describe the preliminary setup and results of 2D experiments on polydisperse granular flows of photoelastic disks down a small flume designed to acquire the forces exerted at the boundaries of the flow and to analyze their effects on an erodible bed. The intended outcome of this research is to provide better information on the complex mechanism of erosion and its effects on avalanche behaviour.

  13. Laser ablation of basal cell carcinomas guided by confocal microscopy (United States)

    Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind


    Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

  14. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer. (United States)

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G


    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  15. Ancient biomolecules from deep ice cores reveal a forested southern Greenland. (United States)

    Willerslev, Eske; Cappellini, Enrico; Boomsma, Wouter; Nielsen, Rasmus; Hebsgaard, Martin B; Brand, Tina B; Hofreiter, Michael; Bunce, Michael; Poinar, Hendrik N; Dahl-Jensen, Dorthe; Johnsen, Sigfus; Steffensen, Jørgen Peder; Bennike, Ole; Schwenninger, Jean-Luc; Nathan, Roger; Armitage, Simon; de Hoog, Cees-Jan; Alfimov, Vasily; Christl, Marcus; Beer, Juerg; Muscheler, Raimund; Barker, Joel; Sharp, Martin; Penkman, Kirsty E H; Haile, James; Taberlet, Pierre; Gilbert, M Thomas P; Casoli, Antonella; Campani, Elisa; Collins, Matthew J


    It is difficult to obtain fossil data from the 10% of Earth's terrestrial surface that is covered by thick glaciers and ice sheets, and hence, knowledge of the paleoenvironments of these regions has remained limited. We show that DNA and amino acids from buried organisms can be recovered from the basal sections of deep ice cores, enabling reconstructions of past flora and fauna. We show that high-altitude southern Greenland, currently lying below more than 2 kilometers of ice, was inhabited by a diverse array of conifer trees and insects within the past million years. The results provide direct evidence in support of a forested southern Greenland and suggest that many deep ice cores may contain genetic records of paleoenvironments in their basal sections.

  16. LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway (United States)

    Xiao, Deshen; Lai, Weiwei; Pan, Yu; Jiang, Yiqun; Chen, Ling; Mao, Chao; Zhou, Jian; Xi, Sichuan; Cao, Ya; Liu, Shuang; Tao, Yongguang


    Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The noncanonical NF-κB pathway is dependent on IKKα. However, the role of IKKα in BCC has not been elucidated. We show here that IKKα is expressed in the nucleus in BCC and non-malignant diseases. Nuclear IKKα could directly bind to the promoters of inflammation factors and LGR5, a stem cell marker, in turn, upregulating LGR5 expression through activation of STAT3 signaling pathway during cancer progression. Activation of STAT3 signaling pathway contributes LGR5 expression in dependent of IKKα after the interplay between STAT3 and IKKα. Meanwhile knockdown of IKKα inhibits tumor growth and transition of epithelial stage to mescheme stage. Taken together, we demonstrate that IKKα functions as a bone fide chromatin regulator in BCC, whose promoted expression contributes to oncogenic transformation via promoting expression stemness- and inflammatory- related genes. Our finding reveals a novel viewpoint for how IKKα may involve in BCCs tumor progression in the inflammatory microenvironment. PMID:27049829

  17. A multi-disciplinary approach to identify shallow gas resources in the basal Foremost Formation (Belly River). We`ve all drilled through it, what have we missed?

    Energy Technology Data Exchange (ETDEWEB)

    Hume, D. [Rakhit Petroleum Consulting Ltd., Calgary, AB (Canada); Crane, R. [Spectrum 2000 Mindware Ltd., (Canada)


    A multi-disciplinary technique has been developed to evaluate the basal Foremost Formation (Belly River). This formation is a major resource for shallow, low pressure gas reserves throughout a large area of southern and central Alberta. However, because of the Formation`s unusual hydrogeologic, petrophysical and mineralogic properties, the full potential of this zone has not yet been realized. The formation is highly susceptible to invasion during drilling. A normal water column is up to 250 per cent overbalanced in the Foremost Formation. The zone is also very prone to formation damage. Fluid samples are therefore very difficult to obtain, and when they are, they are largely mud filtrate. Variable shale volumes and heavy mineral composition also complicate the petrophysical analysis. In this study, a database of over 9,700 correlated well logs, 38 core examinations, 3000 DSTs, 2000 fluid recovery analyses and 11 petrophysical analyses from the area were compiled and analyzed to develop an allostratigraphic framework for the basal Foremost Formation. Potentiometric surface maps were constructed for each of the various allostratigraphic units along with graphs depicting pressure versus elevation. Fluid recoveries were also screened. It was determined that in certain areas the basal Foremost Formation is mostly gas charged. In other areas it occurs as a gas and water system. This information makes it possible to determine whether a given reservoir is potentially gas charged or wet.

  18. On core stability and extendability


    Shellshear, Evan


    This paper investigates conditions under which the core of a TU cooperative game is stable. In particular the author extends the idea of extendability to find new conditions under which the core is stable. It is also shown that these new conditions are not necessary for core stability.

  19. Hollow-Core Fiber Lamp (United States)

    Yi, Lin (Inventor); Tjoelker, Robert L. (Inventor); Burt, Eric A. (Inventor); Huang, Shouhua (Inventor)


    Hollow-core capillary discharge lamps on the millimeter or sub-millimeter scale are provided. The hollow-core capillary discharge lamps achieve an increased light intensity ratio between 194 millimeters (useful) and 254 millimeters (useless) light than conventional lamps. The capillary discharge lamps may include a cone to increase light output. Hollow-core photonic crystal fiber (HCPCF) may also be used.

  20. Basal body structure and composition in the apicomplexans Toxoplasma and Plasmodium. (United States)

    Francia, Maria E; Dubremetz, Jean-Francois; Morrissette, Naomi S


    The phylum Apicomplexa encompasses numerous important human and animal disease-causing parasites, including the Plasmodium species, and Toxoplasma gondii, causative agents of malaria and toxoplasmosis, respectively. Apicomplexans proliferate by asexual replication and can also undergo sexual recombination. Most life cycle stages of the parasite lack flagella; these structures only appear on male gametes. Although male gametes (microgametes) assemble a typical 9+2 axoneme, the structure of the templating basal body is poorly defined. Moreover, the relationship between asexual stage centrioles and microgamete basal bodies remains unclear. While asexual stages of Plasmodium lack defined centriole structures, the asexual stages of Toxoplasma and closely related coccidian apicomplexans contain centrioles that consist of nine singlet microtubules and a central tubule. There are relatively few ultra-structural images of Toxoplasma microgametes, which only develop in cat intestinal epithelium. Only a subset of these include sections through the basal body: to date, none have unambiguously captured organization of the basal body structure. Moreover, it is unclear whether this basal body is derived from pre-existing asexual stage centrioles or is synthesized de novo. Basal bodies in Plasmodium microgametes are thought to be synthesized de novo, and their assembly remains ill-defined. Apicomplexan genomes harbor genes encoding δ- and ε-tubulin homologs, potentially enabling these parasites to assemble a typical triplet basal body structure. Moreover, the UNIMOD components (SAS6, SAS4/CPAP, and BLD10/CEP135) are conserved in these organisms. However, other widely conserved basal body and flagellar biogenesis elements are missing from apicomplexan genomes. These differences may indicate variations in flagellar biogenesis pathways and in basal body arrangement within the phylum. As apicomplexan basal bodies are distinct from their metazoan counterparts, it may be possible to

  1. Genistein decreases basal hepatic cytochrome P450 1A1 protein expression and activity in Swiss Webster mice. (United States)

    Froyen, Erik B; Steinberg, Francene M


    Soy consumption has been associated with risk reduction for chronic diseases such as cancer. One proposed mechanism for cancer prevention by soy is through decreasing cytochrome P450 1A1 (Cyp1a1) activity. However, it is not known with certainty which soy components modulate Cyp1a1, or the characteristics or mechanisms involved in the responses after short-term (<20 days) dietary treatment without concomitant carcinogen-mediated induction. Therefore, the objective was to test the hypothesis that physiologic concentrations of dietary genistein and/or daidzein will decrease basal hepatic Cyp1a1 protein expression and activity in male and female Swiss Webster mice via inhibiting the bindings of aryl hydrocarbon receptor (AhR)-AhR nuclear translocator (ARNT) and estrogen receptor-α to the Cyp1a1 promoter region xenobiotic response element. The mice were fed the AIN-93G diet supplemented with 1500 mg/kg of genistein or daidzein for up to 1 week. Genistein, but not daidzein, significantly decreased basal hepatic microsomal Cyp1a1 protein expression and activity. AhR protein expression was not altered. Molecular mechanisms were investigated in Hepa-1c1c7 cells treated with 5 μmol/L purified aglycones genistein, daidzein, or equol. Cells treated with genistein exhibited inhibitions in ARNT and estrogen receptor-α bindings to the Cyp1a1 promoter region. This study demonstrated that genistein consumption reduced constitutive hepatic Cyp1a1 protein expression and activity, thereby contributing to the understanding of how soy isoflavone aglycones modulate cytochrome P450 biotransformation enzymes.

  2. Shakespeare and the Common Core: An Opportunity to Reboot (United States)

    Turchi, Laura; Thompson, Ayanna


    The Common Core generally eschews mandating texts in favor of promoting critical analysis and rigor. So it's significant that Shakespeare is the only author invoked in imperatives. His explicit inclusion offers a significant opportunity for educators to rethink how we approach Shakespearean instruction. Rather than the traditional learning of…

  3. Integrative Biology: A Capstone Course for an Introductory Biology Core (United States)

    Chaplin, Susan B.; Hartung, Nancy Z.


    A capstone to the biology introductory curriculum was developed with the specific goals of enhancing integration of course content, promoting development of oral presentation skills and critical reading and thinking skills, and introducing ecological principles omitted from the rest of the core. Classes of 12 to 16 students were team taught by…

  4. 知识型团队核心价值观认同对组织竞争力的促进机制研究--基于 Sternberg 成功智力视角的数据检验%The Promoting Mechanisms Research of Core Values Identification of Knowledge -based Research Team for Organization Competitiveness-Based on the Data Certification of Sternberg Success Intelligence

    Institute of Scientific and Technical Information of China (English)

    刘明; 杨韬; 张同建


    利他性偏好在经济学领域对“经济人假设”产生了深远的冲击。知识型人才不仅关注自身的利益,也关注他人、社会和国家的利益。核心价值观认同对知识型人才的技术创造力存在着内在的激励作用。以我国知识型团队为样本数据,借助结构方程模型检验了知识型人才核心价值观认同、成功智力和组织竞争力之间的相关性,发现核心价值观认同对知识型团队组织竞争力促进效应的存在性,为我国知识型团队人力资本开发战略与策略的调整,以及为我国人力资源管理学科建设的推进提供了现实性的理论支持。%The altruistic preference has had a profound impact on "economic human hypothesis"in the field of econom-ics.Knowledge -based talent is not only concerned about their own interests,but also concerned about the interests of oth-ers,society and the state.The core values identification has an inherent incentive for the technology creativity of knowledge talent.Based on the sample data of knowledge -based team and by means of structural equation modeling,this research tests the correlation among core values identification,success intelligence and organization competitiveness,and founds the existence of promoting effect of core values identifying on organization competitiveness of knowledge -based team,which provides a realistic theory reference to adjust the strategy and tactics of human capital management of knowledge -based teams and to promote the disciplines construction of human resource management.

  5. Efeitos do som basal em fendas glóticas Effects of vocal fry incomplete glottal closure

    Directory of Open Access Journals (Sweden)

    Geovana de Paula Bolzan


    in the glottal coaptation and in the amplitude of the vocal folds mucosa vibration; worsen in the voice type; enlargement of noise and Jitter measurements. CONCLUSION: the vocal fry promoted glottal closure reduction and enlargement in the amplitude of the vocal folds mucosa vibration; worsen in the voice type, which became noisier; enlargement of noise and Jitter measurements, suggesting vibratory irregularities, probably due to the basal fry motor adjustments effects when strongly mobilizing the mucosa.

  6. Metrics for Success: Strategies for Enabling Core Facility Performance and Assessing Outcomes. (United States)

    Turpen, Paula B; Hockberger, Philip E; Meyn, Susan M; Nicklin, Connie; Tabarini, Diane; Auger, Julie A


    Core Facilities are key elements in the research portfolio of academic and private research institutions. Administrators overseeing core facilities (core administrators) require assessment tools for evaluating the need and effectiveness of these facilities at their institutions. This article discusses ways to promote best practices in core facilities as well as ways to evaluate their performance across 8 of the following categories: general management, research and technical staff, financial management, customer base and satisfaction, resource management, communications, institutional impact, and strategic planning. For each category, we provide lessons learned that we believe contribute to the effective and efficient overall management of core facilities. If done well, we believe that encouraging best practices and evaluating performance in core facilities will demonstrate and reinforce the importance of core facilities in the research and educational mission of institutions. It will also increase job satisfaction of those working in core facilities and improve the likelihood of sustainability of both facilities and personnel.

  7. Development of an efficient bi-directional promoter with tripartite enhancer employing three viral promoters. (United States)

    Patro, Sunita; Maiti, Indu B; Dey, Nrisingha


    We have developed a novel bi-directional promoter (FsFfCBD) by placing two heterogeneous core-promoters from the Figwort mosaic virus sub-genomic transcript promoter (FsCP, -69 to +31) and Cauliflower mosaic virus 35S promoter (CCP, -89 to +1) respectively on upstream (5') and downstream (3') ends of a tri-hybrid enhancer (FsEFfECE), in reverse orientation. The FsEFfECE domain encompasses three heterologous enhancer fragments from Figwort mosaic virus sub-genomic transcript promoter (FsE, 101 bp, -70 to -170), Figwort mosaic virus full-length transcript promoter (FfE, 196 bp, -249 to -54) and Cauliflower mosaic virus 35S promoter (CE, 254 bp, -343 to -90). The bi-directional nature of the FsFfCBD promoter (coupled to GFP and GUS) was established both in transient systems (onion epidermal cells and tobacco protoplasts) and transgenic plant (Nicotiana tabacum samsun NN) by monitoring the simultaneous expression of GFP and GUS employing fluorescence (for GFP) and biochemical (for GUS) based assays. In transgenic plants, the FsFfCBD promoter was found to be 6.8 and 2.5 times stronger than two parent promoters; Fs and FfC respectively. The bi-directional compound promoter FsFfCBD, composed of three heterologous enhancers with enhanced activity could become a valuable additional tool for efficient plant metabolic engineering and molecular pharming.

  8. Prognostic Value of Basal Serum Thyroglobulin Levels, but Not Basal Antithyroglobulin Antibody (TgAb Levels, in Patients with Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Isa Neshandar Asli


    Full Text Available Objective: The prognostic values of serum thyroglobulin (Tg and antithyroglobulin antibody (TgAb levels, measured immediately before I-131remnant ablation in patients with differentiated thyroid cancer (DTC, have been advocated by some researchers; however, it had controversial outcomes. This study was carried out to examine this dilemma and to check the clinical significance of basal serum Tg and TgAb levels and postablation iodine 131whole body scan(WBS findings in DTC patients. Methods: In this retrospective study, the records of 500 patients with differentiated thyroid cancer, who had undergone treatment between 2003 and 2010, were assessed. Of those, 149 patients with results of basal serum thyroglobulin concentration and whole body scan using radioactive iodine were included. Age, sex, tumour histology, basal thyroglobulin (Tg, anti-thyroglobulin (TgAb and TSH concentration, radioactive iodine doses in each hospitalization, numbers of hospitalization, and results of whole body scans were recorded. The relationship among basal Tg, TgAb, TSH, and whole body scan with hospitalization number and total radioactive iodine doses were assessed. Results: A total of 149 patients, including 123 (83% females and 26 (17% males, with a mean age of 40±15 years, took part in the study. The mean (SD basal Tg, TgAb, and TSH were 91.7±169.2 ng/mL (0.1-1000 ng/mL, 250±893 U/mL (0-9000 U/m L, and 64.8±61.5 µU/mL (30-689 U/mLµ, respectively. A total of 52 (34.9% cases had TgAb levels greater than 100 U/mL. The mean basal Tg in patients who were admitted three or more times was significantly greater than that of patients with one hospitalization (p=0.026. In addition, the mean of Tg in patients who received 7.4 GBq radioactive iodine or less was significantly lower than the others (p=0.003. The mean of TgAb and TSH were not different between these groups. In the results of the whole body scans, patients with metastasis had higher frequency of

  9. Characteristics of basal ganglia aphasia after stroke and the rehabilitative interventions

    Institute of Scientific and Technical Information of China (English)

    Yating Kong; Xifeng Pan; Qimei Zhang


    OBJECTIVE: To introduce the characteristics of basal ganglia aphasia after stroke and the rehabilitative interventions.DATA SOURCES: Articles related to stroke, subcortical aphasia, basal ganglia aphasia and language rehabilitation published in Chinese from January 1988 to December 2005 were searched in Chinese journal full-text database (CJFD) using the keywords of"stroke, basal ganglia aphasia, language rehabilitation" in Chinese. Meanwhile, English articles about aphasia published from January 1982 to December 2005 were searched in and Pubmed database. Besides, several books associated with the contents were looked through manually.STUDY SELECTION: The data were checked primarily, the articles about the pathomechanism and neurolinguistic characteristics of basal ganglia aphasia, diagnostic methods of aphasia and language rehabilitation were selected, and those had no obvious relation with the above contents were excluded.Inclusive criteria: literatures explain the clinical characteristics of basal ganglia aphasia, neurolinguistic pathogenesis and methods of rehabilitation therapy in details. The repetitive studies were excluded.DATA EXTRACTION: Totally 95 literatures about basal ganglia aphasia were collected, including 31 about the clinical characteristics of basal ganglia aphasia, 45 about its neurolinguistic pathogenesis, 5 about the evaluation and classification of aphasia, and 14 about its rehabilitation therapy. Thirty accorded with the inclusive criteria were used for review, and the other 65 were excluded.DATA SYNTHESIS: Concisely introduced the definition, past investigation of basal ganglia aphasia after stroke, then dwelled on the multiplicity neurolinguistics characteristics. Aphasia evaluation was dependent upon clinical aphasic symptoms. The relationship between symptom and focus of infection was explored, and the mechanism of pathosis language behavior on basal ganglia aphasia patients was understood to provide consequence data that could

  10. 国有商业银行组织公平对提升核心竞争力促进机制研究--基于二级分行(地市级分行)样本数据的检验%An Empirical Study on Promoting Mechanism of Organizational Justice of State-owned Commercial Bank on Bank Core Competitiveness---Based on Sample Data Certification of the Secondary Branches (Prefecture-Level Branch)

    Institute of Scientific and Technical Information of China (English)

    黄洪斌; 王忠; 张同建


    国有商业银行竞争优势不足在一定程度上源于组织公平理念认识和应用的滞后。本文基于二级分行的样本数据,借助于结构方程模型,实证分析了组织公平对核心竞争力的促进效应,揭示了分配公平、程序公平、互动公平对内部控制能力、产品开发能力、风险防范能力和市场营销能力的微观促进机理,发现了优势促进路径和不足,旨在为国有商业银行公平性制度设计和文化培育提供理论参考。%The lack of competitive advantage of state-owned commercial banks comes from the lagging of organizational fair application to some extent.Based on the sample data of two-class branches and by means of structural equation modeling, this paper analyses the promoting effect of organizational fair on core competitiveness by empirical research method, reveals the micro-promoting mechanism of distributive justice, procedural justice, interactional justice on the capacity of internal control, product development, risk prevention and marketing capabilities, and discovers the advanta-ges and disadvantages of the promotion path, aiming to provide a theory reference for state-owned commercial banks to design fairness institution and to foster enterprise culture.

  11. Floral gene resources from basal angiosperms for comparative genomics research

    Directory of Open Access Journals (Sweden)

    Zhang Xiaohong


    Full Text Available Abstract Background The Floral Genome Project was initiated to bridge the genomic gap between the most broadly studied plant model systems. Arabidopsis and rice, although now completely sequenced and under intensive comparative genomic investigation, are separated by at least 125 million years of evolutionary time, and cannot in isolation provide a comprehensive perspective on structural and functional aspects of flowering plant genome dynamics. Here we discuss new genomic resources available to the scientific community, comprising cDNA libraries and Expressed Sequence Tag (EST sequences for a suite of phylogenetically basal angiosperms specifically selected to bridge the evolutionary gaps between model plants and provide insights into gene content and genome structure in the earliest flowering plants. Results Random sequencing of cDNAs from representatives of phylogenetically important eudicot, non-grass monocot, and gymnosperm lineages has so far (as of 12/1/04 generated 70,514 ESTs and 48,170 assembled unigenes. Efficient sorting of EST sequences into putative gene families based on whole Arabidopsis/rice proteome comparison has permitted ready identification of cDNA clones for finished sequencing. Preliminarily, (i proportions of functional categories among sequenced floral genes seem representative of the entire Arabidopsis transcriptome, (ii many known floral gene homologues have been captured, and (iii phylogenetic analyses of ESTs are providing new insights into the process of gene family evolution in relation to the origin and diversification of the angiosperms. Conclusion Initial comparisons illustrate the utility of the EST data sets toward discovery of the basic floral transcriptome. These first findings also afford the opportunity to address a number of conspicuous evolutionary genomic questions, including reproductive organ transcriptome overlap between angiosperms and gymnosperms, genome-wide duplication history, lineage

  12. Myxosporean hyperparasites of gill monogeneans are basal to the Multivalvulida

    Directory of Open Access Journals (Sweden)

    Freeman Mark A


    Full Text Available Abstract Background Myxosporeans are known from aquatic annelids but parasitism of platyhelminths by myxosporeans has not been widely reported. Hyperparasitism of gill monogeneans by Myxidium giardi has been reported from the European eel and Myxidium-like hyperparasites have also been observed during studies of gill monogeneans from Malaysia and Japan. The present study aimed to collect new hyperparasite material from Malaysia for morphological and molecular descriptions. In addition, PCR screening of host fish was undertaken to determine whether they are also hosts for the myxosporean. Results Heavy myxosporean infections were observed in monogeneans from two out of 14 fish and were detected from a further five fish using specific PCRs and pooled monogenean DNA. Positive DNA isolates were sequenced and were from a single species of myxosporean. Myxospore morphology was consistent with Myxidium with histozoic development in the parenchymal tissues of the monogenean. Simultaneous infections in the fish could not be confirmed microscopically; however, identical myxosporean DNA could be amplified from kidney, spleen and intestinal tract tissues using the specific PCR. Small subunit (SSU rDNA for the myxosporean was amplified and was found to be most similar (92% to that of another hyperparasitic myxosporean from a gill monogenean from Japan and to numerous multivalvulidan myxosporeans from the genus Kudoa (89-91%. Phylogenetic analyses placed the hyperparasite sequence basally to clades containing Kudoa, Unicapsula and Sphaerospora. Conclusions The myxosporean infecting the gill monogenean, Diplectanocotyla gracilis, from the Indo-Pacific tarpon, Megalops cyprinoides, is described as a new species, Myxidium incomptavermi, based on a histozoic development in the monogenean host and its phylogenetic placement. We have demonstrated for the first time that a myxosporean hyperparasite of gill monogeneans is detectable in the fish host. However

  13. [Basal cell carcinoma of prostate: a report of three cases]. (United States)

    Liu, Z; Ma, L L; Zhang, S D; Lu, M; Tian, Y; He, Q; Jin, J


    To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of basal cell carcinoma (BCC) of prostate. Three cases of BCC of prostate were reported and the relevant literature was reviewed to investigate the diagnosis and treatment of this disease. We analyzed three cases of prostatic BCC. Their ages were within a range of 57 to 83 years. One of them complained of hematuria and two complained of dysuria. All of them presented with prostatic hyperplasia. Two of them presented with high prostate specific antigen (PSA) and one with normal PSA. Case 1 had prostate cancer invasion of bladder, rectal fascia, with lymph node metastasis, bone metastasis and lung metastases. The patient received bladder resection+bilateral ureteral cutaneous ureterostomy+lymph node dissection on November 2, 2014 . Postoperative pathological diagnosis showed BCC. Reexamination of pelvic enhanced MRI in January 8, 2015 suggested pelvic recurrence. Abdominal enhanced CT showed multiple liver metastases and pancreatic metastasis on July 11, 2015. Prostate cancer specific death occurred in October 2015. Case 2 was diagnosed as BCC in prostate biopsy on March 27, 2015. Positron emission tomography and computed tomography (PET-CT) showed pulmonary metastasis and bone metastasis. Then the patient received chemotherapy, endocrine therapy and local radiation therapy. Reexamination of PET-CT on January 11, 2016 showed that the lung metastase tumors and bone metastase tumors were larger than before. Up to January 10, 2016, the patient was still alive. Postoperative pathological changes of transurethral resection of prostate (TURP) in case 3 showed BCC might be considered. The PET-CT suggested residual prostate cancer, which might be associated with bilateral pelvic lymph node metastasis. In April 20, 2016, the review of PET-CT showed pelvic huge irregular hybrid density shadow, about 14.5 cm×10.0 cm×12.9 cm in size, and tumor recurrence was

  14. Formation of Oceanic Lithosphere by Basal Magma Accretion (United States)

    Hamza, V. M.; Cardoso, R. R.; Alexandrino, C. H.


    The thermal models of the lithosphere proposed to date have failed to provide satisfactory accounts of some of the important features in large-scale variations of ocean floor bathymetry and heat flow. The systematic difference between model calculations and observational data have given rise to the so-called “oceanic heat flow paradox”, for which no satisfactory solution has been found for over the last forty years. In the present work, we point out that this paradox is a consequence of the assumption that lateral temperature variations are absent in the sub-lithospheric mantle. In the present work we propose a simple magma accretion model and examine its implications for understanding the thermal field of oceanic lithosphere. The new model (designated VBA) assumes existence of lateral variations in magma accretion rates and temperatures at the boundary zone between the lithosphere and the asthenosphere, similar in character to those observed in magma solidification processes in the upper crust. However, unlike the previous thermal models of the lithosphere, the ratio of advection to conduction heat transfer (the Peclet number) is considered a space dependent variable. The solution to the problem of variable basal heat input has been obtained by the method of integral transform. The results of VBA model simulations reveal that the thickness of the young lithosphere increases with distance from the ridge axis, at rates faster than those predicted by Half-Space Cooling and Plate models. Another noteworthy feature of the new model is its ability to account for the main observational features in the thermal behavior of both young and old oceanic lithosphere. Thus, heat flow and bathymetry variations calculated on the basis of the VBA model provide vastly improved fits to respective observational datasets. More importantly, the improved fits to bathymetry and heat flow have been achieved for the entire age range of oceanic lithosphere and without the need to invoke

  15. Myogenesis in the basal bilaterian Symsagittifera roscoffensis (Acoela

    Directory of Open Access Journals (Sweden)

    Wanninger Andreas


    , Symsagittifera roscoffensis shows a very complex musculature. Although data on presumably basal acoel clades are still scarce, the information currently available suggests an elaborated musculature with longitudinal, circular and U-shaped muscles as being part of the ancestral acoel bodyplan, thus increasing the possibility that Urbilateria likewise had a relatively complicated muscular ground pattern.

  16. Are the basal cells of the mammalian epididymis still an enigma? (United States)

    Arrighi, S


    Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced.

  17. Reconstructing basal boundary conditions in a regional ice sheet model: Application to Jakobshavn Isbræ (United States)

    Habermann, M.; Maxwell, D. A.; Truffer, M.


    A crucial assumption in all ice sheet models concerns the nature and parametrization of the basal boundary condition. Direct observations on large spatial scales are not possible, but inverse methods can be used to determine the distribution of basal properties from surface measurements. We developed open-source iterative inverse algorithms and applied them to PISM, a hybrid ice sheet model that solves a combination of the Shallow Ice and Shallow Shelf Approximations. In a regional-scale model of Jakobshavn Isbræ, the fastest flowing ice stream of Greenland, we invert for basal stickiness over the entire drainage basin. The sensitivity of the reconstructed basal stickiness to the following modeling choices is evaluated: temperature distribution within the ice, definition of the misfit functional, tolerance for the stopping criterion and initial estimates of basal stickiness. The effects and the management of missing data are analyzed. In 2002 the floating tongue of Jakobshavn Isbræ disintegrated catastrophically, leading to increased speeds and rapid thinning of the inland ice. Detailed velocity maps from before and after this breakup allow us to compare retrieved basal parameters and to track the continuing evolution of the basal boundary condition.

  18. Organizational changes of the daughter basal complex during the parasite replication of Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Ke Hu


    Full Text Available The apicomplexans are a large group of parasitic protozoa, many of which are important human and animal pathogens, including Plasmodium falciparum and Toxoplasma gondii. These parasites cause disease only when they replicate, and their replication is critically dependent on the proper assembly of the parasite cytoskeletons during cell division. In addition to their importance in pathogenesis, the apicomplexan parasite cytoskeletons are spectacular structures. Therefore, understanding the cytoskeletal biogenesis of these parasites is important not only for parasitology but also of general interest to broader cell biology. Previously, we found that the basal end of T. gondii contains a novel cytoskeletal assembly, the basal complex, a cytoskeletal compartment constructed in concert with the daughter cortical cytoskeleton during cell division. This study focuses on key events during the biogenesis of the basal complex using high resolution light microscopy, and reveals that daughter basal complexes are established around the duplicated centrioles independently of the structural integrity of the daughter cortical cytoskeleton, and that they are dynamic "caps" at the growing ends of the daughters. Compartmentation and polarization of the basal complex is first revealed at a late stage of cell division upon the recruitment of an EF-hand containing calcium binding protein, TgCentrin2. This correlates with the constriction of the basal complex, a process that can be artificially induced by increasing cellular calcium concentration. The basal complex is therefore likely to be a new kind of centrin-based contractile apparatus.

  19. DMBT1 promotes basal and meconium-induced nitric oxide production in human lung epithelial cells in vitro

    DEFF Research Database (Denmark)

    Müller, Hanna; Weiss, Christel; Renner, Marcus


    Meconium aspiration syndrome (MAS) is characterized by surfactant inactivation and inflammation. As lung epithelial cells up-regulate nitric oxide (NO) in response to inflammation, the NO production following meconium exposition was examined in relation to expression of Deleted in Malignant Brain...

  20. Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules. (United States)

    Yang, Chih-Chao; Graves, Hillary K; Moya, Ivan M; Tao, Chunyao; Hamaratoglu, Fisun; Gladden, Andrew B; Halder, Georg


    Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical-basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non-cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non-cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation.

  1. Uniformity in the basal metabolic rate of marsupials: its causes and consequences Uniformidad en la tasa metabólica basal de marsupiales: sus causas y consecuencias

    Directory of Open Access Journals (Sweden)



    Full Text Available Most of the variation (98.8 % in basal rate of metabolism (BMR in 70 species of marsupials is correlated with body mass, although lowland species have higher basal rates than highland species and burrowers have lower basal rates than non-burrowers. These factors collectively account for 99.2 % of the variation in marsupial BMR. Marsupials differ in BMR from eutherians by having no species with a high basal rate by general mammalian standards, even when consuming vertebrates or grass, food habits that are associated with very high basal rates in eutherians. The absence of high basal rates in marsupials reflects the absence of a correlation of rate of reproduction with basal rate, a correlation present in eutherians. These differences have two consequences: (1 marsupials are less tolerant of cold environments than eutherians, and (2 marsupials coexist with eutherians only when both have food habits associated with low basal rates and therefore when eutherians have reduced rates of reproduction. In Australia and South America marsupial carnivores diversified in the absence of eutherian equivalents. The importation to mainland Australia of dingos by humans appears to have been the immediate cause for the extinction of thylacines, Tasmanian devils, and eastern quolls. Carnivorous marsupials in South America were replaced by eutherians with the completion of the Panamanian land bridge. Macropods, which have lower basal rates than eutherian grazers, survive in central Australia probably because of their adjustment to xeric environments, whereas introduced domestic stock require the provision of water by humansGran parte de la variación (98,5 en la tasa metabólica basal de 70 especies de marsupiales se correlaciona con la masa corporal, aunque las especies de tierras bajas tienes tasas basales mayores que las de tierras altas, y las especies subterráneas tienes BMR’s menores que las no subterráneas. Colectivamente, estos factores dan cuenta de un

  2. Combining a GLP-1 receptor agonist and basal insulin: study evidence and practical considerations. (United States)

    Carris, Nicholas W; Taylor, James R; Gums, John G


    Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin-GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.

  3. Ethanol and reactive species increase basal sequence heterogeneity of hepatitis C virus and produce variants with reduced susceptibility to antivirals. (United States)

    Seronello, Scott; Montanez, Jessica; Presleigh, Kristen; Barlow, Miriam; Park, Seung Bum; Choi, Jinah


    Hepatitis C virus (HCV) exhibits a high level of genetic variability, and variants with reduced susceptibility to antivirals can occur even before treatment begins. In addition, alcohol decreases efficacy of antiviral therapy and increases sequence heterogeneity of HCV RNA but how ethanol affects HCV sequence is unknown. Ethanol metabolism and HCV infection increase the level of reactive species that can alter cell metabolism, modify signaling, and potentially act as mutagen to the viral RNA. Therefore, we investigated whether ethanol and reactive species affected the basal sequence variability of HCV RNA in hepatocytes. Human hepatoma cells supporting a continuous replication of genotype 1b HCV RNA (Con1, AJ242652) were exposed to ethanol, acetaldehyde, hydrogen peroxide, or L-buthionine-S,R-sulfoximine (BSO) that decreases intracellular glutathione as seen in patients. Then, NS5A region was sequenced and compared with genotype 1b HCV sequences in the database. Ethanol and BSO elevated nucleotide and amino acid substitution rates of HCV RNA by 4-18 folds within 48 hrs which were accompanied by oxidative RNA damage. Iron chelator and glutathione ester decreased both RNA damage and mutation rates. Furthermore, infectious HCV and HCV core gene were sufficient to induce oxidative RNA damage even in the absence of ethanol or BSO. Interestingly, the dn/ds ratio and percentage of sites undergoing positive selection increased with ethanol and BSO, resulting in an increased detection of NS5A variants with reduced susceptibility to interferon alpha, cyclosporine, and ribavirin and others implicated in immune tolerance and modulation of viral replication. Therefore, alcohol is likely to synergize with virus-induced oxidative/nitrosative stress to modulate the basal mutation rate of HCV. Positive selection induced by alcohol and reactive species may contribute to antiviral resistance.

  4. [Essential professional core competencies for nurses]. (United States)

    Chen, Yu-Chih


    Core competency is vital to the nursing profession. Such helps guarantee the high quality and effectiveness of delivered care and maintains the social value and status of the nursing profession. This article introduces the definition of nursing core competency and its connotations. The core competency profile for the nursing profession embraces basic behavioral attributes as well as mastery of advanced practice skills. The former include such attributes as gentleness, willingness to serve, keen observation and judgment, efficiency, skillfulness, responsibility and accountability. The latter embraces skills in general care, communication and collaboration, management, self-development, innovation and research, and stress-adjustment. To cultivate competent nurses, academic education should emphasize critical thinking skills, integrate problem-based and evidence-based learning approaches into curricula, and use objective structured clinical examination to evaluate learning outcomes. In the healthcare sector, systematic professional training models such as the clinical ladder with multidiscipline rotation hold the potential to train novice nurses as expert professionals. Meanwhile, to advance the professional capabilities of nurses, nursing administrators should provide a positive work environment to fuel and maintain learning motivation. Education and healthcare systems should work closely together to promote the professional competence of nurses and to strengthen the value of the nursing profession.

  5. Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance. (United States)

    Mohammed, Rabab A A; Ellis, Ian O; Mahmmod, Ali M; Hawkes, E Claire; Green, Andrew R; Rakha, Emad A; Martin, Stewart G


    Basal and triple-negative breast cancer phenotypes are characterised by unfavourable biological behaviour and outcome. Although certain studies have examined their pathological and molecular profile, the vascular characteristics of lymphatic and blood vessels have not been examined. Immunohistochemical staining with podoplanin, CD34 and CD31 was used to examine lymphatic and microvessel density, as well as vascular invasion in 197 basal-like and in 99 triple-negative breast tumours and compared against 200 non-basal and 334 non-triple-negative cases. All specimens were lymph node negative. Vascular invasion was identified as blood or lymphatic vascular invasion by the differential expression of markers. All measurements were correlated with clinicopathological features and prognosis. No significant difference was detected between the basal and triple-negative groups in terms of lymphatic or microvessel density or vascular invasion. However, both the basal and the triple-negative groups showed significantly higher microvessel density than did the non-basal and non-triple-negative groups (P=0.017 and Pcontrols. Interestingly, vascular invasion, almost entirely lymphatic invasion, was detected in 27% of the basal and in 26% of the triple-negative groups with no significant difference in comparison with control groups. In both basal and triple negatives, vascular invasion was associated with poorer survival by univariate and multivariate analyses. The 20-year overall survival rate in basal-like tumours was 55% in vascular invasion-positive cases compared with 73% in vascular invasion-negative tumours (P=0.012), and 46% in triple-negative vascular invasion-positive compared with 79% in vascular invasion-negative tumours (P=0.001). Basal-like vs non-basal-like and triple-negative vs non-triple-negative tumours have similar vascular characteristics in terms of lymphatic vessel density and vascular invasion but higher microvessel density, suggesting that such groups may

  6. Basal buoyancy and fast-moving glaciers: in defense of analytic force balance (United States)

    van der Veen, C. J.


    The geometric approach to force balance advocated by T. Hughes in a series of publications has challenged the analytic approach by implying that the latter does not adequately account for basal buoyancy on ice streams, thereby neglecting the contribution to the gravitational driving force associated with this basal buoyancy. Application of the geometric approach to Byrd Glacier, Antarctica, yields physically unrealistic results, and it is argued that this is because of a key limiting assumption in the geometric approach. A more traditional analytic treatment of force balance shows that basal buoyancy does not affect the balance of forces on ice streams, except locally perhaps, through bridging effects.

  7. Mechanisms and efficacy of vismodegib in the treatment of basal cell carcinoma. (United States)

    Amin, Shivan H; Motamedi, Kevin K; Ochsner, Matthew C; Song, Tara E; Hybarger, C Patrick


    Historically patients with advanced basal cell carcinoma have been subjected to large surgical resections for the treatment of their disease. However, with the development of vismodegib, a first in class molecule that acts to inhibit the hedgehog pathway, patients with advanced and metastatic basal cell carcinoma may have renewed hope in limiting the morbidity involved with surgery. Preliminary data shows a relatively good safety profile and promising results, although further research remains to be conducted. Current progress on utilization of vismodegib for the treatment of advanced basal cell carcinoma is reviewed in this article. Only literature with objective clinical evidence was included in this review.

  8. Understanding core conductor fabrics

    Energy Technology Data Exchange (ETDEWEB)

    Swenson, D E, E-mail: [Affinity Static Control Consulting, LLC 2609 Quanah Drive, Round Rock, Texas, 78681 (United States)


    ESD Association standard test method ANSI/ESD STM2.1 - Garments (STM2.1), provides electrical resistance test procedures that are applicable for materials and garments that have surface conductive or surface dissipative properties. As has been reported in other papers over the past several years{sup 1} fabrics are now used in many industries for electrostatic control purposes that do not have surface conductive properties and therefore cannot be evaluated using the procedures in STM2.1{sup 2}. A study was conducted to compare surface conductive fabrics with samples of core conductor fibre based fabrics in order to determine differences and similarities with regards to various electrostatic properties. This work will be used to establish a new work item proposal within WG-2, Garments, in the ESD Association Standards Committee in the USA.

  9. Complex coacervate core micelles. (United States)

    Voets, Ilja K; de Keizer, Arie; Cohen Stuart, Martien A


    In this review we present an overview of the literature on the co-assembly of neutral-ionic block, graft, and random copolymers with oppositely charged species in aqueous solution. Oppositely charged species include synthetic (co)polymers of various architectures, biopolymers - such as proteins, enzymes and DNA - multivalent ions, metallic nanoparticles, low molecular weight surfactants, polyelectrolyte block copolymer micelles, metallo-supramolecular polymers, equilibrium polymers, etcetera. The resultant structures are termed complex coacervate core/polyion complex/block ionomer complex/interpolyelectrolyte complex micelles (or vesicles); i.e., in short C3Ms (or C3Vs) and PIC, BIC or IPEC micelles (and vesicles). Formation, structure, dynamics, properties, and function will be discussed. We focus on experimental work; theory and modelling will not be discussed. Recent developments in applications and micelles with heterogeneous coronas are emphasized.


    Energy Technology Data Exchange (ETDEWEB)

    Susan S. Sorini; John F. Schabron; Joseph F. Rovani Jr


    Soil sampling and storage practices for volatile organic analysis must be designed to minimize loss of volatile organic compounds (VOCs) from samples. The En Core{reg_sign} sampler is designed to collect and store soil samples in a manner that minimizes loss of contaminants due to volatilization and/or biodegradation. An ASTM International (ASTM) standard practice, D 6418, Standard Practice for Using the Disposable En Core Sampler for Sampling and Storing Soil for Volatile Organic Analysis, describes use of the En Core sampler to collect and store a soil sample of approximately 5 grams or 25 grams for volatile organic analysis and specifies sample storage in the En Core sampler at 4 {+-} 2 C for up to 48 hours; -7 to -21 C for up to 14 days; or 4 {+-} 2 C for up to 48 hours followed by storage at -7 to -21 C for up to five days. This report discusses activities performed during the past year to promote and continue acceptance of the En Core samplers based on their performance to store soil samples for VOC analysis. The En Core sampler is designed to collect soil samples for VOC analysis at the soil surface. To date, a sampling tool for collecting and storing subsurface soil samples for VOC analysis is not available. Development of a subsurface VOC sampling/storage device was initiated in 1999. This device, which is called the Accu Core{trademark} sampler, is designed so that a soil sample can be collected below the surface using a dual-tube penetrometer and transported to the laboratory for analysis in the same container. Laboratory testing of the current Accu Core design shows that the device holds low-level concentrations of VOCs in soil samples during 48-hour storage at 4 {+-} 2 C and that the device is ready for field evaluation to generate additional performance data. This report discusses a field validation exercise that was attempted in Pennsylvania in 2004 and activities being performed to plan and conduct a field validation study in 2006. A draft ASTM

  11. Growth outside the core. (United States)

    Zook, Chris; Allen, James


    Growth in an adjacent market is tougher than it looks; three-quarters of the time, the effort fails. But companies can change those odds dramatically. Results from a five-year study of corporate growth conducted by Bain & Company reveal that adjacency expansion succeeds only when built around strong core businesses that have the potential to become market leaders. And the best place to look for adjacency opportunities is inside a company's strongest customers. The study also found that the most successful companies were able to consistently, profitably outgrow their rivals by developing a formula for pushing out the boundaries of their core businesses in predictable, repeatable ways. Companies use their repeatability formulas to expand into any number of adjacencies. Some companies make repeated geographic moves, as Vodafone has done in expanding from one geographic market to another over the past 13 years, building revenues from $1 billion in 1990 to $48 billion in 2003. Others apply a superior business model to new segments. Dell, for example, has repeatedly adapted its direct-to-customer model to new customer segments and new product categories. In other cases, companies develop hybrid approaches. Nike executed a series of different types of adjacency moves: it expanded into adjacent customer segments, introduced new products, developed new distribution channels, and then moved into adjacent geographic markets. The successful repeaters in the study had two common characteristics. First, they were extraordinarily disciplined, applying rigorous screens before they made an adjacency move. This discipline paid off in the form of learning curve benefits, increased speed, and lower complexity. And second, in almost all cases, they developed their repeatable formulas by studying their customers and their customers' economics very, very carefully.

  12. Transcriptional Auto-Regulation of RUNX1 P1 Promoter. (United States)

    Martinez, Milka; Hinojosa, Marcela; Trombly, Daniel; Morin, Violeta; Stein, Janet; Stein, Gary; Javed, Amjad; Gutierrez, Soraya E


    RUNX1 a member of the family of runt related transcription factors (RUNX), is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  13. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Directory of Open Access Journals (Sweden)

    Milka Martinez

    Full Text Available RUNX1 a member of the family of runt related transcription factors (RUNX, is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  14. Rapid Assessment for basal cavities on Dahomey National Wildlife Refuge: Implications for Present and Future Bat Conservation (United States)

    US Fish and Wildlife Service, Department of the Interior — Survey of mature forested areas on the refuge was done to examine trees with basal cavities for bats. Though the refuge supports many large diameter trees with basal...

  15. Processes and outcomes in school health promotion

    DEFF Research Database (Denmark)

    Simovska, Venka


    This is the second special issue of Health Education which features research, theory and practice based perspectives on what counts as desirable outcomes of health promotion in schools in terms of health as well as education, and the effective processes in schools which lead to these outcomes....... The focus in the first special issue was on highlighting the argument that the question about the outcomes of the health-promoting schools should not be limited to narrowly defined health outcomes but needs to be closely linked with the core tasks and values of the school. Building further on this argument......, the papers in this issue feature a number of research issues of relevance for the effectiveness of the health-promoting schools approach, as well as a variety of research and evaluation methodologies contributing to the debate about what counts as reliable evidence within the health-promoting schools...

  16. Genome-wide analysis of promoter architecture in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Hoskins, Roger A.; Landolin, Jane M.; Brown, James B.; Sandler, Jeremy E.; Takahashi, Hazuki; Lassmann, Timo; Yu, Charles; Booth, Benjamin W.; Zhang, Dayu; Wan, Kenneth H.; Yang, Li; Boley, Nathan; Andrews, Justen; Kaufman, Thomas C.; Graveley, Brenton R.; Bickel, Peter J.; Carninci, Piero; Carlson, Joseph W.; Celniker, Susan E.


    Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLMRACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.


    DEFF Research Database (Denmark)


    A promoter is described. The promoter comprises a nucleotide sequence corresponding to that shown as SEQ ID No. 1 or a variant, homologue or derivative thereof.......A promoter is described. The promoter comprises a nucleotide sequence corresponding to that shown as SEQ ID No. 1 or a variant, homologue or derivative thereof....

  18. Distinctive Reactivities at Biotite Edge and Basal Planes in the Presence of Organic Ligands: Implications for Organic-Rich Geologic CO2 Sequestration. (United States)

    Zhang, Lijie; Jun, Young-Shin


    To better understand how scCO2-saturated brine-mineral interactions can affect safe and efficient geologic CO2 sequestration (GCS), we studied the effects of organic ligands (acetate and oxalate) on biotite dissolution and surface morphological changes. The experimental conditions were chosen to be relevant to GCS sites (95 °C and 102 atm CO2). Quantitative analyses of dissolution differences between biotite edge and basal planes were made. Acetate slightly inhibited biotite dissolution and promoted secondary precipitation. The effect of acetate was mainly pH-induced aqueous acetate speciation and the subsequent surface adsorption. Under the experimental conditions, most of acetate exists as acetic acid and adsorbs to biotite surface Si and Al sites, thereby reducing their release. However, oxalate strongly enhanced biotite dissolution and induced faster and more significant surface morphology changes by forming bidentate mononuclear surface complexes. For the first time, we show that oxalate selectively attacks edge surface sites and enhances biotite dissolution. Thus, oxalate increases the relative reactivity ratio of biotite edge surfaces to basal surfaces, while acetate does not impact this relative reactivity. This study provides new information on reactivity differences at biotite edge and basal planes in the presence of organic ligands, which has implications for safe CO2 storage in organic-rich sites.

  19. Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers


    Jumppanen, Mervi; Gruvberger-Saal, Sofia; Kauraniemi, Päivikki; Tanner, Minna; Bendahl, Pär-Ola; Lundin, Mikael; Krogh, Morten; Kataja, Pasi; Borg, Åke; Fernö, Mårten; Isola, Jorma


    Introduction Basal-phenotype or basal-like breast cancers are characterized by basal epithelium cytokeratin (CK5/14/17) expression, negative estrogen receptor (ER) status and distinct gene expression signature. We studied the clinical and biological features of the basal-phenotype tumors determined by immunohistochemistry (IHC) and cDNA microarrays especially within the ER-negative subgroup. Methods IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers. The gene expression...

  20. Advances in core drilling technology (United States)

    Holdsworth, G.

    Some notable technical advances in drill design were reported at the meeting, held in Canada August 30-September 1, 1982, at the University of Calgary. Chief amongst these was a battery powered, computer assisted electromechanical core drill which has recently been used by the Danes in Greenland to continuously core to the base of the ice sheet at 2038 m. This is the deepest coring operation so far on the Greenland ice sheet. (The record for deep glacier drilling is held by the U.S. Army Cold Regions Research and Engineering Laboratory for the continuous coring through 2164 m of ice to bedrock at Byrd Station, Antarctica, in 1968). In early 1982, a current Soviet core drilling operation was reported to be at a depth of 2000 m at Vostok station, Antarctica, where the total ice thickness is about 4000 m; the goal of core drilling the entire ice thickness there could be achieved before the end of 1983.