Sample records for h1 subtypes differentially

  1. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

    Mora Xavier


    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  2. Differentiation of human influenza A viruses including the pandemic subtype H1N1/2009 by conventional multiplex PCR.

    Furuse, Yuki; Odagiri, Takashi; Okada, Takashi; Khandaker, Irona; Shimabukuro, Kozue; Sawayama, Rumi; Suzuki, Akira; Oshitani, Hitoshi


    April 2009 witnessed the emergence of a novel H1N1 influenza A virus infecting the human population. Currently, pandemic and seasonal influenza viruses are co-circulating in human populations. Understanding the course of the emerging pandemic virus is important. It is still unknown how the novel virus co-circulates with or outcompetes seasonal viruses. Sustainable and detailed influenza surveillance is required throughout the world including developing countries. In the present study, a multiplex PCR using four primers was developed, which was designed to differentiate the pandemic H1N1 virus from the seasonal H1N1 and H3N2 viruses, to obtain amplicons of different sizes. Multiplex PCR analysis could clearly differentiate the three subtypes of human influenza A virus. This assay was performed using 206 clinical samples collected in 2009 in Japan. Between February and April, four samples were subtyped as seasonal H1N1 and four as seasonal H3N2. All samples collected after July were subtyped as pandemic H1N1. Currently, pandemic viruses seem to have replaced seasonal viruses almost completely in Japan. This is a highly sensitive method and its cost is low. Influenza surveillance using this assay would provide significant information on the epidemiology of both pandemic and seasonal influenza.

  3. Fractionation of human H1 subtypes and characterization of a subtype-specific antibody exhibiting non-uniform nuclear staining.

    Parseghian, M H; Clark, R F; Hauser, L J; Dvorkin, N; Harris, D A; Hamkalo, B A


    Four histone H1 subtypes and H1(0) were fractionated from human placental nuclei and purified to homogeneity by a combination of Bio-Rex 70 chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Polyclonal antibodies were generated in rabbits against one of these subtypes designated H1-3. Antibodies reacted only against this subtype in enzyme-linked immunosorbent assays and Western assays; subtype specificity was documented further by Western blotting of cell and nuclear extracts. They crossreacted with monkey H1, but not with H1 from other vertebrates tested. The epitope(s) recognized were mapped by immunoblotting against peptides prepared by cleavage with N-bromosuccinimide (NBS) and alpha-chymotrypsin; it includes the variant amino-terminal tail of the protein as well as a portion of the globular domain. The antibody stains mitotic chromosomes weakly but uniformly and, unlike antibodies that recognize total H1 which show uniform nuclear staining after indirect immunofluorescence localization, anti-H1-3 exhibits preferential labelling of the nuclear periphery. This non-uniform staining suggests compartmentalization of this subtype which may have functional significance with respect to differential chromatin condensation.

  4. Specificities and genomic distribution of somatic mammalian histone H1 subtypes.

    Millán-Ariño, Lluís; Izquierdo-Bouldstridge, Andrea; Jordan, Albert


    Histone H1 is a structural component of chromatin that may have a role in the regulation of chromatin dynamics. Unlike core histones, the linker histone H1 family is evolutionarily diverse and many organisms have multiple H1 variants or subtypes, distinguishable between germ-line and somatic cells. In mammals, the H1 family includes seven somatic H1 variants with a prevalence that varies between cell types and over the course of differentiation, H1.1 to H1.5 being expressed in a replication-dependent manner, whereas H1.0 and H1X are replication-independent. Until recently, it has not been known whether the different variants had specific roles in the regulation of nuclear processes or were differentially distributed across the genome. To address this, an increasing effort has been made to investigate divergent features among H1 variants, regarding their structure, expression patterns, chromatin dynamics, post-translational modifications and genome-wide distribution. Although H1 subtypes seem to have redundant functions, several reports point to the idea that they are also differently involved in specific cellular processes. Initial studies investigating the genomic distribution of H1 variants have started to suggest that despite a wide overlap, different variants may be enriched or preferentially located at different chromatin types, but this may depend on the cell type, the relative abundance of the variants, the differentiation state of the cell, or whether cells are derived from a neoplastic process. Understanding the heterogeneity of the histone H1 family is crucial to elucidate their role in chromatin organization, gene expression regulation and other cellular processes.

  5. Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts.

    Gréen, Anna; Lönn, Anita; Peterson, Kajsa Holmgren; Ollinger, Karin; Rundquist, Ingemar


    Histone H1 is an important constituent of chromatin, which undergoes major structural rearrangements during mitosis. However, the role of H1, multiple H1 subtypes, and H1 phosphorylation is still unclear. In normal human fibroblasts, phosphorylated H1 was found located in nuclei during prophase and in both cytoplasm and condensed chromosomes during metaphase, anaphase, and telophase as detected by immunocytochemistry. Moreover, we detected remarkable differences in the distribution of the histone H1 subtypes H1.2, H1.3, and H1.5 during mitosis. H1.2 was found in chromatin during prophase and almost solely in the cytoplasm of metaphase and early anaphase cells. In late anaphase, it appeared in both chromatin and cytoplasm and again in chromatin during telophase. H1.5 distribution pattern resembled that of H1.2, but H1.5 was partitioned between chromatin and cytoplasm during metaphase and early anaphase. H1.3 was detected in chromatin in all cell cycle phases. We propose therefore, that H1 subtype translocation during mitosis is controlled by phosphorylation, in combination with H1 subtype inherent affinity. We conclude that H1 subtypes, or theirphosphorylated forms, may leave chromatin in a regulated way to give access for chromatin condensing factors or transcriptional regulators during mitosis.

  6. N- and C-terminal domains determine differential nucleosomal binding geometry and affinity of linker histone isotypes H1(0) and H1c.

    Vyas, Payal; Brown, David T


    Eukaryotic linker or H1 histones modulate DNA compaction and gene expression in vivo. In mammals, these proteins exist as multiple isotypes with distinct properties, suggesting a functional significance to the heterogeneity. Linker histones typically have a tripartite structure composed of a conserved central globular domain flanked by a highly variable short N-terminal domain and a longer highly basic C-terminal domain. We hypothesized that the variable terminal domains of individual subtypes contribute to their functional heterogeneity by influencing chromatin binding interactions. We developed a novel dual color fluorescence recovery after photobleaching assay system in which two H1 proteins fused to spectrally separable fluorescent proteins can be co-expressed and their independent binding kinetics simultaneously monitored in a single cell. This approach was combined with domain swap and point mutagenesis to determine the roles of the terminal domains in the differential binding characteristics of the linker histone isotypes, mouse H1(0) and H1c. Exchanging the N-terminal domains between H1(0) and H1c changed their overall binding affinity to that of the other variant. In contrast, switching the C-terminal domains altered the chromatin interaction surface of the globular domain. These results indicate that linker histone subtypes bind to chromatin in an intrinsically specific manner and that the highly variable terminal domains contribute to differences between subtypes. The methods developed in this study will have broad applications in studying dynamic properties of additional histone subtypes and other mobile proteins.

  7. The role of H1 linker histone subtypes in preserving the fidelity of elaboration of mesendodermal and neuroectodermal lineages during embryonic development.

    Nguyen, Giang D; Gokhan, Solen; Molero, Aldrin E; Yang, Seung-Min; Kim, Byung-Ju; Skoultchi, Arthur I; Mehler, Mark F


    H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs) depleted of H1c, H1d and H1e subtypes (H1-KO ESCs) by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers.

  8. The role of H1 linker histone subtypes in preserving the fidelity of elaboration of mesendodermal and neuroectodermal lineages during embryonic development.

    Giang D Nguyen

    Full Text Available H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs depleted of H1c, H1d and H1e subtypes (H1-KO ESCs by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers.

  9. [Visual detection of H1 subtype and identification of N1, N2 subtype of avian influenza virus by reverse transcription loop-mediated isothermal amplification assay].

    Peng, Yi; Xie, Zhi-Xun; Guo, Jie; Zhou, Chen-Yu; Liu, Jia-Bo; Pang, Yao-Shan; Deng, Xian-Wen; Xie, Zhi-Qin; Xie, Li-Ji; Fan, Qing; Luo, Si-Si


    In order to visually detect H1, N1 and N2 subtype of avian influenza virus (AIV), three reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays were developed. According to the sequences of AIV gene available in GenBank, three degenerate primer sets specific to HA gene of H1 subtype AIV, NA gene of N1 and N2 subtype AIV were designed, and the reaction conditions were optimized. The results showed that all the assays had no cross-reaction with other subtype AIV and other avian respiratory pathogens, and the detection limit was higher than that of conventional RT-PCR. These assays were performed in water bath within 50 minutes. Without opening tube, the amplification result could be directly determined by inspecting the color change of reaction system as long as these assays were fin-ished. Fourteen specimens of H1N1 subtype and eight specimens of H1N2 subtype of AIV were identified from the 120 clinical samples by RT-LAMP assays developed, which was consistent with that of virus isolation. These results suggested that the three newly developed RT-LAMEP assays were simple, specific and sensitive and had potential for visual detection of H1, N1 and N2 subtype of AIV in field.

  10. Possible computational filter to detect proteins associated to influenza A subtype H1N1.

    Polanco, Carlos; Buhse, Thomas; Castañón-González, Jorge Alberto; Samaniego, José Lino


    The design of drugs with bioinformatics methods to identify proteins and peptides with a specific toxic action is increasingly recurrent. Here, we identify toxic proteins towards the influenza A virus subtype H1N1 located at the UniProt database. Our quantitative structure-activity relationship (QSAR) approach is based on the analysis of the linear peptide sequence with the so-called Polarity Index Method that shows an efficiency of 90% for proteins from the Uniprot Database. This method was exhaustively verified with the APD2, CPPsite, Uniprot, and AmyPDB databases as well as with the set of antibacterial peptides studied by del Rio et al. and Oldfield et al.

  11. [Differential personality features in adult ADHD subtypes].

    Martínez Ortega, Yolanda; Bosch Munsó, Rosa; Gomà-i-Freixanet, Montserrat; Valero Ventura, Sergi; Ramos-Quiroga, Josep Antoni; Nogueira, Mariana; Casas Brugué, Miguel


    Attention Deficit/Hyperactivity Disorder (ADHD) and personality traits are relatively stable from childhood and across life span. The purpose of this study was to identify differential and discriminative personality traits between clinical subtypes of ADHD in adults. The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) and the Millon Multiaxial Clinical Inventory-II (MCMI-II) were administered to a sample of 146 adults with ADHD. Activity and Aggression-Hostility dimensions from the ZKPQ allowed us to properly classify 75.8% of the inattentive and combined subtypes. Data indicates that ADHD is not a homogeneous entity, but rather, there are significant differences in personality characteristics among clinical subtypes. The results have theoretical implications about the connection between ADHD and personality, and clinical implications regarding diagnosis and treatment designs better tailored to the characteristics of each subtype.

  12. Estrogenic regulation of histamine receptor subtype H1 expression in the ventromedial nucleus of the hypothalamus in female rats.

    Hiroko Mori

    Full Text Available Female sexual behavior is controlled by central estrogenic action in the ventromedial nucleus of the hypothalamus (VMN. This region plays a pivotal role in facilitating sex-related behavior in response to estrogen stimulation via neural activation by several neurotransmitters, including histamine, which participates in this mechanism through its strong neural potentiating action. However, the mechanism through which estrogen signaling is linked to the histamine system in the VMN is unclear. This study was undertaken to investigate the relationship between estrogen and histamine receptor subtype H1 (H1R, which is a potent subtype among histamine receptors in the brain. We show localization of H1R exclusively in the ventrolateral subregion of the female VMN (vl VMN, and not in the dorsomedial subregion. In the vl VMN, abundantly expressed H1R were mostly colocalized with estrogen receptor α. Intriguingly, H1R mRNA levels in the vl VMN were significantly elevated in ovariectomized female rats treated with estrogen benzoate. These data suggest that estrogen can amplify histamine signaling by enhancing H1R expression in the vl VMN. This enhancement of histamine signaling might be functionally important for allowing neural excitation in response to estrogen stimulation of the neural circuit and may serve as an accelerator of female sexual arousal.

  13. Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5

    Yim, Sanggyu; Jeong, Yong-Joo


    Surface protein hemagglutinin (HA) mediates the binding of influenza virus to host cell receptors containing sialic acid, facilitating the entry of the virus into host cells. Therefore, the HA protein is regarded as a suitable target for the development of influenza virus detection devices. In this study, we isolated single-stranded DNA (ssDNA) aptamers binding to the HA1 subunit of subtype H1 (H1-HA1), but not to the HA1 subunit of subtype H5 (H5-HA1), using a counter-systematic evolution of ligands by exponential enrichment (counter-SELEX) procedure. Enzyme-linked immunosorbent assay and surface plasmon resonance studies showed that the selected aptamers bind tightly to H1-HA1 with dissociation constants in the nanomolar range. Western blot analysis demonstrated that the aptamers were binding to H1-HA1 in a concentration-dependent manner, yet were not binding to H5-HA1. Interestingly, the selected aptamers contained G-rich sequences in the central random nucleotides region. Further biophysical analysis showed that the G-rich sequences formed a G-quadruplex structure, which is a distinctive structure compared to the starting ssDNA library. Using flow cytometry analysis, we found that the aptamers did not bind to the receptor-binding site of H1-HA1. These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus. PMID:25901739

  14. Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark

    Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik


    BACKGROUND: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically...... and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. METHODS: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation...... with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. RESULTS: The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene...

  15. Epidemiological and virological characterization of 2009 pandemic influenza A virus subtype H1N1 in Madagascar.

    Orelle, Arnaud; Razanajatovo, Norosoa Harline; Rajatonirina, Soatiana; Hoffmann, Jonathan; Randrianasolo, Laurence; Razafitrimo, Girard Marcellin; Naidoo, Dhamari; Richard, Vincent; Heraud, Jean-Michel


    Madagascar was one of the first African countries to be affected by the 2009 pandemic of influenza A virus subtype H1N1 [A(H1N1)pdm2009] infection. The outbreak started in the capital city, Antananarivo, and then spread throughout the country from October 2009 through February 2010. Specimens from patients presenting with influenza-like illness were collected and shipped to the National Influenza Center in Madagascar for analyses, together with forms containing patient demographic and clinical information. Of the 2303 specimens tested, 1016 (44.1%) and 131 (5.7%) yielded A(H1N1)pdm09 and seasonal influenza virus, respectively. Most specimens (42.0%) received were collected from patients 50 years old to be infected with A(H1N1)pdm09 (odds ratio, 2.1; 95% confidence interval, 1.7-2.6; P Madagascar, no antigenic differences between A(H1N1)pdm09 viruses recovered in Madagascar and those that circulated worldwide were observed. The high proportion of respiratory specimens positive for A(H1N1)pdm09 is consistent with a widespread transmission of the pandemic in Madagascar. The age distribution of cases of A(H1N1)pdm09 infection suggests that children and young adults could be targeted for interventions that aim to reduce transmission during an influenza pandemic.

  16. Structural and Functional Analysis of NS1 and NS2 Proteins of H1N1 Subtype

    Parveen Salahuddin; Asad U.Khan


    Influenza A virus(H1N1),a genetic reassortment of endemic strains of human,avian and swine flu,has crossed species barrier to human and apparently acquired the capability of human to human transmission.Some strains of H5N1 subtype are highly virulent because NS1 protein inhibits antiviral interferon α/β production.Another protein NS2 mediates export of viral ribonucleoprotein from nucleus to the cytoplasm through export signal.In this paper,we have studied structure-function relationships of these proteins of H1N1 subtype and have determined the cause of their pathogenicity.Our results showed that non-conservative mutations slightly stabilized or destabilized structural domains of NS1 or NS1-dsRNA complex,hence slightly increased or decreased the function of NS1 protein and consequently enhanced or reduced the pathogenicity of the H1N1 virus.NS2 protein of different strains carried non-conservative mutations in different domains,resulting in slight loss of function.These mutations slightly decreased the pathogenicity of the virus.Thus,the results confirm the structure-function relation-ships of these viral proteins.

  17. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    Usman Sumo Friend Tambunan; Rizky Archintya Rachmania; Arli Aditya Parikesit


    This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-l-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir.AD3BF2D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

  18. A differentiation-based phylogeny of cancer subtypes.

    Markus Riester


    Full Text Available Histopathological classification of human tumors relies in part on the degree of differentiation of the tumor sample. To date, there is no objective systematic method to categorize tumor subtypes by maturation. In this paper, we introduce a novel computational algorithm to rank tumor subtypes according to the dissimilarity of their gene expression from that of stem cells and fully differentiated tissue, and thereby construct a phylogenetic tree of cancer. We validate our methodology with expression data of leukemia, breast cancer and liposarcoma subtypes and then apply it to a broader group of sarcomas. This ranking of tumor subtypes resulting from the application of our methodology allows the identification of genes correlated with differentiation and may help to identify novel therapeutic targets. Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors.

  19. 部分猪场H1和H3亚型猪流感的血清学调查%Serological Survey of H1 and H3 Subtypes of Swine Influenza in Some Pig Farms

    陈锦成; 张丹琳; 陈敏鸿; 张显浩; 贺东生


    To survey the epidemics of H1, H3 subtypes of swine influenza virus in some scale pig farms in some provinces, 799 swine serum samples were collected from 28 factory pig farms on 12 cities in Guangdong, Hunan and Henan provinces. The antibodies against H1 and H3 subtypes of SIV were determined by HI assay. The results showed that the positive rate of H1 subtype antibody of pigs was 0 to 83. 33% , the average positive rate of pigs was 46. 18% (369/799) and the positive rate of pig farms was 89. 29% (25/28). The positive rate of H3 subtype antibody of pigs was 0 to 100% > the average positive rate of pigs was 61. 33% (490/799) and the positive rate of pig farms was 85. 71% (24/28). The average positive rate of H1 subtype antibody of pigs of Guangdong, Hunan and Henan provinces respectively was 48. 91% , 40. 26% and 50. 67% , the rate of H3 subtype antibody was 58. 55%, 70. 78% and 78. 67%. It showed that the infection of H1 and H3 subtypes of swine influenza virus was widespread in the surveyed pigs of the 3 above regions. The infection rate of H3 subtype was higher than H1 subtype. The epidemics of swine influenza varied in different region.%为了解中国部分省市规模化猪场H1和H3亚型猪流感病毒的流行情况,采用血凝抑制试验对采集于广东、湖南、河南省12个市县28个规模化猪场的799份血清进行H1和H3亚型猪流感病毒的抗体检测.结果表明,H1亚型抗体阳性率在0~83.33%之间,猪抗体总阳性率为46.18%(369/799),猪场阳性率为89.29%(25/28).H3亚型抗体阳性率在0~100.00%之间,猪抗体总阳性率为61.33%(490/799),猪场阳性率为85.71%(24/28).广东、湖南和河南地区H1亚型抗体阳性率分别为48.91%、40.26%和50.67%,H3亚型抗体阳性率分别为58.55%、70.78%和78.67%.在被调查的上述3个地区的猪群中,H1和H3亚型猪流感病毒的感染较为普遍,其中H3亚型感染率高于H1亚型,且各地区猪流感病毒的流行情况存在地域性差异.

  20. Role of H1 linker histones in mammalian development and stem cell differentiation.

    Pan, Chenyi; Fan, Yuhong


    H1 linker histones are key chromatin architectural proteins facilitating the formation of higher order chromatin structures. The H1 family constitutes the most heterogeneous group of histone proteins, with eleven non-allelic H1 variants in mammals. H1 variants differ in their biochemical properties and exhibit significant sequence divergence from one another, yet most of them are highly conserved during evolution from mouse to human. H1 variants are differentially regulated during development and their cellular compositions undergo dramatic changes in embryogenesis, gametogenesis, tissue maturation and cellular differentiation. As a group, H1 histones are essential for mouse development and proper stem cell differentiation. Here we summarize our current knowledge on the expression and functions of H1 variants in mammalian development and stem cell differentiation. Their diversity, sequence conservation, complex expression and distinct functions suggest that H1s mediate chromatin reprogramming and contribute to the large variations and complexity of chromatin structure and gene expression in the mammalian genome. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. 568份疑似甲型H1N1流感病例标本病原学检测结果分析%Results of detection of 568 suspected influenza A virus subtype H1N1 patients

    黄丽华; 唐保晖


    Aim To detect influenza A virus subtype H1N1 in Hechi City from suspected patients by nucleic acid assay. Methods The nucleic acids of influenza A and B viruses and nfluenza A virus subtype H1N1 were simultaneously detected from 568 suspected influenza A virus subtype H1N1 patients by using real time quantitative RT-PCR method (Real-time RT-PCR). Seasonal influenza virus subtype H1N1 and H3N2 would detected from the samples positive forinfluenza A virus nucleic acid,while negative for influenza B virus and influenza A virus subtype H1N1 nucleic acid.Results In the 568 suspected samples,there were 334 samples positive for influenza A H1N1 influenza virus nucleic acid and 14 positive for seasonal influenza virus subtype H1N1 nucleic acid positive,25 positive for seasonal influenza virus subtype H3N2 nucleic acid positive and 40 positive for no-differentiated influenza A virus nucleic acid. Conclusion Laboratory tests provide a basis for sensitive, specific and efficient confirmation and control of influenza A(H1N1 ).%目的 对河池市568份疑似甲型H1N1流感病例标本进行核酸检测,为甲型H1N1流感疫情的防控提供依据.方法 对疑似甲型H1N1流感病例标本用实时荧光定量RT-PCR法(Real-time RT-PCR)检测,检测项目为A型流感病毒核酸、B型流感病毒核酸和甲型H1N1流感病毒核酸,对A型流感病毒核酸阳性而B型流感病毒核酸和甲型H1N1流感病毒核酸均阴性标本再进行季节性流感病毒H1N1、H3N2亚型流感病毒核酸检测.结果 检测疑似病例标本568份,其中甲型H1N1流感病毒核酸阳性334份,季节性流感病毒H1N1亚型核酸阳性14份,季节性流感病毒H3N2亚型核酸阳性25份,A未分型流感病毒核酸阳性40份.结论 实验室检测为甲型H1N1流感疫情的确认、防控以及病人的处理提供了依据,对提高实验窒检测技术的敏感性、特异性和实效性具有重要的意义.

  2. Pre-infection of pigs with Mycoplasma hyopneumoniae modifies outcomes of infection with European swine influenza virus of H1N1, but not H1N2, subtype.

    Deblanc, C; Gorin, S; Quéguiner, S; Gautier-Bouchardon, A V; Ferré, S; Amenna, N; Cariolet, R; Simon, G


    Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease.

  3. Nucleosome linker proteins HMGB1 and histone H1 differentially enhance DNA ligation reactions.

    Yamanaka, Shiho; Katayama, Eisaku; Yoshioka, Ken-ichi; Nagaki, Sumiko; Yoshida, Michiteru; Teraoka, Hirobumi


    We previously reported that HMGB1, which originally binds to chromatin in a manner competitive with linker histone H1 to modulate chromatin structure, enhances both intra-molecular and inter-molecular ligations. In this paper, we found that histone H1 differentially enhances ligation reaction of DNA double-strand breaks (DSB). Histone H1 stimulated exclusively inter-molecular ligation reaction of DSB with DNA ligase IIIbeta and IV, whereas HMGB1 enhanced mainly intra-molecular ligation reaction. Electron microscopy of direct DNA-protein interaction without chemical cross-linking visualized that HMGB1 bends and loops linear DNA to form compact DNA structure and that histone H1 is capable of assembling DNA in tandem arrangement with occasional branches. These results suggest that differences in the enhancement of DNA ligation reaction are due to those in alteration of DNA configuration induced by these two linker proteins. HMGB1 and histone H1 may function in non-homologous end-joining of DSB repair and V(D)J recombination in different manners.

  4. Efficacy of a high-growth reassortant H1N1 influenza virus vaccine against the classical swine H1N1 subtype influenza virus in mice and pigs.

    Wen, Feng; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Yang, Sheng; Zhou, Yan-Jun; Li, Ze-Jun; Tong, Guang-Zhi


    Swine influenza (SI) is an acute, highly contagious respiratory disease caused by swine influenza A viruses (SwIVs), and it poses a potential global threat to human health. Classical H1N1 (cH1N1) SwIVs are still circulating and remain the predominant subtype in the swine population in China. In this study, a high-growth reassortant virus (GD/PR8) harboring the hemagglutinin (HA) and neuraminidase (NA) genes from a novel cH1N1 isolate in China, A/Swine/Guangdong/1/2011 (GD/11) and six internal genes from the high-growth A/Puerto Rico/8/34(PR8) virus was generated by plasmid-based reverse genetics and tested as a candidate seed virus for the preparation of an inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice and pigs challenged with GD/11 virus. Prime and boost inoculation of GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting (HI) antibodies and IgG antibodies for GD/11 in both mice and pigs. Complete protection of mice and pigs against cH1N1 SIV challenge was observed, with significantly fewer lung lesions and reduced viral shedding in vaccine-inoculated animals compared with unvaccinated control animals. Our data demonstrated that the GD/PR8 may serve as the seed virus for a promising SwIVs vaccine to protect the swine population.

  5. Highly efficient H 1-Galerkin mixed finite element method (MFEM) for parabolic integro-differential equation

    石东洋; 廖歆; 唐启立


    A highly effcient H 1-Galerkin mixed finite element method (MFEM) is presented with linear triangular element for the parabolic integro-differential equation. Firstly, some new results about the integral estimation and asymptotic expansions are studied. Then, the superconvergence of order O(h2) for both the original variable u in H1(Ω) norm and the flux p=∇u in H(div,Ω) norm is derived through the interpolation post processing technique. Furthermore, with the help of the asymptotic expansions and a suitable auxiliary problem, the extrapolation solutions with accuracy O(h3) are obtained for the above two variables. Finally, some numerical results are provided to confirm validity of the theoretical analysis and excellent performance of the proposed method.

  6. Histone H3 Methyltransferase Suv39h1 Prevents Myogenic Terminal Differentiation by Repressing MEF2 Activity in Muscle Cells

    Wei Jin


    Full Text Available The myogenic regulatory factors (MRFs and myocyte enhancer factor 2 (MEF2 transcription factors have been extensively studied as key transcription factors that regulate myogenic gene expression. However, few reports on the molecular mechanism that modulates chromatin remodeling during skeletal muscle differentiation are available. We reported here that the expression of the H3-K9 methyltransferase Suv39h1 was decreased during myoblast differentiation. Ectopic expression of Suv39h1 could inhibit myoblast differentiation, increasing H3-K9 methylation levels, whereas knockdown of Suv39h1 stimulated myoblast differentiation. Furthermore, Suv39h1 interacted with MEF2C directly and inhibited MEF2 transcription activity in a dose-dependent manner. Together, our studies revealed a molecular mechanism wherein Suv39h1 modulated myogenic gene expression and activation during skeletal muscle differentiation.

  7. Different subtypes of impulsivity differentiate uncontrolled eating and dietary restraint.

    Leitch, Margaret A; Morgan, Michael J; Yeomans, Martin R


    The current study explored the relationship between three subtypes of impulsivity (Reflection Impulsivity, Impulsive Choice, and Impulsive Action) and measures of uncontrolled eating (TFEQ-D) and restraint (TFEQ-R). Eighty women classified as scoring higher or lower on TFEQ-D and TFEQ-R completed the Matching Familiar Figures Test (MFFT20), Delay Discounting Task (DDT), a Go No Go task, Balloon Analogue Risk Task (BART), and the Barrett Impulsivity Scale-11 (BIS-11). To test whether these relationships were affected by enforced controls overeating, half of the participants fasted the night before and ate breakfast in the laboratory before testing and half had no such control. Women scoring higher on the TFEQ-D were significantly more impulsive on the MFFT20 and BIS-11 overall but not on DDT, Go No Go or BART. Women scoring higher on TFEQ-R were significantly less impulsive on the Go No Go task but did not differ on other measures. The eating manipulation modulated responses on the BART and BIS-11 non-planning scale depending on TFEQ-D classification. These results confirm recent data that high scores on TFEQ-D are related to impulsivity, but imply this relates more to Reflection Impulsivity rather than Impulsive Choice or Action. In contrast restrained eating was associated with better inhibitory control. Taken together, these results suggest that subtypes of impulsivity further differentiate uncontrolled eating and restraint, and suggest that a poor ability to reflect on decisions may underlie some aspects of overeating.

  8. Paper-based enzyme-free immunoassay for rapid detection and subtyping of influenza A H1N1 and H3N2 viruses.

    Lei, Kin Fong; Huang, Chia-Hao; Kuo, Rei-Lin; Chang, Cheng-Kai; Chen, Kuan-Fu; Tsao, Kuo-Chien; Tsang, Ngan-Ming


    Development of rapid screening in the ambulatory environment is the most pressing needs for the control of spread of infectious disease. Despite there are many methods to detect the immunoassay results, quantitative measurement in rapid disease screening is still a great challenge for point-of-care applications. In this work, based on the internal structural protein, i.e., nucleoprotein (NP), and outer surface glycoproteins, i.e., H1 and H3, of the influenza viruses, specific and sensitive immunoassay on paper-based platform was evaluated and confirmed. Detection and subtyping of influenza A H1N1 and H3N2 viruses found in people were demonstrated by colorimetric paper-based sandwich immunoassay. Concentration-dependent response to influenza viruses was shown and the detection limits could achieve 2.7×10(3) pfu/assay for H1 detection and 2.7×10(4) pfu/assay for H3 detection, which are within the clinical relevant level. Moreover, detection of influenza virus from infected cell lysate and clinical samples was demonstrated to further confirm the reliability of the paper-based immunoassay. The use of paper for the development of diagnostic devices has the advantages of lightweight, ease-of-use, and low cost and paper-based immunoassay is appropriate to apply for rapid screening in point-of-care applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development.

    Rai, Kunal; Nadauld, Lincoln D; Chidester, Stephanie; Manos, Elizabeth J; James, Smitha R; Karpf, Adam R; Cairns, Bradley R; Jones, David A


    DNA methylation and histone methylation are two key epigenetic modifications that help govern heterochromatin dynamics. The roles for these chromatin-modifying activities in directing tissue-specific development remain largely unknown. To address this issue, we examined the roles of DNA methyltransferase 1 (Dnmt1) and the H3K9 histone methyltransferase Suv39h1 in zebra fish development. Knockdown of Dnmt1 in zebra fish embryos caused defects in terminal differentiation of the intestine, exocrine pancreas, and retina. Interestingly, not all tissues required Dnmt1, as differentiation of the liver and endocrine pancreas appeared normal. Proper differentiation depended on Dnmt1 catalytic activity, as Dnmt1 morphants could be rescued by active zebra fish or human DNMT1 but not by catalytically inactive derivatives. Dnmt1 morphants exhibited dramatic reductions of both genomic cytosine methylation and genome-wide H3K9 trimethyl levels, leading us to investigate the overlap of in vivo functions of Dnmt1 and Suv39h1. Embryos lacking Suv39h1 had organ-specific terminal differentiation defects that produced largely phenocopies of Dnmt1 morphants but retained wild-type levels of DNA methylation. Remarkably, suv39h1 overexpression rescued markers of terminal differentiation in Dnmt1 morphants. Our results suggest that Dnmt1 activity helps direct histone methylation by Suv39h1 and that, together, Dnmt1 and Suv39h1 help guide the terminal differentiation of particular tissues.

  10. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

    Thomas P Stricker


    Full Text Available Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+ subtype and fourteen triple negative (TN subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3'UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors.

  11. Comparison of shedding characteristics of seasonal influenza virus (subtypes and influenza A(H1N1pdm09; Germany, 2007-2011.

    Thorsten Suess

    Full Text Available BACKGROUND: Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany. METHODS: Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (subtype of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily. RESULTS: We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1, 19 with A(H3N2, 60 with influenza B, and 98 with A(H1N1pdm09. Nine (14% of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0% of 21 children, 9 (21% of 44 adults; p = 0.03. Viral load among patients with influenza-like illness (ILI peaked on illness days 1, 2 or 3 for all (subtypes and declined steadily until days 7-9. Clinical symptom scores roughly paralleled viral shedding dynamics. On the first day prior to symptom onset 30% (12/40 of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4-6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status. CONCLUSION: Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic (subtype, age, antiviral therapy or vaccination; however the power to find moderate differences

  12. Binding of histone H1 to DNA is differentially modulated by redox state of HMGB1.

    Eva Polanská

    Full Text Available HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. In this study we demonstrate that redox state of HMGB1 can significantly modulate the ability of the protein to bind and bend DNA, as well as to promote DNA end-joining. We also report a high affinity binding of histone H1 to hemicatenated DNA loops and DNA minicircles. Finally, we show that reduced HMGB1 can readily displace histone H1 from DNA, while oxidized HMGB1 has limited capacity for H1 displacement. Our results suggested a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA. Possible biological consequences of linker histones H1 replacement by HMGB1 for the functioning of chromatin are discussed.

  13. Traditional Chinese Medicine Therapeutic Characteristics in the Treatment of Influenza A Virus Subtype H1N1 Based on Data Mining%基于文本挖掘分析甲型H1N1流感的中医药治疗特色

    郭洪涛; 郑光; 赵静; 姜淼; 何晓娟; 吕爱平


    Through data mining, raw data was downloaded from the Chinese BioMedical Literature Database (CBM) with keyword as "H1N1". Then, the downloaded, semi-structured data set was converted into fully structured data and stored in the database. Based on the discrete derivative algorithm, the data set was mined for therapeutic char acteristics in traditional Chinese medicine (TCM). The data mining process revealed results as follows. (1) In TCM clinical practice on influenza A virus subtype H1N1, the therapy is focused on dispelling heat and resolving toxicity. (2) The widely used TCM patent medicines are Lian-Hua-Qing-Wen Capsule, Tan-Re-Qing Injection, Qing-Kai Ling Injection, and Shuang-Huang-Lian Injection. (3) Using TCM patent medicine, the syndrome differentiation of influenza A virus subtype H1N1 can be determined into patterns of toxicity, fire (heat), and dampness (phlegm). (4) TCM patent medicines are mainly prescribed by western medicine doctors. However, TCM syndrome differentiation is still an existing problem in the medical practice of modern medicine doctors. (5) In data mining, validating suspi cious results by reviewing them in the original literature is an irreplaceable method.%从中国生物医学文献数据库(CBM)中检索治疗甲型H1N1流感的文献数据,针对半格式化的原始数据,进行格式化转换,存储于大型关系型数据库;针对格式化的数据,采用基于敏感关键词频数统计的离散导数算法,对文献数据进行挖掘处理;针对文本挖掘的结果,结合原文献人工回溯可疑结果,得到以下结论:(1)在治疗甲型H1N1流感的过程中,中药以清热解毒为主;(2)中成药以连花清瘟胶囊、痰热清注射液、清开灵制剂、双黄连制剂为主;(3)以药测证,可推断甲型H1N1流感的发病特点是毒、火(热)、湿(痰);(4)中成药的使用以西医医生为主,但存在辩证使用问题;(5)针对文本挖掘的可疑结果,回溯原文献是一种不可替代的方法.

  14. Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.

    David Metzgar

    Full Text Available For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based or remarkably insensitive (antibody-based. Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A

  15. Does subtype of developmental coordination disorder count: is there a differential effect on outcome following intervention?

    Green, D; Chambers, M E; Sugden, D A


    It is well known that developmental coordination disorder (DCD) is a heterogeneous condition in which children frequently present with co-occurring conditions in addition to their motor difficulties. This study considered whether there would be a differential effect of a group treatment program on subtypes of perceptual and movement problems or associated co-occurring conditions. A subset of children (n=43) from a larger clinical sample (n=100) with DCD participated in a 214 year cross-over intervention study which followed the cognitive orientation to daily occupational performance (CO-OP) approach. Original subtypes were determined by contrasting the current sample with previously published subtyping studies in DCD [Hoare, D. (1994). Subtypes of developmental coordination disorder. Adapted Physical Activity Quarterly, 11, 158-169; Macnab, J. J., Miller, L. T., & Polatajko, H. J. (2001). The search for subtypes of DCD: Is cluster analysis the answer? Human Movement Science, 20, 49-72]. No advantage was conferred to any subtype although children with more profound and complex difficulties at initial assessment, despite progress following intervention, were most likely to have continuing difficulties at the end of the project.

  16. An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes

    Muiño, Elena; Krupinski, Jurek; Carrera, Caty; Gallego-Fabrega, Cristina; Montaner, Joan; Fernández-Cadenas, Israel


    Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation. Methods. We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype. Results. Three polymorphisms, rs1205 (CRP gene), rs1800779, and rs2257073 (NOS3 gene), were associated with cardioembolic stroke (p value stroke subtype (p value: 0.001) and was replicated in an independent cohort (p value: 0.017). The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases (p value: 0.002). Conclusion. The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes. PMID:26355258

  17. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

    Perez-Janices, Noemi; Blanco-Luquin, Idoia; Torrea, Natalia; Liechtenstein, Therese; Escors, David; Cordoba, Alicia; Vicente-Garcia, Francisco; Jauregui, Isabel; De La Cruz, Susana; Illarramendi, José Juan; Coca, Valle; Berdasco, Maria; Kochan, Grazyna; Ibañez, Berta; Lera, José Miguel; Guerrero-Setas, David


    Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID:26284587

  18. An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes

    Elena Muiño


    Full Text Available Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar. However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation. Methods. We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype. Results. Three polymorphisms, rs1205 (CRP gene, rs1800779, and rs2257073 (NOS3 gene, were associated with cardioembolic stroke (p value <0.05. The score generated was only associated with the cardioembolic stroke subtype (p value: 0.001 and was replicated in an independent cohort (p value: 0.017. The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases (p value: 0.002. Conclusion. The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes.

  19. Establishment of oligonucleotide microarray for detection of influenza virus subtypes H1N1 and H3N2%H1N1和H3N2亚型流感病毒基因芯片检测方法的建立

    王慧煜; 梅琳; 侯义宏; 李全芬; 林祥梅; 韩雪清


    为建立同时能鉴别甲型H1N1和猪流感病毒常见亚型的新型基因芯片检测方法,根据GenBank中已发表的甲型流感病毒MP的基因序列和甲型H1N1(2009)和猪流感病毒H1N1、H3N2亚型的基因序列,设计、筛选并合成7对特异性引物和1对通用引物;根据扩增的靶序列,设计并合成14条特异性探针和3条质控探针,制备了甲型H1N1(2009)流感病毒和猪流感病毒H1N1、H3N2亚型基因芯片;并进行了特异性试验、敏感性试验和田间样品的检测。结果显示,该芯片检测方法与猪细小病毒(PPV)、猪瘟病毒(CSFV)、猪繁殖与呼吸综合征病毒(PRRSV)等猪常见病毒无交叉反应;对猪H1N1、猪H3N2和甲型H1N1(2009)流感病毒而言,最低可检测到105、104和105稀释的病毒株。结果证实,该方法特异性强、敏感性高,是一种高通量的甲型H1N1和猪流感常见亚型筛查方法。%Seven pairs of primers specific for different subtypes and a pair of universal primers were carefully designed based on the genomic sequences of A/H1N1 and swine influenza virus retrieved from GenBank database.Several multiplex RT-PCR methods were then developed.Further 14 oligonucleotide probes specific for A/H1N1 and swine influenza virus were designed according to the published gene in target cDNA domains.Then a microarray for A/H1N1 and swine influenza virus was developed with its specificity and sensitivity validated by using swine influenza virus strains and samples from different areas.The results showed that all the subtypes of swine influenza virus and A/H1N1 virus could be identified simultaneously on this microarray with high sensitivity,which could reach to 105 dilute viruses.Furthermore,there was no cross reactions with PPV,CSFV and PRRSV.Therefore the microarray is a useful diagnostic method with high specificity and sensitivity,and could be used for A/H1N1 and swine influenza surveillance.

  20. Dynamic MR imaging: value of differentiating subtypes of peripheral small adenocarcinoma of the lung

    Ohno, Yoshiharu E-mail:; Hatabu, Hiroto; Takenaka, Daisuke; Uematsu, Hidemasa; Ohbayashi, Chiho; Higashino, Takanori; Nogami, Munenobu; Yoshimura, Masahiro; Fujii, Masahiko; Sugimura, Kazuro


    Purpose: To determine the utility of dynamic magnetic resonance imaging (MRI) in the differential subtyping of small adenocarcinomas of the lung. Materials and methods: Twenty-nine pathologically diagnosed peripheral adenocarcinomas (less than 20 mm in diameter) underwent dynamic contrast-enhanced MRI. Maximum relative enhancement ratio, slope of enhancement, and corrected start time of enhancement were calculated from signal intensity-time curve of pulmonary lesion for each subject, and were statistically compared among bronchioloalveolar carcinoma (BAC) group (7 cases), mixed BAC group (10 cases), and adenocarcinoma group (12 cases). Results: Maximum relative enhancement ratio (P<0.001) and slope of enhancement (P<0.001) of BAC group were significantly higher than those of mixed BAC and adenocarcinoma groups. Start times of BAC group were significantly earlier than those of mixed BAC (P=0.0001) and adenocarcinoma groups (P<0.0001). Adapting the thresholds values of MR indexes from the positive tests, sensitivity, specificity, positive predictive value, negative predictive value and accuracy for differentiating BAC from other subtypes were 85.7, 100.0, 100.0, 95.7, and 96.6%, respectively. Conclusions: Dynamic MRI is useful for differentiating subtypes of small peripheral adenocarcinoma.

  1. Molecular Characterization and Phylogenetic Analysis of the Hemagglutinin 1 Protein of Human Influenza A Virus Subtype H1N1 Circulating in Kenya During 2007-2008


    and Mag Attract Virus Mini M48 Kit (Qiagen) according to the manufacturer’s pro- tocols. For RT- PCR amplification , 5 μL of RNA was added to a 50-μL...AAA TGA AAG-3′; and H1HA_1238_R_M13, 5′- CAG GAA ACA GCT ATG ACC AGC TGT GAA TTG RGT GTT CAT TT-3′), using the SuperScript III One-Step RT- PCR System... amplification cycles at 94°C for 15 seconds, at 52°C for 30 seconds, and at 68°C for 75 seconds, with a final extension cycle at 68°C for 5 minutes. All PCR

  2. Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses.

    McCormick, Kara; Jiang, Zhiyong; Zhu, Longchao; Lawson, Steven R; Langenhorst, Robert; Ransburgh, Russell; Brunick, Colin; Tracy, Miranda C; Hurtig, Heather R; Mabee, Leah M; Mingo, Mark; Li, Yanhua; Webby, Richard J; Huber, Victor C; Fang, Ying


    Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes. Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates. This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines.

  3. Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures

    Juric, Dejan; Sale, Sanja; Hromas, Robert A.; Yu, Ron; Wang, Yan; Duran, George E.; Tibshirani, Robert; Einhorn, Lawrence H.; Sikic, Branimir I.


    Germ cell tumors (GCTs) of the testis are the predominant cancer among young men. We analyzed gene expression profiles of 50 GCTs of various subtypes, and we compared them with 443 other common malignant tumors of epithelial, mesenchymal, and lymphoid origins. Significant differences in gene expression were found among major histological subtypes of GCTs, and between them and other malignancies. We identified 511 genes, belonging to several critical functional groups such as cell cycle progression, cell proliferation, and apoptosis, to be significantly differentially expressed in GCTs compared with other tumor types. Sixty-five genes were sufficient for the construction of a GCT class predictor of high predictive accuracy (100% training set, 96% test set), which might be useful in the diagnosis of tumors of unknown primary origin. Previously described diagnostic and prognostic markers were found to be expressed by the appropriate GCT subtype (AFP, POU5F1, POV1, CCND2, and KIT). Several additional differentially expressed genes were identified in teratomas (EGR1 and MMP7), yolk sac tumors (PTPN13 and FN1), and seminomas (NR6A1, DPPA4, and IRX1). Dynamic computation of interaction networks and mapping to existing pathways knowledge databases revealed a potential role of EGR1 in p21-induced cell cycle arrest and intrinsic chemotherapy resistance of mature teratomas. PMID:16306258

  4. Computational design of drug candidates for influenza A virus subtype H1N1 by inhibiting the viral neuraminidase-1 enzyme

    Tambunan Usman Sumo Friend


    Full Text Available It is critical to seek potential alternative treatments for H1N1 infections by inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the activity of neuraminidase- 1 is peptide drug design. In order to increase peptide stability, cyclization is necessary to prevent its digestion by protease enzyme. Cyclization of peptide ligands by formation of disulfide bridges is preferable for designing inhibitors of neuraminidase-1 because of their high activity and specificity. Here we designed ligands by using molecular docking, drug scan and dynamics computational methods. Based on our docking results, short polypeptides of cystein-arginine-methionine-tyrosine- -proline-cysteine (CRMYPC and cysteine-arginine-aspargine- phenylalanine-proline-cysteine (CRNFPC have good residual interactions with the target and the binding energy ΔGbinding of -31.7402 and -31.0144 kcal mol-1, respectively. These values are much lower than those of the standards, and it means that both ligands are more accessible to ligand-receptor binding. Based on drug scan results, both of these ligands are neither mutagenic nor carcinogenic. They also show good oral bioavailability. Moreover, both ligands show relatively stable molecular dynamics progression of RMSD vs. time plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminidase-1

  5. Targeted Differentiation of Regional Ventral Neuroprogenitors and Related Neuronal Subtypes from Human Pluripotent Stem Cells

    Liankai Chi


    Full Text Available Embryoid body (EB formation and adherent culture (AD paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE, while the AD cells mostly adopt a floor-plate (FP fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency. Gene targeting combined with small-molecule screening experiments identified that concomitant inhibition of Wnts, STAT3, and p38 pathways (3i could largely convert FP to MGE under AD conditions. Thus, differentiation paradigms and signaling regulators can be integrated together to specify distinct neuronal subtypes for studying and treating related neurological diseases, such as epilepsy, Alzheimer's disease, and Parkinson's disease.

  6. Differential Effect of Mirror Manipulation on Self-Perception in Social Phobia Subtypes.

    Hofmann, Stefan G; Heinrichs, Nina


    This study employed mirror manipulation to examine differences in self-perception between the DSM-IV subtypes of social phobia (social anxiety disorder). We asked 82 consecutively admitted patients with social phobia to record three positive and three negative characteristics about themselves. Sixty-three percent of them met criteria for a generalized subtype of social phobia (GSP). A random half of the total sample sat in front of a mirror before and during this task. Participants' responses were classified into either positive or negative self-statements concerning their bodily appearance, competence, and socially relevant or non-socially relevant personality characteristics. The mirror manipulation had a differential effect on self-perception in social phobia subtypes. The presence of a mirror led to more positive and negative self statements about bodily appearance, and to fewer negative self-statements about socially-relevant personality characteristics in participants with GSP. In contrast, participants not meeting criteria for GSP responded to mirror exposure only with fewer negative self-statements about non-socially relevant personality characteristics. These results suggest that mirror exposure leads to fewer negative self-statements about private aspects of the self, concerning social situations, while it enhances public self-consciousness in individuals with GSP.

  7. Brain perfusion SPECT with Brodmann areas analysis in differentiating frontotemporal dementia subtypes.

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Kapsalaki, Eftychia; Fezoulidis, Ioannis; Hadjigeorgiou, George; Georgoulias, Panagiotis


    Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO SPECT with Brodmann areas (BA) mapping. NeuroGam software was applied on single photon emission computed tomographic (SPECT) studies for the semi-quantitative evaluation of perfusion in BA and the comparison with the software's normal database. We studied 91 consecutive FTD patients: 21 with behavioural variants (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic regression analyses showed that the BA 28L and 32R could independently differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA 6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain perfusion SPECT with BA mapping can be a useful additional tool in differentiating FTD variants by improving the definition of brain areas that are specifically implicated, resulting in a more accurate differential diagnosis in atypical or uncertain forms of FTD.

  8. CD206+ Cell Number Differentiates Influenza A (H1N1pdm09 from Seasonal Influenza A Virus in Fatal Cases

    Heidi G. Rodriguez-Ramirez


    Full Text Available In 2009, a new influenza A (H1N1 virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1pdm09. Cytokines (inflammatory and anti-inflammatory and cellular markers (macrophages and lymphocytes subpopulation markers were analyzed in lung tissue from both influenza A (H1N1pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1pdm09 and seasonal cases when compared with healthy lung tissue (P<0.05. Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1pdm09 and seasonal influenza virus (P<0.05. Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung were found in influenza A (H1N1pdm09 when compared with seasonal influenza virus (P<0.05, and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1pdm09 (P<0.05. In conclusion, CD206+ cells differentiate between influenza A (H1N1pdm09 and seasonal influenza virus in lung tissue of fatal cases.

  9. CD206+ Cell Number Differentiates Influenza A (H1N1)pdm09 from Seasonal Influenza A Virus in Fatal Cases

    Rodriguez-Ramirez, Heidi G.; Salinas-Carmona, Mario C.; Barboza-Quintana, Oralia; Melo-de la Garza, Americo; Ceceñas-Falcon, Luis Angel; Rangel-Martinez, Lilia M.; Rosas-Taraco, Adrian G.


    In 2009, a new influenza A (H1N1) virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1)pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1)pdm09. Cytokines (inflammatory and anti-inflammatory) and cellular markers (macrophages and lymphocytes subpopulation markers) were analyzed in lung tissue from both influenza A (H1N1)pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1)pdm09 and seasonal cases when compared with healthy lung tissue (P < 0.05). Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1)pdm09 and seasonal influenza virus (P < 0.05). Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung) were found in influenza A (H1N1)pdm09 when compared with seasonal influenza virus (P < 0.05), and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1)pdm09 (P < 0.05). In conclusion, CD206+ cells differentiate between influenza A (H1N1)pdm09 and seasonal influenza virus in lung tissue of fatal cases. PMID:25614715

  10. Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro

    Whitmore, Laura C.; Weems, Megan N.


    Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62Ldim, CD16bright, CD11bbright, CD66bbright, CD63bright surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil–H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease. PMID:28148734

  11. Pig Induced Pluripotent Stem Cell-Derived Neural Rosettes Parallel Human Differentiation Into Sensory Neural Subtypes.

    Webb, Robin L; Gallegos-Cárdenas, Amalia; Miller, Colette N; Solomotis, Nicholas J; Liu, Hong-Xiang; West, Franklin D; Stice, Steven L


    The pig is the large animal model of choice for study of nerve regeneration and wound repair. Availability of porcine sensory neural cells would conceptually allow for analogous cell-based peripheral nerve regeneration in porcine injuries of similar severity and size to those found in humans. After recently reporting that porcine (or pig) induced pluripotent stem cells (piPSCs) differentiate into neural rosette (NR) structures similar to human NRs, here we demonstrate that pig NR cells could differentiate into neural crest cells and other peripheral nervous system-relevant cell types. Treatment with either bone morphogenetic protein 4 or fetal bovine serum led to differentiation into BRN3A-positive sensory cells and increased expression of sensory neuron TRK receptor gene family: TRKA, TRKB, and TRKC. Porcine sensory neural cells would allow determination of parallels between human and porcine cells in response to noxious stimuli, analgesics, and reparative mechanisms. In vitro differentiation of pig sensory neurons provides a novel model system for neural cell subtype specification and would provide a novel platform for the study of regenerative therapeutics by elucidating the requirements for innervation following injury and axonal survival.

  12. Students in Differential Equations and Epidemiology Model a Campus Outbreak of pH1N1

    Meredith L. Greer


    Full Text Available We describe a semester-long collaboration between a mathematics class and a biology class. Students worked together to understand and model the trajectory of the pandemic H1N1, pH1N1, outbreak across campus in fall 2009. Each course had about 30 students and was an upper-level elective for majors. Some mathematics students had taken no college-level biology, and some biology students had taken no college-level mathematics. All students had taken at least three quantitative courses, so they had some experience working with data. Our goals were to allow students to work with and model a real data set that affected them personally, to explore how the outbreak spread within our small campus, and for students to share their areas of expertise. This project created opportunities for synthesis and evaluation.  

  13. B7-H1 Signaling is Integrated During CD8+ T Cell Priming and Restrains Effector Differentiation

    Gibbons, Rachel M.; Liu, Xin; Harrington, Susan M.; Krco, Christopher J.; Kwon, Eugene D.; Dong, Haidong


    A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines with the goal of activating anti-tumor T cell responses. Current formulations for dendritic cell-based immunotherapies have limited effects on patient survival, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Using a brief in vitro priming model, we have found that B7-H1 expressed by activated dendritic cell...

  14. N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

    Ludwig Behnes Carl


    Full Text Available Abstract Background Papillary renal cell carcinoma (RCC represents a rare tumor, which is divided, based on histological criteria, into two subtypes. In contrast to type I papillary RCC type II papillary RCC shows a worse prognosis. So far, reliable immunohistochemical markers for the distinction of these subtypes are not available. Methods In the present study the expression of N(neural-, E(epithelial-, P(placental-, und KSP(kidney specific-cadherin was examined in 22 papillary RCC of histological type I and 18 papillary RCC of histological type II (n = 40. Results All papillary RCC type II displayed a membranous expression for N-cadherin, whereas type I did not show any membranous positivity for N-cadherin. E-cadherin exhibited a stronger, but not significant, membranous as well as cytoplasmic expression in type II than in type I papillary RCC. A diagnostic relevant expression of P- and KSP-cadherin could not be demonstrated in both tumor entities. Conclusion Thus N-cadherin represents the first immunhistochemical marker for a clear cut differentiation between papillary RCC type I and type II and could be a target for therapy and diagnostic in the future. Virtual slides The virtual slide(s for this article can be found here:

  15. Differential effects of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome.

    De Venter, Maud; Illegems, Jela; Van Royen, Rita; Moorkens, Greta; Sabbe, Bernard G C; Van Den Eede, Filip


    There is wide consensus that childhood trauma plays an important role in the aetiology of chronic fatigue syndrome (CFS). The current study examines the differential effects of childhood trauma subtypes on fatigue and physical functioning in individuals suffering from CFS. Participants were 155 well-documented adult, predominantly female CFS patients receiving treatment at the outpatient treatment centre for CFS of the Antwerp University Hospital in Belgium. Stepwise regression analyses were conducted with outcomes of the total score of the Checklist Individual Strength (CIS) measuring fatigue and the scores on the physical functioning subscale of the Medical Outcomes Short Form 36 Health Status Survey (SF-36) as the dependent variables, and the scores on the five subscales of the Traumatic Experiences Checklist (TEC) as the independent variables. The patients' fatigue (β=1.38; p=0.025) and physical functioning scores (β=-1.79; p=0.034) were significantly predicted by childhood sexual harassment. There were no significant effects of emotional neglect, emotional abuse, bodily threat, or sexual abuse during childhood. Of the childhood trauma subtypes investigated, sexual harassment emerged as the most important predictor of fatigue and poor physical functioning in the CFS patients assessed. These findings have to be taken into account in further clinical research and in the assessment and treatment of individuals coping with chronic fatigue syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms

    Pietra, D; Rumi, E; Ferretti, V V; Buduo, C A Di; Milanesi, C; Cavalloni, C; Sant'Antonio, E; Abbonante, V; Moccia, F; Casetti, I C; Bellini, M; Renna, M C; Roncoroni, E; Fugazza, E; Astori, C; Boveri, E; Rosti, V; Barosi, G; Balduini, A; Cazzola, M


    A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation of CALR, the calreticulin gene. A 52-bp deletion (type 1) and a 5-bp insertion (type 2 mutation) are the most frequent variants. These indels might differentially impair the calcium binding activity of mutant calreticulin. We studied the relationship between mutation subtype and biological/clinical features of the disease. Thirty-two different types of CALR variants were identified in 311 patients. Based on their predicted effect on calreticulin C-terminal, mutations were classified as: (i) type 1-like (65%); (ii) type 2-like (32%); and (iii) other types (3%). Corresponding CALR mutants had significantly different estimated isoelectric points. Patients with type 1 mutation, but not those with type 2, showed abnormal cytosolic calcium signals in cultured megakaryocytes. Type 1-like mutations were mainly associated with a myelofibrosis phenotype and a significantly higher risk of myelofibrotic transformation in essential thrombocythemia. Type 2-like CALR mutations were preferentially associated with an essential thrombocythemia phenotype, low risk of thrombosis despite very-high platelet counts and indolent clinical course. Thus, mutation subtype contributes to determining clinical phenotype and outcomes in CALR-mutant myeloproliferative neoplasms. CALR variants that markedly impair the calcium binding activity of mutant calreticulin are mainly associated with a myelofibrosis phenotype. PMID:26449662

  17. Variations of very low-density lipoprotein receptor subtype expression in gastrointestinal adenocarcinoma cells with various differentiations

    Tao Chen; Fan Wu; Feng-Ming Chen; Jun Tian; Shen Qu


    AIM: This study is aimed at investigating the expression and possible significances of very low-density lipoprotein receptor (VLDLR) subtypes in gastroenteric adenocarcinoma tissues and cells with various differentiations. METHODS: Thirty-one cases of gastroenteric carcinoma/ adjacent normal tissues were enrolled in the study, which were diagnosed and classified by the clinicopathological diagnosis. The expression of VLDLR subtypes was detected in gastroenteric carcinoma/adjacent normal tissues and three various differentiated human gastric adenocarcinoma cell lines (MKN28, SGC7901 and MKN45) by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis.RE,SULTS: Two VLDLR subtypes, namely, type Ⅱ VLDLR and type Ⅰ VLDLR, were found to express changes in gastroenteric carcinoma tissues, their adjacent normal tissue, and gastric adenocarcinoma cell lines as well. Type Ⅱ VLDLR is predominantly expressed in poorly- or moderately-differentiated gastroenteric carcinoma tissues and gastric adenocarcinoma cell lines, whereas type ⅠVLDLR is mainly detected in well-differentiated intestinal carcinoma tissues and gastric adenocarcinoma cells compared with the adjacent normal tissues. CONCLUSION: The results suggested that the variations of the VLDLR subtype expression might be correlated with the progress and differentiation of gastroenteric carcinoma.

  18. Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation.

    Renee W Y Chan

    Full Text Available Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004 and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998, the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of alpha2-6-linked sialic acid receptors and human airway trypsin-like (HAT protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the

  19. Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages.

    Ramírez-Martínez, Gustavo; Cruz-Lagunas, Alfredo; Jiménez-Alvarez, Luis; Espinosa, Enrique; Ortíz-Quintero, Blanca; Santos-Mendoza, Teresa; Herrera, María Teresa; Canché-Pool, Elsy; Mendoza, Criselda; Bañales, José L; García-Moreno, Sara A; Morán, Juan; Cabello, Carlos; Orozco, Lorena; Aguilar-Delfín, Irma; Hidalgo-Miranda, Alfredo; Romero, Sandra; Suratt, Benjamin T; Selman, Moisés; Zúñiga, Joaquín


    Infection with pandemic (pdm) A/H1N1 virus induces high levels of pro-inflammatory mediators in blood and lungs of experimental animals and humans. To compare the involvement of seasonal A/PR/8/34 and pdm A/H1N1 virus strains in the regulation of inflammatory responses, we analyzed the changes in the whole-genome expression induced by these strains in macrophages and A549 epithelial cells. We also focused on the functional implications (cytokine production) of the differential induction of suppressors of cytokine signaling (SOCS)-1, SOCS-3, retinoid-inducible gene (RIG)-I and interferon receptor 1 (IFNAR1) genes by these viral strains in early stages of the infection. We identified 130 genes differentially expressed by pdm A/H1N1 and A/PR/8/34 infections in macrophages. mRNA levels of SOCS-1 and RIG-I were up-regulated in macrophages infected with the A/PR/8/34 but not with pdm A/H1N1 virus. mRNA levels of SOCS-3 and IFNAR1 induced by A/PR/8/34 and pdm A/H1N1 strains in macrophages, as well as in A549 cells were similar. We found higher levels of IL-6, TNF-α, IL-10, CCL3, CCL5, CCL4 and CXCL8 (p < 0.05) in supernatants from cultures of macrophages infected with the pdm A/H1N1 virus compared to those infected with the A/PR/8/34 strain, coincident with the lack of SOCS-1 and RIG-I expression. In contrast, levels of INF-α were higher in cultures of macrophages 48h after infection with the A/PR/8/34 strain than with the pdm A/H1N1 virus. These findings suggest that factors inherent to the pdm A/H1N1 viral strain may increase the production of inflammatory mediators by inhibiting SOCS-1 and modifying the expression of antiviral immunity-related genes, including RIG-I, in human macrophages. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Differential drug resistance acquisition in HIV-1 of subtypes B and C.

    Esmeralda A J M Soares

    Full Text Available BACKGROUND: Subtype C is the most prevalent HIV-1 subtype in the world, mainly in countries with the highest HIV prevalence. However, few studies have evaluated the impact of antiretroviral therapy on this subtype. In southern Brazil, the first developing country to offer free and universal treatment, subtypes B and C co-circulate with equal prevalence, allowing for an extensive evaluation of this issue. METHODS AND FINDINGS: Viral RNA of 160 HIV-1+ patients was extracted, and the protease and reverse transcriptase genes were sequenced, subtyped and analyzed for ARV mutations. Sequences were grouped by subtype, and matched to type (PI, NRTI and NNRTI and time of ARV exposure. Statistical analyses were performed to compare differences in the frequency of ARV-associated mutations. There were no significant differences in time of treatment between subtypes B and C groups, although they showed distinct proportions of resistant strains at different intervals for two of three ARV classes. For PI, 26% of subtype B strains were resistant, compared to only 8% in subtype C (p = 0.0288, Fisher's exact test. For NRTI, 54% of subtype B strains were resistant versus 23% of subtype C (p = 0.0012. Differences were significant from 4 years of exposure, and remained so until the last time point analyzed. The differences observed between both subtypes were independent of time under rebound viremia in cases of virologic failure and of the number of HAART regimens used by treated patients. CONCLUSIONS: Our results pointed out to a lower rate of accumulation of mutations conferring resistance to ARV in subtype C than in subtype B. These findings are of crucial importance for current initiatives of ARV therapy roll-out in developing countries, where subtype is C prevalent.

  1. The role of hs-CRP, D-dimer and fibrinogen in differentiating etiological subtypes of ischemic stroke.

    Liu, Li-Bin; Li, Mu; Zhuo, Wen-Yan; Zhang, Yu-Sheng; Xu, An-Ding


    The aim of this study was to evaluate the diagnostic value of the serum biochemical markers high-sensitivity C-reactive protein (hs-CRP), D-dimer (DD) and fibrinogen (Fg) in differentiating etiological subtypes of ischemic stroke. This study was a retrospective case-only study, consecutively including patients with acute ischemic stroke. All patients were classified into subtypes using the TOAST classification system. A total of 317 patients were evaluated. Hs-CRP and DD levels were significantly different among the subtypes and were the highest in CE, followed by LAA and SAA; no significant difference between the subtypes was found for Fg. Hs-CRP > 6.96 mg/L was classified as the CE subtype, with a sensitivity of 41% and a specificity of 74%; DD > 791.30 ng/mL was classified as CE, with a sensitivity of 58% and a specificity of 78%. The combination of hs-CRP and DD classification as CE yielded a sensitivity of 65% and a specificity of 91%. DD > 791.30 ng/mL was considered an independent predictive factor of CE. Hs-CRP and DD could be useful for identifying the etiological subtypes of acute ischemic stroke, especially for predicting CE. The diagnostic value of DD was higher than that of hs-CRP.


    阮宝阳; 陈鸿军; 滕巧泱; 童光志; 于海; 王林; 宫晓倩; 汪秀会; 刘晓敏; 汪琪; 单同领; 李泽君; 刘芹防


    本研究利用RT-PCR技术扩增禽源H1N1亚型猪流感病毒(Swine influenza virus,SIV)的HA1基因片段,将其连接至pCold-TF载体上,菌液鉴定为阳性的克隆经测序验证正确后,提取质粒转化至高表达的表达宿主菌BL21(DE3)中,经IPTG诱导并大量表达目的蛋白。表达产物经过纯化及SDS-PAGE电泳分析,表明重组蛋白以可溶性形式在上清中大量表达,大小约90 kDa,且在15℃、0.8mmol/L IPTG条件下诱导24 h 表达效果最好。通过Ni 柱纯化后,经Western blot分析表明重组表达的蛋白能与禽源H1N1亚型 SIV阳性血清发生特异性反应,具有较好的反应原性。%To express HA1 protein of H1N1 Subtype Swine influenza virus(SIV), the HA1 gene was amplified by RT-PCR and cloned into vector pCold-TF. After being sequenced, the recombinant plasmid was transformed into expression host strain DL21(DE3) then IPTG was added to induce expression. The expressed HA1 fusion protein was purified by Nickel colum and analyzed by SDS-PAGE. The results indicated that recombinant protein was expressed in soluble condition in the supernatant and was about 90 kDa in size. The optimum condition for the expres-sion was that the bacteria was induced for 24 h under the conditions (15℃ and 0.8m mol/L IPTG). The result in Western blot of purified recombi-nant protein showed that the HA1 protein had good antigenicity, and could berecognized by SIV positive serum.

  3. Inter- and Intra-subtype genotypic differences that differentiate Mycobacterium avium subspecies paratuberculosis strains

    Biet Franck


    Full Text Available Abstract Background Mycobacterium avium subspecies paratuberculosis (Map is the aetiological agent of Johne’s disease or paratuberculosis and is included within the Mycobacterium avium complex (MAC. Map strains are of two major types often referred to as ‘Sheep’ or ‘S-type’ and ‘Cattle’ or ‘C-type’. With the advent of more discriminatory typing techniques it has been possible to further classify the S-type strains into two groups referred to as Type I and Type III. This study was undertaken to genotype a large panel of S-type small ruminant isolates from different hosts and geographical origins and to compare them with a large panel of well documented C-type isolates to assess the genetic diversity of these strain types. Methods used included Mycobacterial Interspersed Repetitive Units - Variable-Number Tandem Repeat analysis (MIRU-VNTR, analysis of Large Sequence Polymorphisms by PCR (LSP analysis, Single Nucleotide Polymorphism (SNP analysis of gyr genes, Pulsed-Field Gel Electrophoresis (PFGE and Restriction Fragment Length Polymorphism analysis coupled with hybridization to IS900 (IS900-RFLP analysis. Results The presence of LSPA4 and absence of LSPA20 was confirmed in all 24 Map S-type strains analysed. SNPs within the gyr genes divided the S-type strains into types I and III. Twenty four PFGE multiplex profiles and eleven different IS900-RFLP profiles were identified among the S-type isolates, some of them not previously published. Both PFGE and IS900-RFLP segregated the S-type strains into types I and III and the results concurred with those of the gyr SNP analysis. Nine MIRU-VNTR genotypes were identified in these isolates. MIRU-VNTR analysis differentiated Map strains from other members of Mycobacterium avium Complex, and Map S-type from C-type but not type I from III. Pigmented Map isolates were found of type I or III. Conclusion This is the largest panel of S-type strains investigated to date. The S-type strains

  4. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis.

    van den Ham, Henk-Jan; de Jager, Wilco; Bijlsma, Johannes W J; Prakken, Berent J; de Boer, Rob J


    With the introduction of high-throughput biomarker measurements, traditional analysis of these markers is increasingly difficult. Using samples from a diverse group of patients, we tested the applicability of cluster analysis to these data. Using this method, we aim to visualize some of the patterns specific to certain disease groups. In particular, we focus on juvenile idiopathic arthritis (JIA), a multifactorial autoimmune disorder that ultimately leads to chronic inflammation of the joints. Cytokine measurements were performed using multiplex immunoassays. Using heuristic clustering methods, we set out to compare the pattern of 30 cytokines in plasma and SF of JIA, RA, OA, or diabetes type II patients and healthy controls. Analysis shows that oligo- and polyarticular JIA have similar biomarker profiles, both in plasma and SF. Systemic onset JIA (SoJIA) has a profile distinct from other JIA subtypes, suggesting that they involve different inflammatory processes. SoJIA samples do, however, cluster together with RA in SF, suggesting that these two conditions have similar cytokine profiles. Furthermore, we identify several clusters of ILs and chemokines that are co-expressed, suggesting that they are co-regulated. We show that previously undetected clusters of cytokines and patients can be identified by applying cluster analysis to multiplex data. Cytokine clusters identified in plasma and SF samples were quite different, which underscore the differential cytokine signalling in these two compartments, and suggest that plasma samples may not be suitable for estimating joint biomarker profiles and inflammation.

  5. Exposure to Zinc Sulfate Results in Differential Effects on Olfactory Sensory Neuron Subtypes in Adult Zebrafish

    James T. Hentig


    Full Text Available Zinc sulfate is a known olfactory toxicant, although its specific effects on the olfactory epithelium of zebrafish are unknown. Olfactory organs of adult zebrafish were exposed to zinc sulfate and, after 2, 3, 5, 7, 10 or 14 days, fish were processed for histological, immunohistochemical, ultrastructural, and behavioral analyses. Severe morphological disruption of the olfactory organ was observed two days following zinc sulfate exposure, including fusion of lamellae, epithelial inflammation, and significant loss of anti-calretinin labeling. Scanning electron microscopy revealed the apical surface of the sensory region was absent of ciliated structures, but microvilli were still present. Behavioral analysis showed significant loss of the ability to perceive bile salts and some fish also had no response to amino acids. Over the next several days, olfactory organ morphology, epithelial structure, and anti-calretinin labeling returned to control-like conditions, although the ability to perceive bile salts remained lost until day 14. Thus, exposure to zinc sulfate results in rapid degeneration of the olfactory organ, followed by restoration of morphology and function within two weeks. Zinc sulfate appears to have a greater effect on ciliated olfactory sensory neurons than on microvillous olfactory sensory neurons, suggesting differential effects on sensory neuron subtypes.

  6. Degree of Suppression of Mouse Myoblast Cell Line C2C12 Differentiation Varies According to Chondroitin Sulfate Subtype

    Warita, Katsuhiko; Oshima, Nana; Takeda-Okuda, Naoko; Tamura, Jun-ichi; Hosaka, Yoshinao Z.


    Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C2C12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time. After immunostaining of the formed myotubes with an anti-MHC antibody, we counted the number of nuclei in the myotubes and then calculated the fusion index (FI) as a measure of myotube differentiation. The FI values of all the CS-treated groups were lower than the FI value of the control group, especially the group treated with CS-E, which displayed notable suppression of myotube formation. To confirm that the sugar chain in CS-E is important in the suppression of differentiation, chondroitinase ABC (ChABC), which catabolizes CS, was added to the media. The addition of ChABC led to the degradation of CS-E, and neutralized the suppression of myotube formation by CS-E. Collectively, it can be concluded that the degree of suppression of differentiation depends on the subtype of CS and that CS-E strongly suppresses myogenic differentiation. We conclude that the CS sugar chain has inhibitory action against myoblast cell fusion. PMID:27775651

  7. Histamine increases cytosolic Ca2+ in dibutyryl-cAMP-differentiated HL-60 cells via H1 receptors and is an incomplete secretagogue.

    Seifert, R; Höer, A; Offermanns, S; Buschauer, A; Schunack, W


    Human neutrophils and dibutyryl-cAMP (Bt2cAMP)-differentiated HL-60 cells possess receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), which mediate activation of phospholipase C, with subsequent increase in cytosolic Ca2+ concentration ([Ca2+]i) and activation of specific cell functions. In many cell types, histamine, via H1 receptors, activates phospholipase C, but it is unknown whether neutrophilic cells possess functional H1 receptors. We compared the effects of histamine with those of fMet-Leu-Phe on activation of these cells. In Bt2cAMP-differentiated HL-60 cells, substances increased [Ca2+]i in the effectiveness order fMet-Leu-Phe greater than histamine greater than betahistine. Pertussis toxin diminished fMet-Leu-Phe-induced rises in [Ca2+]i to a greater extent than those induced by histamine. H1 but not H2 antagonists inhibited histamine- and betahistine-induced rises in [Ca2+]i. fMet-Leu-Phe and histamine activated phospholipase C and increased [Ca2+]i through release of Ca2+ from intracellular stores and sustained influx of Ca2+ from the extracellular space. The substances also induced Mn2+ influx. Ca2+ and Mn2+ influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl)-1H-imida zole hydrochloride (SK&F 96365). The stimulatory effects of histamine on [Ca2+]i were more sensitive to inhibition by 4 beta-phorbol 12-myristate 13-acetate than were those of fMet-Leu-Phe. Unlike fMet-Leu-Phe, histamine did not activate superoxide anion formation, release of beta-glucuronidase, and tyrosine phosphorylation. In neutrophils, histamine and betahistine did not induce rises in [Ca2+]i. Our data show that (i) in Bt2cAMP-differentiated HL-60 cells, histamine increases [Ca2+]i via H1 receptors coupled to pertussis toxin-sensitive and possibly, pertussis toxin-insensitive heterotrimeric regulatory guanine nucleotide-binding proteins, (ii) histamine activates nonselective cation channels, and (iii

  8. Comparison of Pandemrix and Arepanrix, two pH1N1 AS03-adjuvanted vaccines differentially associated with narcolepsy development.

    Jacob, Louis; Leib, Ryan; Ollila, Hanna M; Bonvalet, Mélodie; Adams, Christopher M; Mignot, Emmanuel


    Narcolepsy onset in children has been associated with the 2009 influenza A H1N1 pandemic and vaccination with Pandemrix. However it was not clearly observed with other adjuvanted pH1N1 vaccines such as Arepanrix or Focetria. Our aim was to characterize the differences between Pandemrix and Arepanrix that might explain the risk for narcolepsy after Pandemrix vaccination using 2D-DIGE and mass spectrometry (MS). We found that Pandemrix (2009 batch) and Arepanrix (2010 batch) showed 5 main viral proteins: hemagglutinin HA1 and HA2 subunits, neuraminidase NA, nucleoprotein NP, and matrix protein MA1 and non-viral proteins from the Gallus gallus growth matrix used in the manufacturing of the vaccines. Latticed patterns of HA1, HA2 and NA indicated charge and molecular weight heterogeneity, a phenomenon likely caused by glycosylation and sulfation. Overall, Pandemrix contained more NP and NA, while Arepanrix displayed a larger diversity of viral and chicken proteins, with the exception of five chicken proteins (PDCD6IP, TSPAN8, H-FABP, HSP and TUB proteins) that were relatively more abundant in Pandemrix. Glycosylation patterns were similar in both vaccines. A higher degree of deamidation and dioxidation was found in Pandemrix, probably reflecting differential degradation across batches. Interestingly, HA1 146N (residue 129N in the mature protein) displayed a 10-fold higher deamidation in Arepanrix versus Pandemrix. In recent vaccine strains and Focetria, 146N is mutated to D which is associated with increased production yields suggesting that 146N deamidation may have also occurred during the manufacturing of Arepanrix. The presence of 146N in large relative amounts in Pandemrix and the wild type virus and in lower relative quantities in Arepanrix or other H1N1 vaccines may have affected predisposition to narcolepsy.

  9. Differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human H1 receptors.

    Hishinuma, Shigeru; Sugawara, Kenta; Uesawa, Yoshihiro; Fukui, Hiroyuki; Shoji, Masaru


    Differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine H1 receptors. In this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human H1 receptors and their structural determinants. The binding enthalpy and entropy of 20 antihistamines were estimated with the van't Hoff equation using their dissociation constants obtained from their displacement curves against the binding of [(3)H]mepyramine to membrane preparations of Chinese hamster ovary cells expressing human H1 receptors at various temperatures from 4°C to 37°C. Structural determinants of antihistamines for their thermodynamic binding properties were assessed by quantitative structure-activity relationship (QSAR) analyses. We found that entropy-dependent binding was more evident in second- than first-generation antihistamines, resulting in enthalpy-entropy compensation between the binding forces of first- and second-generation antihistamines. QSAR analyses indicated that enthalpy-entropy compensation was determined by the sum of degrees, maximal electrostatic potentials, water-accessible surface area and hydrogen binding acceptor count of antihistamines to regulate their affinity for receptors. In conclusion, it was revealed that entropy-dependent hydrophobic interaction was more important in the binding of second-generation antihistamines, even though the hydrophilicity of second-generation antihistamines is generally increased. Furthermore, their structural determinants responsible for enthalpy-entropy compensation were explored by QSAR analyses. These findings may contribute to understanding the fundamental mechanisms of how the affinity of ligands for their receptors is regulated.

  10. Food addiction in a Spanish sample of eating disorders: DSM-5 diagnostic subtype differentiation and validation data.

    Granero, Roser; Hilker, Ines; Agüera, Zaida; Jiménez-Murcia, Susana; Sauchelli, Sarah; Islam, Mohammed A; Fagundo, Ana B; Sánchez, Isabel; Riesco, Nadine; Dieguez, Carlos; Soriano, José; Salcedo-Sánchez, Cristina; Casanueva, Felipe F; De la Torre, Rafael; Menchón, José M; Gearhardt, Ashley N; Fernández-Aranda, Fernando


    Although the concept of 'food addiction' (FA) has raised growing interest because of evidence for similarities between substance dependence and excessive food intake, there is a lack of studies that explore this construct among the wide spectrum of eating disorders (EDs). Besides providing validation scores of a Spanish version of the Yale FA Scale (YFAS-S), this study examined the prevalence of 'FA' among ED subtypes compared with healthy-eating controls (HCs) and the association between 'FA' scores, eating symptomatology and general psychopathology. A sample of 125 adult women with ED, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy-eating women participated in the study. All participants were assessed with the YFAS-S, the ED Inventory-2 and the Symptom Checklist-Revised. Results showed that the internal structure of the one-dimensional solution for the YFAS-S was very good (α = 0.95). The YFAS-S has a good discriminative capacity to differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) = 72.8%; area under receiver operating characteristic curve = 0.90) and a good Se to screen for specific ED subtypes. YFAS-S scores were associated with higher levels of negative affect and depression, higher general psychopathology, more severe eating pathology and greater body mass index. When comparing the prevalence of 'FA' between ED subtypes, the lowest prevalence of 'FA', measured with the YFAS-S, was for the anorexia nervosa (AN) restrictive subtype with 50%, and the highest was for the AN binge-purging subtype (85.7%), followed by bulimia nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS-S scores are associated with bingeing ED-subtype patients and with more eating severity and psychopathology. Although the 'FA' construct is able to differentiate between ED and HC, it needs to be further explored. Copyright © 2014 John Wiley & Sons, Ltd and

  11. Temporal lobe epilepsy subtypes, differential patterns of cerebral perfusion on ictal SPECT

    Ho, SS; Berkovic, SF; McKay, WJ; Kalnins, RM; Bladin, PF


    Purpose: We studied cerebral perfusion patterns in the various subtypes of TLE, as determined by pathology and good outcome after temporal lobectomy (as confirmation of temporal origin). Methods: We studied clinical features and ictal technetium 99m hexamethyl-propyleneamineoxime (Tc-99m-HMPAO) sing

  12. Differentiating patterns of substance misuse by subtypes of antisocial traits in male offenders

    Brennan, G.M.; Stuppy-Sullivan, A.M.; Brazil, I.A.; Baskin-Sommers, A.R.


    Among criminal offenders, two subtypes of antisocial traits, psychopathy and externalizing-only, are associated with an especially elevated risk for substance use disorders (SUDs). The present study examined the associations of these traits with patterns of substance misuse. In a sample of 1410 male

  13. Human Embryonic Stem Cell derived Cardiomyocytes self-arrange with areas of different subtypes during differentiation

    Vestergaard, Maj Linea; Grubb, Søren J; Rasmussen, Karen Koefod


    The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESC) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of CMs derived from hESCs (h...

  14. Differentiating Youth Who Sexually Abuse: Applying a Multidimensional Framework when Assessing and Treating Subtypes

    Rasmussen, Lucinda A.


    Recent empirical research has shown that children with sexual behavior problems and adolescents who offend sexually are diverse populations consisting of several subtypes (Hall, Mathews, & Pearce, 2002; Pithers, Gray, Busconi, & Houchens, 1998; Worling, 2001). This article reviews the descriptive and empirical research related to identifying…

  15. Differentiating Youth Who Sexually Abuse: Applying a Multidimensional Framework when Assessing and Treating Subtypes

    Rasmussen, Lucinda A.


    Recent empirical research has shown that children with sexual behavior problems and adolescents who offend sexually are diverse populations consisting of several subtypes (Hall, Mathews, & Pearce, 2002; Pithers, Gray, Busconi, & Houchens, 1998; Worling, 2001). This article reviews the descriptive and empirical research related to identifying…

  16. Differential transcription-activating capability of NS1 proteins from different influenza virus subtypes expressed in yeast


    Influenza A virus NS1 protein is an important regulatory factor with multiple functions and contributes greatly to viral pathogenesis.In the present study,transcription-activating potential of NS1 from different influenza A virus subtypes was examined in yeast two-hybrid system.The bait vectors contain-ing different NS1 genes,along with an empty prey vector,were transformed into yeast AH109(for growth assay on QDO plate and α-galactosidase assay),and Y187(for β-galactosidase assay).AH109 transformants with NS1 gene from H1N1,H5N1,and H9N2 viruses grew vigorously on the QDO plate and secreted high level of α-galactosidase.Also,Y187 bearing the above NS1 genes exhibited en-hanced β-galactosidase activity.Nevertheless,H3N2-NS1-transformed AH109 and Y187 yeasts did not grow on QDO plate and secrete β-galactosidase,respectively.These findings denote the remarkable variation in NS1 proteins from different influenza A virus subtypes on the transcription-stimulating capability in yeast.

  17. Differential transcription-activating capability of NS1 proteins from different influenza virus subtypes expressed in yeast

    LI WeiZhong; WANG GeFei; ZENG Jun; ZHANG DanGui; ZHANG Heng; CHEN XiaoXuan; CHEN Ying; Li KangSheng


    Influenza A virus NS1 protein is an important regulatory factor with multiple functions and contributes greatly to viral pathogenesis. In the present study, transcription-activating potential of NS1 from dif-ferent influenza A virus subtypes was examined in yeast two-hybrid system. The bait vectors contain-ing different NS1 genes, along with an empty prey vector, were transformed into yeast AH109(for growth assay on QDO plate and a-galactosidase assay), and Y187(for β-galactosidase assay). AH109transformants with NS1 gene from H1N1, H5N1, and HgN2 viruses grew vigorously on the QDO plate and secreted high level of a-galactosidase. Also, Y187 bearing the above NS1 genes exhibited en-hanced β-galactosidase activity. Nevertheless, H3N2-NSl-transformed AH109 and Y187 yeasts did not grow on QDO plate and secrete β-galactosidase, respectively. These findings denote the remarkable variation in NS1 proteins from different influenza A virus subtypes on the transcription-stimulating capability in yeast.

  18. 16S rRNA partial gene sequencing for the differentiation and molecular subtyping of Listeria species.

    Hellberg, Rosalee S; Martin, Keely G; Keys, Ashley L; Haney, Christopher J; Shen, Yuelian; Smiley, R Derike


    Use of 16S rRNA partial gene sequencing within the regulatory workflow could greatly reduce the time and labor needed for confirmation and subtyping of Listeria monocytogenes. The goal of this study was to build a 16S rRNA partial gene reference library for Listeria spp. and investigate the potential for 16S rRNA molecular subtyping. A total of 86 isolates of Listeria representing L. innocua, L. seeligeri, L. welshimeri, and L. monocytogenes were obtained for use in building the custom library. Seven non-Listeria species and three additional strains of Listeria were obtained for use in exclusivity and food spiking tests. Isolates were sequenced for the partial 16S rRNA gene using the MicroSeq ID 500 Bacterial Identification Kit (Applied Biosystems). High-quality sequences were obtained for 84 of the custom library isolates and 23 unique 16S sequence types were discovered for use in molecular subtyping. All of the exclusivity strains were negative for Listeria and the three Listeria strains used in food spiking were consistently recovered and correctly identified at the species level. The spiking results also allowed for differentiation beyond the species level, as 87% of replicates for one strain and 100% of replicates for the other two strains consistently matched the same 16S type.

  19. Differential reward processing in subtypes of adult attention deficit hyperactivity disorder.

    Edel, Marc-Andreas; Enzi, Björn; Witthaus, Henning; Tegenthoff, Martin; Peters, Sören; Juckel, Georg; Lissek, Silke


    Abnormalities in reward processing have been found in adolescents and adults with ADHD using the 'Monetary Incentive Delay' (MID) task. However, ADHD groups in previous studies were heterogeneous regarding ADHD subtype, gender and, in part, drug treatment status. This study sought to compare neural activations in the ventral striatum (VS) and prefrontal regions during reward processing in homogenous ADHD subtype groups and healthy adults, using the MID task. In total, 24 drug-naïve, right-handed male adults with ADHD (12 subjects with combined type (ADHD-ct) and 12 subjects with predominantly inattentive (ADHD-it) type ADHD), and twelve healthy right-handed male control subjects were included. Compared to ADHD-ct and healthy subjects, ADHD-it subjects showed a bilateral ventral striatal deficit during reward anticipation. In contrast, ADHD-ct subjects showed orbitofrontal hyporesponsiveness to reward feedback when compared with ADHD-it and healthy subjects. This is the first fMRI study that delineates dysfunctional and subtype-divergent neural and behavioural reward processing in adults with ADHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Differential diagnosis of transient ischemic attack subtypes according to their mechanisms as indicated by neurosonography and neuroimaging

    Iwamoto, Toshihiko; Oyama, Tetsuo; Kiuchi, Akihiro; Ohno, Daiji; Kanaya, Kiyoshi; Takasaki, Masaru [Tokyo Medical Coll. (Japan)


    This study was conducted to propose a classification of transient ischemic attacks (TIA) and the diagnostic procedure for differentiating TIA subtypes by neurosonography and neuroimaging, and apply them in clinical practice. TIA was classified into 5 subtypes; microembolic (type I), hemodynamic (type II), lacunar (type III), cardioembolic (type IV), and the other TIAs (type V). Twenty-two patients with carotid TIA were studied using carotid ultrasonography (US), angiography (AG), brain CT, and I{sup 123}-IMP SPECT. US revealed ulcerative plaque, stenosis, and occlusion. In 5 cases of occlusion and 8 of stenosis confirmed by AG, both US and AG findings indicated that 13 patients with severe carotid lesions were type I or II TIAs. CT demonstrated 11 patients with lacunae, 3 with watershed infarction, and 2 with cortical infarction. Of the 16 cases, 7 were symptomatic including 4 patients with type III TIA. SPECT showed diffuse hypoperfusion in 5 patients, all of whom had infarction and severely stenotic carotid lesions. These 5 were all type II TIA. One patient with atrial fibrillation but without any significant carotid lesion was considered to be a type IV TIA. Clinical data showed a high incidence of attacks and stroke occurrence in type II TIA, even though all were treated with antithrombotic drugs. This suggested that the type II TIA could have a mechanism other than thrombus formation. Furthermore, retinal symptom and/or cervical bruit due to carotid lesion were frequently observed in type I and II TIAs. Long-duration attack, which might be induced by a small infarction neighboring the symptomatic area, was seen in type III TIA. In conclusion, TIA subtypes could be identified clinico-pathophysiologically according to these diagnostic procedures and seemed to be useful in developing the most appropriate treatment for TIA, although neurosonography and neuroimaging were necessary to differentiate them. (K.H.)

  1. An H1-Galerkin Nonconforming Mixed Finite Element Method for Integro-Differential Equation of Parabolic Type%抛物型积分微分方程的非协调H1-Galerkin混合有限元方法

    石东洋; 王海红


    H1-Galerkin nonconforming mixed finite element methods are analyzed for integro-differential equation of parabolic type.By use of the typical characteristic of the elements,we obtain that the Galerkin mixed approximations have the same rates of convergence as in the classical mixed method,but without LBB stability condition.

  2. Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity.

    Mihalas, Anca B; Elsen, Gina E; Bedogni, Francesco; Daza, Ray A M; Ramos-Laguna, Kevyn A; Arnold, Sebastian J; Hevner, Robert F


    Intermediate progenitors (IPs) amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice. Upon Tbr2 inactivation, fewer neurons were produced by immediate differentiation and laminar fates were shifted upward. Genesis of subventricular mitoses was, however, not reduced in the context of a Tbr2-null cortex. Instead, neuronal and laminar differentiation were disrupted and delayed. Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers.

  3. Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity

    Anca B. Mihalas


    Full Text Available Intermediate progenitors (IPs amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice. Upon Tbr2 inactivation, fewer neurons were produced by immediate differentiation and laminar fates were shifted upward. Genesis of subventricular mitoses was, however, not reduced in the context of a Tbr2-null cortex. Instead, neuronal and laminar differentiation were disrupted and delayed. Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers.

  4. Analysis of HA gene sequence of a subtype H1N1 swine influenza virus isolated from Guangxi strains%H1N1猪流感病毒广西分离株HA基因序列分析

    颜健华; 梁丹洁; 李春英; 徐贤坤; 胡巧云; 孙翔翔; 何奇松; 熊毅


    [目的]了解H1N1猪流感病毒广西分离株的分子特征,为广西猪流感疫情监控提供参考依据.[方法]采用RT-PCR对2011年分离获得的H1N1猪流感病毒广西分离株(A/swine/Guangxi/1/2011)的HA基因进行扩增,然后利用DNASTAR分析软件对测序基因片段进行整个阅读框架的核苷酸序列及其推导氨基酸序列同源性比对分析,并用MEGA 4.0绘制遗传进化树.[结果]广西分离株HA基因长1701 bp,编码566个氨基酸,核苷酸序列与经典SIV的同源性为88.0%~99.6%,与季节性H1N1人流感病毒的同源性为76.3%~77.3%,与欧洲类禽SⅣ分离株的同源性为72.9%~75.4%,与2009甲型H1N1流感病毒的同源性为99.2%~99.6%;从核苷酸遗传进化树可知,广西分离株与类禽H1N1流感病毒和人H1N1流感病毒分离株的亲缘关系较远,而与2009甲型H 1N l流感病毒分离株的亲缘关系最近.广西分离毒株HA基因的裂解位点序列为IPSIQSR↓G,具有典型低致病性流感病毒的分子生物学特征;共有8个糖基化位点,其中6个位于HAl区,两个位于HA2区;广西分离株HA蛋白RBS位点的氨基酸同时具有人和猪流感病毒的特点.[结论]广西分离株(A/swine/Guangxi/1/2011)属于2009甲型H1N1流感病毒.%[Objective]This study was to determine molecular biology information of HA gene of H 1N 1 swine influenza virus isolated from Guangxi strains to provide references for monitoring swine flu in Guangxi.[Method]To analyze HA gene of H1N1 from Genbank,the primer was designed,and then HA genes of A/swine/Guangxi/1/2011 (H1N1) influenza virus were cloned,sequenced and compared via DNASTAR software.A phylogenetic tree was made using MEGA 4.0.[Result]The results indicated that the length of HA gene was 1701 bp and coded for 566 amino acids.Comparing with classical swine influenza H1N1,human-like H1N1 and Eurasian avian-like H1N1,the nucleotide homologies of HA genes were from 88.0% to 99.6%,from 76.3% to

  5. Differential interactions of cerebellin precursor protein (Cbln) subtypes and neurexin variants for synapse formation of cortical neurons.

    Joo, Jae-Yeol; Lee, Sung-Jin; Uemura, Takeshi; Yoshida, Tomoyuki; Yasumura, Misato; Watanabe, Masahiko; Mishina, Masayoshi


    Trans-synaptic interaction of postsynaptic glutamate receptor δ2 and presynaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates synapse formation in the cerebellum [T. Uemura, S.J. Lee, M. Yasumura, T. Takeuchi, T. Yoshida, M. Ra, R. Taguchi, K. Sakimura, M. Mishina, Cell 141 (2010) 1068-1079]. This finding raises a question whether other Cbln family members interact with NRXNs to regulate synapse formation in the forebrain. Here, we showed that Cbln1 and Cbln2 induced presynaptic differentiation of cultured cortical neurons, while Cbln4 exhibited little activity. When compared with neuroligin 1, Cbln1 and Cbln2 induced preferentially inhibitory presynaptic differentiation rather than excitatory one in cortical cultures. The synaptogenic activities of Cbln1 and Cbln2 were suppressed by the addition of the extracellular domain of NRXN1β to the cortical neuron cultures. Consistently, Cbln1 and Cbln2 showed robust binding activities to NRXN1α and three β-NRXNs, while only weak interactions were observed between Cbln4 and NRXNs. The interactions of Cbln1, Cbln2 and Cbln4 were selective for NRXN variants containing splice segment (S) 4. Affinities for NRXNs estimated by surface plasmon resonance analysis were variable among Cbln subtypes. Cbln1 showed higher affinities to NRXNs than Cbln2, while the binding ability of Cbln4 was much lower than those of Cbln1 and Cbln2. The affinities of Cbln1 and Cbln2 were comparable between NRXN1α and NRXN1β, but those for NRXN2β and NRXN3β were lower. These results suggest that Cbln subtypes exert synaptogenic activities in cortical neurons by differentially interacting with NRXN variants containing S4.

  6. Brn3a regulates neuronal subtype specification in the trigeminal ganglion by promoting Runx expression during sensory differentiation

    Raisa Eng S


    Full Text Available Abstract The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression of early neurogenic genes; here we describe a second major role for Brn3a in the specification of sensory subtypes in the trigeminal ganglion (TG. Sensory neurons initially co-express multiple Trk-family neurotrophin receptors, but are later marked by the unique expression of TrkA, TrkB or TrkC. Maturation of these sensory subtypes is known to depend on the expression of Runx transcription factors. Newborn Brn3a knockout mice fail to express TrkC, which is associated in the TG with mechanoreceptors, plus a set of functional genes associated with nociceptor subtypes. In embryonic Brn3a-/- ganglia, the normal expression of Runx3 is never initiated in TrkC+ neurons, and Runx1 expression is greatly attenuated in TrkA+ nociceptors. These changes are accompanied by expanded expression of TrkB in neurons that abnormally express multiple Trks, followed by the loss of TrkC and TrkA expression. In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a. Chromatin immunoprecipitation confirms that Brn3a binds in vivo to a conserved upstream enhancer element within histone H3-acetylated chromatin in the Runx3 locus. Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.

  7. Pre-infection of pigs with Mycoplasma hyopneumoniae induces oxidative stress that influences outcomes of a subsequent infection with a swine influenza virus of H1N1 subtype.

    Deblanc, C; Robert, F; Pinard, T; Gorin, S; Quéguiner, S; Gautier-Bouchardon, A V; Ferré, S; Garraud, J M; Cariolet, R; Brack, M; Simon, G


    The severity of swine influenza is highly variable and can be exacerbated by many factors, such as a pre-infection of pigs with Mycoplasma hyopneumoniae (Mhp). The aim of this study was to investigate the oxidative stress induced by Mhp and the impact of this stress on the evolution of an infection with the European avian-like swine H1N1 influenza virus. Two experimental trials (E1 and E2), which differed only by the feed delivered to the animals, were conducted on SPF pigs. In each trial, one group of nine 6-week-old pigs was inoculated intra-tracheally with Mhp and H1N1 at 21 days intervals and a mock-infected group (8 pigs) was included. Clinical signs were observed, blood samples were collected throughout the study and pathogens were detected in nasal swabs and lung tissues. Results indicated that Mhp infection induced an oxidative stress in E1 and E2, but its level was more important in E2 than in E1 three weeks post-Mhp inoculation, before H1N1 infection. In both trials, a strong inflammatory response and a response to the oxidative stress previously induced by Mhp appeared after H1N1 infection. However, the severity of influenza disease was significantly more marked in E2 as compared to E1, as revealed by prolonged hyperthermia, stronger reduction in mean daily weight gain and earlier viral shedding. These results suggested that severity of flu syndrome and reduction in animal performance may vary depending on the level of oxidative stress at the moment of the influenza infection, and that host responses could be influenced by the feed.

  8. Interaction pattern of Arg 62 in the A-pocket of differentially disease-associated HLA-B27 subtypes suggests distinct TCR binding modes.

    Elisa Nurzia

    Full Text Available The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL and TIS (RRLPIFSRL, and the viral peptides pLMP2 (RRRWRRLTV and NPflu (SRYWAIRTR. Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K and non-conservative (R62A B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.

  9. Direct and indirect measures of sexual maturity preferences differentiate subtypes of child sexual abusers.

    Schmidt, Alexander F; Gykiere, Kim; Vanhoeck, Kris; Mann, Ruth E; Banse, Rainer


    To aid risk assessment, management, and treatment planning it is essential to assess child sexual abusers' deviant sexual interests (DSI) and preferences (DSP) for sex with children. However, measurement of DSI/DSP is fraught with psychometric problems. In consequence, research interest has shifted to latency-based indirect measures as a measurement approach to complement self-report and physiological assessment. Utilizing the Explicit and Implicit Sexual Interest Profile (EISIP)-a multimethod approach consisting of self-report, viewing time, and Implicit Association Test (IAT) DSI/DSP measures-we replicated phallometric DSI/DSP differences between child sexual abuser subgroups in a sample of intrafamilial, extrafamilial, and child pornography offenders. DSI/DSP was associated with recidivism risk, offense-behavioral measures of pedophilic interest, and sexual fantasizing. It also negatively correlated with antisociality. Distinguishing between child sexual abuser subtypes and being related to recidivism risk, the EISIP is a useful tool for sexual offender assessments.

  10. Nested RT-PCR method for the detection of European avian-like H1 swine inlfuenza A virus

    WEI Yan-di; PEI Xing-yao; ZHANG Yuan; YU Chen-fang; SUN Hong-lei; LIU Jin-hua; PU Juan


    Swine inlfuenza A virus (swine IAV) circulates worldwide in pigs and poses a serious public health threat, as evidenced by the 2009 H1N1 inlfuenza pandemic. Among multiple subtypes/lineages of swine inlfuenza A viruses, European avian-like (EA) H1N1 swine IAV has been dominant since 2005 in China and caused infections in humans in 2010. Highly sensitive and speciifc methods of detection are required to differentiate EA H1N1 swine IAVs from viruses belonging to other lineages and subtypes. In this study, a nested reverse transcription (RT)-PCR assay was developed to detect EA H1 swine IAVs. Two primer sets (outer and inner) were designed speciifcaly to target the viral hemagglutinin genes. Speciifc PCR products were obtained from al tested EA H1N1 swine IAV isolates, but not from other lineages of H1 swine IAVs, other subtypes of swine IAVs, or other infectious swine viruses. The sensitivity of the nested RT-PCR was improved to 1 plaque forming unit (PFU) mL–1which was over 104 PFU mL–1 for a previously established multiplex RT-PCR method. The nested RT-PCR results obtained from screening 365 clinical samples were consistent with those obtained using conventional virus isolation methods combined with sequencing. Thus, the nested RT-PCR assay reported herein is more sensitive and suitable for the diagnosis of clinical infections and surveilance of EA H1 swine IAVs in pigs and humans.

  11. Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

    S. James (Sally); J. Fox (James); F. Afsari (Farinaz); J. Lee (Jennifer); S. Clough (Sally); C. Knight (Charlotte); J. Ashmore (James); P. Ashton (Peter); O. Preham (Olivier); M.J. Hoogduijn (Martin); R.D.A.R. Ponzoni (Raquel De Almeida Rocha); Y. Hancock; M. Coles (Mark); P.G. Genever (Paul)


    textabstractBone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis

  12. Glutamate receptor δ1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with neurexins through cerebellin precursor protein subtypes.

    Yasumura, Misato; Yoshida, Tomoyuki; Lee, Sung-Jin; Uemura, Takeshi; Joo, Jae-Yeol; Mishina, Masayoshi


    Glutamate receptor (GluR) δ1 is widely expressed in the developing forebrain, whereas GluRδ2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans-synaptic interaction of postsynaptic GluRδ2 and pre-synaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitatory synapse formation in the cerebellum. Thus, a question arises whether GluRδ1 regulates synapse formation in the forebrain. In this study, we showed that the N-terminal domain of GluRδ1 induced inhibitory presynaptic differentiation of some populations of cultured cortical neurons. When Cbln1 or Cbln2 was added to cultures, GluRδ1 expressed in HEK293T cells induced preferentially inhibitory presynaptic differentiation of cultured cortical neurons. The synaptogenic activity of GluRδ1 was suppressed by the addition of the extracellular domain of NRXN1α or NRXN1β containing splice segment 4. Cbln subtypes directly bound to the N-terminal domain of GluRδ1. The synaptogenic activity of GluRδ1 in the presence of Cbln subtypes correlated well with their binding affinities. When transfected to cortical neurons, GluRδ1 stimulated inhibitory synapse formation in the presence of Cbln1 or Cbln2. These results together with differential interactions of Cbln subtypes with NRXN variants suggest that GluRδ1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with NRXNs containing splice segment 4 through Cbln subtypes.

  13. B7-H1在结直肠癌血管内皮细胞与内皮细胞中的差异性表达及机制%Differential expression of B7-H1 between colorectal carcinoma vascular endothelial cells and endothelial cells and the mechanism

    施强; 郑勇斌; 罗海平; 刘克杰; 曹峰瑜; 丁瑜; 童仕伦


    目的 探讨共刺激分子B7-H1在结直肠癌血管内皮细胞(CCVEC)与内皮细胞(EC)中的差异性表达及机制.方法 应用免疫组织化学、实时定量聚合酶链反应(Real-time PCR)及Western blot等检测CCVEC与EC的B7-H1差异性表达,并通过白细胞介素(IL)-10、干扰素(IFN)-γ和双因子联合(BFC)的阳性与阴性干预来探讨其机制.差异性表达3组(CCVEC、EC和共培养成纤维细胞组),阳性干预4组(IL-10、IFN-γ、BFC、CCVEC组),阴性干预4组(IL-10中和组、IFN-γ中和组、BFC中和组、CCVEC组),干预前后分别检测EC的B7-H1表达.结果 与EC的阴性表达不同,CCVECB7-H1阳性细胞表达率为(75.00±17.41)%,中位染色评分为3.13;阳性干预IL-10、IFN-γ与BFC刺激EC后,其B7-H1表达率分别为(29.58±4.86)%、(32.08±5.08)%和(34.79±4.40)%,评分为1.46、1.58和1.71(P >0.05),但与CCVEC差异有统计学意义(P<0.05);阴性干预IL-10、IFN-γ与BFC中和后,EC B7-H1表达率分别为(36.21±4.05)%、(31.04±3.56)%和(7.02±2.31)%,评分为1.89、1.61、0.62(P <0.05).且B7-H1 mRNA与蛋白表达比较也证实了该结果.结论 B7-H1为区别EC与CCVEC的分子标志物之一,其表达与肿瘤微环境相关,IL-10和IFN-γ为微环境中的重要相关作用因子.%Objective To investigate the differential expression of costimulatory molecules B7-H1 between colorectal carcinoma vascular endothelial cells (CCVEC) and endothelial cells (EC) and the mechanism.Methods Immunohistochemistry,real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting were applied to detect the differential expression of B7-H1 between CCVEC and human umbilical vein endothelial cells (HUVEC).Intervened positively with interleukin (IL)-10 or interferon (IFN)-γ or Bi-factor combined (BFC) and negative handle with anti-IL-10 neutralization antibody or anti-IFN-γ neutralization antibody or BFC neutralization antibodies to investigate the differential

  14. Role of toll like receptors in irritable bowel syndrome: differential mucosal immune activation according to the disease subtype.

    Liliana Belmonte

    Full Text Available BACKGROUND: The irritable bowel syndrome (IBS is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. METHODOLOGY AND FINDINGS: In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed. TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1β. CONCLUSIONS: Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.

  15. Differential effect of specific gr/gr deletion subtypes on spermatogenesis in the Chinese Han population.

    Yang, Y; Ma, M; Li, L; Su, D; Chen, P; Ma, Y; Liu, Y; Tao, D; Lin, L; Zhang, S


    As a common variation in the azoospermia factor c (AZFc) region of Y chromosome, the gr/gr deletion is regarded as a significant risk factor for spermatogenic impairment, whereas the association of the deletion's phenotypic expression with Y-chromosomal background is still a subject of debate. To further investigate the contribution of the deletion to spermatogenic impairment in different Y-chromosomal haplogroups, the partial AZFc deletion was detected with AZFc-specific sequence tagged sites, gene dosage and gene copy analyses of deleted in azoospermia (DAZ), chromodomain Y1 (CDY1) and basic protein Y2 (BPY2) in 1426 azoo/oligozoospermic and 672 normozoospermic men from a Chinese population. The haplogrouping was performed in 231 deletion carriers with 12 polymorphic loci of Y chromosome. As a result, five gr/gr rearrangement types in eight Y haplogroups were observed, in which the simple gr/gr deletion was the most common type, and its frequency was significantly higher in men with azoo/oligozoospermia relative to normozoospermia. Also the distribution of gr/gr-rearranged Y haplogroups was significantly different between the two groups, in which gr/gr-deleted haplogroups C and DE were more common in men with azoo/oligozoospermia. In the 6 gr/gr copy deletion haplotypes, the frequencies of DAZ1/DAZ2+CDY1a or CDY1b deletion were significantly higher in men with azoo/oligozoospermia, while all DAZ3/DAZ4+CDY1b+BPY2.2 or 2.3 deletions were found only in haplogroup Q1 without any distribution difference between the azoo/oligozoospermic and normozoospermic groups. This study provided further evidence for the existence of multiple subtypes of gr/gr deletion and indicates that gr/gr-DAZ1/DAZ2 deletion is a significant risk factor. However, the association of the phenotypic variation of gr/gr deletion with Y-chromosomal haplogroups is not definite yet, because of the limited amounts of the deletions observed in each of the haplogroups and the lack of the quantitative

  16. A Nonconforming Arbitrary Quadrilateral H1-Galerkin Mixed Finite Element Method for Hyperbolic Type Integro-differential Equation%双曲型积分微分方程的非协调任意四边形H1-Galerkin混合有限元方法

    王海红; 郭城


    针对双曲型积分微分方程问题,研究了非协调任意四边形H1-Galerkin混合有限元方法.在半离散格式下,利用所选单元本身的特点,在不需要Ritz-Volterra投影的情况下得到了与传统协调混合有限元方法相同的误差估计.%A nonconforming arbitrary quadrilateral H1 -Galerkin mixed finite element method for hyperbolic type integro-differential equations problem was studied. By use of the characteristic of the chosen finite elements, the same error estimates as in the traditional conforming mixed finite elements methods were derived in semi-discrete formulation without using Ritz-Volterra projection.

  17. A Multiplex RT-PCR Assay for Detection and Differentiation of Avian-Origin Canine H3N2, Equine-Origin H3N8, Human-Origin H3N2, and H1N1/2009 Canine Influenza Viruses

    Sun, Honglei; Pu, Juan; Liu, Jinhua; Sun, Yipeng


    Virological and serological surveys have documented that H1N1/2009, avian-origin canine H3N2 (cH3N2), seasonal human-origin H3N2 (hH3N2), and equine-origin H3N8 influenza viruses are consistently circulating in dogs. In the present study, a multiplex reverse-transcriptase polymerase chain reaction (mRT-PCR) assay was developed for simultaneous detection and differentiation of these influenza viruses. Four primer sets were designed to target the hemagglutinin genes of H1N1/2009, cH3N2, hH3N2, and H3N8 canine influenza viruses (CIVs). This mRT-PCR assay demonstrated high specificity and sensitivity for the four CIV subtypes. Additionally, mRT-PCR results obtained from 420 clinical samples were consistent with those obtained by the conventional virus isolation method. Our mRT-PCR assay is reliable for clinical diagnosis and rapid identification of CIVs. PMID:28107507

  18. Heterologous expression of human H1 histones in yeast.

    Albig, W; Runge, D M; Kratzmeier, M; Doenecke, D


    The complete set of seven human H1 histone subtype genes was heterologously expressed in yeast. Since Saccharomyces cerevisiae lacks standard histone H1 we could isolate each recombinantly expressed human H1 subtype in pure form without contamination by endogenous H I histones. For isolation of the H1 histones in this expression system no tagging was needed and the isoforms could be extracted with the authentic primary structure by a single extraction step with 5%(0.74 M) perchloric acid. The isolated H1 histone proteins were used to assign the subtype genes to the corresponding protein spots or peaks after two-dimensional gel electrophoresis and capillary zone electrophoresis, respectively. This allowed us to correlate transcriptional data with protein data, which was barely possible until now.

  19. Differential deployment of REST and CoREST promotes glial subtype specification and oligodendrocyte lineage maturation.

    Joseph J Abrajano

    Full Text Available BACKGROUND: The repressor element-1 (RE1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST. CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation. METHODOLOGY/PRINCIPAL FINDINGS: We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS and oligodendrocyte (OL lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes. CONCLUSIONS/SIGNIFICANCE: Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes

  20. Optical coherence tomography (OCT) combined with videokeratography to differentiate mild keratoconus subtypes

    Rabinowitz, Yaron S.; Li, Xiaohui; Canedo, Ana Laura Caiado; Ambrosio, Renato; Bykhovskaya, Yelena


    Background/Aims To develop parameters using a combination of optical coherence tomography (OCT) and videokeratography to ‘early’ detect keratoconus. Methods We performed videokeratography, wavefront analysis and measured OCT indices on 180 normal, 46 moderate keratoconus, 54 early keratoconus, 7 ‘forme fruste’ keratoconus and 16 keratoconus ‘suspect” eyes, to determine the most sensitive parameters for separating these groups. Results A combination of videokeratography and OCT indices (I-S value and Minimum pachymetry) was statistically the most significant in separating the keratoconus groups from normals (Pkeratoconus as being abnormal with 7 normals misclassified (misclassification rate of 2.7%). By adding keratoconus ‘suspects’ to the analysis and an I-S value of 1.2 as a cut of point, we classified 5 ‘suspects’ as normal and 11 normals as abnormal (misclassification rate 7.8%). The PA/I-S index, with a cut of point of 100, reduced this misclassification rate to 4.4%. Conclusion These results suggest that OCT combined with videokeratography may be more useful for differentiating mild forms of keratoconus, than videokeratography alone. PMID:24763472

  1. Use of MRI in Differentiation of Papillary Renal Cell Carcinoma Subtypes: Qualitative and Quantitative Analysis.

    Doshi, Ankur M; Ream, Justin M; Kierans, Andrea S; Bilbily, Matthew; Rusinek, Henry; Huang, William C; Chandarana, Hersh


    The purpose of this study was to determine whether qualitative and quantitative MRI feature analysis is useful for differentiating type 1 from type 2 papillary renal cell carcinoma (PRCC). This retrospective study included 21 type 1 and 17 type 2 PRCCs evaluated with preoperative MRI. Two radiologists independently evaluated various qualitative features, including signal intensity, heterogeneity, and margin. For the quantitative analysis, a radiology fellow and a medical student independently drew 3D volumes of interest over the entire tumor on T2-weighted HASTE images, apparent diffusion coefficient parametric maps, and nephrographic phase contrast-enhanced MR images to derive first-order texture metrics. Qualitative and quantitative features were compared between the groups. For both readers, qualitative features with greater frequency in type 2 PRCC included heterogeneous enhancement, indistinct margin, and T2 heterogeneity (all, p Quantitative analysis revealed that apparent diffusion coefficient, HASTE, and contrast-enhanced entropy were greater in type 2 PRCC (p quantitative and qualitative model had an AUC of 0.859. Qualitative features within the model had interreader concordance of 84-95%, and the quantitative data had intraclass coefficients of 0.873-0.961. Qualitative and quantitative features can help discriminate between type 1 and type 2 PRCC. Quantitative analysis may capture useful information that complements the qualitative appearance while benefiting from high interobserver agreement.

  2. Differentiation of papillary renal cell carcinoma subtypes on CT and MRI.

    Egbert, Nathan D; Caoili, Elaine M; Cohan, Richard H; Davenport, Matthew S; Francis, Isaac R; Kunju, L Priya; Ellis, James H


    The objective of our study was to determine the frequency of atypical papillary renal cell carcinomas (RCCs) and identify imaging differences between type 1 and type 2 papillary RCCs once atypical papillary RCC tumors have been excluded. Eighty-two papillary RCC tumors were classified at pathology as type 1, type 2, or atypical. The CT and MRI examinations of these tumors were reviewed. Imaging features such as tumor size, margins, heterogeneity, and enhancement were assessed and the findings in type 1 and type 2 tumors were compared. There were 43 type 1 and 13 type 2 tumors. Atypical histologic features (i.e., tumors containing both type 1 and type 2 components, clear cells, or components with atypically high nuclear grade [in type 1 tumors] or low nuclear grade [in type 2 tumors]) were seen in 26 tumors. On CT, type 2 tumors more commonly had infiltrative margins (p = 0.05) and were more likely to have calcifications (p = 0.04) than type 1 tumors, although these features were seen in all tumor types. Type 2 tumors were also more heterogeneous than type 1 tumors (p = 0.04). On CT, 11 papillary RCCs showed enhancement of less than 20 HU, seven of which showed enhancement of less than 10 HU. On MRI, all tumors showed enhancement on subtraction images. Nearly one third of papillary RCCs in our patient population had atypical features at histology. On CT and MRI, there are some significant differences in imaging features between type 1 and type 2 tumors; however, substantial overlap precludes categorization on a per-patient basis. On CT, many papillary RCCs do not enhance, indicating that assessment of enhancement alone is insufficient for differentiating papillary RCCs from hyperdense cysts.

  3. Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.

    Rodrigo D Cunha

    Full Text Available BACKGROUND: HIV-1 subtype B is the most prevalent in developed countries and, consequently, it has been extensively studied. On the other hand, subtype C is the most prevalent worldwide and therefore is a reasonable target for future studies. Here we evaluate the acquisition of resistance and the viability of HIV-1 subtype B and C RT clones from different isolates that were subjected to in vitro selection pressure with zidovudine (ZDV and lamivudine (3TC. METHODS/PRINCIPAL FINDINGS: MT4 cells were infected with chimeric virus pseudotyped with RT from subtype B and C clones, which were previously subjected to serial passage with increasing concentrations of ZDV and 3TC. The samples collected after each passage were analyzed for the presence of resistance mutations and VL. No differences were found between subtypes B and C in viral load and resistance mutations when these viruses were selected with 3TC. However, the route of mutations and the time to rebound of subtype B and C virus were different when subjected to ZDV treatment. In order to confirm the role of the mutations detected, other clones were generated and subjected to in vitro selection. RT subtype B virus isolates tended to acquire different ZDV resistance mutations (Q151M and D67N or T215Y, D67D/N and F214L compared to subtype C (D67N, K70R, T215I or T215F. CONCLUSIONS/SIGNIFICANCE: This study suggests that different subtypes have a tendency to react differently to antiretroviral drug selection in vitro. Consequently, the acquisition of resistance in patients undergoing antiretroviral therapy can be dependent on the subtypes composing the viral population.

  4. Alteration of protein levels during influenza virus H1N1 infection in host cells: a proteomic survey of host and virus reveals differential dynamics.

    Susann Kummer

    Full Text Available We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1 infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC. We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG enrichment tests to uncover co-regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of viral infection. For the first time we are able to describe dynamic changes of the cellular and, of note, the viral proteome in a time dependent manner simultaneously. Through cluster analysis, time dependent patterns of protein abundances revealed highly dynamic up- and/or down-regulation processes. Taken together our study provides strong evidence that virus infection has a major impact on the cell status at the protein level.

  5. H1N1 Influenza

    ... Nutrient Shortfall Questionnaire Home Diseases and Conditions H1N1 Influenza H1N1 Influenza Condition Family HealthKids and Teens Share H1N1 ... Contents1. Overview2. Symptoms3. Prevention4. Treatment What is H1N1 influenza?H1N1 influenza (also known as swine flu) is an ...

  6. A Nonconforming H1-Galerkin Expanded Mixed Finite Element Method for Semilinear Parabolic Partial Differential Equations%拟线性抛物问题的非协调 H1-Galerkin扩展混合有限元方法∗

    石东洋; 郭城; 王海红


      抛物方程在热的传导、溶质的弥散以及多孔介质的渗流等问题中有着广泛的应用。本文综合 H1-Galerkin 混合有限元方法与扩展混合有限元方法的优点,针对一类拟线性抛物问题,提出了在半离散和向后的 Euler 全离散格式下非协调的 H1-Galerkin 扩展混合有限元方法。该方法利用真解的插值,不需要利用投影,从而得到有限元解的存在唯一性和格式的稳定性,以及和以往协调元相同的误差估计。%The parabolic partial differential equations have wide range of applications in the heat transmission, the solute dissemination, porous media seepage and so on. In this paper, the nonconforming Galerkin expanded finite element method for a class of quasi-linear partial dif-ferential equations is proposed both for semi-discrete and back-ward Euler full discrete schemes by applying the advantages of Galerkin mixed finite element method and expanded finite ele-ment method. The same error estimates as the conforming case in the previous literature, the existence and uniqueness of the finite element solutions and the stability of the schemes are obtained by means of the interpolation of the true solutions instead of projections.

  7. H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix(®) vaccination.

    Ambati, Aditya; Valentini, Davide; Montomoli, Emanuele; Lapini, Guilia; Biuso, Fabrizio; Wenschuh, Holger; Magalhaes, Isabelle; Maeurer, Markus


    A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix(®) vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251-265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.

  8. Analysis of the Differentiation of Kenyon Cell Subtypes Using Three Mushroom Body-Preferential Genes during Metamorphosis in the Honeybee (Apis mellifera L.)

    Okude, Genta; Fujiyuki, Tomoko; Shirai, Kenichi; Kubo, Takeo


    The adult honeybee (Apis mellifera L.) mushroom bodies (MBs, a higher center in the insect brain) comprise four subtypes of intrinsic neurons: the class-I large-, middle-, and small-type Kenyon cells (lKCs, mKCs, and sKCs, respectively), and class-II KCs. Analysis of the differentiation of KC subtypes during metamorphosis is important for the better understanding of the roles of KC subtypes related to the honeybee behaviors. In the present study, aiming at identifying marker genes for KC subtypes, we used a cDNA microarray to comprehensively search for genes expressed in an MB-preferential manner in the honeybee brain. Among the 18 genes identified, we further analyzed three genes whose expression was enriched in the MBs: phospholipase C epsilon (PLCe), synaptotagmin 14 (Syt14), and discs large homolog 5 (dlg5). Quantitative reverse transcription-polymerase chain reaction analysis revealed that expression of PLCe, Syt14, and dlg5 was more enriched in the MBs than in the other brain regions by approximately 31-, 6.8-, and 5.6-fold, respectively. In situ hybridization revealed that expression of both Syt14 and dlg5 was enriched in the lKCs but not in the mKCs and sKCs, whereas expression of PLCe was similar in all KC subtypes (the entire MBs) in the honeybee brain, suggesting that Syt14 and dlg5, and PLCe are available as marker genes for the lKCs, and all KC subtypes, respectively. In situ hybridization revealed that expression of PLCe is already detectable in the class-II KCs at the larval fifth instar feeding stage, indicating that PLCe expression is a characteristic common to the larval and adult MBs. In contrast, expression of both Syt14 and dlg5 became detectable at the day three pupa, indicating that Syt14 and dlg5 expressions are characteristic to the late pupal and adult MBs and the lKC specific molecular characteristics are established during the late pupal stages. PMID:27351839

  9. Analysis of the Differentiation of Kenyon Cell Subtypes Using Three Mushroom Body-Preferential Genes during Metamorphosis in the Honeybee (Apis mellifera L..

    Shota Suenami

    Full Text Available The adult honeybee (Apis mellifera L. mushroom bodies (MBs, a higher center in the insect brain comprise four subtypes of intrinsic neurons: the class-I large-, middle-, and small-type Kenyon cells (lKCs, mKCs, and sKCs, respectively, and class-II KCs. Analysis of the differentiation of KC subtypes during metamorphosis is important for the better understanding of the roles of KC subtypes related to the honeybee behaviors. In the present study, aiming at identifying marker genes for KC subtypes, we used a cDNA microarray to comprehensively search for genes expressed in an MB-preferential manner in the honeybee brain. Among the 18 genes identified, we further analyzed three genes whose expression was enriched in the MBs: phospholipase C epsilon (PLCe, synaptotagmin 14 (Syt14, and discs large homolog 5 (dlg5. Quantitative reverse transcription-polymerase chain reaction analysis revealed that expression of PLCe, Syt14, and dlg5 was more enriched in the MBs than in the other brain regions by approximately 31-, 6.8-, and 5.6-fold, respectively. In situ hybridization revealed that expression of both Syt14 and dlg5 was enriched in the lKCs but not in the mKCs and sKCs, whereas expression of PLCe was similar in all KC subtypes (the entire MBs in the honeybee brain, suggesting that Syt14 and dlg5, and PLCe are available as marker genes for the lKCs, and all KC subtypes, respectively. In situ hybridization revealed that expression of PLCe is already detectable in the class-II KCs at the larval fifth instar feeding stage, indicating that PLCe expression is a characteristic common to the larval and adult MBs. In contrast, expression of both Syt14 and dlg5 became detectable at the day three pupa, indicating that Syt14 and dlg5 expressions are characteristic to the late pupal and adult MBs and the lKC specific molecular characteristics are established during the late pupal stages.

  10. Comparative characterization of botulinum neurotoxin subtypes F1 and F7 featuring differential substrate recognition and cleavage mechanisms.

    Guo, Jiubiao; Chan, Edward Wai Chi; Chen, Sheng


    BoNT/F7, one of the seven subtypes of botulinum neurotoxin type F (F1 to F7), is the second-most divergent subtype of this group. Despite sharing >60% identity with BoNT/F1 at both holotoxin and enzymatic domain levels, it requires an N-terminal extended peptide substrate for efficient substrate cleavage, suggesting its unique substrate recognition and specificity mechanism. Substrate mapping and saturation mutagenesis analysis revealed that VAMP2 (20-65) was likely a minimally effective substrate for LC/F7 (light chain of BoNT/F7), and in addition, LC/F7 recognized VAMP2 in a unique way, which differed significantly from that of LC/F1, although both of them share similar substrate binding and hydrolysis mode. LC/F7 utilizes distinct pockets for specific substrate binding and recognition in particular for the B1, B2 and S2 sites recognitions. Our findings provide insights into the distinct substrate recognition features of BoNT subtypes and useful information for therapy development for BoNT/F. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. H1 at HERA Exhibition


    H1 is one of the two large detectors installed at HERA, the first electron-proton accelerator, located at DESY in Hamburg. The H1 collaboration regroups physicists from 32institutes of 11countries all over the world.

  12. Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants


    novel A/H1N1 outbreak strain, raising immediate concerns for public health as well as for pork and poultry production industries worldwide. As with...outbreak management have reviewed the pathology of influenza with respect to rapid deterioration and patient deaths attributable to secondary

  13. Differential response of immunohistochemically defined breast cancer subtypes to anthracycline-based adjuvant chemotherapy with or without paclitaxel.

    George Fountzilas

    Full Text Available BACKGROUND: The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER, progesterone receptor (PgR, HER2, Ki67, cytokeratin 5 (CK5, and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67(low; luminal B (ER/PgR-positive, HER2-negative, Ki67(high; luminal-HER2 (ER/PgR-positive, HER2-positive; HER2-enriched (ER-negative, PgR-negative, HER2-positive; triple-negative (TNBC (ER-negative, PgR-negative, HER2-negative; and basal core phenotype (BCP (TNBC, CK5-positive and/or EGFR-positive. RESULTS: After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS and overall survival (OS rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31-2.80, Wald's p = 0.001 and for death 2.53 (95% CI: 1.62-3.60, p<0.001. Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors

  14. Distributed Subtyping

    Baehni, Sébastien; Barreto, Joao; Guerraoui, Rachid


    One of the most frequent operations in object-oriented programs is the "instanceof" test, also called the "subtyping" test or the "type inclusion" test. This test determines if a given object is an instance of some type. Surprisingly, despite a lot of research on distributed object-oriented languages and systems, almost no work has been devoted to the implementation of this test in a distributed environment. This paper presents the first algorithm to implement the "subtyping" test on an obje...

  15. [cAMP analogue 8-CPT-cAMP inducing differentiation in the M2b subtype of acute myeloid leukemia cell line Kasumi-1].

    Zhu, Qi; Hu, Jun-Pei; Jia, Pei-Min; Wang, Zhen-Yi; Tong, Jian-Hua


    This study was aimed to investigate the possible effects of cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the M(2b) subtype of acute myeloid leukemia (AML-M(2b)) cells. AML-M(2b) is characterized by the non-random chromosome translocation t (8; 21) (q22; q22), through which AML1 (acute myeloid leukemia 1) gene on chromosome 21 is fused with ETO (eight twenty-one) gene on chromosome 8, coding correspondent AML1-ETO fusion protein, which plays a crucial role in the leukemogenesis of AML-M(2b). The AML-M(2b) cell line Kasumi-1 cells were used as an in vitro model. The influences of 8-CPT-cAMP on the proliferation and differentiation of Kasumi-1 cells were evaluated according to cellular morphology, changes in cell surface antigen and cell cycle, as well as nitroblue-tetrazolium (NBT) assay. Meanwhile, semi-quantity RT-PCR and Western blot assay were used to detect the degradation of AML1-ETO fusion protein in Kasumi-1 cells before and after the treatment. The results showed that 8-CPT-cAMP (200 micromol/L) could significantly inhibit cell growth and induce differentiation of Kasumi-1 cells. However, it must be pointed out that 8-CPT-cAMP-induced differentiation in Kasumi-1 is not a typical terminal differentiation. Furthermore, 8-CPT-cAMP exerted little influence on the expression of AML1-ETO fusion gene and its product in Kasumi-1 cells. In conclusion, the 8-CPT-cAMP induced differentiation in Kasumi-1 cells. This results may provide experimental and theoretical basis for the breakthrough of differentiation-induced therapy extended to another leukemia.

  16. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

    Hergeth, Sonja P; Schneider, Robert


    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

  17. H1抗组胺药%H1-antihistamines

    张罗; 韩德民


    While histamine plays an important role in the pathogenesis of allergic diseases, such as allergic rhinitis, H1-antihistamines, which have been using in the treatment of allergic diseases for more than 70 years, are considered as the cornerstone of the medication of allergic diseases. In this review, we discuss the history of histamine studies and anti - histamine discovery, the histamine receptors, as well as the mechanisms and the safety of H1-antihistamines.

  18. Differential expression of somatostatin receptor subtype-related genes and proteins in non-functioning and functioning adrenal cortex adenomas.

    Pisarek, Hanna; Krupiński, Roman; Kubiak, Robert; Borkowska, Edyta; Pawlikowski, Marek; Winczyk, Katarzyna


    Adrenocortical adenomas display highly variable expressions of somatostatin receptor (SSTR) subtypes, whose expression is mandatory (although not always sufficient) to achieve the positive effects of somatostatin (SST) analog therapy. Immunohistochemistry (IHC) is the main method used to investigate receptor protein expression. The molecular biology method - polymerase chain reaction (PCR) - is also often used to investigate receptor expression. Nevertheless, the expression of receptor mRNA and the respective receptor protein is not always synchronized. The aim of this study was to investigate SSTR expression by IHC in adrenal adenomas, to compare the results to data obtained by real-time PCR and to determine whether hormonally functioning and non-functioning adenomas differ in this respect. Adrenocortical adenomas were removed surgically from 13 females and 2 males. The tissues were obtained from 9 non-functioning and 6 functioning adenomas. The intensity of IHC reaction was scored semiquantitatively by two independent observers. Real-time PCR was performed using pairs of primers in a reaction amplified along a gradient of temperatures. Amplified DNA was measured by monitoring SYBR-Green fluorescence. In non-functioning tumors, compatibility between IHC and PCR results was observed for SSTR 1 and 2 in 62.5% of the samples. Fifty percent of patients demonstrated compatibility for SSTR 4 and 5 and 37.5% for SSTR 3. In hormonally active adenomas, total compatibility of both methods was noted for SSTR 2 (100%). The compatibility obtained for SSTR 5 was 66.6%. We conclude that receptor gene and respective receptor protein expression are not always synchronized. Messenger RNA detection alone is not sufficient to predict the presence of the receptor protein acting as a target for SST and its analogs.

  19. In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography.

    Boone, Marc; Suppa, Mariano; Miyamoto, Makiko; Marneffe, Alice; Jemec, Gregor; Del Marmol, Veronique


    High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot whereby an exponential function becomes linear has been implemented on HD-OCT signals. The relative attenuation factor (µraf ) at different skin layers could be assessed.. IV-OP of superficial BCC with high diagnostic accuracy (DA) and high negative predictive values (NPV) were (i) decreased µraf in lower part of epidermis and (ii) increased epidermal thickness (E-T). IV-OP of nodular BCC with good to high DA and NPV were (i) less negative µraf in papillary dermis compared to normal adjacent skin and (ii) significantly decreased E-T and papillary dermal thickness (PD-T). In infiltrative BCC (i) high µraf in reticular dermis compared to normal adjacent skin and (ii) presence of peaks and falls in reticular dermis had good DA and high NPV. HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with IV-OP analysis of BCC. This permits BCC sub-differentiation with higher accuracy than in vivo HD-OCT analysis of morphology alone.

  20. Mortar Finite Volume Element Method for Parabolic Integro-differential Equations:H1 Error Estimation%抛物积分-微分方程的Mortar型有限体积元方法H1-范数的误差估计




  1. Hyperpolarization-activated cyclic nucleotide-gated cation channel subtypes differentially modulate the excitability of murine small intestinal afferents

    Ying-Ping Wang; Bi-Ying Sun; Qian Li; Li Dong; Guo-Hua Zhang; David Grundy; Wei-Fang Rong


    AIM: To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels in regulating the excitability of vagal and spinal gut afferents.METHODS: The mechanosensory response of mesen-teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissociated dorsal root ganglia (DRG) and nodose ganglia (NG) neurons retrogradely labeled from the small intestine through injection of a fluorescent marker (DiI). The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry.RESULTS: Ramp distension of the small intestine evoked biphasic increases in the afferent nerve activity, reflecting the activation of low- and high-threshold fibers.HCN blocker CsCl (5 mmol/L) preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold responses. The effect of CsCl was mimicked by the more selective HCN blocker ZD7288 (10 ?mol/L). In 71.4% of DiI labeled DRG neurons (n = 20) and 90.9% of DiI labeled NG neurons (n = 10), an inward current (Ih current) was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCl. In neurons expressing Ih current, a typical "sag" was observed upon injection of hyperpolarizing current pulses in current-clamp recordings. CsCl abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochemistry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respectively.CONCLUSION: HCNs differentially regulate the excitability of vagal and spinal afferent of murine small intestine.

  2. Meis/UNC-62 isoform dependent regulation of CoupTF-II/UNC-55 and GABAergic motor neuron subtype differentiation.

    Campbell, Richard F; Walthall, Walter W


    Gene regulatory networks orchestrate the assembly of functionally related cells within a cellular network. Subtle differences often exist among functionally related cells within such networks. How differences are created among cells with similar functions has been difficult to determine due to the complexity of both the gene and the cellular networks. In Caenorhabditis elegans, the DD and VD motor neurons compose a cross-inhibitory, GABAergic network that coordinates dorsal and ventral muscle contractions during locomotion. The Pitx2 homologue, UNC-30, acts as a terminal selector gene to create similarities and the Coup-TFII homologue, UNC-55, is necessary for creating differences between the two motor neuron classes. What is the organizing gene regulatory network responsible for initiating the expression of UNC-55 and thus creating differences between the DD and VD motor neurons? We show that the unc-55 promoter has modules that contain Meis/UNC-62 binding sites. These sites can be subdivided into regions that are capable of activating or repressing UNC-55 expression in different motor neurons. Interestingly, different isoforms of UNC-62 are responsible for the activation and the stabilization of unc-55 transcription. Furthermore, specific isoforms of UNC-62 are required for proper synaptic patterning of the VD motor neurons. Isoform specific regulation of differentiating neurons is a relatively unexplored area of research and presents a mechanism for creating differences among functionally related cells within a network. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Differential Amino Acid, Carbohydrate and Lipid Metabolism Perpetuations Involved in a Subtype of Rheumatoid Arthritis with Chinese Medicine Cold Pattern

    Hongtao Guo


    Full Text Available Pattern classification is a key approach in Traditional Chinese Medicine (TCM, and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS and gas chromatography/mass spectrometry (GC/MS platforms in conjunction with the Ingenuity Pathway Analysis (IPA software. Three main processes of metabolism, including amino acid, carbohydrate and lipid were focused on for function analysis. The results showed that 29 and 19 differential metabolites were found in cold and heat patterns respectively, compared with healthy controls. The perturbation of amino acid metabolism (increased essential amino acids, carbohydrate metabolism (galactose metabolism and lipid metabolism, were found to be involved in both cold and heat pattern RA. In particular, more metabolic perturbations in protein and collagen breakdown, decreased glycolytic activity and aerobic oxidation, and increased energy utilization associated with RA cold pattern patients. These findings may be useful for obtaining a better understanding of RA pathogenesis and for achieving a better efficacy in RA clinical practice.

  4. The DSM-5 dissociative-PTSD subtype: can levels of depression, anxiety, hostility, and sleeping difficulties differentiate between dissociative-PTSD and PTSD in rape and sexual assault victims?

    Armour, Cherie; Elklit, Ask; Lauterbach, Dean; Elhai, Jon D


    The DSM-5 currently includes a dissociative-PTSD subtype within its nomenclature. Several studies have confirmed the dissociative-PTSD subtype in both American Veteran and American civilian samples. Studies have begun to assess specific factors which differentiate between dissociative vs. non-dissociative PTSD. The current study takes a novel approach to investigating the presence of a dissociative-PTSD subtype in its use of European victims of sexual assault and rape (N=351). Utilizing Latent Profile Analyses, we hypothesized that a discrete group of individuals would represent a dissociative-PTSD subtype. We additionally hypothesized that levels of depression, anger, hostility, and sleeping difficulties would differentiate dissociative-PTSD from a similarly severe form of PTSD in the absence of dissociation. Results concluded that there were four discrete groups termed baseline, moderate PTSD, high PTSD, and dissociative-PTSD. The dissociative-PTSD group encompassed 13.1% of the sample and evidenced significantly higher mean scores on measures of depression, anxiety, hostility, and sleeping difficulties. Implications are discussed in relation to both treatment planning and the newly published DSM-5. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake.

    Seibold, Petra; Vrieling, Alina; Heinz, Judith; Obi, Nadia; Sinn, Hans-Peter; Flesch-Janys, Dieter; Chang-Claude, Jenny


    Inconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking. We used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50-74 and diagnosed with invasive tumours 2001-2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed. Overall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93-1.64, and HR 1.29, 95% CI 0.95-1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13-2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60-1.98; Pheterogeneity=0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02-3.65, and HR 2.08, 95% CI 1.40-3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22-10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be

  6. H-1 Upgrades (4BW/4BN) (H-1 Upgrades)


    Nautical Miles R&M - Reliability and Maintainability RM - Reference Model TV-1 - Technical Standards Profile Univ . - Universal H-1 Upgrades December 2015...Speed (kts) 165 165 135 139 139 Payload (Hot Day) (lbs) 3500 lbs 3500 lbs 2500 lbs 6 Wing Stations 4 Universal Under Wing Stations 3429 3429 Weapon...Stations Universal Mounts 6 6 4 4 4 Precision Guided Munitions 16 16 12 16 16 Maneuverability/Agility (G’s) -0.5 to +2.5 -0.5 to +2.5 -0.5 to +2.5 -0.5 to

  7. Histone H1c decreases markedly in postreplicative stages of chicken spermatogenesis.

    Boix, J; Mezquita, C


    The relative proportions of four major chicken histone H1 subtypes (referred to as H1a, H1b, H1c and H1d) change markedly in different chicken tissues. The relative amount of H1c is higher in nonreplicating somatic tissues, such as liver, than in replicating immature testis. The proportion of H1c sharply decreases as spermatogenesis proceeds, being much lower in mature than in immature testis. It has been proposed that the relative increment of H1c correlates with low rates of cell division in chicken tissues. It was assumed that the sharp decrease in H1c observed during maturation of chicken testis was a consequence of the intensification of proliferative activity in spermatogonia (Berdnikov et al., 1976). Our results, however, clearly show that the decrease of H1c during maturation is due to the low levels of this protein in postreplicative stages of spermatogenesis, where H1c is barely detectable. These results suggest that the presence of the arginine-rich H1c subtype would neither be compatible with the relaxed structure of acetylated chromatin present in active replicating cells nor with the hyperacetylated chromatin characteristic of postreplicative late spermatids undergoing the nucleohistone nucleoprotamine transition.

  8. Magnetic resonance imaging and spectroscopy reveal differential hippocampal changes in anhedonic and resilient subtypes of the chronic mild stress rat model.

    Delgado y Palacios, Rafael; Campo, Adriaan; Henningsen, Kim; Verhoye, Marleen; Poot, Dirk; Dijkstra, Jouke; Van Audekerke, Johan; Benveniste, Helene; Sijbers, Jan; Wiborg, Ove; Van der Linden, Annemie


    Repeated exposure to mild stressors induces anhedonia-a core symptom of major depressive disorder-in up to 70% of the stress-exposed rats, whereas the remaining show resilience to stress. This chronic mild stress (CMS) model is well documented as an animal model of major depressive disorder. We examined the morphological, microstructural, and metabolic characteristics of the hippocampus in anhedonic and stress resilient rats that may mark the differential behavioral outcome. Anhedonic (n = 8), resilient (n = 8), and control (n = 8) rats were subjected to in vivo diffusion kurtosis imaging, high-resolution three-dimensional magnetic resonance imaging and proton magnetic resonance spectroscopy. Diffusion kurtosis parameters were decreased in both CMS-exposed groups. A significant inward displacement in the ventral part of the right hippocampus was apparent in the resilient subjects and an increase of the glutamate:total creatine ratio and N-acetylaspartylglutamate:total creatine was observed in the anhedonic subjects. Diffusion kurtosis imaging discloses subtle substructural changes in the hippocampus of CMS-exposed animals irrespective of their anhedonic or resilient nature. In contrast, proton magnetic resonance spectroscopy and magnetic resonance imaging-based shape change analysis of the hippocampus allowed discrimination of these two subtypes of stress sensitivity. Although the precise mechanism discriminating their behavior is yet to be elucidated, the present study underlines the role of the hippocampus in the etiology of depression and the induction of anhedonia. Our results reflect the potency of noninvasive magnetic resonance methods in preclinical settings with key translational benefit to and from the clinic. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María


    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.

  10. Strategies for subtyping influenza viruses circulating in the Danish pig population

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona


    in the Danish pig population functional and rapid subtyping assays are required. The conventional RT-PCR influenza subtyping assays developed by Chiapponi et al. (2003) have been implemented and used for typing of influenza viruses found positive in a pan influenza A real time RT-PCR assay. The H1 and N1 assays...... assays based on RT-PCR and subsequent sequencing were implemented for the four subtypes H1, H3, N1, and N2. The assays were based on primer sets published by the WHO, but slightly modified for improved detection of Danish subtype variants. Sequencing of circulating influenza viruses is beneficial since......Influenza viruses are endemic in the Danish pig population and the dominant circulating subtypes are H1N1, a Danish H1N2 reassortant, and H3N2. Here we present our current and future strategies for influenza virus subtyping. For diagnostic and surveillance of influenza subtypes circulating...

  11. Do HIV-1 non-B subtypes differentially impact resistance mutations and clinical disease progression in treated populations? Evidence from a systematic review

    Madhavi Bhargava


    Full Text Available There are 31 million adults living with HIV-1 non-B subtypes globally, and about 10 million are on antiretroviral therapy (ART. Global evidence to guide clinical practice on ART response in HIV-1 non-B subtypes remains limited. We systematically searched 11 databases for the period 1996 to 2013 for evidence. Outcomes documented included time to development of AIDS and/or death, resistance mutations, opportunistic infections, and changes in CD4 cell counts and viral load. A lack of consistent reporting of all clinical end points precluded a meta-analysis. In sum, genetic diversity that precipitated differences in disease progression in ART-naïve populations was minimized in ART-experienced populations, although variability in resistance mutations persisted across non-B subtypes. To improve the quality of patient care in global settings, recording HIV genotypes at baseline and at virologic failure with targeted non-B subtype-based point-of-care resistance assays and timely phasing out of resistance-inducing ART regimens is recommended.

  12. Differential neural correlates of set-shifting in the bingeing-purging and restrictive subtypes of anorexia nervosa : An fMRI study

    Van Autreve, Sara; De Baene, W.; Baeken, Chris; van Heeringen, Kees; Vancayseele, Nikita; Vervaet, Myriam


    In this study, possible differences in the neural correlates of set-shifting abilities between the restrictive (AN-R) and bingeing/purging (AN-BP) subtypes of anorexia nervosa have been explored. Three groups of participants performed a set-shifting task during functional magnetic resonance imaging:

  13. Diffusion-Weighted Imaging Using a Readout-Segmented, Multishot EPI Sequence at 3 T Distinguishes between Morphologically Differentiated and Undifferentiated Subtypes of Thyroid Carcinoma—A Preliminary Study

    Stefan Schob


    Full Text Available BACKGROUND: Thyroid carcinomas represent the most frequent endocrine malignancies. Recent studies were able to distinguish malignant from benign nodules of the thyroid gland with diffusion-weighted imaging (DWI. Although this differentiation is undoubtedly helpful, presurgical discrimination between well-differentiated and undifferentiated carcinomas would be crucial to define the optimal treatment algorithm. Therefore, the aim of this study was to investigate if readout-segmented multishot echo planar DWI is able to differentiate between differentiated and undifferentiated subtypes of thyroid carcinomas. PATIENTS AND METHODS: Fourteen patients with different types of thyroid carcinomas who received preoperative DWI were included in our study. In all lesions, apparent diffusion coefficient (ADCmin, ADCmean, ADCmax, and D were estimated on the basis of region of interest measurements after coregistration with T1-weighted, postcontrast images. All tumors were resected and analyzed histopathologically. Ki-67 index, p53 synthesis, cellularity, and total and average nucleic areas were estimated using ImageJ version 1.48. RESULTS: Analysis of variance revealed a statistically significant difference in ADCmean values between differentiated and undifferentiated thyroid carcinomas (P = .022. Spearman Rho calculation identified significant correlations between ADCmax and cell count (r = 0.541, P = .046 as well as between ADCmax and total nuclei area (r = 0.605, P = .022. CONCLUSION: DWI can distinguish between differentiated and undifferentiated thyroid carcinomas.

  14. The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains.

    Koçer, Zeynep A; Carter, Robert; Wu, Gang; Zhang, Jinghui; Webster, Robert G


    Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans.

  15. Outbreak of influenza A(H1N1) in a school in southern England.

    Goddard, N.; Paynter, S.; Paget, J.


    An outbreak of influenza A (subtype H1N1) has occurred in a primary school in West Sussex, southern England [1]. The first cases of illness occurred during the first week of May 2004. One child was admitted to hospital during that week with symptoms of fever, confusion, headache, and conjunctivitis.

  16. What is the role of histone H1 heterogeneity? A functional model emerges from a 50 year mystery

    Missag Hagop Parseghian


    Full Text Available For the past 50 years, understanding the function of histone H1 heterogeneity has been mired in confusion and contradiction. Part of the reason for this is the lack of a working model that tries to explain the large body of data that has been collected about the H1 subtypes so far. In this review, a global model is described largely based on published data from the author and other researchers over the past 20 years. The intrinsic disorder built into H1 protein structure is discussed to help the reader understand that these histones are multi-conformational and adaptable to interactions with different targets. We discuss the role of each structural section of H1 (as we currently understand it, but we focus on the H1's C-terminal domain and its effect on each subtype's affinity, mobility and compaction of chromatin. We review the multiple ways these characteristics have been measured from circular dichroism to FRAP analysis, which has added to the sometimes contradictory assumptions made about each subtype. Based on a tabulation of these measurements, we then organize the H1 variants according to their ability to condense chromatin and produce nucleosome repeat lengths amenable to that compaction. This subtype variation generates a continuum of different chromatin states allowing for fine regulatory control and some overlap in the event one or two subtypes are lost to mutation. We also review the myriad of disparate observations made about each subtype, both somatic and germline specific ones, that lend support to the proposed model. Finally, to demonstrate its adaptability as new data further refines our understanding of H1 subtypes, we show how the model can be applied to experimental observations of telomeric heterochromatin in aging cells.

  17. A phylogeny-based global nomenclature system and automated annotation tool for H1 hemagglutinin genes from swine influenza A viruses

    The H1 subtype of influenza A viruses (IAV) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from non-swine hosts, swine H1 have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based...

  18. Microdroplet sandwich real-time rt-PCR for detection of pandemic and seasonal influenza subtypes.

    Stephanie L Angione

    Full Text Available As demonstrated by the recent 2012/2013 flu epidemic, the continual emergence of new viral strains highlights the need for accurate medical diagnostics in multiple community settings. If rapid, robust, and sensitive diagnostics for influenza subtyping were available, it would help identify epidemics, facilitate appropriate antiviral usage, decrease inappropriate antibiotic usage, and eliminate the extra cost of unnecessary laboratory testing and treatment. Here, we describe a droplet sandwich platform that can detect influenza subtypes using real-time reverse-transcription polymerase chain reaction (rtRT-PCR. Using clinical samples collected during the 2010/11 season, we effectively differentiate between H1N1p (swine pandemic, H1N1s (seasonal, and H3N2 with an overall assay sensitivity was 96%, with 100% specificity for each subtype. Additionally, we demonstrate the ability to detect viral loads as low as 10(4 copies/mL, which is two orders of magnitude lower than viral loads in typical infected patients. This platform performs diagnostics in a miniaturized format without sacrificing any sensitivity, and can thus be easily developed into devices which are ideal for small clinics and pharmacies.

  19. Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y

    Sakaki Yoshiyuki


    Full Text Available Abstract Background SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA, but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase (PI3K is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E, each of which show a different phenotype during RA-mediated differentiation. Findings SH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor (BDNF for full differentiation. After exposing cells to a PI3K inhibitor, LY294002, we identified 386 genes and categorised these genes into two clusters dependent on the PI3K signalling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster, including 158 neural genes, was greatly reduced in SK-N-SH cells and partially impaired in SH-SY5Y-E cells, which is consistent with a defect in the neuronal phenotype of these cells. Additional stimulation with BDNF induced a set of neural genes that were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in differentiated SH-SY5Y-A cells. Conclusion We identified gene clusters controlled by PI3K- and TRKB-mediated signalling pathways during the differentiation of two subtypes of SH-SY5Y cells. The TRKB-mediated bypass pathway compensates for impaired neural function generated by defects in several signalling pathways, including PI3K in SH-SY5Y-E cells. Our expression profiling data will be useful for further elucidation of the signal transduction-transcriptional network involving PI3K or TRKB.

  20. Histone H1 phosphorylation occurs site-specifically during interphase and mitosis: identification of a novel phosphorylation site on histone H1.

    Sarg, Bettina; Helliger, Wilfried; Talasz, Heribert; Förg, Barbara; Lindner, Herbert H


    H1 histones, isolated from logarithmically growing and mitotically enriched human lymphoblastic T-cells (CCRF-CEM), were fractionated by reversed phase and hydrophilic interaction liquid chromatography, subjected to enzymatic digestion, and analyzed by amino acid sequencing and mass spectrometry. During interphase the four H1 subtypes present in these cells differ in their maximum phosphorylation levels: histone H1.5 is tri-, H1.4 di-, and H1.3 and H1.2, only monophosphorylated. The phosphorylation is site-specific and occurs exclusively on serine residues of SP(K/A)K motifs. The phosphorylation sites of histone H1.5 from mitotically enriched cells were also examined. In contrast to the situation in interphase, at mitosis there were additional phosphorylations, exclusively at threonine residues. Whereas the tetraphosphorylated H1.5 arises from the triphosphosphorylated form by phosphorylation of one of two TPKK motifs in the C-terminal domain, namely Thr137 and Thr154, the pentaphosphorylated H1.5 was the result of phosphorylation of one of the tetraphosphorylated forms at a novel nonconsensus motif at Thr10 in the N-terminal tail. Despite the fact that histone H1.5 has five (S/T)P(K/A)K motifs, all of these motifs were never found to be phosphorylated simultaneously. Our data suggest that phosphorylation of human H1 variants occurs nonrandomly during both interphase and mitosis and that distinct serine- or threonine-specific kinases are involved in different cell cycle phases. The order of increased phosphorylation and the position of modification might be necessary for regulated chromatin decondensation, thus facilitating processes of replication and transcription as well as of mitotic chromosome condensation.

  1. Avian influenza viruses that cause highly virulent infections in humans exhibit distinct replicative properties in contrast to human H1N1 viruses

    Simon, Philippe F.; de La Vega, Marc-Antoine; Paradis, Éric; Mendoza, Emelissa; Coombs, Kevin M.; Kobasa, Darwyn; Beauchemin, Catherine A. A.


    Avian influenza viruses present an emerging epidemiological concern as some strains of H5N1 avian influenza can cause severe infections in humans with lethality rates of up to 60%. These have been in circulation since 1997 and recently a novel H7N9-subtyped virus has been causing epizootics in China with lethality rates around 20%. To better understand the replication kinetics of these viruses, we combined several extensive viral kinetics experiments with mathematical modelling of in vitro infections in human A549 cells. We extracted fundamental replication parameters revealing that, while both the H5N1 and H7N9 viruses replicate faster and to higher titers than two low-pathogenicity H1N1 strains, they accomplish this via different mechanisms. While the H7N9 virions exhibit a faster rate of infection, the H5N1 virions are produced at a higher rate. Of the two H1N1 strains studied, the 2009 pandemic H1N1 strain exhibits the longest eclipse phase, possibly indicative of a less effective neuraminidase activity, but causes infection more rapidly than the seasonal strain. This explains, in part, the pandemic strain’s generally slower growth kinetics and permissiveness to accept mutations causing neuraminidase inhibitor resistance without significant loss in fitness. Our results highlight differential growth properties of H1N1, H5N1 and H7N9 influenza viruses.

  2. Genetic correlation between current circulating H1N1 swine and human influenza viruses.

    Lu, Lu; Yin, Yanbo; Sun, Zhongsheng; Gao, Lei; Gao, George F; Liu, Sidang; Sun, Lei; Liu, Wenjun


    H1N1 is the main subtype influenza A virus circulating in human and swine population, and has long been a threat to economy and public health. To explore the genetic correlation between current circulating H1N1 swine and human influenza viruses. Three new H1N1 swine influenza viruses (SIVs) were isolated and genomes sequencing were conducted followed by phylogenetic and molecular analysis of all swine and human H1N1 influenza viruses isolated in China in the past five years. Homology and phylogenetic analysis revealed that the three isolates possessed different characteristics: the genome of A/Swine/Shandong/1112/2008 was closely related to that of classical H1N1 SIV, while A/Swine/Shandong/1123/2008 was a reassortant with NS gene from the human-like H3N2 influenza virus and other genes from the classical H1N1 SIV, and A/Swine/Fujian/0325/2008 fell into a lineage of seasonal human H1N1 influenza viruses. Genetically, 2009 H1N1 influenza A viruses (2009 H1N1) in China were contiguous to the SIV lineages rather than the seasonal H1N1 human influenza virus's lineage. Furthermore, molecular analysis among human and swine influenza viruses provided more detail information for understanding their genetic correlation. These results suggested that in China in the past five years, the classical, avian-like and human-like H1N1 SIV existed in swine herds and the reassortment between H1N1 swine and H3N2 human influenza viruses was identified. In addition, the present data showed no evidence to support a strong correlation between the 2009 H1N1 and the swine influenza virus circulating in China. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Genome evolution of novel influenza A (H1N1)viruses in humans

    KOU Zheng; HU SongNian; LI TianXian


    The epidemic situation of A H1N1 flu arose in North America in April 2009,which rapidly expanded to three continents of Europe,Asia and Africa,with the risk ranking up to 5.Until May 13th,the flu virus of A H1N1 had spread into 33 countries and regions,with a laboratory confirmed case number of 5728,including 61 deaths.Based on IRV and EpiFluDB database,425 parts of A H1N1 flu virus sequence were achieved,followed by sequenced comparison and evolution analysis.The results showed that the current predominant A H1N1 flu virus was a kind of triple reassortment A flu virus:(i) HA,NA,MP,NP and NS originated from swine influenza virus;PB2 and PA originated from bird influenza virus;PB1 originated from human influenza virus.(ii) The origin of swine influenza virus could be subdivided as follows:HA,NP and NS originated from classic swine influenza virus of H1N1 subtype;NA and MP originated from bird origin swine influenza virus of H1N1 subtype.(iii) A H1N1 flu virus experienced no significant mutation during the epidemic spread,accompanied with no reassortment of the virus genome.In the paper,the region of the representative strains for sequence analysis (A/California/04/2009 (H1N1) and A/Mexico/4486/2009 (H1N1)) included USA and Mexico and was relatively wide,which suggested that the analysis results were convincing.

  4. A computational docking study on the pH dependence of peptide binding to HLA-B27 sub-types differentially associated with ankylosing spondylitis

    Serçinoğlu, Onur; Özcan, Gülin; Kabaş, Zeynep Kutlu; Ozbek, Pemra


    A single amino acid difference (Asp116His), having a key role in a pathogenesis pathway, distinguishes HLA-B*27:05 and HLA-B*27:09 sub-types as associated and non-associated with ankylosing spondylitis, respectively. In this study, molecular docking simulations were carried out with the aim of comprehending the differences in the binding behavior of both alleles at varying pH conditions. A library of modeled peptides was formed upon single point mutations aiming to address the effect of 20 naturally occurring amino acids at the binding core peptide positions. For both alleles, computational docking was applied using Autodock 4.2. Obtained free energies of binding (FEB) were compared within the peptide library and between the alleles at varying pH conditions. The amino acid preferences of each position were studied enlightening the role of each on binding. The preferred amino acids for each position of pVIPR were found to be harmonious with experimental studies. Our results indicate that, as the pH is lowered, the capacity of HLA-B*27:05 to bind peptides in the library is largely lost. Hydrogen bonding analysis suggests that the interaction between the main anchor positions of pVIPR and their respective binding pocket residues are affected from the pH the most, causing an overall shift in the FEB profiles.

  5. MAL2 and tumor protein D52 (TPD52 are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    Fanayan Susan


    Full Text Available Abstract Background The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52, which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Methods Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. Results MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p Conclusions MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

  6. Multiple H1-antihistamine-induced urticaria.

    Inomata, Naoko; Tatewaki, Satoko; Ikezawa, Zenro


    H(1)-antihistamines are widely used in the treatment of various allergic diseases. Particularly, a cornerstone of the management of chronic idiopathic urticaria is treatment with H(1)-antihistamines. However, a few cases of H(1)-antihistamine-induced urticaria have been reported. A 34-year-old woman presented with a 4-month history of recurrent urticaria, which was prominently exacerbated by the administration of H(1)-antihistamines. The patient consented to a provocation test of fexofenadine among drugs including cetirizine and hydroxyzine, which were suspected of inducing severe symptoms in episodes. One hour after challenge with 12 mg fexofenadine (one-fifth of the therapeutic dose), a urticarial reaction rapidly developed on nearly the entire body with remarkably increased levels of plasma histamine (190 nmol/L) and plasma leukotriene B4 (150 pg/mL). In challenge tests with other antihistamines, generalized urticaria occurred 5 and 1 h after intake of 10 mg loratadine and 10 mg bepotastine, respectively, whereas challenges with chlorpheniramine, mequitazine and azelastine were all negative. Skin prick tests with H(1)-antihistamines used in the challenges were all negative, indicating that the urticarial reactions after challenges with the causative drugs might not be immunoglobulin E-mediated. Among the causative drugs in our case, cetirizine and hydroxyzine are the piperazine derivatives, whereas fexofenadine, bepotastine, ebastine and loratadine are the piperidine derivatives. The chemical structures of both derivatives are very similar. Therefore, in this case, H(1)-antihistamine-induced urticaria may have been due to cross-reactivity between metabolites of these drugs, but not to drugs before metabolization. Hypersensitivity to H(1)-antihistamines should be considered when urticarial lesions worsen after H(1)-antihistamine treatment.

  7. Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression.

    Dlugolenski, Daniel; Jones, Les; Howerth, Elizabeth; Wentworth, David; Tompkins, S Mark; Tripp, Ralph A


    Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment

  8. Development and validation of a quantitative PCR assay using multiplexed hydrolysis probes for detection and quantification of Theileria orientalis isolates and differentiation of clinically relevant subtypes.

    Bogema, D R; Deutscher, A T; Fell, S; Collins, D; Eamens, G J; Jenkins, C


    Theileria orientalis is an emerging pathogen of cattle in Asia, Australia, and New Zealand. This organism is a vector-borne hemoprotozoan that causes clinical disease characterized by anemia, abortion, and death, as well as persistent subclinical infections. Molecular methods of diagnosis are preferred due to their sensitivity and utility in differentiating between pathogenic and apathogenic genotypes. Conventional PCR (cPCR) assays for T. orientalis detection and typing are laborious and do not provide an estimate of parasite load. Current real-time PCR assays cannot differentiate between clinically relevant and benign genotypes or are only semiquantitative without a defined clinical threshold. Here, we developed and validated a hydrolysis probe quantitative PCR (qPCR) assay which universally detects and quantifies T. orientalis and identifies the clinically associated Ikeda and Chitose genotypes (UIC assay). Comparison of the UIC assay results with previously validated universal and genotype-specific cPCR results demonstrated that qPCR detects and differentiates T. orientalis with high sensitivity and specificiy. Comparison of quantitative results based on percent parasitemia, determined via blood film analysis and packed cell volume (PCV) revealed significant positive and negative correlations, respectively. One-way analysis of variance (ANOVA) indicated that blood samples from animals with clinical signs of disease contained statistically higher concentrations of T. orientalis DNA than animals with subclinical infections. We propose clinical thresholds to assist in classifying high-, moderate-, and low-level infections and describe how parasite load and the presence of the Ikeda and Chitose genotypes relate to disease.

  9. Influenza A (H1N1) pneumonia: HRCT findings

    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Zanetti, Glaucia [Escola de Medicina de Petropolis, RJ (Brazil); Hochhegger, Bruno [Santa Casa de Misericordia de Porto Alegre, RS (Brazil)


    Objective: to describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. Methods: we retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. Results: the most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. Conclusions: the most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or cranio caudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms. (author)

  10. Cuba vs H1N1 Influenza

    Gail Reed


    Full Text Available El Comité Editorial de MediSur agradece a Gail Reed, editora de Medicc Review la autorización expresa, para reproducir el artículo titulado “Cuba vs H1N1 Influenza”. Este trabajo resume el esfuerzo realizado por todos los organismos en Cuba y en especial el Ministerio de Salud Pública en la lucha para disminuir los efectos de la influenza H1N1 en la población. El artículo original se puede encontrar en: Reed G. Faceoff: Cuba vs H1N1 Influenza. MEDICC Review. 2010; 12(1:6-12. Disponible en:

  11. Subtypes of irritable bowel syndrome in children and adolescents

    Pharmacologic treatments for irritable bowel syndrome (IBS) and medical management of symptoms are increasingly based on IBS subtype, so it is important to accurately differentiate patients. Few studies have classified subtypes of pediatric IBS, and conclusions have been challenged by methodologic l...

  12. Molecular characterization of an H1N2 swine influenza virus isolated in Miyazaki, Japan, in 2006.

    Saito, Takehiko; Suzuki, Hirofumi; Maeda, Koji; Inai, Koji; Takemae, Nobuhiro; Uchida, Yuko; Tsunemitsu, Hiroshi


    Swine influenza virus (SIV) was isolated from a farm in Miyazaki Prefecture in Japan in July 2006. An isolate was genetically subtyped as H1N2 and was designated A/swine/Miyazaki/1/2006 (H1N2). The nucleotide sequences of all eight viral RNA segments were determined, and then phylogenetic analysis was performed using the neighbor-joining method. All segments were shown to be closely related to those of Japanese SIV H1N2 isolates, which have been circulating since the 1980s. The results indicate the persistence of the SIV H1N2 subtype in the Japanese pig population for more than two decades and emphasize the importance of continuous surveillance for SIV.

  13. Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (Carassius auratus)

    Illing, Nicola; Troskie, Brigitte E.; Nahorniak, Carol S.; Janet P Hapgood; Peter, Richard E.; Millar, Robert P.


    In the goldfish (Carassius auratus) the two endogenous forms of gonadotropin-releasing hormone (GnRH), namely chicken GnRH II ([His5,Trp7,Tyr8]GnRH) and salmon GnRH ([Trp7,Leu8]GnRH), stimulate the release of both gonadotropins and growth hormone from the pituitary. This control is thought to occur by means of the stimulation of distinct GnRH receptors. These receptors can be distinguished on the basis of differential gonadotropin and growth hormone releasing activities of naturally occurring...

  14. Antiviral Prophylaxis and H1N1


    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  15. Cell Lines Expressing Nuclear and/or Mitochondrial RNAse H1 | NCI Technology Transfer Center | TTC

    The National Institute of Child Health & Human Development (NICHD), Program in Genomics of Differentiation, seeks interested parties to further co-develop small molecule inhibitors of RNase H1, especially in regards to genome instability, transcription, and translation.

  16. [Immune Protection against H9N2 Provided by H1N1 Pre-infection in Pigs].

    Wang, Jia; Wu, Maocai; Hong, Wenshan; Zheng, Zuoyi; Chen, Rirong


    To explore the impact of the history of infection by the influenza A virus subtype H1N1 on secondary infection by the influenza A virus subtype H9N2, pigs non-infected and pre-infected with H1N1 were inoculated with H9N2 in parallel to compare nasal shedding and seroconversion patterns. Unlike pigs without a background of H1N1 infection, nasal shedding was not detected in pigs pre-infected with H1N1. Both groups generated antibodies against H9N2. However, levels of H1N1 antibodies in pigs pre-infected with H1N1 increased quickly and dramatically after challenge with H9N2. Cross-reaction was not observed between H1N1 antibodies and H9N2 viruses. These findings suggest that circulation of the H1N1 virus might be a barrier to the introduction and transmission of the avian H9N2 virus, thereby delaying its adaptation in pigs.

  17. H1 histones: current perspectives and challenges.

    Harshman, Sean W; Young, Nicolas L; Parthun, Mark R; Freitas, Michael A


    H1 and related linker histones are important both for maintenance of higher-order chromatin structure and for the regulation of gene expression. The biology of the linker histones is complex, as they are evolutionarily variable, exist in multiple isoforms and undergo a large variety of posttranslational modifications in their long, unstructured, NH2- and COOH-terminal tails. We review recent progress in understanding the structure, genetics and posttranslational modifications of linker histones, with an emphasis on the dynamic interactions of these proteins with DNA and transcriptional regulators. We also discuss various experimental challenges to the study of H1 and related proteins, including limitations of immunological reagents and practical difficulties in the analysis of posttranslational modifications by mass spectrometry.

  18. [The Spanish adapted version of the Children's Communication Checklist identifies disorders of pragmatic use of language and differentiates between clinical subtypes].

    Crespo-Eguilaz, N; Magallon, S; Sanchez-Carpintero, R; Narbona, J


    The Children's Communication Checklist (CCC) by Bishop is a useful scale for evaluation of pragmatic verbal abilities in school children. The aim of the study is to ascertain the validity and reliability of the CCC in Spanish. Answers to the CCC items by parents of 360 children with normal intelligence were analyzed. There were five groups: 160 control children; 68 children with attention deficit hyperactivity disorder, 77 with procedural non-verbal disorder, 25 children with social communication disorder and 30 with autism spectrum disorder. Investigations included: factorial analysis in order to cluster checklist items, reliability analyses of the proposed scales and discriminant analysis to check whether the scale correctly classifies children with pragmatic verbal abilities. Seven factors were obtained (Kaiser-Meyer-Olkin: 0.852) with moderate similarity with those of the original scale: social relationships, interests, and five more that can be grouped into pragmatic verbal ability (conversational abilities, coherence-comprehension, empathy nonverbal communication and appropriateness). All factors are significantly correlated with each other in the control group, and the five that compose pragmatic verbal ability correlate with each other in the clinical groups (Pearson r). The scales have good reliability (Cronbach's alpha: 0.914). The questionnaire correctly classifies 98.9% of grouped cases with and without pragmatic disorder and 78% of subjects in their appropriate clinical group. Besides, the questionnaire allows to differentiate the pathologies according to the presence and intensity of the symptoms. This Spanish version of the CCC is highly valid and reliable. The proposed statistics can be used as normative-reference values.

  19. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland

    Laura McDonald


    Full Text Available RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER/progesterone receptor (PR/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer.

  20. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland.

    McDonald, Laura; Ferrari, Nicola; Terry, Anne; Bell, Margaret; Mohammed, Zahra M; Orange, Clare; Jenkins, Alma; Muller, William J; Gusterson, Barry A; Neil, James C; Edwards, Joanne; Morris, Joanna S; Cameron, Ewan R; Blyth, Karen


    RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER)/progesterone receptor (PR)/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV) promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer.

  1. Subtyping Stuttering II

    Seery, Carol Hubbard; Watkins, Ruth V.; Mangelsdorf, Sarah C.; Shigeto, Aya


    This paper is the second in a series of two articles exploring subtypes of stuttering, and it addresses the question of whether and how language ability and temperament variables may be relevant to the study of subtypes within the larger population of children who stutter. Despite observations of varied profiles among young children who stutter, efforts to identify and characterize subtypes of stuttering have had limited influence on theoretical or clinical understanding of the disorder. This manuscript briefly highlights research on language and temperament in young children who stutter, and considers whether the results can provide guidance for efforts to more effectively investigate and elucidate subtypes in childhood stuttering. Issues from the literature that appear relevant to research on stuttering subtypes include: (a) the question of whether stuttering is best characterized as categorical or continuous; (b) interpretation of individual differences in skills and profiles; and (c) the fact that, during the preschool years, the interaction among domains such as language and temperament are changing very rapidly, resulting in large differences in developmental profiles within relatively brief chronological age periods. PMID:17825669

  2. Una ecuación diferencial para el cálculo de las funciones de Jost para potenciales regulares Aplicación al sistema e‾+ H(1s A differential equation for the calculation of the functions de jost for regular potentials Application to the system e

    Héctor Maya Taboada


    matrix S. In most of the existent methods in theory of collisions for the calculation of the function Fl first is necessary to know the regular solution of the treated system, which is obtained of the solution of the radial equation of Schrodinger, to be able to find the function Fl later. With the methodology proposed in this work an ordinary lineal differential equation of second order it is obtained whose solution in the asymptotic boundary coincides with the function Fl. The advantage of the present work is that solving the differential equation mentioned before one can obtain in a direct way the function Fl without having to find the regular solution of the problem. Another advantage is that not caring the initial conditions (real that are chosen for the solution of the differential equation, the same elements of the matrix S, are always obtained. As an example and test of the methodology, it is solved this differential equation numerically for the elastic scattering of electrons by hydrogen atoms in the ground state to low energy (e− + H(1s, obtaining for this system the function Fl, the elements of the matrix S and the phase shifts. The data obtained for the phase shifts are compared with the calculated by Klaus Bartschat.

  3. Seroepidemiologic Investigation of an Outbreak of Pandemic Influenza A H1N1 2009 Aboard a U.S. Navy Vessel - San Diego, 2009


    Naval Health Research Center Seroepidemiologic Investigation of An Outbreak of Pandemic Influenza A H1N1 2009 Aboard A US Navy Vessell – San...Journal Article 3. DATES COVERED (from – to) 2009 4. TITLE Seroepidemiologic Investigation of an Outbreak of Pandemic Influenza A H1N1 2009...outbreaks. 15. SUBJECT TERMS Adolescent; adult; Disease Outbreaks; H1N1 Subtype/genetics; epidemiology; Influenza A Virus; military personnel 16

  4. T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

    Campo, Joseph J.; Cicéron, Micheline; Raccurt, Christian P.; Beau De Rochars, Valery E. M.


    Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects. Plasma samples were analyzed with a P. falciparum protein microarray, which demonstrated serologic reactivity to 3,877 P. falciparum proteins of known serologic reactivity; however, no antigen-antibody reactions delineating asymptomatics from symptomatics were identified. In contrast, differences in cellular responses were observed. Flow cytometric analysis of patient peripheral blood mononuclear cells co-cultured with P. falciparum infected erythrocytes demonstrated a statistically significant increase in the proportion of T regulatory cells (CD4+ CD25+ CD127-), and increases in unique populations of both NKT-like cells (CD3+ CD8+ CD56+) and CD8mid T cells in asymptomatics compared to symptomatics. Also, CD38+/HLA-DR+ expression on γδ T cells, CD8mid (CD56-) T cells, and CD8mid CD56+ NKT-like cells decreased upon exposure to infected erythrocytes in both groups. Cytometric bead analysis of the co-culture supernatants demonstrated an upregulation of monocyte-activating chemokines/cytokines in asymptomatics, while immunomodulatory soluble factors were elevated in symptomatics. Principal component analysis of these expression values revealed a distinct clustering of individual responses within their respective phenotypic groups. This is the first comprehensive investigation of immune responses to P. falciparum in Haiti, and describes unique cell-mediated immune repertoires that delineate individuals

  5. Mitochondrial haplogroup H1 in north Africa: an early holocene arrival from Iberia.

    Claudio Ottoni

    Full Text Available The Tuareg of the Fezzan region (Libya are characterized by an extremely high frequency (61% of haplogroup H1, a mitochondrial DNA (mtDNA haplogroup that is common in all Western European populations. To define how and when H1 spread from Europe to North Africa up to the Central Sahara, in Fezzan, we investigated the complete mitochondrial genomes of eleven Libyan Tuareg belonging to H1. Coalescence time estimates suggest an arrival of the European H1 mtDNAs at about 8,000-9,000 years ago, while phylogenetic analyses reveal three novel H1 branches, termed H1v, H1w and H1x, which appear to be specific for North African populations, but whose frequencies can be extremely different even in relatively close Tuareg villages. Overall, these findings support the scenario of an arrival of haplogroup H1 in North Africa from Iberia at the beginning of the Holocene, as a consequence of the improvement in climate conditions after the Younger Dryas cold snap, followed by in situ formation of local H1 sub-haplogroups. This process of autochthonous differentiation continues in the Libyan Tuareg who, probably due to isolation and recent founder events, are characterized by village-specific maternal mtDNA lineages.

  6. Review to better understand the macroscopic subtypes and histogenesis of intrahepatic cholangiocarcinoma

    Yuichi; Sanada; Yujo; Kawashita; Satomi; Okada; Takashi; Azuma; Shigetoshi; Matsuo


    Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma(ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.


    M N Slarovoitova


    Full Text Available Aim: to allot clinical forms of juvenile systemic scleroderma (JSSD. Material and methods: investigation and dynamic observation of 60 patients aged 14-54 (mean age 25.1 ±7.2 with onset of disease in child's and adolescent’s ages from 1 to 16 years old ( in average 11. 4±3.8 year old and disease duration from 1 to 39 years (in average 13.1 ±7.9. Results: 55% of patients demonstrated JSSD subtype with focal cutaneous lesion of different localization. The possibility of overlap-syndrome development in JSSD patients with onset in adolescent age typical for SSD-rheumatoid arthritis, SSD-polymvositis should be underlined. Conclusion: knowledge of different clinical forms and courses of the disease, modern diagnostics and early beginning of differential JSSD treatment will enable us to improve the prognosis and disease outcome.

  8. Influenza Stigma during the 2009 H1N1 Pandemic.

    Earnshaw, Valerie A; Quinn, Diane M


    The current study examines the extent to which H1N1 was stigmatized at the height of the 2009 H1N1 pandemic in the U.S. and explores the role that H1N1 stigma played in people's desire for physical distance from others with H1N1. H1N1 was the most stigmatized disease, with participants endorsing greater prejudice towards people with H1N1 than people with cancer or HIV/AIDS. Further, H1N1 stigma partially mediated the relationship between participants' perceptions that H1N1 was threatening and their desire for physical distance from people with H1N1. Therefore, H1N1 stigma played a role in, but was not entirely responsible for, the relationship between perceptions that H1N1 was threatening and desire for distance from others with H1N1.

  9. Pathological Gambling Subtypes

    Vachon, David D.; Bagby, R. Michael


    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  10. Clinical value of posture test in subtype differentiation of primary aldosteronism%体位试验对鉴别原发性醛固酮增多症分型的价值

    邢玉微; 邹俊杰; 石勇铨; 刘志民


    Objective To evaluate the value of posture test in the subtype differentiation of primary aldosteronism.Methods In total,91 patients with primary aldosteronism were divided into the aldosterone-producing adenoma (n =43)and idiopathic hyperaldosteronism groups (IHA,n =48).General characteris-tics,renin activity and aldosterone changes after posture test were statistically compared between two groups.Results Age,gender constitution,systolic and diastolic pressure and plasma potassium did not significantly differ between two groups (all P >0.05).Compared with IHA group,renin activity was significantly lower whereas aldosterone changes and the ratio of aldosterone /renin activity were significantly higher after saline ad-ministration in the aldosterone-producing adenoma group (all P 30% eleva-tion.In the IHA group,aldosterone level in a standing posture was elevated compared with that in a lying pos-ture including 8 cases with 30% elevation.The percentage of patients with 0.05).Conclusions Posture test contributes to directly identif-ying the aldosterone-producing adenoma with decreasing aldosterone level in a standing posture.For those with elevated aldosterone level after a standing posture,comprehensive tests are required to differentiate the subtype of primary aldosteronism.%目的:探讨体位试验对鉴别原发性醛固酮增多症分型的价值。方法将91例原发性醛固酮增多症患者分为醛固酮瘤组(43例)及特发性醛固酮增多症(IHA)组(48例),比较2组的一般特征及体位试验后肾素活性、醛固酮的变化特点。结果2组的年龄、性别构成比、收缩压、舒张压、血钾比较差异无统计学意义(P 均>0.05),醛固酮瘤组滴注生理盐水后肾素活性低于 IHA组,而滴注生理盐水后血浆醛固酮及醛固酮与肾素活性比值均高于 IHA 组(P 均<0.05)。体位试验显示醛固酮瘤组患者立位血浆醛固酮较卧位下降的有19例,升高的有24

  11. Effects of histone deacetylase inhibitor trichostatin A on proliferation and adipogenic differentiation of C3H1OT1/2 mesenchymal stem cells%去乙酰化酶抑制剂TSA对间充质干细胞C3H10T1/2增殖和成脂分化的影响

    吴伟; 季菊玲; 王奎标; 李智耀; 龚雨琴; 季煜华


    采用MTT和流式细胞术分别检测不同浓度的TSA对C3H10T1/2细胞活性和细胞周期分布的影响;油红O染色检测TSA对其成脂分化的影响,实时定量PCR检测TSA对成脂分化的关键转录因子PPAR-γ,以及成脂分化标志物Fabp4和Adipoq mRNA转录的影响.研究去乙酰化酶抑制剂TSA对间充质干细胞C3H1OT1/2增殖和成脂分化的影响及其可能的作用机制.结果显示TSA浓度为1、10和30 nmol/L呈浓度依赖性地抑制C3H10T1/2细胞活性,改变细胞形态,并将其细胞周期抑制在G0/G1期;TSA浓度为10nmol/L明显抑制C3H10T1/2细胞的成脂分化作用,并呈浓度依赖性地抑制PPAR-γ、Fabp4和Adipoq mRNA的转录.表明TSA呈剂量依赖性地抑制间充质干细胞C3H10T1/2的增殖和成脂分化,除转录水平调控外,非组蛋白如细胞骨架相关蛋白可能也参与TSA的抑制作用.%To investigate the effects of histone deactylase (HDA) inhibitor trichostatin A on proliferation and adipogenic differentiation of C3H10T1/2 mesenchymal stem cells as well as the underlying mechanism.MTT assay and flow cytometry-based cell cycle analysis were used to evaluate the effects of trichostatin (TSA) at different concentrations on cell viability and cell cycle of cultured C3H10T1/2 cells.The influence of serial concentrations of TSA on adipogenic differentiation of C3H10T1/2 cells was determined by oil red O staining.The effects of TSA on the expression of PPAR-γ, a key adipogenic transcription factor, and the Fabp4 and Adipoq, the two adipogenic differentiation markers, were determined by realtime PCR.Our results showed that the TSA inhibited the proliferation of C3H10T1/2 cells in a dose-dependent manner and the cell cycle of C3H10T1/2 cells was arrested at G0/G1 phase.Moreover, the morphology of C3H10T1/2 cells was found to be flattened by treatment with TSA.The adipogenic differentiation of C3H10T1/2 cells and the expression of PPAR-γ, Fabp4 and Adipoq were suppressed by TSA in a

  12. Antifungal properties of wheat histones (H1-H4) and purified wheat histone H1.

    De Lucca, Anthony J; Heden, Lars-Olof; Ingber, Bruce; Bhatnagar, Deepak


    Wheat ( Triticum spp.) histones H1, H2, H3, and H4 were extracted, and H1 was further purified. The effect of these histones on specific fungi that may or may not be pathogenic to wheat was determined. These fungi included Aspergillus flavus , Aspergillus fumigatus , Aspergillus niger , Fusarium oxysporum , Fusarium verticillioides , Fusarium solani , Fusarium graminearum , Penicillium digitatum , Penicillium italicum , and Greeneria uvicola . Non-germinated and germinating conidia of these fungi were bioassayed separately. The non-germinated and germinating conidia of all Fusarium species were highly susceptible to the mixture (H1-H4) as well as pure H1, with viability losses of 99-100% found to be significant (p histone mixture and pure H1. F. graminearum was the most sensitive to histone activity. The histones were inactive against all of the non-germinated Penicillium spp. conidia. However, they significantly reduced the viability of the germinating conidia of the Penicillium spp. conidia, with 95% loss at 2.5 μM. Non-germinated and germinating conidia viability of the Aspergillus spp. and G. uvicola were unaffected when exposed to histones up to 10 μM. Results indicate that Fusarium spp. pathogenic to wheat are susceptible to wheat histones, indicating that these proteins may be a resistance mechanism in wheat against fungal infection.

  13. Phylogenetic analysis of surface proteins of novel H1N1 virus isolated from 2009 pandemic.

    Danishuddin, Mohd; Khan, Shahper N; Khan, Asad U


    Swine Influenza Virus (H1N1) is a known causative agent of swine flu. Transmission of Swine Influenza Virus form pig to human is not a common event and may not always cause human influenza. The 2009 outbreak by subtype H1N1 in humans is due to transfer of Swine Influenza Virus from pig to human. Thus to analyze the origin of this novel virus we compared two surface proteins (HA and NA) with influenza viruses of swine, avian and humans isolates recovered from 1918 to 2008 outbreaks. Phylogenetic analyses of hemagglutinin gene from 2009 pandemic found to be clustered with swine influenza virus (H1N2) circulated in U.S.A during the 1999-2004 outbreaks. Whereas, neuraminidase gene was clustered with H1N1 strains isolated from Europe and Asia during 1992-2007 outbreaks. This study concludes that the new H1N1 strain appeared in 2009 outbreak with high pathogenicity to human was originated as result of re-assortment (exchange of gene). Moreover, our data also suggest that the virus will remain sensitive to the pre-existing therapeutic strategies.

  14. Cardiac potassium channel subtypes

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter


    that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure......About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...

  15. Antibody titers against swine influenza subtypes determined by the hemagglutination inhibition test are highly dependent on the strain

    Trebbien, Ramona; Nielsen, Jens; Bøtner, Anette

    In Denmark there are three circulating strains of swine influenza H1N1, H1N2 and H3N2. The H1N2 is different from the H1N2 subtypes circulating in other European countries. The Danish subtype is a reassortment between the two Danish circulating swine influenza subtypes H1N1 and H3N2. From...... a diagnostic and epidemiological point of view it is crucial to clarify whether the immunological response to one subtype protects against infection with the other subtype. The hemagglutination inhibition test (HI-test) has been used widely to determine the presence of antibodies in serum against influenza...... viruses. In the present study the HI-test was used to determine antibody response from experimental infected pigs. The aim of the study was to evaluate the antibody response against the new Danish influenza subtype H1N2 (H1N2dk) and to examine the level of crossprotection/reaction between the two...

  16. Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus.

    Guo, Chun-yan; Tang, Yi-gui; Qi, Zong-li; Liu, Yang; Zhao, Xiang-rong; Huo, Xue-ping; Li, Yan; Feng, Qing; Zhao, Peng-hua; Wang, Xin; Li, Yuan; Wang, Hai-fang; Hu, Jun; Zhang, Xin-jian


    To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines.

  17. 2009 H1N1 Influenza 2009 H1N1 Influenza

    Seth J. Sullivan, MD; Robert M. Jacobson, MD; Walter R. Dowdle, PhD; and Gregory A. Poland


    Full Text Available Within 2 months of its discovery last spring, a novel influenza A (H1N1 virus, currently referred to as 2009 H1N1, caused the first influenza pandemic in decades. The virus has caused disproportionate disease among young people with early reports of virulence similar to that of seasonal influenza. This clinical review provides an update encompassing the virology, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the 2009 H1N1 virus. Because information about this virus, its prevention,and treatment are rapidly evolving, readers are advised to seek additional information. We performed a literature search of PubMed using the following keywords: H1N1, influenza, vaccine, pregnancy, children, treatment, epidemiology, and review. Studies were selected for inclusion in this review on the basis of their relevance. Recent studies and articles were preferred.

    El Editor de este número especial agradece la autorización expresa, mediante comunicación escrita en nuestro poder, de los autores del trabajo “2009 H1N1 Influenza”, así como de los editores de la revista Mayo Clinic Proceedings, para su reproducción, como publicación secundaria en Medisur, artículo de revisión seleccionado por nosotros, que resume buena parte de los nuevos conocimientos adquiridos a partir de la literatura médica reciente relacionada con esta pandemia, durante el año 2009.

    De este modo, el artículo que a continuación de reproduce para los lectores de Medisur, está basado íntegramente en el estudio previamente publicado como: Sullivan SJ, Jacobson RM, Dowdle WR, Poland GA. 2009 H1N1 Influenza. Mayo Clin Proc. 2010;85(1:64-76.

    A continuación el resumen:

    Within 2 months of its discovery last spring, a novel influenza A (H1N1 virus, currently referred to as 2009 H1N1, caused the first influenza pandemic in decades. The virus has caused disproportionate disease among young people with early reports of virulence similar

  18. H1-antihistamines for chronic spontaneous urticaria.

    Sharma, Maulina; Bennett, Cathy; Cohen, Stuart N; Carter, Ben


    Background Chronic spontaneous urticaria (CSU) is characterised by the development of crops of red, itchy, raised weals or hives with no identifiable external cause.Objectives To assess the effects of H1-antihistamines for CSU.Search methods We searched the following databases up to June 2014: Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE(from 1946), EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers and checked articles for references to relevant randomised controlled trials.Selection criteria We included randomised controlled trials of H1-antihistamines for CSU. Interventions included single therapy or a combination of H1-antihistamines compared with no treatment (placebo) or another active pharmacological compound at any dose.Data collection and analysis We used standard methodological procedures as expected by The Cochrane Collaboration.Our primary outcome measures were proportion of participants with complete suppression of urticaria: 'good or excellent' response,50% or greater improvement in quality of life measures, and adverse events.We present risk ratios (RR) with 95% confidence intervals(CIs). Main results We identified 73 studies (9759 participants); 34 studies provided data for 23 comparisons. The duration of the intervention was up to two weeks (short-term) or longer than two weeks and up to three months (intermediate-term).Cetirizine 10mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this same outcome, comparison of desloratadine versus placebo in the intermediate term (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97, 95% CI 1.04 to 245.04)favoured desloratadine, but no differences were seen between 5 mg and 10 mg for short-term treatment.Levocetirizine 20 mg per day (short-term) was more effective for complete suppression of

  19. Factors associated with vaccination against Influenza A (H1N1 in the elderly

    Janaína Fonseca Victor


    Full Text Available This study aimed to investigate the sociodemographic, clinical and behavioral factors and receiving information about the vaccine against pandemic influenza A (H1N1 associated with vaccination of elderly people. Study of quantitative and transversal nature, in which 286 elderly residents in Fortaleza, CE, Brazil participated. The association between variables was analyzed by the Pearson chi-square test, considering a 95% confidence interval and significance level (p≤0.05. The results revealed that, unlike the sociodemographic characteristics, many clinical, behavioral and informational aspects correlated significantly with adherence to Influenza A (H1N1 vaccination. It is believed that the findings can be used in strategies to control and prevent infection by viral subtypes within the elderly population, extensible even to other vaccine-preventable diseases, especially in light of possible future pandemics.

  20. Possible basis for the emergence of H1N1 viruses with pandemic potential from avian hosts.

    Koçer, Zeynep A; Krauss, Scott; Zanin, Mark; Danner, Angela; Gulati, Shelly; Jones, Jeremy C; Friedman, Kimberly; Graham, Allison; Forrest, Heather; Seiler, Jon; Air, Gillian M; Webster, Robert G


    Influenza A viruses of the H1N1 subtype have emerged from the avian influenza gene pool in aquatic birds and caused human pandemics at least twice during the past century. Despite this fact, surprisingly little is known about the H1N1 gene pool in the aquatic bird reservoir. A preliminary study showed that an H1N1 virus from a shorebird of the Charadriiformes order was transmitted between animals through the airborne route of infection, whereas an H1N1 virus from a bird of the Anseriformes order was not. Here we show that two of the three H1N1 viruses isolated from Charadriiformes species in 2009 were transmitted between animals through the airborne route of infection, and five H1N1 isolates from Anseriformes species were not. The one H1N1 virus from a Charadriiformes species that failed to transmit through the airborne route was a reassortant possessing multiple internal gene segments from Anseriformes species. The molecular differences between the airborne-transmissible and non-airborne-transmissible H1N1 viruses were multigenic, involving the selection of virus with human-like receptor-binding specificity (α2-6 sialic acid) and multiple differences in the polymerase complex, mainly in the PB2, PB1-F2, and nonstructural genes.

  1. Crystalline 1H-1,2,3-triazol-5-ylidenes

    Bertrand, Guy; Gulsado-Barrios, Gregorio; Bouffard, Jean; Donnadieu, Bruno


    The present invention provides novel and stable crystalline 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of making 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of using 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes in catalytic reactions.

  2. HIV-1 subtypes in Yugoslavia.

    Stanojevic, Maja; Papa, Anna; Papadimitriou, Evagelia; Zerjav, Sonja; Jevtovic, Djordje; Salemovic, Dubravka; Jovanovic, Tanja; Antoniadis, Antonis


    To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.

  3. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan


    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza.

  4. The hemagglutinin structure of an avian H1N1 influenza A virus

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang; Zhang, Qian; Wu, Caiming; Zhang, Rongfu; Cai, Qixu; Song, Wenjun; Yuen, Kwok-Yung; (U. Hong Kong); (Inter. Inst. Infect. Imm.); (Xiamen)


    The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptor binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.

  5. Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site

    Narayanan MM


    Full Text Available Manoj M Narayanan,1,2 Chandrasekhar B Nair,2 Shilpa K Sanjeeva,2 PV Subba Rao,2 Phani K Pullela,1,2 Colin J Barrow11Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia; 2Bigtec Pvt Ltd, Rajajinagar, Bangalore, IndiaAbstract: Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1. The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present.Keywords: neuraminidase, influenza, H1N1, multiligand, binding energy, molecular docking, virus

  6. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination.

    Partinen, Markku; Kornum, Birgitte Rahbek; Plazzi, Giuseppe; Jennum, Poul; Julkunen, Ilkka; Vaarala, Outi


    Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger.

  7. Subtyping Obsessive-Compulsive Disorder: Neuropsychological Correlates

    Catherine L. Harris


    Full Text Available We administered neuropsychological measures considered sensitive to prefrontal dysfunction (both orbitofrontal and dorsolateral prefrontal neocortex to obsessive-compulsive disorder (OCD patients and control subjects. OCD subjects exhibited performance deficits, in comparison to community controls, on three measures sensitive to orbitofrontal neocortex dysfunction. Contrary to expectation, OCD patients also exhibited performance deficits on measures sensitive to dorsolateral prefrontal neocortex dysfunction. However, distinct neurocognitive profiles emerged when we examined the impact of comorbid schizotypal personality features on neuropsychological test performance. Primary OCD patients displayed impaired performance on measures sensitive to orbitofrontal dysfunction; however, they did not differ from control subjects on tests of dorsolateral function. OCD subjects presenting with schizotypal personality features performed poorly not only on tests sensitive to orbitofrontal dysfunction, but also on tests sensitive to dorsolateral dysfunction. Findings suggest that OCD can be subdivided into clinical subtypes, and distinct prefrontal subsystems may be differentially involved in these subtypes.

  8. Effect of the novel influenza A (H1N1 virus in the human immune system.

    Evangelos J Giamarellos-Bourboulis

    Full Text Available BACKGROUND: The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. METHODOLOGY/PRINCIPAL FINDINGS: Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL-1beta, IL-6, IL-18, interferon (FN-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs. CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

  9. Comparative biochemical analysis of recombinant reverse transcriptase enzymes of HIV-1 subtype B and subtype C

    Moisi Daniella


    Full Text Available Abstract Background HIV-1 subtype C infections account for over half of global HIV infections, yet the vast focus of HIV-1 research has been on subtype B viruses which represent less than 12% of the global pandemic. Since HIV-1 reverse transcriptase (RT is a major target of antiviral therapy, and since differential drug resistance pathways have been observed among different HIV subtypes, it is important to study and compare the enzymatic activities of HIV-1 RT derived from each of subtypes B and C as well as to determine the susceptibilities of these enzymes to various RT inhibitors in biochemical assays. Methods Recombinant subtype B and C HIV-1 RTs in heterodimeric form were purified from Escherichia coli and enzyme activities were compared in cell-free assays. The efficiency of (- ssDNA synthesis was measured using gel-based assays with HIV-1 PBS RNA template and tRNA3Lys as primer. Processivity was assayed under single-cycle conditions using both homopolymeric and heteropolymeric RNA templates. Intrinsic RNase H activity was compared using 5'-end labeled RNA template annealed to 3'-end recessed DNA primer in a time course study in the presence and absence of a heparin trap. A mis-incorporation assay was used to assess the fidelity of the two RT enzymes. Drug susceptibility assays were performed both in cell-free assays using recombinant enzymes and in cell culture phenotyping assays. Results The comparative biochemical analyses of recombinant subtype B and subtype C HIV-1 reverse transcriptase indicate that the two enzymes are very similar biochemically in efficiency of tRNA-primed (- ssDNA synthesis, processivity, fidelity and RNase H activity, and that both enzymes show similar susceptibilities to commonly used NRTIs and NNRTIs. Cell culture phenotyping assays confirmed these results. Conclusions Overall enzyme activity and drug susceptibility of HIV-1 subtype C RT are comparable to those of subtype B RT. The use of RT inhibitors (RTIs

  10. Analysis list: Suv39h1 [Chip-atlas[Archive

    Full Text Available Suv39h1 Pluripotent stem cell + mm9

  11. Fine mapping of posttranslational modifications of the linker histone H1 from Drosophila melanogaster.

    Ana Villar-Garea

    Full Text Available The linker histone H1 binds to the DNA in between adjacent nucleosomes and contributes to chromatin organization and transcriptional control. It is known that H1 carries diverse posttranslational modifications (PTMs, including phosphorylation, lysine methylation and ADP-ribosylation. Their biological functions, however, remain largely unclear. This is in part due to the fact that most of the studies have been performed in organisms that have several H1 variants, which complicates the analyses. We have chosen Drosophila melanogaster, a model organism, which has a single H1 variant, to approach the study of the role of H1 PTMs during embryonic development. Mass spectrometry mapping of the entire sequence of the protein showed phosphorylation only in the ten N-terminal amino acids, mostly at S10. For the first time, changes in the PTMs of a linker H1 during the development of a multicellular organism are reported. The abundance of H1 monophosphorylated at S10 decreases as the embryos age, which suggests that this PTM is related to cell cycle progression and/or cell differentiation. Additionally, we have found a polymorphism in the protein sequence that can be mistaken with lysine methylation if the analysis is not rigorous.

  12. 2009 H1N1 Flu Vaccine Facts

    ... please turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of Contents ... the H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials conducted ...

  13. Histone H1 Limits DNA Methylation in Neurospora crassa.

    Seymour, Michael; Ji, Lexiang; Santos, Alex M; Kamei, Masayuki; Sasaki, Takahiko; Basenko, Evelina Y; Schmitz, Robert J; Zhang, Xiaoyu; Lewis, Zachary A


    Histone H1 variants, known as linker histones, are essential chromatin components in higher eukaryotes, yet compared to the core histones relatively little is known about their in vivo functions. The filamentous fungus Neurospora crassa encodes a single H1 protein that is not essential for viability. To investigate the role of N. crassa H1, we constructed a functional FLAG-tagged H1 fusion protein and performed genomic and molecular analyses. Cell fractionation experiments showed that H1-3XFLAG is a chromatin binding protein. Chromatin-immunoprecipitation combined with sequencing (ChIP-seq) revealed that H1-3XFLAG is globally enriched throughout the genome with a subtle preference for promoters of expressed genes. In mammals, the stoichiometry of H1 impacts nucleosome repeat length. To determine if H1 impacts nucleosome occupancy or nucleosome positioning in N. crassa, we performed micrococcal nuclease digestion in the wild-type and the [Formula: see text]hH1 strain followed by sequencing (MNase-seq). Deletion of hH1 did not significantly impact nucleosome positioning or nucleosome occupancy. Analysis of DNA methylation by whole-genome bisulfite sequencing (MethylC-seq) revealed a modest but global increase in DNA methylation in the [Formula: see text]hH1 mutant. Together, these data suggest that H1 acts as a nonspecific chromatin binding protein that can limit accessibility of the DNA methylation machinery in N. crassa.

  14. Histone H1 Limits DNA Methylation in Neurospora crassa

    Michael Seymour


    Full Text Available Histone H1 variants, known as linker histones, are essential chromatin components in higher eukaryotes, yet compared to the core histones relatively little is known about their in vivo functions. The filamentous fungus Neurospora crassa encodes a single H1 protein that is not essential for viability. To investigate the role of N. crassa H1, we constructed a functional FLAG-tagged H1 fusion protein and performed genomic and molecular analyses. Cell fractionation experiments showed that H1-3XFLAG is a chromatin binding protein. Chromatin-immunoprecipitation combined with sequencing (ChIP-seq revealed that H1-3XFLAG is globally enriched throughout the genome with a subtle preference for promoters of expressed genes. In mammals, the stoichiometry of H1 impacts nucleosome repeat length. To determine if H1 impacts nucleosome occupancy or nucleosome positioning in N. crassa, we performed micrococcal nuclease digestion in the wild-type and the ΔhH1 strain followed by sequencing (MNase-seq. Deletion of hH1 did not significantly impact nucleosome positioning or nucleosome occupancy. Analysis of DNA methylation by whole-genome bisulfite sequencing (MethylC-seq revealed a modest but global increase in DNA methylation in the ΔhH1 mutant. Together, these data suggest that H1 acts as a nonspecific chromatin binding protein that can limit accessibility of the DNA methylation machinery in N. crassa.

  15. Detection of Seasonal Influenza H1N1 and H3N2 Viruses using RT-PCR Assay during 2009 Pandemic Influenza in Golestan Province

    Zhand, S. (MSc


    Full Text Available Background and Objective: The emergence of a novel H1N1influenza A virus of animal origin with transmissibility from human to human poses pandemic concern. Current subtypes of Seasonal influenza A viruses spread in human are influenza A H1N1 influenza A H3N2 and influenza type B viruses. The aim of this study was to determine current strains of the H3N2 and new H1N1 subtypes of influenza A virus from patients suspected influenza infection in 2009 flu pandemic in Golestan province, Iran. Material and Methods: In this descriptive study, respiratory samples (n = 153 from patients with acute respiratory symptoms were collected in 2009 flu pandemic applied during 2009 pandemic influenza in Golestan province. After reverse transcription of extracted viral RNA, PCR was developed for both H1N1and H3N2subtypes using CDC specific primers. Results: The mean age of patients was 16.59. Of them 45.1% were male. Thirteen (8.49% were infected with seasonal influenza H1N1 and 25(16.33% with seasonal H3N2influenza. Conclusion: The rate of infection with seasonal H1N1and H3N2is similar to other studies reported from Iran, but lower than the rate reported from other parts of the world

  16. Sequence Characterization of matrix protein (M1 in influenza A viruses (H1, H3 and H5

    Jun Zhang


    Full Text Available This study brings the analysis of amino acid sequences of matrix protein (M1 from the influenza virus A (H1N1, H3N2 and H5N1 during 2007-2208. 741 sequences of M1 were compared, of them, H1N1 388; H3N2 251 and H5N1 102. Even though, the M1 is relatively conserved among the influenza A viruses, we found some variations in the M1 among the viruses, H1N1, H3N2 and H5N1. The nuclear localization signal at amino acid 101 to 105 is RKLKR for H1N1 and H3N2, but for H5N1 is KKLKR. All differences of amino acid in M1 of H1, H3 and H5 were listed. 80 sequences of M1 of H1N1 H3N2 and H5N1 were used for phylogenetic analysis. There is no reasontantment found in the M1 among these subtypes. Further study is needed to study the differences of the function of M1 among H1N1, H3N2 and H5N1. The M1 of H5N1 may contribute to the high pathogenesis to this virus.

  17. Subtyping Animal Influenza Virus with General Multiplex RT-PCR and Liquichip High Throughput (GMPLex)

    Zhi-feng Qin; Bing Cheng; Zhou-xi Ruan; Ying-zuo Bi; Joseph J Giambrone; Hong-zhuan Wu; Jie Sun; Ti-kang Lu; Shao-ling Zeng; Qun-yi Hua; Qing-yan Ling; Shu-kun Chen; Jian-qiang Lv; Cai-hong Zhang


    This study developed a multiplex RT-PCR integrated with luminex technology to rapidly subtype simultaneously multiple influenza viruses.Primers and probes were designed to amplify NS and M genes of influenza A viruses HA gene of H1,H3,H5,H7,H9 subtypes,and NA gene of the N1 and N2 subtypes.Universal super primers were introduced to establish a multiplex RT-PCR (GM RT-PCR).It included three stages of RT-PCR amplification,and then the RT-PCR products were further tested by LiquiChip probe,combined to give an influenza virus (Ⅳ) rapid high throughput subtyping test,designated as GMPLex.The IV GMPLex rapid high throughput subtyping test presents the following features:high throughput,able to determine the subtypes of 9 target genes in H1,H3,H5,H7,H9,N1,and N2 subtypes of the influenza A virus at one time; rapid,completing the influenza subtyping within 6 hours; high specificity,ensured the specificity of the different subtypes by using two nested degenerate primers and one probe,no cross reaction occurring between the subtypes,no non-specific reactions with other pathogens and high sensitivity.When used separately to detect the product of single GM RT-PCR for single H5 or N1 gene,the GMPLex test showed a sensitivity of 105(=280ELD50) forboth tests and the Luminex qualitative ratio results were 3.08 and 3.12,respectively.When used to detect the product of GM RT-PCR for HSN1 strain at the same time,both showed a sensitivity of 10-4(=2800 ELD50).The GMPLex rapid high throughput subtyping test can satisfy the needs of influenza rapid testing.

  18. Influenza A (H1N1. Radiological Patterns Influenza A (H1N1. Patrones Radiológicos

    Martha Yudey Rodriguez Pino


    Full Text Available The influenza A (H1N1 has a wide radiological spectrum, difficult to differentiate from other epidemic respiratory diseases. One of the distinctive elements seems to be the quick evolution of the imagenologic lesions in the sick persons, as well as the slow resolution of these manifestations. The chest fillm is of vital importance to make a precise diagnosis, and it constitutes an indispensable tool for the identification of the cases according to the affection degree (light, moderate, and severe, besides contributing as an essential way to the classification of the patients according to a grade of uncertainty. Although as a confirmation complementary is not definitive, it is important in defining if a case is suspicious or probable.La influenza A (H1N1 tiene un espectro radiológico amplio, difícil de diferenciar de otras enfermedades respiratorias no epidémicas. Uno de los elementos distintivos parece estar en relación con la rápida evolución de las lesiones imagenológicas en los enfermos afectados, así como la lenta resolución de estas manifestaciones. La radiografía de tórax es de vital importancia para hacer un diagnóstico preciso, constituye una herramienta indispensable para la notificación de los casos según el grado de afección (leve, moderada, severa, además de contribuir de manera esencial a la clasificación de los pacientes según el grado de incertidumbre pues, aunque no es un complementario confirmatorio, sí es importante a la hora de definir si un caso es sospechoso o probable.

  19. Psychopathy subtypes and psychopathic violence

    Koshkina Ekaterina Nikolaevna


    This article analyses two main subtypes of psychopathy and its characteristic traits that allow to differ them from each other. Following that, the existence of more specific subtypes of psychopathy and sociopathy is argued on the basis of the recent researches. Also, the inclination of psychopaths and sociopaths to various kinds of violence is examined.

  20. Estimation of type- and subtype-specific influenza vaccine effectiveness in Victoria, Australia using a test negative case control method, 2007-2008

    Grant Kristina A


    Full Text Available Abstract Background Antigenic variation of influenza virus necessitates annual reformulation of seasonal influenza vaccines, which contain two type A strains (H1N1 and H3N2 and one type B strain. We used a test negative case control design to estimate influenza vaccine effectiveness (VE against influenza by type and subtype over two consecutive seasons in Victoria, Australia. Methods Patients presenting with influenza-like illness to general practitioners (GPs in a sentinel surveillance network during 2007 and 2008 were tested for influenza. Cases tested positive for influenza by polymerase chain reaction and controls tested negative for influenza. Vaccination status was recorded by sentinel GPs. Vaccine effectiveness was calculated as [(1 - adjusted odds ratio × 100%]. Results There were 386 eligible study participants in 2007 of whom 50% were influenza positive and 19% were vaccinated. In 2008 there were 330 eligible study participants of whom 32% were influenza positive and 17% were vaccinated. Adjusted VE against A/H3N2 influenza in 2007 was 68% (95% CI, 32 to 85% but VE against A/H1N1 (27%; 95% CI, -92 to 72% and B (84%; 95% CI, -2 to 98% were not statistically significant. In 2008, the adjusted VE estimate was positive against type B influenza (49% but negative for A/H1N1 (-88% and A/H3N2 (-66%; none was statistically significant. Conclusions Type- and subtype-specific assessment of influenza VE is needed to identify variations that cannot be differentiated from a measure of VE against all influenza. Type- and subtype-specific influenza VE estimates in Victoria in 2007 and 2008 were generally consistent with strain circulation data.

  1. Transcriptome classification reveals molecular subtypes in psoriasis

    Ainali Chrysanthi


    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  2. Histamine H1 receptor occupancy and pharmacodynamics of second generation H1-antihistamines.

    Gillard, M; Benedetti, M Strolin; Chatelain, P; Baltes, E


    The predictive efficacy of drugs in humans is frequently estimated from both a high affinity for their receptor as measured in vitro and a long plasmatic half-life. This is grossly misleading since one key parameter is missing: drug concentration at the receptor site in vivo. As a case study we compared the efficacies of three H(1) antihistamines in inhibiting histamine-induced wheal and flare in humans at two different time points with the above mentioned parameters. It is concluded that estimating in vivo receptor occupancy, which takes into account both the affinity of the drug for the receptor and its free plasma concentration, is a far better predictor for human pharmacodynamics and hence antihistamine potency, than considering in vitro affinity and plasmatic half-life only.

  3. Luminosity measurement in H1; Mesure de la luminosite pour l'experience H1

    Frisson, T


    At HERA, luminosity is determined on-line and bunch by bunch by measuring the Bremsstrahlung spectrum from e-p collisions. The Hl collaboration has built a completely new luminosity system in order to sustain the harsh running conditions after the fourfold luminosity increase. Namely, the higher synchrotron radiation doses and the increased event pile-up have governed the design of the two major components, a radiation resistant quartz-fibre electro-magnetic calorimeter, and a fast read-out electronic with on-line energy histogram loading at a rate of 500 kHz. The group was in charge of the electronic and the on-line data analysis of the new luminosity system. In this thesis, I present analysis tools and methods to improve the precision of the luminosity measurement. The energy scale and acceptance calculation methods set out in this thesis permit these values to be determined every four minutes, to an accuracy of 0.5 parts per thousand for the energy scale and 2 parts per thousand for the acceptance. From these results, the degree of accuracy obtained on the luminosity measurement is between 6.5 and 9.5 parts per thousand. These results are currently undergoing validation, with the aim of becoming the standard H1 method. I also studied quasi-elastic Compton events to cross-check the luminosity measurement using the 2003- 2004 and 2005 data. Indeed, this process has a well calculable cross section and a clear experimental signature. The leptonic final state consists of a coplanar e-gamma system, both observable in the central H1 detector. (author)

  4. An H1 histone gene from rainbow trout (Salmo gairdnerii).

    Mezquita, J; Connor, W; Winkfein, R J; Dixon, G H

    A 1.7-kbp DNA region from the 10.2-kb cluster containing the five rainbow trout histone genes has been subcloned in pBR322 and completely sequenced. It contains a trout histone H1 gene together with its 5' and 3' flanking sequences. This H1 gene codes for a H1 variant different from the major trout testis H1 previously sequenced by Macleod et al. (1977). Northern blots of total RNA from trout testis, kidney, and liver indicate that this H1 gene is expressed in all three tissues but that the level of H1 mRNA is much higher in testis than in other tissues. The lack of heterogeneity in the sizes and 5' initiation sites of trout H1 mRNAs is surprising in view of the substantial heterogeneity of H1 variant proteins observed previously. The coding sequence of the H1 gene shows strong evidence of repeated partial duplications of a hexapeptide motif of the form Ala.Ala.Ala.Lys.Lys.Pro and of a pentapeptide phosphorylation-site sequence, Lys.Ser.Pro.Lys.Lys, during its evolution. Comparisons are drawn between this gene and the coding sequences of other vertebrate H1 genes from chicken and Xenopus, and a strong homology is seen in the region of amino acids 22-101, which form the hydrophobic "head" of the H1 molecule. The 5' and 3' regulatory signals in the trout H1 are also compared with those of H1 genes from other sequences.

  5. Expression of the novel gene NM23-H1B in ovarian cancer

    LI Wen; LIU Yan; JIN Zhi-Jun; FENG You-ji; XU Ling-ling


    Objective:To study the expression of the human novel gene NM23-H1B in ovarian cancer. Methods: Totally 24 samples from patients with epithelial ovarian tumor at different clinical stages and 4 from normal ovaries were examined for NM23-H1B mRNA expression by RT-PCR and Northern blot. Results: All samples expressed NM23-H1B mRNA through RT-PCR, while the level of expression in ovarian tumor was higher than that of normal ovary. The results of Northern blot showed that NM23-H1B was overexpressed in ovarian cancer while lowexpressed in normal ovary or low malignant potential (LMP). The level of expression at early stage cancer(stageⅠand Ⅱ) was higher than those in advanced cancer(stage Ⅲ and Ⅳ). In early stage carcinoma, the expression level was involved in the differentiation of tumor cell, and well-differentiated cancer expressed NM23-H1B mRNA in comparatively higher level. Conclusion: The novel gene NM23-N1B is closely correlated with the ovarian cancer.

  6. Influenza A Viruses Detected in Swine in Southern Germany after the H1N1 Pandemic in 2009.

    Pippig, J; Ritzmann, M; Büttner, M; Neubauer-Juric, A


    Infections with influenza A viruses (IAV) are highly prevalent in swine populations, and stable cocirculation of at least three lineages has been well documented in European swine - till 2009. However, since the emergence of the human pandemic pdmH1N1 virus in 2009, which has been (re)introduced into individual swine herds worldwide, the situation has been changing. These variations in the respective IAV pools within pig populations are of major interest, and the zoonotic potential of putative emerging viruses needs to be evaluated. As data on recent IAV in swine from southern Germany were relatively sparse, the purpose of this study was to determine the major IAV subtypes actually present in this region. To this aim, from 2010 to 2013, 1417 nasal swabs or lung tissue samples from pigs with respiratory disease were screened for IAV genomes. Overall, in 130 holdings IAV genomes were detected by real-time RT-PCR targeting the matrix protein gene. For further analyses, several PCR protocols were adapted to quickly subtype between H1, pdmH1, H3, N1 and N2 sequences. Taken together, cocirculation of the three stable European lineages of IAV was confirmed for Bavaria. H1N1 sequences were identified in 59, whereas H1N2 genomes were only diagnosed in 14, and H3N2 in 9 of the holdings analysed. However, pdmH1 in combination with N1 was detected in 2010, 2012 and 2013 confirming a presence, albeit in low prevalence, likewise pdmH1N2 reassortant viruses. Interestingly, individual cases of coinfections with more than one subtype were diagnosed. Partial genome sequences were determined and phylogenetic analyses performed. Clearly other than in the human population classically circulating IAV have not been displaced by pdmH1N1 in Bavarian swine. However, some interesting viruses were detected. Further surveillance of these viruses in the Bavarian pig population will be of major importance, to monitor future developments. © 2016 Blackwell Verlag GmbH.

  7. Selective brain gray matter atrophy associated with APOE ε4 and MAPT H1 in subjects with mild cognitive impairment.

    Goñi, Joaquín; Cervantes, Sebastián; Arrondo, Gonzalo; Lamet, Isabel; Pastor, Pau; Pastor, María A


    The aim of our study was to elucidate whether specific patterns of gray matter loss were associated with apolipoprotein E ε4 (APOE ε4) and microtubule-associated protein tau (MAPT)-H1) genetic variants in subjects with mild cognitive impairment (MCI) at a baseline visit. Gray matter voxel-based morphometry analysis of T1 magnetic resonance imaging scans were performed in 65 amnestic-MCI subjects. MCI APOE ε4 carriers compared with non-carriers showed increased brain atrophy in right hippocampus and rostral amygdala, superior and middle temporal gyrus, and right parietal operculum, including inferior frontal gyrus, inferior parietal, and supramarginal gyrus. MAPT-H1/H1 MCI carriers showed an increased bilateral atrophy in superior frontal gyri (including frontal eye fields and left prefrontal cortex) and precentral gyrus but also unilateral left atrophy in the inferior temporal gyrus and calcarine gyrus. In addition, MCI subjects carrying both APOE ε4 and MAPT-H1/H1 variants showed gray matter loss in the supplementary motor area and right pre- and postcentral gyri. The effect of APOE ε4 on gray matter loss in right hippocampus suggests that, at least in some AD sub-types, the neuronal vulnerability could be increased in the right hemisphere. The pattern of frontal gray matter loss observed among MCI MAPT H1/H1 carriers has also been found in other tauopathies, suggesting that MCI may share etiological factors with other tauopathies. Frontal and parietal cortex vulnerability was found when adding MAPT H1/H1 and APOE ε4 effects, suggesting a synergistic effect of these variants. These results could be due to changes in APOE ε4 and MAPT expression.

  8. Linker histone H1 and protein-protein interactions

    Kalashnikova, Anna A; Rogge, Ryan A.; Hansen, Jeffrey C


    Linker histones H1 are ubiquitous chromatin proteins that play important roles in chromatin compaction, transcription regulation, nucleosome spacing and chromosome spacing. H1 function in DNA and chromatin structure stabilization is well studied and established. The current paradigm of linker histone mode of function considers all other cellular roles of linker histones to be a consequence from H1 chromatin compaction and repression. Here we review the multiple processes regulated by linker h...

  9. H1N1快速治疗计

    罗炯尧; 陈艳莲



  10. H1N1: pandemia e perspectiva atual H1N1: overview and perspectives

    Nancy Bellei


    Full Text Available O vírus influenza de origem suína, A/California/04/2009 (H1N1, foi inicialmente detectado no México e determinou a pandemia de influenza de 2009. Em agosto de 2010, a Organização Mundial da Saúde (OMS declarou o início da fase pós-pandêmica. As características dessa última pandemia foram marcadamente diferentes das anteriores. O vírus emergiu de rearranjos genéticos originários em hospedeiro mamífero não humano, demonstrou transmissibilidade interespécies e afetou a população humana de forma diferente dos vírus pandêmicos anteriores (1918, 1957 e 1968 com maior morbidade e mortalidade em crianças e adultos jovens. Atualmente, o vírus apresenta padrão sazonal da mesma forma que o influenza A H3N2 e o influenza B, mantendo, até o momento, o mesmo perfil de patogenicidade, espectro clínico e sensibilidade a antivirais. A cepa foi incluída na vacina sazonal trivalente anual recomendada, principalmente para proteção dos grupos de risco mais vulneráveis a complicações pelas diferentes cepas de influenza.The swine origin influenza virus A/CALIFORNIA/04/2009 (H1N1 was first detected in Mexico and determined the 2009 influenza pandemic. In August 2010, World Health Organization (WHO declared the beginning of the post-pandemic period. This last pandemic was distinctly different from previous ones. The virus emerged from genetic rearrangement in non-human mammalian host. Moreover, its inter-species transmission is fully reported. However, it affected human population differently from previous pandemic viruses (1918, 1957, 1968, with increased morbidity and mortality among children and young adults. Currently, the virus has a seasonal pattern in the same way as influenza A H3N2 and influenza B, maintaining the same pathogenicity profile, clinical spectrum and sensitivity to antiviral agents. The strain was included in the annual trivalent seasonal vaccine formulation, mainly for risk groups, which are more vulnerable to

  11. Main: 1H1Y [RPSD[Archive

    Full Text Available 1H1Y イネ Rice Oryza sativa L. D-Ribulose-5-Phosphate 3-Epimerase Oryza Sativa Molecu...V. 326 127 2003 3-Epimerase, Oxidative Pentose Phosphate Pathway, Isomerase SWS:Q9SE42,Q9SE42|EMBL; AF189365; AAF01048.1; -.|PDB; 1H...1Y; X-ray; A/B=1-228.|PDB; 1H1Z; X-ray; A/B=1-228.|Gramene; Q9SE42; -.|GO; GO:001685...ELIQSIKAKGMRPGVSLRPGTPVEEVFPLVEAENPVELVLVMTVEPGFGGQKFMPEMMEKVRALRKKYPSLDIEVDGGLGPSTIDVAASAGANCIVAGSSIFGAAEPGEVISALRKSVEGSQNKS rice_1H1Y.jpg ...

  12. Pityriasis rosea following influenza (H1N1 vaccination

    Jeng-Feng Chen


    Full Text Available Pityriasis rosea is a distinct papulosquamous skin eruption that has been attributed to viral reactivation, certain drug exposures or rarely, vaccination. Herein, we reported a clinicopathlogically typical case of pityriasis rosea that developed after the H1N1 vaccination. With a global H1N1 vaccination program against the pandemic H1N1 influenza, patients should be apprised of the possibility of such rare but benign skin reaction to avoid unnecessary fear. Furthermore, a brief review of the current reported skin adverse events related to the novel H1N1 vaccination in Taiwan is presented here.

  13. Subtyping of type A influenza by sequencing the variable regions of HA gene specifically amplified with RT-PCR

    YAN An; DING GuoHui; ZHOU ZhenFeng; DONG Hui; ZHANG YaKun; ZHU Lei; HE YunGang; ZHANG GuoQing; LI YiXue; SUN Bing; HUANG Zhong; LAN Ke; JIN Li; WANG HongYan; WANG XiaoNing; YANG Zhong; ZHONG Yang; DAI JianXin; GUO YaJun; WANG Hao; CHE XiaoYan; WU Fan; YUAN ZhenGan; ZHANG Xi; CAO ZhiWei; ZHOU XiaoNong; ZHOU JiaHai; MA ZhiYong; TONG GuangZhi; ZHAO GuoPing; JIN WeiRong; XIONG Hui


    The outbreak of a novel influenza A (H1N1) virus across the globe poses a threat to human health.It is of paramount importance to develop a rapid,reliable and inexpensive diagnostic procedure.Based on the bioinformatic information from public database,primers specific for influenza A virus surface protein haemagglutinin (HA) of several subtypes (including H1,H2,H3,H5,H7 and H9) were designed.Primer-specific PCR products were subjected to sequencing for accurately distinguishing H1 and H3 subtypes from others.This sequencing-based detection method will not only be applied to rapid detection and simultaneous subtype identification of new influenza A virus H1N1,but also provide the strategies to monitor other new types of influenza virus with explosive potential.

  14. Multiplex PCR followed by restriction length polymorphism analysis for the subtyping of bovine herpesvirus 5 isolates

    Maidana; Morano, C.D.; Cianfrinid; de Campos, F.; Roehe, P.M.; Siedler, B.; G. De Stefano; Mauroy, Axel; Thiry, Etienne; Romera, S. A.


    Abstract Background: Several types and subtypes of bovine herpesviruses 1 and 5 (BoHV-1 and BoHV-5) have been associated to different clinical conditions of cattle, making type/subtype differentiation essential to understand the pathogenesis and epidemiology of BoHV infections. BoHV-5 subtyping is currently carried out by BstEII restriction enzyme analysis (REA) of the complete virus genome. This method allowed the description of three subtypes, one of which is the most widespread while ...

  15. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent;

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

  16. VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection.

    Cho, I-R; Kaowinn, S; Song, J; Kim, S; Koh, S S; Kang, H-Y; Ha, N-C; Lee, K H; Jun, H-S; Chung, Y-H


    Although H-1 parvovirus is used as an antitumor agent, not much is known about the relationship between its specific tropism and oncolytic activity. We hypothesize that VP2, a major capsid protein of H-1 virus, determines H-1-specific tropism. To assess this, we constructed chimeric H-1 viruses expressing Kilham rat virus (KRV) capsid proteins, in their complete or partial forms. Chimeric H-1 viruses (CH1, CH2 and CH3) containing the whole KRV VP2 domain could not induce cytolysis in HeLa, A549 and Panc-1 cells. However, the other chimeric H-1 viruses (CH4 and CH5) expressing a partial KRV VP2 domain induced cytolysis. Additionally, the significant cytopathic effect caused by CH4 and CH5 infection in HeLa cells resulted from preferential viral amplification via DNA replication, RNA transcription and protein synthesis. Modeling of VP2 capsid protein showed that two variable regions (VRs) (VR0 and VR2) of H-1 VP2 protein protrude outward, because of the insertion of extra amino-acid residues, as compared with those of KRV VP2 protein. This might explain the precedence of H-1 VP2 protein over KRV in determining oncolytic activity in human cancer cells. Taking these results together, we propose that the VP2 protein of oncolytic H-1 parvovirus determines its specific tropism in human cancer cells.

  17. Chromatin structure-dependent conformations of the H1 CTD.

    Fang, He; Wei, Sijie; Lee, Tae-Hee; Hayes, Jeffrey J


    Linker histones are an integral component of chromatin but how these proteins promote assembly of chromatin fibers and higher order structures and regulate gene expression remains an open question. Using Förster resonance energy transfer (FRET) approaches we find that association of a linker histone with oligonucleosomal arrays induces condensation of the intrinsically disordered H1 CTD in a manner consistent with adoption of a defined fold or ensemble of folds in the bound state. However, H1 CTD structure when bound to nucleosomes in arrays is distinct from that induced upon H1 association with mononucleosomes or bare double stranded DNA. Moreover, the H1 CTD becomes more condensed upon condensation of extended nucleosome arrays to the contacting zig-zag form found in moderate salts, but does not detectably change during folding to fully compacted chromatin fibers. We provide evidence that linker DNA conformation is a key determinant of H1 CTD structure and that constraints imposed by neighboring nucleosomes cause linker DNAs to adopt distinct trajectories in oligonucleosomes compared to H1-bound mononucleosomes. Finally, inter-molecular FRET between H1s within fully condensed nucleosome arrays suggests a regular spatial arrangement for the H1 CTD within the 30 nm chromatin fiber. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system.

    Kevin T Eade

    Full Text Available During neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and Tv4, we test whether the subtype transcription factor networks that direct differentiation during development are required persistently for long-term maintenance of subtype identity. By conditional transcription factor knockdown in adult Tv neurons after normal development, we find that most transcription factors within the Tv1/Tv4 subtype transcription networks are indeed required to maintain Tv1/Tv4 subtype-specific gene expression in adults. Thus, gene expression profiles are not simply "locked-in," but must be actively maintained by persistent developmental transcription factor networks. We also examined the cross-regulatory relationships between all transcription factors that persisted in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory relationships that had existed between these transcription factors during development were no longer present in the mature adult neuron. This points to key differences between developmental and maintenance transcriptional regulatory networks in individual neurons. Together, our results provide novel insight showing that the maintenance of subtype identity is an active process underpinned by persistently active, combinatorially-acting, developmental transcription factors. These findings have implications for understanding the maintenance of all long-lived cell types and the functional degeneration of neurons in the aging brain.

  19. Histone H1 Variants in Arabidopsis Are Subject to Numerous Post-Translational Modifications, Both Conserved and Previously Unknown in Histones, Suggesting Complex Functions of H1 in Plants.

    Kotliński, Maciej; Rutowicz, Kinga; Kniżewski, Łukasz; Palusiński, Antoni; Olędzki, Jacek; Fogtman, Anna; Rubel, Tymon; Koblowska, Marta; Dadlez, Michał; Ginalski, Krzysztof; Jerzmanowski, Andrzej


    Linker histones (H1s) are conserved and ubiquitous structural components of eukaryotic chromatin. Multiple non-allelic variants of H1, which differ in their DNA/nucleosome binding properties, co-exist in animal and plant cells and have been implicated in the control of genetic programs during development and differentiation. Studies in mammals and Drosophila have revealed diverse post-translational modifications of H1s, most of which are of unknown function. So far, it is not known how this pattern compares with that of H1s from other major lineages of multicellular Eukaryotes. Here, we show that the two main H1variants of a model flowering plant Arabidopsis thaliana are subject to a rich and diverse array of post-translational modifications. The distribution of these modifications in the H1 molecule, especially in its globular domain (GH1), resembles that occurring in mammalian H1s, suggesting that their functional significance is likely to be conserved. While the majority of modifications detected in Arabidopsis H1s, including phosphorylation, acetylation, mono- and dimethylation, formylation, crotonylation and propionylation, have also been reported in H1s of other species, some others have not been previously identified in histones.

  20. Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.

    Alonso, Cristina; Fernández-Ramos, David; Varela-Rey, Marta; Martínez-Arranz, Ibon; Navasa, Nicolás; Van Liempd, Sebastiaan M; Lavín Trueba, José L; Mayo, Rebeca; Ilisso, Concetta P; de Juan, Virginia G; Iruarrizaga-Lejarreta, Marta; delaCruz-Villar, Laura; Mincholé, Itziar; Robinson, Aaron; Crespo, Javier; Martín-Duce, Antonio; Romero-Gómez, Manuel; Sann, Holger; Platon, Julian; Van Eyk, Jennifer; Aspichueta, Patricia; Noureddin, Mazen; Falcón-Pérez, Juan M; Anguita, Juan; Aransay, Ana M; Martínez-Chantar, María Luz; Lu, Shelly C; Mato, José M


    Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis. We collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis. Livers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice. In an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be

  1. Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-24.

    Maja Studencka


    Full Text Available Elucidation of the biological role of linker histone (H1 and heterochromatin protein 1 (HP1 in mammals has been difficult owing to the existence of a least 11 distinct H1 and three HP1 subtypes in mice. Caenorhabditis elegans possesses two HP1 homologues (HPL-1 and HPL-2 and eight H1 variants. Remarkably, one of eight H1 variants, HIS-24, is important for C. elegans development. Therefore we decided to analyse in parallel the transcriptional profiles of HIS-24, HPL-1/-2 deficient animals, and their phenotype, since hpl-1, hpl-2, and his-24 deficient nematodes are viable. Global transcriptional analysis of the double and triple mutants revealed that HPL proteins and HIS-24 play gene-specific roles, rather than a general repressive function. We showed that HIS-24 acts synergistically with HPL to allow normal reproduction, somatic gonad development, and vulval cell fate decision. Furthermore, the hpl-2; his-24 double mutant animals displayed abnormal development of the male tail and ectopic expression of C. elegans HOM-C/Hox genes (egl-5 and mab-5, which are involved in the developmental patterning of male mating structures. We found that HPL-2 and the methylated form of HIS-24 specifically interact with the histone H3 K27 region in the trimethylated state, and HIS-24 associates with the egl-5 and mab-5 genes. Our results establish the interplay between HPL-1/-2 and HIS-24 proteins in the regulation of positional identity in C. elegans males.

  2. Impact on pregnancies in south Brazil from the influenza A (H1N1 pandemic: cohort study.

    André Anjos da Silva

    Full Text Available INTRODUCTION: The emergence of a new subtype of the influenza virus in 2009 generated interest in the international medical community, the media, and the general population. Pregnant women are considered to be a group at risk of serious complications related to the H1N1 influenza virus. The aim of this study was to evaluate the outcomes and teratogenic effects of pregnancies exposed to the H1N1 virus during the Influenza A epidemic that occurred in the state of Rio Grande do Sul in 2009. METHODS: This is an uncontrolled prospective cohort study of pregnant women with suspected symptoms of Influenza A who were reported in the Information System for Notifiable Diseases-Influenza (SINAN-Influenza during the epidemic of 2009 (database from the state of Rio Grande do Sul, Brazil. There were 589 cases of pregnant women with suspected infection. Among these, 243 were tested by PCR and included in the analysis. The main outcome measures were: maternal deaths, pregnancy outcome, stillbirths, premature births, low birth weight, congenital malformations, and odds ratios for H1N1+ and non-H1N1 pregnant women. RESULTS: There were one hundred and sixty-three (67% confirmed cases of H1N1, 34 cases (14% of seasonal Influenza A and 46 (19% who were negative for Influenza A. There was no difference between the three groups in clinical parameters of the disease. There were 24 maternal deaths--18 of them had H1N1. There were 8 stillbirths--5 were children of H1N1 infected mothers. There were no differences in perinatal outcomes. CONCLUSIONS: The present data do not indicate an increase in teratogenic risk from exposure to the influenza A (H1N1 virus. These results will help to strengthen the data and clarify the health issues that arose after the pandemic.

  3. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O. [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States); Tumpey, Terrence M. [Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA (United States); Pushko, Peter, E-mail: [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States)


    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  4. H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells

    Akira Kunitomi


    Full Text Available Embryonic stem cells (ESCs are a hallmark of ideal pluripotent stem cells. Epigenetic reprogramming of induced pluripotent stem cells (iPSCs has not been fully accomplished. iPSC generation is similar to somatic cell nuclear transfer (SCNT in oocytes, and this procedure can be used to generate ESCs (SCNT-ESCs, which suggests the contribution of oocyte-specific constituents. Here, we show that the mammalian oocyte-specific linker histone H1foo has beneficial effects on iPSC generation. Induction of H1foo with Oct4, Sox2, and Klf4 significantly enhanced the efficiency of iPSC generation. H1foo promoted in vitro differentiation characteristics with low heterogeneity in iPSCs. H1foo enhanced the generation of germline-competent chimeric mice from iPSCs in a manner similar to that for ESCs. These findings indicate that H1foo contributes to the generation of higher-quality iPSCs.

  5. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.

    Welsh, M D; Baird, P M; Guelbenzu-Gonzalo, M P; Hanna, A; Reid, S M; Essen, S; Russell, C; Thomas, S; Barrass, L; McNeilly, F; McKillen, J; Todd, D; Harkin, V; McDowell, S; Choudhury, B; Irvine, R M; Borobia, J; Grant, J; Brown, I H


    The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.

  6. Why are second-generation H1-antihistamines minimally sedating?

    Hu, Yawen; Sieck, Deidra E; Hsu, Walter H


    H1-antihistamines are widely used in treating allergic disorders, e.g., conjunctivitis, urticaria, dermatitis and asthma. The first-generation H1-antihistamines have a much greater sedative effect than the second-generation H1-antihistamines. Researchers could not offer a satisfactory explanations until late 1990s when studies showed that second-generation H1-antihistamines were substrates of P-glycoprotein. P-glycoprotein, expressed in the blood-brain barrier, acts as an efflux pump to decrease the concentration of H1-antihistamines in the brain, which minimizes drug effects on the central nervous system and results in less sedation. P-glycoprotein is found in the apical side of the epithelium. It consists of transmembrane domains that bind substrates/drugs and nucleotide-binding domains that bind and hydrolyze ATP to generate energy for the drug efflux. This review mainly discusses interactions between P-glycoprotein and commonly used second-generation H1-antihistamines. In addition, it describes other possible determining factors of minimal sedating properties of second-generation H1-antihistamines.

  7. A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets.

    Akila Jayaraman

    Full Text Available The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA to α2→6 sialylated glycan receptors (human receptors. Here we report that a single point mutation (Ile219→Lys; a base pair change in the glycan receptor-binding site (RBS of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.

  8. Computer-aided assessment of pulmonary disease in novel swine-origin H1N1 influenza on CT

    Yao, Jianhua; Dwyer, Andrew J.; Summers, Ronald M.; Mollura, Daniel J.


    The 2009 pandemic is a global outbreak of novel H1N1 influenza. Radiologic images can be used to assess the presence and severity of pulmonary infection. We develop a computer-aided assessment system to analyze the CT images from Swine-Origin Influenza A virus (S-OIV) novel H1N1 cases. The technique is based on the analysis of lung texture patterns and classification using a support vector machine (SVM). Pixel-wise tissue classification is computed from the SVM value. The method was validated on four H1N1 cases and ten normal cases. We demonstrated that the technique can detect regions of pulmonary abnormality in novel H1N1 patients and differentiate these regions from visually normal lung (area under the ROC curve is 0.993). This technique can also be applied to differentiate regions infected by different pulmonary diseases.

  9. Persistence of the 2009 pandemic influenza A (H1N1 virus in water and on non-porous surface.

    Amélie Dublineau

    Full Text Available Knowledge of influenza A virus survival in different environmental conditions is a key element for the implementation of hygiene and personal protection measures by health authorities. As it is dependent on virus isolates even within the same subtype, we studied the survival of the 2009 H1N1 pandemic (H1N1pdm virus in water and on non-porous surface. The H1N1pdm virus was subjected to various environmental parameters over time and tested for infectivity. In water, at low and medium salinity levels and 4°C, virus survived at least 200 days. Increasing temperature and salinity had a strong negative effect on the survival of the virus which remained infectious no more than 1 day at 35°C and 270 parts per thousand (ppt of salt. Based on modeled data, the H1N1pdm virus retained its infectivity on smooth non-porous surface for at least 7 days at 35°C and up to 66 days at 4°C. The H1N1pdm virus has thus the ability to persist in water and on glass surface for extended periods of time, even at 35°C. Additional experiments suggest that external viral structures in direct contact with the environment are mostly involved in loss of virus infectivity.

  10. Severe swine influenza A (H1N1) versus severe human seasonal influenza A (H3N2): clinical comparisons.

    Cunha, Burke A; Pherez, Francisco M; Strollo, Stephanie; Syed, Uzma; Laguerre, Marianne


    At the beginning of the swine influenza (H1N1) pandemic in the spring of 2009, there were still stories of human seasonal influenza A circulating in the New York area. Adult patients admitted with influenza-like illnesses (ILIs) (fever > 102°F, dry cough, and myalgias) presented diagnostic problems. First, clinicians had to differentiate ILIs from influenza, and then differentiate human seasonal influenza A from H1N1 in hospitalized adults with ILIs and negative chest films (no focal segmental/lobar infiltrates). Human seasonal influenza A was diagnosed by rapid influenza diagnostic tests (RIDTs), but H1N1 was often RIDT negative. Reverse transcriptase-polymerase chain reaction for H1N1 was restricted or not available. The Winthrop-University Hospital Infectious Disease Division developed clinical diagnostic criteria (a diagnostic weighted point score system) to rapidly and clinically diagnose H1N1 in patients with negative RIDTs. The point score system was modified and shortened for ease of use, that is, the diagnostic H1N1 triad (any 3 of 4) (ILI, see above) plus thrombocytopenia, relative lymphopenia, elevated serum transaminases, or an elevated creatine phosphokinase. Our clinical experience during the pandemic allowed us to develop the swine diagnostic H1N1 triad. In the process, similarities and differences between human seasonal influenza A and H1N1 were noted. We present 2 illustrative cases of severe influenza, one due to human seasonal influenza A and one due to H1N1, for clinical consideration reflective of our experiences early in the H1N1 pandemic in 2009.

  11. 甲型H1N1流感



    @@ 2009年3月以来,许多国家先后发生甲型H1N1流感.甲型H1N1流感原名猪流感,为避免"猪流感"一词对人们的误导,世界卫生组织将此前被称为猪流感的新型致命病毒更名为"AH1N1型流感"(influenza A (H1N1)),我国按惯例称为"甲型H1N1流感". 世卫组织已将该病警告级别提高到6级,表明它将会成为全球性流行病.

  12. Interplay between histone H1 structure and function.

    Roque, Alicia; Ponte, Inma; Suau, Pedro


    H1 linker histones are involved both in the maintenance of higher-order chromatin structure and in gene regulation. Histone H1 exists in multiple isoforms, is evolutionarily variable and undergoes a large variety of post-translational modifications. We review recent progress in the understanding of the folding and structure of histone H1 domains with an emphasis on the interactions with DNA. The importance of intrinsic disorder and hydrophobic interactions in the folding and function of the carboxy-terminal domain (CTD) is discussed. The induction of a molten globule-state in the CTD by macromolecular crowding is also considered. The effects of phosphorylation by cyclin-dependent kinases on the structure of the CTD, as well as on chromatin condensation and oligomerization, are described. We also address the extranuclear functions of histone H1, including the interaction with the β-amyloid peptide. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. H1-antihistamines induce vacuolation in astrocytes through macroautophagy

    Hu, Wei-Wei; Yang, Ying; Wang, Zhe; Shen, Zhe; Zhang, Xiang-Nan [Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 (China); Wang, Guang-Hui [College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123 (China); Chen, Zhong, E-mail: [Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 (China)


    H1-antihistamines induce vacuolation in vascular smooth muscle cells, which may contribute to their cardiovascular toxicity. The CNS toxicity of H1-antihistamines may also be related to their non-receptor-mediated activity. The aim of this study was to investigate whether H1-antihistamines induce vacuolation in astrocytes and the mechanism involved. The H1-antihistamines induced large numbers of giant vacuoles in astrocytes. Such vacuoles were marked with both the lysosome marker Lysotracker Red and the alkalescent fluorescence dye monodansylcadaverine, which indicated that these vacuoles were lysosome-like acidic vesicles. Quantitative analysis of monodansylcadaverine fluorescence showed that the effect of H1-antihistamines on vacuolation in astrocytes was dose-dependent, and was alleviated by extracellular acidification, but aggravated by extracellular alkalization. The order of potency to induce vacuolation at high concentrations of H1-antihistamines (diphenhydramine > pyrilamine > astemizole > triprolidine) corresponded to their pKa ranking. Co-treatment with histamine and the histamine receptor-1 agonist trifluoromethyl toluidide did not inhibit the vacuolation. Bafilomycin A1, a vacuolar (V)-ATPase inhibitor, which inhibits intracellular vacuole or vesicle acidification, clearly reversed the vacuolation and intracellular accumulation of diphenhydramine. The macroautophagy inhibitor 3-methyladenine largely reversed the percentage of LC3-positive astrocytes induced by diphenhydramine, while only partly reversing the number of monodansylcadaverine-labeled vesicles. In Atg5{sup −/−} mouse embryonic fibroblasts, which cannot form autophagosomes, the number of vacuoles induced by diphenhydramine was less than that in wild-type cells. These results indicated that H1-antihistamines induce V-ATPase-dependent acidic vacuole formation in astrocytes, and this is partly mediated by macroautophagy. The pKa and alkalescent characteristic of H1-antihistamines may be the

  14. Early Detection of Pandemic (H1N1) 2009, Bangladesh

    Rahman, Mustafizur; Al Mamun, Abdullah; Haider, Mohammad Sabbir; Zaman, Rashid Uz; Karmakar, Polash Chandra; Nasreen, Sharifa; Muneer, Syeda Mah-E; Homaira, Nusrat; Goswami, Doli Rani; Ahmed, Be-Nazir; Husain, Mohammad Mushtuq; Jamil, Khondokar Mahbuba; Khatun, Selina; Ahmed, Mujaddeed; Chakraborty, Apurba; Fry, Alicia; Widdowson, Marc-Alain; Bresee, Joseph; Azim, Tasnim; Alamgir, A.S.M.; Brooks, Abdullah; Hossain, Mohamed Jahangir; Klimov, Alexander; Rahman, Mahmudur; Luby, Stephen P.


    To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population. PMID:22257637

  15. The Correlation of p53 and nm23-H1 Expression with Invasivenes and Metastasis in Esophageal Carcinoma

    LIULigang; PANTiecheng; 等


    Objective:To study the relationship between expression of p53 and nm23-H1 and differentiation,invasiveness and metastasis in human esophageal carcinoma,and the correlation between expression of p53 and nm23-H1.Methods:Expression of p53 and nm23-H1 in 50 patients with squamous cell carcinoma of esophagus was detected by using immunohistochemical S-P methods.Results:35 caes(70%) and 32 cases(64%) of esophageal squamous cell carcinoma were positive for nm23-H1 protein and p53 protein,respectivel.The expression of nm23-H1 was related to lymphatic metastasis(P0.05).The lymphatic metastasis location positive group had a very lower expression of nm23-H1 and the negative rage was 70.8% ,but the negative group had a higher expression and the positive rate was 65.4% ,The expression of p53 was related to tumor differentiation and invasiveness(P0.05).Among the three grups,the high differentiation group had the lowest expression of p53 and the positive rate was 29.2%,but the low differentiation group had the highest positvie rate(71.4%) ,As for tmor invasiveness,the group of outer membrane of esophagus infiltrated had the highest p53 proten positive rate (56%) .but in the group of mucous or submucous layer infiltrated p53 protein was not detectable.The low expression of nm23-H1 and the high expression of p53 were also correlated.The expression of nm23-H1 and p53 were both correlated with TNM stage of esophageal carcinoma (P<0.05).The better esophageal carcinomas differentiated,the lower nm23-H1 expressed and higher p53 expressed.Conclusion Low expression of nm23-H1 and high expression of p53 play an important role in the progression of squamous cell carcinoma of esophagus.Nm 23-H1 might be a gene marker in the prophecy of patients' prognosis and benefit tumor treatment clinically.

  16. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand; Osteoklastische Fingerarthrose - Subtyp der Handpolyarthrose

    Dihlmann, W. [Radiologische Praxis, Hamburg-Barmbek (Germany); Dihlmann, A. [Berufsgenossenschaftliches Unfallkrankenhaus Hamburg (Germany)


    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.) [Deutsch] Ziel: Beschreibung eines Subtyps der Arthrosis deformans an der Hand, der als osteoklastische Arthrose bezeichnet wird. Patienten und Methode: Retrospektive Analyse der Handroentgenaufnahmen von 150 Frauen und 100 Maennern mit Roentgenbefunden der Arthrosis deformans. Ergebnisse: 5% der Frauen und 2% der maennlichen Patienten des durchgesehenen Krankenguts zeigten an mindestens einem Fingergelenk eine Arthrose mit subchondralen Osteolysen an einem oder beiden artikulierenden Knochen, die mindestens ein Drittel der Phalanxlaenge erfasst hatten. Diese subchondralen Osteolysen gehen ueber die Groesse und Form der arthrotischen Geroellzysten, die lediglich im knoechernen (epiphysaeren) Gelenksockel sitzen, weit hinaus. Sie koennen innerhalb eines Jahres entstehen. Schlussfolgerung: Die osteoklastische Arthrose der Finger ist ein Subtyp der Handpolyarthrose. Nach Verlaufsbeobachtungen wird vermutet, dass eine

  17. Extracellular vesicles shed by melanoma cells contain a modified form of H1.0 linker histone and H1.0 mRNA-binding proteins

    Schiera, Gabriella; Di Liegro, Carlo Maria; Puleo, Veronica; Colletta, Oriana; Fricano, Anna; Cancemi, Patrizia; Di Cara, Gianluca; Di Liegro, Italia


    Extracellular vesicles (EVs) are now recognized as a fundamental way for cell-to-cell horizontal transfer of properties, in both physiological and pathological conditions. Most of EV-mediated cross-talk among cells depend on the exchange of proteins, and nucleic acids, among which mRNAs, and non-coding RNAs such as different species of miRNAs. Cancer cells, in particular, use EVs to discard molecules which could be dangerous to them (for example differentiation-inducing proteins such as histone H1.0, or antitumor drugs), to transfer molecules which, after entering the surrounding cells, are able to transform their phenotype, and even to secrete factors, which allow escaping from immune surveillance. Herein we report that melanoma cells not only secrete EVs which contain a modified form of H1.0 histone, but also transport the corresponding mRNA. Given the already known role in tumorigenesis of some RNA binding proteins (RBPs), we also searched for proteins of this class in EVs. This study revealed the presence in A375 melanoma cells of at least three RBPs, with apparent MW of about 65, 45 and 38 kDa, which are able to bind H1.0 mRNA. Moreover, we purified one of these proteins, which by MALDI-TOF mass spectrometry was identified as the already known transcription factor MYEF2. PMID:27633859

  18. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability.

    Frielink, N; Schuengel, C; Embregts, P


    According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic motivation for people with intellectual disability (ID) due to their cognitive limitations. The current study challenges this proposal by testing whether the four subtypes of extrinsic motivation can be differentiated among people with ID as well. The subtypes of extrinsic motivation were measured using two adapted versions of the Self-Regulation Questionnaire, one regarding exercise and one regarding support. In total, 186 adults with mild to borderline ID participated in the study. Results supported the distinction between the four subtypes of extrinsic motivation regarding both exercise and support. In addition, the correlation coefficients supported a quasi-simplex pattern of correlations among the subtypes, indicating that adjacent subtypes were more closely related than non-adjacent subtypes. Moreover, the study showed sufficient Cronbach's alphas and test-retest reliabilities for early stage research. Overall, the results of the current study provide initial evidence for the universality of the four subtypes of extrinsic motivation across populations with and without ID. © 2017 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

  19. The dissociative subtype of posttraumatic stress disorder: rationale, clinical and neurobiological evidence, and implications.

    Lanius, Ruth A; Brand, Bethany; Vermetten, Eric; Frewen, Paul A; Spiegel, David


    Clinical and neurobiological evidence for a dissociative subtype of posttraumatic stress disorder (PTSD) has recently been documented. A dissociative subtype of PTSD is being considered for inclusion in the forthcoming Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to address the symptoms of depersonalization and derealization found among a subset of patients with PTSD. This article reviews research related to the dissociative subtype including antecedent, concurrent, and predictive validators as well as the rationale for recommending the dissociative subtype. The relevant literature pertaining to the dissociative subtype of PTSD was reviewed. Latent class analyses point toward a specific subtype of PTSD consisting of symptoms of depersonalization and derealization in both veteran and civilian samples of PTSD. Compared to individuals with PTSD, those with the dissociative subtype of PTSD also exhibit a different pattern of neurobiological response to symptom provocation as well as a differential response to current cognitive behavioral treatment designed for PTSD. We recommend that consideration be given to adding a dissociative subtype of PTSD in the revision of the DSM. This facilitates more accurate analysis of different phenotypes of PTSD, assist in treatment planning that is informed by considering the degree of patients' dissociativity, will improve treatment outcome, and will lead to much-needed research about the prevalence, symptomatology, neurobiology, and treatment of individuals with the dissociative subtype of PTSD. © 2012 Wiley Periodicals, Inc.

  20. Extreme evolutionary conservation of functionally important regions in H1N1 influenza proteome.

    Samantha Warren

    Full Text Available The H1N1 subtype of influenza A virus has caused two of the four documented pandemics and is responsible for seasonal epidemic outbreaks, presenting a continuous threat to public health. Co-circulating antigenically divergent influenza strains significantly complicates vaccine development and use. Here, by combining evolutionary, structural, functional, and population information about the H1N1 proteome, we seek to answer two questions: (1 do residues on the protein surfaces evolve faster than the protein core residues consistently across all proteins that constitute the influenza proteome? and (2 in spite of the rapid evolution of surface residues in influenza proteins, are there any protein regions on the protein surface that do not evolve? To answer these questions, we first built phylogenetically-aware models of the patterns of surface and interior substitutions. Employing these models, we found a single coherent pattern of faster evolution on the protein surfaces that characterizes all influenza proteins. The pattern is consistent with the events of inter-species reassortment, the worldwide introduction of the flu vaccine in the early 80's, as well as the differences caused by the geographic origins of the virus. Next, we developed an automated computational pipeline to comprehensively detect regions of the protein surface residues that were 100% conserved over multiple years and in multiple host species. We identified conserved regions on the surface of 10 influenza proteins spread across all avian, swine, and human strains; with the exception of a small group of isolated strains that affected the conservation of three proteins. Surprisingly, these regions were also unaffected by genetic variation in the pandemic 2009 H1N1 viral population data obtained from deep sequencing experiments. Finally, the conserved regions were intrinsically related to the intra-viral macromolecular interaction interfaces. Our study may provide further insights

  1. Molecular characterization of H1N1 influenza A viruses from human cases in North America

    WU Bin; WANG ChengMin; DONG GuoYing; LUO Jing; ZHAO BaoHua; HE HongXuan


    Subtypes of H1N1 influenza virus can be found in humans in North America,while they are also associated with the infection of swine.Characterization of the genotypes of viral strains in human populations is important to understand the source and distribution of viral strains.Genomic and protein sequences of 10 isolates of the 2009 outbreak of influenza A (H1N1) virus in North America were obtained from GenBank database.To characterize the genotypes of these viruses,phylogenetic trees of genes PB2,PB1,PA,HA,NP,NA,NS and M were constructed by Phylip3.67 program and N-Linked glycosylation sites of HA,NA,PB2,NS1 and M2 proteins were analyzed online by NetNGIyc1.0 program.Phylogenetic analysis indicated that these isolates are virtually identical but may be recombinant viruses because their genomic fragments come from different viruses.The isolates also contain a characteristic lowly pathogenic amino acid motif at their HA cleavage sites (IPSIQSR↓GL),and an E residue at position 627 of the PB2 protein which shows its high affinity to humans.The homologous model of M proteins showed that the viruses had obtained the ability of anti-amantadine due to the mutation at the drug-sensitive site,while sequence analysis of NA proteins indicated that the viruses are still susceptible to the neuraminidase inhibitor drug (i.e.oseltamivir and zanamivir) because no mutations have been observed.Our results strongly suggested that the viruses responsible for the 2009 outbreaks of influenza A (H1N1) virus have the ability to cross species barriers to infect human and mammalian animals based on molecular analysis.These findings may further facilitate the therapy and prevention of possible transmission from North America to other countries.

  2. Theoretical Investigation on Excitation, Ionization and Capture in H(1s, 2s) + H(1s, 2s) Collisions

    CHEN Lan-Fang; ZHU Xiao-Long; MA Xin-Wen; LIU Ling; HE Bin; WANG Jian-Guo; Ratko JANEV


    @@ Cross sections of electron-loss in H(1s)+ H(1s) collisions and total collisional destruction of H(2s) in H(1s) + H(2s) collisions are calculated by four-body classical-trajectory Monte Carlo (CTMC) method and compared with previous theoretical and experimental data over the energy range of 4-100 keV. For the former a good agreement is obtained within different four-body CTMC calculations, and for the incident energy Ep > 10 keV, comparison with the experimental data shows a better agreement than the results calculated by the impact parameter approx-imation. For the latter, our theory predicts the correct experimental behaviour, and the discrepancies between our results and experimental ones are less than 30%. Based on the successive comparison with experiments, the cross sections for excitation to H(2p), single- and double-ionization and H- formation in H(2s)+H(2s) collisions are calculated in the energy range of 4-100 keV for the first time, and compared with those in H(1s)+H(1s) and H(1s)+H(2s) collisions.

  3. Linker Histone H1.2 Cooperates with Cul4A and PAF1 to Drive H4K31 Ubiquitylation-Mediated Transactivation

    Kyunghwan Kim


    Full Text Available Increasing evidence suggests that linker histone H1 can influence distinct cellular processes by acting as a gene-specific regulator. However, the mechanistic basis underlying such H1 specificity and whether H1 acts in concert with other chromatin-altering activities remain unclear. Here, we show that one of the H1 subtypes, H1.2, stably interacts with Cul4A E3 ubiquitin ligase and PAF1 elongation complexes and that such interaction potentiates target gene transcription via induction of H4K31ubiquitylation, H3K4me3, and H3K79me2. H1.2, Cul4A, and PAF1 are functionally cooperative because their individual knockdown results in the loss of the corresponding histone marks and the deficiency of target gene transcription. H1.2 interacts with the serine 2-phosphorylated form of RNAPII, and we argue that it recruits the Cul4A and PAF1 complexes to target genes by bridging the interaction between the Cul4A and PAF1 complexes. These data define an expanded role for H1 in regulating gene transcription and illustrate its dependence on the elongation competence of RNAPII.

  4. A novel sequence-based antigenic distance measure for H1N1, with application to vaccine effectiveness and the selection of vaccine strains

    Pan, Keyao; Subieta, Krystina C.; Deem, Michael W.


    H1N1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. Precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. We here introduce a sequence-based method to predict vaccine effectiveness in humans. Historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition assay data from ferret animal model studies. Interestingly, the expected vaccine effectiveness is greater against H1N1 than H3N2, suggesting a stronger immune response against H1N1 than H3N2. The evolution rate of hemagglutinin in H1N1 is also shown to be greater than that in H3N2, presumably due to greater immune selection pressure. PMID:21123189

  5. Dyscalculia and Attention Deficit Subtypes


    The association of specific academic deficits with attention deficit disorder (ADD) subtypes was determined in 20 students (ages 8-12) with ADD with hyperactivity (ADD/H) compared to 20 with ADD without hyperactivity (ADD/noH), at the Department of Educational Psychology, University of Texas at Austin, TX.

  6. Electrophysiological Correlates of Dyslexic Subtypes.

    Flynn, Jane M.; And Others


    The construct validity of Boder's typology of dyslexia was investigated using quantified electroencephalography with 39 children (ages 7-11) during a reading task and at rest. Results supported beta frequency differences in anticipated regions by dyslexia subtype during the reading task. However, the direction of difference hypothesis was not…

  7. NovelH1N1inlfuenzaAvirusinfectioninapatient withacuterejectionafterlivertransplantation

    Jiang-Juan He; Sheng Yan; Min Zhang; Wei-Lin Wang; Shu-Sen Zheng


    BACKGROUND: The 2009 H1N1 inlfuenza A virus was ifrst identiifed in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppression. There are limited reports of 2009 H1N1 inlfuenza in liver transplant recipients, especially in China. METHODS: We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 inlfuenza A virus. He received therapy for acute rejection after transplantation and was conifrmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir (75 mg, orally twice daily) and had a benign hospital course, with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS: The 2009 H1N1 inlfuenza in this hospitalized transplant recipient was relatively mild, and prolonged viral shedding was not noted. Oseltamivir can be a valid measure in immunocompromised individuals.

  8. Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

    Li, Wenfu


    Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

  9. H1N1 in dialysis units: Prevention and management

    Karkar Ayman


    Full Text Available Dialysis patients are at increased risk of contracting influenza A H1N1 and deve-loping serious illness. Increasing the awareness of dialysis patients and continuous education and training of medical staff on early recognition and management of influenza A H1N1 can help in saving the life of patients. Antiviral drugs and influenza vaccines are effective in providing ade-quate immunity in dialysis patients with strict implementation of infection control policies and procedures can help in preventing and controlling the dissemination of influenza A H1N1 in dia-lysis units. We report a case of a patient who presented with HINI influenza and developed acute kidney injury during his hospitalization and his course with disease.

  10. H1N1, globalization and the epidemiology of inequality.

    Sparke, Matthew; Anguelov, Dimitar


    This paper examines the lessons learned from the 2009 H1N1 pandemic in relation to wider work on globalization and the epidemiology of inequality. The media attention and economic resources diverted to the threats posed by H1N1 were significant inequalities themselves when contrasted with weaker responses to more lethal threats posed by other diseases associated with global inequality. However, the multiple inequalities revealed by H1N1 itself in 2009 still provide important insights into the future of global health in the context of market-led globalization. These lessons relate to at least four main forms of inequality: (1) inequalities in blame for the outbreak in the media; (2) inequalities in risk management; (3) inequalities in access to medicines; and (4) inequalities encoded in the actual emergence of new flu viruses.

  11. Characteristics of the mouse genomic histamine H1 receptor gene

    Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others


    We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

  12. Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health.

    Kong, Weili; Wang, Feibing; Dong, Bin; Ou, Changbo; Meng, Demei; Liu, Jinhua; Fan, Zhen-Chuan


    Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens.

  13. Simultaneous detection and differentiation by multiplex real time RT-PCR of highly pathogenic avian influenza subtype H5N1 classic (clade 2.2.1 proper and escape mutant (clade 2.2.1 variant lineages in Egypt

    Arafa Abdel-Satar


    Full Text Available Abstract Background The endemic status of highly pathogenic avian influenza virus (HPAIV of subtype H5N1 in Egypt continues to devastate the local poultry industry and poses a permanent threat for human health. Several genetically and antigenically distinct H5N1 lineages co-circulate in Egypt: Strains of clade 2.2.1 proper replicate mainly in backyard birds causing the bulk of human infections, while a variant lineage within 2.2.1 (2.2.1v appears to be perpetuated mainly in commercial poultry farms in Egypt. Viruses of the 2.2.1v lineage represent drift variants escaping from conventional vaccine-induced immunity and some of these strains also escaped detection by commercial real time reverse transcriptase PCR (RT-qPCR protocols due to mismatches in the primers/probe binding sites. Results We developed therefore a versatile, sensitive and lineage-specific multiplex RT-qPCR for detection and typing of H5N1 viruses in Egypt. Analytical characterization was carried out using 50 Egyptian HPAIV H5N1 strains isolated since 2006 and 45 other avian influenza viruses (AIV. A detection limit of 400 cRNA copies per ml sample matrix was found. Higher diagnostic sensitivity of the multiplex assay in comparison to other generic H5 or M-gene based RT-qPCR assays were found by examination of 63 swab samples from experimentally infected chickens and 50 AIV-positive swab samples from different host species in the field in Egypt. Conclusions The new multiplex RT-qPCR assay could be useful for rapid high-throughput monitoring for the presence of HPAIV H5N1 in commercial poultry in Egypt. It may also aid in prospective epidemiological studies to further delineate and better control spread of HPAIV H5N1 in Egypt.

  14. Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: public health risk implications.

    Stincarelli, Maria; Arvia, Rosaria; De Marco, Maria Alessandra; Clausi, Valeria; Corcioli, Fabiana; Cotti, Claudia; Delogu, Mauro; Donatelli, Isabella; Azzi, Alberta; Giannecchini, Simone


    Exploring the reassortment ability of the 2009 pandemic H1N1 (A/H1N1pdm09) influenza virus with other circulating human or avian influenza viruses is the main concern related to the generation of more virulent or new variants having implications for public health. After different coinfection experiments in human A549 cells, by using the A/H1N1pdm09 virus plus one of human seasonal influenza viruses of H1N1 and H3N2 subtype or one of H11, H10, H9, H7 and H1 avian influenza viruses, several reassortant viruses were obtained. Among these, the HA of H1N1 was the main segment of human seasonal influenza virus reassorted in the A/H1N1pdm09 virus backbone. Conversely, HA and each of the three polymerase segments, alone or in combination, of the avian influenza viruses mainly reassorted in the A/H1N1pdm09 virus backbone. Of note, A/H1N1pdm09 viruses that reassorted with HA of H1N1 seasonal human or H11N6 avian viruses or carried different combination of avian origin polymerase segments, exerted a higher replication effectiveness than that of the parental viruses. These results confirm that reassortment of the A/H1N1pdm09 with circulating low pathogenic avian influenza viruses should not be misjudged in the prediction of the next pandemic. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Influenza-A viruses in ducks in northwestern Minnesota: fine scale spatial and temporal variation in prevalence and subtype diversity.

    Benjamin R Wilcox

    Full Text Available Waterfowl from northwestern Minnesota were sampled by cloacal swabbing for Avian Influenza Virus (AIV from July-October in 2007 and 2008. AIV was detected in 222 (9.1% of 2,441 ducks in 2007 and in 438 (17.9% of 2,452 ducks in 2008. Prevalence of AIV peaked in late summer. We detected 27 AIV subtypes during 2007 and 31 during 2008. Ten hemagglutinin (HA subtypes were detected each year (i.e., H1, 3-8, and 10-12 during 2007; H1-8, 10 and 11 during 2008. All neuraminidase (NA subtypes were detected during each year of the study. Subtype diversity varied between years and increased with prevalence into September. Predominant subtypes during 2007 (comprising ≥5% of subtype diversity included H1N1, H3N6, H3N8, H4N6, H7N3, H10N7, and H11N9. Predominant subtypes during 2008 included H3N6, H3N8, H4N6, H4N8, H6N1, and H10N7. Additionally, within each HA subtype, the same predominant HA/NA subtype combinations were detected each year and included H1N1, H3N8, H4N6, H5N2, H6N1, H7N3, H8N4, H10N7, and H11N9. The H2N3 and H12N5 viruses also predominated within the H2 and H12 subtypes, respectively, but only were detected during a single year (H2 and H12 viruses were not detected during 2007 and 2008, respectively. Mallards were the predominant species sampled (63.7% of the total, and 531 AIV were isolated from this species (80.5% of the total isolates. Mallard data collected during both years adequately described the observed temporal and spatial prevalence from the total sample and also adequately represented subtype diversity. Juvenile mallards also were adequate in describing the temporal and spatial prevalence of AIV as well as subtype diversity.

  16. Genetic characterisation of the recent foot-and-mouth disease virus subtype A/IRN/2005

    Klein, Jörn; Hussain, Manzoor; Ahmad, Munir


    Background According to the World Reference Laboratory for FMD, a new subtype of FMDV serotype A was detected in Iran in 2005. This subtype was designated A/IRN/2005, and rapidly spread throughout Iran and moved westwards into Saudi Arabia and Turkey where it was initially detected from August 2005...... and subsequently caused major disease problems in the spring of 2006. The same subtype reached Jordan in 2007. As part of an ongoing project we have also detected this subtype in Pakistan with the first positive samples detected in April 2006. To characterise this subtype in detail, we have sequenced and analysed...... or subclinical outcome of FMD. Indications of differential susceptibility for developing a subclinical course of disease between Asian buffaloes and cattle have been detected. Furthermore, hitherto unknown insertions of 2 amino acids before the second start codon, as well as sublineage specific amino acids have...

  17. Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2)

    Skovgaard, Kerstin; Cirera, Susanna; Vasby, Ditte;


    This study aimed at providing a better understanding of the involvement of innate immune factors, including miRNA, in the local host response to influenza virus infection. Twenty pigs were challenged by influenza A virus subtype H1N2. Expression of microRNA (miRNA), mRNA and proteins were...... results suggest that, in addition to a wide range of innate immune factors, miRNAs may also be involved in controlling acute influenza infection in pigs....

  18. Decreased Serologic Response in Vaccinated Military Recruits during 2011 Correspond to Genetic Drift in Concurrent Circulating Pandemic A/H1N1 Viruses


    responsible pathogens , and pathogen subtypes. To counter outbreaks of influenza, the trivalent inactivated vaccine (TIV) has been used to protect...increased virulence in mouse models [47]. The reversion mutation S84N, Figure 4. Phylogenetic analysis of the hemagglutinin (HA) gene of influenza pH1N1...members for periodic HIV testing and operationally required pre- and post-deployment blood draws [51]. Baseline samples were shipped to NHRC on dry

  19. Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2)

    Skovgaard, Kerstin; Cirera, Susanna; Vasby, Ditte


    This study aimed at providing a better understanding of the involvement of innate immune factors, including miRNA, in the local host response to influenza virus infection. Twenty pigs were challenged by influenza A virus subtype H1N2. Expression of microRNA (miRNA), mRNA and proteins were...... results suggest that, in addition to a wide range of innate immune factors, miRNAs may also be involved in controlling acute influenza infection in pigs....

  20. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein......Influenza vaccines with the ability to induce immune responses cross-reacting with drifted virus variants would be of great advantage for vaccine development against seasonal and emerging new strains. We demonstrate that gene gun administrated DNA vaccine encoding HA and NA and/or NP and M proteins...

  1. Computed tomography findings in patients with H1N1 influenza A infection

    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Zanetti, Glaucia [Faculdade de Medicina de Petropolis (FMP), RJ (Brazil)


    The present study aimed to review high resolution computed tomography findings in patients with H1N1 influenza A infection. The most common tomographic findings include ground-glass opacities, areas of consolidation or a combination of both patterns. Some patients may also present bronchial wall thickening, airspace nodules, crazy-paving pattern, perilobular opacity, air trapping and findings related to organizing pneumonia. These abnormalities are frequently bilateral, with subpleural distribution. Despite their non specificity, it is important to recognize the main tomographic findings in patients affected by H1N1 virus in order to include this possibility in the differential diagnosis, characterize complications and contribute in the follow-up, particularly in cases of severe disease. (author)

  2. Pneumococcal Pneumonia and Pandemic H1N1


    Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1.  Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/6/2012.

  3. H1N1 Message from the Acting Surgeon General


    In this podcast, Acting Surgeon General Dr. Steven Galson discusses what you can do to protect yourself from H1N1 flu.  Created: 5/13/2009 by U.S. Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC).   Date Released: 5/13/2009.

  4. H1N1 Influenza A hos mennesker og svin

    Larsen, Lars Erik


    Den nye pandemiske influenza A stamme H1N1 er hovedsagelig et nyt virus, som spredes mellem mennesker, men virusset er formodentlig opstået ved blanding af to svineinfluenza-virus og har derfor bibeholdt evnen til at kunne smitte fra mennesker til svin og fra svin til svin. Det er derfor vigtigt...

  5. H1N1 Influenza A hos mennesker og svin

    Larsen, Lars Erik


    Den nye pandemiske influenza A stamme H1N1 er hovedsagelig et nyt virus, som spredes mellem mennesker, men virusset er formodentlig opstået ved blanding af to svineinfluenza-virus og har derfor bibeholdt evnen til at kunne smitte fra mennesker til svin og fra svin til svin. Det er derfor vigtigt...

  6. H1N1 Flu and Antiviral Drugs


    This podcast discusses the use of antiviral drugs for treating and preventing the H1N1 flu virus.  Created: 5/2/2009 by Coordinating Center for Infectious Diseases, National Center for Immunization and Respiratory Diseases, Influenza Division (CCID/NCIRD/ID).   Date Released: 5/2/2009.

  7. PTEN Interacts with Histone H1 and Controls Chromatin Condensation

    Zhu Hong Chen


    Full Text Available Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development, and metabolism. Here, we report on the interplay of PTEN, histone H1, and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may reduce chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling.

  8. Novel H1N1 Flu and Camp


    This podcast gives tips to stay healthy and help prevent infection with novel H1N1 flu if your child or someone you know is going to camp.  Created: 6/30/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 6/30/2009.

  9. Pandemic (H1N1) 2009 in captive cheetah.

    Crossley, Beate; Hietala, Sharon; Hunt, Tania; Benjamin, Glenn; Martinez, Marie; Darnell, Daniel; Rubrum, Adam; Webby, Richard


    We describe virus isolation, full genome sequence analysis, and clinical pathology in ferrets experimentally inoculated with pandemic (H1N1) 2009 virus recovered from a clinically ill captive cheetah that had minimal human contact. Evidence of reverse zoonotic transmission by fomites underscores the substantial animal and human health implications of this virus.

  10. Dissipative electron drift modes in the H1-NF stellarator

    Nadeem, M.; Rafiq, T.; Persson, M. [Chalmers Univ. of Technology, Goeteborg (Sweden). Dept. of Electromagnetics


    A resistive drift wave model is developed from the two fluids theory, and the associated eigenvalue problem is solved using the ballooning mode formalism for the 3D equilibrium magnetic field configuration of the H-1NF stellarator. The frequency spectrum and the localization of electron drift modes are driven unstable by collisional dissipation of electrons along the magnetic field lines. (orig.)

  11. Narcolepsy and H1N1 Influenza Vaccination

    J Gordon Millichap


    Full Text Available The incidence of narcolepsy between January 2000 and December 2010 in children in western Sweden and its relation to the Pandemrix H1N1 influenza vaccination were assessed by collection of data from hospital and clinic medical records and by parent telephone interviews.

  12. Bis(4H-1,2,4-triazol-3-yldisulfane

    Dongsheng Liu


    Full Text Available The title compound, C4H4N6S2, was synthesized by the reaction of 3-mercapto-1H-1,2,4-triazole with sodium hydroxide in ethanol. The molecule possesses a crystallographically imposed twofold axis. Intermolecular N—H...N hydrogen bonds link the molecules into chains along the c axis.

  13. Stay Informed About Novel H1N1 Influenza


    This podcast discusses things you can do everyday to avoid getting sick from infectious diseases, such as the novel H1N1 flu.  Created: 5/4/2009 by National Center for Health Marketing.   Date Released: 5/4/2009.

  14. A Reflex of *H1 in Hieroglyphic Luvian?

    Rasmussen, Jens Elmegård


    Criticizing Kloekhorst's assumption that Hieroglyphic Luvian á stands for /?a/ with a glottal stop continuing PIE *H1, this paper suggests the alternative reading /e/, which is found to be better in keeping with phonetic pointers from the transcription of proper names, Lycian cognates, and overall...

  15. Prehospital Identification of Stroke Subtypes in Chinese Rural Areas

    Hai-Qiang Jin; Jin-Chao Wang; Yong-An Sun; Pu Lyu; Wei Cui; Yuan-Yuan Liu; Zhi-Gang Zhen


    Background:Differentiating intracerebral hemorrhage (ICH) from cerebral infarction as early as possible is vital for the timely initiation of different treatments.This study developed an applicable model for the ambulance system to differentiate stroke subtypes.Methods:From 26,163 patients initially screened over 4 years,this study comprised 1989 consecutive patients with potential first-ever acute stroke with sudden onset of the focal neurological deficit,conscious or not,and given ambulance transport for admission to two county hospitals in Yutian County of Hebei Province.All the patients underwent cranial computed tomography (CT) or magnetic resonance imaging to confirm the final diagnosis based on stroke criteria.Correlation with stroke subtype clinical features was calculated and Bayes' discriminant model was applied to discriminate stroke subtypes.Results:Among the 1989 patients,797,689,109,and 394 received diagnoses of cerebral infarction,ICH,subarachnoid hemorrhage,and other forms of nonstroke,respectively.A history of atrial fibrillation,vomiting,and diabetes mellitus were associated with cerebral infarction,while vomiting,systolic blood pressure ≥180 mmHg,and age <65 years were more typical of ICH.For noncomatose stroke patients,Bayes' discriminant model for stroke subtype yielded a combination of multiple items that provided 72.3% agreement in the test model and 79.3% in the validation model; for comatose patients,corresponding agreement rates were 75.4% and 73.5%.Conclusions:The model herein presented,with multiple parameters,can predict stroke subtypes with acceptable sensitivity and specificity before CT scanning,either in alert or comatose patients.This may facilitate prehospital management for patients with stroke.

  16. Distinct DNA methylation profiles in subtypes of orofacial cleft.

    Sharp, Gemma C; Ho, Karen; Davies, Amy; Stergiakouli, Evie; Humphries, Kerry; McArdle, Wendy; Sandy, Jonathan; Davey Smith, George; Lewis, Sarah J; Relton, Caroline L


    Epigenetic data could help identify risk factors for orofacial clefts, either by revealing a causal role for epigenetic mechanisms in causing clefts or by capturing information about causal genetic or environmental factors. Given the evidence that different subtypes of orofacial cleft have distinct aetiologies, we explored whether children with different cleft subtypes showed distinct epigenetic profiles. In whole-blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome. We then carried out epigenome-wide association studies (EWAS) to test the association between methylation at each site and cleft subtype (cleft lip only (CLO) n = 50; cleft palate only (CPO) n = 50; cleft lip and palate (CLP) n = 50). We also compared methylation in the blood to methylation in the lip or palate tissue using genome-wide data from the same 150 children and conducted an EWAS of CLO compared to CLP in lip tissue. We found four genomic regions in blood differentially methylated in CLO compared to CLP, 17 in CPO compared to CLP and 294 in CPO compared to CLO. Several regions mapped to genes that have previously been implicated in the development of orofacial clefts (for example, TBX1, COL11A2, HOXA2, PDGFRA), and over 250 associations were novel. Methylation in blood correlated with that in lip/palate at some regions. There were 14 regions differentially methylated in the lip tissue from children with CLO and CLP, with one region (near KIAA0415) showing up in both the blood and lip EWAS. Our finding of distinct methylation profiles in different orofacial cleft (OFC) subtypes represents a promising first step in exploring the potential role of epigenetic modifications in the aetiology of OFCs and/or as clinically useful biomarkers of OFC subtypes.

  17. Gene specific actions of thyroid hormone receptor subtypes.

    Jean Z Lin

    Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.

  18. C-terminal functional unit of Rapana thomasiana (marine snail, gastropod) hemocyanin isoform RtH1: isolation and characterization.

    Parvanova, Katja; Idakieva, Krassimira; Todinova, Svetla; Genov, Nicolay


    Rapana thomasiana hemocyanin (RtH) is a mixture of two hemocyanin (Hc) isoforms termed RtH1 and RtH2. Both subunit types are built up of eight functional units (FUs). The C-terminal functional unit (RtH1-h) of the Rapana Hc subunit 1 has been isolated by limited trypsinolysis of the subunit polypeptide chain. The oxy- and apo-forms of the unit are characterized by fluorescence spectroscopy. Upon excitation of RtH1-h at 295 or 280 nm, tryptophyl residues buried in the hydrophobic interior of the protein globule determine the fluorescence emission. This is confirmed by quenching experiments with acrylamide, cesium chloride and potassium iodide. The copper-dioxygen system at the binuclear active site quenches the indole emission of the oxy-RtH1-h. The removal of this system increases the fluorescence quantum yield and causes structural rearrangement of the microenvironment of the emitting tryptophyl residues in the apo-RtH1-h. The thermal stability of the apo-RtH1-h is characterized fluorimetrically by the "melting" temperature T(m) (65 degrees C) and by the transition temperature T(m) (83 degrees C) obtained by differential scanning calorimetry for oxy-RtH1-h. The results confirm the role of the copper-dioxygen complex for the stabilization of the Hc structure in solution.

  19. Molecular treatment of the ion-pair formation reaction in H(1s) + H(1s) collisions

    Borondo, F.; Martin, F.; Yaez, M.


    All the available theoretical calculations of the cross section for the ion-pair formation reaction H(1s)+H(1s)..-->..H/sup +/H/sup -/(1s/sup 2/) have been performed using methods that are only valid at high collision energies. They get good agreement with the experiments for impact energies greater than 25 keV, but fail completely at smaller energies. In this work we report the cross section for this reaction at impact energies less than 10 keV, calculated in the framework of the impact-parameter approximation and using the molecular method with a common translation factor.

  20. The role of sigma factor RpoH1 in the pH stress response of Sinorhizobium meliloti

    Pühler Alfred


    Full Text Available Abstract Background Environmental pH stress constitutes a limiting factor for S. meliloti survival and development. The response to acidic pH stress in S. meliloti is versatile and characterized by the differential expression of genes associated with various cellular functions. The purpose of this study was to gain detailed insight into the participation of sigma factors in the complex stress response system of S. meliloti 1021 using pH stress as an effector. Results In vitro assessment of S meliloti wild type and sigma factor mutants provided first evidence that the sigma factor RpoH1 plays a major role in the pH stress response. Differential expression of genes related to rhizobactin biosynthesis was observed in microarray analyses performed with the rpoH1 mutant at pH 7.0. The involvement of the sigma factor RpoH1 in the regulation of S. meliloti genes upon pH stress was analyzed by comparing time-course experiments of the wild type and the rpoH1 mutant. Three classes of S. meliloti genes could be identified, which were transcriptionally regulated in an RpoH1-independent, an RpoH1-dependent or in a complex manner. The first class of S. meliloti genes, regulated in an RpoH1-independent manner, comprises the group of the exopolysaccharide I biosynthesis genes and also the group of genes involved in motility and flagellar biosynthesis. The second class of S. meliloti genes, regulated in an RpoH1-dependent manner, is composed of genes known from heat shock studies, like ibpA, grpE and groEL5, as well as genes involved in translation like tufA and rplC. Finally, the third class of S. meliloti genes was regulated in a complex manner, which indicates that besides sigma factor RpoH1, further regulation takes place. This was found to be the case for the genes dctA, ndvA and smc01505. Conclusions Clustering of time-course microarray data of S. meliloti wild type and sigma factor rpoH1 mutant allowed for the identification of gene clusters, each with a

  1. Differential actions of peripheral corticotropin-releasing factor (CRF), urocortin II, and urocortin III on gastric emptying and colonic transit in mice: role of CRF receptor subtypes 1 and 2.

    Martínez, Vicente; Wang, Lixin; Rivier, Jean E; Vale, Wylie; Taché, Yvette


    Peripheral CRF inhibits gastric emptying and stimulates colonic motor function in rats. We investigated the role of CRF(1) and CRF(2) receptors in i.p. CRF-induced alterations of gut transit in conscious mice using selective CRF(1) and CRF(2) ligands injected i.p. Gastric emptying 2 h after ingestion of a solid chow meal and colonic transit (time to expel a bead inserted into the distal colon) were determined simultaneously. Rat/human (r/h)CRF, which has CRF(1) > CRF(2) binding affinity, decreased distal colonic transit time at lower doses (6-12 microg/kg) than those inhibiting gastric emptying (20-60 microg/kg). Ovine CRF, a preferential CRF(1) receptor agonist (6-60 microg/kg), reduced significantly the colonic transit time without altering gastric emptying, whereas the selective CRF(2) receptor agonists mouse urocortin II (20-60 microg/kg) and urocortin III (120 microg/kg) inhibited significantly gastric emptying without modifying colonic transit. The CRF(1)/CRF(2) receptor antagonist, astressin (30-120 microg/kg), dose dependently prevented r/hCRF (20 microg/kg)-induced inhibition of gastric emptying and reduction of colonic transit time. The selective CRF(1) receptor antagonists, NBI-27914 (C(18)H(20)Cl(4)N(4)C(7)H(8)O(3)S) and CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine) (5-30 mg/kg), dose dependently blocked r/hCRF action on the colon without influencing the gastric response, whereas the CRF(2) receptor antagonist, antisauvagine-30 (30-100 microg/kg), dose dependently abolished r/hCRF-induced delayed gastric emptying and had no effect on colonic response. These data show that i.p. r/hCRF-induced opposite actions on upper and lower gut transit in conscious mice are mediated by different CRF receptor subtypes: the activation of CRF(1) receptors stimulates colonic propulsive activity, whereas activation of CRF(2) receptors inhibits gastric emptying.

  2. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini


    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.

  3. A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.

    Nicola Clementi

    Full Text Available The interest in broad-range anti-influenza A monoclonal antibodies (mAbs has recently been strengthened by the identification of anti-hemagglutinin (HA mAbs endowed with heterosubtypic neutralizing activity to be used in the design of "universal" prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.

  4. Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice.

    Haba, Hasumi; Nomura, Tadashi; Suto, Fumikazu; Osumi, Noriko


    Interneurons in the olfactory bulb (OB) play essential roles in the processing of olfactory information. They are classified into several subpopulations by the expression of different neurochemical markers. Here we focused on a transcription factor Pax6, and examined its expression and function in distinct subtypes of OB interneurons. We identified Pax6 expression in specific subtypes of interneurons in the external plexiform layer (EPL). The number of these interneuron subtypes was dramatically decreased in Pax6 heterozygous mutant mice. These results indicate that Pax6 is required for differentiation and/or maintenance of EPL interneurons in the adult mouse OB.

  5. Identification of an atypical etiological head and neck squamous carcinoma subtype featuring the CpG island methylator phenotype

    K. Brennan


    Further distinguishing features of this ‘CIMP-Atypical’ subtype include an antiviral gene expression profile associated with pro-inflammatory M1 macrophages and CD8+ T cell infiltration, CASP8 mutations, and a well-differentiated state corresponding to normal SOX2 copy number and SOX2OT hypermethylation. We developed a gene expression classifier for the CIMP-Atypical subtype that could classify atypical disease features in two independent patient cohorts, demonstrating the reproducibility of this subtype. Taken together, these findings provide unprecedented evidence that atypical HNSCC is molecularly distinct, and postulates the CIMP-Atypical subtype as a distinct clinical entity that may be caused by chronic inflammation.

  6. Mensajes importantes sobre la influenza H1N1: Higiene (H1N1 Flu Awareness: Hygiene)


    Este podcast aborda brevemente las formas de protegerse contra el virus nuevo de la influenza H1N1.  Created: 5/6/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 5/6/2009.

  7. Mensajes importantes sobre la influenza H1N1: Comunidad (H1N1 Flu Awareness: Community)


    Este podcast aborda brevemente los planes de la comunidad frente al brote del virus nuevo de la influenza H1N1.  Created: 5/6/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 5/6/2009.

  8. Differential diagnosis of juvenile ankylosing spondylitis and juvenile rheumatoid arthritis by subtypes of HLA-B27 alleles%少儿强直性脊柱炎与幼儿类风湿性关节炎HLA-B27亚型的鉴别诊断

    林琳; 吴凤歧; 张新根; 刘雅琴; 王江


    the relationship of JAS and JRA with HLA-B27 allele subtypes and its role in the pathogenesis so as to find out the testing methods for earlier diagnosis of JAS or JRA. DESIGN:Non-random control laboratory study. SETTING,PARTICIPANTS and INTERVENTLONS:A total of 60 patients diagnosed with JAS or JRA in Beijing Children's Hospital were recruited,including 5 fathers or mothers from 5 patients' families, compared with 9 normal controls(from 200 donors for bone marrow transplantation).We studied 74 cases of HLA-B27 allele subtypes and analyzed their correlation by using PCR/SSP. MAIN OUTCOME MEASURES:Correlation of JAS and JRA with HLA-B27 allele subtypes; difference of HLA-B 2704 between JAS and JRA; data of patients' families.Haplotypes analysis and homozygote analysis on patients' families showed that there existed a close link between HLA-B* 2704 and C* 1202,but not with HLA-A,and that JAS had a remarkable tendency of family inheritance.RESULTS:HLA-B* 2704, * 2705, * 2702 and * 2707 were found in the cases.In JAS group, allelic frequency of HLA-B27 was B* 2704 56.25% , B* 2705 40.63% and B* 2702 3.13% ,respectively.However,in JRA group,it was B* 2705 60.7% ,B* 2704 28.57% ,B* 2702 3.57% and B* 2707 7.14%,respectively.Comparison between JAS and JRA showed that the allelic frequency of HLA-B* 2704 in JAS patients was higher than that in JAS patients(RR=3.21,P< 0.05). CONCLUSION:The susceptibility of JAS is positively associated with subtypes HLA-B* 2704.Testing HLA-B27 subtypes may be a valuable marker in differential diagnosis of JAS and JRA.

  9. Expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma

    Ying-Bin Liu; Jian-Wei Wang; Gui-Long Deng; Hai-Jun Li; Xue-Dong Feng; Hao-Ran Qian; Shun-Liang Gao; Xiao-Peng Chen; Shu-You Peng; He-Qing Fang; Yu-Lian Wu; Cheng-Hong Peng; Zhe Tang; Bin Xu


    AIM: To explore the relation between heparanase (HPA)and nm23-H1 in hepatocellular carcinoma (HCC), and whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC.METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry (S-P method) were used to measure the expressions of HPA mRNA and nm23-H1protein in primary tumor tissue and paracancerous tissue of 33 cases of HCC. Paracancerous tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up.RESULTS: The positive expression of HPA gene was significantly higher in primary tumor tissues of HCC (48.5%,L6/33) as compared to the paracancerous tissues of HCC and normal controls (3.03%, 1/33) (P<0.01). HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver.The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and in the group with metastasis or recurrence during the follow-up were significantly higher than those in the group with low tendency to metastasis or recurrence (62.5% vs 37.5%,P<0.05) and in the group without metastasis or recurrence (78.6% vs 21.4%, P<0.01). The poorly differentiated tumor and tumor of TNM stages Ⅲ-Ⅳ had a higher positive rate of HPA gene expression than the well differentiated tumor and tumor of TNM stages Ⅰ-Ⅱ (66.7% vs 33.3%, P<0.05). The positive expression rate of nm23-H1 protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (45.5, 72.7, 88.9%, P<0.05). nm23-H1 expression was not related with the size of tumor, envelope formation,AFP level, HBsAg state, cirrhosis of liver, Edmondson grade,and TNM stage (P>0.05). The positive rates of nm23-H1 in the group with high tendency to metastasis and recurrence and in patients with

  10. Comparative evaluation of acute respiratory distress syndrome in patients with and without H1N1 infection at a tertiary care referral center

    Tanvir Samra


    Full Text Available H1N1 subtype of influenza A virus has clinical presentation ranging from mild flu like illness to severe lung injury and acute respiratory distress syndrome (ARDS. The aim of our study was to compare the demographic characteristics, clinical presentation, and mortality of critically ill patients with (H1N1+ and without H1N1 infection (H1N1-. We retrospectively analyzed medical charts of patients admitted in "Swine Flu ICU" with ARDS from August 2009 to May 2010. Real-time reverse transcriptase polymerase chain reaction (RT-PCR assay was used for detection of H1N1 virus in the respiratory specimens. Clinical data from 106 (H1N1 , 45; H1N1+, 61 patients was collected and compared. Mean delay in presentation to our hospital was 5.7 ± 3.1 days and co-morbidities were present in two-fifth of the total admissions. Sequential Organ Failure Assessment (SOFA score of patients with and without H1N1 infection was comparable; 7.8 ± 3.5 and 6.6 ± 3.1 on day 1 and 7.2 ± 4.5 and 6.5 ± 3.1 on day 3, respectively. H1N1+ patients were relatively younger in age (34.2 ± 12.9 years vs. 42.8 ± 18.1, P = 0.005 but presented with significantly lower PaO 2 :FiO 2 ratio (87.3 ± 48.7 vs. 114 ± 51.7 in comparison to those who subsequently tested as H1N1 . The total leucocyte counts were significantly lower in H1N1+ patients during the first four days of illness but incidence of renal failure (P = 0.02 was higher in H1N1+ patients. The mortality in both the groups was high (H1N1+, 77%; H1N1, 68% but comparable. There was a mean delay of 5.7 ± 3.1 days in initiation of antivirals. Patients with H1N1 infection were relatively younger in age and with a significantly higher incidence of refractory hypoxia and acute renal failure. Mortality from ARDS reported in our study in both the groups was high but comparable.

  11. Description and characterization of HBWR Series H-1 test rods

    Wagoner, S.R.; Barner, J.O.; Welty, R.K.


    The as-built characterization results are presented for the HBWR Series H-1 test rods to be irradiated as part of the Fuel Performance Improvement Program (FPIP). The irradiation of these rods is to be conducted in the Halden Boiling Water Reactor (HBWR). Series H-1 consists of twelve rods for irradiation and six spares. Rod design types include (1) a reference dished pellet design, (2) an annular pellet design, (3) an annular pellet design combined with graphite-coated cladding, and (4) a packed-particle (vipac) design. The report, which describes the fabrication and detailed characterization results for the rods, is divided into four major sections: (1) experiment description, (2) process development required to fabricate the test rods, (3) methods and procedures used to fabricate and characterize the rods, and (4) a summary of the characterization results.

  12. 10 Years of Object-Oriented Analysis on H1

    Laycock, Paul


    Over a decade ago, the H1 Collaboration decided to embrace the object-oriented paradigm and completely redesign its data analysis model and data storage format. The event data model, based on the RooT framework, consists of three layers - tracks and calorimeter clusters, identified particles and finally event summary data - with a singleton class providing unified access. This original solution was then augmented with a fourth layer containing user-defined objects. This contribution will summarise the history of the solutions used, from modifications to the original design, to the evolution of the high-level end-user analysis object framework which is used by H1 today. Several important issues are addressed - the portability of expert knowledge to increase the efficiency of data analysis, the flexibility of the framework to incorporate new analyses, the performance and ease of use, and lessons learned for future projects.

  13. Influenza A (H1N1) 2009: a pandemic alarm

    Madhu Khanna; Neha Gupta; Ankit Gupta; V K Vijayan


    At this critical juncture when the world has not yet recovered from the threat of avian influenza, the virus has returned in the disguise of swine influenza, a lesser known illness common in pigs. It has reached pandemic proportions in a short time span with health personnel still devising ways to identify the novel H1N1 virus and develop vaccines against it. The H1N1 virus has caused a considerable number of deaths within the short duration since its emergence. Presently, there are no effective methods to contain this newly emerged virus. Therefore, a proper and clear insight is urgently required to prevent an outbreak in the future and make preparations that may be planned well in advance. This review is an attempt to discuss the historical perspective of the swine flu virus, its epidemiology and route of transmission to better understand the various control measures that may be taken to fight the danger of a global pandemic.

  14. Clinical profile of the first 1000 fatalities for influenza A (H1N1 in Mexico

    Germ and aacute;n Fajardo-Dolci


    Full Text Available Background: Influenza is an acute respiratory disease responsible for several episodes of high mortality throughout human history. In 2009, Mexico experienced an atypical influenza outbreak caused by a mutant strain of the influenza A (H1N1 subtype, which generated significant mortality. The aim of this paper was to analyze the clinical and sociodemographic conditions of the first 1000 fatalities recorded during this outbreak. Methods: We conducted a study based on an analysis of the clinical files of patients positive for influenza A (H1N1 using Real-Time-Polymerase Chain Reaction (RT-PCR to conduct an analysis of deaths compared to deaths in the general population. Results: The majority of deaths occurred in patients aged 35-84 years (65.8%. Average time between symptom onset and death was 13.8 days, with an average of 7.8 days from time of hospitalization until death. Ca. 25% of deaths occurred in residents from Mexico City and from the nearby State of Mexico. In the majority of cases, we found that patients who died had a low educational and socioeconomic status along with co-morbidities such as metabolic syndrome and its individual components, as well as respiratory illnesses. In 80% of cases, patients received mechanical ventilation, and a similar percentage received antiviral therapy (oseltamivir, zanamivir. Conclusions: The primary-care level was not utilized by patients who died from influenza. The higher prevalence of chronic degenerative diseases among deaths compared with the general population indicates that these groups of patients should be considered and prioritized in the event of future outbreaks. [Int J Res Med Sci 2015; 3(11.000: 3008-3014

  15. Influenza A pandemic (H1N1) 2009 virus infection

    BAI Lu; CAO Bin; WANG Chen


    The clinical spectrum of the 2009 pandemic influenza A (H1N1) infection ranged from self-limited mild illness to progressive pneumonia,or even a fatal outcome.We summarize the clinical manifestations,risk factors for severe and fatal cases,pathologic findings and treatment of this disease in this paper based on current reports from different regions of the world.

  16. Searches for New Physics Using H1 and ZEUS Data



    Recent searches for new physics in ep collisions performed by the H1 and ZEUS collaborations are presented. Limits on different contact interaction models, large extra dimensions, R-parity violating SUSY, excited fermions and anomalous flavour-changing top couplings are shown. In addition, searches for new physics in exclusive final states such as events with isolated leptons and large missing transverse momentum or multi-lepton final states are presented.

  17. Spread of H1N1 within Households


    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.  Created: 3/29/2010 by Emerging Infectious Diseases.   Date Released: 3/29/2010.

  18. Heterosubtypic immunity to influenza A virus infections in mallards may explain existence of multiple virus subtypes.

    Neus Latorre-Margalef

    Full Text Available Wild birds, particularly duck species, are the main reservoir of influenza A virus (IAV in nature. However, knowledge of IAV infection dynamics in the wild bird reservoir, and the development of immune responses, are essentially absent. Importantly, a detailed understanding of how subtype diversity is generated and maintained is lacking. To address this, 18,679 samples from 7728 Mallard ducks captured between 2002 and 2009 at a single stopover site in Sweden were screened for IAV infections, and the resulting 1081 virus isolates were analyzed for patterns of immunity. We found support for development of homosubtypic hemagglutinin (HA immunity during the peak of IAV infections in the fall. Moreover, re-infections with the same HA subtype and related prevalent HA subtypes were uncommon, suggesting the development of natural homosubtypic and heterosubtypic immunity (p-value = 0.02. Heterosubtypic immunity followed phylogenetic relatedness of HA subtypes, both at the level of HA clades (p-value = 0.04 and the level of HA groups (p-value = 0.05. In contrast, infection patterns did not support specific immunity for neuraminidase (NA subtypes. For the H1 and H3 Clades, heterosubtypic immunity showed a clear temporal pattern and we estimated within-clade immunity to last at least 30 days. The strength and duration of heterosubtypic immunity has important implications for transmission dynamics of IAV in the natural reservoir, where immune escape and disruptive selection may increase HA antigenic variation and explain IAV subtype diversity.

  19. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

    David L. Wachter


    Full Text Available Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin. Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A. In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies.

  20. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

    Wachter, David L.; Hartmann, Arndt; Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander; Bayer, Christian M.; Agaimy, Abbas


    Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies. PMID:24701575

  1. Histamine H1 antagonists and clinical characteristics of febrile seizures

    Zolaly MA


    Full Text Available Mohammed A ZolalyDepartment of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi ArabiaBackground: The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures.Methods: The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children's Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever.Results: Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine.Conclusion: Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.Keywords: antihistamine, nonantihistamine, histamine H1 antagonist, febrile seizures

  2. Aptamers that bind to the hemagglutinin of the recent pandemic influenza virus H1N1 and efficiently inhibit agglutination.

    Gopinath, Subash C B; Kumar, Penmetcha K R


    Influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza A viruses. In this study we have selected RNA aptamers (D-12 and D-26) that specifically target the HA protein of the recent pandemic influenza virus pdmH1N1 (A/California/07/2009). Among the selected aptamers the D-26 aptamer showed higher affinity for the HA of pdmH1N1 and was able to distinguish HA derived from other sub-types of influenza A viruses. The affinity of the D-26 aptamer was further improved upon incorporation of 2'-fluoropyrimidines to a level of 67 fM. Furthermore, the high affinity D-12 and D-26 aptamers were tested for their ability to interfere with HA-glycan interactions using a chicken red blood cell (RBC) agglutination assay. At a concentration of 200 nM the D-26 aptamer completely abolished the agglutination of RBCs, whereas D-12 only did so at 400 nM. These studies suggest that the selected aptamer D-26 not only has a higher affinity and specificity for the HA of pdmH1N1 but also has a better ability to efficiently interfere with HA-glycan interactions compared with the D-12 aptamer. The D-26 aptamer warrants further study regarding its application in developing topical virucidal products against the pdmH1N1 virus and also in surveillance of the pdmH1N1 influenza virus.

  3. [Rapid detection of novel avian influenza virus subtype H7N9 by multiplex real-time RT-PCR].

    Luo, Bao-Zheng; Mo, Qiu-Hua; Li, Ru-Shu; Bo, Qing-Ru; Xu, Hai-Nie; Sha, Cai-Hua; Liao, Xiu-Yun


    In order to develop a rapid detection kit for novel avian influenza virus (AIV) subtype H7N9, two sets of specific primers and probes were designed based on the nucleotide sequences of hemagglutinin antigen (HA) and neuraminidase antigen (NA) of novel H7N9 virus (2013) available in GenBank to establish the method of TaqMan probe-based multiplex real-time RT-PCR for rapid detection of AIV subtype H7N9. The primer and probe of HA were for all H7 subtype AIVs, while the primer and probe of NA were only for novel N9 subtype AIVs. The results showed that this method had high sensitivity and specificity. This method was applicable to the testing of positive standard sample with a minimum concentration of 10 copies/microL; it not only distinguished H7 subtype from H1, H3, H5, H6, and H9 subtypes, but also distinguished novel N9 subtype from traditional N9 subtype. A total of 2700 samples from Zhuhai, China were tested by this method, and the results were as expected. For the advantages of sensitivity and specificity, the method holds promise for wide application.

  4. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.

    Gerloff, Nancy A; Khan, Salah Uddin; Zanders, Natosha; Balish, Amanda; Haider, Najmul; Islam, Ausraful; Chowdhury, Sukanta; Rahman, Mahmudur Ziaur; Haque, Ainul; Hosseini, Parviez; Gurley, Emily S; Luby, Stephen P; Wentworth, David E; Donis, Ruben O; Sturm-Ramirez, Katharine; Davis, C Todd


    Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year

  5. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.

    Nancy A Gerloff

    Full Text Available Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50 were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the

  6. HIV-1 LTR subtype and perinatal transmission.

    Blackard, J T; Renjifo, B; Fawzi, W; Hertzmark, E; Msamanga, G; Mwakagile, D; Hunter, D; Spiegelman, D; Sharghi, N; Kagoma, C; Essex, M


    Multiple subtypes of HIV-1 have been identified; however, there is little data on the relative transmissibility of viruses belonging to different subtypes. A matched case-control study addressed whether viruses with different long terminal repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR subtype was determined for 45 matched cases and controls who participated in a clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype recombinant sequences were identified. Exact matched logistic regression analysis showed that viruses containing subtype A or intersubtype recombinant LTRs were 3.2 and 4.8 times more likely to be transmitted from mother to infant than viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times more likely to be transmitted than those with subtype D LTRs. These differences in transmission were independent of maternal CD4 at enrollment. Thus, it appears that HIV-1 subtype may be associated with differing rates of perinatal transmission in Tanzania. Copyright 2001 Academic Press.

  7. Community responses to communication campaigns for influenza A (H1N1: a focus group study

    Gray Lesley


    Full Text Available Abstract Background This research was a part of a contestable rapid response initiative launched by the Health Research Council of New Zealand and the Ministry of Health in response to the 2009 influenza A pandemic. The aim was to provide health authorities in New Zealand with evidence-based practical information to guide the development and delivery of effective health messages for H1N1 and other health campaigns. This study contributed to the initiative by providing qualitative data about community responses to key health messages in the 2009 and 2010 H1N1 campaigns, the impact of messages on behavioural change and the differential impact on vulnerable groups in New Zealand. Methods Qualitative data were collected on community responses to key health messages in the 2009 and 2010 Ministry of Health H1N1 campaigns, the impact of messages on behaviour and the differential impact on vulnerable groups. Eight focus groups were held in the winter of 2010 with 80 participants from groups identified by the Ministry of Health as vulnerable to the H1N1 virus, such as people with chronic health conditions, pregnant women, children, Pacific Peoples and Māori. Because this study was part of a rapid response initiative, focus groups were selected as the most efficient means of data collection in the time available. For Māori, focus group discussion (hui is a culturally appropriate methodology. Results Thematic analysis of data identified four major themes: personal and community risk, building community strategies, responsibility and information sources. People wanted messages about specific actions that they could take to protect themselves and their families and to mitigate any consequences. They wanted transparent and factual communication where both good and bad news is conveyed by people who they could trust. Conclusions The responses from all groups endorsed the need for community based risk management including information dissemination. Engaging

  8. A Novel Duplex Real-Time Reverse-Transcription PCR Assay for the Detection of Influenza A and the Novel Influenza A(H1N1 Strain

    Theo P. Sloots


    Full Text Available Timely implementation of antiviral treatment and other public health based responses are dependent on accurate and rapid diagnosis of the novel pandemic influenza A(H1N1 strain. In this study we developed a duplex real-time PCR (RT-PCR (dFLU-TM assay for the simultaneous detection of a broad range of influenza A subtypes and specific detection of the novel H1N1 2009 pandemic strain. The assay was compared to the combined results of two previously described monoplex RT-PCR assays using 183 clinical samples and 10 seasonal influenza A isolates. Overall, the results showed that the dFLU-TM RT-PCR method is suitable for detection of influenza A, including the novel H1N1 pandemic strain, in clinical samples.

  9. Modulation of behavior by the histaminergic system: lessons from H(1)R-and H(2)R-deficient mice.

    Schneider, Erich H; Neumann, Detlef; Seifert, Roland


    Besides acting in the immune system, histamine is also a neurotransmitter in the central nervous system. The H1R causes central side effects, e.g. of first generation antihistamines, antidepressants or antipsychotics and represents the component of the central histaminergic system most extensively studied in behavior experiments with knock-out mice. Central effects of H2R are similar, but only few behavioral results from knockout models are available. We summarize the behavior phenotype of H1R- and H2R-deficient mice, revealing histaminergic modulation of behaviors like locomotor activity, cognition, emotional states, arousal, sleep and wakefulness, circadian rhythm, pain perception, food intake and energy consumption, respiration and susceptibility to seizures. Knock-out models demonstrate several central effects of H1R and H2R that are not clinically and therapeutically exploited to date. We critically discuss problems and pitfalls of both the knock-out mouse technique and the pharmacological approach with receptor-selective ligands. The behavioral characterization of Hrh1(-/-)- and Hrh2(-/-)-mice is crucial, because many pharmacological agents lack the required selectivity to unequivocally address the functions of a single histamine receptor subtype.

  10. Post-translational modifications of linker histone H1 variants in mammals

    Starkova, T. Yu; Polyanichko, A. M.; Artamonova, T. O.; Khodorkovskii, M. A.; Kostyleva, E. I.; Chikhirzhina, E. V.; Tomilin, A. N.


    The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2–H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.

  11. Breast cancer molecular subtypes: from TNBC to QNBC

    Hon, Jane Date C; Singh, Baljit; Sahin, Aysegul; Du, Gang; Wang, Jinhua; Wang, Vincent Y; Deng, Fang-Ming; Zhang, David Y; Monaco, Marie E; Lee, Peng


    Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

  12. Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics

    Seredick Steve D


    Full Text Available Abstract Background Precise matching between motoneuron subtypes and the muscles they innervate is a prerequisite for normal behavior. Motoneuron subtype identity is specified by the combination of transcription factors expressed by the cell during its differentiation. Here we investigate the roles of Mnx family transcription factors in specifying the subtypes of individually identified zebrafish primary motoneurons. Results Zebrafish has three Mnx family members. We show that each of them has a distinct and temporally dynamic expression pattern in each primary motoneuron subtype. We also show that two Mnx family members are expressed in identified VeLD interneurons derived from the same progenitor domain that generates primary motoneurons. Surprisingly, we found that Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the CaP motoneuron subtype. Mnx proteins are, however, required for differentiation of the MiP motoneuron subtype. We previously showed that MiPs require two temporally-distinct phases of Islet1 expression for normal development. Here we show that in the absence of Mnx proteins, the later phase of Islet1 expression is initiated but not sustained, and MiPs become hybrids that co-express morphological and molecular features of motoneurons and V2a interneurons. Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear to be entirely transformed to a CaP morphology. Conclusions Our results suggest that Mnx proteins promote MiP subtype identity by suppressing both interneuron development and CaP axon pathfinding. This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons.

  13. Novel Influenza A (H1N1) Virus Infection in Children: Chest Radiographic and CT Evaluation

    Choi, Min Jeong; Lee, Young Seok; Lee, Jee Young; Lee, Kun Song [Dankook University College of Medicine, Dankook University Hospital, Cheonan (Korea, Republic of)


    The purpose of this study was to evaluate the chest radiographic and CT findings of novel influenza A (H1N1) virus infection in children, the population that is more vulnerable to respiratory infection than adults. The study population comprised 410 children who were diagnosed with an H1N1 infection from August 24, 2009 to November 11, 2009 and underwent chest radiography at Dankook University Hospital in Korea. Six of these patients also underwent chest CT. The initial chest radiographs were classified as normal or abnormal. The abnormal chest radiographs and high resolution CT scans were assessed for the pattern and distribution of parenchymal lesions, and the presence of complications such as atelectasis, pleural effusion, and pneumomediastinum. The initial chest radiograph was normal in 384 of 410 (94%) patients and abnormal in 26 of 410 (6%) patients. Parenchymal abnormalities seen on the initial chest radiographs included prominent peribronchial marking (25 of 26, 96%), consolidation (22 of 26, 85%), and ground-glass opacities without consolidation (2 of 26, 8%). The involvement was usually bilateral (19 of 26, 73%) with the lower lung zone predominance (22 of 26, 85%). Atelectasis was observed in 12 (46%) and pleural effusion in 11 (42%) patients. CT (n = 6) scans showed peribronchovascular interstitial thickening (n = 6), ground-glass opacities (n = 5), centrilobular nodules (n = 4), consolidation (n = 3), mediastinal lymph node enlargement (n = 5), pleural effusion (n = 3), and pneumomediastinum (n = 3). Abnormal chest radiographs were uncommon in children with a swine-origin influenza A (H1N1) virus (S-OIV) infection. In children, H1N1 virus infection can be included in the differential diagnosis, when chest radiographs and CT scans show prominent peribronchial markings and ill-defined patchy consolidation with mediastinal lymph node enlargement, pleural effusion and pneumomediastinum

  14. Spillback transmission of European H1N1 avian-like swine influenza viruses to turkeys: A strain-dependent possibility?

    Bonfante, Francesco; Fusaro, Alice; Tassoni, Luca; Patrono, Livia Victoria; Milani, Adelaide; Maniero, Silvia; Salviato, Annalisa; Terregino, Calogero


    In 1979, an avian influenza virus of the H1N1 subtype began to circulate in European swine herds, rapidly replacing classical swine H1N1 viruses. Spill-back transmissions to turkeys were recorded occasionally, but they might have been underreported due to the asymptomatic nature of the infection and the lack of specific surveillance. In our study, we evaluated the infectivity and transmissibility in turkeys of seven strains of H1N1 avian-like swine viruses isolated from 1979 to 2006, and compared them with their closest progenitor A/duck/Bavaria/1/77 (H1N1), to establish whether the adaptation to pigs has gradually decreased their fitness in turkeys. Our data indicate that the circulation of European H1N1 in pigs might have impaired the possibility of infecting turkeys. Nevertheless, the two swine-origin strains, which showed the ability to replicate and transmit in turkeys, possess typical swine-like genetic traits, not different from the rest of the tested isolates, suggesting replication of avian-like swine H1N1 viruses in turkeys as a strain-dependent polygenic feature.

  15. On total variation flows with H-1 penalty

    Wunderli, Thomas


    We analyze the time flow of a version of the Rudin-Osher-Fatemi [5] model for image restoration using the bounded variation semi-norm with H-1 penalty. We will define an appropriate weak solution of the time flow and prove existence and uniqueness of the solution using the method of semigroups, as used by Andreu, Ballester, Caselles, Mazön [1] for their analysis of total variation flow without penalty. We also note two interesting properties for the time solutions.

  16. Underreporting of 2009 H1N1 Influenza Cases


    Influenza cases are difficult to track because many people don't go to the doctor or get tested for flu when they're sick. The first months of the 2009 H1N1 influenza pandemic were no different. In this podcast, CDC's Dr. Carrie Reed discusses a study in the December issue of Emerging Infectious Diseases that looked at the actual number of cases reported and estimated the true number of cases when correcting for underreporting.  Created: 12/8/2009 by Emerging Infectious Diseases.   Date Released: 12/8/2009.

  17. Genetic contributions to subtypes of aggression


    Boys and girls may display different styles of aggression. The aim of this study was to identify subtypes of aggression within the Child Behavior Checklist (CBCL) aggression scale, and determine their characteristics for both sexes. Maternal CBCL ratings of 7449 7-year-old twin pairs were analyzed using principal components analyses to identify subtypes of aggression, and structural equation modeling to carry out genetic analyses. Two aggression subtypes were identified: relational and direct...

  18. Discovery and validation of breast cancer subtypes

    Bukholm Ida RK


    Full Text Available Abstract Background Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. Results Based upon the analysis of 599 microarrays (five separate cDNA microarray datasets using a novel approach, we present evidence in support of the most consistently identifiable subtypes of breast cancer tumor tissue microarrays being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2 subtypes. We validate all three subtypes statistically and show the subtype to which a sample belongs is a significant predictor of overall survival and distant-metastasis free probability. Conclusion As a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.

  19. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  20. Subsisting H1N1 influenza memory responses are insufficient to protect from pandemic H1N1 influenza challenge in C57BL/6 mice

    Sage, Leo K.; Fox, Julie M.; Tompkins, Stephen M.; Ralph A. Tripp


    The 2009 swine-origin pandemic H1N1 (pH1N1) influenza virus transmitted and caused disease in many individuals immune to pre-2009 H1N1 influenza virus. Whilst extensive studies on antibody-mediated pH1N1 cross-reactivity have been described, few studies have focused on influenza-specific memory T-cells. To address this, the immune response in pre-2009 H1N1 influenza-immune mice was evaluated after pH1N1 challenge and disease pathogenesis was determined. The results show that despite homology ...

  1. Safety profile of bilastine: 2nd generation H1-antihistamines.

    Scaglione, F


    Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

  2. Neuraminidase subtyping of avian influenza viruses with PrimerHunter-designed primers and quadruplicate primer pools.

    Huang, Yanyan; Khan, Mazhar I; Khan, Mazhar; Măndoiu, Ion; Măndoiu, Ion I


    We have previously developed a software package called PrimerHunter to design primers for PCR-based virus subtyping. In this study, 9 pairs of primers were designed with PrimerHunter and successfully used to differentiate the 9 neuraminidase (NA) genes of avian influenza viruses (AIVs) in multiple PCR-based assays. Furthermore, primer pools were designed and successfully used to decrease the number of reactions needed for NA subtyping from 9 to 4. The quadruplicate primer-pool method is cost-saving, and was shown to be suitable for the NA subtyping of both cultured AIVs and uncultured AIV swab samples. The primers selected for this study showed excellent sensitivity and specificity in NA subtyping by RT-PCR, SYBR green-based Real-time PCR and Real-time RT-PCR methods. AIV RNA of 2 to 200 copies (varied by NA subtypes) could be detected by these reactions. No unspecific amplification was displayed when detecting RNAs of other avian infectious viruses such as Infectious bronchitis virus, Infectious bursal disease virus and Newcastle disease virus. In summary, this study introduced several sensitive and specific PCR-based assays for NA subtyping of AIVs and also validated again the effectiveness of the PrimerHunter tool for the design of subtyping primers.

  3. Childhood adversity subtypes and depressive symptoms in early and late adolescence.

    St Clair, Michelle C; Croudace, Tim; Dunn, Valerie J; Jones, Peter B; Herbert, Joe; Goodyer, Ian M


    Within a longitudinal study of 1,005 adolescents, we investigated how exposure to childhood psychosocial adversities was associated with the emergence of depressive symptoms between 14 and 17 years of age. The cohort was classified into four empirically determined adversity subtypes for two age periods in childhood (0-5 and 6-11 years). One subtype reflects normative/optimal family environments (n = 692, 69%), while the other three subtypes reflect differential suboptimal family environments (aberrant parenting: n = 71, 7%; discordant: n = 185, 18%; and hazardous: n = 57, 6%). Parent-rated child temperament at 14 years and adolescent self-reported recent negative life events in early and late adolescence were included in models implementing path analysis. There were gender-differentiated associations between childhood adversity subtypes and adolescent depressive symptoms. The discordant and hazardous subtypes were associated with elevated depressive symptoms in both genders but the aberrant parenting subtype only so in girls. Across adolescence the associations between early childhood adversity and depressive symptoms diminished for boys but remained for girls. Emotional temperament was also associated with depressive symptoms in both genders, while proximal negative life events related to depressive symptoms in girls only. There may be neurodevelopmental factors that emerge in adolescence that reduce depressogenic symptoms in boys but increase such formation in girls.

  4. B7-H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells.

    Sheng-Jia Shi

    Full Text Available BACKGROUND AND OBJECTIVE: The investigation concerning the B7-H1 expression in colorectal cancer cells is at an early stage. It is unclear whether B7-H1 expression may have diagnostic or prognostic value in colorectal carcinoma. Additionally, how B7-H1 is associated with the clinical features of colorectal carcinoma is not known. In order to investigate the relationship between B7-H1 and colorectal cancer, we analyzed B7-H1 expression and its effect in clinical specimens and HCT116 cells. METHODS: Paraffin-embedded specimens from 143 eligible patients were used to investigate the expression of CD274 by immunohistochemistry. We also examined whether B7-H1 itself may be related to cell proliferation, apoptosis, migration and invasion in colon cancer HCT116 cells. RESULTS: Our results show that B7-H1 was highly expressed in colorectal carcinoma and was significantly associated with cell differentiation status and TNM (Tumor Node Metastasis stage. Patients with positive B7-H1 expression showed a trend of shorter survival time. Using multivariate analysis, we demonstrate that positive B7-H1 expression is an independent predictor of colorectal carcinoma prognosis. Our results indicate that B7-H1 silencing with siRNA inhibits cell proliferation, migration and invasion. Furthermore, cell apoptosis was also increased by B7-H1 inhibition. CONCLUSIONS: Positive B7-H1 expression is an independent predictor for colorectal carcinoma prognosis. Moreover, knockdown of B7-H1 can inhibit cell proliferation, migration and invasion.

  5. Antiviral Protein of Momordica charantia L. Inhibits Different Subtypes of Influenza A

    Viroj Pongthanapisith


    Full Text Available The new antiviral activity of the protein extracted from Momordica charantia was determined with different subtypes of influenza A. The protein was purified from the seed of M. charantia using an anion exchanger and a Fast Protein Liquid Chromatography (FPLC system. At the concentration of 1.401 mg/mL, the protein did not exhibit cytotoxicity in Madin-Darby canine kidney cells (MDCK but inhibited FFU influenza A/PR/8/34 H1N1 virus at 56.50%, 65.72%, and 100% inhibition by the protein treated before the virus (pretreated, the protein treated alongside with the virus (simultaneously treated, and the protein treated after the virus (posttreated during incubation, respectively. Using 5, 25, and 100 TCID50 of influenza A/New Caledonia/20/99 H1N1, A/Fujian/411/01 H3N2 and A/Thailand/1(KAN-1/2004 H5N1, the IC50 was calculated to be 100, 150, and 200; 75, 175, and 300; and 40, 75, and 200 μg/mL, respectively. Our present finding indicated that the plant protein inhibited not only H1N1 and H3N2 but also H5N1 subtype. As a result of the broad spectrum of its antiviral activity, this edible plant can be developed as an effective therapeutic agent against various and even new emerging subtypes of influenza A.

  6. Pandemic (H1N1 influenza in Diyarbakir, 2009

    Meliksah Ertem


    Full Text Available  Objective: This study was conducted to evaluate the pandemic (H1N1 influenza outbreak in 2009. Method: Influenza like illness (ILI cases were reported between the 36th to 53rd weeks of the pandemic, from all health centres. 731 nasopharyngeal swabs were collected from ILI cases. Results: The first H1N1 confirmed case was reported at the 36th week and an increasing trend continued. At the 43rd week the outbreak reached its maximum level and at the 53rd week the level had decreased to the level at the start. During the outbreak 31117 cases were reported as ILI and 635 cases were hospitalized (hospitalization rate was 2.0% and 17 H1N1 laboratory confirmed cases died (mortality rate 11.5/1.000.000. Symptoms of laboratory confirmed cases were similar to seasonal influenza. Coughing (90.9%, fever (84.5%, running nose (69.5%, headache (73.4%, diarrhoea (17.5% were the some of the symptoms in laboratory confirmed cases. The median interval between the onset of symptoms and hospital admission was 3.5 days (min: 1, max: 11 days and this was 7.5 days for the occurrence of death. Conclusion: During 36th to 53rd week an important outbreak of ILI was occurred. The mortality rate was not so high as expected but the infectivity was high. The delay for hospital admission may lead to higher mortality particularly for pregnant women.Key Words: Pandemic influenza; H1N1; case fatality rate; hospitalization rateDiyarbakır’da pandemik (H1N1 influenza, 2009Amaç: Bu çalışmada 2009 yılında -Türkiye’de pandemik influenza salgınını değerlendirmek amaçlanmıştır. Yöntem: Diyarbakır ’da 36 ve 53. haftalar arasında tüm sağlık kuruluşlarından influenza benzeri hastalık rapor edilmiştir. 731 nazofaringeal sürüntü alınmıştır. Bulgular: İlk H1N1 doğrulanmış vaka 36.haftada rapor edilmiştir ve vaka sayıları zaman içinde artış göstermiştir. 43. haftada salgın başlamış ve 53. haftada başlangıç düzeyine inmiştir.Salgın s

  7. High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.

    Komadina, Naomi; Quiñones-Parra, Sergio M; Kedzierska, Katherine; McCaw, James M; Kelso, Anne; Leder, Karin; McVernon, Jodie


    Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc.

  8. H1N1: pandemia e perspectiva atual


    O vírus influenza de origem suína, A/California/04/2009 (H1N1), foi inicialmente detectado no México e determinou a pandemia de influenza de 2009. Em agosto de 2010, a Organização Mundial da Saúde (OMS) declarou o início da fase pós-pandêmica. As características dessa última pandemia foram marcadamente diferentes das anteriores. O vírus emergiu de rearranjos genéticos originários em hospedeiro mamífero não humano, demonstrou transmissibilidade interespécies e afetou a população humana de form...

  9. Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility.

    Stefano Merler

    Full Text Available BACKGROUND: A common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated. METHODS: The level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40, was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model. RESULTS: By comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%. Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI. CONCLUSIONS: Our results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in

  10. Citrullination regulates pluripotency and histone H1 binding to chromatin

    Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony


    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.

  11. Technicon H*1 Hematology System: Optical Design Considerations

    Colella, G. M.; Tycko, D. H.; Groner, W.


    The Technicon H*1 systemTM is a clinical laboratory flow cytometer which performs a complete hematology profile, providing quantitative information on the various types of cells in a blood sample. A light-scattering method, using a HeNe laser, determines in a single flow channel the red cell count, platelet count, and the distributions of red cell volume, red cell hemoglobin concentration, and platelet volume. To accomplish this the scattered light from each red cell in the sample is measured in real time at two angular intervals. The cell volume and the hemoglobin concentration within the cell are derived from these two measurements. Severe accuracy and precision specifications are placed on the medically important red cell count (RBC) and the mean red cell volume (MCV). From the point of view of optical system design, the dominant factor is the requirement that RBC and MCV have precision and accuracy of the order of 2%. Signal-to-noise and scattering-angle definition requirements dictated the choice of a HeNe laser light source. The optics includes an illumination system for producing a sharply defined, uniformly illuminated scattering region and a detection system which must accurately define the accepted scattering angles. In previous cytometric methods for determining MCV only a single quantity was measured for each cell. Such methods cannot disentangle the independent effects of cell size and hemoglobin concentration on the measurement, thus compromising MCV accuracy. The present double-angle scattering method overcomes this accuracy problem. The H*1 red cell method, the supporting optical design and data demonstrating that the use of this technique eliminates interference between the observed red cell indices are presented.

  12. Transsexual subtypes : Clinical and theoretical significance

    Smith, YLS; van Goozen, SHM; Kuiper, AJ; Cohen-Kettenis, PT


    The present study was designed to investigate whether transsexuals can be validly subdivided into subtypes on the basis of sexual orientation, and whether differences between subtypes of transsexuals are similar for male-to-female (ME) and female-to-male transsexuals (FMs). Within a large transsexua

  13. Molecular Subtypes of Uterine Leiomyosarcoma and Correlation with Clinical Outcome

    Joyce N. Barlin


    Full Text Available The molecular etiology of uterine leiomyosarcoma (ULMS is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS and normal myometrium (NL to identify clinically relevant molecular subtypes. Discovery cases included 29 NL and 23 ULMS specimens. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. Fourteen NL and 44 ULMS independent archival samples were used for external validation. Molecular subgroups were correlated with clinical outcome. Pathway analyses of differentially expressed genes between ULMS and NL samples identified overrepresentation of cell cycle regulation, DNA repair, and genomic integrity. External validation confirmed differential expression in 31 genes (P < 4.4 × 10−4, Bonferroni corrected, with 84% of the overexpressed genes, including CDC7, CDC20, GTSE1, CCNA2, CCNB1, and CCNB2, participating in cell cycle regulation. Unsupervised clustering of ULMS identified two clades that were reproducibly associated with progression-free (median, 4.0 vs 26.0 months; P = .02; HR, 0.33 and overall (median, 18.2 vs 77.2 months; P = .04; HR, 0.33 survival. Cell cycle genes play a key role in ULMS sarcomagenesis, providing opportunities for therapeutic targeting. Reproducible molecular subtypes associated with clinical outcome may permit individualized adjuvant treatment after clinical trial validation.

  14. ADHD-hyperactive/impulsive subtype in adults

    Stephen V. Faraone


    Full Text Available This is the first study to evaluate ADHD-hyperactive/impulsive subtype in a large clinical sample of adults with ADHD. The Quality of Life, Effectiveness, Safety and Tolerability (QuEST study included 725 adults who received clinician diagnoses of any ADHD subtype. Cross-sectional baseline data from 691 patients diagnosed with the hyperactive/impulsive (HI, inattentive (IA and combined subtypes were used to compare the groups on the clinician administered ADHD-RS, clinical features and health-related quality of life. A consistent pattern of differences was found between the ADHD-I and combined subtypes, with the combined subtype being more likely to be diagnosed in childhood, more severe symptom severity and lower HRQL. Twenty-three patients out of the total sample of 691 patients (3% received a clinician diagnosis of ADHD - hyperactive/impulsive subtype. Review of the ratings on the ADHD-RS-IV demonstrated, however, that this group had ratings of inattention comparable to the inattentive group. There were no significant differences found between the ADHD-HI and the other subtypes in symptom severity, functioning or quality of life. The hyperactive/impulsive subtype group identified by clinicians in this study was not significantly different from the rest of the sample. By contrast, significant differences were found between the inattentive and combined types. This suggests that in adults, hyperactivity declines and inattention remains significant, making the hyperactive/impulsive subtype as defined by childhood criteria a very rare condition and raising questions as to the validity of the HI subtype in adults.

  15. 2009 pandemic influenza A (H1N1 virus outbreak and response--Rwanda, October, 2009-May, 2010.

    Justin Wane

    Full Text Available BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1pdm09 (pH1N1 was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL. Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532 of specimens tested influenza positive; of these 96% (n = 510 were influenza A and 4% (n = 22 were influenza B. Of cases testing influenza A positive, 96.8% (n = 494, 3% (n = 15, and 0.2% (n = 1 were A(H1N1pdm09, Seasonal A(H3 and Seasonal A(non-subtyped, respectively. Among laboratory-confirmed cases, 263 (53.2% were children <15 years and 275 (52% were female. In total, 58 (12% cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days. All cases recovered and there were no deaths. Overall, 339 (68% confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532 were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532, asthma 0.8% (4/532, cardiac disease 1.5% (8/532, pregnancy 0.6% (3/532, diabetes mellitus 0.4% (2/532, and chronic malnutrition 0.8% (4/532. CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to

  16. Statistical support for subtypes in posttraumatic stress disorder: the how and why of subtype analysis.

    Dalenberg, Constance J; Glaser, Dale; Alhassoon, Omar M


    A number of researchers have argued for the existence of different subtypes of posttraumatic stress disorder (PTSD). In the current paper we present criteria by which to assess these putative subtypes, clarify potential pitfalls of the statistical methods employed to determine them, and propose alternative methods for such determinations. Specifically, three PTSD subtypes are examined: (1) complex PTSD, (2) externalizing/internalizing PTSD, and (3) dissociative/nondissociative PTSD. In addition, three criteria are proposed for subtype evaluation, these are the need for (1) reliability and clarity of definition, (2) distinctions between subtypes either structurally or by mechanism, and (3) clinical meaningfulness. Common statistical evidence for subtyping, such as statistical mean difference and cluster analysis, are presented and evaluated. Finally, more robust statistical methods are suggested for future research on PTSD subtyping. © 2012 Wiley Periodicals, Inc.

  17. Lymphatic metastasis and nm23H1 genetic instability in Chinese colon cancer patients

    Zhi-Hong Su; Ji-Cheng Li


    AIM: To investigate the pathogenic mechanism of colon cancer at the molecular level and to elucidate the relationship between intercellular adhesion molecule-1 (ICAM-1) and nm23H1 genes and Chinese patients with colon cancer.METHODS: DNA was extracted from paraffin-embedded materials. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze MSI and LOH. Expression of ICAM-1 was detected by Envision immunohistochemistry. Experimental results were analyzed with Leica-Qwin computer imaging techniques and SPSS software of statistics.RESULTS: ICAM-1 expression of lymphatic endothelium was negative in normal colon and positive in colon cancer respedively.The number of lymphatics positive for ICAM-1 was gradually increased with degree of cancer invasion (P<0.01). In the group with metastasis of colon cancer, the number of lymphatics positive for ICAM-1 in lymph nodes was more than that in the group with no metastasis (P<0.01). The frequency of MSI, LOH and nm23H1 protein was 26.67%, 20.00% and 53.33% in colon cancer, respectively. In TNM staging, MSI (43.75%) and nm23H1 protein (81.25%) in stages Ⅰ+Ⅱ were detected more easily than the corresponding indexes (MSI:7.14%, P<0.05 and nm23H1: 21.43%, P<0.01) in stages Ⅲ+Ⅳ. By comparison, the frequency of LOH (35.71%) in stages Ⅲ+Ⅳ was more than that of LOH (6.25%, P<0.05)in stages Ⅰ+Ⅱ. LOH exhibited a rising trend along with the Duke's staging. nm23H1 protein in the group of tubular adenocarcinoma (60.00%) was higher expressed than that in the group of mucoid adenocarcinoma (20.00%) (P<0.01),and exhibited a rising trend with the differentiation degrees of tubular adenocarcinoma. nm23H1 protein in MSI positive group was higher expressed (75%) than that in MSI negative group (45.45%, P<0.05).CONCLUSION: The expression of ICAM-1 in lymphatic vessels is beneficial to the judgement of the invasion and metastasis ability of colon cancer and the anti-tumor immunity

  18. Boiling peanut Ara h 1 results in the formation of aggregates with reduced allergenicity

    F. Blanc; Y.M. Vissers; K. Adel-Patient; N.M. Rigby; A.R. Mackie; A.P. Gunning; N.K. Wellner; P.S. Skov; L. Przybylski-Nicaise; B. Ballmer-Weber; L. Zuidmeer-Jongejan; Z. Szepfalusi; J. Ruinemans-Koerts; A.P.H. Jansen; H. Bernard; J.M. Wal; H.F.J. Savelkoul; H.J. Wichers; E.N.C. Mills


    Scope: Roasting rather than boiling and Maillard modifications may modulate peanut allergenicity. We investigated how these factors affect the allergenic properties of a major peanut allergen, Ara h 1. Methods and results: Ara h 1 was purified from either raw (N-Ara h 1) or roasted (R-Ara h 1) peanu

  19. Linker histone variant H1T targets rDNA repeats.

    Tani, Ruiko; Hayakawa, Koji; Tanaka, Satoshi; Shiota, Kunio


    H1T is a linker histone H1 variant that is highly expressed at the primary spermatocyte stage through to the early spermatid stage of spermatogenesis. While the functions of the somatic types of H1 have been extensively investigated, the intracellular role of H1T is unclear. H1 variants specifically expressed in germ cells show low amino acid sequence homology to somatic H1s, which suggests that the functions or target loci of germ cell-specific H1T differ from those of somatic H1s. Here, we describe the target loci and function of H1T. H1T was expressed not only in the testis but also in tumor cell lines, mouse embryonic stem cells (mESCs), and some normal somatic cells. To elucidate the intracellular localization and target loci of H1T, fluorescent immunostaining and ChIP-seq were performed in tumor cells and mESCs. We found that H1T accumulated in nucleoli and predominantly targeted rDNA repeats, which differ from somatic H1 targets. Furthermore, by nuclease sensitivity assay and RT-qPCR, we showed that H1T repressed rDNA transcription by condensing chromatin structure. Imaging analysis indicated that H1T expression affected nucleolar formation. We concluded that H1T plays a role in rDNA transcription, by distinctively targeting rDNA repeats.

  20. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

    Ji-Ah Kang

    Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  1. Classifying anatomical subtypes of subjective memory impairment.

    Jung, Na-Yeon; Seo, Sang Won; Yoo, Heejin; Yang, Jin-Ju; Park, Seongbeom; Kim, Yeo Jin; Lee, Juyoun; Lee, Jin San; Jang, Young Kyoung; Lee, Jong Min; Kim, Sung Tae; Kim, Seonwoo; Kim, Eun-Joo; Na, Duk L; Kim, Hee Jin


    We aimed to categorize subjective memory impairment (SMI) individuals based on their patterns of cortical thickness and to propose simple models that can classify each subtype. We recruited 613 SMI individuals and 613 age- and gender-matched normal controls. Using hierarchical agglomerative cluster analysis, SMI individuals were divided into 3 subtypes: temporal atrophy (12.9%), minimal atrophy (52.4%), and diffuse atrophy (34.6%). Individuals in the temporal atrophy (Alzheimer's disease-like atrophy) subtype were older, had more vascular risk factors, and scored the lowest on neuropsychological tests. Combination of these factors classified the temporal atrophy subtype with 73.2% accuracy. On the other hand, individuals with the minimal atrophy (non-neurodegenerative) subtype were younger, were more likely to be female, and had depression. Combination of these factors discriminated the minimal atrophy subtype with 76.0% accuracy. We suggest that SMI can be largely categorized into 3 anatomical subtypes that have distinct clinical features. Our models may help physicians decide next steps when encountering SMI patients and may also be used in clinical trials.

  2. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

    Taosheng Xu

    RNA-TF-mRNA sub-networks vary across different identified subtypes. In addition, pathway enrichment analyses show that the top pathways involving the most differentially expressed genes in each of the identified subtypes are different. The results would provide valuable information for understanding the mechanisms characterising different cancer subtypes and assist the design of treatment therapies. All datasets and the R scripts to reproduce the results are available online at the website:

  3. Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

    Tsuge, Mitsuru; Oka, Takashi; Yamashita, Nobuko; Saito, Yukie; Fujii, Yosuke; Nagaoka, Yoshiharu; Yashiro, Masato; Tsukahara, Hirokazu; Morishima, Tsuneo


    Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

  4. Neural network subtyping of depression.

    Florio, T M; Parker, G; Austin, M P; Hickie, I; Mitchell, P; Wilhelm, K


    To examine the applicability of a neural network classification strategy to examine the independent contribution of psychomotor disturbance (PMD) and endogeneity symptoms to the DSM-III-R definition of melancholia. We studied 407 depressed patients with the clinical dataset comprising 17 endogeneity symptoms and the 18-item CORE measure of behaviourally rated PMD. A multilayer perception neural network was used to fit non-linear models of varying complexity. A linear discriminant function analysis was also used to generate a model for comparison with the non-linear models. Models (linear and non-linear) using PMD items only and endogeneity symptoms only had similar rates of successful classification, while non-linear models combining both PMD and symptoms scores achieved the best classifications. Our current non-linear model was superior to a linear analysis, a finding which may have wider application to psychiatric classification. Our non-linear analysis of depressive subtypes supports the binary view that melancholic and non-melancholic depression are separate clinical disorders rather than different forms of the same entity. This study illustrates how non-linear modelling with neural networks is a potentially fruitful approach to the study of the diagnostic taxonomy of psychiatric disorders and to clinical decision-making.

  5. GC–MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons

    Siwen Liu


    Full Text Available Borna disease virus (BDV persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC–MS metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12, Strain V-infected cells (n = 12, and CON cells (n = 11. Partial least squares discriminant analysis (PLS-DA was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON, 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON, and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V. Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

  6. A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

    Boonsathorn, Naphatsawan; Panthong, Sumolrat [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Koksunan, Sarawut [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya [National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Prachasupap, Apichai [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Sasaki, Tadahiro [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); Yasugi, Mayo [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); Ono, Ken-ichiro [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Arai, Yasuha [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); and others


    Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

  7. PLC-γ1 signaling plays a subtype-specific role in postbinding cell entry of influenza A virus.

    Zhu, Liqian; Ly, Hinh; Liang, Yuying


    Host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. In this study, we report the engagement of host phosphoinositide-specific phospholipase γ1 (PLC-γ1) in mediating cell entry of influenza virus H1N1 but not H3N2 subtype. Both PLC-γ1-specific inhibitor and short hairpin RNA (shRNA) strongly suppress the replication of H1N1 but not H3N2 viruses in cell culture, suggesting that PLC-γ1 plays an important subtype-specific role in the influenza viral life cycle. Further analyses demonstrate that PLC-γ1 activation is required for viral postbinding cell entry. In addition, H1N1, but not H3N2, infection leads to the phosphorylation of PLC-γ1 at Ser 1248 immediately after infection and independent of viral replication. We have further shown that H1N1-induced PLC-γ1 activation is downstream of epidermal growth factor receptor (EGFR) signaling. Interestingly, both H1N1 and H3N2 infections activate EGFR, but only H1N1 infection leads to PLC-γ1 activation. Taking our findings together, we have identified for the first time the subtype-specific interplay of host PLC-γ1 signaling and H1N1 virus that is critical for viral uptake early in the infection. Our study provides novel insights into how virus interacts with the cellular signaling network by demonstrating that viral determinants can regulate how the host signaling pathways function in virally infected cells.

  8. Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation.

    Kwit, Krzysztof; Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona


    The present study was planned to study the effect of various subtypes of swine influenza virus (SIV) circulating among pigs (H1N2, H3N2 and emerging pandemic strain of H1N1 influenza A virus (H1N1pdm09) on the course of pregnancy in naïve gilts experimentally infected during the last month of pregnancy. In addition, the clinical course of infection, distribution of viruses in various tissues (blood, placenta, fetal lung), and selected immunological, reproductive and productive parameters were also investigated. All SIV-inoculated gilts became infected. No abortions, stillbirths, intrauterine deaths or mummified fetuses were observed. No clinical signs of influenza virus infection or other disorders were observed in piglets born from infected and control gilts. There was a significant decrease in the number and frequency of lymphocytes in gilts inoculated with all influenza viruses. In general, the concentrations of IL-6, IL-10 and TNF-α were significantly higher in SIV-inoculated gilts as than in control animals, while IL-4 and IFN-γ were not detected in plasma at any time post-inoculation in SIV- or mock-inoculated gilts. No evidence for transplacental transmission of SIV was found. Viremia was also not observed in any of the infected females. On the basis of recent results, we hypothesize that pregnancy failure observed during SIV infection under field conditions is probably related to high fever and pro-inflammatory cytokines rather than a direct effect of the virus on the placenta, embryo or fetus.

  9. Histological subtypes of oral non-tonsillar squamous cell carcinoma in dogs.

    Nemec, A; Murphy, B; Kass, P H; Verstraete, F J M


    Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location.

  10. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  11. High-resolution subtyping of Staphylococcus aureus strains by means of Fourier-transform infrared spectroscopy.

    Johler, Sophia; Stephan, Roger; Althaus, Denise; Ehling-Schulz, Monika; Grunert, Tom


    Staphylococcus aureus causes a variety of serious illnesses in humans and animals. Subtyping of S. aureus isolates plays a crucial role in epidemiological investigations. Metabolic fingerprinting by Fourier-transform infrared (FTIR) spectroscopy is commonly used to identify microbes at species as well as subspecies level. In this study, we aimed to assess the suitability of FTIR spectroscopy as a tool for S. aureus subtyping. To this end, we compared the subtyping performance of FTIR spectroscopy to other subtyping methods such as pulsed field gel electrophoresis (PFGE) and spa typing in a blinded experimental setup and investigated the ability of FTIR spectroscopy for identifying S. aureus clonal complexes (CC). A total of 70 S. aureus strains from human, animal, and food sources were selected, for which clonal complexes and a unique virulence and resistance gene pattern had been determined by DNA microarray analysis. FTIR spectral analysis resulted in high discriminatory power similar as obtained by spa typing and PFGE. High directional concordance was found between FTIR spectroscopy based subtypes and capsular polysaccharide expression detected by FTIR spectroscopy and the cap specific locus, reflecting strain specific expression of capsular polysaccharides and/or other surface glycopolymers, such as wall teichoic acid, peptidoglycane, and lipoteichoic acid. Supervised chemometrics showed only limited possibilities for differentiation of S. aureus CC by FTIR spectroscopy with the exception of CC45 and CC705. In conclusion, FTIR spectroscopy represents a valuable tool for S. aureus subtyping, which complements current molecular and proteomic strain typing.

  12. Drug Resistance in Non-B Subtype HIV-1: Impact of HIV-1 Reverse Transcriptase Inhibitors

    Kamalendra Singh


    Full Text Available Human immunodeficiency virus (HIV causes approximately 2.5 million new infections every year, and nearly 1.6 million patients succumb to HIV each year. Several factors, including cross-species transmission and error-prone replication have resulted in extraordinary genetic diversity of HIV groups. One of these groups, known as group M (main contains nine subtypes (A-D, F-H and J-K and causes ~95% of all HIV infections. Most reported data on susceptibility and resistance to anti-HIV therapies are from subtype B HIV infections, which are prevalent in developed countries but account for only ~12% of all global HIV infections, whereas non-B subtype HIV infections that account for ~88% of all HIV infections are prevalent primarily in low and middle-income countries. Although the treatments for subtype B infections are generally effective against non-B subtype infections, there are differences in response to therapies. Here, we review how polymorphisms, transmission efficiency of drug-resistant strains, and differences in genetic barrier for drug resistance can differentially alter the response to reverse transcriptase-targeting therapies in various subtypes.

  13. Four subtypes of self-neglect in older adults: results of a latent class analysis.

    Burnett, Jason; Dyer, Carmel B; Halphen, John M; Achenbaum, W A; Green, Charles E; Booker, James G; Diamond, Pamela M


    To determine whether there are subtypes of elder self-neglect (SN) with different risk factors that can be targeted using medical and social interventions. Cohort study using archived data of Adult Protective Services (APS) substantiated cases of elder SN between January 1, 2004, and December 31, 2008. Houston, Harris County, Texas. Adults aged 65 and older with APS region VI substantiated SN between January 1, 2004, and December 31, 2008 (N = 5,686). Adult Protective Services caseworkers used the Client Assessment and Risk Evaluation (CARE) tool during home investigations, assessing risk of harm in the domains of living conditions, financial status, physical and medical status, mental health, and social connectedness. Latent class analysis was used to identify unique subtypes of elder SN. Four unique subtypes of elder SN were identified, with approximately 50% of individuals manifesting physical and medical neglect problems. Other subtypes included environmental neglect (22%), global neglect (21%), and financial neglect (9%). Older age, Caucasian descent, and mental status problems were more strongly associated with global neglect behaviors. African Americans were more likely to experience financial and environmental neglect than Caucasians and non-white Hispanics. Elder SN consists of unique subtypes that may be amenable to customized multidisciplinary interventions. Future studies are needed to determine whether these subtypes impose differential mortality risks and whether multidisciplinary tailored interventions can reduce SN and prevent early mortality. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  14. Functional conservation and coherence of HIV-1 subtype A Vpu alleles

    Romani, Bizhan; Kavyanifard, Amirarsalan; Allahbakhshi, Elham


    Functional studies of HIV-1 proteins are normally conducted using lab adapted strains of HIV-1. The extent of those functions in clinical strains is sometimes unknown. In this study, we amplified and sequenced HIV-1 Vpu from 10 Iranian patients infected with HIV-1. Phylogenetic analysis indicated that the Vpu alleles were closely related to the CRF35_AD from Iran and subtype A Vpu. We addressed some of the well-established functions of the HIV-1 Vpu, as well as some of its recently reported functions. Ability of the clinical strains of subtype A Vpu alleles for downregulation of CD4 was similar to that of the lab adapted NL4.3 Vpu. Majority of the subtype A Vpu alleles performed stronger than NL4.3 Vpu for downregulation of SNAT1. The Vpu alleles differentially induced downregulation of HLA-C, ranging from no effect to 88% downregulation of surface HLA-C. Downregulation of tetherin and enhancement of virus release was similar for the subtype A Vpu alleles and NL4.3. Subtype A Vpu alleles were more potent when compared with NL4.3 for inhibition of NF-κB activation. Our study shows that subtype A Vpu alleles exert the classical functions of HIV-1 Vpu. PMID:28317943

  15. Reproductive history and risk of three breast cancer subtypes defined by three biomarkers.

    Phipps, Amanda I; Buist, Diana S M; Malone, Kathleen E; Barlow, William E; Porter, Peggy L; Kerlikowske, Karla; Li, Christopher I


    Breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 expression are biologically distinct and thus, may have distinct etiologies. In particular, it is plausible that risk factors operating through hormonal mechanisms are differentially related to risk of such tumor subtypes. Using data from the Breast Cancer Surveillance Consortium, we explored associations between reproductive history and three breast cancer subtypes. Data on parity and age at first birth were collected from 743,623 women, 10,896 of whom were subsequently diagnosed with breast cancer. Cases were classified into three subtypes based on tumor maker expression: (1) ER positive (ER+, N = 8,203), (2) ER negative/PR negative/HER2 positive (ER-/PR-/HER2+, N = 288), or (3) ER-, PR-, and HER2-negative (triple-negative, N = 645). Associations with reproductive history, evaluated using Cox regression, differed significantly across tumor subtypes. Nulliparity was most strongly associated with risk of ER+ breast cancer [hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.23-1.39]; late age at first birth was most strongly associated with risk of ER-/PR-/HER2+ disease (HR = 1.83, 95% CI: 1.31-2.56). Neither parity nor age at first birth was associated with triple-negative breast cancer. In contrast to ER+ and ER-/PR-/HER2+ subtypes, reproductive history does not appear to be a risk factor for triple-negative breast cancer.

  16. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Helena Grgić

    Full Text Available The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1pdm09. One H1N2 isolate had hemagglutinin (HA, polymerase A (PA and non-structural (NS genes closely related to A(H1N1pdm09, and neuraminidase (NA, matrix (M, polymerase B1 (PB1, polymerase B2 (PB2, and nucleoprotein (NP genes originating from a triple-reassortant H3N2 virus (tr H3N2. The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  17. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir


    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  18. TGF-β Blood Levels Distinguish Between Influenza A (H1N1)pdm09 Virus Sepsis and Sepsis due to Other Forms of Community-Acquired Pneumonia.

    Rendón-Ramirez, Erick J; Ortiz-Stern, Alejandro; Martinez-Mejia, Corazon; Salinas-Carmona, Mario C; Rendon, Adrian; Mata-Tijerina, Viviana L; Rosas-Taraco, Adrian G


    There is a strong interest in finding adequate biomarkers to aid in the diagnosis and prognosis of influenza A (H1N1)pdm09 virus infection. In this study, serum levels of inflammatory cytokines and laboratory markers were evaluated to assess their usefulness as biomarkers of influenza A (H1N1)pdm09 and their association with fatal cases. Serum samples of consecutive patients with a clinical presentation suggestive of influenza A (H1N1)pdm09 and progression to sepsis were evaluated. Serum inflammatory cytokines and routine laboratory tests were performed and correlated with positivity for influenza A (H1N1)pdm09 influenza by real time reverse transcription polymerase chain reaction and the results of three clinical severity scores (Sequential Organ Failure Assessment [SOFA], CURB-65, and Acute Physiology and Chronic Health Evaluation II [APACHE II]). High SOFA scores and some of its individual components, but not CURB-65 or APACHE II scores, correlate with fatal cases regardless of etiology. Total and unconjugated bilirubin, Ca(++), Cl(-), prothrombin times, and partial thromboplastin times discriminate influenza A (H1N1)pdm09 from other causes of community-acquired pneumonia. High levels of IL-8, IL-10, and IL-17 were increased in influenza A (H1N1)pdm09 patients when compared with controls (pH1N1)pdm09 patients and non-(H1N1)pdm09 patients when compared with controls (pH1N1)pdm09 patients, and patients with other causes of community-acquired pneumonia. TGF-β levels were negatively correlated with SOFA on admission in influenza A (H1N1)pdm09 patients. TGF-β levels are a useful tool for differentiating influenza A (H1N1)pdm09 from other causes of pneumonia progressing to sepsis.

  19. The Molecular Epidemiological Study of HCV Subtypes among Intravenous Drug Users and Non-Injection Drug Users in China.

    Jun Tao

    Full Text Available More than half of intravenous drug users (IDUs in China suffer from the Hepatitis C virus (HCV. The virus is also more prevalent in non-injection drug users (NIDUs than in the general population. However, not much is known about HCV subtype distribution in these populations.Our research team conducted a cross-sectional study in four provinces in China. We sampled 825 IDUs and 244 NIDUs (1162 total, genotyped each DU's virus, and performed a phylogenetic analysis to differentiate HCV subtypes.Nucleic acid testing (NAT determined that 82% percent (952/1162 of samples were HCV positive; we subtyped 90% (859/952 of these. We found multiple HCV subtypes: 3b (249, 29.0%, 3a (225, 26.2%, 6a (156, 18.2%, 1b (137, 15.9%, 6n (50, 5.9%, 1a (27, 3.1%, and 2a (15, 1.7%. An analysis of subtype distributions adjusted for province found statistically significant differences between HCV subtypes in IDUs and NIDUs.HCV subtypes 3b, 3a, 6a, and 1b were the most common in our study, together accounting for 89% of infections. The subtype distribution differences we found between IDUs and NIDUs suggested that sharing syringes was not the most likely pathway for HCV transmission in NIDUs. However, further studies are needed to elucidate how NIDUs were infected.

  20. 组胺H_1受体与拮抗剂的相互作用%The Interactions between Histamine H1 Receptor and Histamine H1 Receptor Antagonists



    利用分子对接手段对H1受体与组胺以及各种拮抗剂的相互作用进行研究发现,组胺和各类拮抗剂与靶点之间的相互作用各有不同。组胺与靶点间的相互作用是以氢键为主的电性相互作用。经典的H1受体拮抗剂与受体间则以p-π、π-π相互作用为主,而无嗜睡作用的H1受体拮抗剂更是氢键、p-π、π-π相互作用皆有体现。%Through the method of docking, a study on the interactions between H1 receptor and H, receptor antagonists as well as histamine was carried out. The results indicated that the interactions between H1 receptor and histamine were dominated by H - bond, while the ones between H1 receptor and classic H1 receptor antagonists were mainly about p-π and π-πinteractions, and those with nonsedating histamine H1 receptor antagonists were including all three kinds of interactions mentioned above.

  1. Frontotemporal dementia and its subtypes

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A


    BACKGROUND: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel gene...

  2. Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES is Consistently Increased

    Gonzales, Rachel M.; Daly, Don S.; Tan, Ruimin; Marks, Jeffrey R.; Zangar, Richard C.


    Background: Current biomarkers for breast cancer have little potential for detection. We determined if breast cancer subtypes influence circulating protein biomarkers. Methods: A sandwich-ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated based on breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses. Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P<0.01 for each analysis) in all four subtypes, with areas under receiver operating characteristic curves (AUC) that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets. Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true and false positive screens for breast cancer. Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods.

  3. Mycobacterium kansasii Subtype I Is Associated With Clarithromycin Resistance in China

    Li, Yanming; Pang, Yu; Tong, Xunliang; Zheng, Huiwen; Zhao, Yanlin; Wang, Chen


    Mycobacterium kansasii is the second most common cause of slowly growing non-tuberculous mycobacteria diseases in China. The aim of the present study was to analyze M. kansasii subtypes isolated from patients in China, and to explore the antimicrobial susceptibility of the differentiation among these diverse subtypes. A total of 78 M. kansasii strains from 16 provinces of China were enrolled in this study. Amikacin (AMK) was the most highly active against M. kansasii strains, and only 4 isolates (5.1%) exhibited in vitro resistance to AMK. The percentage of levofloxacin (LFX) resistant strains among the 78 M. kansasii isolates was 39.7% (31/78), which was significantly higher than that of moxifloxacin (16.7%, P = 0.001) and gatifloxacin (19.2%, P = 0.005). By using PCR-restriction fragment analysis of the hsp65 gene (PRA), all the isolates were classified as four different subtypes. Of these four subtypes, M. kansasii subtype I was the most frequent genotype in China, accounting for 71.8% (56/78) of M. kansasii isolates. Resistance to clarithromycin (CLA) was noted in 26.8% (15/56) of subtype I isolates, which was significant higher than that of other subtypes (4.5%, P = 0.031). DNA sequencing revealed that the presence of mutations in 23S rRNA was associated with 56.2% (9/16) of CLA-resistant M. kansasii isolates. In conclusion, our data demonstrate that AMK is the most active agent against M. kansasii in vitro, while the high proportion of CLA resistance is noted in M. kansasii isolates. In addition, the predominant subtype I is associated with CLA resistance in China. PMID:28082964

  4. Mutations in polymerase genes enhanced the virulence of 2009 pandemic H1N1 influenza virus in mice.

    Wenfei Zhu

    Full Text Available Influenza A virus can infect a wide variety of animal species with illness ranging from mild to severe, and is a continual cause for concern. Genetic mutations that occur either naturally or during viral adaptation in a poorly susceptible host are key mechanisms underlying the evolution and virulence of influenza A virus. Here, the variants containing PA-A36T or PB2-H357N observed in the mouse-adapted descendants of 2009 pandemic H1N1 virus (pH1N1, A/Sichuan/1/2009 (SC, were characterized. Both mutations enhanced polymerase activity in mammalian cells. These effects were confirmed using recombinant SC virus containing polymerase genes with wild type (WT or mutant PA or PB2. The PA-A36T mutant showed enhanced growth property compared to the WT in both human A549 cells and porcine PK15 cells in vitro, without significant effect on viral propagation in murine LA-4 cells and pathogenicity in mice; however, it did enhance the lung virus titer. PB2-H357N variant demonstrated growth ability comparable to the WT in A549 cells, but replicated well in PK15, LA-4 cells and in mice with an enhanced pathogenic phenotype. Despite such mutations are rare in nature, they could be observed in avian H5 and H7 subtype viruses which were currently recognized to pose potential threat to human. Our findings indicated that pH1N1 may adapt well in mammals when acquiring these mutations. Therefore, future molecular epidemiological surveillance should include scrutiny of both markers because of their potential impact on pathogenesis.

  5. Continued dominance of pandemic A(H1N1 2009 influenza in Victoria, Australia in 2010

    James E. Fielding


    Full Text Available The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95% were influenza A infections - 1001 (55% pandemic A(H1N1 2009, 4 (<1% A(H3N2 and 807 (45% not subtyped; 88 (5% were influenza B; and 14 (< 1% were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9% were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene.

  6. Molecular Identification and Subtype Analysis of Blastocystis.

    Stensvold, C Rune; Clark, C Graham


    Several typing methods have been used in studies aiming to unravel the molecular epidemiology of Blastocystis, which is one of the most common intestinal parasites in human and many non-human hosts. Such studies have the potential to add to knowledge on Blastocystis transmission, host specificity, phylogeography, and clinical and public health significance, but rely on robust, standardized methods by which data can be generated and compared directly between studies. One of the most used methods is "barcoding,", which involves single-round PCR amplification and sequencing of partial small subunit ribosomal RNA genes of the parasites. Recently, a publicly available online facility was developed for quick and standardized identification of subtypes (ribosomal lineages) and subtype alleles (variation within subtypes) based on sequence data obtained by barcoding PCR. Moreover, a modified barcoding approach is now available using nested PCR, which enables detection of mixed subtype infections. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  7. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M


    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  8. Ameaça e controle da gripe A(H1N1: uma análise discursiva de Veja, IstoÉ e Época Threat and control of influenza A (H1N1: a discursive analysis of Brazilian magazines Veja, IstoÉ and Época

    Isaltina Maria de Azevedo Mello Gomes


    differentiated 'new edition' of flu, due to the identification of a new subtype of influenza virus that could be as lethal as the old one. A similar fear to what had been experienced also with avian influenza in 1997, prompting officials to remain on alert. This article aims to evaluate the production of news on influenza A(H1N1 in the three main national magazines in Brazil. We chose to analyze the eigth covers of magazines Veja, IstoÉ and Época published during the first months of the pandemic, in the beginning of 2009. Based on concepts of Discourse Analysis and Journalism Theory, the analysis indicates that the news can be divided into two phases, focusing initially on the alarm over the fear of new virus and deaths recorded and afterwards on the control due to the finding that the disease presented less risk than previously thought and to the actions taken to fight it.

  9. Programming and reprogramming neuronal subtypes in the central nervous system.

    Rouaux, Caroline; Bhai, Salman; Arlotta, Paola


    Recent discoveries in nuclear reprogramming have challenged the dogma that the identity of terminally differentiated cells cannot be changed. The identification of molecular mechanisms that reprogram differentiated cells to a new identity carries profound implications for regenerative medicine across organ systems. The central nervous system (CNS) has historically been considered to be largely immutable. However, recent studies indicate that even the adult CNS is imparted with the potential to change under the appropriate stimuli. Here, we review current knowledge regarding the capability of distinct cells within the CNS to reprogram their identity and consider the role of developmental signals in directing these cell fate decisions. Finally, we discuss the progress and current challenges of using developmental signals to precisely direct the generation of individual neuronal subtypes in the postnatal CNS and in the dish.

  10. Efficacy of vaccination with different combinations of MF59-adjuvanted and nonadjuvanted seasonal and pandemic influenza vaccines against pandemic H1N1 (2009) influenza virus infection in ferrets.

    van den Brand, Judith M A; Kreijtz, Joost H C M; Bodewes, Rogier; Stittelaar, Koert J; van Amerongen, Geert; Kuiken, Thijs; Simon, James; Fouchier, Ron A M; Del Giudice, Giuseppe; Rappuoli, Rino; Rimmelzwaan, Guus F; Osterhaus, Albert D M E


    Serum antibodies induced by seasonal influenza or seasonal influenza vaccination exhibit limited or no cross-reactivity against the 2009 pandemic swine-origin influenza virus of the H1N1 subtype (pH1N1). Ferrets immunized once or twice with MF59-adjuvanted seasonal influenza vaccine exhibited significantly reduced lung virus titers but no substantial clinical protection against pH1N1-associated disease. However, priming with MF59-adjuvanted seasonal influenza vaccine significantly increased the efficacy of a pandemic MF59-adjuvanted influenza vaccine against pH1N1 challenge. Elucidating the mechanism involved in this priming principle will contribute to our understanding of vaccine- and infection-induced correlates of protection. Furthermore, a practical consequence of these findings is that during an emerging pandemic, the implementation of a priming strategy with an available adjuvanted seasonal vaccine to precede the eventual pandemic vaccination campaign may be useful and life-saving.

  11. Regioselectivity in the Thermal Rearrangement of Unsymmetrical 4-Methyl-4H-1,2,4-triazoles to 1-Methyl-1H-1,2,4-triazoles

    Per H.J. Carlsen


    Full Text Available The rearrangement of 4-methyl-3,5-diaryl-4H-1,2,4-triazoles to the corresponding 1-methyl-3,5-diaryl-1H-1,2,4-triazoles showed regioselectivity comparable to that observed for the alkylation of 3,5-diaryl-1H-1,2,4-triazoles. This lends support to a proposed mechanism for the rearrangement that involves consecutive nucleophilic displacements steps.

  12. Burden of the 1999-2008 seasonal influenza epidemics in Italy: comparison with the H1N1v (A/California/07/09) pandemic.

    Lai, Piero Luigi; Panatto, Donatella; Ansaldi, Filippo; Canepa, Paola; Amicizia, Daniela; Patria, Antonio Giuseppe; Gasparini, Roberto


    Despite preventive efforts, seasonal influenza epidemics are responsible for substantial morbidity and mortality every year worldwide, including developed countries. The A/H1N1v pandemic imposed a considerable healthcare and economic burden. In order to obtain an accurate estimate of the economic burden of influenza, and hence to guide policymakers effectively, systematic studies are necessary. To this end, data from epidemiological surveillance are essential. To estimate the impact of the 1999-2008 seasonal influenza epidemics and the H1N1v pandemic, we analyzed data from the Italian Influenza Surveillance System (CIRI NET). In the period 1999-2008, the Italian surveillance network consisted of sentinel general practitioners and pediatricians, who reported cases of Influenza-Like Illness (ILI) and Acute Respiratory Infections (ARI ) observed during their clinical practice from mid-October to late April each year; reports were sent to the Center for Research on Influenza and other Viral Infections (CIRI -IV). CIRI -IV receives data from 9 of the 20 Italian regions: Liguria, Abruzzo, Calabria, Friuli Venezia Giulia, Lombardy, Puglia, Sicily, Tuscany and Umbria. Previous estimates of influenza case costs were used in economic evaluations. Clinical-epidemiological and virological surveillance of the seasonal epidemics from 1999-2008 showed that the highest epidemic period was 2004-2005, when a new variant of the H3N2 influenza virus subtype emerged (A/California/07/04). Indeed, the highest peak of morbidity in the decade occurred in February 2005 (12.6 per 1,000 inhabitants). In 1999-2008, H1N1 subtype strains circulated and co-circulated with strains belonging to the H3N2 subtype and B type. Regarding B viruses in 2001-02, viruses belonged to the B/Victoria/02/07 lineage re-emerged, and in subsequent years co-circulated with viruses belonging to the B/Yamagata/lineage. The estimated costs of seasonal epidemics from 1999-2008 in Italy ranged from €15 to €20

  13. Hypertension Subtypes among Hypertensive Patients in Ibadan

    Abiodun M. Adeoye


    Full Text Available Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH, isolated systolic hypertension (ISH, isolated diastolic hypertension (IDH, and systolic-diastolic hypertension (SDH. Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5% and IDH (4.9% versus 4.7% were more prevalent among females, ISH (10.1% versus 6.2% was higher among males (P=0.048. Female subjects were more obese (P<0.0001 and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.

  14. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

    Cuevas, Maria Teresa; Pozo, Francisco; Guerra, Susana; García-Barreno, Blanca; Martinez-Orellana, Pamela; Pérez-Breña, Pilar; Montoya, Maria; Melero, Jose Antonio; Pizarro, Manuel; Ortin, Juan; Casas, Inmaculada; Nieto, Amelia


    Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32). PMID:23326447

  15. Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo.

    Qu, Song; Li, Xiao-Yu; Liang, Zhong-Guo; Li, Ling; Huang, Shi-Ting; Li, Jia-Quan; Li, Dan-Rong; Zhu, Xiao-Dong


    Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPC in vitro and in vivo. Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated. In vivo tests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (PA3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (PA3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required.

  16. Economic impacts of a hypothetical H1N1 pandemic : a cross-sectional analysis.

    Smith, Braeton J.; Shaneyfelt, Calvin R.


    A NISAC study on the economic effects of a hypothetical H1N1 pandemic was done in order to assess the differential impacts at the state and industry levels given changes in absenteeism, mortality, and consumer spending rates. Part of the analysis was to determine if there were any direct relationships between pandemic impacts and gross domestic product (GDP) losses. Multiple regression analysis was used because it shows very clearly which predictors are significant in their impact on GDP. GDP impact data taken from the REMI PI+ (Regional Economic Models, Inc., Policy Insight +) model was used to serve as the response variable. NISAC economists selected the average absenteeism rate, mortality rate, and consumer spending categories as the predictor variables. Two outliers were found in the data: Nevada and Washington, DC. The analysis was done twice, with the outliers removed for the second analysis. The second set of regressions yielded a cleaner model, but for the purposes of this study, the analysts deemed it not as useful because particular interest was placed on determining the differential impacts to states. Hospitals and accommodation were found to be the most important predictors of percentage change in GDP among the consumer spending variables.

  17. Boiling peanut Ara h 1 results in the formation of aggregates with reduced allergenicity.

    Blanc, Fany; Vissers, Yvonne M; Adel-Patient, Karine; Rigby, Neil M; Mackie, Alan R; Gunning, A Patrick; Wellner, Nikolaus K; Skov, Per S; Przybylski-Nicaise, Laetitia; Ballmer-Weber, Barbara; Zuidmeer-Jongejan, Laurian; Szépfalusi, Zsolt; Ruinemans-Koerts, Janneke; Jansen, Ad P H; Bernard, Hervé; Wal, Jean-Michel; Savelkoul, Huub F J; Wichers, Harry J; Mills, E N Clare


    Roasting rather than boiling and Maillard modifications may modulate peanut allergenicity. We investigated how these factors affect the allergenic properties of a major peanut allergen, Ara h 1. Ara h 1 was purified from either raw (N-Ara h 1) or roasted (R-Ara h 1) peanuts. Boiling (100°C 15 min; H-Ara h 1) resulted in a partial loss of Ara h 1 secondary structure and formation of rod-like branched aggregates with reduced IgE-binding capacity and impaired ability to induce mediator release. Glycated Ara h 1 (G-Ara h 1) formed by boiling in the presence of glucose behaved similarly. However, H- and G-Ara h1 retained the T-cell reactivity of N-Ara h 1. R-Ara h 1 was denatured, comprised compact, globular aggregates, and showed no evidence of glycation but retained the IgE-binding capacity of the native protein. Ara h 1 aggregates formed by boiling were morphologically distinct from those formed by roasting and had lower allergenic activity. Glycation had no additional effect on Ara h 1 allergenicity compared with heating alone. Taken together with published data on the loss of Ara h 2/6 from boiled peanuts, this supports the hypothesis that boiling reduces the allergenicity of peanuts. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy

    Esposito Susanna


    Full Text Available Abstract A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6% and in all 17 samples (100%; p

  19. [Analysis of HA and NA Genes of Influenza A H1N1 Virus in Yunnan Province during 2009-2014].

    Li, Juan; Zhao, Xiaonan; Cao, Yihui; Ning, Deming; Fu, Xiaoqing; Xu, Wen


    To analyze influenza pathogen spectrum in Yunnan province during 2009-2014 years, and analyze HA and NA genes of influenza A H1N1. Analysis was made on the monitoring date of influenza cases in Yunnan province in recent 6 years, 23 strains of influenza virus of HA and NA gene was sequenced and analyzed by MEGA 5 software to construct phylogenetic tree. 4 times of influenza AH1N1 epidemic peak were monitored from 2009-2014 years in Yunnan Province, as the nucleic acid detection results of influenza A H1N1 accounted for 28.8% of the total. The sequencing result showed that HA and NA gene were divided into 3 groups, one was detected with H275Y mutation strains. Influenza A H1N1 is one of the important subtypes in Yunnan province and their genes have divided into three branches during the period of 2009-2014 years, the vast majority of influenza a H1N1 are still sensitive to neuraminidase inhibitors.

  20. Influenza A Viruses of Swine (IAV-S) in Vietnam from 2010 to 2015: Multiple Introductions of A(H1N1)pdm09 Viruses into the Pig Population and Diversifying Genetic Constellations of Enzootic IAV-S.

    Takemae, Nobuhiro; Harada, Michiyo; Nguyen, Phuong Thanh; Nguyen, Tung; Nguyen, Tien Ngoc; To, Thanh Long; Nguyen, Tho Dang; Pham, Vu Phong; Le, Vu Tri; Do, Hoa Thi; Vo, Hung Van; Le, Quang Vinh Tin; Tran, Tan Minh; Nguyen, Thanh Duy; Thai, Phuong Duy; Nguyen, Dang Hoang; Le, Anh Quynh Thi; Nguyen, Diep Thi; Uchida, Yuko; Saito, Takehiko


    Active surveillance of influenza A viruses of swine (IAV-S) involving 262 farms and 10 slaughterhouses in seven provinces in northern and southern Vietnam from 2010 to 2015 yielded 388 isolates from 32 farms; these viruses were classified into H1N1, H1N2, and H3N2 subtypes. Whole-genome sequencing followed by phylogenetic analysis revealed that the isolates represented 15 genotypes, according to the genetic constellation of the eight segments. All of the H1N1 viruses were entirely A(H1N1)pdm09 viruses, whereas all of the H1N2 and H3N2 viruses were reassortants among 5 distinct ancestral viruses: H1 and H3 triple-reassortant (TR) IAV-S that originated from North American pre-2009 human seasonal H1, human seasonal H3N2, and A(H1N1)pdm09 viruses. Notably, 93% of the reassortant IAV-S retained M genes that were derived from A(H1N1)pdm09, suggesting some advantage in terms of their host adaptation. Bayesian Markov chain Monte Carlo analysis revealed that multiple introductions of A(H1N1)pdm09 and TR IAV-S into the Vietnamese pig population have driven the genetic diversity of currently circulating Vietnamese IAV-S. In addition, our results indicate that a reassortant IAV-S with human-like H3 and N2 genes and an A(H1N1)pdm09 origin M gene likely caused a human case in Ho Chi Minh City in 2010. Our current findings indicate that human-to-pig transmission as well as cocirculation of different IAV-S have contributed to diversifying the gene constellations of IAV-S in Vietnam.

  1. Recrudescent Wave of A/H1N1pdm09 Influenza Viruses in Winter 2012-2013 in Kashmir, India.

    Koul, Parvaiz; Khan, Umar; Bhat, Khursheed; Saha, Siddhartha; Broor, Shobha; Lal, Renu; Chadha, Mandeep


    Some parts of world, including India observed a recrudescent wave of influenza A/H1N1pdm09 in 2012. We undertook a study to examine the circulating influenza strains, their clinical association and antigenic characteristics to understand the recrudescent wave of A/H1N1pdm09 from November 26, 2012 to Feb 28, 2013 in Kashmir, India. Of the 751 patients (545 outpatient and 206 hospitalized) presenting with acute respiratory infection at a tertiary care hospital in Srinagar; 184 (24.5%) tested positive for influenza. Further type and subtype analysis revealed that 106 (58%) were influenza A (H1N1pdm09 =105, H3N2=1) and 78 (42%) were influenza B. The influenza positive cases had a higher frequency of chills, nasal discharge, sore throat, body aches and headache, compared to influenza negative cases. Of the 206 patients hospitalized for pneumonia/acute respiratory distress syndrome or an exacerbation of an underlying lung disease, 34 (16.5%) tested positive for influenza (22 for H1N1pdm09, 11 for influenza B). All influenza-positive patients received oseltamivir and while most patients responded well to antiviral therapy and supportive care, 6 patients (4 with H1N1pdm09 and 2 with influenza B) patients died of progressive respiratory failure and multi-organ dysfunction. Following a period of minimal circulation, H1N1pdm09 re-emerged in Kashmir in 2012-2013, causing serious illness and fatalities. As such the healthcare administrators and policy planners need to be wary and monitor the situation closely.

  2. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity.

    Zhang, Anna J X; To, Kelvin K W; Li, Can; Lau, Candy C Y; Poon, Vincent K M; Chan, Chris C S; Zheng, Bo-Jian; Hung, Ivan F N; Lam, Karen S L; Xu, Aimin; Yuen, Kwok-Yung


    Obesity is associated with a high circulating leptin level and severe 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) infection. The mechanism for severe lung injury in obese patients and the specific treatment strategy remain elusive. We studied the pathogenesis of A(H1N1)pdm09 infection in a mouse model of diet-induced obesity. Obese mice had significantly higher initial pulmonary viral titer and mortality after challenge with A(H1N1)pdm09, compared with age-matched lean mice. Compared with lean mice, obese mice had heightened proinflammatory cytokine and chemokine levels and more severe pulmonary inflammatory damage. Furthermore, obese mice had a higher preexisting serum leptin level but a lower preexisting adiponectin level. Recombinant mouse leptin increased the interleukin 6 (IL-6) messenger RNA expression in mouse single-lung-cell preparations, mouse macrophages, and mouse lung epithelial cell lines infected with A(H1N1)pdm09. Administration of anti-leptin antibody improved the survival of infected obese mice, with associated reductions in pulmonary levels of the proinflammatory cytokines IL-6 and interleukin 1β but not the pulmonary viral titer. Our findings suggest that preexisting high levels of circulating leptin contribute to the development of severe lung injury by A(H1N1)pdm09 in mice with diet-induced obesity. The therapeutic strategy of leptin neutralization for the reduction of proinflammatory responses and pulmonary damage in obese patients warrants further investigations.

  3. The progress of research on influenza A(H1N1)%甲型H1N1流感的研究进展

    雷晓燕; 孙永红


    Influenza A(H1N1)virus is a re-mixed strains of human influenza virus genes,avian influenza virus gene and swine influenza virus gene.Influenza A(H1N1)pandemic influenza has spread around the world,which has drawn worldwide attention.In order to early discovery,early diagnosis,early treatment and effective prevention of Influenza A(H1N1),we describe the characteristics of linfluenza A(H1N1)virus,epidemiology,pathogenesis,clinical manifestations,laboratory examination and effective treatment and preventive measures.%甲型H1N1流感病毒是人流感病毒基因、禽流感病毒基因和猪流感病毒基因混合的重配株,其造成的疫情来势凶猛,引起世界各国的广泛关注.为了早发现、早诊断、早治疗及有效地预防甲型H1N1流感,本文综述了甲型H1N1流感病毒的特点、流行病学、致人发病的机制、甲型H1N1流感患者的临床表现、实验室检查及有效的治疗和预防措施.

  4. 20 CFR 655.705 - What Federal agencies are involved in the H-1B and H-1B1 programs, and what are the...


    ... Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in Specialty Occupations... petition, whether the occupation named in the labor condition application is a specialty occupation or...

  5. Mimotopes selected with neutralizing antibodies against multiple subtypes of influenza A

    Zhong Yanwei


    Full Text Available Abstract Background The mimotopes of viruses are considered as the good targets for vaccine design. We prepared mimotopes against multiple subtypes of influenza A and evaluate their immune responses in flu virus challenged Balb/c mice. Methods The mimotopes of influenza A including pandemic H1N1, H3N2, H2N2 and H1N1 swine-origin influenza virus were screened by peptide phage display libraries, respectively. These mimotopes were engineered in one protein as multi- epitopes in Escherichia coli (E. coli and purified. Balb/c mice were immunized using the multi-mimotopes protein and specific antibody responses were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. The lung inflammation level was evaluated by hematoxylin and eosin (HE. Results Linear heptopeptide and dodecapeptide mimotopes were obtained for these influenza virus. The recombinant multi-mimotopes protein was a 73 kDa fusion protein. Comparing immunized infected groups with unimmunized infected subsets, significant differences were observed in the body weight loss and survival rate. The antiserum contained higher HI Ab titer against H1N1 virus and the lung inflammation level were significantly decreased in immunized infected groups. Conclusions Phage-displayed mimotopes against multiple subtypes of influenza A were accessible to the mouse immune system and triggered a humoral response to above virus.

  6. Associative algebra deformations of the Connes-Moscovici's Hopf algebra $\\mathcal{H}_1$

    Fialowski, Alice; Wagemann, Friedrich


    We compute the second Hochschild cohomology space $HH^2(\\mathcal{H}_1)$ of Connes-Moscovici's Hopf algebra $\\mathcal{H}_1$, giving the infinitesimal deformations (up to equivalence) of the associative structure. $HH^2(\\mathcal{H}_1)$ is shown to be one dimensional, and thus Connes-Moscovici's formal deformation of $\\mathcal{H}_1$ using Rankin-Cohen brackets is unique up to equivalence.

  7. Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis

    Jung, Hwa Sik; Park, Chan-Ho; Park, Young Tae; Bae, Mi Ae; Lee, Youn Im; Kang, Byung Ju; Jegal, Yangjin; Ahn, Jong Joon; Lee, Taehoon


    H1-antihistamine is generally a well-tolerated and safe drug. However, in resemblance with all other drugs, H1-antihistamines can also prompt adverse drug reactions (ADRs). We recently encountered the very unusual ADR of H1-antihistamine-induced gynecomastia. A 21-year-old man with idiopathic anaphylaxis was treated with ebastine (Ebastel), a second-generation H1-antihistamine, for the prevention of anaphylaxis. Three months later, the patient remained well without anaphylaxis, but had newly ...

  8. Associative algebra deformations of the Connes-Moscovici's Hopf algebra $\\mathcal{H}_1$

    Fialowski, Alice; Wagemann, Friedrich


    We compute the second Hochschild cohomology space $HH^2(\\mathcal{H}_1)$ of Connes-Moscovici's Hopf algebra $\\mathcal{H}_1$, giving the infinitesimal deformations (up to equivalence) of the associative structure. $HH^2(\\mathcal{H}_1)$ is shown to be one dimensional, and thus Connes-Moscovici's formal deformation of $\\mathcal{H}_1$ using Rankin-Cohen brackets is unique up to equivalence.

  9. Subtype distribution of Blastocystis isolates from synanthropic and zoo animals and identification of a new subtype

    Stensvold, C. R.; Alfellani, M. A.; Nørskov-Lauritsen, S.


    Blastocystis isolates from 56 Danish synanthropic and zoo animals, 62 primates primarily from United Kingdom (UK) collections and 16 UK primate handlers were subtyped by PCR, sequencing and phylogenetic analysis. A new subtype (ST) from primates and artiodactyls was identified and designated...

  10. Comparative pathogenesis of a subtype A with a subtype B avian pneumovirus in turkeys.

    Van de Zande, S; Nauwynck, H; De Jonghe, S; Pensaert, M


    This paper describes a study in which the pathogenesis of avian pneumovirus strains, isolated in Belgium, and belonging to the two subtypes A and B, were compared in 2-week-old turkeys. After oculonasal inoculation, animals were either observed for clinical signs or killed for pathological and virological examination. Virus titration and immunofluorescence were performed on the conjunctivae, turbinates, sinuses, upper and lower part of the trachea, lungs and air sacs. No differences were seen between the two subtypes concerning respiratory signs, or macroscopic and microscopic lesions in the respiratory tract. Slight variations were found in site and extent of virus replication. First, only subtype A was able to invade the lower parts of the respiratory tract (bronchi), whereas viral antigens were not detected in the lungs with subtype B. Secondly, the subtype A strain infected two times more epithelial cells at all levels of the upper respiratory tract compared to subtype B. Thirdly, the amount of virus produced at different sites along the respiratory tract was lower in subtype B-inoculated turkeys than in subtype A-inoculated ones.

  11. Clinical application and analysis of H1 receptor blockers%H1受体阻断剂的临床应用与分析



    目的 分析本院H1受体阻断剂的临床应用情况,为临床合理用药提供科学参考.方法 回顾性分析本院临床应用H1受体阻断剂的种类、用药金额、用药频度、日均用药费用以及药物的利用指数等.结果 本院H1受体阻断剂的临床用药基本合理,其中第一代H1受体阻断剂中苯海拉明针剂、异丙嗪针剂的DUI>1,用药不合理;第二代H1受体阻断剂中仅特非那定片的DIU>1;本院第一代H1受体阻断剂的临床用量显著少于第二代H1受体阻断剂,P<0.01.结论 第一代H1受体阻断剂临床用量逐渐下降,第二代H1受体阻断剂的临床用量显著高于第一代H1受体阻断剂的临床用量.

  12. Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic.

    Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S


    Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

  13. A case with myocarditis secondary to Influenza virus (H1N1

    Fesih Aktar


    Full Text Available Although influenza is an acute and uncomplicated disease, that limits itself in the healthy children, it may lead to death by rarely forming the sickness. The most common complication of influenza is pneumonia and it is a rare complication which is developed together with myocarditis by influenza A and B viruses. A 32 months-old male patient was admitted for rapidly developed respiratory distress and tachycardia after fever, cough, vomiting, malaise and runny nose. His general status was medium, he had conscious and had hepatomegaly, tachycardia, dyspnea, tachypnea, intercostal-subcostal retractions and bilateral rhonchus. Cardiac enzyme levels and other laboratory parameters were found normal. Myocarditis and ejection fraction was determined as 42% in echocardiography. However, hospitalization hours between 24 and 48, the patient, whose significant respiratory compromise developed, was intubated and fastened to a mechanical ventilator. H1N1 is produce in nasopharyngeal swab culture at the sixth day of follow-up. Because we think H1N1 virus was responsible from current myocarditis, oseltamivir treatment was initiated. In the fourth day of the treatment the patient’s fever returned to normal, in the ninth day a dramatic recovery was observed. In tracking echocardiography, a significant improvement was observed in the ejection fraction and myocarditis picture compared with admission time. This case was presented in order to remind that in a patients, who present with influenza findings but have respiratory distress and tachycardia in addition to lower respiratory tract infection, myocarditis should also be considered in the differential diagnosis and to remind that promising results could be obtained with the early diagnosis and treatment.

  14. Factors Influencing School Closure and Dismissal Decisions: Influenza A (H1N1), Michigan 2009

    Dooyema, Carrie A.; Copeland, Daphne; Sinclair, Julie R.; Shi, Jianrong; Wilkins, Melinda; Wells, Eden; Collins, Jim


    Background: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. Methods: We distributed an online…

  15. 26 CFR 1.643(h)-1 - Distributions by certain foreign trusts through intermediaries.


    ... intermediaries. 1.643(h)-1 Section 1.643(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(h)-1... section, FT is deemed to have distributed XYZ stock with a value of 85X to C on December 1, 2001. (h...

  16. Data of evolutionary structure change: 1CR9H-1RUKH [Confc[Archive


  17. Molecular Characterization of Avian-like H1N1 Swine Influenza A Viruses Isolated in Eastern China, 2011

    Xian Qi; Yuning Pan; Yuanfang Qin; Rongqiang Zu; Fengyang Tang; Minghao Zhou; Hua Wang; Yongchun Song


    Currently,three predominant subtypes of influenza virus are prevalent in pig populations worldwide:H1N1,H3N2,and H1N2.European avian-like H1N1 viruses,which were initially detected in European pig populations in 1979,have been circulating in pigs in eastern China since 2007.In this study,six influenza A viruses were isolated from 60 swine lung samples collected from January to April 2011 in eastern China.Based on whole genome sequencing,molecular characteristics of two isolates were determined.Phylogenetic analysis showed the eight genes of the two isolates were closely related to those of the avian-like H1N1 viruses circulating in pig populations,especially similar to those found in China.Four potential glycosylation sites were observed at positions 13,26,198,277 in the HA1 proteins of the two isolates.Due to the presence of a stop codon at codon 12,the isolates contained truncated PB1-F2 proteins.In this study,the isolates contained 591Q,627E and 701N in the polymerase subunit PB2,which had been shown to be determinants of virulence and host adaptation.The isolates also had a D rather than E at position 92 of the NS1,a marker of mammalian adaptation.Both isolates contained the GPKV motif at the PDZ ligand domain of the 3' end of the NS1,a characteristic marker of the European avian-like swine viruses since about 1999,which is distinct from those of avian,human and classical swine viruses.The M2 proteins of the isolates have the mutation (S31N),a characteristic marker of the European avian-like swine viruses since about 1987,which may confer resistance to amantadine and rimantadine antivirals.Our findings further emphasize the importance of surveillance on the genetic diversity of influenza A viruses in pigs,and raise more concerns about the occurrence of cross-species transmission events.

  18. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    Ashkani, Jahanshah; Naidoo, Kevin J.


    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  19. Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China.

    Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan


    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.

  20. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines.

    Balaji Manicassamy


    Full Text Available The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5,000 deaths worldwide. Early epidemiological findings indicated a low level of infection in the older population (>65 years with the pandemic virus, and a greater susceptibility in people younger than 35 years of age, a phenomenon correlated with the presence of cross-reactive immunity in the older population. It is unclear what virus(es might be responsible for this apparent cross-protection against the 2009 pandemic H1N1 virus. We describe a mouse lethal challenge model for the 2009 pandemic H1N1 strain, used together with a panel of inactivated H1N1 virus vaccines and hemagglutinin (HA monoclonal antibodies to dissect the possible humoral antigenic determinants of pre-existing immunity against this virus in the human population. By hemagglutinination inhibition (HI assays and vaccination/challenge studies, we demonstrate that the 2009 pandemic H1N1 virus is antigenically similar to human H1N1 viruses that circulated from 1918-1943 and to classical swine H1N1 viruses. Antibodies elicited against 1918-like or classical swine H1N1 vaccines completely protect C57B/6 mice from lethal challenge with the influenza A/Netherlands/602/2009 virus isolate. In contrast, contemporary H1N1 vaccines afforded only partial protection. Passive immunization with cross-reactive monoclonal antibodies (mAbs raised against either 1918 or A/California/04/2009 HA proteins offered full protection from death. Analysis of mAb antibody escape mutants, generated by selection of 2009 H1N1 virus with these mAbs, indicate that antigenic site Sa is one of the conserved cross-protective epitopes. Our findings in mice agree with serological data showing high prevalence of 2009 H1N1 cross-reactive antibodies only in the older population, indicating that prior infection with 1918-like viruses or vaccination against the 1976 swine H1N1 virus in the USA are likely to provide protection against the 2009

  1. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles

    Tchou Julia


    Full Text Available Abstract Background Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2 of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. Methods To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC and six Her2+. Results We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER + cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer. Conclusions These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer.

  2. Precise subtyping for synchronous multiparty sessions

    Mariangiola Dezani-Ciancaglini


    Full Text Available The notion of subtyping has gained an important role both in theoretical and applicative domains: in lambda and concurrent calculi as well as in programming languages. The soundness and the completeness, together referred to as the preciseness of subtyping, can be considered from two different points of view: operational and denotational. The former preciseness has been recently developed with respect to type safety, i.e. the safe replacement of a term of a smaller type when a term of a bigger type is expected. The latter preciseness is based on the denotation of a type which is a mathematical object that describes the meaning of the type in accordance with the denotations of other expressions from the language. The result of this paper is the operational and denotational preciseness of the subtyping for a synchronous multiparty session calculus. The novelty of this paper is the introduction of characteristic global types to prove the operational completeness.

  3. GABAA receptor subtype involvement in addictive behaviour.

    Stephens, D N; King, S L; Lambert, J J; Belelli, D; Duka, T


    GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarize the evidence that variations in genes encoding GABAA receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABAA receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarize the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABAA receptor subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. Transcriptomics and Proteomics in the Study of H1N1 2009

    Lijun Zhang; Xiaojun Zhang; Qing Ma; Fang Ma; Honghao Zhou


    Influenza A virus (HINI) 2009, a new swine-origin influenza A virus, has been spread worldwidely and causedgreat public fear. High-throughput transcriptomics and proteomies methods are now being used to identify H1N1and H1N1-host interaction. This article reviews recent transcriptomics and proteomics research in H1N1 diagnosis,treatment, and H1N1 virus-host interaction, to offer some help for further understanding the infection mechanismand controlling H1N1 transmission.

  5. 儿童如何预防甲型H1N1流感




  6. Investigating the link between molecular subtypes of glioblastoma, epithelial-mesenchymal transition, and CD133 cell surface protein.

    Hadi Zarkoob

    Full Text Available In this manuscript, we use genetic data to provide a three-faceted analysis on the links between molecular subclasses of glioblastoma, epithelial-to-mesenchymal transition (EMT and CD133 cell surface protein. The contribution of this paper is three-fold: First, we use a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrate that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between genes up regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provide evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we study the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrate that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM displays similarity with the signatures of both EMT and CD133, it also exhibits some differences with each of these signatures that are partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together these data shed light on the role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme.

  7. Review of renal cell carcinoma and its common subtypes in radiology

    Gavin Low; Guan Huang; Winnie Fu; Zaahir Moloo; Safwat Girgis


    Representing 2%-3% of adult cancers, renal cell carcinoma(RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and posttreatment follow-up of RCC, with attention focused on the common subtypes.

  8. Stroma-associated master regulators of molecular subtypes predict patient prognosis in ovarian cancer

    Zhang, Shengzhe; Jing, Ying; Zhang, Meiying; Zhang, Zhenfeng; Ma, Pengfei; Peng, Huixin; Shi, Kaixuan; Gao, Wei-Qiang; Zhuang, Guanglei


    High-grade serous ovarian carcinoma (HGS-OvCa) has the lowest survival rate among all gynecologic cancers and is hallmarked by a high degree of heterogeneity. The Cancer Genome Atlas network has described a gene expression-based molecular classification of HGS-OvCa into Differentiated, Mesenchymal, Immunoreactive and Proliferative subtypes. However, the biological underpinnings and regulatory mechanisms underlying the distinct molecular subtypes are largely unknown. Here we showed that tumor-infiltrating stromal cells significantly contributed to the assignments of Mesenchymal and Immunoreactive clusters. Using reverse engineering and an unbiased interrogation of subtype regulatory networks, we identified the transcriptional modules containing master regulators that drive gene expression of Mesenchymal and Immunoreactive HGS-OvCa. Mesenchymal master regulators were associated with poor prognosis, while Immunoreactive master regulators positively correlated with overall survival. Meta-analysis of 749 HGS-OvCa expression profiles confirmed that master regulators as a prognostic signature were able to predict patient outcome. Our data unraveled master regulatory programs of HGS-OvCa subtypes with prognostic and potentially therapeutic relevance, and suggested that the unique transcriptional and clinical characteristics of ovarian Mesenchymal and Immunoreactive subtypes could be, at least partially, ascribed to tumor microenvironment. PMID:26530441

  9. The identification of family subtype based on the assessment of subclinical levels of psychosis in relatives

    Derks Eske M


    Full Text Available Abstract Background Schizophrenia is a complex psychiatric disorder characterized by high phenotypic heterogeneity. Previous studies have distinguished between familial and sporadic forms of schizophrenia and have suggested clinical differentiation between patients and relatives from sporadic and multiplex families. We will introduce a more refined method to distinguish between family subtypes based on psychosis dimension profiles in the relatives of schizophrenia patients. Methods Positive, negative, disorganization, mania, and depression scores were assessed in 1,392 relatives. Mixed Model Latent Class Analysis was used to identify family subtypes. A family subtype is a relatively homogeneous group of families with similar symptom profiles in the relatives in these families. Next, we investigated in 616 schizophrenia patients whether family subtype was associated with symptom profiles, IQ, cannabis dependence/abuse, or age of onset of psychosis. Results Based on the data of relatives, we identified two different family types: “healthy” and “at risk for psychiatric disorder”. Patients from at risk families obtained higher positive scores compared to patients from healthy families (Wald(1 = 6.6293, p = 0.010. No significant differences were found in any of the remaining variables. Conclusions Our findings confirm the existence of high-risk families and although we did not establish an etiological basis for the distinction between family types, genetic studies might reveal whether family subtype is associated with genetic heterogeneity.

  10. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping


    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  11. Subtyping of new Brazilian avian metapneumovirus isolates from chickens and turkeys by reverse transcriptase-nested-polymerase chain reaction.

    D'Arce, Regina C F; Coswig, Lia T; Almeida, Renata S; Trevisol, Iara M; Monteiro, Maria C B; Rossini, Lavínia I; Di Fabio, José; Hafez, Hafez M; Arns, Clarice W


    The aim of this study was to improve a reverse transcriptase (RT)-nested-polymerase chain reaction (PCR) able to differentiate avian pneumovirus (APV) subtypes A and B, and to characterize new Brazilian isolates. Representative APV strains and clinical field samples from chickens and turkey flocks were amplified in the chicken embryo-related cell line. Viral RNA was extracted from harvested cells, and submitted to cDNA synthesis. The primers utilized for RT-PCR were compatible with the G gene of both the A and B subtypes of APV, while the nested primers were subtype specific. This approach showed that three new APVs from chickens and one from turkeys were subtype A, confirmed by sequencing. This is the first report of APV isolation from turkeys in Brazil. Four other APVs were detected and classified as subtype A by RT-nested-PCR. These optimized techniques could be useful for differentiation of APV subtypes A and B, proving to be a valuable molecular epidemiological tool.

  12. H1N1 influenza A virus neuraminidase modulates infectivity in mice.

    Ferraris, Olivier; Escuret, Vanessa; Bouscambert, Maude; Casalegno, Jean-Sébastien; Jacquot, Frédéric; Raoul, Hervé; Caro, Valérie; Valette, Martine; Lina, Bruno; Ottmann, Michèle


    In the 2years since the onset of the H1N1 2009 pandemic virus (H1N1pdm09), sporadic cases of oseltamivir-resistant viruses have been reported. We investigated the impact of oseltamivir-resistant neuraminidase from H1N1 Brisbane-like (seasonal) and H1N1pdm09 viruses on viral pathogenicity in mice. Reassortant viruses with the neuraminidase from seasonal H1N1 virus were obtained by co-infection of a H1N1pdm09 virus and an oseltamivir-resistant H1N1 Brisbane-like virus. Oseltamivir-resistant H1N1pdm09 viruses were also isolated from patients. After biochemical characterization, the pathogenicity of these viruses was assessed in a murine model. We confirmed a higher infectivity, in mice, of the H1N1pdm09 virus compared to seasonal viruses. Surprisingly, the oseltamivir-resistant H1N1pdm09 virus was more infectious than its sensitive counterpart. Moreover, the association of H1N1pdm09 hemagglutinin and an oseltamivir-resistant neuraminidase improved the infectivity of reassortant viruses in mice, regardless of the NA origin: seasonal (Brisbane-like) or pandemic strain. This study highlights the need to closely monitor the emergence of oseltamivir-resistant viruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. The origin of a novel kind of reassortant (H1N2) of influenza A virus


    Genetic analysis of three H1N2 viruses indicated that only HA genes of H1N2 viruses were similar to that of A/Guangdong/6/91(H1N1) virus (PR8-like strain), while the other seven genes of them were similar to those of H3N2 virus circulating in man in 1995. Therefore, it could be considered that the H1N2 viruses were derived from reassortment between PR8-like strain and H3N2 virus circulating in man in 1995. However, the genomes of H1N2 viruses were very similar to each other. So the H1N2 viruses isolated in 1998 were not derived from new reassortment between PR8-like strain and H3N2 virus circulating in man in 1998, but derived from the evolution of H1N2 virus found in 1995.

  14. Salmonella source attribution based on microbial subtyping

    Barco, Lisa; Barrucci, Federica; Olsen, John Elmerdahl


    Source attribution of cases of food-borne disease represents a valuable tool for identifying and prioritizing effective food-safety interventions. Microbial subtyping is one of the most common methods to infer potential sources of human food-borne infections. So far, Salmonella microbial subtyping...... source attribution models have been implemented by using serotyping and phage-typing data. Molecular-based methods may prove to be similarly valuable in the future, as already demonstrated for other food-borne pathogens like Campylobacter. This review assesses the state of the art concerning Salmonella...... in the context of their potential applicability for Salmonella source attribution studies....

  15. Advances in Molecular Serotyping and Subtyping of Escherichia coli

    Pina M. Fratamico


    Full Text Available E. coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing E. coli have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtyping and molecular serotyping methods for E. coli, which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS of E. coli is replacing established subtyping methods such as pulsed-field gel electrophoresis (PFGE, providing a major advancement in the ability to investigate food-borne disease outbreaks and for trace-back to sources. A variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O- and H-group determination and the presence of virulence genes and other genetic markers.

  16. The N-terminal domain determines the affinity and specificity of H1 binding to chromatin

    Oeberg, Christine, E-mail: [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden); Belikov, Sergey, E-mail: [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)


    Highlights: Black-Right-Pointing-Pointer wt Human histone H1.4 and hH1.4 devoid of N-terminal domain, {Delta}N-hH1.4, were compared. Black-Right-Pointing-Pointer Both histones bind to chromatin, however, {Delta}N-hH1.4 displays lower binding affinity. Black-Right-Pointing-Pointer Interaction of {Delta}N-hH1.4 with chromatin includes a significant unspecific component. Black-Right-Pointing-Pointer N-terminal domain is a determinant of specificity of histone H1 binding to chromatin. -- Abstract: Linker histone H1, one of the most abundant nuclear proteins in multicellular eukaryotes, is a key component of the chromatin structure mainly due to its role in the formation and maintenance of the 30 nm chromatin fiber. It has a three-domain structure; a central globular domain flanked by a short N-terminal domain and a long, highly basic C-terminal domain. Previous studies have shown that the binding abilities of H1 are at large determined by the properties of the C-terminal domain; much less attention has been paid to role of the N-terminal domain. We have previously shown that H1 can be reconstituted via cytoplasmic mRNA injection in Xenopus oocytes, cells that lack somatic H1. The heterologously expressed H1 proteins are incorporated into in vivo assembled chromatin at specific sites and the binding event is monitored as an increase in nucleosomal repeat length (NRL). Using this setup we have here compared the binding properties of wt-H1.4 and hH1.4 devoid of its N-terminal domain ({Delta}N-hH1.4). The {Delta}N-hH1.4 displays a drastically lower affinity for chromatin binding as compared to the wild type hH1.4. Our data also indicates that {Delta}N-hH1.4 is more prone to unspecific chromatin binding than the wild type. We conclude that the N-terminal domain of H1 is an important determinant of affinity and specificity of H1-chromatin interactions.

  17. Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl-3H-1λ3,2-benziodaoxol-3-one

    Nico Santschi


    Full Text Available The synthesis of 5-nitro-1-(trifluoromethyl-3H-1λ3,2-benziodaoxol-3-one (3, a hypervalent-iodine-based electrophilic trifluoromethylating reagent, is described. Whereas considerations based on cyclic voltammetry and X-ray structural properties would predict an inferior reactivity when compared to the non-nitrated derivative 2, 19F NMR kinetic studies showed that this new derivative is almost one order of magnitude more reactive. Furthermore, differential scanning calorimetry measurements indicated that, in addition, it is also safer to handle.

  18. In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009

    Christopher; VAVRICKA; GAO; George; F


    The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza viruses.We analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes.We compared their differences and similarities systematically.Based on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor.The D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported work.This HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion function.The 2009 S-OIV HA also has an extra glycosylation site at position 276.Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation site.The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined.These results are critical for understanding the pathogenicity of the virus and host immune response against the virus.


    O. A. Antelava


    Full Text Available The lecture considers the problem of rare systemic connective tissue diseases, such as idiopathic inflammatory myopathies (IIMs. It underlines the clinical and immunological heterogeneity of their subtypes, which defines therapeutic tactics and prognosis. The diagnostic criteria for IIMs are given. A differential diagnostic algorithm based on the exclusion of phenotypically similar forms of myopathies of different genesis is proposed. 

  20. Subtype-specific patterns of molecular mutations in acute myeloid leukemia.

    Rose, D; Haferlach, T; Schnittger, S; Perglerová, K; Kern, W; Haferlach, C


    Acute myeloid leukemia (AML) can be grouped into morphologically or genetically defined subtypes. Today, the AML phenotype-genotype associations, that is, FAB/WHO (French-American-British/World Health Organization) definitions and recurrent molecular mutations, are not fully understood. Therefore, we evaluated the impact of molecular mutations on the AML differentiation stage by molecular profiling of 4373 adult de novo AML patients in 7 cytomorphological subtypes. We investigated mutations in 20 genes, including myeloid transcription factors (CEBPA, RUNX1), tumor suppressors (TP53, WT1), DNA modifiers (DNMT3A, IDH1/2, TET2), chromatin modifiers (ASXL1, MLL), signal transduction genes (FLT3, KRAS, NRAS) and NPM1. The most frequently mutated genes per cytomorphological subtype were RUNX1 in M0 (43%), NPM1 in M1 (42%), DNMT3A in M2 (26%), NPM1 in M4 (57%), M5a (49%) and M5b (70%) and TP53 in M6 (36%). Although some gene mutations were frequent in several cytomorphological subtypes, a series of associations of co-occurring mutations with distinct phenotypes were identified for molecularly defined subcohorts. FLT3, NPM1 and WT1 mutations were associated with an immature phenotype in myeloblastic AML, whereas other combinations involving ASXL1, RUNX1, MLL-PTD, CEBPA or KRAS were more frequent in myeloblastic AML with maturation. Within the NPM1 mutated subcohort, ASXL1 mutations were significantly associated with a monoblastic differentiation and DNMT3A mutations with a monocytic phenotype.

  1. Vitamin D Levels, Natural H1N1 Infection and Response to H1N1 Vaccine among HIV-Infected Individuals.

    Momplaisir, Florence; Frank, Ian; Meyer, Wa; Kim, Deborah; Kappes, Rosemary; Tebas, Pablo


    BACKGROUND: Beyond its role in calcium homeostasis, vitamin D plays a critical role in immunological responses to pathogens. We evaluated the relationship between 25-OH vitamin D levels and susceptibility to natural H1N1 infection and H1N1 vaccine responses in HIV infected individuals. METHODS: This was a sub study of an H1N1 vaccine trial conducted at the University of Pennsylvania in 2009/10. We compared the 25-OH vitamin D levels among individuals with and without baseline evidence of prior H1N1 infection and between vaccine responders and non-responders. RESULTS: 120 participants enrolled in the trial, 71% male, 68% African American, median age 46 years. The majority had controlled HIV disease. At baseline, 86% had 25-OH vitamin D levels < 30 ng/ml and 54% had levels < 20 ng/ml. Thirty participants (25%) had evidence of prior H1N1 exposure. There was no difference in mean 25-OH vitamin D levels among patients with or without prior natural H1N1 infection (21 ng/ml vs 20 ng/ml, p=0.72). Among participants without previous H1N1 exposure, only 61% developed protective antibody titers following vaccination. 25-OH vitamin D levels were similar between vaccine responders (20 ng/ml) and non-responders (20 ng/ml) (p=0.83). CONCLUSION: Although 25-OH vitamin D deficiency was very common among HIV-infected individuals, it was not associated with natural susceptibility to H1N1 or to vaccine responses.

  2. Research progress of severe influenza A H1N1%重症甲型H1N1流感研究进展

    王涛; 高占成


    甲型H1N1流感最新疫情的突出特点是重症和死亡病例数显著增加,有关我国重症甲型H1N1流感患者的临床特征、预后、危险因素等方面的研究尚未见相关报道.本文拟对国外有关这方面的研究进行总结,为我国重症甲型H1N1流感的诊断及治疗提供借鉴.%The latest epidemic of influenza A H1N1 is characterized by the significant increase of severe and dead cases. The researches about clinical features, prognosis, risk factors and other aspects of Chinese patients with severe influenza A H1N1 have not been reported. This paper is to summarize foreign researches and provide a reference for the diagnosis and treatment of severe influenza A H1N1 in China.

  3. Predicting H1N1 vaccine uptake and H1N1-related health beliefs: the role of individual difference in consideration of future consequences.

    Nan, Xiaoli; Kim, Jarim


    This research examines the influence of individual difference in consideration of future consequences on H1N1 vaccine uptake and H1N1-related health beliefs (i.e., perceived susceptibility to and severity of the H1N1 flu, perceived efficacy and safety of the H1N1 vaccine, and perceived self-efficacy in obtaining the H1N1 vaccine). A survey of 411 college students showed that consideration of future consequences had no direct effect on vaccine uptake, but higher consideration of future consequences was associated with greater perceived severity of the flu, higher perceived effectiveness of the vaccine, and greater perceived self-efficacy. Additional analysis suggested that consideration of future consequences had a significant indirect effect on vaccine uptake through perceived vaccine efficacy. Results of the study also revealed gender and racial differences in some of the H1N1-related health beliefs. Implications of the findings for vaccine risk communication are discussed.

  4. The use of New Generation H1 Receptor Blockers and Advantages in Terms of Reliability

    Muhammed Yayla


    Full Text Available H1 receptor blockers are one of the most commonly prescribed medications in the treatment of allergic disorders. These disease have reduced life quality of people and prevalent in the world. H1 receptor blockers has been used since 1940 and lead to some adverse effects such as sedation because of their chemical and pharmacological properties. Therefore new generations have been studied for reduced their adverse effect. The aims of this review are to exhibit advantages of new produced H1 receptor blockers compared to classical antihistamines and demonstrate efficacies of clinical uses of new produced H1 antihistamines. New generation H1 receptor blockers which have been developed after 1980s has less lipophilic properties and their sedative effects are minimized compared to classical antihistamines. Also, their specificity, affinity for H1 receptors and antihistaminergic effects are higher than classical H1 receptor blockers. Although new generation H1 receptor blockers are better tolerated than classical H1 receptor blockers, some of them lead to potential cardio toxicity. Consequently new generation H1 receptor blockers are reliable and efficient drugs, they provide convenience in the treatment of allergic disorders and prevent development of phobia against drugs.

  5. Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics.

    Bernier, Morgan; Luo, Yi; Nwokelo, Kingsley C; Goodwin, Michelle; Dreher, Sarah J; Zhang, Pei; Parthun, Mark R; Fondufe-Mittendorf, Yvonne; Ottesen, Jennifer J; Poirier, Michael G


    H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF binding. These findings show that nucleosomes remain dynamic, while H1 is bound and H1 dissociation is not required for TF binding within the nucleosome. Furthermore, our H3K56 acetylation measurements suggest that a single-histone PTM can define regions of the genome that are not regulated by H1.

  6. Characterization of muscarinic receptor subtypes in human tissues

    Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.


    The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with (/sup 3/H)Pirenzepine and (/sup 3/H)N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M/sub 1/ neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M/sub 1/, the cardiac M/sub 2/ and the glandular M/sub 3/.

  7. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Rosa Dolz-Marco


    Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

  8. Subtyping Ageism: Policy Issues in Succession and Consumption.

    North, Michael S; Fiske, Susan T


    Ageism research tends to lump "older people" together as one group, as do policy matters that conceptualize everyone over-65 as "senior." This approach is problematic primarily because it often fails to represent accurately a rapidly growing, diverse, and healthy older population. In light of this, we review the ageism literature, emphasizing the importance of distinguishing between the still-active "young-old" and the potentially more impaired "old-old" (Neugarten, 1974). We argue that ageism theory has disproportionately focused on the old-old and differentiate the forms of age discrimination that apparently target each elder subgroup. In particular, we highlight the young-old's plights predominantly in the workplace and tensions concerning succession of desirable resources; by contrast, old-old predicaments likely center on consumption of shared resources outside of the workplace. For both social psychological researchers and policymakers, accurately subtyping ageism will help society best accommodate a burgeoning, diverse older population.

  9. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    Perez Villamil Beatriz


    Full Text Available Abstract Background Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Methods Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV. Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Results Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01; Dukes B,C and D:HR = 1.87(1.07-3.25. Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and the other tumor subtypes. Conclusions We have identified novel molecular subtypes in colon cancer with distinct biological and clinical behavior that are established from the initiation of the tumor. Tumor microenvironment is important for the classification and for the malignant power of the tumor. Differential gene sets and biological pathways characterize each tumor subtype reflecting underlying mechanisms of carcinogenesis that may be used for the selection of targeted therapeutic procedures. This classification may contribute to an improvement in the management of the patients with CRC and to a

  10. Linking social and spatial networks to viral community phylogenetics reveal subtype specific transmission dynamics in African lions.

    Fountain-Jones, Nicholas M; Packer, Craig; Troyer, Jennifer L; VanderWaal, Kimberly; Robinson, Stacie; Jacquot, Maude; Craft, Meggan E


    1.Heterogeneity within pathogen species can have important consequences for how pathogens transmit across landscapes; however, discerning different transmission routes is challenging. 2.Here we apply both phylodynamic and phylogenetic community ecology techniques to examine the consequences of pathogen heterogeneity on transmission by assessing subtype specific transmission pathways in a social carnivore. 3.We use comprehensive social and spatial network data to examine transmission pathways for three subtypes of feline immunodeficiency virus (FIVPle ) in African lions (Panthera leo) at multiple scales in the Serengeti National Park, Tanzania. We used FIVPle molecular data to examine the role of social organization and lion density in shaping transmission pathways and tested to what extent vertical (i.e., father and/or mother offspring relationships) or horizontal (between unrelated individuals) transmission underpinned these patterns for each subtype. Using the same data, we constructed subtype specific FIVPle co-occurrence networks and assessed what combination of social networks, spatial networks, or co-infection best structured the FIVPle network. 4.While social organization (i.e., pride) was an important component of FIVPle transmission pathways at all scales, we find that FIVPle subtypes exhibited different transmission pathways at within- and between-pride scales. A combination of social and spatial networks, coupled with consideration of subtype co-infection, was likely to be important for FIVPle transmission for the two major subtypes, but the relative contribution of each factor was strongly subtype specific. 5.Our study provides evidence that pathogen heterogeneity is important in understanding pathogen transmission, which could have consequences for how endemic pathogens are managed. Furthermore, we demonstrate that community phylogenetic ecology coupled with phylodynamic techniques can reveal insights into the differential evolutionary pressures acting

  11. Proteomic maps of breast cancer subtypes

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina


    oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell...

  12. Subtyping Male Perpetrators of Intimate Partner Violence

    Fowler, Katherine A.; Westen, Drew


    Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male…

  13. A Taxometric Investigation of Developmental Dyslexia Subtypes

    O'Brien, Beth A.; Wolf, Maryanne; Lovett, Maureen W.


    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with…

  14. A Taxometric Investigation of Developmental Dyslexia Subtypes

    O'Brien, Beth A.; Wolf, Maryanne; Lovett, Maureen W.


    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with…

  15. Modelling influenza A(H1N1) 2009 epidemics using a random network in a distributed computing environment.

    González-Parra, Gilberto; Villanueva, Rafael-J; Ruiz-Baragaño, Javier; Moraño, Jose-A


    In this paper we propose the use of a random network model for simulating and understanding the epidemics of influenza A(H1N1). The proposed model is used to simulate the transmission process of influenza A(H1N1) in a community region of Venezuela using distributed computing in order to accomplish many realizations of the underlying random process. These large scale epidemic simulations have recently become an important application of high-performance computing. The network model proposed performs better than the traditional epidemic model based on ordinary differential equations since it adjusts better to the irregularity of the real world data. In addition, the network model allows the consideration of many possibilities regarding the spread of influenza at the population level. The results presented here show how well the SEIR model fits the data for the AH1N1 time series despite the irregularity of the data and returns parameter values that are in good agreement with the medical data regarding AH1N1 influenza virus. This versatile network model approach may be applied to the simulation of the transmission dynamics of several epidemics in human networks. In addition, the simulation can provide useful information for the understanding, prediction and control of the transmission of influenza A(H1N1) epidemics.

  16. Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer

    Lin-Bo Wang; Zhi-Nong Jiang; Miao-Ying Fan; Chao-Yang Xu; Wen-Jun Chen; Jian-Guo Shen


    AIM:To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer.METHODS:One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed.Differences in histology of the primary and metastatic gastric cancer were assessed.MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer.RESULTS:Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177)and primary gastric cancer in 75.7% (134/177) of the patients.The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%).MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer,while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer.CONCLUSION:Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer.This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.

  17. North American triple reassortant and Eurasian H1N1 swine influenza viruses do not readily reassort to generate a 2009 pandemic H1N1-like virus.

    Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J; Richt, Jürgen A


    The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment. IMPORTANCE The 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of

  18. Recombination analysis and homology alignment of full-length genome sequences of die novel A/H1N1 influenza virus in 2009%2009年新型甲型H1N1流感病毒全基因组序列重组分析及同源性比对

    鹿文英; 殷建华; 李淑华; 韩磊; 韩一芳; 苏彤; 曹广文


    Objective To analyze the genetic variation and recombination of the novel A/H1N1 influenza pandemic virus in 2009. Methods Full-length sequence of typical novel A/H1N1 influenza virus was downloaded from NCBI database. MEGA4.0 software was used to connect and align the eight fragments of the virus. Then the fragments of different subtypes such as H1N1, H5N1 and H3N2 of the historical strains from different hosts, including human, poultry and pigs, were connected and aligned in the same way. A phylogenetic tree was constructed by NJ method. The recombination analysis of 2009 pandemic virus was made with Simplot 3. 5.1 software. Results There was no clear variation (identity was 99.69% - 99. 93%) in the novel A/H1N1 influenza virus from April to September, 2009. Simplot and MEGA analysis indicated that the PB2, PB1, PA, HA, NP and NS of the novel A/H1N1 virus might originally evolve from the swine and human H1N1 virus isolated in North America (identity was 95. 25%, 95.08%, 95.21%, 93.52%, 95.23% and 94.78%, respectively). NA and MP showed high homology with the European swine H1N1 virus, the identity was 90.21% and 94.43%, respectively. Full-length sequence of the novel A/H1N1 influenza virus had a highest similarity with swine H1N1 virus isolated from North America (identity was 92.22%). Conclusions The novel A/H1N1 influenza pandemic virus in 2009 was originated from the reassortment and evolution of swine H1N1 2005 pandemic virus in North America, and the NA and MP fragments of European swine H1N1. There is no clear variation in novel influenza virus up to now. The novel A/H1N1 influenza vaccine possesses protective effect.%目的 分析2009年新型甲型H1N1流感爆发以来流感病毒的全基因组进化变异及重组情况.方法 从NCBI基因数据库下载2009年新型甲型H1N1流感病毒(A/H1N1)代表性全基因组序列,先用MEGA4.0软件对8个基因序列片段进行比对和拼接;然后将历史上流行的H1N1、H5N1、H3N2等不同宿

  19. Transcriptional coexpression network reveals the involvement of varying stem cell features with different dysregulations in different gastric cancer subtypes.

    Kalamohan, Kalaivani; Periasamy, Jayaprakash; Bhaskar Rao, Divya; Barnabas, Georgina D; Ponnaiyan, Srigayatri; Ganesan, Kumaresan


    Despite the advancements in the cancer therapeutics, gastric cancer ranks as the second most common cancers with high global mortality rate. Integrative functional genomic investigation is a powerful approach to understand the major dysregulations and to identify the potential targets toward the development of targeted therapeutics for various cancers. Intestinal and diffuse type gastric tumors remain the major subtypes and the molecular determinants and drivers of these distinct subtypes remain unidentified. In this investigation, by exploring the network of gene coexpression association in gastric tumors, mRNA expressions of 20,318 genes across 200 gastric tumors were categorized into 21 modules. The genes and the hub genes of the modules show gastric cancer subtype specific expression. The expression patterns of the modules were correlated with intestinal and diffuse subtypes as well as with the differentiation status of gastric tumors. Among these, G1 module has been identified as a major driving force of diffuse type gastric tumors with the features of (i) enriched mesenchymal, mesenchymal stem cell like, and mesenchymal derived multiple lineages, (ii) elevated OCT1 mediated transcription, (iii) involvement of Notch activation, and (iv) reduced polycomb mediated epigenetic repression. G13 module has been identified as key factor in intestinal type gastric tumors and found to have the characteristic features of (i) involvement of embryonic stem cell like properties, (ii) Wnt, MYC and E2F mediated transcription programs, and (iii) involvement of polycomb mediated repression. Thus the differential transcription programs, differential epigenetic regulation and varying stem cell features involved in two major subtypes of gastric cancer were delineated by exploring the gene coexpression network. The identified subtype specific dysregulations could be optimally employed in developing subtype specific therapeutic targeting strategies for gastric cancer.

  20. Origin and future distribution of the new A (H1N1) influenza virus emerging in North America in 2009

    CHEN JiMing; SUN YingXue; LIU Shuo; JIANG WenMing; CHEN Jie; HOU GuangYu; LI JinPing


    The origin of the new A (H1N1) influenza virus recently emerging in North America is a hot controversial topic of significance in disease control and risk assessment.Some experts claimed that it was an unusually mongrelized mix of human,avian and swine influenza viruses,while some others concluded that it was totally a simple re-assortment hybrid of two lineages of swine influenza viruses.Here the phylogenetic diversity of the viral PB1,PA and PB2 gene sequences using online web servers,and the results suggest that all the 8 genetic segments of the new virus were possibly from two lineages of swine influenza viruses,and one of the lineage was a mongrelized mix of human,avian and swine influenza viruses emerging in the world approximately 10 years ago.Considering the recent epidemiological trends of the new virus,we believe it will spread more widely in the world and persist long in human populations.It also could spread among swine populations.The future wide spreading of the new virus may coincide the disappearance of a subtype of previous human influenza A virus.

  1. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)


    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  2. Molecular epidemiology and phylogenetic analysis of HA gene of influenza A(H1N1)pdm09 strain during 2010-2014 in Dalian, North China.

    Han, Yan; Sun, Nan; Lv, Qiu-Yue; Liu, Dan-Hong; Liu, Da-Peng


    The objective of the present study was to evaluate the epidemiology of influenza A(H1N1)pdm09 and its hemagglutinin (HA) molecular and phylogenetic analysis during 2010-2014 in Dalian, North China. A total of 3717 influenza-like illness (ILI) cases were tested by real-time PCR and 493 were found to be positive. Out of these 493 cases, 121 were subtype influenza A(H1N1)pdm09, of which 14 cases were reported in 2010-2011, 29 in 2012-2013, and 78 in 2013-2014. HA coding regions of 45 isolates were compared to that of the vaccine strain A/California/7/09(H1N1), and a number of variations were detected. P83S, S185T, S203T, R223Q, and I321V mutations were observed in all of the Dalian isolates. Furthermore, a high proportion >71 % of the strains possessed the variation D97N and K283E. Phylogenetic analysis confirmed the close match of the majority of circulating strains with the vaccine strains. However, it also reveals a trend of strains to accumulate amino acid variations and form new phylogenetic groups.

  3. Thermodynamical study of interaction of histone H1 chromosomal protein and mitoxantrone anticancer drug

    Jafargholizadeh, Naser [Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Zargar, Seyed Jalal, E-mail: [Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Safarian, Shahrokh; Habibi-Rezaei, Mehran [Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of)


    Highlights: Black-Right-Pointing-Pointer For the first time, our results show mitoxantrone anticancer drug binds to histone H1, via hydrophobic, hydrogen, van der Waals and electrostatic interactions. Black-Right-Pointing-Pointer Binding of mitoxantrone molecules to histone H1 is positive cooperative. Black-Right-Pointing-Pointer Histone H1 may be considered as a new target for mitoxantrone at the chromatin level. - Using ultraviolet spectroscopy technique, we have investigated the interaction of anticancer drug, mitoxantrone with calf thymus histone H1 chromosomal protein in 100 mM phosphate buffer, pH 7.0, at temperatures 300 and 310 K. UV spectroscopy results show interactions between mitoxantrone and histone H1 with a positive cooperative binding process which was confirmed by Scatchard plot. According to the obtained results, it is concluded that histone H1 can be considered as a target for mitoxantrone binding at the chromatin level.

  4. Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis.

    Jung, Hwa Sik; Park, Chan-Ho; Park, Young Tae; Bae, Mi Ae; Lee, Youn Im; Kang, Byung Ju; Jegal, Yangjin; Ahn, Jong Joon; Lee, Taehoon


    H1-antihistamine is generally a well-tolerated and safe drug. However, in resemblance with all other drugs, H1-antihistamines can also prompt adverse drug reactions (ADRs). We recently encountered the very unusual ADR of H1-antihistamine-induced gynecomastia. A 21-year-old man with idiopathic anaphylaxis was treated with ebastine (Ebastel), a second-generation H1-antihistamine, for the prevention of anaphylaxis. Three months later, the patient remained well without anaphylaxis, but had newly developed gynecomastia. Because anaphylaxis recurred after the cessation of H1-antihistamine, the preventive medication was changed to omalizumab. A few months later, his gynecomastia had entirely disappeared. Physicians should be aware of this exceptional ADR of H1-antihistamine.

  5. Linkage disequilibrium and association of MAPT H1 in Parkinson disease.

    Skipper, Lisa; Wilkes, Kristen; Toft, Mathias; Baker, Matthew; Lincoln, Sarah; Hulihan, Mary; Ross, Owen A; Hutton, Mike; Aasly, Jan; Farrer, Matthew


    The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. More controversial is that the same haplotype has been associated with Parkinson disease (PD). Using H1-specific single-nucleotide polymorphisms, we demonstrate that MAPT H1 is a misnomer and consists of a family of recombining H1 alleles. Population genetics, linkage disequilibrium, and association analyses have shown that specific MAPT H1 subhaplotypes are preferentially associated with Parkinson disease. Using a sliding scale of MAPT H1-specific haplotypes--in age/sex-matched PD cases and controls from central Norway--we have refined the disease association to within an approximately 90-kb interval of the 5' end of the MAPT locus.

  6. Linkage Disequilibrium and Association of MAPT H1 in Parkinson Disease

    Skipper, Lisa; Wilkes, Kristen; Toft, Mathias; Baker, Matthew; Lincoln, Sarah; Hulihan, Mary; Ross, Owen A.; Hutton, Mike; Aasly, Jan; Farrer, Matthew


    The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. More controversial is that the same haplotype has been associated with Parkinson disease (PD). Using H1-specific single-nucleotide polymorphisms, we demonstrate that MAPT H1 is a misnomer and consists of a family of recombining H1 alleles. Population genetics, linkage disequilibrium, and association analyses have shown that specific MAPT H1 subhaplotypes are preferentially associated with Parkinson disease. Using a sliding scale of MAPT H1-specific haplotypes—in age/sex-matched PD cases and controls from central Norway—we have refined the disease association to within an ∼90-kb interval of the 5′ end of the MAPT locus. PMID:15297935

  7. 直击甲型H1N1流感


    @@ 甲型H1N1流感是什么 甲型H1N1流感是一种由A型甲型H1N1流感病毒引起的猪呼吸系统疾病,该病毒可在猪群中造成流感暴发.这次在实验室已被证实的引发疫情的病毒是甲型H1N1流感病毒A(H1N1)亚型,是一种之前从未在人和猪身上出现过的新型甲型H1N1流感病毒;

  8. Challenge of N95 Filtering Facepiece Respirators with Viable H1N1 Influenza Aerosols (Postprint)



  9. Molecular characterization and phylogenetic analysis of Middle East 2009 H1N1 pdm isolates

    Ghaleb Adwan


    Objective:To study hemagglutinin genetic evolution of some Middle East(ME) 2009 H1N1 pdm isolates and compared them with prototype vaccine strain [A/California/07/2009 (H1N1)], which is used as a vaccine strain in the Northern Hemisphere2010-2011.Methods: Nucleotide and/or amino acid sequences ofHA gene of fifty-fourME 2009 H1N1 pdm isolates were retrieved from GenBank Database by using BasicBLAST engine. Phylogenetic trees were established for both nucleotide and amino acid sequences using the muscle algorithm of the computer programCLC free workbench 5.6.1 JREsoftware. Amino acids alignment was also done to compare sequences HA1 domains of HA genes of ME 2009 H1N1 pdm isolates (n=39) with amino acid sequence of prototype vaccine strain A/California/07/2009 (H1N1).Results: Phylogenetic analysis of amino acids and nucleotides of theHA gene of theME 2009 H1N1 pdm isolates confirmed their evolutionary position in cluster with prototype vaccine strain (A/California/07/2009 (H1N1)) which is used as vaccine strain in the Northern Hemisphere2010-2011. Antigenically, theME 2009 H1N1pdm isolates were homogeneous and closely related to prototype vaccine. Only a few amino acid substitutions in the HA among the ME2009 H1N1 pdm isolates were analyzed.Conclusions:The current influenza vaccine is expected to provide a good protection againstME 2009 H1N1 pdm because it contains strains withH1 HA [A/California/07/2009 (H1N1)]-like strain.

  10. 成人甲型H1N1流感的诊治



    成人甲型H1N1流感是由甲型H1N1流感病毒感染引起的新型呼吸道传染病。甲型H1N1流感病毒属于正黏病毒科(Orthomyxoviridae),甲型流感病毒属(Influenza virus A)。

  11. nm23H1 expression and its role in the evolution of non-gastrointestinal malignancies

    Shailendra Kapoor


    The role of nm23H1 genetic instability is not limited to gastrointestinal malignancies. A similar close relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies. For instance, in oral malignant melanomas with lymphoid metastasis, the nm23H1 expression is significantly lower in contrast to tumors with no lymphoid metastasis.Similarly, increased metastasis is seen in non small cell lung cancers following down regulation of nm23H1 in conjunction with KAI-1 down regulation.There is an inverse relationship between tumor stage and metastasis and nm23H1 expression in individuals with prostate carcinomas and a similar relationship exists between microsatellite instability of the nm23H1 gene and ovarian carcinogenesis. For instance, nearly 70.5% of stageⅠ-Ⅱ ovarian tumors express nm23H1 in sharp contrast to only 25% of stage Ⅲ-Ⅳ ovarian tumors. As is clearly evident, nm23H1 has a major role in gastrointestinal and non-gastrointestinal carcinogenesis.The coming few years will hopefully see the development of new strategies by virtue of which we can alter nm23H1 expression and thus decrease the risk of metastasis in malignant tumors.

  12. Synthesis and Dual Histamine H1 and H2 Receptor Antagonist Activity of Cyanoguanidine Derivatives


    Premedication with a combination of histamine H1 receptor (H1R) and H2 receptor (H2R) antagonists has been suggested as a prophylactic principle, for instance, in anaesthesia and surgery. Aiming at pharmacological hybrids combining H1R and H2R antagonistic activity, a series of cyanoguanidines 14–35 was synthesized by linking mepyramine-type H1R antagonist substructures with roxatidine-, tiotidine-, or ranitidine-type H2R antagonist moieties. N-desmethylmepyramine was connected via a poly-met...

  13. Single-Molecule Studies of the Linker Histone H1 Binding to DNA and the Nucleosome.

    Yue, Hongjun; Fang, He; Wei, Sijie; Hayes, Jeffrey J; Lee, Tae-Hee


    Linker histone H1 regulates chromatin structure and gene expression. Investigating the dynamics and stoichiometry of binding of H1 to DNA and the nucleosome is crucial to elucidating its functions. Because of the abundant positive charges and the strong self-affinity of H1, quantitative in vitro studies of its binding to DNA and the nucleosome have generated results that vary widely and, therefore, should be interpreted in a system specific manner. We sought to overcome this limitation by developing a specially passivated microscope slide surface to monitor binding of H1 to DNA and the nucleosome at a single-molecule level. According to our measurements, the stoichiometry of binding of H1 to DNA and the nucleosome is very heterogeneous with a wide distribution whose averages are in reasonable agreement with previously published values. Our study also revealed that H1 does not dissociate from DNA or the nucleosome on a time scale of tens of minutes. We found that histone chaperone Nap1 readily dissociates H1 from DNA and superstoichiometrically bound H1 from the nucleosome, supporting a hypothesis whereby histone chaperones contribute to the regulation of the H1 profile in chromatin.

  14. Fasting plasma glucose is an independent predictor for severity of H1N1 pneumonia

    Sun Xiwen


    Full Text Available Abstract Background The pandemic influenza A (H1N1 virus emerged during 2009 and has spread worldwide. This virus can cause injuries to the lungs, liver, and heart. However, data regarding whether this influenza virus can affect pancreatic islets are limited. We investigated the effects of influenza A (H1N1 pneumonia on fasting plasma glucose (FPG and islet function, and evaluated possible correlations between biochemical test results and the severity of H1N1 pneumonia. Methods We performed a retrospective analysis of patients either diagnosed with or suspected of having H1N1 pneumonia who were admitted to our hospital in 2009. Possible associations between FPG levels and H1N1 virus infection were assessed by logistic regression. Correlation and regression analyses were used to assess relationships between FPG and biochemical test results. Associations between admission days and significant data were assessed by single factor linear regression. To evaluate effects of H1N1 on pancreatic β-cell function, results of a resistance index (homa-IR, insulin function index (homa-β, and insulin sensitivity index (IAI were compared between a H1N1 group and a non-H1N1 group by t-tests. Results FPG was significantly positively associated with H1N1 virus infection (OR = 1.377, 95%CI: 1.062-1.786; p = 0.016. FPG was significantly correlated with AST (r = 0.215; p = 0.039, LDH (r = 0.400; p = 0.000, BUN (r = 0.28; p = 0.005, and arterial Oxygen Saturation (SaO2; r = -0.416; p = 0.000 in the H1N1 group. H1N1 patients who were hypoxemic (SaO22 in the H1N1 group with hypoxia (SaO22 levels in patients with high FPG levels (≥7 mmol/L were significantly lower than those of H1N1 patients with low FPG levels ( Conclusions FPG on admission could be an independent predictor for the severity of H1N1 pneumonia. Elevated FPG induced by H1N1 pneumonia is not a result of direct damage to pancreatic β-cells, but arises from various factors' combinations caused by H1N1

  15. Reasons for Low Pandemic H1N1 2009 Vaccine Acceptance within a College Sample

    Russell D. Ravert


    Full Text Available This study examined health beliefs associated with novel influenza A (H1N1 immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% reported having received an H1N1 vaccine. In regression analysis, H1N1 immunization was associated with seasonal flu vaccine history, perceived vaccine effectiveness, perceived obstacles to vaccination, and vaccine safety concerns. Qualitative results illustrate the relationship of beliefs to vaccine decisions, particularly in demonstrating that students often held concerns that vaccine could cause H1N1 or side effects. Vaccine safety, efficacy, and obstacles to immunization were major considerations in deciding whether to accept the H1N1 pandemic vaccine. Therefore, focusing on those aspects might be especially useful in future vaccine efforts within the college population.

  16. H1N1病毒全球疫情防治


    1、H1N1全病毒灭活疫苗(SlV inactivated vaccines)在已研制的H1N1疫苗中,技术最成熟并用于生产的主要是H1NI型和H3N2亚型单价或双价H1N1全病毒灭活疫苗。其形式多为油佐剂疫苗,灭活剂一般采用甲醛或BEI。据报

  17. 中药治疗甲型H1N1流感浅见




  18. Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection.

    Zang, Farong; Chen, Yinghu; Lin, Zhendong; Cai, Zhijian; Yu, Lei; Xu, Feng; Wang, Jiaoli; Zhu, Weiguo; Lu, Huoquan


    Autophagy can mediate antiviral immunity. However, it remains unknown whether autophagy regulates the immune response of dendritic cells (DCs) to influenza A (H1N1) pdm09 infection. In this study, we found that infection with the H1N1 virus induced DC autophagy in an endocytosis-dependent manner. Compared with autophagy-deficient Beclin-1(+/-) mice, we found that bone-marrow-derived DCs from wild-type mice (WT BMDCs) presented a more mature phenotype on H1N1 infection. Wild-type BMDCs secreted higher levels of interleukin-6 (IL-6), tumour necrosis factor- α (TNF-α), interferon-β (IFN-β), IL-12p70 and IFN-γ than did Beclin-1(+/-) BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs exhibited increased activation of extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and nuclear factor-κB as well as IFN regulatory factor 7 nuclear translocation. Blockade of autophagosomal and lysosomal fusion by bafilomycin A1 decreased the co-localization of H1N1 viruses, autophagosomes and lysosomes as well as the secretion of IL-6, TNF-α and IFN-β in H1N1-infected BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4(+) T-cell proliferation and driving T helper type 1, 2 and 17 cell differentiation while inhibiting CD4(+) Foxp3(+) regulatory T-cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the ovalbumin antigen to CD8(+) T cells. We consistently found that Beclin-1(+/-) BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4(+) and CD8(+) T-cell responses, which produced lower levels of IL-6, TNF-α and IFN-β in vivo. Our data indicate that autophagy is important in the regulation of the DC immune response to H1N1 infection, thereby extending our understanding of host immune responses to the virus.

  19. Investigation of Pathogenesis of H1N1 Influenza Virus and Swine Streptococcus suis Serotype 2 Co-Infection in Pigs by Microarray Analysis.

    Lin, Xian; Huang, Canhui; Shi, Jian; Wang, Ruifang; Sun, Xin; Liu, Xiaokun; Zhao, Lianzhong; Jin, Meilin


    Swine influenza virus and Streptococcus suis are two important contributors to the porcine respiratory disease complex, and both have significant economic impacts. Clinically, influenza virus and Streptococcus suis co-infections in pigs are very common, which often contribute to severe pneumonia and can increase the mortality. However, the co-infection pathogenesis in pigs is unclear. In the present study, co-infection experiments were performed using swine H1N1 influenza virus and Streptococcus suis serotype 2 (SS2). The H1N1-SS2 co-infected pigs exhibited more severe clinical symptoms, serious pathological changes, and robust apoptosis of lungs at 6 days post-infection compared with separate H1N1 and SS2 infections. A comprehensive gene expression profiling using a microarray approach was performed to investigate the global host responses of swine lungs against the swine H1N1 infection, SS2 infection, co-infection, and phosphate-buffered saline control. Results showed 457, 411, and 844 differentially expressed genes in the H1N1, SS2, and H1N1-SS2 groups, respectively, compared with the control. Noticeably, genes associated with the immune, inflammatory, and apoptosis responses were highly overexpressed in the co-infected group. Pathway analysis indicated that the cytokine-cytokine receptor interactions, MAPK, toll-like receptor, complement and coagulation cascades, antigen processing and presentation, and apoptosis pathway were significantly regulated in the co-infected group. However, the genes related to these were less regulated in the separate H1N1 and SS2 infection groups. This observation suggested that a certain level of synergy was induced by H1N1 and SS2 co-infection with significantly stronger inflammatory and apoptosis responses, which may lead to more serious respiratory disease syndrome and pulmonary pathological lesion.

  20. Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1 virus infection: an observational cohort study

    Youn You-Sook


    Full Text Available Abstract Background There was a pandemic influenza around the world in 2009 including South Korea since last pandemic occurred four decades ago. We aimed to evaluate the epidemiological and clinical characteristics of this infection in childhood. Methods We evaluated the epidemiologic characteristics of all the subjects infected with the 2009 H1N1 influenza A virus (2,971 patients, ≤ 15 years of age, and the clinical and laboratory findings of the inpatients (217 patients, 80 had pneumonia between 1 September 2009 and 31 January 2010 in a single hospital throughout the epidemic. Results The age distribution of all the subjects was relatively even. Over 90% of cases occurred during a two-month period. Two hundred and five patients (94.5% received oseltamivir within 48 h of fever onset, and 97% of inpatients defervesced within 48 h of medication. The group with pneumonia included more males than females, and had higher leukocytes counts with lower lymphocyte differentials than the group without pneumonia. The white blood cell count and lymphocyte differential were associated with the severity of pneumonia. Corticosteroid treatment for severe pneumonia patients was highly effective in preventing disease progression. Conclusion Children of all ages affected with even rates of infection, but males were predominant in pneumonia patients. Pneumonia patients showed lymphopenia and its severity was associated with the severity of illness. Our results suggest that the mechanism of lung injury in 2009 H1N1 virus infection may be associated with the host immune response.

  1. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    Charles Nfon

    Full Text Available There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI. In addition, heterologous cell mediated immunity (CMI was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  2. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn


    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  3. H1N1 Influenza Flu:Report of 130 Cases%甲型H1N1流行性感冒临床分析

    吴传芬; 何爱民


    Objective To explore the diagnosis and treatment of H1N1 pandemic influenza. Methods Clinical characteristics and treatment of 130 cases of H1N1 influenza were retrospectively analyzed. Results Patients with mild H1N1 flu responsed to the supportive treatment by traditional Chinese medicine, Lianhuaqingwen capsule while severe patients with complicated infections responsed to combined anti - infection traditional Chinese medicine therapy , supportive treatment, and oseltamivir, an anti -influenza virus neuraminidase inhibitor. Comparison of WBC count, lymphocyte fraction, neutrophil fraction, and platelet count between hefore and after treatment showed significant differences ( P < 0.05 ) . Conclusion H1N1 pandemic influenza spread widely and rapidly, which were easily be infected. Combination of anti - infection traditional Chinese medicine therapy , supportive treatment, and oseltamivir is effective in treating H1N1 flu with complicated infections.%目的 探讨甲型H1N1流行性感冒(流感)的诊断、治疗要点.方法 回顾性分析130例甲型H1N1流感患者的临床特点、治疗方法.结果 病情轻的甲型H1N1流感患者给予中成药连花清瘟胶囊对症、支持治疗有效;病情重合并感染者给予抗感染中药对症、支持治疗基础上,加用神经氨酸酶抑制剂奥司他韦抗病毒治疗有效.130例患者治疗前后白细胞计数、淋巴细胞分数、中性粒细胞分数、血小板计数比较,差异均有统计学意义(P<0.05).结论 甲型H1N1流感传播广而迅猛,人群普遍易感.抗病毒(神经氨酸酶抑制剂奥司他韦)、中成药(连花清瘟胶囊)及对症支持治疗合并感染者有效.

  4. Distribution and characterization of subtypes of penile intraepithelial neoplasia and their association with invasive carcinomas: a pathological study of 139 lesions in 121 patients.

    Chaux, Alcides; Velazquez, Elsa F; Amin, Ali; Soskin, Ana; Pfannl, Rolf; Rodríguez, Ingrid M; Barreto, José E; Lezcano, Cecilia; Ayala, Gustavo; Netto, George J; Cubilla, Antonio L


    We are presenting the morphological features of 121 cases of atypical penile intraepithelial lesions. The term penile intraepithelial neoplasia (PeIN) was used to encompass all of them, and lesions were classified into 2 major groups, differentiated and undifferentiated. The latter was further divided in warty, basaloid, and warty-basaloid subtypes. Ninety-five cases were associated with invasive squamous cell carcinomas. Differentiated lesions predominated (68%), followed by warty-basaloid (14%), basaloid (11%), and warty (7%) subtypes. Multifocality was found in 15% of the cases. Differentiated lesions were preferentially located in foreskin, whereas warty and/or basaloid subtypes were more prevalent in the glans. The former lesions were preferentially seen in association with keratinizing variants of squamous carcinoma, whereas the latter subtypes were found mostly in conjunction with invasive warty, basaloid, and warty-basaloid carcinomas. Lichen sclerosus was present in 51% of cases of differentiated lesions and absent in warty and/or basaloid subtypes. In summary, PeIN can be classified into 4 distinctive morphological subtypes. The proper pathological characterization of these lesions may provide important clues to the understanding of the pathogenesis and natural history of penile cancer.

  5. Comparison of STIR turbo SE imaging and diffusion-weighted imaging of the lung: capability for detection and subtype classification of pulmonary adenocarcinomas

    Koyama, Hisanobu; Ohno, Yoshiharu; Onishi, Yumiko; Matsumoto, Keiko; Nogami, Munenobu; Takenaka, Daisuke; Sugimura, Kazuro [Kobe University Graduate School of Medicine, Department of Radiology, Kobe, Hyogo (Japan); Aoyama, Nobukazu [Kobe University Hospital, Division of Radiology, Kobe (Japan); Nishio, Wataru [Kobe University Graduate School of Medicine, Division of Cardiovascular, Thoracic and Pediatric Surgery, Kobe (Japan); Ohbayashi, Chiho [Hyogo Cancer Center, Division of Pathology, Akashi (Japan)


    The aim of the study was to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) for detection and subtype classification in pulmonary adenocarcinomas through comparison with short TI inversion recovery turbo spin-echo imaging sequence (STIR). Thirty-two patients (mean age, 65.2 years) with 33 adenocarcinomas (mean diameter, 27.6 mm) were enrolled in this study. The detection rates of both sequences were compared. The ADC values on DWI and the contrast ratio (CR) between cancer and muscle on STIR were measured and those were compared across subtype classifications. Finally, ROC-based positive tests were performed to differentiate subtype classifications, and differentiation capabilities were compared. The DWI detection rate [85% (28/33)] was significantly lower than that of STIR [100% (33/33), P < 0.05]. The ADC values showed no significant difference regarding subtype classification; however, the CRs of bronchio-alveolar carcinomas (BACs) were significantly lower than those of other types (P < 0.05). When threshold values for differentiating BACs from others were adapted, the sensitivity and accuracy of DWI were significantly lower than those of STIR (P < 0.05). For differentiating adenocarcinomas with mixed subtypes from those with no BA component, there were no significant differences between the two sequences. STIR is more sensitive for detection and subtype classification than DWI. (orig.)

  6. An equine herpesvirus 1 (EHV-1) vectored H1 vaccine protects against challenge with swine-origin influenza virus H1N1.

    Said, Abdelrahman; Damiani, Armando; Ma, Guanggang; Kalthoff, Donata; Beer, Martin; Osterrieder, Nikolaus


    In 2009, a novel swine-origin H1N1 influenza A virus (S-OIV), antigenically and genetically divergent from seasonal H1N1, caused a flu pandemic in humans. Development of an effective vaccine to limit transmission of S-OIV in animal reservoir hosts and from reservoir hosts to humans and animals is necessary. In the present study, we constructed and evaluated a vectored vaccine expressing the H1 hemagglutinin of a recent S-OIV isolate using equine herpesvirus 1 (EHV-1) as the delivery vehicle. Expression of the recombinant protein was demonstrated by immunofluorescence and western blotting and the in vitro growth properties of the modified live vector were found to be comparable to those of the parental virus. The EHV-1-H1 vaccine induced an influenza virus-specific antibody response when inoculated into mice by both the intranasal and subcutaneous routes. Upon challenge infection, protection of vaccinated mice could be demonstrated by reduction of clinical signs and faster virus clearance. Our study shows that an EHV-1-based influenza H1N1 vaccine may be a promising alternative for protection against S-OIV infection.

  7. Sensory subtypes and associated outcomes in children with autism spectrum disorders.

    Ausderau, Karla K; Sideris, John; Little, Lauren M; Furlong, Melissa; Bulluck, John C; Baranek, Grace T


    Sensory features are prevalent and heterogeneous across children with ASD and these features have been associated with child outcomes. Identification of clinically defined sensory subtypes may enhance our understanding of unique phenotypes that have implications for etiology, prognosis, and intervention. This longitudinal study used a national online survey aimed to identify associations of previously validated sensory subtypes to specific child and family characteristics and functional outcomes [vineland adaptive behavior scale-II (VABS) and parenting stress index short form (PSI)]. The sensory experiences questionnaire-3.0 was collected from caregivers with children with ASD, ages 2-12, at two time points (Time 1, n = 1307, Time 2, n = 884), 1 year apart. Functional outcomes assessments were collected at the second time point. A latent profile transition analysis (LPTA) was used to test associations, and results indicated that the attenuated-preoccupied subtype presented with the significantly lowest levels of VABS adaptive behavior composite scores compared to the other three sensory subtypes. Both the VABS maladaptive behavior index and the total PSI score were significantly highest in the extreme-mixed subtype. These results underscore the clinical utility of this subtyping approach for differentiating characteristics and functional outcomes associated with clinically defined sensory phenotypes. These findings may have implications for better understanding etiology, prognosis, and more precise targets for interventions designed to ameliorate sensory difficulties, and ultimately mitigate negative developmental consequences and parenting stress. Autism Res 2016, 9: 1316-1327. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  8. 科学面对甲型H1N1流感



    @@ 一、主题的提出 2009年10月,甲型H1N1流感在全国迅速蔓延,出现了一些死亡案例,每天新闻都播报全国甲型H1N1流感疫情,由于当时还没找到特别有效的防治办法,引起很多人的恐慌.为了帮助师生更好地面对甲型H1N1流感,我们开展了"科学面对甲型H1N1流感"综合实践活动. 二、活动背景 由国家卫生部发布的中国内地甲型H1N1流感疫情形势及活动前对学生的调查发现,部分初中学生缺乏对甲型H1N1流感的科学认识,对甲型H1N1流感普遍持恐慌心理;还有部分初中学生未意识到感染甲型H1N1流感的潜在危险,不知道感染甲型H1N1流感的危险行为.这样,他们就成了感染甲型H1N1流感的脆弱人群和预防甲型H1N1流感健康教育的重点人群,所以有必要对初中学生进行这方面的教育.

  9. 甲型H1N1流感患者的护理%Influenza A H1N1 influenza patient care