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Sample records for factors possess distinct

  1. Plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.

    PubMed

    Al-Khattaf, Fatimah S; Tremp, Annie Z; Dessens, Johannes T

    2015-02-01

    The invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. The pellicle is characterised by a double-layered 'inner membrane complex' (IMC) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (SPN). The SPN consists of intermediate filaments, whose major constituents include a family of proteins called alveolins. Here, we re-appraise the alveolins in the genus Plasmodium with respect to their repertoire, structure and interrelatedness. Amongst 13 family members identified, we distinguish two domain types that, albeit distinct at the primary structure level, are structurally related and contain tandem repeats with a consensus 12-amino acid periodicity. Analysis in Plasmodium berghei of the most divergent alveolin, PbIMC1d, reveals a zoite-specific expression in ookinetes and a subcellular localisation in the pellicle, consistent with its predicted role as a SPN component. Knockout of PbIMC1d gives rise to a wild-type phenotype with respect to ookinete morphogenesis, tensile strength, gliding motility and infectivity, presenting the first example of apparent functional redundancy amongst alveolin family members.

  2. Biologically distinct subtypes of Mycobacterium avium differ in possession of insertion sequence IS901.

    PubMed

    Kunze, Z M; Portaels, F; McFadden, J J

    1992-09-01

    Mycobacterium avium causes disease, principally tuberculosis in immunocompromised individuals. It is the most frequent cause of disseminated infections in AIDS patients in the West. The pathogen is also associated with disease in animals, chiefly birds and livestock, and may be isolated from environmental samples such as soil and water. Analysis of strains of M. avium isolated from clinical, veterinary, and environmental sources for the presence of the mycobacterial insertion sequences IS900 and IS901 demonstrates the specific association of IS901 to animal pathogenic M. avium strains. In contrast, most clinical M. avium strains and all AIDS-derived strains examined so far lacked IS901. Significant differences in the plasmid contents and serotypes of strains with and without IS901 were also found. We therefore suggest that the presence of IS901 divides M. avium into two clearly distinct subtypes with differing host range, virulence, plasmid possession, and serotyping antigens. By using DNA sequence data from IS901 and M. avium DNA, a set of polymerase chain reactions were developed for the specific detection and differentiation of these subtypes.

  3. Duck Hepatitis A virus possesses a distinct type IV internal ribosome entry site element of picornavirus.

    PubMed

    Pan, Meng; Yang, Xiaorong; Zhou, Lei; Ge, Xinna; Guo, Xin; Liu, Jinhua; Zhang, Dabing; Yang, Hanchun

    2012-01-01

    Sequence analysis of duck hepatitis virus type 1 (DHV-1) led to its classification as the only member of a new genus, Avihepatovirus, of the family Picornaviridae, and so was renamed duck hepatitis A virus (DHAV). The 5' untranslated region (5' UTR) plays an important role in translation initiation and RNA synthesis of the picornavirus. Here, we provide evidence that the 651-nucleotide (nt)-long 5' UTR of DHAV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and within BHK cells. Comparative sequence analysis showed that the 3' part of the DHAV 5' UTR is similar to the porcine teschovirus 1 (PTV-1) IRES in sequence and predicted secondary structure. Further mutational analyses of the predicted domain IIId, domain IIIe, and pseudoknot structure at the 3' end of the DHAV IRES support our predicted secondary structure. However, unlike the case for the PTV-1 IRES element, analysis of various deletion mutants demonstrated that the optimally functional DHAV IRES element with a size of approximately 420 nt is larger than that of PTV-1 and contains other peripheral domains (Id and Ie) that do not exist within the type IV IRES elements. The domain Ie, however, could be removed without significant loss of activity. Surprisingly, like the hepatitis A virus (HAV) IRES element, the activity of DHAV IRES could be eliminated by expression of enterovirus 2A protease. These findings indicate that the DHAV IRES shares common features with type IV picornavirus IRES elements, whereas it exhibits significant differences from type IV IRESs. Therefore, we propose that DHAV possesses a distinct type IV IRES element of picornavirus.

  4. Cocoa procyanidins with different degrees of polymerization possess distinct activities in models of colonic inflammation.

    PubMed

    Bitzer, Zachary T; Glisan, Shannon L; Dorenkott, Melanie R; Goodrich, Katheryn M; Ye, Liyun; O'Keefe, Sean F; Lambert, Joshua D; Neilson, Andrew P

    2015-08-01

    Procyanidins are available in the diet from sources such as cocoa and grapes. Procyanidins are unique in that they are comprised of repeating monomeric units and can exist in various degrees of polymerization. The degree of polymerization plays a role in determining the biological activities of procyanidins. However, generalizations cannot be made regarding the correlation between procyanidin structure and bioactivity because the size-activity relationship appears to be system dependent. Our aim was to screen fractions of procyanidins with differing degrees of polymerization in vitro for anti-inflammatory activities in models of colonic inflammation. Monomeric, oligomeric and polymeric cocoa procyanidin fractions were screened using cell models of disrupted membrane integrity and inflammation in human colon cells. High-molecular-weight polymeric procyanidins were the most effective at preserving membrane integrity and reducing secretion of interleukin-8 in response to inflammatory stimuli. Conversely, oligomeric procyanidins appeared to be the least effective. These results suggest that polymeric cocoa procyanidins may be the most effective for preventing loss of gut barrier function and epithelial inflammation, which are critical steps in the pathogenesis of metabolic endotoxemia, inflammatory bowel disease and colon cancer. Therefore, further investigations of the potential health-protective benefits of cocoa procyanidins with distinct degrees of polymerization, particularly high-molecular-weight procyanidins, are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Cocoa Procyanidins with Different Degrees of Polymerization Possess Distinct Activities in Models of Colonic Inflammation

    PubMed Central

    Bitzer, Zachary T.; Glisan, Shannon L.; Dorenkott, Melanie R.; Goodrich, Katheryn M.; Ye, Liyun; O’Keefe, Sean F.; Lambert, Joshua D.; Neilson, Andrew P.

    2015-01-01

    Procyanidins are available in the diet from sources such as cocoa and grapes. Procyanidins are unique in that they are comprised of repeating monomeric units and can exist in various degrees of polymerization. The degree of polymerization plays a role in determining the biological activities of procyanidins. However, generalizations cannot be made regarding the correlation between procyanidin structure and bioactivity, because the size-activity relationship appears to be system-dependent. Our aim was to screen fractions of procyanidins with differing degrees of polymerization in vitro for anti-inflammatory activities in models of colonic inflammation. Monomeric, oligomeric, and polymeric cocoa procyanidin fractions were screened using cell models of disrupted membrane integrity and inflammation in human colon cells. High molecular weight polymeric procyanidins were the most effective at preserving membrane integrity and reducing secretion of interleukin-8 in response to inflammatory stimuli. Conversely, oligomeric procyanidins appeared to be the least effective. These results suggest that polymeric cocoa procyanidins may be the most effective for preventing loss of gut barrier function and epithelial inflammation, which are critical steps in the pathogenesis of metabolic endotoxemia, inflammatory bowel disease, and colon cancer. Therefore, further investigations of the potential health-protective benefits of cocoa procyanidins with distinct degrees of polymerization, particularly high molecular weight procyanidins, are warranted. PMID:25869594

  6. Risk factors for spirit possession among school girls in southern Thailand.

    PubMed

    Trangkasombat, U; Su-Umpan, U; Churujiporn, V; Nukhew, O; Haruhanpong, V

    1998-07-01

    In September 1993, at a school in the south of Thailand, an outbreak of spirit possession suddenly afflicted 32 girls aged 9-14 years. A case-control study was done to investigate factors that predispose a child to spirit possession. Psychiatric evaluation was done on 32 cases and 34 matched controls. Parents were interviewed regarding the child's psychosocial history. Results of the study were as follows. Children with spirit possession were first-born and came from small families with 1-3 children. Compared with the controls their family life was characterized by more psychosocial stressors and there were significantly higher rates of psychiatric disorders, anxious and fearful character traits, histrionic character traits and history of recurrent trance states. The history of traumatic experiences and exposure to spirit possession ceremonies were more frequent in spirit-possessed children than in the control group but the difference was not significant. This study showed that being first-born from a small family, individual vulnerability especially psychiatric disorders, problematic character traits and dissociative tendency were significant risk factors in the development of possession states in children.

  7. Isopycnic separation of Escherichia coli cultures possessing colonization factor antigen I.

    PubMed Central

    Giesa, F R; Zajac, I; Bartus, H F; Actor, P

    1982-01-01

    A culture of Escherichia coli possessing colonization factor antigen I was subjected to isopycnic separation on Percoll gradients. The results demonstrated successful division of the culture into two populations: (i) bacteria which cause mannose-resistant hemagglutination and (ii) bacteria which lack the ability to hemagglutinate in the presence of mannose. PMID:6286714

  8. A teleost complement factor Ba possesses antimicrobial activity and inhibits bacterial infection in fish.

    PubMed

    Li, Xue-Peng; Sun, Li

    2017-01-24

    Complement factor B (Bf) is a component of the complement system. Following activation of the alternative pathway of the complement system, factor B is cleaved into Ba and Bb fragments. In fish, the Bf of rainbow trout is known to act as a C3 convertase, but the function of the Ba fragment is essentially unknown. In this study, we examined the expression patterns of tongue sole Cynoglossus semilaevis Bf (named CsBf) and the biological activity of the Ba fragment of CsBf (named CsBa). CsBf possesses the conserved domains of Bf and shares 39.9%-56.4% sequence identities with other fish Bf. CsBf expression was high in liver, muscle, and heart, and low in intestine, blood, and kidney. Bacterial infection significantly induced CsBf expression in kidney, spleen, and liver in a time-dependent manner. Recombinant CsBa (rCsBa) exhibited apparent binding capacities to bacteria and tongue sole peripheral blood leukocytes, and binding of rCsBa to bacteria inhibited bacterial growth. When overexpressed in tongue sole, CsBa significantly reduced bacterial dissemination in fish tissues. Together these results indicate for the first time that a fish Ba possesses antibacterial effect as well as immune cell-binding capacity, and thus probably plays a role in host immune defense against bacterial infection.

  9. Reconstitution of recombinant human replication factor C (RFC) and identification of an RFC subcomplex possessing DNA-dependent ATPase activity.

    PubMed

    Ellison, V; Stillman, B

    1998-03-06

    Replication factor C (RFC) is a five-subunit protein complex required for coordinate leading and lagging strand DNA synthesis during S phase and DNA repair in eukaryotic cells. It functions to load the proliferating cell nuclear antigen (PCNA), a processivity factor for polymerases delta and epsilon, onto primed DNA templates. This process, which is ATP-dependent, is carried out by 1) recognition of the primer terminus by RFC () binding to and disruption of the PCNA trimer, and then 3) topologically linking the PCNA to the DNA. In this report, we describe the purification and properties of recombinant human RFC expressed in Sf9 cells from baculovirus expression vectors. Like native RFC derived from 293 cells, recombinant RFC was found to support SV40 DNA synthesis and polymerase delta DNA synthesis in vitro and to possess an ATPase activity that was highly stimulated by DNA and further augmented by PCNA. Assembly of RFC was observed to involve distinct subunit interactions in which both the 36- and 38-kDa subunits interacted with the 37-kDa subunit, and the 40-kDa subunit interacted with the 36-kDa subunit-37-kDa subunit subcomplex. The 140-kDa subunit was found to require interactions primarily with the 38- and 40-kDa subunits for incorporation into the complex. In addition, a stable subcomplex lacking the 140-kDa subunit, although defective for DNA replication, was found to possess DNA-dependent ATPase activity that was not responsive to the addition of PCNA.

  10. Does the possession of virulence factor genes mean that those genes will be active?

    PubMed

    Edberg, Stephen C

    2009-01-01

    There are a number of relationships the host can establish with the microbes we ingest. For the vast majority of microbes, they have a short-lived liaison with the human host. Either they are destroyed by the stomach acid or bile, or can not establish even a temporary residency in the gastrointestinal tract. Early in life the mucosal surfaces of the body establishes a resident, and generally stable, normal flora. These normal flora microbes, the majority of which are bacteria, have specific receptors for specific areas of the alimentary tract. If the foreign microbe can establish residency, it then may transiently or permanently become part of the normal flora. However, in order to produce disease, it must possess an additional set of virulence factors. While some of these are known, many are not. Those that are known include enzymes, such as protease, lipase, and esterase. Accordingly, VFAR may not be associated with human disease and its presence or absence has no public health meaning.

  11. Effectiveness of and Factors Related to Possession of a Mother and Child Health Handbook: An Analysis Using Propensity Score Matching

    ERIC Educational Resources Information Center

    Kawakatsu, Yoshito; Sugishita, Tomohiko; Oruenjo, Kennedy; Wakhule, Stephen; Kibosia, Kennedy; Were, Eric; Honda, Sumihisa

    2015-01-01

    Background: Mother and Child Health handbooks (MCH handbooks) serve as useful health education tools for mothers and sources of information that allow health care professionals to understand patient status. Therefore, it is necessary to clarify the effectiveness of and identify the factors related to possession of an MCH handbook among parents in…

  12. Effectiveness of and Factors Related to Possession of a Mother and Child Health Handbook: An Analysis Using Propensity Score Matching

    ERIC Educational Resources Information Center

    Kawakatsu, Yoshito; Sugishita, Tomohiko; Oruenjo, Kennedy; Wakhule, Stephen; Kibosia, Kennedy; Were, Eric; Honda, Sumihisa

    2015-01-01

    Background: Mother and Child Health handbooks (MCH handbooks) serve as useful health education tools for mothers and sources of information that allow health care professionals to understand patient status. Therefore, it is necessary to clarify the effectiveness of and identify the factors related to possession of an MCH handbook among parents in…

  13. An Explanation of the Distinction between Developmental Factors and Mechanisms

    ERIC Educational Resources Information Center

    Laski, Elida V.

    2017-01-01

    This paper provides five clear, relatable examples that can help students understand the distinction between the term "factors" and "mechanisms" in Developmental Psychology. The examples emphasize the idea that factors are related to changes in ways that moderate development, but are not causal. On the other hand, the term…

  14. When Does the Factor-Mixture Distinction Matter?

    ERIC Educational Resources Information Center

    Loken, Eric

    2012-01-01

    Von Davier, Naemi, and Roberts (this issue) present a nice summary of the statistical ambiguity often encountered in making distinctions between qualitative and quantitative constructs. In this commentary, the author begins with two broad points. The first is that the mixture/factor arguments are most intriguing when firmly embedded in a…

  15. Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection.

    PubMed

    Diner, Benjamin A; Lum, Krystal K; Toettcher, Jared E; Cristea, Ileana M

    2016-11-15

    The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses. How mammalian cells detect and respond to DNA viruses that replicate in the nucleus is poorly understood. Here, we decipher the distinct functions of two viral DNA sensors, IFI16 and cGAS, during active immune signaling upon infection with two herpesviruses, herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV). We show that IFI16

  16. Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection

    PubMed Central

    Diner, Benjamin A.; Lum, Krystal K.; Toettcher, Jared E.

    2016-01-01

    ABSTRACT The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses. PMID:27935834

  17. Malaria parasites possess a telomere repeat-binding protein that shares ancestry with transcription factor IIIA.

    PubMed

    Bertschi, Nicole L; Toenhake, Christa G; Zou, Angela; Niederwieser, Igor; Henderson, Rob; Moes, Suzette; Jenoe, Paul; Parkinson, John; Bartfai, Richard; Voss, Till S

    2017-03-13

    Telomere repeat-binding factors (TRFs) are essential components of the molecular machinery that regulates telomere function. TRFs are widely conserved across eukaryotes and bind duplex telomere repeats via a characteristic MYB-type domain. Here, we identified the telomere repeat-binding protein PfTRZ in the malaria parasite Plasmodium falciparum, a member of the Alveolate phylum for which TRFs have not been described so far. PfTRZ lacks an MYB domain and binds telomere repeats via a C2H2-type zinc finger domain instead. In vivo, PfTRZ binds with high specificity to the telomeric tract and to interstitial telomere repeats upstream of subtelomeric virulence genes. Conditional depletion experiments revealed that PfTRZ regulates telomere length homeostasis and is required for efficient cell cycle progression. Intriguingly, we found that PfTRZ also binds to and regulates the expression of 5S rDNA genes. Combined with detailed phylogenetic analyses, our findings identified PfTRZ as a remote functional homologue of the basic transcription factor TFIIIA, which acquired a new function in telomere maintenance early in the apicomplexan lineage. Our work sheds unexpected new light on the evolution of telomere repeat-binding proteins and paves the way for dissecting the presumably divergent mechanisms regulating telomere functionality in one of the most deadly human pathogens.

  18. Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

    SciTech Connect

    Andersen, A.S.; Kjeldsen, T.; Wiberg, F.C.; Christensen, P.M.; Rasmussen, J.S.; Norris, K.; Moeller, K.B.; Moeller, N.P.H. )

    1990-08-14

    To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the {alpha}-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor.

  19. Reward and punishment act as distinct factors in guiding behavior.

    PubMed

    Kubanek, Jan; Snyder, Lawrence H; Abrams, Richard A

    2015-06-01

    Behavior rests on the experience of reinforcement and punishment. It has been unclear whether reinforcement and punishment act as oppositely valenced components of a single behavioral factor, or whether these two kinds of outcomes play fundamentally distinct behavioral roles. To this end, we varied the magnitude of a reward or a penalty experienced following a choice using monetary tokens. The outcome of each trial was independent of the outcome of the previous trial, which enabled us to isolate and study the effect on behavior of each outcome magnitude in single trials. We found that a reward led to a repetition of the previous choice, whereas a penalty led to an avoidance of the previous choice. Surprisingly, the effects of the reward magnitude and the penalty magnitude revealed a pronounced asymmetry. The choice repetition effect of a reward scaled with the magnitude of the reward. In a marked contrast, the avoidance effect of a penalty was flat, not influenced by the magnitude of the penalty. These effects were mechanistically described using a reinforcement learning model after the model was updated to account for the penalty-based asymmetry. The asymmetry in the effects of the reward magnitude and the punishment magnitude was so striking that it is difficult to conceive that one factor is just a weighted or transformed form of the other factor. Instead, the data suggest that rewards and penalties are fundamentally distinct factors in governing behavior.

  20. Reward and punishment act as distinct factors in guiding behavior

    PubMed Central

    Kubanek, Jan; Snyder, Lawrence H; Abrams, Richard A

    2015-01-01

    Behavior rests on the experience of reinforcement and punishment. It has been unclear whether reinforcement and punishment act as oppositely valenced components of a single behavioral factor, or whether these two kinds of outcomes play fundamentally distinct behavioral roles. To this end, we varied the magnitude of a reward or a penalty experienced following a choice using monetary tokens. The outcome of each trial was independent of the outcome of the previous trial, which enabled us to isolate and study the effect on behavior of each outcome magnitude in single trials. As expected, we found that a reward led to a repetition of the previous choice, whereas a penalty led to an avoidance of the previous choice. However, the effects of the reward magnitude and the penalty magnitude revealed a striking asymmetry. The choice repetition effect of a reward strongly scaled with the magnitude of the reward. In a marked contrast, the avoidance effect of a penalty was flat, not influenced by the magnitude of the penalty. These effects were mechanistically described using the Reinforcement Learning model after the model was updated to account for the penalty-based asymmetry. The asymmetry in the effects of the reward magnitude and the punishment magnitude was so striking that it is diffcult to conceive that one factor is just a weighted or transformed form of the other factor. Instead, the data suggest that rewards and penalties are fundamentally distinct factors in governing behavior. PMID:25824862

  1. Effectiveness of and factors related to possession of a mother and child health handbook: an analysis using propensity score matching.

    PubMed

    Kawakatsu, Yoshito; Sugishita, Tomohiko; Oruenjo, Kennedy; Wakhule, Stephen; Kibosia, Kennedy; Were, Eric; Honda, Sumihisa

    2015-12-01

    Mother and Child Health handbooks (MCH handbooks) serve as useful health education tools for mothers and sources of information that allow health care professionals to understand patient status. Therefore, it is necessary to clarify the effectiveness of and identify the factors related to possession of an MCH handbook among parents in rural Western Kenya using propensity score matching (PSM). A community-based cross-sectional survey using a structured questionnaire was conducted in rural western Kenya from August to September, 2011. We targeted 2560 mothers with children aged 12-24 months. Both PSM and multivariate logistic analyses were used in this study. Impacts of 5.9, 9.4, and 12.6 percentage points for higher health knowledge and for proper health-seeking behavior for fever and diarrhea, respectively, were statistically significant. The significant factors affecting possession of the MCH Handbook were the child's sex, the caregiver's relationship to the child, maternal age, health knowledge, birth interval, household wealth index and CHW performance accordingly. An MCH handbook was an effective tool for improving both health knowledge and health-seeking behavior in Kenya. The further distribution and utilization of an MCH handbook is expected to be an effective way to improve both maternal and child health. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. A third distinct tumor necrosis factor receptor of orthopoxviruses

    PubMed Central

    Loparev, Vladimir N.; Parsons, Joseph M.; Knight, Janice C.; Panus, Joanne Fanelli; Ray, Caroline A.; Buller, R. Mark L.; Pickup, David J.; Esposito, Joseph J.

    1998-01-01

    Cowpox virus Brighton red strain (CPV) contains a gene, crmD, which encodes a 320-aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively, to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC. The crmD gene was interrupted in three other cowpox strains examined and absent in various other orthopoxviruses; however, four strains of ectromelia virus (ECT) examined contained an intact crmD (97% identity to CPV crmD) and lacked cognates of crmB and crmC. The protein, CrmD, contains a transport signal; a 151-aa cysteine-rich region with 21 cysteines that align with human TNFRII ligand-binding region cysteines; and C-terminal region sequences that are highly diverged from cellular TNFR C-terminal region sequences involved in signal transduction. Bacterial maltose-binding proteins containing the CPV or ECT CrmD cysteine-rich region bound TNF and lymphotoxin-α (LTα) and blocked their in vitro cytolytic activity. Secreted viral CrmD bound TNF and LTα and was detectable after the early stage of replication, using nonreducing conditions, as 60- to 70-kDa predominant and 90- to 250-kDa minor disulfide-linked complexes that were able to be reduced to a 46-kDa form and deglycosylated to a 38-kDa protein. Cells infected with CPV produced extremely low amounts of CrmD compared with ECT. Possessing up to three TNFRs, including CrmD, which is secreted as disulfide-linked complexes in varied amounts by CPV and ECT, likely enhances the dynamics of the immune modulating mechanisms of orthopoxviruses. PMID:9520445

  3. Subsurface fluids from basement basalt of the Juan de Fuca Ridge possess microbial communities that are distinct from overlying sediments and surrounding seawater

    NASA Astrophysics Data System (ADS)

    Jungbluth, S.; Bowers, R. M.; Lin, H.; Hsieh, C.; Cowen, J. P.; Rappe, M. S.

    2013-12-01

    Hydrothermal circulation of fluids through the porous and permeable ocean basement fuels a deep subsurface microbial community that remains poorly characterized due to the logistical and methodological constraints associated with sampling the sediment-covered seafloor. Ocean Drilling Program and Integrated Ocean Drilling Program holes penetrating 1.2-3.5 million-years old sediment-covered basaltic crust of the Juan de Fuca Ridge flank fitted with Circulation Obviation Retrofit Kit (CORK) borehole observatories have enabled sampling of chemically-reducing basement fluids over the course of multiple years (2008-2013). Consistent and reliable access to pristine fluids from the ocean crust is due to improvements to CORK observatories, through incorporation of microbiologically-friendly materials, and fluid sampling techniques and equipment. By analyzing ~1.7 million reads of the small subunit ribosomal RNA (SSU rRNA) gene by next-generation Illumina sequencing from marine sediment, deep seawater, and 24 crustal fluid samples spanning multiple years and boreholes (1025C, U1301A, U1362A, and U1362), a distinct subseafloor biosphere dominated by the domain Bacteria was uncovered. Fluids from borehole U1301A sampled annually over the course of three years each had distinct microbial community structure and were dominated by the Proteobacteria. In contrast, fluids from boreholes 1362A and 1362B, located ~500 meters to the northeast, contained lineages phylogenetically related to the phylum Nitrospirae in highest abundance. The domain Archaea was was dominated by either the phylum Crenarchaeota (borehole U1301A) or the Euryarchaeota (boreholes 1025C, U1362A and U1362B). SSU rRNA genes phylogenetically affiliated with known lineages of methane producing Euryarchaeota (e.g. Methanobacteria) were the most abundant archaeal group detected in fluids from Holes U1362A and U1362B, predominantly within samples originating from the deepest subsurface sampling horizon (~200 meters sub

  4. Sudden infant death syndrome: risk factor profiles for distinct subgroups.

    PubMed

    Kohlendorfer, U; Kiechl, S; Sperl, W

    1998-05-15

    The authors investigated risk profiles of sudden infant death syndrome (SIDS) as a function of age at death. A case-control study carried out in the Tyrol region of Austria enrolled 99 infants who died of SIDS between 1984 and 1994 and 136 randomly selected controls. Early and late SIDS (< 120 days of age vs. > or = 120 days) were defined according to the clear-cut bimodal age-at-death distribution. Inadequate antenatal care, low parental social and educational level, and the prone sleeping position were risk conditions that applied to both early and late SIDS. A marked seasonal variation (winter preponderance) was the most outstanding feature of late SIDS. A gestational age of < 37 weeks (odds ratio (OR) = 8.4, 95% confidence interval (CI) 2.6-26.0), repeated episodes of apnea (OR = 5.7, 95% CI 1.2-27.0), low birth weight (< 2,500 g) (OR = 3.4, 95% CI 1.1-11.0), a family history of sudden infant death (OR = 2.9, 95% CI 1.1-7.5), and maternal smoking during pregnancy (OR = 2.2, 95% CI 1.0-4.5) were associated with early SIDS. This study identified two distinct subgroups of SIDS infants characterized by different risk conditions and ages at death. These results underline a multiple-cause hypothesis for SIDS etiology which involves a genetic predisposition, immaturity in the first months of life, and environmental factors acting at various ages.

  5. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    SciTech Connect

    Migliaccio, Christopher T. . E-mail: christopher.migliaccio@umontana.edu; Hamilton, Raymond F.; Holian, Andrij

    2005-06-01

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO{sub 2}). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis.

  6. [Prevalence of weapons possession and associated factors and involvement in physical aggression among adolescents 15 to 18 years of age: a population-based study].

    PubMed

    Silva, Ricardo Azevedo da; Jansen, Karen; Godoy, Russélia Vanila; Souza, Luciano Dias Mattos; Horta, Bernardo Lessa; Pinheiro, Ricardo Tavares

    2009-12-01

    This cross-sectional, population-based study aimed to evaluate the prevalence of weapons possession and associated factors and involvement in physical aggression among adolescents 15 to 18 years of age (n = 960) in the city of Pelotas, Rio Grande do Sul State, Brazil. Ninety of the city's 448 census tracts were selected, and 86 houses in each tract were visited. The statistical analysis used Poisson regression. Prevalence rates in the sample were 22.8% for involvement in fights with physical aggression and 9.6% for weapons possession in the previous 12 months. The study concluded that young males that use alcohol and/or illegal drugs and present minor psychiatric disorders show a higher probability of weapons possession and involvement in physical fights.

  7. Human leukocyte inhibitory factor (LIF): two distinct molecular species.

    PubMed

    Brown, A P; Rocklin, R E

    1979-03-01

    Human leukocyte inhibitory factor or LIF was generated in vitro by stimulating blood lymphocytes with concanavalin A (Con A). The control and Con A active supernatants were partially purified by gel filtration on Sephadex G-100. The fraction containing LIF (68,000 daltons) activity was then subjected to isoelectric focusing (pH 3 to 10 ampholines) in a sucrose gradient. Two LIF activities were reproducibly recovered by this procedure. One molecular form was found to have an isoelectric point of approximately pH 5.0 and the other approximately pH 8.5. Both molecular species were rechromatographed on Sephadex G-75 and found to have the same apparent m.w. (68 to 75,000). Furthermore, the biologic activity of both factors was destroyed after treatment with diisopropylphosphofluoridate, suggesting that they may be esterases.

  8. Arabidopsis thaliana GPAT8 and GPAT9 are localized to the ER and possess distinct ER retrieval signals: functional divergence of the dilysine ER retrieval motif in plant cells.

    PubMed

    Gidda, Satinder K; Shockey, Jay M; Rothstein, Steven J; Dyer, John M; Mullen, Robert T

    2009-10-01

    Glycerol-3-phosphate acyltransferase (GPAT; EC 2.3.1.15) catalyzes the committed step in the production of glycerolipids, which are major components of cellular membranes, seed storage oils, and epicuticular wax coatings. While the biochemical activities of GPATs have been characterized in detail, the cellular features of these enzymes are only beginning to emerge. Here we characterized the phylogenetic relationships and cellular properties of two GPAT enzymes from the relatively large Arabidopsis thaliana GPAT family, including GPAT8, which is involved in cutin biosynthesis, and GPAT9, which is a new putative GPAT that has extensive homology with a GPAT from mammalian cells involved in storage oil formation and, thus, may have a similar role in plants. Immunofluorescence microscopy of transiently-expressed myc-epitope-tagged GPAT8 and GPAT9 revealed that both proteins were localized to the endoplasmic reticulum (ER), and differential permeabilization experiments indicated that their N- and C-termini were oriented towards the cytosol. However, these two proteins contained distinct types of ER retrieval signals, with GPAT8 possessing a divergent type of dilysine motif (-KK-COOH rather than the prototypic -KKXX-COOH or -KXKXX-COOH motif) and GPAT9 possessing a hydrophobic pentapeptide motif (-phi-X-X-K/R/D/E-phi-; where phi are large hydrophobic amino acid residues). Notably, the divergent dilysine motif in GPAT8 only functioned effectively when additional upstream residues were included to provide the proper protein context. Extensive mutational analyses of the divergent dilysine motif, based upon sequences present in the C-termini of other GPAT8s from various plant species, further expanded the functional definition of this molecular targeting signal, thereby providing insight to the targeting signals in other GPAT family members as well as other ER-resident membrane proteins within plant cells.

  9. PC12 cell mutants that possess low- but not high-affinity nerve growth factor receptors neither respond to nor internalize nerve growth factor

    PubMed Central

    1986-01-01

    Four mutant PC12 pheochromocytoma cell lines that are nerve growth factor (NGF)-nonresponsive (PC12nnr) have been selected from chemically mutagenized cultures by a double selection procedure: failure both to grow neurites in the presence of NGF and to survive in NGF-supplemented serum-free medium. The PC12nnr cells were deficient in all additional NGF responses surveyed: abatement of cell proliferation, changes in glycoprotein composition, induction of ornithine decarboxylase, rapid changes in protein phosphorylation, and cell surface ruffling. However, PC12nnr cells closely resembled non-NGF-treated PC12 cells in most properties tested: cell size and shape; division rate; protein, phosphoprotein, and glycoprotein composition; and cell surface morphology. All four PC12nnr lines differed from PC12 cells in three ways in addition to failure of NGF response: PC12nnr cells failed to internalize bound NGF by the normal, saturable, high-affinity mechanism present in PC12 cells. The PC12nnr cells bound NGF but entirely, or nearly entirely, at low-affinity sites only, whereas PC12 cells possess both high- and low-affinity NGF binding sites. The responses to dibutyryl cyclic AMP that were tested appeared to be enhanced or altered in the PC12nnr cells compared to PC12 cells. Internalization of, and responses to, epidermal growth factor were normal in the PC12nnr cells ruling out a generalized defect in hormonal binding, uptake, or response mechanisms. These findings are consistent with a causal association between the presence of high-affinity NGF receptors and of NGF responsiveness and internalization. A possible relationship is also suggested between regulation of cAMP responses and regulation of NGF responses or NGF receptor affinity. PMID:3005338

  10. Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults

    PubMed Central

    Neuhaus, John M.; Chiong, Winston

    2016-01-01

    Abstract Background: Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. Methods: The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). Results: In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p < 0.001) and Hispanic older Americans (29.0%, p = 0.006). Gender, age, retired or disabled employment status, educational attainment, religious affiliation, Internet access, preferences for physician-centered decision making, and desiring longevity regardless of functional status were independent predictors of advance directive possession. In fully adjusted multivariable models with all predictors included, black older Americans remained significantly less likely than white older Americans to have an advance directive (odds ratio [OR] = 0.42, 95% confidence interval [CI] = 0.24–0.75), whereas the effect of Hispanic ethnicity was no longer statistically significant (OR = 0.65, 95% CI = 0.39–1.1). Conclusion: In a nationally representative sample, black race is an independent predictor for advance directive possession. This association remains even after adjustment for other demographic variables, religious characteristics, and personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning. PMID:26840850

  11. Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults.

    PubMed

    Huang, Ivy A; Neuhaus, John M; Chiong, Winston

    2016-02-01

    Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p < 0.001) and Hispanic older Americans (29.0%, p = 0.006). Gender, age, retired or disabled employment status, educational attainment, religious affiliation, Internet access, preferences for physician-centered decision making, and desiring longevity regardless of functional status were independent predictors of advance directive possession. In fully adjusted multivariable models with all predictors included, black older Americans remained significantly less likely than white older Americans to have an advance directive (odds ratio [OR] = 0.42, 95% confidence interval [CI] = 0.24-0.75), whereas the effect of Hispanic ethnicity was no longer statistically significant (OR = 0.65, 95% CI = 0.39-1.1). In a nationally representative sample, black race is an independent predictor for advance directive possession. This association remains even after adjustment for other demographic variables, religious characteristics, and personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning.

  12. Plant Actin-Depolymerizing Factors Possess Opposing Biochemical Properties Arising from Key Amino Acid Changes throughout Evolution.

    PubMed

    Nan, Qiong; Qian, Dong; Niu, Yue; He, Yongxing; Tong, Shaofei; Niu, Zhimin; Ma, Jianchao; Yang, Yang; An, Lizhe; Wan, Dongshi; Xiang, Yun

    2017-02-01

    Functional divergence in paralogs is an important genetic source of evolutionary innovation. Actin-depolymerizing factors (ADFs) are among the most important actin binding proteins and are involved in generating and remodeling actin cytoskeletal architecture via their conserved F-actin severing or depolymerizing activity. In plants, ADFs coevolved with actin, but their biochemical properties are diverse. Unfortunately, the biochemical function of most plant ADFs and the potential mechanisms of their functional divergence remain unclear. Here, in vitro biochemical analyses demonstrated that all 11 ADF genes in Arabidopsis thaliana exhibit opposing biochemical properties. Subclass III ADFs evolved F-actin bundling (B-type) function from conserved F-actin depolymerizing (D-type) function, and subclass I ADFs have enhanced D-type function. By tracking historical mutation sites on ancestral proteins, several fundamental amino acid residues affecting the biochemical functions of these proteins were identified in Arabidopsis and various plants, suggesting that the biochemical divergence of ADFs has been conserved during the evolution of angiosperm plants. Importantly, N-terminal extensions on subclass III ADFs that arose from intron-sliding events are indispensable for the alteration of D-type to B-type function. We conclude that the evolution of these N-terminal extensions and several conserved mutations produced the diverse biochemical functions of plant ADFs from a putative ancestor.

  13. Gallibacterium elongation factor-Tu possesses amyloid-like protein characteristics, participates in cell adhesion, and is present in biofilms.

    PubMed

    López-Ochoa, Jaqueline; Montes-García, J Fernando; Vázquez, Candelario; Sánchez-Alonso, Patricia; Pérez-Márquez, Victor M; Blackall, Patrick J; Vaca, Sergio; Negrete-Abascal, Erasmo

    2017-09-01

    Gallibacterium, which is a bacterial pathogen in chickens, can form biofilms. Amyloid proteins present in biofilms bind Congo red dye. The aim of this study was to characterize the cell-surface amyloid-like protein expressed in biofilms formed by Gallibacterium strains and determine the relationship between this protein and curli, which is an amyloid protein that is commonly expressed by members of the Enterobacteriaceae family. The presence of amyloid-like proteins in outer membrane protein samples from three strains of G. anatis and one strain of Gallibacterium genomospecies 2 was evaluated. A protein identified as elongation factor-Tu (EF-Tu) by mass spectrometric analysis and in silico analysis was obtained from the G. anatis strain F149(T). This protein bound Congo red dye, cross-reacted with anti-curli polyclonal serum, exhibited polymerizing properties and was present in biofilms. This protein also reacted with pooled serum from chickens that were experimentally infected with G. anatis, indicating the in vivo immunogenicity of this protein. The recombinant EF-Tu purified protein, which was prepared from G. anatis 12656-12, polymerizes under in vitro conditions, forms filaments and interacts with fibronectin and fibrinogen, all of which suggest that this protein functions as an adhesin. In summary, EF-Tu from G. anatis presents amyloid characteristics, is present in biofilms and could be relevant for the pathogenesis of G. anatis.

  14. Plant Actin-Depolymerizing Factors Possess Opposing Biochemical Properties Arising from Key Amino Acid Changes throughout Evolution[OPEN

    PubMed Central

    Nan, Qiong; Niu, Yue; He, Yongxing; Tong, Shaofei; Niu, Zhimin; Ma, Jianchao; Yang, Yang; An, Lizhe; Wan, Dongshi

    2017-01-01

    Functional divergence in paralogs is an important genetic source of evolutionary innovation. Actin-depolymerizing factors (ADFs) are among the most important actin binding proteins and are involved in generating and remodeling actin cytoskeletal architecture via their conserved F-actin severing or depolymerizing activity. In plants, ADFs coevolved with actin, but their biochemical properties are diverse. Unfortunately, the biochemical function of most plant ADFs and the potential mechanisms of their functional divergence remain unclear. Here, in vitro biochemical analyses demonstrated that all 11 ADF genes in Arabidopsis thaliana exhibit opposing biochemical properties. Subclass III ADFs evolved F-actin bundling (B-type) function from conserved F-actin depolymerizing (D-type) function, and subclass I ADFs have enhanced D-type function. By tracking historical mutation sites on ancestral proteins, several fundamental amino acid residues affecting the biochemical functions of these proteins were identified in Arabidopsis and various plants, suggesting that the biochemical divergence of ADFs has been conserved during the evolution of angiosperm plants. Importantly, N-terminal extensions on subclass III ADFs that arose from intron-sliding events are indispensable for the alteration of D-type to B-type function. We conclude that the evolution of these N-terminal extensions and several conserved mutations produced the diverse biochemical functions of plant ADFs from a putative ancestor. PMID:28123105

  15. Prostaglandin E₂ possesses different potencies in inducing Vascular Endothelial Growth Factor and Interleukin-8 production in COPD human lung fibroblasts.

    PubMed

    Bonanno, Anna; Albano, Giusy Daniela; Siena, Liboria; Montalbano, Angela Marina; Riccobono, Loredana; Anzalone, Giulia; Chiappara, Giuseppina; Gagliardo, Rosalia; Profita, Mirella; Sala, Angelo

    2016-03-01

    We studied the role of PGE2, its biosynthetic enzymes and its receptors, in regulating the functions of lung fibroblasts through the production of Vascular Endothelial Growth Factor (VEGF) and Interleukin-8 (IL-8) in COPD subjects. Lung fibroblasts from Control (C) (n=6), Smoker (HS) (n=6) and COPD patients (n=8) were cultured, and basal PGE2, VEGF, and IL-8 measured in supernatants by ELISA. COX-1/COX-2 and EP receptors expression were assessed by western blot and by RT-PCR. Release of VEGF and IL-8 by human fetal lung fibroblasts (HFL-1; lung, diploid, human) was evaluated under different conditions. PGE2, VEGF, and IL-8 levels, COX-2, EP2, and EP4 protein expression and mRNA were increased in COPD when compared to Controls. Low concentrations of synthetic PGE2 increased the release of VEGF in HFL-1, but higher concentrations were needed to induce the release of IL-8. This effect was mimicked by an EP2 agonist and modulated by an EP4 antagonist. In the airways of COPD subjects, fibroblast-derived PGE2 may regulate angiogenesis and inflammation through the production of VEGF and IL-8 respectively, suggesting that the increase in expression of COX-2, EP2 and EP4 observed in COPD fibroblasts may contribute to steering the role of PGE2 from homeostatic to pro-inflammatory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Identification of an anti-lipopolysacchride factor possessing both antiviral and antibacterial activity from the red claw crayfish Cherax quadricarinatus.

    PubMed

    Lin, Feng-Yu; Gao, Yan; Wang, Hao; Zhang, Qiu-Xia; Zeng, Chang-Lin; Liu, Hai-Peng

    2016-10-01

    It is well-known that anti-lipopolysacchride factors (ALFs) are involved in the recognition and elimination of invading pathogens. In this study, the full-length ALF cDNA sequence of the red claw crayfish Cherax quadricarinatus (termed CqALF) was cloned from a suppression subtractive hybridization library constructed using red claw crayfish hematopoietic tissue cell (Hpt cell) cultures following challenge with white spot syndrome virus (WSSV). The full-length cDNA sequence of CqALF was 863 bp, and the open reading frame encoded 123 amino acids with a signal peptide in the N-terminus and a conserved LPS-binding domain. Unlike most ALFs, which are highly expressed in haemocytes, high expression levels of CqALF were detected in epithelium, the stomach and eyestalks, while lower expression was detected in Hpt, nerves, the heart, muscle tissue, gonads, haemocytes, intestines, gills and the hepatopancreas. To further explore the biological activities of CqALF, mature recombinant CqALF protein (rCqALF) was expressed and purified using a eukaryotic expression system, and an antimicrobial activity test was carried out. rCqALF clearly exerted antiviral activity, as evidenced by the severe disruption of the envelope of intact WSSV virions following co-incubation of virions with rCqALF. Additionally, pre-incubation of WSSV with rCqALF resulted in both a significant reduction in WSSV replication in red claw crayfish Hpt cell cultures and an increased survival rate among animals. Furthermore, rCqALF was effective against both Gram-negative bacteria and Gram-positive bacteria, particularly Shigella flexneri and Staphylococcus aureus. A membrane integrity assay suggested that rCqALF was unlikely to disrupt bacterial membrane integrity compared to cecropin P1. Taken together, these data suggest that CqALF may play an important role in immune defence in the crustacean C. quadricarinatus.

  17. Strategies of Clausal Possession

    ERIC Educational Resources Information Center

    Langacker, Ronald W.

    2003-01-01

    Across languages, clauses expressing possession, location, and existence exhibit many similarities. To capture their evident affinity, it is often claimed that possessives derive--synclironically or diaclironically--from expressions of location/existence. This localist account obscures a basic contrast between two broad classes of possessive…

  18. Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription factor CIB1 by distinct mechanisms.

    PubMed

    Liu, Hongtao; Wang, Qin; Liu, Yawen; Zhao, Xiaoying; Imaizumi, Takato; Somers, David E; Tobin, Elaine M; Lin, Chentao

    2013-10-22

    Plants possess multiple photoreceptors to mediate light regulation of growth and development, but it is not well understood how different photoreceptors coordinate their actions to jointly regulate developmental responses, such as flowering time. In Arabidopsis, the photoexcited cryptochrome 2 interacts with the transcription factor CRYPTOCHROME-INTERACTING basic helix-loop-helix 1 (CIB1) to activate transcription and floral initiation. We show that the CIB1 protein expression is regulated by blue light; CIB1 is highly expressed in plants exposed to blue light, but levels of the CIB1 protein decreases in the absence of blue light. We demonstrate that CIB1 is degraded by the 26S proteasome and that blue light suppresses CIB1 degradation. Surprisingly, although cryptochrome 2 physically interacts with CIB1 in response to blue light, it is not the photoreceptor mediating blue-light suppression of CIB1 degradation. Instead, two of the three light-oxygen-voltage (LOV)-domain photoreceptors, ZEITLUPE and LOV KELCH PROTEIN 2, but not FLAVIN-BINDING KELCH REPEAT 1, are required for the function and blue-light suppression of degradation of CIB1. These results support the hypothesis that the evolutionarily unrelated blue-light receptors, cryptochrome and LOV-domain F-box proteins, mediate blue-light regulation of the same transcription factor by distinct mechanisms.

  19. Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription factor CIB1 by distinct mechanisms

    PubMed Central

    Liu, Hongtao; Wang, Qin; Liu, Yawen; Zhao, Xiaoying; Imaizumi, Takato; Somers, David E.; Tobin, Elaine M.; Lin, Chentao

    2013-01-01

    Plants possess multiple photoreceptors to mediate light regulation of growth and development, but it is not well understood how different photoreceptors coordinate their actions to jointly regulate developmental responses, such as flowering time. In Arabidopsis, the photoexcited cryptochrome 2 interacts with the transcription factor CRYPTOCHROME-INTERACTING basic helix–loop–helix 1 (CIB1) to activate transcription and floral initiation. We show that the CIB1 protein expression is regulated by blue light; CIB1 is highly expressed in plants exposed to blue light, but levels of the CIB1 protein decreases in the absence of blue light. We demonstrate that CIB1 is degraded by the 26S proteasome and that blue light suppresses CIB1 degradation. Surprisingly, although cryptochrome 2 physically interacts with CIB1 in response to blue light, it is not the photoreceptor mediating blue-light suppression of CIB1 degradation. Instead, two of the three light–oxygen–voltage (LOV)-domain photoreceptors, ZEITLUPE and LOV KELCH PROTEIN 2, but not FLAVIN-BINDING KELCH REPEAT 1, are required for the function and blue-light suppression of degradation of CIB1. These results support the hypothesis that the evolutionarily unrelated blue-light receptors, cryptochrome and LOV-domain F-box proteins, mediate blue-light regulation of the same transcription factor by distinct mechanisms. PMID:24101505

  20. The tissue factor pathway inhibitor 1 of Sciaenops ocellatus possesses antimicrobial activity and is involved in the immune response against bacterial infection.

    PubMed

    Zhang, Min; Sun, Li

    2011-03-01

    Tissue factor pathway inhibitor 1 (TFPI-1) is a Kunitz-type serine protease inhibitor that regulates the activation of tissue factor-induced coagulation. In teleosts, TFPI-1-like sequences have been found to exist in two species (Danio rerio and Cyprinus carpio); however, the potential function of fish TFPI-1 has not been investigated. In this study, we identified and analyzed a TFPI-1 homologue, SoTFPI-1, from red drum (Sciaenops ocellatus). The deduced amino acid sequence of SoTFPI-1 is 284 residues in length and contains three Kunitz domains, an acidic N-terminus, and a basic C-terminus. SoTFPI-1 shares 49.5% and 46.9% overall sequence identities with the TFPI-1 of D. rerio and C. carpio, respectively. Quantitative real time RT-PCR analysis showed that constitutive SoTFPI-1 expression occurred, in increasing order, in kidney, brain, liver, gill, blood, spleen, muscle, and heart. Bacterial infection and lipopolysaccharide exposure upregulated SoTFPI-1 expression in kidney in time-dependent manners. Recombinant SoTFPI-1 (rSoTFPI-1) purified from Escherichia coli exhibits not only serine protease inhibitor activity but also bactericidal activity in a manner that is independent of any host factors. A synthetic peptide, TO17, corresponding to the C-terminal basic region of SoTFPI-1 also possesses antibacterial effect that is more potent than that of the full-length rSoTFPI-1. Taken together, these results demonstrate that (i) SoTFPI-1 is a biologically active serine protease inhibitor endowed with bactericidal property; (ii) provide the first indication that teleost TFPI-1 is likely to be involved in anti-microbial infection and thus is linked to innate immune defense.

  1. Nominalization of Possessive Sentences

    ERIC Educational Resources Information Center

    Rugaleva, Anelja

    1977-01-01

    Nominalization of possessive sentences in Russian is discussed. It is maintained that all lexical surface items originate as terms in a situation model, and that their actualization as different parts of speech is language-specific. Language data are used to support a locative interpretation of the semantic model. (CHK)

  2. Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA Synthesis and Possesses Nucleoprotein Chaperone Activity.

    PubMed

    Minakuchi, M; Sugiyama, K; Kato, Y; Naito, T; Okuwaki, M; Kawaguchi, A; Nagata, K

    2017-02-01

    The genome of influenza virus (viral RNA [vRNA]) is associated with the nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical viral ribonucleoprotein (vRNP) complexes. The NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using a Saccharomyces cerevisiae replicon system and a single-gene deletion library of Saccharomyces cerevisiae (T. Naito, Y. Kiyasu, K. Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata, Proc Natl Acad Sci USA, 104:18235-18240, 2007, https://doi.org/10.1073/pnas.0705856104). In infected Prp18 knockdown (KD) cells, the synthesis of vRNA, cRNA, and viral mRNAs was reduced. Prp18 was found to stimulate in vitro viral RNA synthesis through its interaction with NP. Analyses using in vitro RNA synthesis reactions revealed that Prp18 dissociates newly synthesized RNA from the template after the early elongation step to stimulate the elongation reaction. We found that Prp18 functions as a chaperone for NP to facilitate the formation of NP-RNA complexes. Based on these results, it is suggested that Prp18 accelerates influenza virus RNA synthesis as an NP chaperone for the processive elongation reaction.

  3. Qualitatively distinct factors contribute to elevated rates of paranoia in autism and schizophrenia.

    PubMed

    Pinkham, Amy E; Sasson, Noah J; Beaton, Derek; Abdi, Hervé; Kohler, Christian G; Penn, David L

    2012-08-01

    A converging body of clinical and empirical reports indicates that autism features elevated rates of paranoia comparable to those of individuals with paranoid schizophrenia. However, the distinct developmental courses and symptom manifestations of these two disorders suggest that the nature of paranoid ideation may differ between them in important and meaningful ways. To evaluate this hypothesis, we compared patterns of responses on the Paranoia Scale between actively paranoid individuals with schizophrenia (SCZP), individuals with schizophrenia who were not actively paranoid (SCZNP), adults with an Autism Spectrum Disorder (ASD), and healthy controls. Despite an overall similar level of heightened paranoia in the ASD and SCZP groups, discriminant correspondence analysis (DiCA) revealed that these groups were characterized by unique underlying factors. Paranoia in the SCZP group was defined by a factor based upon victimization, suspicion, and threat of harm. Whereas paranoia in the ASD group was partially characterized by this factor, it was distinguished from SCZP by an additional pattern of responses reflective of increased social cynicism. These findings indicate that paranoia in ASD is supported by qualitative factors distinct from schizophrenia and highlight mechanistic differences in the formation of paranoid ideation that may inform the development of disorder-specific treatments.

  4. Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes.

    PubMed

    Morena, Deborah; Maestro, Nicola; Bersani, Francesca; Forni, Paolo Emanuele; Lingua, Marcello Francesco; Foglizzo, Valentina; Šćepanović, Petar; Miretti, Silvia; Morotti, Alessandro; Shern, Jack F; Khan, Javed; Ala, Ugo; Provero, Paolo; Sala, Valentina; Crepaldi, Tiziana; Gasparini, Patrizia; Casanova, Michela; Ferrari, Andrea; Sozzi, Gabriella; Chiarle, Roberto; Ponzetto, Carola; Taulli, Riccardo

    2016-03-17

    Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity.

  5. Schizophrenia or possession?

    PubMed

    Irmak, M Kemal

    2014-06-01

    Schizophrenia is typically a life-long condition characterized by acute symptom exacerbations and widely varying degrees of functional disability. Some of its symptoms, such as delusions and hallucinations, produce great subjective psychological pain. The most common delusion types are as follows: "My feelings and movements are controlled by others in a certain way" and "They put thoughts in my head that are not mine." Hallucinatory experiences are generally voices talking to the patient or among themselves. Hallucinations are a cardinal positive symptom of schizophrenia which deserves careful study in the hope it will give information about the pathophysiology of the disorder. We thought that many so-called hallucinations in schizophrenia are really illusions related to a real environmental stimulus. One approach to this hallucination problem is to consider the possibility of a demonic world. Demons are unseen creatures that are believed to exist in all major religions and have the power to possess humans and control their body. Demonic possession can manifest with a range of bizarre behaviors which could be interpreted as a number of different psychotic disorders with delusions and hallucinations. The hallucination in schizophrenia may therefore be an illusion-a false interpretation of a real sensory image formed by demons. A local faith healer in our region helps the patients with schizophrenia. His method of treatment seems to be successful because his patients become symptom free after 3 months. Therefore, it would be useful for medical professions to work together with faith healers to define better treatment pathways for schizophrenia.

  6. A minimum of two distinct heritable factors are required to explain correlation structures in proliferating lymphocytes

    PubMed Central

    Markham, John F.; Wellard, Cameron J.; Hawkins, Edwin D.; Duffy, Ken R.; Hodgkin, Philip D.

    2010-01-01

    During the adaptive immune response, lymphocyte populations undergo a characteristic three-phase process: expansion through a series of cell divisions; cessation of expansion; and, finally, most of the accumulated lymphocytes die by apoptosis. The data used, thus far, to inform understanding of these processes, both in vitro and in vivo, are taken from flow cytometry experiments. One significant drawback of flow cytometry is that individual cells cannot be tracked, so that it is not possible to investigate interdependencies in the fate of cells within a family tree. This deficit in experimental information has recently been overcome by Hawkins et al. (Hawkins et al. 2009 Proc. Natl Acad. Sci. USA 106, 13 457–13 462 (doi:10.1073/pnas.0905629106)), who reported on time-lapse microscopy experiments in which B-cells were stimulated through the TLR-9 receptor. Cells stimulated in this way do not aggregate, so that data regarding family trees can be recorded. In this article, we further investigate the Hawkins et al. data. Our conclusions are striking: in order to explain the familial correlation structure in division times, death times and propensity to divide, a minimum of two distinct heritable factors are necessary. As the data show that two distinct factors are necessary, we develop a stochastic model that has two heritable factors and demonstrate that it can reproduce the key features of the data. This model shows that two heritable factors are sufficient. These deductions have a clear impact upon biological understanding of the adaptive immune response. They also necessitate changes to the fundamental premises behind the tools developed by statisticians to draw deductions from flow cytometry data. Finally, they affect the mathematical modelling paradigms that are used to study these systems, as these are widely developed based on assumptions of cellular independence that are not accurate. PMID:20053654

  7. Distinctive diet-tissue isotopic discrimination factors derived from the exclusive bamboo-eating giant panda.

    PubMed

    Han, Han; Wei, Wei; Nie, Yonggang; Zhou, Wenliang; Hu, Yibo; Wu, Qi; Wei, Fuwen

    2016-11-01

    Stable isotope analysis is very useful in animal ecology, especially in diet reconstruction and trophic studies. Differences in isotope ratios between consumers and their diet, termed discrimination factors, are essential for studies of stable isotope ecology and are species-specific and tissue-specific. Given the specialized bamboo diet and clear foraging behavior, here, we calculated discrimination factors for carbon and nitrogen isotopes from diet to tissues (tooth enamel, hair keratin and bone collagen) for the giant panda (Ailuropoda melanoleuca), a species derived from meat-eating ancestors. Our results showed that carbon discrimination factor obtained from giant panda tooth enamel (ε (13) Cdiet-enamel = 10.0‰) and nitrogen discrimination factors from hair keratin (Δ(15) Ndiet-hair = 2.2‰) and bone collagen (Δ(15) Ndiet-collagen = 2.3‰) were lower, and carbon discrimination factors from hair keratin (Δ(13) Cdiet-hair = 5.0‰) and bone collagen (Δ(13) Cdiet-collagen = 6.1‰) were higher than those of other mammalian carnivores, omnivores and herbivores. Such distinctive values are likely the result of a low-nutrient and specialized bamboo diet, carnivore-like digestive system and exceptionally low metabolism in giant pandas.

  8. Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells.

    PubMed

    Ghosh, S; Strum, J C; Sciorra, V A; Daniel, L; Bell, R M

    1996-04-05

    Previous studies demonstrated that the cysteine-rich amino-terminal domain of Raf-1 kinase interacts selectively with phosphatidylserine (Ghosh, S., Xie, W. Q., Quest, A. F. G., Mabrouk, G. M., Strum, J. C., and Bell, R. M. (1994) J. Biol. Chem. 269, 10000-10007). Further analysis showed that full-length Raf-1 bound to both phosphatidylserine and phosphatidic acid (PA). Specifically, a carboxyl-terminal domain of Raf-1 kinase (RafC; residues 295 648 of human Raf-1) interacted strongly with phosphatidic acid. The binding of RafC to PA displayed positive cooperativity with Hill numbers between 3.3 and 6.2; the apparent Kd ranged from 4.9 +/- 0.6 to 7.8 +/- 0.9 mol % PA. The interaction of RafC with PA displayed a pH dependence distinct from the interaction between the cysteine-rich domain of Raf-1 and PA. Also, the RafC-PA interaction was unaffected at high ionic strength. Of all the lipids tested, only PA and cardiolipin exhibited high affinity binding; other acidic lipids were either ineffective or weakly effective. By deletion mutagenesis, the PA binding site within RafC was narrowed down to a 35-amino acid segment between residues 389 and 423. RafC did not bind phosphatidyl alcohols; also, inhibition of PA formation in Madin-Darby canine kidney cells by treatment with 1% ethanol significantly reduced the translocation of Raf-1 from the cytosol to the membrane following stimulation with 12-O-tetradecanoylphorbol-13-acetate. These results suggest a potential role of the lipid second messenger, PA, in the regulation of translocation and subsequent activation of Raf-1 in vivo.

  9. Distinct and stage specific nuclear factors regulate the expression of falcipains, Plasmodium falciparum cysteine proteases

    PubMed Central

    Sunil, Sujatha; Chauhan, Virander S; Malhotra, Pawan

    2008-01-01

    Background Plasmodium falciparum cysteine proteases (falcipains) play indispensable roles in parasite infection and development, especially in the process of host erythrocyte rupture/invasion and hemoglobin degradation. No detailed molecular analysis of transcriptional regulation of parasite proteases especially cysteine proteases has yet been reported. In this study, using a combination of transient transfection assays and electrophoretic mobility shift assays (EMSA), we demonstrate the presence of stage specific nuclear factors that bind to unique sequence elements in the 5'upstream regions of the falcipains and probably modulate the expression of cysteine proteases. Results Falcipains differ in their timing of expression and exhibit ability to compensate each other's functions at asexual blood stages of the parasite. Present study was undertaken to study the transcriptional regulation of falcipains. Transient transfection assay employing firefly luciferase as a reporter revealed that a ~1 kb sequence upstream of translational start site is sufficient for the functional transcriptional activity of falcipain-1 gene, while falcipain-2, -2' and -3 genes that exist within 12 kb stretch on chromosome 11 require ~2 kb upstream sequences for the expression of reporter luciferase activity. EMSA analysis elucidated binding of distinct nuclear factors to specific sequences within the 5'upstream regions of falcipain genes. Analysis of falcipains' 5'upstream regulatory regions did not reveal the presence of sequences known to bind general eukaryotic factors. However, we did find parasite specific sequence elements such as poly(dA) poly(dT) tracts, CCAAT boxes and a single 7 bp-G rich sequence, (A/G)NGGGG(C/A) in the 5' upstream regulatory regions of these genes, thereby suggesting the role(s) of Plasmodium specific transcriptional factors in the regulation of falcipain genes. Conclusion Taken together, these results suggest that expression of Plasmodium cysteine proteases is

  10. Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes

    PubMed Central

    Morena, Deborah; Maestro, Nicola; Bersani, Francesca; Forni, Paolo Emanuele; Lingua, Marcello Francesco; Foglizzo, Valentina; Šćepanović, Petar; Miretti, Silvia; Morotti, Alessandro; Shern, Jack F; Khan, Javed; Ala, Ugo; Provero, Paolo; Sala, Valentina; Crepaldi, Tiziana; Gasparini, Patrizia; Casanova, Michela; Ferrari, Andrea; Sozzi, Gabriella; Chiarle, Roberto; Ponzetto, Carola; Taulli, Riccardo

    2016-01-01

    Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity. DOI: http://dx.doi.org/10.7554/eLife.12116.001 PMID:26987019

  11. Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes

    PubMed Central

    Li, Xu; Wang, Wenqi; Wang, Jiadong; Malovannaya, Anna; Xi, Yuanxin; Li, Wei; Guerra, Rudy; Hawke, David H; Qin, Jun; Chen, Junjie

    2015-01-01

    The current knowledge on how transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated by protein–protein interactions remains limited. Here, we performed proteomics analyses of soluble and chromatin-associated complexes of 56 TFs, including the targets of many signalling pathways involved in development and cancer, and 37 members of the Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high-confident protein–protein interactions. We found that most TFs form very distinct protein complexes on and off chromatin. Using this data set, we categorized the transcription-related or unrelated regulators for general or specific TFs. Our study offers a valuable resource of protein–protein interaction networks for a large number of TFs and underscores the general principle that TFs form distinct location-specific protein complexes that are associated with the different regulation and diverse functions of these TFs. PMID:25609649

  12. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease

    PubMed Central

    Beck, Michael W.; Derrick, Jeffrey S.; Kerr, Richard A.; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C.; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D.; Kim, Kwang S.; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2016-01-01

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal–Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs. PMID:27734843

  13. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease.

    PubMed

    Beck, Michael W; Derrick, Jeffrey S; Kerr, Richard A; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D; Kim, Kwang S; Lee, Joo-Yong; Ruotolo, Brandon T; Lim, Mi Hee

    2016-10-13

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

  14. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Beck, Michael W.; Derrick, Jeffrey S.; Kerr, Richard A.; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C.; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D.; Kim, Kwang S.; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2016-10-01

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

  15. Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major

    PubMed Central

    Späth, Gerald F.; Epstein, Linda; Leader, Ben; Singer, Steven M.; Avila, Herbert A.; Turco, Salvatore J.; Beverley, Stephen M.

    2000-01-01

    Protozoan parasites of the genus Leishmania undergo a complex life cycle involving transmission by biting sand flies and replication within mammalian macrophage phagolysosomes. A major component of the Leishmania surface coat is the glycosylphosphatidylinositol (GPI)-anchored polysaccharide called lipophosphoglycan (LPG). LPG has been proposed to play many roles in the infectious cycle, including protection against complement and oxidants, serving as the major ligand for macrophage adhesion, and as a key factor mitigating host responses by deactivation of macrophage signaling pathways. However, all structural domains of LPG are shared by other major surface or secretory products, providing a biochemical redundancy that compromises the ability of in vitro tests to establish whether LPG itself is a virulence factor. To study truly lpg− parasites, we generated Leishmania major lacking the gene LPG1 [encoding a putative galactofuranosyl (Galf) transferase] by targeted gene disruption. The lpg1− parasites lacked LPG but contained normal levels of related glycoconjugates and GPI-anchored proteins. Infections of susceptible mice and macrophages in vitro showed that these lpg− Leishmania were highly attenuated. Significantly and in contrast to previous LPG mutants, reintroduction of LPG1 into the lpg− parasites restored virulence. Thus, genetic approaches allow dissection of the roles of this complex family of interrelated parasite virulence factors, and definitively establish the role of LPG itself as a parasite virulence factor. Because the lpg1− mutant continue to synthesize bulk GPI-anchored Galf-containing glycolipids other than LPG, a second pathway distinct from the Golgi-associated LPG synthetic compartment must exist. PMID:10908670

  16. Two Fundamentally Distinct PCNA Interaction Peptides Contribute to Chromatin Assembly Factor 1 Function▿

    PubMed Central

    Ben-Shahar, Tom Rolef; Castillo, Araceli G.; Osborne, Michael J.; Borden, Katherine L. B.; Kornblatt, Jack; Verreault, Alain

    2009-01-01

    Chromatin assembly factor 1 (CAF-1) deposits histones H3 and H4 rapidly behind replication forks through an interaction with the proliferating cell nuclear antigen (PCNA), a DNA polymerase processivity factor that also binds to a number of replication enzymes and other proteins that act on nascent DNA. The mechanisms that enable CAF-1 and other PCNA-binding proteins to function harmoniously at the replication fork are poorly understood. Here we report that the large subunit of human CAF-1 (p150) contains two distinct PCNA interaction peptides (PIPs). The N-terminal PIP binds strongly to PCNA in vitro but, surprisingly, is dispensable for nucleosome assembly and only makes a modest contribution to targeting p150 to DNA replication foci in vivo. In contrast, the internal PIP (PIP2) lacks one of the highly conserved residues of canonical PIPs and binds weakly to PCNA. Surprisingly, PIP2 is essential for nucleosome assembly during DNA replication in vitro and plays a major role in targeting p150 to sites of DNA replication. Unlike canonical PIPs, such as that of p21, the two p150 PIPs are capable of preferentially inhibiting nucleosome assembly, rather than DNA synthesis, suggesting that intrinsic features of these peptides are part of the mechanism that enables CAF-1 to function behind replication forks without interfering with other PCNA-mediated processes. PMID:19822659

  17. Activated STAT1 transcription factors conduct distinct saltatory movements in the cell nucleus.

    PubMed

    Speil, Jasmin; Baumgart, Eugen; Siebrasse, Jan-Peter; Veith, Roman; Vinkemeier, Uwe; Kubitscheck, Ulrich

    2011-12-07

    The activation of STAT transcription factors is a critical determinant of their subcellular distribution and their ability to regulate gene expression. Yet, it is not known how activation affects the behavior of individual STAT molecules in the cytoplasm and nucleus. To investigate this issue, we injected fluorescently labeled STAT1 in living HeLa cells and traced them by single-molecule microscopy. We determined that STAT1 moved stochastically in the cytoplasm and nucleus with very short residence times (<0.03 s) before activation. Upon activation, STAT1 mobility in the cytoplasm decreased ∼2.5-fold, indicating reduced movement of STAT1/importinα/β complexes to the nucleus. In the nucleus, activated STAT1 displayed a distinct saltatory mobility, with residence times of up to 5 s and intermittent diffusive motion. In this manner, activated STAT1 factors can occupy their putative chromatin target sites within ∼2 s. These results provide a better understanding of the timescales on which cellular signaling and regulated gene transcription operate at the single-molecule level.

  18. Three R2R3-MYB transcription factors regulate distinct floral pigmentation patterning in Phalaenopsis spp.

    PubMed

    Hsu, Chia-Chi; Chen, You-Yi; Tsai, Wen-Chieh; Chen, Wen-Huei; Chen, Hong-Hwa

    2015-05-01

    Orchidaceae are well known for their fascinating floral morphologic features, specialized pollination, and distinctive ecological strategies. With their long-lasting flowers of various colors and pigmentation patterning, Phalaenopsis spp. have become important ornamental plants worldwide. In this study, we identified three R2R3-MYB transcription factors PeMYB2, PeMYB11, and PeMYB12. Their expression profiles were concomitant with red color formation in Phalaenopsis spp. flowers. Transient assay of overexpression of three PeMYBs verified that PeMYB2 resulted in anthocyanin accumulation, and these PeMYBs could activate the expression of three downstream structural genes Phalaenopsis spp. Flavanone 3-hydroxylase5, Phalaenopsis spp. Dihydroflavonol 4-reductase1, and Phalaenopsis spp. Anthocyanidin synthase3. In addition, these three PeMYBs participated in the distinct pigmentation patterning in a single flower, which was revealed by virus-induced gene silencing. In the sepals/petals, silencing of PeMYB2, PeMYB11, and PeMYB12 resulted in the loss of the full-red pigmentation, red spots, and venation patterns, respectively. Moreover, different pigmentation patterning was regulated by PeMYBs in the sepals/petals and lip. PeMYB11 was responsive to the red spots in the callus of the lip, and PeMYB12 participated in the full pigmentation in the central lobe of the lip. The differential pigmentation patterning was validated by RNA in situ hybridization. Additional assessment was performed in six Phalaenopsis spp. cultivars with different color patterns. The combined expression of these three PeMYBs in different ratios leads to a wealth of complicated floral pigmentation patterning in Phalaenopsis spp.

  19. Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses

    PubMed Central

    Petrenko, Natalia; Chereji, Raˇzvan V.; McClean, Megan N.; Morozov, Alexandre V.; Broach, James R.

    2013-01-01

    All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to “hedge their bets” in responding to an uncertain future, and to balance growth and survival in an unpredictable environment. PMID:23615444

  20. Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses.

    PubMed

    Petrenko, Natalia; Chereji, Razvan V; McClean, Megan N; Morozov, Alexandre V; Broach, James R

    2013-06-01

    All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to "hedge their bets" in responding to an uncertain future, and to balance growth and survival in an unpredictable environment.

  1. Finding subtypes of transcription factor motif pairs with distinct regulatory roles

    PubMed Central

    Bais, Abha Singh; Kaminski, Naftali; Benos, Panayiotis V.

    2011-01-01

    DNA sequences bound by a transcription factor (TF) are presumed to contain sequence elements that reflect its DNA binding preferences and its downstream-regulatory effects. Experimentally identified TF binding sites (TFBSs) are usually similar enough to be summarized by a ‘consensus’ motif, representative of the TF DNA binding specificity. Studies have shown that groups of nucleotide TFBS variants (subtypes) can contribute to distinct modes of downstream regulation by the TF via differential recruitment of cofactors. A TFA may bind to TFBS subtypes a1 or a2 depending on whether it associates with cofactors TFB or TFC, respectively. While some approaches can discover motif pairs (dyads), none address the problem of identifying ‘variants’ of dyads. TFs are key components of multiple regulatory pathways targeting different sets of genes perhaps with different binding preferences. Identifying the discriminating TF–DNA associations that lead to the differential downstream regulation is thus essential. We present DiSCo (Discovery of Subtypes and Cofactors), a novel approach for identifying variants of dyad motifs (and their respective target sequence sets) that are instrumental for differential downstream regulation. Using both simulated and experimental datasets, we demonstrate how current motif discovery can be successfully leveraged to address this question. PMID:21486752

  2. Further evidence for a human B cell activating factor distinct from IL-4.

    PubMed

    Diu, A; Février, M; Mollier, P; Charron, D; Banchereau, J; Reinherz, E L; Thèze, J

    1990-01-01

    Supernatants from activated human T cell clones were previously shown to contain B cell-activating factor (BCAF), an activity which results in polyclonal resting B cell stimulation. In the present study, we investigate the relationship between this activity and human interleukin-4 which was also shown to act on resting B cells. The supernatant of the T cell clone TT9 contains IL-4 but anti-IL-4 antiserum does not affect the response of B cells as measured by thymidine uptake or cell volume increase. Furthermore, IL-4 induces Fc epsilon-receptor (CD23) expression on 30% of unstimulated human B cells, whereas BCAF-containing supernatants from clone P2, that do not contain detectable amounts of IL-4, promote B cell proliferation without inducing CD23 expression. Our results therefore establish that IL-4 and BCAF are distinct activities and suggest that they trigger different activation pathways in human B cells. In addition, culture of B cells with T cell supernatants for 72 hr induces a three- to fourfold increase in the expression of HLA-DR, -DP, and -DQ antigens in 50% of B cells. The addition of inhibiting concentrations of anti-IFN-gamma, LT, or IL-4 antisera to the cultures does not change these results. Finally, 30% of B cells cultured with T cell supernatants leave the G1 phase of the cell cycle and 20% reach mitosis. Taken together, our findings further support the existence of a B cell-activating factor responsible for the activation of resting human B cells.

  3. Distinct functions of dispersed GATA factor complexes at an endogenous gene locus.

    PubMed

    Grass, Jeffrey A; Jing, Huie; Kim, Shin-Il; Martowicz, Melissa L; Pal, Saumen; Blobel, Gerd A; Bresnick, Emery H

    2006-10-01

    The reciprocal expression of GATA-1 and GATA-2 during hematopoiesis is an important determinant of red blood cell development. Whereas Gata2 is preferentially transcribed early in hematopoiesis, elevated GATA-1 levels result in GATA-1 occupancy at sites upstream of the Gata2 locus and transcriptional repression. GATA-2 occupies these sites in the transcriptionally active locus, suggesting that a "GATA switch" abrogates GATA-2-mediated positive autoregulation. Chromatin immunoprecipitation (ChIP) coupled with genomic microarray analysis and quantitative ChIP analysis with GATA-1-null cells expressing an estrogen receptor ligand binding domain fusion to GATA-1 revealed additional GATA switches 77 kb upstream of Gata2 and within intron 4 at +9.5 kb. Despite indistinguishable GATA-1 occupancy at -77 kb and +9.5 kb versus other GATA switch sites, GATA-1 functioned uniquely at the different regions. GATA-1 induced histone deacetylation at and near Gata2 but not at the -77 kb region. The -77 kb region, which was DNase I hypersensitive in both active and inactive states, conferred equivalent enhancer activities in GATA-1- and GATA-2-expressing cells. By contrast, the +9.5 kb region exhibited considerably stronger enhancer activity in GATA-2- than in GATA-1-expressing cells, and other GATA switch sites were active only in GATA-1- or GATA-2-expressing cells. Chromosome conformation capture analysis demonstrated higher-order interactions between the -77 kb region and Gata2 in the active and repressed states. These results indicate that dispersed GATA factor complexes function via long-range chromatin interactions and qualitatively distinct activities to regulate Gata2 transcription.

  4. Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

    PubMed

    Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja

    2017-05-01

    Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P<0.0001), higher rates of obesity (53.4% versus 26.9%; P<0.0001), and significantly higher levels of plasma aldosterone (11.3±9.8 versus 8.9±7.4 ng/dL; P=0.005), plasma renin activity (4.9±10.2 versus 2.5±5.0 ng/mL per hour; P=0.001), 24-hour urinary aldosterone (13.4±10.0 versus 8.2±6.2 µg/24 h; P<0.0001), and sodium excretion (195.9±92.0 versus 146.8±67.1 mEq/24 h; P<0.0001). Among patients with resistant hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

  5. Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

    PubMed

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

    2009-05-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging.

  6. Risk Factors for Fecal Colonization with Multiple Distinct Strains of Escherichia coli Among Long-Term Care Facility Residents

    PubMed Central

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N.

    2009-01-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with two or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest future efforts to efficiently identify diversity of colonizing strains will be challenging. PMID:19292660

  7. Instant noodle intake and dietary patterns are associated with distinct cardiometabolic risk factors in Korea.

    PubMed

    Shin, Hyun Joon; Cho, Eunyoung; Lee, Hae-Jeung; Fung, Teresa T; Rimm, Eric; Rosner, Bernard; Manson, JoAnn E; Wheelan, Kevin; Hu, Frank B

    2014-08-01

    The consumption of instant noodles is relatively high in Asian populations. It is unclear whether a higher intake of instant noodles is associated with cardiometabolic risk independent of overall dietary patterns. We therefore investigated the association using the Korean National Health and Nutrition Examination Survey IV 2007-2009, a nationally representative cross-sectional survey of the Korean population with a clustered, multistage, stratified, and rolling sampling design. A total of 10,711 adults (54.5% women) 19-64 y of age were analyzed, with adjustment for sampling design complexity. Diet was assessed by using a 63-item food-frequency questionnaire. We identified 2 major dietary patterns with the use of principal components analysis: the "traditional dietary pattern" (TP), rich in rice, fish, vegetables, fruit, and potatoes, and the "meat and fast-food pattern" (MP), with less rice intake but rich in meat, soda, fried food, and fast food including instant noodles. The highest MP quintile was associated with increased prevalence of abdominal obesity (OR: 1.41; 95% CI: 1.05, 1.90), LDL cholesterol ≥130 mg/dL (1.3 g/L) (OR: 1.57, 95% CI 1.26, 1.95), decreased prevalence of low HDL cholesterol (OR: 0.65; 95% CI: 0.53, 0.80), and high triglycerides [≥150 mg/dL (1.5 g/L); OR: 0.73; 95% CI: 0.57, 0.93]. The highest quintile for the TP was associated with decreased prevalence of elevated blood pressure (OR: 0.73; 95% CI: 0.59, 0.90) and marginally lower trends for abdominal obesity (OR: 0.76; 95% CI: 0.58, 0.98; P-trend = 0.06), but neither of the dietary patterns was associated with prevalence of metabolic syndrome. The consumption of instant noodles ≥2 times/wk was associated with a higher prevalence of metabolic syndrome (OR: 1.68; 95% CI: 1.10, 2.55) in women but not in men (OR: 0.93; 95% CI: 0.58, 1.49; P-interaction = 0.04). The 2 major dietary patterns were associated with distinct cardiometabolic risk factors. The consumption of instant noodles was

  8. Activity of distinct growth factor receptor network components in breast tumors uncovers two biologically relevant subtypes.

    PubMed

    Rahman, Mumtahena; MacNeil, Shelley M; Jenkins, David F; Shrestha, Gajendra; Wyatt, Sydney R; McQuerry, Jasmine A; Piccolo, Stephen R; Heiser, Laura M; Gray, Joe W; Johnson, W Evan; Bild, Andrea H

    2017-04-26

    The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection and InteGratioN (ASSIGN) was used to estimate pathway activity for GFRN components in 1119 breast tumors from The Cancer Genome Atlas (TCGA) and across 55 breast cancer cell lines from the Integrative Cancer Biology Program (ICBP43). These signatures were investigated for their relationship to pro- and anti-apoptotic protein expression and drug response in breast cancer cell lines. Application of these signatures to breast tumor gene expression data identified two novel discrete phenotypes characterized by concordant, aberrant activation of either the HER2, IGF1R, and AKT pathways ("the survival phenotype") or the EGFR, KRAS (G12V), RAF1, and BAD pathways ("the growth phenotype"). These phenotypes described a significant amount of the variability in the total expression data across breast cancer tumors and characterized distinctive patterns in apoptosis evasion and drug response. The growth phenotype expressed lower levels of BIM and higher levels of MCL-1 proteins. Further, the growth phenotype was more sensitive to common chemotherapies and targeted therapies directed at EGFR and MEK. Alternatively, the survival phenotype was more sensitive to drugs inhibiting HER2, PI3K, AKT, and mTOR, but more resistant to chemotherapies. Gene expression profiling revealed a bifurcation pattern

  9. Six distinct nuclear factors interact with the 75-base-pair repeat of the Moloney murine leukemia virus enhancer.

    PubMed Central

    Speck, N A; Baltimore, D

    1987-01-01

    Binding sites for six distinct nuclear factors on the 75-base-pair repeat of the Moloney murine leukemia virus enhancer have been identified by an electrophoretic mobility shift assay combined with methylation interference. Three of these factors, found in WEHI 231 nuclear extracts, which we have named LVa, LVb, and LVc (for leukemia virus factors a, b, and c) have not been previously identified. Nuclear factors that bind to the conserved simian virus 40 corelike motif, the NF-1 motif, and the glucocorticoid response element were also detected. Testing of multiple cell lines showed that most factors appeared ubiquitous, except that the NF-1 binding factor was found neither in nuclear extracts from MEL cells nor in the embryonal carcinoma cell lines PCC4 and F9, and core-binding factor was relatively depleted from MEL and F9 nuclear extracts. Images PMID:3561410

  10. The Daiokanzoto (TJ-84) Kampo Formulation Reduces Virulence Factor Gene Expression in Porphyromonas gingivalis and Possesses Anti-Inflammatory and Anti-Protease Activities

    PubMed Central

    Fournier-Larente, Jade; Azelmat, Jabrane; Yoshioka, Masami; Hinode, Daisuke; Grenier, Daniel

    2016-01-01

    Kampo formulations used in Japan to treat a wide variety of diseases and to promote health are composed of mixtures of crude extracts from the roots, bark, leaves, and rhizomes of a number of herbs. The present study was aimed at identifying the beneficial biological properties of Daiokanzoto (TJ-84), a Kampo formulation composed of crude extracts of Rhubarb rhizomes and Glycyrrhiza roots, with a view to using it as a potential treatment for periodontal disease. Daiokanzoto dose-dependently inhibited the expression of major Porphyromonas gingivalis virulence factors involved in host colonization and tissue destruction. More specifically, Daiokanzoto reduced the expression of the fimA, hagA, rgpA, and rgpB genes, as determined by quantitative real-time PCR. The U937-3xκB-LUC monocyte cell line transfected with a luciferase reporter gene was used to evaluate the anti-inflammatory properties of Daiokanzoto. Daiokanzoto attenuated the P. gingivalis-mediated activation of the NF-κB signaling pathway. It also reduced the secretion of pro-inflammatory cytokines (IL-6 and CXCL8) by lipopolysaccharide-stimulated oral epithelial cells and gingival fibroblasts. Lastly, Daiokanzoto, dose-dependently inhibited the catalytic activity of matrix metalloproteinases (-1 and -9). In conclusion, the present study provided evidence that Daiokanzoto shows potential for treating and/or preventing periodontal disease. The ability of this Kampo formulation to act on both bacterial pathogens and the host inflammatory response, the two etiological components of periodontal disease, is of high therapeutic interest. PMID:26859747

  11. Epilepsy, hysteria, and "possession". A historical essay.

    PubMed

    Glaser, G H

    1978-04-01

    A historical essay is presented relating concepts of epilepsy, hysteria, and "possession." The designation "hysteroepilepsy" is placed into the context of combined phenomena in individual subject instances. An association of psychotic states resembling a schizoprenic disorder is indicated as occurring in certain epileptic patients, especially some complex partial seizures (i.e., temporal lobe-psychomotor type). Phenomena of possession may appear within any of these entities. Differential diagnosis now is aided greatly by ulilization of monitoring with combined split screen television viewing and recording of the patient's behavior and the concomitant electroencephalogram. Treatment is directed both medically and toward alleviation of contributing and precipitating psychological and sociological factors.

  12. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

    PubMed

    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  13. In vitro Evidence for Two Distinct Hippocampal Growth Factors: Basis of Neuronal Plasticity?

    NASA Astrophysics Data System (ADS)

    Crutcher, Keith A.; Collins, Frank

    1982-07-01

    The rat hippocampal formation was tested for the presence of factors that would accelerate neurite extension from chick parasympathetic (ciliary ganglion) or sympathetic (lumbar chain) neurons in vitro. Two growth factors were identified in extracts of this brain region. One accelerated neurite extension from sympathetic neurons and was blocked by antiserum to nerve growth factor. The other accelerated neurite extension from parasympathetic neurons but was not affected by the antiserum. These results suggest that specific growth factors account for the specificity of neuronal sprouting.

  14. The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.

    PubMed

    Andersson, Lisa S; Swinburne, June E; Meadows, Jennifer R S; Broström, Hans; Eriksson, Susanne; Fikse, W Freddy; Frey, Rebecka; Sundquist, Marie; Tseng, Chia T; Mikko, Sofia; Lindgren, Gabriella

    2012-03-01

    Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p (raw) = 2.34 × 10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.

  15. Distinct Factors Shape Aquatic and Sedimentary Microbial Community Structures in the Lakes of Western China

    PubMed Central

    Yang, Jian; Jiang, Hongchen; Wu, Geng; Liu, Wen; Zhang, Guojing

    2016-01-01

    Little is known about the relative importance of spatial and environmental factors to structuring aquatic and sedimentary microbial biogeography in lakes. Here, we investigated the microbial community composition (MCC) of the water (n = 35) and sediment (n = 35) samples from 16 lakes in western China (salinity: freshwater to salt saturation; pairwise geographical distance: 9–2027 km) using high-throughput sequencing and evaluated the relative importance of spatial and environmental factors to microbial (including total, abundant, and rare) distributions. Our results showed that spatial factors were more important than environmental factors in shaping the biogeography of aquatic and sedimentary microbial communities in the studied lakes, and spatial factors on abundant microbial community was stronger than that on the total/rare microbial communities. Moreover, sedimentary rare MCC might be more sensitive to environmental factors than its aquatic counterpart. Such different biogeography responses of total, abundant, and rare communities to environmental and spatial factors could be ascribed to different physiochemical properties between water and sediment. Collectively, this study expands our understanding of factors shaping microbial biogeography of total, abundant, and rare communities between waters and sediments of lakes. PMID:27877171

  16. Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors.

    PubMed Central

    Dionne, C A; Crumley, G; Bellot, F; Kaplow, J M; Searfoss, G; Ruta, M; Burgess, W H; Jaye, M; Schlessinger, J

    1990-01-01

    The fibroblast growth factor (FGF) family consists of at least seven closely related polypeptide mitogens which exert their activities by binding and activation of specific cell surface receptors. Unanswered questions have been whether there are multiple FGF receptors and what factors determine binding specificity and biological response. We report the complete cDNA cloning of two human genes previously designated flg and bek. These genes encode two similar but distinct cell surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a single transmembrane domain, and a cytoplasmic portion containing a tyrosine kinase domain with a typical kinase insert. The expression of these two cDNAs in transfected NIH 3T3 cells led to the biosynthesis of proteins of 150 kd and 135 kd for flg and bek, respectively. Direct binding experiments with radiolabeled acidic FGF (aFGF) or basic FGF (bFGF), inhibition of binding with native growth factors, and Scatchard analysis of the binding data indicated that bek and flg bind either aFGF or bFGF with dissociation constants of (2-15) x 10(-11) M. The high affinity binding of two distinct growth factors to each of two different receptors represents a unique double redundancy without precedence among polypeptide growth factor-receptor interactions. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:1697263

  17. Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum

    NASA Astrophysics Data System (ADS)

    Tian, Xinhui; Yue, Rongcai; Zeng, Huawu; Li, Honglin; Shan, Lei; He, Weiwei; Shen, Yunheng; Zhang, Weidong

    2015-11-01

    Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)-1 and (-)-1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)-1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (-)-1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)-1 and (-)-1.

  18. The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

    SciTech Connect

    Liu, Tong; Yu, Rong; Jin, Shao-Bo; Han, Liwei; Lendahl, Urban; Zhao, Jian; Nistér, Monica

    2013-11-01

    Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

  19. Sperm and spermatids contain different proteins and bind distinct egg factors.

    PubMed

    Teperek, Marta; Miyamoto, Kei; Simeone, Angela; Feret, Renata; Deery, Michael J; Gurdon, John B; Jullien, Jerome

    2014-09-19

    Spermatozoa are more efficient at supporting normal embryonic development than spermatids, their immature, immediate precursors. This suggests that the sperm acquires the ability to support embryonic development during spermiogenesis (spermatid to sperm maturation). Here, using Xenopus laevis as a model organism, we performed 2-D Fluorescence Difference Gel Electrophoresis (2D-DIGE) and mass spectrometry analysis of differentially expressed proteins between sperm and spermatids in order to identify factors that could be responsible for the efficiency of the sperm to support embryonic development. Furthermore, benefiting from the availability of egg extracts in Xenopus, we also tested whether the chromatin of sperm could attract different egg factors compared to the chromatin of spermatids. Our analysis identified: (1) several proteins which were present exclusively in sperm; but not in spermatid nuclei and (2) numerous egg proteins binding to the sperm (but not to the spermatid chromatin) after incubation in egg extracts. Amongst these factors we identified many chromatin-associated proteins and transcriptional repressors. Presence of transcriptional repressors binding specifically to sperm chromatin could suggest its preparation for the early embryonic cell cycles, during which no transcription is observed and suggests that sperm chromatin has a unique protein composition, which facilitates the recruitment of egg chromatin remodelling factors. It is therefore likely that the acquisition of these sperm-specific factors during spermiogenesis makes the sperm chromatin suitable to interact with the maternal factors and, as a consequence, to support efficient embryonic development.

  20. Biomass digestibility is predominantly affected by three factors of wall polymer features distinctive in wheat accessions and rice mutants

    PubMed Central

    2013-01-01

    Background Wheat and rice are important food crops with enormous biomass residues for biofuels. However, lignocellulosic recalcitrance becomes a crucial factor on biomass process. Plant cell walls greatly determine biomass recalcitrance, thus it is essential to identify their key factors on lignocellulose saccharification. Despite it has been reported about cell wall factors on biomass digestions, little is known in wheat and rice. In this study, we analyzed nine typical pairs of wheat and rice samples that exhibited distinct cell wall compositions, and identified three major factors of wall polymer features that affected biomass digestibility. Results Based on cell wall compositions, ten wheat accessions and three rice mutants were classified into three distinct groups each with three typical pairs. In terms of group I that displayed single wall polymer alternations in wheat, we found that three wall polymer levels (cellulose, hemicelluloses and lignin) each had a negative effect on biomass digestibility at similar rates under pretreatments of NaOH and H2SO4 with three concentrations. However, analysis of six pairs of wheat and rice samples in groups II and III that each exhibited a similar cell wall composition, indicated that three wall polymer levels were not the major factors on biomass saccharification. Furthermore, in-depth detection of the wall polymer features distinctive in rice mutants, demonstrated that biomass digestibility was remarkably affected either negatively by cellulose crystallinity (CrI) of raw biomass materials, or positively by both Ara substitution degree of non-KOH-extractable hemicelluloses (reverse Xyl/Ara) and p-coumaryl alcohol relative proportion of KOH-extractable lignin (H/G). Correlation analysis indicated that Ara substitution degree and H/G ratio negatively affected cellulose crystallinity for high biomass enzymatic digestion. It was also suggested to determine whether Ara and H monomer have an interlinking with cellulose chains

  1. Inhibition of the TEF/TEAD transcription factor activity by nuclear calcium and distinct kinase pathways.

    PubMed

    Thompson, M; Andrade, V A; Andrade, S J; Pusl, T; Ortega, J M; Goes, A M; Leite, M F

    2003-02-07

    Transcription enhancer factor (TEF/TEAD) is a family of four transcription factors that share a common TEA-DNA binding domain and are involved in similar cellular functions, such as cell differentiation and proliferation. All adult tissues express at least one of the four TEAD genes, so this family of transcription factors may be of widespread importance, yet little is known about their regulation. Here we examine the factors that regulate TEAD activity in CHO cells. RT-PCR indicated the presence of TEAD-1, TEAD-3, and both isoforms of TEAD-4, but not TEAD-2. Quantitative measurements showed that TEAD-4 is most abundant, followed by TEAD-3, then TEAD-1. We examined the relative effects of nuclear and cytosolic Ca(2+) on TEAD activity, since TEAD proteins are localized to the nucleus and since free Ca(2+) within the nucleus selectively regulates transcription in some systems. Chelation of nuclear but not cytosolic Ca(2+) increased TEAD activity two times above control. Inhibition of mitogen-activated protein kinase (MAPK) also increased TEAD activity, while cAMP decreased TEAD activity, and protein kinase C had no effect. Together, these results show that nuclear Ca(2+), MAPK, and cAMP each negatively regulate the activity of the TEAD transcription factor.

  2. Distinct immunoregulatory properties of macrophage migration inhibitory factors encoded by Eimeria parasites and their chicken host

    USDA-ARS?s Scientific Manuscript database

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in host defense against a variety of microorganisms including protozoan parasites. Interestingly, some microbial pathogens also express a MIF-like protein, although its role in disease pathogenesi...

  3. Murine thymic NK cells are distinct from ILC1s and have unique transcription factor requirements.

    PubMed

    Gabrielli, Sara; Sun, Mengxi; Bell, April; Zook, Erin C; de Pooter, Renee F; Zamai, Loris; Kee, Barbara L

    2017-03-09

    Group 1 innate lymphoid cells include natural killer (NK) cells and ILC1s, which mediate the response to intracellular pathogens. Thymic NK (tNK) cells were described with hybrid features of immature NK cells and ILC1 but whether these cells are related to NK cells or ILC1 has not been fully investigated. We report that murine tNK cells expressed the NK-cell associated transcription factor EOMES and developed independent of the essential ILC1 factor TBET, confirming their placement within the NK lineage. Moreover, tNK cells resemble NK cells rather than ILC1 in their requirements for the E protein transcription factor inhibitor ID2. We provide further insight into the mechanisms governing tNK-cell development by showing that the transcription factor ETS1 prevented tNK cell acquisition of the conventional NK-cell maturation markers CD11b and KLRG1. Our data reveal few ILC1 in the thymus and clarify the identity and developmental requirements of tNK cells. This article is protected by copyright. All rights reserved.

  4. Higher Order Factor Convergence and Divergence of Two Distinct Personality Systems: Cattell's HSPQ and Jackson's PRF

    ERIC Educational Resources Information Center

    Nesselroade, John B.; Bates, Paul B.

    1975-01-01

    Seeks empirical evidence of convergence of concepts measured by two personality inventories--Cattell's High School Personality Questionnaire and Jackson's Personality Research Form. Implication of the levels of factor convergence obtained in relation to theory building and prediction are discussed. (RC)

  5. Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages

    USGS Publications Warehouse

    DeBoer, Jason A.; Pope, Kevin L.

    2015-01-01

    Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age-0 larval’; age 0 during autumn: ‘age-0 juvenile’; and age 1 during autumn: ‘age-1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age-0 larval, age-0 juvenile and age-1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage-specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year-class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.

  6. Defining Distinct Negative Beliefs about Uncertainty: Validating the Factor Structure of the Intolerance of Uncertainty Scale

    ERIC Educational Resources Information Center

    Sexton, Kathryn A.; Dugas, Michel J.

    2009-01-01

    This study examined the factor structure of the English version of the Intolerance of Uncertainty Scale (IUS; French version: M. H. Freeston, J. Rheaume, H. Letarte, M. J. Dugas, & R. Ladouceur, 1994; English version: K. Buhr & M. J. Dugas, 2002) using a substantially larger sample than has been used in previous studies. Nonclinical…

  7. Individual ball possession in soccer

    PubMed Central

    Hoernig, Martin

    2017-01-01

    This paper describes models for detecting individual and team ball possession in soccer based on position data. The types of ball possession are classified as Individual Ball Possession (IBC), Individual Ball Action (IBA), Individual Ball Control (IBC), Team Ball Possession (TBP), Team Ball Control (TBC) und Team Playmaking (TPM) according to different starting points and endpoints and the type of ball control involved. The machine learning approach used is able to determine how long the ball spends in the sphere of influence of a player based on the distance between the players and the ball together with their direction of motion, speed and the acceleration of the ball. The degree of ball control exhibited during this phase is classified based on the spatio-temporal configuration of the player controlling the ball, the ball itself and opposing players using a Bayesian network. The evaluation and application of this approach uses data from 60 matches in the German Bundesliga season of 2013/14, including 69,667 IBA intervals. The identification rate was F = .88 for IBA and F = .83 for IBP, and the classification rate for IBC was κ = .67. Match analysis showed the following mean values per match: TBP 56:04 ± 5:12 min, TPM 50:01 ± 7:05 min and TBC 17:49 ± 8:13 min. There were 836 ± 424 IBC intervals per match and their number was significantly reduced by -5.1% from the 1st to 2nd half. The analysis of ball possession at the player level indicates shortest accumulated IBC times for the central forwards (0:49 ± 0:43 min) and the longest for goalkeepers (1:38 ± 0:58 min), central defenders (1:38 ± 1:09 min) and central midfielders (1:27 ± 1:08 min). The results could improve performance analysis in soccer, help to detect match events automatically, and allow discernment of higher value tactical structures, which is based on individual ball possession. PMID:28692649

  8. Individual ball possession in soccer.

    PubMed

    Link, Daniel; Hoernig, Martin

    2017-01-01

    This paper describes models for detecting individual and team ball possession in soccer based on position data. The types of ball possession are classified as Individual Ball Possession (IBC), Individual Ball Action (IBA), Individual Ball Control (IBC), Team Ball Possession (TBP), Team Ball Control (TBC) und Team Playmaking (TPM) according to different starting points and endpoints and the type of ball control involved. The machine learning approach used is able to determine how long the ball spends in the sphere of influence of a player based on the distance between the players and the ball together with their direction of motion, speed and the acceleration of the ball. The degree of ball control exhibited during this phase is classified based on the spatio-temporal configuration of the player controlling the ball, the ball itself and opposing players using a Bayesian network. The evaluation and application of this approach uses data from 60 matches in the German Bundesliga season of 2013/14, including 69,667 IBA intervals. The identification rate was F = .88 for IBA and F = .83 for IBP, and the classification rate for IBC was κ = .67. Match analysis showed the following mean values per match: TBP 56:04 ± 5:12 min, TPM 50:01 ± 7:05 min and TBC 17:49 ± 8:13 min. There were 836 ± 424 IBC intervals per match and their number was significantly reduced by -5.1% from the 1st to 2nd half. The analysis of ball possession at the player level indicates shortest accumulated IBC times for the central forwards (0:49 ± 0:43 min) and the longest for goalkeepers (1:38 ± 0:58 min), central defenders (1:38 ± 1:09 min) and central midfielders (1:27 ± 1:08 min). The results could improve performance analysis in soccer, help to detect match events automatically, and allow discernment of higher value tactical structures, which is based on individual ball possession.

  9. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

    PubMed Central

    Viktorovskaya, Olga V.; Greco, Todd M.; Cristea, Ileana M.; Thompson, Sunnie R.

    2016-01-01

    Background There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. Methodology/Principal Findings Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. Conclusions/Significance The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with

  10. Hematopoietic and Leukemic Stem Cells Have Distinct Dependence on Tcf1 and Lef1 Transcription Factors.

    PubMed

    Yu, Shuyang; Li, Fengyin; Xing, Shaojun; Zhao, Tianyan; Peng, Weiqun; Xue, Hai-Hui

    2016-05-20

    Hematopoietic and leukemic stem cells (HSCs and LSCs) have self-renewal ability to maintain normal hematopoiesis and leukemia propagation, respectively. Tcf1 and Lef1 transcription factors are expressed in HSCs, and targeting both factors modestly expanded the size of the HSC pool due to diminished HSC quiescence. Functional defects of Tcf1/Lef1-deficient HSCs in multi-lineage blood reconstitution was only evident under competitive conditions or when subjected to repeated regenerative stress. These are mechanistically due to direct positive regulation of Egr and Tcf3 by Tcf1 and Lef1, and significantly, forced expression of Egr1 in Tcf1/Lef1-deficient HSCs restored HSC quiescence. In a preclinical CML model, loss of Tcf1/Lef1 did not show strong impact on leukemia initiation and progression. However, when transplanted into secondary recipients, Tcf1/Lef1-deficient LSCs failed to propagate CML. By induced deletion of Tcf1 and Lef1 in pre-established CML, we further demonstrated an intrinsic requirement for these factors in LSC self-renewal. When combined with imatinib therapy, genetic targeting of Tcf1 and Lef1 potently diminished LSCs and conferred better protection to the CML recipients. LSCs are therefore more sensitive to loss of Tcf1 and Lef1 than HSCs in their self-renewal capacity. The differential requirements in HSCs and LSCs thus identify Tcf1 and Lef1 transcription factors as novel therapeutic targets in treating hematological malignancies, and inhibition of Tcf1/Lef1-regulated transcriptional programs may thus provide a therapeutic window to eliminate LSCs with minimal side effect on normal HSC functions.

  11. Distinct and Shared Transcriptomes Are Regulated by Microphthalmia-Associated Transcription Factor Isoforms in Mast Cells1

    PubMed Central

    Shahlaee, Amir H.; Brandal, Stephanie; Lee, Youl-Nam; Jie, Chunfa; Takemoto, Clifford M.

    2008-01-01

    The Microphthalmia-associated transcription factor (Mitf) is an essential basic helix-loop-helix leucine zipper transcription factor for mast cell development. Mice deficient in Mitf harbor a severe mast cell deficiency, and Mitf-mutant mast cells cultured ex vivo display a number of functional defects. Therefore, an understanding of the genetic program regulated by Mitf may provide important insights into mast cell differentiation. Multiple, distinct isoforms of Mitf have been identified in a variety of cell types; we found that Mitf-a, Mitf-e, and Mitf-mc were the major isoforms expressed in mast cells. To determine the physiologic function of Mitf in mast cells, we restored expression of these isoforms in primary mast cells from Mitf−/−mice. We found that these isoforms restored granular morphology and integrin-mediated migration. By microarray analysis, proteases, signaling molecules, cell surface receptor, and transporters comprised the largest groups of genes up-regulated by all isoforms. Furthermore, we found that isoforms also regulated distinct genes sets, suggesting separable biological activities. This work defines the transcriptome regulated by Mitf in mast cells and supports its role as master regulator of mast cell differentiation. Expression of multiple isoforms of this transcription factor may provide for redundancy of biological activities while also allowing diversity of function. PMID:17182576

  12. Besieged by devils--thoughts on possession and possession states.

    PubMed

    Prins, H

    1992-07-01

    Aspects of possession are reviewed in historical, cultural and clinical contexts. Consideration is given to differential diagnosis and management. It is suggested that a multi-disciplinary approach is required for a condition that stands at the boundaries of psychiatry. Two quotations from Elizabethan playwrights are relevant to the theme of this paper: 'Beware you do not conjure up a spirit you cannot lay' Ben Johnson, The New Inn (Act III, Scene ii) 'Farewell the tranquil mind: farewell content.' Shakespeare, Othello (Act III, Scene iii).

  13. Distinction of Risk Factors for Superficial vs Organ-Space Surgical Site Infections After Pancreatic Surgery.

    PubMed

    Elliott, Irmina A; Chan, Carmen; Russell, Tara A; Dann, Amanda M; Williams, Jennifer L; Damato, Lauren; Chung, Hallie; Girgis, Mark D; Hines, O Joe; Reber, Howard A; Donahue, Timothy R

    2017-07-12

    Surgical site infection (SSI) rates are increasingly used as a quality metric. However, risk factors for SSI in pancreatic surgery remain undefined. To stratify superficial and organ-space SSIs after pancreatectomy and investigate their modifiable risk factors. This retrospective analysis included 201 patients undergoing pancreatic surgery at a university-based tertiary referral center from July 1, 2013, through June 30, 2015, and 10 371 patients from National Surgical Quality Improvement Program-Hepatopancreaticobiliary (NSQIP-HPB) Collaborative sites from January 1, 2014, through December 31, 2015. Superficial, deep-incisional, and organ-space SSIs, as defined by NSQIP. Among the 201 patients treated at the single center (108 men [53.7%] and 93 women [46.3%]; median age, 48.6 years [IQR, 41.4-57.3 years]), 58 had any SSI (28.9%); 28 (13.9%), superficial SSI; 8 (4%), deep-incisional SSI; and 24 (11.9%), organ-space SSI. Independent risk factors for superficial SSI were preoperative biliary stenting (odds ratio [OR], 4.81; 95% CI, 1.25-18.56; P = .02) and use of immunosuppressive corticosteroids (OR, 13.42; 95% CI, 1.64-109.72; P = .02), whereas soft gland texture was the only risk factor for organ-space SSI (OR, 4.45; 95% CI, 1.35-14.66; P = .01). Most patients with organ-space infections also had grades B/C fistulae (15 of 24 [62.5%] vs 4 of 143 [2.8%] in patients with no SSI; P < .001). Organ/space but not superficial SSI was associated with an increased rate of sepsis (7 of 24 [29.2%] vs 4 of 143 [2.8%]; P < .001) and prolonged length of hospital stay (12 vs 8 days; P = .04). Among patients in the NSQIP-HPB Collaborative, 2057 (19.8%) had any SSI; 719 (6.9%), superficial SSI; 207 (2%), deep-incisional SSI; and 1287 (12.4%), organ-space SSI. Preoperative biliary stenting was confirmed as an independent risk factor for superficial SSI (OR, 2.07; 95% CI, 1.58-2.71; P < .001). In this larger data set, soft gland texture was an

  14. Distinct responses of baseline and stress-induced corticosterone levels to genetic and environmental factors.

    PubMed

    Homberger, Benjamin; Jenni-Eiermann, Susanne; Jenni, Lukas

    2015-01-01

    Glucocorticoid (GC) hormones, i.e. corticosterone (CORT) in birds, support physiological homeostasis and facilitate adaptations to stressful situations. However, maintaining high GC levels are energetically costly and interfere with other physiological processes. To keep the balance of costs and benefits of GC hormones, various mechanisms act to adapt GC levels to environmental conditions on different timescales, i.e. over generations, between parents and their offspring and within the life-time of a single individual. We elucidated whether two strains (domesticated and wild) of grey partridges (Perdix perdix) differed in the developmental trajectories of baseline and stress response CORT throughout the first 80 days of life. We also explored the potential of prenatal and postnatal factors, e.g. parental origin, predictable vs. unpredictable food treatments, individual and social factors to modify these trajectories. Baseline CORT was similar between strains and unaffected by perinatal food treatments. It was negatively related to body size and body condition. Conversely, the CORT stress response was not markedly affected by physiological condition. It was stronger in wild than in domesticated birds and it increased with age. Birds subjected to prenatal unpredictable food supply exhibited an accelerated development of the CORT stress response which could reflect an adaptive maternal effect. We conclude that the vital role of baseline CORT may allow little adaptive scope since changes can quickly become detrimental. In contrast, the CORT stress response may show considerable adaptive potential which might ultimately support homeostasis in a changing environment.

  15. 50 CFR 20.33 - Possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Possession limit. 20.33 Section 20.33... PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.33 Possession limit. No person shall possess more migratory game birds taken in the United States than the possession limit or the aggregate...

  16. 50 CFR 20.33 - Possession limit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Possession limit. 20.33 Section 20.33... PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.33 Possession limit. No person shall possess more migratory game birds taken in the United States than the possession limit or the aggregate...

  17. Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects

    PubMed Central

    Wada, Hiromichi; Ura, Shuichi; Kitaoka, Shuji; Satoh-Asahara, Noriko; Horie, Takahiro; Ono, Koh; Takaya, Tomohide; Takanabe-Mori, Rieko; Akao, Masaharu; Abe, Mitsuru; Morimoto, Tatsuya; Murayama, Toshinori; Yokode, Masayuki; Fujita, Masatoshi; Shimatsu, Akira; Hasegawa, Koji

    2011-01-01

    The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to

  18. Transforming growth factor-β1 in the cerebrospinal fluid of patients with distinct neurodegenerative diseases.

    PubMed

    Masuda, Tomoyuki; Itoh, Junko; Koide, Takuya; Tomidokoro, Yasushi; Takei, Yosuke; Ishii, Kazuhiro; Tamaoka, Akira

    2017-01-01

    A chronic inflammatory condition may underlie neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). For example, both PD and AD patients show an increase in transforming growth factor-β1 (TGF-β1) levels in their cerebrospinal fluid (CSF). TGF-β1 is a cytokine that inhibits inflammation. In the present study, using an enzyme-linked immunosorbent assay, we tested the hypothesis that the level of TGF-β1 in the CSF of patients with amyotrophic lateral sclerosis (ALS), spinocerebellar degeneration (SCD), or multiple system atrophy-cerebellar subtype (MSA-C) would be elevated compared with that of normal controls. We found that TGF-β1 levels in the CSF were not significantly different between these patients and normal controls. Our data suggest that the level of TGF-β1 in the CSF is an unreliable biomarker of ALS, SCD, and MSA-C.

  19. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.

    PubMed

    Dengler, Hart S; Baracho, Gisele V; Omori, Sidne A; Bruckner, Shane; Arden, Karen C; Castrillon, Diego H; DePinho, Ronald A; Rickert, Robert C

    2008-12-01

    The transcription factors Foxo1, Foxo3 and Foxo4 modulate cell fate 'decisions' in diverse systems. Here we show that Foxo1-dependent gene expression was critical at many stages of B cell differentiation. Early deletion of Foxo1 caused a substantial block at the pro-B cell stage due to a failure to express interleukin 7 receptor-alpha. Foxo1 inactivation in late pro-B cells resulted in an arrest at the pre-B cell stage due to lower expression of the recombination-activating genes Rag1 and Rag2. Deletion of Foxo1 in peripheral B cells led to fewer lymph node B cells due to lower expression of L-selectin and failed class-switch recombination due to impaired upregulation of the gene encoding activation-induced cytidine deaminase. Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function.

  20. Neurobiological actions by three distinct subtypes of brain-derived neurotrophic factor: Multi-ligand model of growth factor signaling.

    PubMed

    Mizui, Toshiyuki; Ishikawa, Yasuyuki; Kumanogoh, Haruko; Kojima, Masami

    2016-03-01

    Brain-derived neurotrophic factor (BDNF) is one of the most active members of the neurotrophin family. BDNF not only regulates neuronal survival and differentiation, but also functions in activity-dependent plasticity processes such as long-term potentiation (LTP), long-term depression (LTD), learning, and memory. Like other growth factors, BDNF is produced by molecular and cellular mechanisms including transcription and translation, and functions as a bioactive molecule in the nervous system. Among these mechanisms, a particular post-translational mechanism, namely the conversion of precursor BDNF into mature BDNF by proteolytic cleavage, was not fully understood. In this review, we discuss the manner through which this post-translational mechanism alters the biological actions of BDNF protein. In addition to the initially elucidated findings on BDNF, the biological roles of precursor BDNF and the BDNF pro-peptide, especially synaptic plasticity, will be extensively discussed. Recent findings on the BDNF pro-peptide will provide new insights for understanding the mechanisms of action of the pro-peptides of growth factors.

  1. Identification and characterization of four novel peptide motifs that recognize distinct regions of the transcription factor CP2.

    PubMed

    Kang, Ho Chul; Chung, Bo Mee; Chae, Ji Hyung; Yang, Sung-Il; Kim, Chan Gil; Kim, Chul Geun

    2005-03-01

    Although ubiquitously expressed, the transcriptional factor CP2 also exhibits some tissue- or stage-specific activation toward certain genes such as globin in red blood cells and interleukin-4 in T helper cells. Because this specificity may be achieved by interaction with other proteins, we screened a peptide display library and identified four consensus motifs in numerous CP2-binding peptides: HXPR, PHL, ASR and PXHXH. Protein-database searching revealed that RE-1 silencing factor (REST), Yin-Yang1 (YY1) and five other proteins have one or two of these CP2-binding motifs. Glutathione S-transferase pull-down and coimmunoprecipitation assays showed that two HXPR motif-containing proteins REST and YY1 indeed were able to bind CP2. Importantly, this binding to CP2 was almost abolished when a double amino acid substitution was made on the HXPR sequence of REST and YY1 proteins. The suppressing effect of YY1 on CP2's transcriptional activity was lost by this point mutation on the HXPR sequence of YY1 and reduced by an HXPR-containing peptide, further supporting the interaction between CP2 and YY1 via the HXPR sequence. Mapping the sites on CP2 for interaction with the four distinct CP2-binding motifs revealed at least three different regions on CP2. This suggests that CP2 recognizes several distinct binding motifs by virtue of employing different regions, thus being able to interact with and regulate many cellular partners.

  2. KIT mutations confer a distinct gene expression signature in core binding factor leukaemia.

    PubMed

    Lück, Sonja C; Russ, Annika C; Du, Juan; Gaidzik, Verena; Schlenk, Richard F; Pollack, Jonathan R; Döhner, Konstanze; Döhner, Hartmut; Bullinger, Lars

    2010-03-01

    Core binding factor (CBF) leukaemias, characterized by either inv(16)(p13.1q22) or t(8;21)(q22;q22), constitute acute myeloid leukaemia (AML) subgroups with favourable prognosis. However, 40-50% of patients relapse, emphasizing the need for risk-adapted treatment approaches. In this regard, studying secondary genetic aberrations, such as mutations of the KIT gene, is of great interest, particularly as they can be targeted by receptor tyrosine kinase inhibitors (TKI). However, so far little is known about the biology underlying KIT-mutated CBF leukaemias. We analysed gene expression profiles of 83 CBF AML cases with known KIT mutation status in order to gain novel insights in KIT-mutated CBF pathogenesis. KIT-mutated cases were characterized by deregulation of genes belonging to the NFkB signalling complex suggesting impaired control of apoptosis. Notably, a subgroup of KIT wildtype cases was also characterized by the KIT mutation signature due to yet unknown aberrations. Our data suggest that this CBF leukaemia subgroup might profit from TKI therapy, however, the relevance of the KIT mutation-associated signature remains to be validated prior to clinical implementation. Nevertheless, the existence of such a signature supports the notion of relevant biological differences in CBF leukaemia and might serve as diagnostic tool in the future.

  3. Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease

    PubMed Central

    Steele, Andrew D.; Hutter, Gregor; Jackson, Walker S.; Heppner, Frank L.; Borkowski, Andrew W.; King, Oliver D.; Raymond, Gregory J.; Aguzzi, Adriano; Lindquist, Susan

    2008-01-01

    Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease ≈20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease. PMID:18757733

  4. Targeting N-cadherin through fibroblast growth factor receptor-4: distinct pathogenetic and therapeutic implications.

    PubMed

    Ezzat, Shereen; Zheng, Lei; Winer, Daniel; Asa, Sylvia L

    2006-11-01

    Several molecular aberrations have been implicated in the pathogenesis of pituitary tumors, but few have proven thus far to be of therapeutic value. Pituitary tumor-derived fibroblast growth factor receptor-4 (ptd-FGFR4) is an alternatively transcribed cytoplasmic isoform lacking most of the extracellular domain. This oncogene recapitulates the morphological features of human pituitary tumors in transgenic mice. To investigate the therapeutic potential of targeting ptd-FGFR4, we examined the impact of FGFR4 tyrosine kinase inhibition in xenografted mice. GH4 pituitary cells expressing ptd-FGFR4 develop into invasive tumors. Systemic treatment of mice bearing ptd-FGFR4 tumors with the FGFR-selective inhibitor PD173074 resulted in recovery of membranous N-cadherin staining and a significant reduction in tumor volume with less invasive growth behavior. Mutation of tyrosine Y754F in ptd-FGFR4 abrogated the effect of PD173074-mediated inhibition. The pivotal role of N-cadherin as a mediator of this pituitary cell growth was demonstrated by small interfering RNA mediated down-regulation, which promoted invasive growth in xenografted mice. To validate this model in primary human pituitary tumors, we examined the expression of ptd-FGFR4, N-cadherin, and clinical behavior. Loss of membranous N-cadherin correlated with cytoplasmic FGFR4 expression and with tumor invasiveness in surgically resected human pituitary tumors. Primary human pituitary tumor cells treated with PD173074 showed restoration of N-cadherin to the membrane with dephosphorylation of retinoblastoma protein. These data highlight the pathogenetic significance of N-cadherin misexpression and emphasize the importance of FGFR partnership in mediating its functions.

  5. Distinct receptors for insulin-like growth factor I in rat renal glomeruli and tubules

    SciTech Connect

    Pillion, D.J.; Haskell, J.F.; Meezan, E.

    1988-10-01

    Purified preparations of renal glomeruli and tubules were obtained by a procedure involving perfusion of rat kidneys with magnetic iron oxide particles to selectively separate the iron-containing glomeruli from the nonmagnetic tubules. Detergent-soluble extracts of both renal glomerular and tubular membranes showed high-affinity, specific binding of 125I-labeled insulin-like growth factor I (125I-IGF-I), whereas degradation of this peptide hormone was minimal during a 90-min incubation at 22 degrees C in the presence of 2.5 mM EDTA and 5 mM N-ethylmaleimide. The affinity of these receptors for IGF-I appeared identical in the two types of renal tissue, since 50% inhibition of 125I-IGF-I binding to both glomerular and tubular tissue occurred in the presence of approximately 3 x 10(-9) M unlabeled IGF-I. In contrast, insulin was much less effective at blocking 125I-IGF-I binding to either tissue, with 1 x 10(-6) M insulin required to produce 50% inhibition of binding. Relative to 125I-IGF-I binding, 125I-insulin binding to glomerular and tubular tissue was significantly lower per milligram protein. 125I-IGF-I was specifically cross-linked to a glomerular receptor subunit that migrated as two discrete bands with relative molecular weight (Mr) of 140,000-150,000 on sodium dodecyl sulfate polyacrylamide gels in the presence of 40 mM dithiothreitol. In contrast, 125I-IGF-I was cross-linked to a tubular receptor subunit that migrated as two discrete bands but at a slightly different position, with Mr of 120,000-140,000.

  6. Constrained positive matrix factorization: Elemental ratios, spatial distinction, and chemical transport model source contributions

    NASA Astrophysics Data System (ADS)

    Sturtz, Timothy M.

    Source apportionment models attempt to untangle the relationship between pollution sources and the impacts at downwind receptors. Two frameworks of source apportionment models exist: source-oriented and receptor-oriented. Source based apportionment models use presumed emissions and atmospheric processes to estimate the downwind source contributions. Conversely, receptor based models leverage speciated concentration data from downwind receptors and apply statistical methods to predict source contributions. Integration of both source-oriented and receptor-oriented models could lead to a better understanding of the implications sources have on the environment and society. The research presented here investigated three different types of constraints applied to the Positive Matrix Factorization (PMF) receptor model within the framework of the Multilinear Engine (ME-2): element ratio constraints, spatial separation constraints, and chemical transport model (CTM) source attribution constraints. PM10-2.5 mass and trace element concentrations were measured in Winston-Salem, Chicago, and St. Paul at up to 60 sites per city during two different seasons in 2010. PMF was used to explore the underlying sources of variability. Information on previously reported PM10-2.5 tire and brake wear profiles were used to constrain these features in PMF by prior specification of selected species ratios. We also modified PMF to allow for combining the measurements from all three cities into a single model while preserving city-specific soil features. Relatively minor differences were observed between model predictions with and without the prior ratio constraints, increasing confidence in our ability to identify separate brake wear and tire wear features. Using separate data, source contributions to total fine particle carbon predicted by a CTM were incorporated into the PMF receptor model to form a receptor-oriented hybrid model. The level of influence of the CTM versus traditional PMF was

  7. Interactions between lower urinary tract symptoms and cardiovascular risk factors determine distinct patterns of erectile dysfunction: a latent class analysis.

    PubMed

    Barbosa, João A B A; Muracca, Eduardo; Nakano, Élcio; Assalin, Adriana R; Cordeiro, Paulo; Paranhos, Mario; Cury, José; Srougi, Miguel; Antunes, Alberto A

    2013-12-01

    dysfunction. Applying a risk factor interaction model to prospective trials could reveal distinct classes of drug responses and help define optimal treatment strategies for specific groups. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Distinct Stromal Cell Factor Combinations Can Separately Control Hematopoietic Stem Cell Survival, Proliferation, and Self-Renewal

    PubMed Central

    Wohrer, Stefan; Knapp, David J.H.F.; Copley, Michael R.; Benz, Claudia; Kent, David G.; Rowe, Keegan; Babovic, Sonja; Mader, Heidi; Oostendorp, Robert A.J.; Eaves, Connie J.

    2014-01-01

    Summary Hematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation, and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential are variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings point to the molecular basis of HSC control and expansion. PMID:24910437

  9. Involuntary mass spirit possession among the Miskitu.

    PubMed

    Wedel, Johan

    2012-01-01

    This paper seeks to understand the outbreaks and the development of grisi siknis, a form of mass spirit possession among the Miskitu of north-eastern Nicaragua. Earlier documented outbreaks typically involved a few adolescents, however, in recent years, violent large-scale epidemics have taken place, involving many people of all ages. This has coincided with recent developments in Miskitu society marked by conflicts, contradictions and tense social relations. The anthropological field technique of participant-observation was used. The research took place during 11 months from 2005 to 2008 in the port town of Puerto Cabezas. A total of 38 informants were interviewed. Group discussions, narratives and informal and semi-structured interviews were carried out, as well as participation in healing rituals. The paper shows that socio-economic, cultural, personal as well as environmental factors all contribute to outbreaks of grisi siknis. The affliction has previously been considered a 'culture-bound syndrome' only occurring among the Miskitu. However, when viewed in a more contemporary context and cross-cultural perspective, grisi siknis shows similarities with other forms of involuntary mass spirit possession, particularly in the ways it is manifested, experienced and appears to be spreading. The paper argues that the phenomenon should no longer be considered a 'culture-bound condition' but in fact a Miskitu version of involuntary mass spirit possession. Further research that seeks to understand other forms of involuntary mass spirit possession should emphasize the social, personal and environmental context as well as cross-cultural comparisons in order to encompass fully the role of culture in relation to illness and suffering.

  10. Two distinct types of neuronal asymmetries are controlled by the Caenorhabditis elegans zinc finger transcription factor die-1

    PubMed Central

    Cochella, Luisa; Tursun, Baris; Hsieh, Yi-Wen; Galindo, Samantha; Johnston, Robert J.; Chuang, Chiou-Fen; Hobert, Oliver

    2014-01-01

    Left/right asymmetric features of animals are either randomly distributed on either the left or right side within a population (“antisymmetries”) or found stereotypically on one particular side of an animal (“directional asymmetries”). Both types of asymmetries can be found in nervous systems, but whether the regulatory programs that establish these asymmetries share any mechanistic features is not known. We describe here an unprecedented molecular link between these two types of asymmetries in Caenorhabditis elegans. The zinc finger transcription factor die-1 is expressed in a directionally asymmetric manner in the gustatory neuron pair ASE left (ASEL) and ASE right (ASER), while it is expressed in an antisymmetric manner in the olfactory neuron pair AWC left (AWCL) and AWC right (AWCR). Asymmetric die-1 expression is controlled in a fundamentally distinct manner in these two neuron pairs. Importantly, asymmetric die-1 expression controls the directionally asymmetric expression of gustatory receptor proteins in the ASE neurons and the antisymmetric expression of olfactory receptor proteins in the AWC neurons. These asymmetries serve to increase the ability of the animal to discriminate distinct chemosensory inputs. PMID:24361693

  11. Two distinct types of neuronal asymmetries are controlled by the Caenorhabditis elegans zinc finger transcription factor die-1.

    PubMed

    Cochella, Luisa; Tursun, Baris; Hsieh, Yi-Wen; Galindo, Samantha; Johnston, Robert J; Chuang, Chiou-Fen; Hobert, Oliver

    2014-01-01

    Left/right asymmetric features of animals are either randomly distributed on either the left or right side within a population ("antisymmetries") or found stereotypically on one particular side of an animal ("directional asymmetries"). Both types of asymmetries can be found in nervous systems, but whether the regulatory programs that establish these asymmetries share any mechanistic features is not known. We describe here an unprecedented molecular link between these two types of asymmetries in Caenorhabditis elegans. The zinc finger transcription factor die-1 is expressed in a directionally asymmetric manner in the gustatory neuron pair ASE left (ASEL) and ASE right (ASER), while it is expressed in an antisymmetric manner in the olfactory neuron pair AWC left (AWCL) and AWC right (AWCR). Asymmetric die-1 expression is controlled in a fundamentally distinct manner in these two neuron pairs. Importantly, asymmetric die-1 expression controls the directionally asymmetric expression of gustatory receptor proteins in the ASE neurons and the antisymmetric expression of olfactory receptor proteins in the AWC neurons. These asymmetries serve to increase the ability of the animal to discriminate distinct chemosensory inputs.

  12. Spatial isolation and environmental factors drive distinct bacterial and archaeal communities in different types of petroleum reservoirs in China

    NASA Astrophysics Data System (ADS)

    Gao, Peike; Tian, Huimei; Wang, Yansen; Li, Yanshu; Li, Yan; Xie, Jinxia; Zeng, Bing; Zhou, Jiefang; Li, Guoqiang; Ma, Ting

    2016-02-01

    To investigate the spatial distribution of microbial communities and their drivers in petroleum reservoir environments, we performed pyrosequencing of microbial partial 16S rRNA, derived from 20 geographically separated water-flooding reservoirs, and two reservoirs that had not been flooded, in China. The results indicated that distinct underground microbial communities inhabited the different reservoirs. Compared with the bacteria, archaeal alpha-diversity was not strongly correlated with the environmental variables. The variation of the bacterial and archaeal community compositions was affected synthetically, by the mining patterns, spatial isolation, reservoir temperature, salinity and pH of the formation brine. The environmental factors explained 64.22% and 78.26% of the total variance for the bacterial and archaeal communities, respectively. Despite the diverse community compositions, shared populations (48 bacterial and 18 archaeal genera) were found and were dominant in most of the oilfields. Potential indigenous microorganisms, including Carboxydibrachium, Thermosinus, and Neptunomonas, were only detected in a reservoir that had not been flooded with water. This study indicates that: 1) the environmental variation drives distinct microbial communities in different reservoirs; 2) compared with the archaea, the bacterial communities were highly heterogeneous within and among the reservoirs; and 3) despite the community variation, some microorganisms are dominant in multiple petroleum reservoirs.

  13. Spatial isolation and environmental factors drive distinct bacterial and archaeal communities in different types of petroleum reservoirs in China

    PubMed Central

    Gao, Peike; Tian, Huimei; Wang, Yansen; Li, Yanshu; Li, Yan; Xie, Jinxia; Zeng, Bing; Zhou, Jiefang; Li, Guoqiang; Ma, Ting

    2016-01-01

    To investigate the spatial distribution of microbial communities and their drivers in petroleum reservoir environments, we performed pyrosequencing of microbial partial 16S rRNA, derived from 20 geographically separated water-flooding reservoirs, and two reservoirs that had not been flooded, in China. The results indicated that distinct underground microbial communities inhabited the different reservoirs. Compared with the bacteria, archaeal alpha-diversity was not strongly correlated with the environmental variables. The variation of the bacterial and archaeal community compositions was affected synthetically, by the mining patterns, spatial isolation, reservoir temperature, salinity and pH of the formation brine. The environmental factors explained 64.22% and 78.26% of the total variance for the bacterial and archaeal communities, respectively. Despite the diverse community compositions, shared populations (48 bacterial and 18 archaeal genera) were found and were dominant in most of the oilfields. Potential indigenous microorganisms, including Carboxydibrachium, Thermosinus, and Neptunomonas, were only detected in a reservoir that had not been flooded with water. This study indicates that: 1) the environmental variation drives distinct microbial communities in different reservoirs; 2) compared with the archaea, the bacterial communities were highly heterogeneous within and among the reservoirs; and 3) despite the community variation, some microorganisms are dominant in multiple petroleum reservoirs. PMID:26838035

  14. Spatial isolation and environmental factors drive distinct bacterial and archaeal communities in different types of petroleum reservoirs in China.

    PubMed

    Gao, Peike; Tian, Huimei; Wang, Yansen; Li, Yanshu; Li, Yan; Xie, Jinxia; Zeng, Bing; Zhou, Jiefang; Li, Guoqiang; Ma, Ting

    2016-02-03

    To investigate the spatial distribution of microbial communities and their drivers in petroleum reservoir environments, we performed pyrosequencing of microbial partial 16S rRNA, derived from 20 geographically separated water-flooding reservoirs, and two reservoirs that had not been flooded, in China. The results indicated that distinct underground microbial communities inhabited the different reservoirs. Compared with the bacteria, archaeal alpha-diversity was not strongly correlated with the environmental variables. The variation of the bacterial and archaeal community compositions was affected synthetically, by the mining patterns, spatial isolation, reservoir temperature, salinity and pH of the formation brine. The environmental factors explained 64.22% and 78.26% of the total variance for the bacterial and archaeal communities, respectively. Despite the diverse community compositions, shared populations (48 bacterial and 18 archaeal genera) were found and were dominant in most of the oilfields. Potential indigenous microorganisms, including Carboxydibrachium, Thermosinus, and Neptunomonas, were only detected in a reservoir that had not been flooded with water. This study indicates that: 1) the environmental variation drives distinct microbial communities in different reservoirs; 2) compared with the archaea, the bacterial communities were highly heterogeneous within and among the reservoirs; and 3) despite the community variation, some microorganisms are dominant in multiple petroleum reservoirs.

  15. Distinct Growth Factor Families Are Recruited in Unique Spatiotemporal Domains during Long-Term Memory Formation in Aplysia californica.

    PubMed

    Kopec, Ashley M; Philips, Gary T; Carew, Thomas J

    2015-06-03

    Several growth factors (GFs) have been implicated in long-term memory (LTM), but no single GF can support all of the plastic changes that occur during memory formation. Because GFs engage highly convergent signaling cascades that often mediate similar functional outcomes, the relative contribution of any particular GF to LTM is difficult to ascertain. To explore this question, we determined the unique contribution of distinct GF families (signaling via TrkB and TGF-βr-II) to LTM formation in Aplysia. We demonstrate that TrkB and TGF-βr-II signaling are differentially recruited during two-trial training in both time (by trial 1 or 2, respectively) and space (in distinct subcellular compartments). These GFs independently regulate MAPK activation and synergistically regulate gene expression. We also show that trial 1 TrkB and trial 2 TGF-βr-II signaling are required for LTM formation. These data support the view that GFs engaged in LTM formation are interactive components of a complex molecular network.

  16. Conserved interaction between distinct Krüppel-associated box domains and the transcriptional intermediary factor 1 β

    PubMed Central

    Abrink, Magnus; Ortiz, José A.; Mark, Charlotta; Sanchez, Cecilia; Looman, Camilla; Hellman, Lars; Chambon, Pierre; Losson, Régine

    2001-01-01

    The Krüppel-associated box (KRAB) domain, originally identified as a 75-aa sequence present in numerous Krüppel-type zinc-finger proteins, is a potent DNA-binding-dependent transcriptional repression domain that is believed to function through interaction with the transcriptional intermediary factor 1 (TIF1) β. On the basis of sequence comparison and phylogenetic analysis, we have recently defined three distinct subfamilies of KRAB domains. In the present study, individual members of each subfamily were tested for transcriptional repression and interaction with TIF1β and two other closely related family members (TIF1α and TIF1γ). All KRAB variants were shown, (i) to repress transcription when targeted to DNA through fusion to a heterologous DNA-binding domain in mammalian cells, and (ii) to interact specifically with TIF1β, but not with TIF1α or TIF1γ. Taken together, these results implicate TIF1β as a common transcriptional corepressor for the three distinct subfamilies of KRAB zinc-finger proteins and suggest a high degree of conservation in the molecular mechanism underlying their transcriptional repression activity. PMID:11171966

  17. A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases

    PubMed Central

    Quezada, Cindy M.; Hicks, Stuart W.; Galán, Jorge E.; Stebbins, C. Erec

    2009-01-01

    Processes as diverse as receptor binding and signaling, cytoskeletal dynamics, and programmed cell death are manipulated by mimics of host proteins encoded by pathogenic bacteria. We show here that the Salmonella virulence factor SspH2 belongs to a growing class of bacterial effector proteins that harness and subvert the eukaryotic ubiquitination pathway. This virulence protein possesses ubiquitination activity that depends on a conserved cysteine residue. A crystal structure of SspH2 reveals a canonical leucine-rich repeat (LRR) domain that interacts with a unique E3 ligase [which we have termed NEL for Novel E3 Ligase] C-terminal fold unrelated to previously observed HECT or RING-finger E3 ligases. Moreover, the LRR domain sequesters the catalytic cysteine residue contained in the NEL domain, and we suggest a mechanism for activation of the ligase requiring a substantial conformational change to release the catalytic domain for function. We also show that the N-terminal domain targets SspH2 to the apical plasma membrane of polarized epithelial cells and propose a model whereby binding of the LRR to proteins at the target site releases the ligase domain for site-specific function. PMID:19273841

  18. A Family of Salmonella Virulence Factors Functions as a Distinct Class of Autoregulated E3 Ubiquitin Ligases

    SciTech Connect

    Quezada, C.; Hicks, S; Galan, J; Stebbins, C

    2009-01-01

    Processes as diverse as receptor binding and signaling, cytoskeletal dynamics, and programmed cell death are manipulated by mimics of host proteins encoded by pathogenic bacteria. We show here that the Salmonella virulence factor SspH2 belongs to a growing class of bacterial effector proteins that harness and subvert the eukaryotic ubiquitination pathway. This virulence protein possesses ubiquitination activity that depends on a conserved cysteine residue. A crystal structure of SspH2 reveals a canonical leucine-rich repeat (LRR) domain that interacts with a unique E{sub 3} ligase [which we have termed NEL for Novel E{sub 3} Ligase] C-terminal fold unrelated to previously observed HECT or RING-finger E{sub 3} ligases. Moreover, the LRR domain sequesters the catalytic cysteine residue contained in the NEL domain, and we suggest a mechanism for activation of the ligase requiring a substantial conformational change to release the catalytic domain for function. We also show that the N-terminal domain targets SspH2 to the apical plasma membrane of polarized epithelial cells and propose a model whereby binding of the LRR to proteins at the target site releases the ligase domain for site-specific function.

  19. Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family.

    PubMed

    Dai, Qi; Ren, Aiming; Westholm, Jakub O; Duan, Hong; Patel, Dinshaw J; Lai, Eric C

    2015-01-01

    Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain ("BEN-solo" factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional

  20. Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family

    PubMed Central

    Dai, Qi; Ren, Aiming; Westholm, Jakub O.; Duan, Hong; Patel, Dinshaw J.

    2015-01-01

    Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain (“BEN-solo” factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional

  1. 50 CFR 648.125 - Possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession limit. 648.125 Section 648.125... § 648.125 Possession limit. (a) No person shall possess more than 10 scup in, or harvested from, the EEZ... moratorium permit are subject to this possession limit. The owner, operator, and crew of a charter or party...

  2. 50 CFR 648.145 - Possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession limit. 648.145 Section 648.145... Fishery § 648.145 Possession limit. (a) No person shall possess more than 25 black sea bass, in, or... that is not eligible for a black sea bass moratorium permit are subject to this possession limit. The...

  3. Pressure-overload cardiac hypertrophy is associated with distinct alternative splicing due to altered expression of splicing factors.

    PubMed

    Kim, Taeyong; Kim, Jin Ock; Oh, Jae Gyun; Hong, Seong-Eui; Kim, Do Han

    2014-01-01

    Chronic pressure-overload cardiac hypertrophy is associated with an increased risk of morbidity/mortality, largely due to maladaptive remodeling and dilatation that progresses to dilated cardiomyopathy. Alternative splicing is an important biological mechanism that generates proteomic complexity and diversity. The recent development of next-generation RNA sequencing has improved our understanding of the qualitative signatures associated with alternative splicing in various biological conditions. However, the role of alternative splicing in cardiac hypertrophy is yet unknown. The present study employed RNA-Seq and a bioinformatic approach to detect the RNA splicing regulatory elements involved in alternative splicing during pressure-overload cardiac hypertrophy. We found GC-rich exonic motifs that regulate intron retention in 5' UTRs and AT-rich exonic motifs that are involved in exclusion of the AT-rich elements that cause mRNA instability in 3' UTRs. We also identified motifs in the intronic regions involved in exon exclusion and inclusion, which predicted splicing factors that bind to these motifs. We found, through Western blotting, that the expression levels of three splicing factors, ESRP1, PTB and SF2/ASF, were significantly altered during cardiac hypertrophy. Collectively, the present results suggest that chronic pressure-overload hypertrophy is closely associated with distinct alternative splicing due to altered expression of splicing factors.

  4. Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-kappa B response element

    SciTech Connect

    Nagasaki, Haruka; Yoshimura, Takeshi; Aoki, Naohito

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Inflammation status in adipocytes can be monitored by the new assay system. Black-Right-Pointing-Pointer Only an aliquot of conditioned medium is required without cell lysis. Black-Right-Pointing-Pointer Inflammation-attenuating compounds can be screened more conveniently. -- Abstract: We have established 3T3-L1 cells possessing a secretory Gaussia luciferase (GLuc) gene under the control of nuclear factor-kappa B (NF-{kappa}B) response element. The 3T3-L1 cells named 3T3-L1-NF-{kappa}B-RE-GLuc could differentiate into adipocyte as comparably as parental 3T3-L1 cells. Inflammatory cytokines such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-1{beta} induced GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes in a concentration- and time-dependent manner. GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes was also induced when cultured with RAW264.7 macrophages and was dramatically enhanced by lipopolysaccharide (LPS)-activated macrophages. An NF-{kappa}B activation inhibitor BAY-11-7085 and an antioxidant N-acetyl cysteine significantly suppressed GLuc secretion induced by macrophages. Finally, we found that rosemary-derived carnosic acid strongly suppressed GLuc secretion induced by macrophages and on the contrary up-regulated adiponectin secretion. Collectively, by using 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes, inflammation status can be monitored in real time and inflammation-attenuating compounds can be screened more conveniently.

  5. Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells.

    PubMed

    Goodall, Jane; Carreira, Suzanne; Denat, Laurence; Kobi, Dominique; Davidson, Irwin; Nuciforo, Paolo; Sturm, Richard A; Larue, Lionel; Goding, Colin R

    2008-10-01

    The origin of tumor heterogeneity is poorly understood, yet it represents a major barrier to effective therapy. In melanoma and in melanocyte development, the microphthalmia-associated transcription factor (Mitf) controls survival, differentiation, proliferation, and migration/metastasis. The Brn-2 (N-Oct-3, POU3F2) transcription factor also regulates melanoma proliferation and is up-regulated by BRAF and beta-catenin, two key melanoma-associated signaling molecules. Here, we show that Brn-2 also regulates invasiveness and directly represses Mitf expression. Remarkably, in melanoma biopsies, Mitf and Brn-2 each mark a distinct subpopulation of melanoma cells, providing a striking illustration of melanoma tumor heterogeneity with implications for melanoma therapy.

  6. MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II

    PubMed Central

    Pannu, Hariyadarshi; Tran-Fadulu, Van; Papke, Christina L.; Scherer, Steve; Liu, Yaozhong; Presley, Caroline; Guo, Dongchuan; Estrera, Anthony L.; Safi, Hazim J.; Brasier, Allan R.; Vick, G. Wesley; Marian, A.J.; Raman, C.S.; Buja, L. Maximilian; Milewicz, Dianna M.

    2010-01-01

    Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in ~20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone and three families with TAAD/PDA, we identified novel mutations in two families with TAAD/PDA, but none in families with TAAD alone. Histopathological analysis of aortic sections from two individuals with MYH11 mutations revealed SMC disarray and focal hyperplasia of SMCs in the aortic media. SMC hyperplasia leading to significant lumen narrowing in some of the vessels of the adventitia was also observed. Insulin-like growth factor-1 (IGF-1) was upregulated in mutant aortas as well as explanted SMCs, but no increase in transforming growth factor-β expression or downstream targets was observed. Enhanced expression of angiotensin-converting enzyme and markers of Angiotensin II (Ang II) vascular inflammation (macrophage inflammatory protein-1α and β) were also found. These data suggest that MYH11 mutations are likely to be specific to the phenotype of TAAD/PDA and result in a distinct aortic and occlusive vascular pathology potentially driven by IGF-1 and Ang II. PMID:17666408

  7. Distinct Roles for Interfacial Hydration in Site-Specific DNA Recognition by ETS-Family Transcription Factors.

    PubMed

    Xhani, Suela; Esaki, Shingo; Huang, Kenneth; Erlitzki, Noa; Poon, Gregory M K

    2017-04-06

    The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. Unlike other ETS homologues, such as Ets-1, DNA recognition by PU.1 is highly sensitive to its osmotic environment due to excess interfacial hydration in the complex. To investigate interfacial hydration in the two homologues, we mutated a conserved tyrosine residue, which is exclusively engaged in coordinating a well-defined water contact between the protein and DNA among ETS proteins, to phenylalanine. The loss of this water-mediated contact blunted the osmotic sensitivity of PU.1/DNA binding, but did not alter binding under normo-osmotic conditions, suggesting that PU.1 has evolved to maximize osmotic sensitivity. The homologous mutation in Ets-1, which was minimally sensitive to osmotic stress due to a sparsely hydrated interface, reduced DNA-binding affinity at normal osmolality but the complex became stabilized by osmotic stress. Molecular dynamics simulations of wildtype and mutant PU.1 and Ets-1 in their free and DNA-bound states, which recapitulated experimental features of the proteins, showed that abrogation of this tyrosine-mediated water contact perturbed the Ets-1/DNA complex not through disruption of interfacial hydration, but by inhibiting local dynamics induced specifically in the bound state. Thus, a configurationally identical water-mediated contact plays mechanistically distinct roles in mediating DNA recognition by structurally homologous ETS transcription factors.

  8. Three R2R3-MYB Transcription Factors Regulate Distinct Floral Pigmentation Patterning in Phalaenopsis spp.1[OPEN

    PubMed Central

    Hsu, Chia-Chi; Chen, You-Yi; Tsai, Wen-Chieh; Chen, Wen-Huei; Chen, Hong-Hwa

    2015-01-01

    Orchidaceae are well known for their fascinating floral morphologic features, specialized pollination, and distinctive ecological strategies. With their long-lasting flowers of various colors and pigmentation patterning, Phalaenopsis spp. have become important ornamental plants worldwide. In this study, we identified three R2R3-MYB transcription factors PeMYB2, PeMYB11, and PeMYB12. Their expression profiles were concomitant with red color formation in Phalaenopsis spp. flowers. Transient assay of overexpression of three PeMYBs verified that PeMYB2 resulted in anthocyanin accumulation, and these PeMYBs could activate the expression of three downstream structural genes Phalaenopsis spp. Flavanone 3-hydroxylase5, Phalaenopsis spp. Dihydroflavonol 4-reductase1, and Phalaenopsis spp. Anthocyanidin synthase3. In addition, these three PeMYBs participated in the distinct pigmentation patterning in a single flower, which was revealed by virus-induced gene silencing. In the sepals/petals, silencing of PeMYB2, PeMYB11, and PeMYB12 resulted in the loss of the full-red pigmentation, red spots, and venation patterns, respectively. Moreover, different pigmentation patterning was regulated by PeMYBs in the sepals/petals and lip. PeMYB11 was responsive to the red spots in the callus of the lip, and PeMYB12 participated in the full pigmentation in the central lobe of the lip. The differential pigmentation patterning was validated by RNA in situ hybridization. Additional assessment was performed in six Phalaenopsis spp. cultivars with different color patterns. The combined expression of these three PeMYBs in different ratios leads to a wealth of complicated floral pigmentation patterning in Phalaenopsis spp. PMID:25739699

  9. Non-additive interactions involving two distinct elements mediate sloppy-paired regulation by pair-rule transcription factors

    PubMed Central

    Prazak, Lisa; Fujioka, Miki; Gergen, J. Peter

    2010-01-01

    The relatively simple combinatorial rules responsible for establishing the initial metameric expression of sloppy-paired-1 (slp1) in the Drosophila blastoderm embryo make this system an attractive model for investigating the mechanism of regulation by pair rule transcription factors. This investigation of slp1 cis-regulatory architecture identifies two distinct elements, a proximal early stripe element (PESE) and a distal early stripe element (DESE) located from −3.1 kb to −2.5 kb and from −8.1 kb to −7.1 kb upstream of the slp1 promoter, respectively, that mediate this early regulation. The proximal element expresses only even-numbered stripes and mediates repression by Even-skipped (Eve) as well as by the combination of Runt and Fushi-tarazu (Ftz). A 272 basepair sub-element of PESE retains Eve-dependent repression, but is expressed throughout the even-numbered parasegments due to the loss of repression by Runt and Ftz. In contrast, the distal element expresses both odd and even-numbered stripes and also drives inappropriate expression in the anterior half of the odd-numbered parasegments due to an inability to respond to repression by Eve. Importantly, a composite reporter gene containing both early stripe elements recapitulates pair-rule gene-dependent regulation in a manner beyond what is expected from combining their individual patterns. These results indicate interactions involving distinct cis-elements contribute to the proper integration of pair-rule regulatory information. A model fully accounting for these results proposes that metameric slp1 expression is achieved through the Runt-dependent regulation of interactions between these two pair-rule response elements and the slp1 promoter. PMID:20435028

  10. The CXC Chemokine Receptor 4 Ligands Ubiquitin and Stromal Cell-derived Factor-1α Function through Distinct Receptor Interactions*

    PubMed Central

    Saini, Vikas; Staren, Daniel M.; Ziarek, Joshua J.; Nashaat, Zayd N.; Campbell, Edward M.; Volkman, Brian F.; Marchese, Adriano; Majetschak, Matthias

    2011-01-01

    Recently, we identified extracellular ubiquitin as an endogenous CXC chemokine receptor (CXCR) 4 agonist. However, the receptor selectivity and molecular basis of the CXCR4 agonist activity of ubiquitin are unknown, and functional consequences of CXCR4 activation with ubiquitin are poorly defined. Here, we provide evidence that ubiquitin and the cognate CXCR4 ligand stromal cell-derived factor (SDF)-1α do not share CXCR7 as a receptor. We further demonstrate that ubiquitin does not utilize the typical two-site binding mechanism of chemokine-receptor interactions, in which the receptor N terminus is important for ligand binding. CXCR4 activation with ubiquitin and SDF-1α lead to similar Gαi-responses and to a comparable magnitude of phosphorylation of ERK-1/2, p90 ribosomal S6 kinase-l and Akt, although phosphorylations occur more transiently after activation with ubiquitin. Despite the similarity of signal transduction events after activation of CXCR4 with both ligands, ubiquitin possesses weaker chemotactic activity than SDF-lα in cell migration assays and does not interfere with productive entry of HIV-1 into P4.R5 multinuclear activation of galactosidase indicator cells. Unlike SDF-1α, ubiquitin lacks interactions with an N-terminal CXCR4 peptide in NMR spectroscopy experiments. Binding and signaling studies in the presence of antibodies against the N terminus and extracellular loops 2/3 of CXCR4 confirm that the ubiquitin CXCR4 interaction is independent of the N-terminal receptor domain, whereas blockade of extracellular loops 2/3 prevents receptor binding and activation. Our findings define ubiquitin as a CXCR4 agonist, which does not interfere with productive cellular entry of HIV-1, and provide new mechanistic insights into interactions between CXCR4 and its natural ligands. PMID:21757744

  11. Distinct Contributory Factors Determine Basophil-Allergen Sensitivity in Grass Pollen Rhinitis and in Anaphylactic Wasp Venom Allergy.

    PubMed

    Korošec, Peter; Šilar, Mira; Kopač, Peter; Eržen, Renato; Zidarn, Mihaela; Košnik, Mitja

    2016-01-01

    We sought to determine whether basophil-allergen sensitivity could be transferred to donor basophils by passive IgE sensitisation in allergic rhinitis and anaphylactic Hymenoptera venom hypersensitivity. We studied 15 wasp venom-, 19 grass pollen- and 2 house dust mite-allergic patients, 2 healthy donors, and 8 wasp venom-allergic donors. In all subjects, we first evaluated the initial basophil response to wasp venom, grass pollen, or house dust mite allergen. Donor basophils were then stripped, sensitised with the different patients' serum IgE, and challenged with the corresponding allergen. The CD63 response of donor basophils was then compared with initial basophil responses. In wasp venom-allergic subjects, the IgE transfer did not reflect the initial basophil-allergen sensitivity, because the venom IgE of subjects with high or low basophil sensitivity induced comparable responsiveness in healthy donor basophils. Furthermore, vice versa, when we sensitised the donor basophils of wasp venom-allergic individuals with different wasp venom or house dust mite IgE, we demonstrated that their response was predictable by their initial basophil allergen sensitivity. In the rhinitis allergy model, the IgE transfer correlated with the patients' initial basophil responsiveness because the grass pollen IgE of the subjects with high basophil allergen sensitivity induced significantly higher responsiveness of donor basophils than the IgE of subjects with initially low basophil allergen sensitivity. Our results suggest that basophil allergen sensitivity evaluated by flow-cytometric CD63 analysis depends on two distinct contribution factors. In anaphylactic Hymenoptera allergy, the major factor was intrinsic cellular sensitivity, whereas in pollen allergy, the major factor was allergen-specific IgE on the cell surface. © 2016 S. Karger AG, Basel.

  12. The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing.

    PubMed

    Tanikawa, M; Sanjiv, K; Helleday, T; Herr, P; Mortusewicz, O

    2016-12-19

    Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress.

  13. The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing

    PubMed Central

    Tanikawa, M; Sanjiv, K; Helleday, T; Herr, P; Mortusewicz, O

    2016-01-01

    Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress. PMID:27991914

  14. A Novel Approach to Identify Two Distinct Receptor Binding Surfaces of Insulin-like Growth Factor II*S⃞

    PubMed Central

    Alvino, Clair L.; McNeil, Kerrie A.; Ong, Shee Chee; Delaine, Carlie; Booker, Grant W.; Wallace, John C.; Whittaker, Jonathan; Forbes, Briony E.

    2009-01-01

    Very little is known about the residues important for the interaction of insulin-like growth factor II (IGF-II) with the type 1 IGF receptor (IGF-1R) and the insulin receptor (IR). Insulin, to which IGF-II is homologous, is proposed to cross-link opposite halves of the IR dimer through two receptor binding surfaces, site 1 and site 2. In the present study we have analyzed the contribution of IGF-II residues equivalent to insulin's two binding surfaces toward the interaction of IGF-II with the IGF-1R and IR. Four “site 1” and six “site 2” analogues were produced and analyzed in terms of IGF-1R and IR binding and activation. The results show that Val43, Phe28, and Val14 (equivalent to site 1) are critical to IGF-1R and IR binding, whereas mutation to alanine of Gln18 affects only IGF-1R and not IR binding. Alanine substitutions at Glu12, Asp15, Phe19, Leu53, and Glu57 analogues resulted in significant (>2-fold) decreases in affinity for both the IGF-1R and IR. Furthermore, taking a novel approach using a monomeric, single-chain minimized IGF-1R we have defined a distinct second binding surface formed by Glu12, Phe19, Leu53, and Glu57 that potentially engages the IGF-1R at one or more of the FnIII domains. PMID:19139090

  15. Yeast silencing factor Sir4 and a subset of nucleoporins form a complex distinct from nuclear pore complexes.

    PubMed

    Lapetina, Diego L; Ptak, Christopher; Roesner, Ulyss K; Wozniak, Richard W

    2017-10-02

    Interactions occurring at the nuclear envelope (NE)-chromatin interface influence both NE structure and chromatin organization. Insights into the functions of NE-chromatin interactions have come from the study of yeast subtelomeric chromatin and its association with the NE, including the identification of various proteins necessary for tethering subtelomeric chromatin to the NE and the silencing of resident genes. Here we show that four of these proteins-the silencing factor Sir4, NE-associated Esc1, the SUMO E3 ligase Siz2, and the nuclear pore complex (NPC) protein Nup170-physically and functionally interact with one another and a subset of NPC components (nucleoporins or Nups). Importantly, this group of Nups is largely restricted to members of the inner and outer NPC rings, but it lacks numerous others including cytoplasmically and nucleoplasmically positioned Nups. We propose that this Sir4-associated Nup complex is distinct from holo-NPCs and that it plays a role in subtelomeric chromatin organization and NE tethering. © 2017 Lapetina et al.

  16. Distinct Roles for Lymphotoxin-α and Tumor Necrosis Factor in the Control of Leishmania donovani Infection

    PubMed Central

    Engwerda, Christian R.; Ato, Manabu; Stäger, Simona; Alexander, Clare E.; Stanley, Amanda C.; Kaye, Paul M.

    2004-01-01

    Tumor necrosis factor (TNF) is critical for the control of visceral leishmaniasis caused by Leishmania donovani. However, the role of the related cytokine lymphotoxin (LT) α in this infection is unknown. Here we report that C57BL/6 mice deficient in TNF (B6.TNF−/−) or LTα (B6.LTα−/−) have increased susceptibility to hepatic L. donovani infection. Furthermore, the outcome of infection in bone marrow chimeric mice is dependent on donor hematopoietic cells, indicating that developmental defects in lymphoid organs were not responsible for increased susceptibility to L. donovani. Although both LTα and TNF regulated the migration of leukocytes into the sinusoidal area of the infected liver, their roles were distinct. LTα was essential for migration of leukocytes from periportal areas, an event consistent with LTα-dependent up-regulation of VCAM-1 on liver sinusoid lining cells, whereas TNF was essential for leukocyte recruitment to the liver. During visceral leishmaniasis, both cytokines were produced by radio-resistant cells and by CD4+ T cells. LTα and TNF production by the former was required for granuloma assembly, while production of these cytokines by CD4+ T cells was necessary to control parasite growth. The production of inducible nitric oxide synthase was also found to be deficient in TNF- and LTα-deficient infected mice. These results demonstrate that both LTα and TNF are required for control of L. donovani infection in noncompensatory ways. PMID:15579454

  17. Distinct Expression of Various Angiogenesis Factors in Mice Brain After Whole-Brain Irradiation by X-ray.

    PubMed

    Deng, Zhezhi; Huang, Haiwei; Wu, Xiaohong; Wu, Mengmeng; He, Guoyong; Guo, Junjie

    2017-02-01

    Radiation-induced brain injury (RBI) is the most serious complication after radiotherapy. However, the etiology of RBI remains elusive. In order to evaluate the effect of X-rays on normal brain tissue, adult male BALB/C mice were subjected to whole-brain exposure with a single dose of 10 Gy or sham radiation. The structure and number of mice brain vessels were investigated 1, 7, 30, 90 and 180 days after irradiation by H&E staining and immune-fluorescence staining. Compared with sham control mice, in addition to morphological changes, a significant reduction of microvascular density was detected in irradiated mice brains. Whole-brain irradiation also caused damage in tight junction (TJ). Increased expression of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was observed in irradiated mouse brains showed by Western Blot. Immune-fluorescence staining results also verified the co-labeling of GFAP and VEGF after whole-brain irradiation. Furthermore, the protein expression levels of other angiogenesis factors, angiopoietin-1 (Ang-1), endothelial-specific receptor tyrosine kinase (Tie-2), and angiopoietin-2 (Ang-2) in brain were determined by Western Blot. Increased expression of Ang-2 was shown in irradiated mouse brains. In contrast, whole-brain irradiation significantly decreased Ang-1 and Tie-2 expression. Our data indicated that X-rays induced time-dependent microvascular injury and activation of astrocytes after whole-brain irradiation in mouse brain. Distinct regulation of VEGF/Ang2 and Ang-1/Tie-2 are closely associated with RBI, suggesting that angiogenesis interventions might be beneficial for patients with RBI.

  18. 50 CFR 648.145 - Possession limit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Possession limit. 648.145 Section 648.145... Fishery § 648.145 Possession limit. Link to an amendment published at 76 FR 60638, Sept. 29, 2011. (a) No... bass moratorium permit are subject to this possession limit. The owner, operator, and crew of a charter...

  19. Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

    PubMed Central

    Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

    2010-01-01

    Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour. PMID:19653930

  20. Bacillus cereus enterotoxins act as major virulence factors and exhibit distinct cytotoxicity to different human cell lines.

    PubMed

    Jeßberger, Nadja; Dietrich, Richard; Bock, Stefanie; Didier, Andrea; Märtlbauer, Erwin

    2014-01-01

    A comparative analysis on the relevance of the Bacillus cereus enterotoxins Nhe (nonhemolytic enterotoxin), HBL (haemolysin BL) and CytK (cytotoxin K) was accomplished, concerning their toxic activity towards different target cell lines. Overall, among the components secreted by the reference strains for Nhe and HBL, the enterotoxin complexes accounted for over 90% of the total toxicity. Vero and primary endothelial cells (HUVEC) were highly susceptible to Nhe, whereas Hep-G2, Vero and A549 reacted most sensitive to Nhe plus HBL. For CytK the highest toxicity was observed on CaCo-2 cells. As HBL positive strains always produce Nhe in parallel, the specific contribution of both enterotoxin complexes to the overall observed cytotoxic effects was determined by consecutively removing their single components. While in most cell lines Nhe and HBL contributed more or less equally (40-60%) to cytotoxicity, the relative activity of Nhe was approximately 90% in HUVEC, and that of HBL 75% in A549 cells. With U937, a nearly Nhe resistant cell line was identified for the first time. This distinct susceptibility of cell lines was confirmed by investigating a set of 37 B. cereus strains. Interestingly, whereas Nhe is the enterotoxin mainly responsible for cell death as determined by WST-1 bioassays, more rapid pore formation was observed when HBL was present, pointing to a different mode of action of the two enterotoxin complexes. Furthermore, correlation was observed between cytotoxicity of solely Nhe producing strains and NheB. Cytotoxicity of Nhe/HBL producing isolates correlated with the expression of HBL L1, NheB and HBL B. In conclusion, the observed susceptibilities of target cell lines of different histological origin underline that B. cereus enterotoxins represent major virulence factors and that toxicity is not restricted to gastrointestinal infections. The varying contribution of Nhe and HBL to total cytotoxicity strongly indicates that Nhe as well as HBL specific B

  1. Phosphorylation of Williams syndrome transcription factor by MAPK induces a switching between two distinct chromatin remodeling complexes.

    PubMed

    Oya, Hiroyuki; Yokoyama, Atsushi; Yamaoka, Ikuko; Fujiki, Ryoji; Yonezawa, Masayoshi; Youn, Min-Young; Takada, Ichiro; Kato, Shigeaki; Kitagawa, Hirochika

    2009-11-20

    Changes in the environment of a cell precipitate extracellular signals and sequential cascades of protein modification and elicit nuclear transcriptional responses. However, the functional links between intracellular signaling-dependent gene regulation and epigenetic regulation by chromatin-modifying proteins within the nucleus are largely unknown. Here, we describe novel epigenetic regulation by MAPK cascades that modulate formation of an ATP-dependent chromatin remodeling complex, WINAC (WSTF Including Nucleosome Assembly Complex), an SWI/SNF-type complex containing Williams syndrome transcription factor (WSTF). WSTF, a specific component of two chromatin remodeling complexes (SWI/SNF-type WINAC and ISWI-type WICH), was phosphorylated by the stimulation of MAPK cascades in vitro and in vivo. Ser-158 residue in the WAC (WSTF/Acf1/cbpq46) domain, located close to the N terminus of WSTF, was identified as a major phosphorylation target. Using biochemical analysis of a WSTF mutant (WSTF-S158A) stably expressing cell line, the phosphorylation of this residue (Ser-158) was found to be essential for maintaining the association between WSTF and core BAF complex components, thereby maintaining the ATPase activity of WINAC. WINAC-dependent transcriptional regulation of vitamin D receptor was consequently impaired by this WSTF mutation, but the recovery from DNA damage mediated by WICH was not impaired. Our results suggest that WSTF serves as a nuclear sensor of the extracellular signals to fine-tune the chromatin remodeling activity of WINAC. WINAC mediates a previously unknown MAPK-dependent step in epigenetic regulation, and this MAPK-dependent switching mechanism between the two functionally distinct WSTF-containing complexes might underlie the diverse functions of WSTF in various nuclear events.

  2. HTLV-1 bZIP Factor RNA and Protein Impart Distinct Functions on T-cell Proliferation and Survival.

    PubMed

    Mitobe, Yuichi; Yasunaga, Jun-ichirou; Furuta, Rie; Matsuoka, Masao

    2015-10-01

    Infection of T cells with human T-cell leukemia virus type-1 (HTLV-1) induces clonal proliferation and is closely associated with the onset of adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. Although Tax expression is frequently suppressed in HTLV-1-infected cells, the accessory gene, HTLV-1 bZIP factor (HBZ), is continuously expressed and has been implicated in HTLV-1 pathogenesis. Here, we report that transduction of mouse T cells with specific mutants of HBZ that distinguish between its RNA and protein activity results in differential effects on T-cell proliferation and survival. HBZ RNA increased cell number by attenuating apoptosis, whereas HBZ protein induced apoptosis. However, both HBZ RNA and protein promoted S-phase entry of T cells. We further identified that the first 50 bp of the HBZ coding sequence are required for RNA-mediated cell survival. Transcriptional profiling of T cells expressing wild-type HBZ, RNA, or protein revealed that HBZ RNA is associated with genes involved in cell cycle, proliferation, and survival, while HBZ protein is more closely related to immunological properties of T cells. Specifically, HBZ RNA enhances the promoter activity of survivin, an inhibitor of apoptosis, to upregulate its expression. Inhibition of survivin using YM155 resulted in impaired proliferation of several ATL cell lines as well as a T-cell line expressing HBZ RNA. The distinct functions of HBZ RNA and protein may have several implications for the development of strategies to control the proliferation and survival mechanisms associated with HTLV-1 infection and ATL.

  3. Phosphorylation of Williams Syndrome Transcription Factor by MAPK Induces a Switching between Two Distinct Chromatin Remodeling Complexes*

    PubMed Central

    Oya, Hiroyuki; Yokoyama, Atsushi; Yamaoka, Ikuko; Fujiki, Ryoji; Yonezawa, Masayoshi; Youn, Min-Young; Takada, Ichiro; Kato, Shigeaki; Kitagawa, Hirochika

    2009-01-01

    Changes in the environment of a cell precipitate extracellular signals and sequential cascades of protein modification and elicit nuclear transcriptional responses. However, the functional links between intracellular signaling-dependent gene regulation and epigenetic regulation by chromatin-modifying proteins within the nucleus are largely unknown. Here, we describe novel epigenetic regulation by MAPK cascades that modulate formation of an ATP-dependent chromatin remodeling complex, WINAC (WSTF Including Nucleosome Assembly Complex), an SWI/SNF-type complex containing Williams syndrome transcription factor (WSTF). WSTF, a specific component of two chromatin remodeling complexes (SWI/SNF-type WINAC and ISWI-type WICH), was phosphorylated by the stimulation of MAPK cascades in vitro and in vivo. Ser-158 residue in the WAC (WSTF/Acf1/cbpq46) domain, located close to the N terminus of WSTF, was identified as a major phosphorylation target. Using biochemical analysis of a WSTF mutant (WSTF-S158A) stably expressing cell line, the phosphorylation of this residue (Ser-158) was found to be essential for maintaining the association between WSTF and core BAF complex components, thereby maintaining the ATPase activity of WINAC. WINAC-dependent transcriptional regulation of vitamin D receptor was consequently impaired by this WSTF mutation, but the recovery from DNA damage mediated by WICH was not impaired. Our results suggest that WSTF serves as a nuclear sensor of the extracellular signals to fine-tune the chromatin remodeling activity of WINAC. WINAC mediates a previously unknown MAPK-dependent step in epigenetic regulation, and this MAPK-dependent switching mechanism between the two functionally distinct WSTF-containing complexes might underlie the diverse functions of WSTF in various nuclear events. PMID:19776015

  4. Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets.

    PubMed

    Yamamoto, N; Yamaguchi, H; Ohmura, K; Yokoyama, T; Yoshifuji, H; Yukawa, N; Kawabata, D; Fujii, T; Morita, S; Nagata, S; Mimori, T

    2014-04-01

    Impaired clearance of apoptotic cells is a potential trigger of systemic lupus erythematosus (SLE). Milk fat globule epidermal growth factor 8 (MFG-E8) plays an important role in the clearance of dying cells. Previously, we reported serum MFG-E8 was elevated in some SLE patients. Here we further investigated the prevalence of MFG-E8 in active SLE and other autoimmune diseases and also tried to clarify the characteristics of MFG-E8-positive and -negative SLE. Serum MFG-E8 was measured in 40 active non-treated SLE patients, 104 disease controls and 104 healthy controls by ELISA. Clinical characteristics and serum cytokine profiles were compared between MFG-E8-positive and MFG-E8-negative SLE patients. Prevalence of MFG-E8 was significantly higher in SLE patients (40%) than in various controls (p < 0.05). MFG-E8 level became negative after treatment, and increased again upon relapse. When compared, MFG-E8-positive SLE patients showed higher immune complex (p = 0.021) and lower complement (p = 0.004 for CH50). In contrast, MFG-E8-negative SLE patients tended to show higher CRP (p = 0.094). There was a positive correlation between MFG-E8 level and immune complex level (r s = 0.49, p = 0.049). TNF-α (p = 0.019), IFN-γ (p = 0.031) and IL-10 (p = 0.013) were significantly higher in MFG-E8-positive SLE. MFG-E8-positive SLE and -negative SLE may have different clinical features, the one with stronger immunological response and the other with stronger inflammatory response, and those two groups may be two distinct subtypes of SLE driven by different mechanisms. Further, MFG-E8 could be used as a biomarker for diagnosis and monitoring of disease activity in certain SLE patients.

  5. Distinct roles for transforming growth factor-β2 and tumour necrosis factor-α in immune deviation elicited by hapten-derivatized antigen-presenting cells

    PubMed Central

    Hecker, K H; Niizeki, H; Streilein, J W

    1999-01-01

    The role of antigen-presenting cells (APC) in the induction of antigen-specific unresponsiveness was examined, using two functionally distinct murine macrophage hybridomas, #59 and #63 cells. Derivatized with the hapten (dinitrofluorobenzene; DNFB), #59 cells induced contact hypersensitivity (CH) in mice. Hapten-derivatized #63 cells failed to induce CH. Instead, they prevented recipients from acquiring CH when exposed subsequently to a sensitizing dose of the hapten. Similarly, hapten-derivatized #59 cells, pretreated in vitro with transforming growth factor-β2 (TGF-β2) lost their capacity to evoke CH, and induced tolerance. Hapten-derivatized #63 cells and TGF-β2-treated #59 cells eliminated CH in mice sensitized to hapten. Reverse transcription–polymerase chain reaction analysis of mRNAs for various accessory molecules important in T-cell activation revealed that #63 and TGF-β2-treated #59 cells differed only in their expression of tumour necrosis factor-α (TNF-α) mRNA. The latter expressed higher levels of TNF-α mRNA than did untreated #59 cells. As a consequence, #63 and TGF-β2-treated #59 cells, both of which induce tolerance, secrete TNF-α protein unlike untreated #59 cells, which do not induce tolerance to hapten. Since neutralizing anti-TNF-α antibodies abrogated the tolerogenic potential of #63 cells in vivo, we conclude that TGF-β2 equips hapten-bearing APC with the capacity to evoke systemic immune deviation in which CH is selectively silenced. We speculate that one effect of TGF-β2 is to cause APC to up-regulate TNF-α production. In turn, this cytokine biases the functional property of responding hapten-specific T cells in a direction that not only interferes with acquisition, but suppresses induction of CH. PMID:10233718

  6. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... an open access herring permit or a Limited Access Incidental Catch Herring Permit, and only as... the area. (4) A vessel issued an open access herring permit may fish for, possess, or land up to 6,600... limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring...

  7. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... an open access herring permit or a Limited Access Incidental Catch Herring Permit, and only as... the area. (4) A vessel issued an open access herring permit may fish for, possess, or land up to 6,600... limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring...

  8. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... an open access herring permit or a Limited Access Incidental Catch Herring Permit, and only as... the area. (4) A vessel issued an open access herring permit may fish for, possess, or land up to 6,600... limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring...

  9. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... an open access herring permit or a Limited Access Incidental Catch Herring Permit, and only as... the area. (4) A vessel issued an open access herring permit may fish for, possess, or land up to 6,600... limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring...

  10. Possession and Morality in Early Development

    ERIC Educational Resources Information Center

    Rochat, Philippe

    2011-01-01

    From the moment children say "mine!" by two years of age, objects of possession change progressively from being experienced as primarily unalienable property (i.e., something that is absolute or nonnegotiable), to being alienable (i.e., something that is negotiable in reciprocal exchanges). As possession begins to be experienced as alienable, the…

  11. Possession and Morality in Early Development

    ERIC Educational Resources Information Center

    Rochat, Philippe

    2011-01-01

    From the moment children say "mine!" by two years of age, objects of possession change progressively from being experienced as primarily unalienable property (i.e., something that is absolute or nonnegotiable), to being alienable (i.e., something that is negotiable in reciprocal exchanges). As possession begins to be experienced as alienable, the…

  12. Epilepsy and religious experiences: Voodoo possession.

    PubMed

    Carrazana, E; DeToledo, J; Tatum, W; Rivas-Vasquez, R; Rey, G; Wheeler, S

    1999-02-01

    Epileptic seizures have a historical association with religion, primarily through the concept of spirit possession. Five cases where epileptic seizures were initially attributed to Voodoo spirit possession are presented. The attribution is discussed within the context of the Voodoo belief system.

  13. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... in Area 1 only if issued an open access herring permit or a Limited Access Incidental Catch Herring... issued an open access herring permit may not fish for, possess, or land more than 6,600 lb (3 mt) of... access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring from or...

  14. 50 CFR 648.25 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Atlantic Mackerel, Squid, and Butterfish Fisheries § 648.25 Possession restrictions. (a) Atlantic mackerel. During a closure of the directed Atlantic mackerel fishery that occurs prior to June 1, vessels may not fish for, possess, or land more than 20,000 lb (9.08 mt) of Atlantic mackerel per trip at any time,...

  15. 50 CFR 648.25 - Possession restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Atlantic Mackerel, Squid, and Butterfish Fisheries § 648.25 Possession restrictions. Link to an amendment published at 76 FR 60620, Sept. 29, 2011. (a) Atlantic mackerel. During a closure of the directed Atlantic mackerel fishery that occurs prior to June 1, vessels may not fish for, possess, or land more than...

  16. Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid

    PubMed Central

    Owens, Christopher M.; Song, Byeongwoon; Perron, Michel J.; Yang, Peter C.; Stremlau, Matthew; Sodroski, Joseph

    2004-01-01

    In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIVmac is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1 capsid, changing them to the corresponding residues found on the SIVmac capsid. We identified two distinct pathways of escape from early, postentry restriction in monkey cells. One set of mutants that were altered near the base of the cyclophilin A-binding loop of the N-terminal capsid domain or in the interdomain linker exhibited a decreased ability to bind the restricting factor(s). Consistent with the location of this putative factor-binding site, cyclophilin A and the restricting factor(s) cooperated to achieve the postentry block. A second set of mutants that were altered in the ridge formed by helices 3 and 6 of the N-terminal capsid domain efficiently bound the restricting factor(s) but were resistant to the consequences of factor binding. These results imply that binding of the simian restricting factor(s) is not sufficient to mediate the postentry block to HIV-1 and that SIVmac capsids escape the block by decreases in both factor binding and susceptibility to the effects of the factor(s). PMID:15113921

  17. Are semantic and phonological fluency based on the same or distinct sets of cognitive processes? Insights from factor analyses in healthy adults and stroke patients.

    PubMed

    Schmidt, Charlotte S M; Schumacher, Lena V; Römer, Pia; Leonhart, Rainer; Beume, Lena; Martin, Markus; Dressing, Andrea; Weiller, Cornelius; Kaller, Christoph P

    2017-05-01

    Verbal fluency for semantic categories and phonological letters is frequently applied to studies of language and executive functions. Despite its popularity, it is still debated whether measures of semantic and phonological fluency reflect the same or distinct sets of cognitive processes. Word generation in the two task variants is believed to involve different types of search processes. Findings from the lesion and neuroimaging literature further suggest a stronger reliance of phonological and semantic fluency on frontal and temporal brain areas, respectively. This evidence for differential cognitive and neural contributions is, however, strongly challenged by findings from factor analyses, which have consistently yielded only one explanatory factor. As all previous factor-analytical approaches were based on very small item sets, this apparent discrepancy may be due to methodological limitations. In this study, we therefore applied a German version of the verbal fluency task with 8 semantic (i.e. categories) and 8 phonological items (i.e. letters). An exploratory factor analysis with oblique rotation in N=69 healthy young adults indeed revealed a two-factor solution with markedly different loadings for semantic and phonological items. This pattern was corroborated by a confirmatory factor analysis in a sample of N=174 stroke patients. As results from both samples also revealed a substantial portion of common variance between the semantic and phonological factor, the present data further demonstrate that semantic and phonological verbal fluency are based on clearly distinct but also on shared sets of cognitive processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Possession and carrying of firearms among suburban youth.

    PubMed Central

    Sheley, J F; Brewer, V E

    1995-01-01

    Despite a growing body of anecdotal evidence suggesting the spread of firearms to suburban juvenile populations, most studies of firearm activity by juveniles focus either on urban youth or on nationally representative samples that blur urban and nonurban distinctions. This study represents the first systematic empirical investigation specifically of a suburban population of juveniles. The authors examine both ownership and carrying behaviors, distinguish types of handguns involved, and assess the influence of drug activity, violent criminality, and the perception of one's social environment as dangerous upon the possession and carrying of firearms. Among the variables linked at the bivariate level to possession and carrying of guns were sex, involvement in criminal activity, involvement in drug activity, and most indicators of a dangerous social environment. At the multivariate level, however, only sex was associated with possession of a revolver, and only sex, criminal activity (for boys only), and one indicator of dangerous environment (having been threatened with a gun, for girls only) were associated with possession of an automatic or semiautomatic handgun. Aside from sex, criminal and drug activities were associated with gun carrying. Despite its importance among urban samples, in this study the dangerous environment was not linked to firearm activity. Possible reasons for this difference are explored in the conclusion. PMID:7838938

  19. Possession and carrying of firearms among suburban youth.

    PubMed

    Sheley, J F; Brewer, V E

    1995-01-01

    Despite a growing body of anecdotal evidence suggesting the spread of firearms to suburban juvenile populations, most studies of firearm activity by juveniles focus either on urban youth or on nationally representative samples that blur urban and nonurban distinctions. This study represents the first systematic empirical investigation specifically of a suburban population of juveniles. The authors examine both ownership and carrying behaviors, distinguish types of handguns involved, and assess the influence of drug activity, violent criminality, and the perception of one's social environment as dangerous upon the possession and carrying of firearms. Among the variables linked at the bivariate level to possession and carrying of guns were sex, involvement in criminal activity, involvement in drug activity, and most indicators of a dangerous social environment. At the multivariate level, however, only sex was associated with possession of a revolver, and only sex, criminal activity (for boys only), and one indicator of dangerous environment (having been threatened with a gun, for girls only) were associated with possession of an automatic or semiautomatic handgun. Aside from sex, criminal and drug activities were associated with gun carrying. Despite its importance among urban samples, in this study the dangerous environment was not linked to firearm activity. Possible reasons for this difference are explored in the conclusion.

  20. Two distinct allotypic determinants on the antigen-specific suppressor and enhancing T cell factors that are encoded by genes linked to the immunoglobulin heavy chain locus

    PubMed Central

    1982-01-01

    The alloantiserum was raised in BALB/c (H-2d, Igh-1a) mice hyperimmunized with spleen cells of Igh allotype congenic mice, CB-20 (H-2d, Igh-1b). It was found to define the new allotypic determinants (distinct from B cell Igh constant region determinants: Igh allotype) expressed only on a small population of T cells belonging to the Thy-1 dull-stained Lyt-2- or Lyt-2+ population of Igh-1b mice. Genes coding for the determinants were shown to be accommodated somewhere in the right side of the Igh variable region gene (Igh-V) cluster, as the antibody activity was completely absorbed with BAB-14 thymocytes. It was also demonstrated that the products detected by the antiserum represent the allotypic determinants (probably constant region determinants) on the antigen-binding moiety of the antigen-specific augmenting (TaF) and suppressor (TsF) T cell factors. Moreover, determinants on TsF were found to be distinct from those on TaF. Therefore, it can be suggested that the two genes coding for the T cell allodeterminants (distinct from those of the B cell Igh) are located in the right side of the B cell Igh-V on the 12th chromosome, and that both encode the antigen-recognition units of the functionally distinct T cell factors. PMID:6172538

  1. Subself theory and reincarnation/possession.

    PubMed

    Lester, David

    2004-12-01

    A subself model of the mind is used to account for multiple personality, possession, the spirit controls of mediums, reincarnation, and the auditory hallucinations of schizophrenics, with suggestions for empirical research.

  2. 22 CFR 72.14 - Nominal possession; property not normally taken into physical possession.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... into physical possession. 72.14 Section 72.14 Foreign Relations DEPARTMENT OF STATE PROTECTION AND... States Citizens and Nationals § 72.14 Nominal possession; property not normally taken into physical... acton is not a taking of physical possession by the officer. Before releasing the property, the consular...

  3. Examining the Factor Structure of the Self-Compassion Scale in Four Distinct Populations: Is the Use of a Total Scale Score Justified?

    PubMed

    Neff, Kristin D; Whittaker, Tiffany A; Karl, Anke

    2017-01-31

    This study examined the factor structure of the Self-Compassion Scale (SCS) using a bifactor model, a higher order model, a 6-factor correlated model, a 2-factor correlated model, and a 1-factor model in 4 distinct populations: college undergraduates (N = 222), community adults (N = 1,394), individuals practicing Buddhist meditation (N = 215), and a clinical sample of individuals with a history of recurrent depression (N = 390). The 6-factor correlated model demonstrated the best fit across samples, whereas the 1- and 2-factor models had poor fit. The higher order model also showed relatively poor fit across samples, suggesting it is not representative of the relationship between subscale factors and a general self-compassion factor. The bifactor model, however, had acceptable fit in the student, community, and meditator samples. Although fit was suboptimal in the clinical sample, results suggested an overall self-compassion factor could still be interpreted with some confidence. Moreover, estimates suggested a general self-compassion factor accounted for at least 90% of the reliable variance in SCS scores across samples, and item factor loadings and intercepts were equivalent across samples. Results suggest that a total SCS score can be used as an overall mesure of self-compassion.

  4. Exorcism and possession in psychotherapy practice.

    PubMed

    Henderson, J

    1982-03-01

    There has been an evolution in the layman's concept of mental disorder. Medieval belief in possession by demons and witches gave way to a 19th century medical model and more recently classical psychoanalytic formulations. Concurrently professional helping endeavor has moved increasingly from a more traditionally medical to psychotherapeutic process, and from a classical psychotherapeutic process wherein the therapist remained to a degree unresponsive and detached to a more modern emphasis on such qualities as empathy, sensitivity, reliability, and optimism as ingredients of successful psychotherapeutic practice. Freud's account of Haizmann's demonological neurosis usefully formulates the possession concept in psychological terms. However, recent developments in psychotherapeutic practice argue for a validity in the possession model of psychological distress. The possessing forces of object relations psychology are of course not the possessing demons and witches of medieval times but the possessing good and bad objects of early intrapsychic life set up through processes of introjection and incorporation in response to frustration in the early infant-mother relationship. Points of similarity in this comparison should not obscure features of contrast--ther is no place for histrionic manipulation nor for a moralistic attitude in the practice of psychotherapy. A case is described to illustrate these points.

  5. Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1.

    PubMed

    Hartmann, Kristina; Corvey, Carsten; Skerka, Christine; Kirschfink, Michael; Karas, Michael; Brade, Volker; Miller, Jennifer C; Stevenson, Brian; Wallich, Reinhard; Zipfel, Peter F; Kraiczy, Peter

    2006-09-01

    Borrelia burgdorferi, the aetiological agent of Lyme disease, employs sophisticated means to survive in diverse mammalian hosts. Recent studies demonstrated that acquisition of complement regulators factor H and factor H-like protein-1 (FHL-1) allows spirochetes to resist complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASPs) that bind factor H and/or FHL-1. In this study we have identified and characterized one of those B. burgdorferi proteins, named BbCRASP-2. BbCRASP-2 is distinct from the four previously identified factor H/FHL-1-binding CRASPs of B. burgdorferi strains. The single copy of the gene encoding BbCRASP-2, cspZ, is located on the linear plasmid lp28-3. BbCRASP-2 is highly divergent from the factor H/FHL-1-binding protein BbCRASP-1 and from members of the factor H-binding Erp (OspE/F-related) protein family. Peptide mapping analysis revealed that the factor H/FHL-1 binding site is discontinuous and it was found that C-terminal truncations abrogate factor H and FHL-1 binding. The predominant BbCRASP-2 binding site of both host complement regulators was mapped to the short consensus repeat 7 (SCR 7). Factor H and FHL-1 bound to BbCRASP-2 maintain cofactor activity for factor I-mediated C3b inactivation and accelerate the decay of the C3 convertase. Expression of BbCRASP-2 in serum-sensitive B. burgdorferi mutant B313 increased resistance to complement-mediated lysis. The characterization of BbCRASP-2 now provides a complete picture of the three diverse complement regulator-binding protein families of B. burgdorferi yielding new insights into the pathogenesis of Lyme disease.

  6. The Basic Helix-Loop-Helix Transcription Factor PIF5 Acts on Ethylene Biosynthesis and Phytochrome Signaling by Distinct Mechanisms

    USDA-ARS?s Scientific Manuscript database

    HYTOCHROME-INTERACTING FACTOR5 (PIF5), a basic helix-loop-helix transcription factor, interacts specifically with the photoactivated form of phytochrome B (phyB). Here, we report that dark-grown Arabidopsis thaliana seedlings overexpressing PIF5 (PIF5-OX) exhibit exaggerated apical hooks and short h...

  7. Ethnicity and Sex Distinctions in Patterns of Aptitude Factor Scores in a Sample of Urban High School Seniors

    ERIC Educational Resources Information Center

    Hennessy, James J.; Merrifield, Philip R.

    1978-01-01

    Three aptitude factor scores for each of 2,985 college bound urban high school seniors were used to compare patterns and levels of performance by sex and ethnic group membership. Significant differences in levels of performance between Blacks, Hispanics, Caucasian Jewish, and Caucasian Gentile were found on factors labeled Verbal, Reasoning, and…

  8. The possessions at Loudun: tracking the discourse of dissociation.

    PubMed

    Stephenson, Craig E

    2017-09-01

    Embedded in the history of dissociation is the best known case of possession in European history, the 17(th) century possessions at Loudun, France (1632-1638). The exorcisms and the trial drew crowds from all over Europe, the outcome prefiguring the direction in which the Western science of mind would be carried. The published debate about the possessed and obsessed Ursuline nuns of Loudun spans four centuries. One can track how theorizing about dissociation changed over time, with psychological contributions by Jean Martin Charcot, Georges Gilles de la Tourette, Pierre Janet, Michel Foucault and Michel de Certeau. Freud's psychoanalytic notion of demonological neurosis emphasized defensive strategies and a diabolic parody of adulthood. Jung's concepts of demonism and possession highlighted dissociated complexes that assimilate the ego and unseat the self, rendering a life 'provisional'. Dissociation as possession provides a through-line in Jung's Collected Works, from his 1902 dissertation to one of the last essays he wrote, in 1961. Within the context of psychotherapy, therapists and patients work towards psychological containment, consciously reorienting themselves to the presence of unconscious factors, personifying, embodying and thereby incorporating images of dissociated Otherness into the experience of selfhood. © 2017, The Society of Analytical Psychology.

  9. Possession Divestment by Sales in Later Life

    PubMed Central

    Ekerdt, David J.; Addington, Aislinn

    2015-01-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers’ capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers’ efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view. PMID:26162722

  10. Possession divestment by sales in later life.

    PubMed

    Ekerdt, David J; Addington, Aislinn

    2015-08-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers' capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers' efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view.

  11. Social appearance anxiety, perfectionism, and fear of negative evaluation: distinct or shared risk factors for social anxiety and eating disorders?

    PubMed

    Levinson, Cheri A; Rodebaugh, Thomas L; White, Emily K; Menatti, Andrew R; Weeks, Justin W; Iacovino, Juliette M; Warren, Cortney S

    2013-08-01

    Social anxiety and eating disorders are highly comorbid. Social appearance anxiety (i.e., fear of negative evaluation of one's appearance), general fear of negative evaluation, and perfectionism have each been proposed as risk factors for both social anxiety disorder and the eating disorders. However, no research to date has examined all three factors simultaneously. Using structural equation modeling in two diverse samples (N=236; N=136) we tested a model in which each of these risk factors were uniquely associated with social anxiety and eating disorder symptoms. We found support for social appearance anxiety as a shared risk factor between social anxiety and eating disorder symptoms, whereas fear of negative evaluation was a risk factor only for social anxiety symptoms. Despite significant zero-order relationships, two facets of perfectionism (high standards and maladaptive perfectionism) did not emerge as a risk factor for either disorder when all constructs were considered. These results were maintained when gender, body mass index, trait negative affect, and depression were included in the model. It is possible that treating negative appearance evaluation fears may reduce both eating disorder and social anxiety symptoms.

  12. Identification of the DNA damage-responsive element of RNR2 and evidence that four distinct cellular factors bind it.

    PubMed Central

    Elledge, S J; Davis, R W

    1989-01-01

    The RNR2 gene encodes the small subunit of ribonucleotide reductase, the enzyme that catalyzes the first step in the pathway for the production of the deoxyribonucleotides needed for DNA synthesis. Transcription of this gene is induced approximately 20-fold in response to environmental stimuli that damage DNA or block DNA replication. Deletion and subcloning analysis identified two, and possibly three, upstream activating sequences (UAS) and one repressing (URS) element in the RNR2 regulatory region. A 42-base-pair (bp) fragment from this region was found to be necessary for proper regulation of RNR2 and to be capable of conferring DNA damage inducibility upon a heterologous promoter. This fragment contained both positively and negatively acting sequences. Four DNA-binding factors interacted with the RNR2 regulatory region. One factor was identified as the GRF1 protein, the product of the RAP1 gene. GRF1 bound to the UAS2 element of RNR2, which was found to be directly adjacent to the 42-bp fragment. UAS2 activity was repressed by the 42-bp fragment. Three other factors bound to the 42-bp fragment; one of these factors, RRF3, had a second binding site in the RNR2 promoter. These factors are likely to mediate the response of RNR2 to DNA damage. Images PMID:2685561

  13. Determination of ligand-binding specificity by alternative splicing: Two distinct growth factor receptors encoded by a single gene

    SciTech Connect

    Miki, T.; Bottaro, D.P.; Fleming, T.P.; Smith, C.L.; Chan, A.M.L.; Aaronson, S.A. ); Burgess, W.H. )

    1992-01-01

    Expression cDNA cloning and structural analysis of the human keratinocyte growth factor receptor (KGFR) revealed identity with one of the fibroblast growth factor (FGF) receptors encoded by the bek gene (FGFR-2), except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. Genomic analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells, and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript. Thus, two growth factor receptors with different ligand-binding specificities and expression patterns are encoded by alternative transcripts of the same gene.

  14. Two distinct nuclear factors bind the conserved regulatory sequences of a rabbit major histocompatibility complex class II gene.

    PubMed Central

    Sittisombut, N

    1988-01-01

    The constitutive coexpression of the major histocompatibility complex (MHC) class II genes in B lymphocytes requires positive, trans-acting transcriptional factors. The need for these trans-acting factors has been suggested by the reversion of the MHC class II-negative phenotype of rare B-lymphocyte mutants through somatic cell fusion with B cells or T-cell lines. The mechanism by which the trans-acting factors exert their effect on gene transcription is unknown. The possibility that two highly conserved DNA sequences, located 90 to 100 base pairs (bp) (the A sequence) and 60 to 70 bp (the B sequence) upstream of the transcription start site of the class II genes, are recognized by the trans-acting factors was investigated in this study. By using the gel electrophoresis retardation assay, a minimum of two proteins which specifically bound the conserved A or B sequence of a rabbit DP beta gene were identified in murine nuclear extracts of a B-lymphoma cell line, A20-2J. Fractionation of nuclear extract through a heparin-agarose column allowed the identification of one protein, designated NF-MHCIIB, which bound an oligonucleotide containing the B sequence and protected the entire B sequence in the DNase I protection analysis. Another protein, designated NF-MHCIIA, which bound an oligonucleotide containing the A sequence and partially protected the 3' half of this sequence, was also identified. NF-MHCIIB did not protect a CCAAT sequence located 17 bp downstream of the B sequence. The possible relationship between these DNA-binding factors and the trans-acting factors identified in the cell fusion experiments is discussed. Images PMID:3133552

  15. A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells.

    PubMed

    Almaden, Jonathan V; Tsui, Rachel; Liu, Yi C; Birnbaum, Harry; Shokhirev, Maxim N; Ngo, Kim A; Davis-Turak, Jeremy C; Otero, Dennis; Basak, Soumen; Rickert, Robert C; Hoffmann, Alexander

    2014-12-24

    BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences.

  16. Maize Lc transcription factor enhances biosynthesis of anthocyanins, distinct proanthocyanidins and phenylpropanoids in apple (Malus domestica Borkh.).

    PubMed

    Li, Houhua; Flachowsky, Henryk; Fischer, Thilo C; Hanke, Magda-Viola; Forkmann, Gert; Treutter, Dieter; Schwab, Wilfried; Hoffmann, Thomas; Szankowski, Iris

    2007-10-01

    Flavonoids are a large family of polyphenolic compounds with manifold functions in plants. Present in a wide range of vegetables and fruits, flavonoids form an integral part of the human diet and confer multiple health benefits. Here, we report on metabolic engineering of the flavonoid biosynthetic pathways in apple (Malus domestica Borkh.) by overexpression of the maize (Zea mays L.) leaf colour (Lc) regulatory gene. The Lc gene was transferred into the M. domestica cultivar Holsteiner Cox via Agrobacterium tumefaciens-mediated transformation which resulted in enhanced anthocyanin accumulation in regenerated shoots. Five independent Lc lines were investigated for integration of Lc into the plant genome by Southern blot and PCR analyses. The Lc-transgenic lines contained one or two Lc gene copies and showed increased mRNA levels for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), flavanone 3 beta-hydroxylase (FHT), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin reductases (LAR), anthocyanidin synthase (ANS) and anthocyanidin reductase (ANR). HPLC-DAD and LC-MS analyses revealed higher levels of the anthocyanin idaein (12-fold), the flavan 3-ol epicatechin (14-fold), and especially the isomeric catechin (41-fold), and some distinct dimeric proanthocyanidins (7 to 134-fold) in leaf tissues of Lc-transgenic lines. The levels of phenylpropanoids and their derivatives were only slightly increased. Thus, Lc overexpression in Malus domestica resulted in enhanced biosynthesis of specific flavonoid classes, which play important roles in both phytopathology and human health.

  17. The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis

    PubMed Central

    Revilla-i-Domingo, Roger; Bilic, Ivan; Vilagos, Bojan; Tagoh, Hiromi; Ebert, Anja; Tamir, Ido M; Smeenk, Leonie; Trupke, Johanna; Sommer, Andreas; Jaritz, Markus; Busslinger, Meinrad

    2012-01-01

    Pax5 controls the identity and development of B cells by repressing lineage-inappropriate genes and activating B-cell-specific genes. Here, we used genome-wide approaches to identify Pax5 target genes in pro-B and mature B cells. In these cell types, Pax5 bound to 40% of the cis-regulatory elements defined by mapping DNase I hypersensitive (DHS) sites, transcription start sites and histone modifications. Although Pax5 bound to 8000 target genes, it regulated only 4% of them in pro-B and mature B cells by inducing enhancers at activated genes and eliminating DHS sites at repressed genes. Pax5-regulated genes in pro-B cells account for 23% of all expression changes occurring between common lymphoid progenitors and committed pro-B cells, which identifies Pax5 as an important regulator of this developmental transition. Regulated Pax5 target genes minimally overlap in pro-B and mature B cells, which reflects massive expression changes between these cell types. Hence, Pax5 controls B-cell identity and function by regulating distinct target genes in early and late B lymphopoiesis. PMID:22669466

  18. Epidemic Population Structure of Pseudomonas aeruginosa: Evidence for a Clone That Is Pathogenic to the Eye and That Has a Distinct Combination of Virulence Factors

    PubMed Central

    Lomholt, Jeanet A.; Poulsen, Knud; Kilian, Mogens

    2001-01-01

    The genetic structure of a population of Pseudomonas aeruginosa, isolated from patients with keratitis, endophthalmitis, and contact lens-associated red eye, contact lens storage cases, urine, ear, blood, lungs, wounds, feces, and the environment was determined by multilocus enzyme electrophoresis. The presence and characteristics of virulence factors were determined by restriction fragment length polymorphism analysis with DNA probes for lasA, lasB, aprA, exoS, exoT, exoU, and ctx and by zymography of staphylolysin, elastase, and alkaline protease. These analyses revealed an epidemic population structure of P. aeruginosa, characterized by frequent recombination in which a particular successful clone may increase, predominate for a time, and then disasappear as a result of recombination. Epidemic clones were found among isolates from patients with keratitis. They were characterized by high activity of a hitherto-unrecognized size variant of elastase, high alkaline protease activity, and possession of the exoU gene encoding the cytotoxic exoenzyme U. These virulence determinants are not exclusive traits in strains causing keratitis, as strains with other properties may cause keratitis in the presence of predisposing conditions. There were no uniform patterns of characteristics of isolates from other types of infection; however, all strains from urinary tract infections possessed the exoS gene, all strains from environment and feces and the major part of keratitis and wound isolates exhibited high elastase and alkaline protease activity, and all strains from feces showed high staphylolysin activity, indicating that these virulence factors may be important in the pathogenesis of these infectious diseases. PMID:11553572

  19. Identification of Distinct Bacillus thuringiensis 4A4 Nematicidal Factors Using the Model Nematodes Pristionchus pacificus and Caenorhabditis elegans

    PubMed Central

    Iatsenko, Igor; Nikolov, Angel; Sommer, Ralf J.

    2014-01-01

    Bacillus thuringiensis has been extensively used for the biological control of insect pests. Nematicidal B. thuringiensis strains have also been identified; however, virulence factors of such strains are poorly investigated. Here, we describe virulence factors of the nematicidal B. thuringiensis 4A4 strain, using the model nematodes Pristionchus pacificus and Caenorhabditis elegans. We show that B. thuringiensis 4A4 kills both nematodes via intestinal damage. Whole genome sequencing of B. thuringiensis 4A4 identified Cry21Ha, Cry1Ba, Vip1/Vip2 and β-exotoxin as potential nematicidal factors. Only Cry21Ha showed toxicity to C. elegans, while neither Cry nor Vip toxins were active against P. pacificus, when expressed in E. coli. Purified crystals also failed to intoxicate P. pacificus, while autoclaved spore-crystal mixture of B. thuringiensis 4A4 retained toxicity, suggesting that primary β-exotoxin is responsible for P. pacificus killing. In support of this, we found that a β-exotoxin-deficient variant of B. thuringiensis 4A4, generated by plasmid curing lost virulence to the nematodes. Thus, using two model nematodes we revealed virulence factors of the nematicidal strain B. thuringiensis 4A4 and showed the multifactorial nature of its virulence. PMID:25025708

  20. Identification of distinct Bacillus thuringiensis 4A4 nematicidal factors using the model nematodes Pristionchus pacificus and Caenorhabditis elegans.

    PubMed

    Iatsenko, Igor; Nikolov, Angel; Sommer, Ralf J

    2014-07-14

    Bacillus thuringiensis has been extensively used for the biological control of insect pests. Nematicidal B. thuringiensis strains have also been identified; however, virulence factors of such strains are poorly investigated. Here, we describe virulence factors of the nematicidal B. thuringiensis 4A4 strain, using the model nematodes Pristionchus pacificus and Caenorhabditis elegans. We show that B. thuringiensis 4A4 kills both nematodes via intestinal damage. Whole genome sequencing of B. thuringiensis 4A4 identified Cry21Ha, Cry1Ba, Vip1/Vip2 and β-exotoxin as potential nematicidal factors. Only Cry21Ha showed toxicity to C. elegans, while neither Cry nor Vip toxins were active against P. pacificus, when expressed in E. coli. Purified crystals also failed to intoxicate P. pacificus, while autoclaved spore-crystal mixture of B. thuringiensis 4A4 retained toxicity, suggesting that primary β-exotoxin is responsible for P. pacificus killing. In support of this, we found that a β-exotoxin-deficient variant of B. thuringiensis 4A4, generated by plasmid curing lost virulence to the nematodes. Thus, using two model nematodes we revealed virulence factors of the nematicidal strain B. thuringiensis 4A4 and showed the multifactorial nature of its virulence.

  1. Public and Private School Distinction, Regional Development Differences, and Other Factors Influencing the Success of Primary School Students in Turkey

    ERIC Educational Resources Information Center

    Sulku, Seher Nur; Abdioglu, Zehra

    2015-01-01

    This study investigates the factors influencing the success of students in primary schools in Turkey. TIMSS 2011 data for Turkey, measuring the success of eighth-grade students in the field of mathematics, were used in an econometric analysis, performed using classical linear regression models. Two hundred thirty-nine schools participated in the…

  2. Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia

    PubMed Central

    Ladroue, Charline; Hoogewijs, David; Gad, Sophie; Carcenac, Romain; Storti, Federica; Barrois, Michel; Gimenez-Roqueplo, Anne-Paule; Leporrier, Michel; Casadevall, Nicole; Hermine, Olivier; Kiladjian, Jean-Jacques; Baruchel, André; Fakhoury, Fadi; Bressac-de Paillerets, Brigitte; Feunteun, Jean; Mazure, Nathalie; Pouysségur, Jacques; Wenger, Roland H.; Richard, Stéphane; Gardie, Betty

    2012-01-01

    Background Congenital secondary erythrocytoses are due to deregulation of hypoxia inducible factor resulting in overproduction of erythropoietin. The most common germline mutation identified in the hypoxia signaling pathway is the Arginine 200-Tryptophan mutant of the von Hippel-Lindau tumor suppressor gene, resulting in Chuvash polycythemia. This mutant displays a weak deficiency in hypoxia inducible factor α regulation and does not promote tumorigenesis. Other von Hippel-Lindau mutants with more deleterious effects are responsible for von Hippel-Lindau disease, which is characterized by the development of multiple tumors. Recently, a few mutations in gene for the prolyl hydroxylase domain 2 protein (PHD2) have been reported in cases of congenital erythrocytosis not associated with tumor formation with the exception of one patient with a recurrent extra-adrenal paraganglioma. Design and Methods Five PHD2 variants, four of which were novel, were identified in patients with erythrocytosis. These PHD2 variants were functionally analyzed and compared with the PHD2 mutant previously identified in a patient with polycythemia and paraganglioma. The capacity of PHD2 to regulate the activity, stability and hydroxylation of hypoxia inducible factor α was assessed using hypoxia-inducible reporter gene, one-hybrid and in vitro hydroxylation assays, respectively. Results This functional comparative study showed that two categories of PHD2 mutants could be distinguished: one category with a weak deficiency in hypoxia inducible factor α regulation and a second one with a deleterious effect; the mutant implicated in tumor occurrence belongs to the second category. Conclusions As observed with germline von Hippel-Lindau mutations, there are functional differences between the PHD2 mutants with regards to hypoxia inducible factor regulation. PHD2 mutation carriers do, therefore, need careful medical follow-up, since some mutations must be considered as potential candidates for

  3. Stage I-IIA Non-Bulky Hodgkin's Lymphoma. Is Further Distinction Based on Prognostic Factors Useful? The Stanford Experience

    SciTech Connect

    Advani, Ranjana H.; Hoppe, Richard T.; Maeda, Lauren S.; Baer, David M.; Mason, Joseph; Rosenberg, Saul A.; Horning, Sandra J.

    2011-12-01

    Purpose: In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center. Methods and Materials: This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n = 84 patients) or 20-Gy (n = 17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors. Results: At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n = 55%; European Organization for Research and Treatment of Cancer, n = 33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n = 61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p = 0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged. Conclusions: The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.

  4. Cost Comparison Among Provable Data Possession Schemes

    DTIC Science & Technology

    2016-03-01

    possession,” in Proceedings of the 11th International Conference on Ap- plied Cryptography and Network Security. Berlin, Heidelberg: Springer-Verlag, 2013...curves,” in Security and Cryptography (SECRYPT), 2013 International Conference on, July 2013, pp. 1–12. [19] R. S. Kumar and A. Saxena, “Data integrity

  5. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  6. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  7. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  8. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  9. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  10. 50 CFR 648.105 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... fish boxes having a liquid capacity of 18.2 gal (70 L), or a volume of not more than 4,320 in 3 (2.5 ft... Summer Flounder Fisheries § 648.105 Possession restrictions. (a) Unless otherwise specified pursuant to... that person is the owner or operator of a fishing vessel issued a summer flounder moratorium permit, or...

  11. The distinctive profile of risk factors of nasopharyngeal carcinoma in comparison with other head and neck cancer types

    PubMed Central

    Abdulamir, AS; Hafidh, RR; Abdulmuhaimen, N; Abubakar, F; Abbas, KA

    2008-01-01

    Background Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types. Methods 122 HNCA patients and 100 control subjects were studied in the region of the Middle East. Three types of HNCA were involved in our study, NPC, carcinoma of larynx (CL), and hypopharyngeal carcinoma (HPC). The risk factors studied were the level of EBV serum IgG and IgA antibodies measured by ELISA, age, sex, smoking, alcohol intake, histology, and family history of the disease. Results EBV serum level of IgG and IgA antibodies was higher in NPC than CL, HPC, and control groups (p < 0.01). NPC was associated with lymphoepithelioma (LE) tumors, males, regular alcohol intake, and regular smoking while CL and HPC were not (p < 0.05). CL and HPC were associated with SCC tumors (p < 0.05). Furthermore, NPC, unlike CL and HPC groups, was not affected by the positive family history of HNCA (p > 0.05). The serum levels of EBV IgG and IgA antibodies were higher in LE tumors, regular smokers, younger patients, and negative family history groups of NPC patients than SCC tumors, non-regular smokers, older patients and positive family history groups respectively (p < 0.05) while this was not found in the regular alcoholics (p > 0.05). Conclusion It was concluded that risk factors of NPC deviate much from that of other HNCA. EBV, smoking, alcohol intake, LE tumors, male patient, and age > 54 years were hot risk factors of NPC while SCC and positive family history of the disease were not. Earlier incidence, smoking, LE tumors, and negative family history of the disease in NPC patients were associated much clearly with EBV. It is proposed that

  12. Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor.

    PubMed Central

    Burbach, K M; Poland, A; Bradfield, C A

    1992-01-01

    A cDNA encoding the murine Ah receptor (Ahb-1 allele for aromatic hydrocarbon responsiveness) has been isolated and characterized. Analysis of the deduced protein sequence revealed a region with similarity to the basic region/helix-loop-helix (BR/HLH) motif found in many transcription factors that undergo dimerization for function. In addition to the BR/HLH domain, the N-terminal domain of the Ah receptor has extensive sequence similarity to the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein and two regulatory proteins of Drosophila, Sim and Per. Photoaffinity labeling and peptide mapping studies indicate that the Ah receptor binds agonist at a domain that lies within this conserved N-terminal domain. The Ah receptor appears to be a ligand-activated transcription factor with a helix-loop-helix motif similar to those found in a variety of DNA-binding proteins, including Myc and MyoD. Images PMID:1325649

  13. Distinct work-related, clinical and psychological factors predict return to work following treatment in four different cancer types.

    PubMed

    Cooper, Alethea F; Hankins, Matthew; Rixon, Lorna; Eaton, Emma; Grunfeld, Elizabeth A

    2013-03-01

    Many factors influence return to work (RTW) following cancer treatment. However specific factors affecting RTW across different cancer types are unclear. This study examined the role of clinical, sociodemographic, work and psychological factors in RTW following treatment for breast, gynaecological, head and neck, and urological cancer. A 12-month prospective questionnaire study was conducted with 290 patients. Cox regression analyses were conducted to calculate hazard ratios (HR) for time to RTW. Between 89-94% of cancer survivors returned to work. Breast cancer survivors took the longest to return (median 30 weeks), and urology cancer survivors returned the soonest (median 5 weeks). Earlier return among breast cancer survivors was predicted by a greater sense of control over their cancer at work (HR 1.2; 95% CI: 1.09-1.37) and by full-time work (HR 2.1; CI: 1.24-3.4). Predictive of a longer return among gynaecological cancer survivors was a belief that cancer treatment may impair ability to work (HR 0.75; CI: 0.62-0.91). Among urological cancer survivors constipation was predictive of longer RTW (HR 0.99; CI: 0.97-1.00), whereas undertaking flexible working was predictive of returning sooner (HR 1.70; CI: 1.07-2.7). Head and neck cancer survivors who perceived greater negative consequences of their cancer took longer to return (HR 0.27; CI: 0.11-0.68). Those reporting better physical functioning returned sooner (HR1.04; CI: 1.01-1.08). A different profile of predictive factors emerged for the four cancer types. In addition to optimal symptom management and workplace adaptations, the findings suggest that eliciting and challenging specific cancer and treatment-related perceptions may facilitate RTW. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

    PubMed Central

    Weinstein, M J; Chute, L E

    1984-01-01

    We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

  15. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7.

    PubMed Central

    Marié, I; Durbin, J E; Levy, D E

    1998-01-01

    Interferon (IFN) genes are among the earliest transcriptional responses to virus infection of mammalian cells. Although the regulation of the IFNbeta gene has been well characterized, the induction of the large family of IFNalpha genes has remained obscure. We report that the IFNalpha genes can be divided into two groups: an immediate-early response gene (IFNalpha4) which is induced rapidly and without the need for ongoing protein synthesis; and a set of genes that display delayed induction, consisting of at least IFNalpha2, 5, 6 and 8, which are induced more slowly and require cellular protein synthesis. One protein that must be synthesized for induction of the delayed gene set is IFN itself, presumably IFNalpha4 or IFNbeta, which stimulates the Jak-Stat pathway through the IFN receptor, resulting in activation of the transcription factor interferon-stimulated gene factor 3 (ISGF3). Among the IFN-stimulated genes induced through this positive feedback loop is the IFN regulatory factor (IRF) protein, IRF7. Induction of IRF7 protein in response to IFN and its subsequent activation by phosphorylation in response to virus-specific signals, involving two C-terminal serine residues, are required for induction of the delayed IFNalpha gene set. PMID:9822609

  16. Five factor model personality traits relate to adult attention-deficit/hyperactivity disorder but not to their distinct neurocognitive profiles.

    PubMed

    Van Dijk, Fiona E; Mostert, Jeannette; Glennon, Jeffrey; Onnink, Marten; Dammers, Janneke; Vasquez, Alejandro Arias; Kan, Cornelis; Verkes, Robbert Jan; Hoogman, Martine; Franke, Barbara; Buitelaar, Jan K

    2017-08-19

    Deficits in multiple neuropsychological domains and specific personality profiles have been observed in attention-deficit/hyperactivity disorder (ADHD). In this study we investigated whether personality traits are related to neurocognitive profiles in adults with ADHD. Neuropsychological performance and Five Factor Model (FFM) personality traits were measured in adults with ADHD (n = 133) and healthy controls (n = 132). Three neuropsychological profiles, derived from previous community detection analyses, were investigated for personality trait differences. Irrespective of cognitive profile, participants with ADHD showed significantly higher Neuroticism and lower Extraversion, Agreeableness, and Conscientiousness than healthy controls. Only the FFM personality factor Openness differed significantly between the three profiles. Higher Openness was more common in those with aberrant attention and inhibition than those with increased delay discounting and atypical working memory / verbal fluency. The results suggest that the personality trait Openness, but not any other FFM factor, is linked to neurocognitive profiles in ADHD. ADHD symptoms rather than profiles of cognitive impairment have associations with personality traits. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation.

    PubMed

    Duarte, Fabiana M; Fuda, Nicholas J; Mahat, Dig B; Core, Leighton J; Guertin, Michael J; Lis, John T

    2016-08-01

    The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use precision run-on sequencing (PRO-seq) to examine the genome-wide heat shock (HS) response in Drosophila and the function of two key transcription factors on the immediate transcription activation or repression of all genes regulated by HS. We identify the primary HS response genes and the rate-limiting steps in the transcription cycle that GAGA-associated factor (GAF) and HS factor (HSF) regulate. We demonstrate that GAF acts upstream of promoter-proximally paused RNA polymerase II (Pol II) formation (likely at the step of chromatin opening) and that GAF-facilitated Pol II pausing is critical for HS activation. In contrast, HSF is dispensable for establishing or maintaining Pol II pausing but is critical for the release of paused Pol II into the gene body at a subset of highly activated genes. Additionally, HSF has no detectable role in the rapid HS repression of thousands of genes.

  18. Distinct effects on the dendritic arbor occur by microbead versus bath administration of brain-derived neurotrophic factor.

    PubMed

    O'Neill, Kate M; Kwon, Munjin; Donohue, Katherine E; Firestein, Bonnie L

    2017-07-11

    Proper communication among neurons depends on an appropriately formed dendritic arbor, and thus, aberrant changes to the arbor are implicated in many pathologies, ranging from cognitive disorders to neurodegenerative diseases. Due to the importance of dendritic shape to neuronal network function, the morphology of dendrites is tightly controlled and is influenced by both intrinsic and extrinsic factors. In this work, we examine how brain-derived neurotrophic factor (BDNF), one of the most well-studied extrinsic regulators of dendritic branching, affects the arbor when it is applied locally via microbeads to cultures of hippocampal neurons. We found that local application of BDNF increases both proximal and distal branching in a time-dependent manner and that local BDNF application attenuates pruning of dendrites that occurs with neuronal maturation. Additionally, we examined whether cytosolic PSD-95 interactor (cypin), an intrinsic regulator of dendritic branching, plays a role in these changes and found strong evidence for the involvement of cypin in BDNF-promoted increases in dendrites after 24 but not 48 h of application. This current study extends our previous work in which we found that bath application of BDNF for 72 h, but not shorter times, increases proximal dendrite branching and that this increase occurs through transcriptional regulation of cypin. Moreover, this current work illustrates how dendritic branching is regulated differently by the same growth factor depending on its spatial localization, suggesting a novel pathway for modulation of dendritic branching locally.

  19. Two distinct factors bind to the rabbit uteroglobin TATA-box region and are required for efficient transcription.

    PubMed Central

    Klug, J; Knapp, S; Castro, I; Beato, M

    1994-01-01

    The rabbit uteroglobin gene is expressed in a variety of epithelial cell types like the lung Clara cells and the glandular and luminal epithelial cells of the endometrium. Expression in Clara cells is on a high constitutive level, whereas expression in the rabbit endometrium is under tight hormonal control. One important element of the rabbit uteroglobin gene mediating its efficient transcription in two epithelial cell lines from human endometrium (Ishikawa) and lung (NCI-H441) is its noncanonical TATA box (TACA). Here, we show that two factors (TATA core factor [TCF] and TATA palindrome factor [TPF]) different from the TATA-box binding protein bind to the DNA major groove at two adjacent sites within the uteroglobin TATA-box region and that one of them (TCF) is specifically expressed in cell lines derived from uteroglobin-expressing tissues. The binding sites for TCF and TPF, respectively, are both required for efficient transcription in Ishikawa and NCI-H441 cells. Mutation of the TACA box, which we show is a poor TATA box in functional terms, to a canonical TATA motif does not affect TCF and TPF binding. Therefore, we suggest that the function of the unusual cytosine could be to reduce rabbit uteroglobin expression in cells lacking TCF and that the interaction of TATA-box binding protein with the weak TACA site is facilitated in TCF- and TPF-positive cells. Images PMID:8065353

  20. A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

    NASA Astrophysics Data System (ADS)

    Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

    1995-10-01

    Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

  1. Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates.

    PubMed Central

    Favatier, F; Polla, B S

    2001-01-01

    Exposure of eukaryotic cells to a variety of reactive-oxygen-intermediate (ROI)-mediated sources of cellular injury, including heavy metals and UV radiation, induces the expression of heat-shock (HS) and stress-related genes among which is a 32-34 kDa protein identified as inducible haem oxygenase-1 (HO-1). We previously showed that tobacco smoke (TS), a potent source of oxidants leading to oxidative stress, induces both HS proteins (HSPs) and HO-1 in normal human monocytes. Here we investigated the induction mechanisms of human HO-1 gene expression by TS in the human premonocytic line U937. Northern blotting and flow cytometry revealed a dose- and time-dependent induction of HO-1 mRNA and protein by TS. In order to clarify the role of transacting factors in this induction, electrophoretic mobility-shift analysis was performed with nuclear extracts from control, TS-, cadmium (Cd)- or H(2)O(2)-exposed cells, incubated with consensus elements and binding sites of the promoter region of HO-1[heat-shock factor (HSF), nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1)] and the cadmium-responsive element (CdRE) isolated by Takeda, Ishizawa, Sato, Yoshida and Shibahara [(1994) J. Biol. Chem. 269, 22858-22867]. We report an inhibition of NF-kappaB activation by TS, no effect on AP-1 and a strong activation of CdRE-binding activity, whereas cadmium chelation from TS only partially prevented HO-1 induction. H(2)O(2) also activated the CdRE-binding activity, and pretreatment with N-acetyl-L-cysteine, which replenishes the intracellular levels of GSH, suppressed, in TS-treated cells, both the CdRE-binding activity and the increased HO-1 expression. PMID:11171043

  2. The SFT-1 and OXA-1 respiratory chain complex assembly factors influence lifespan by distinct mechanisms in C. elegans

    PubMed Central

    2013-01-01

    Background C. elegans mitochondrial (Mit) mutants have disrupted mitochondrial electron transport chain function, yet, surprisingly, they are often long-lived, a property that has offered unique insights into the molecular mechanisms of aging. In this study, we examine the phenotypic consequences of reducing the expression of the respiratory chain complex assembly factors sft-1 (homologous to human SURF1) and oxa-1 (homologous to human OXA1) by RNA interference (RNAi). Mutations in human SURF1 are associated with Leigh syndrome, a neurodegenerative condition of the brain caused by cytochrome oxidase (COX) deficiency. Both SURF1 and OXA1 are integral proteins of the inner mitochondrial membrane, functioning in the COX assembly pathway. Results RNAi of both of these genes in C. elegans is associated with increased longevity, but the mechanism by which lifespan is extended is different in each case. sft-1(RNAi) animals display lifespan extension that is dependent on the daf-16 insulin-like signaling pathway, and associated with sensitivity to oxidative stress. oxa-1(RNAi) animals, in contrast, exhibit increased longevity that is at least partially independent of daf-16, and associated with a reduced developmental rate and increased resistance to oxidative stress. Conclusions This study further delineates the consequences of mitochondrial dysfunction within a whole organism that will ultimately help provide new models for human mitochondrial-associated diseases. The difference in phenotype observed upon down-regulation of these two COX assembly factors, as well as phenotypic differences between these factors and other respiratory chain components analyzed thus far, illustrates the complex inter-relationships that exist among energy metabolism, reproduction and aging even in this simplest of metazoan model organisms. PMID:24472117

  3. Induction of prostaglandin E synthesis in normal and neoplastic macrophages: role for colony-stimulating factor(s) distinct from effects on myeloid progenitor cell proliferation.

    PubMed Central

    Kurland, J I; Pelus, L M; Ralph, P; Bockman, R S; Moore, M A

    1979-01-01

    The biosynthesis of prostaglandin E (PGE) by normal and neoplastic macrophages is intrinsically linked to their synthesis of, and exposure to, myeloid colony-stimulating factors (CS-factors). The defect in responsiveness to endotoxin lipopolysaccharide (LPS) by macrophages from C3H/HeJ mice extends equally to the synthesis of CS-factor and PGE. However, C3H/HeJ macrophages can be stimulated to synthesize PGE by treatment with agents other than LPS [zymosan, tuberculin purified protein derivative, concanavalin A, poly(I).poly(C)], which also stimulate CS-factor production, or by the addition of various preparations of soluble CS-factor. In peritoneal wash preparations, constitutive PGE synthesis occurred in rapidly sedimenting macrophage cells, whereas constitutive CS-factor production and inducible PGE synthesis occurred in slower sedimenting adherent cells. A similar functional heterogeneity in CS-factor and PGE production was found in neoplastic macrophagae cell lines. The association of elevated CS-factor levels and PGE synthesis by macrophages suggests a role for CS-factor in many of the physiological responses heretofore associated with elevated tissue levels of the E type prostaglandins. PMID:313054

  4. Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

    PubMed Central

    Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L.; Symes, Karen

    2005-01-01

    Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRα or PDGFRβ is embryonic lethal. In Xenopus embryos, disruption of PDGFRα signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFRα function in this process, we have analyzed all known effector-binding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFRαs, we have identified a role for phospholipase Cγ (PLCγ) in protecting cells from death. PDGFRα-mediated cell survival requires PLCγ and phosphatidylinositol 3-kinase signaling, and that PDGFRα with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFRα signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFRα signaling through PLCγ and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos. PMID:15919820

  5. Hepatocyte growth factor triggers distinct mechanisms of Asef and Tiam1 activation to induce endothelial barrier enhancement

    PubMed Central

    Higginbotham, Katherine; Tian, Yufeng; Gawlak, Grzegorz; Moldobaeva, Nurgul; Shah, Alok; Birukova, Anna A.

    2014-01-01

    Previous reports described important role of hepatocyte growth factor (HGF) in mitigation of pulmonary endothelial barrier dysfunction and cell injury induced by pathologic agonists and mechanical forces. HGF protective effects have been associated with Rac-GTPase signaling pathway activated by Rac-specific guanine nucleotide exchange factor Tiam1 and leading to enhancement of intercellular adherens junctions. This study tested involvement of a novel Rac-specific activator, Asef, in endothelial barrier enhancement by HGF and investigated a mechanism of HGF-induced Asef activation. Si-RNA-based knockdown of Tiam1 and Asef had an additive effect on attenuation of HGF-induced Rac activation and endothelial cell (EC) barrier enhancement. Tiam1 and Asef activation was abolished by pharmacologic inhibitors of HGF receptor and PI3-kinase. In contrast to Tiam1, Asef interacted with APC and associated with microtubule fraction upon HGF stimulation. EC treatment by low dose nocodazole to inhibit peripheral microtubule dynamics partially attenuated HGF-induced Asef peripheral translocation, but had negligible effect on Tiam1 translocation. These effects were associated with attenuation of HGF-induced barrier enhancement in EC pretreated with low ND dose and activation of Rac and its cytoskeletal effectors PAK1 and cortactin. These data demonstrate, that in addition to microtubule-independent Tiam1 activation, HGF engages additional microtubule- and APC-dependent pathway of Asef activation. These mechanisms may complement each other to provide the fine tuning of Rac signaling and endothelial barrier enhancement in response to various agonists. PMID:25101856

  6. Hepatocyte growth factor triggers distinct mechanisms of Asef and Tiam1 activation to induce endothelial barrier enhancement.

    PubMed

    Higginbotham, Katherine; Tian, Yufeng; Gawlak, Grzegorz; Moldobaeva, Nurgul; Shah, Alok; Birukova, Anna A

    2014-11-01

    Previous reports described an important role of hepatocyte growth factor (HGF) in mitigation of pulmonary endothelial barrier dysfunction and cell injury induced by pathologic agonists and mechanical forces. HGF protective effects have been associated with Rac-GTPase signaling pathway activated by Rac-specific guanine nucleotide exchange factor Tiam1 and leading to enhancement of intercellular adherens junctions. This study tested involvement of a novel Rac-specific activator, Asef, in endothelial barrier enhancement by HGF and investigated a mechanism of HGF-induced Asef activation. Si-RNA-based knockdown of Tiam1 and Asef had an additive effect on attenuation of HGF-induced Rac activation and endothelial cell (EC) barrier enhancement. Tiam1 and Asef activation was abolished by pharmacologic inhibitors of HGF receptor and PI3-kinase. In contrast to Tiam1, Asef interacted with APC and associated with microtubule fraction upon HGF stimulation. EC treatment by low dose nocodazole to inhibit peripheral microtubule dynamics partially attenuated HGF-induced Asef peripheral translocation, but had negligible effect on Tiam1 translocation. These effects were associated with attenuation of HGF-induced barrier enhancement in EC pretreated with low ND dose and activation of Rac and its cytoskeletal effectors PAK1 and cortactin. These data demonstrate, that in addition to microtubule-independent Tiam1 activation, HGF engages additional microtubule- and APC-dependent pathway of Asef activation. These mechanisms may complement each other to provide the fine tuning of Rac signaling and endothelial barrier enhancement in response to various agonists. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations

    PubMed Central

    Kristjansdottir, G; Sandling, J K; Bonetti, A; Roos, I M; Milani, L; Wang, C; Gustafsdottir, S M; Sigurdsson, S; Lundmark, A; Tienari, P J; Koivisto, K; Elovaara, I; Pirttilä, T; Reunanen, M; Peltonen, L; Saarela, J; Hillert, J; Olsson, T; Landegren, U; Alcina, A; Fernández, O; Leyva, L; Guerrero, M; Lucas, M; Izquierdo, G; Matesanz, F; Syvänen, A-C

    2008-01-01

    Background: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case–control cohorts from Spain and Sweden, and a set of MS trio families from Finland. Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases. PMID:18285424

  8. Characterization of Two Homeodomain Transcription Factors with Critical but Distinct Roles in Virulence in the Vascular Pathogen Verticillium dahliae.

    PubMed

    Sarmiento-Villamil, J L; Prieto, P; Klosterman, S J; García-Pedrajas, M D

    2017-07-20

    Vascular wilt caused by Verticillium dahliae is a destructive disease that represents a chronic economic problem on crop production worldwide. In this work we characterized two new regulators of pathogenicity in this species. Vph1 (VDAG_06555) was identified in a candidate gene approach as a putative homolog of the transcription factor Ste12. Vhb1 (VDAG_08786), identified in a forward genetics approach, is similar to the homeobox transcription factor Htf1, reported as a regulator of conidiogenesis in several fungi. Deletion of vph1 did not affect vegetative growth whereas deletion of vhb1 greatly reduced sporulation rates in liquid medium. Both mutants failed to induce Verticillium wilt symptoms. However, unlike Δvph1, Δvhb1 could be re-isolated from the vascular system of some asymptomatic plants. Confocal microscopy further indicated that Δvph1 and Δvhb1 differed in their behaviour in planta; Δvph1 could not penetrate the root cortex while Δvhb1 was impaired in its ability to colonize the xylem. In agreement with these observations, only Δvhb1 could penetrate cellophane paper. On cellophane, wildtype and Δvhb1 strains produced numerous short branches with swollen tips resembling the hyphopodia formed on root surfaces, contrasting with Δvph1, which generated unbranched long filaments without swollen tips. A microarray analysis showed that these differences in growth were associated with differences in global transcription patterns, and allowed us to identify a large set of novel genes potentially involved in virulence in V. dahliae. Ste12 homologs are known regulators of invasive growth but Vhb1 is the first putative Htf1 homolog identified with a critical role in virulence. This article is protected by copyright. All rights reserved. © 2017 BSPP and John Wiley & Sons Ltd.

  9. Tracking the actions and possessions of agents

    PubMed Central

    Gelman, Susan A.; Noles, Nicholaus S.; Stilwell, Sarah

    2014-01-01

    We propose that there is a powerful human disposition to track the actions and possessions of agents. In two experiments, 3-year-olds and adults viewed sets of objects, learned a new fact about one of the objects in each set (either that it belonged to the participant, or that it possessed a particular label), and were queried about either the taught fact or an unrelated dimension (preference) immediately after a spatiotemporal transformation, and after a delay. Adults uniformly tracked object identity under all conditions, whereas children tracked identity more when taught ownership versus labeling information, and only regarding the taught fact (not the unrelated dimension). These findings suggest that the special attention that children and adults pay to agents readily extends to include inanimate objects. That young children track an object’s history, despite their reliance on surface features on many cognitive tasks, suggests that unobservable historical features are foundational in human cognition. PMID:25111732

  10. Immobilized nerve growth factor and microtopography have distinct effects on polarization versus axon elongation in hippocampal cells in culture.

    PubMed

    Gomez, Natalia; Lu, Yi; Chen, Shaochen; Schmidt, Christine E

    2007-01-01

    Cell interfacing with biomaterial surfaces dictates important aspects of cell behavior. In particular, axon extension in neurons is effectively influenced by surface properties, both for the initial formation of an axon as well as for the maintenance of axon growth. Here, we investigated how neurons behaved on poly(dimethyl siloxane) (PDMS) surfaces decorated with biochemical and physical cues presented individually or in combination. In particular, nerve growth factor (NGF) was covalently tethered to PDMS to create a bioactive surface, and microtopography was introduced to the material in the form of microchannels. Embryonic hippocampal neurons were used to investigate the impact of these surface cues on polarization (i.e., axon initiation or axogenesis) and overall axon length. We found that topography had a more pronounced effect on polarization (68% increase over controls) compared to immobilized NGF (0.1 ng/mm(2)) (27% increase). However, the effect of NGF was negligible when both types of stimuli were simultaneously presented on the biomaterial surface. In addition to axon formation, chemical and physical cues are also involved in axon growth following the initiation process. Interestingly, for the same studies described above, the effects of microchannels and NGF were opposite from the effects on polarization; the most evident effect was for the immobilized growth factor (10% increase in axon length with respect to controls) whereas there was no effect in general for the microtopography. More importantly, when the two surface stimuli were presented in combination, a synergistic increase in axon length was detected (25% increase with respect to controls), which could be a result of faster polarization triggered by topography plus enhanced growth from NGF. Additionally, axon orientation was also analyzed and we found the well-known tendency of perpendicular or parallel axonal alignment to be dependent on the width and depth of the channels. This investigation

  11. Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for monitoring oncogenic signaling pathways in various cancer cells.

    PubMed

    Du, Yuhong; Li, Zijian; Li, Lian; Chen, Zhuo Georgia; Sun, Shi-Yong; Chen, Peifang; Shin, Dong M; Khuri, Fadlo R; Fu, Haian

    2009-01-01

    Targeting dysregulated signaling pathways in tumors has led to the development of a novel class of signal transduction inhibitors, including inhibitors of the epidermal growth factor (EGF) receptor (EGFR). To dissect oncogenic pathways, identify key pathway determinants, and evaluate the efficacy of targeted agents, it is vital to develop technologies that allow the detection of temporal signaling events under physiological conditions. Here we report the application of a label-free optical biosensor to reveal the rapid response of cancer cells to EGF, expressed as a dynamic mass redistribution (DMR) signal. In response to EGF, squamous cell carcinoma of the head and neck cells exhibited a rapid rise in DMR signal, whereas lung adenocarcinoma cells showed a biphasic DMR profile, suggesting a cell type-dependent DMR response. Pharmacological studies suggested the importance of EGFR and the phosphatidylinositol-3 kinase pathway in mediating the EGF-induced DMR response. The defined DMR signatures offer a simple yet sensitive tool for evaluating EGFR-targeted agents, as shown with gefitinib and erlotinib. The assay can also be used for cell-based high-throughput screening of EGF pathway inhibitors, as demonstrated by its robust performance in a 384-well plate format (Z' > 0.5). This technology is applicable to other oncogenic pathways for the discovery of novel therapeutic agents for the treatment of various cancers.

  12. Distinctive cutaneous and systemic features associated with antitranscriptional intermediary factor-1γ antibodies in adults with dermatomyositis.

    PubMed

    Fiorentino, David F; Kuo, Karen; Chung, Lorinda; Zaba, Lisa; Li, Shufeng; Casciola-Rosen, Livia

    2015-03-01

    Antibodies against transcriptional intermediary factor (TIF)-1γ are associated with malignancy in dermatomyositis (DM). Identification of clinical findings associated with anti-TIF-1γ antibodies in DM is a high priority for both patient diagnosis and risk assessment. We sought to define the clinical phenotype of patients with anti-TIF-1γ DM. Using a novel, sensitive, and specific assay for anti-TIF-1γ antibodies, we retrospectively tested plasma from 134 adult patients with DM and examined associations between anti-TIF-1γ antibodies and particular clinical and laboratory features. In all, 55 (41%) patients had autoantibodies to TIF-1γ. Anti-TIF-1γ positive patients were less likely to have systemic features including interstitial lung disease, Raynaud phenomenon, and arthritis/arthralgia. Patients with TIF-1γ autoantibodies had more extensive skin involvement, and some patients manifested characteristic findings including palmar hyperkeratotic papules, psoriasis-like lesions and a novel finding of hypopigmented and telangiectatic ("red on white") patches. This was a retrospective study from a single tertiary referral center. TIF-1γ is the most commonly targeted DM-specific autoantigen in adults in a large US cohort. Although these patients tend to have less systemic involvement, their skin disease is often extensive and characteristic. Recognition of cutaneous findings in anti-TIF-1γ positive patients may allow more accurate and timely diagnosis and effective treatment of patients with DM. Copyright © 2014 American Academy of Dermatology, Inc. All rights reserved.

  13. How distinctive are morningness and eveningness from the Big Five factors of personality? A meta-analytic investigation.

    PubMed

    Lipnevich, Anastasiya A; Credè, Marcus; Hahn, Elisabeth; Spinath, Frank M; Roberts, Richard D; Preckel, Franzis

    2017-03-01

    This study explores relations between measures of individuals' circadian preferences and the Big Five. To this end, we compared a model of circadian preferences that acknowledges morningness (M) and eveningness (E) as separate dimensions to that of a model that places M and E on a single continuum (M-E). Analyses of 620 correlations from 44 independent samples (N = 16,647) revealed weak to modest relations between both dimensions of circadian preferences and the Big Five personality traits. The strongest observed relation was found between Conscientiousness and M (ρ = .37). In the next step, regression analyses revealed that personality traits accounted for between 10.9% and 16.4% of the variance in circadian preferences. Of all the Big Five dimensions, Conscientiousness exhibited the strongest unique relation with M (β = .32), E (β = -.26), and M-E (β = .32). Extraversion and Openness exhibited moderate unique relations with E (β = .23 and β = .17, respectively), whereas relations with M (β = .00 and β = .04), and M-E (β = -.05 and β = -.06) were relatively weak. Neuroticism exhibited a modest unique and negative relation with M (β = -.16), and Agreeableness was largely unrelated to all circadian preference variables. To determine whether these findings translated into anything of applied significance, we explored relations between circadian preference and academic performance. M and E incremented slightly over the Big Five factors in predicting grade-point average. Theoretical and practical implications of these findings are discussed. (PsycINFO Database Record

  14. Characterization of FNR* mutant proteins indicates two distinct mechanisms for altering oxygen regulation of the Escherichia coli transcription factor FNR.

    PubMed Central

    Bates, D M; Lazazzera, B A; Kiley, P J

    1995-01-01

    In order to gain insight into the mechanism by which the Escherichia coli transcription factor FNR* is activated in response to anaerobiosis, we have analyzed FNR mutant proteins which, unlike the wild-type protein, stimulate gene expression in the presence of oxygen in vivo. Cell extracts containing seven different FNR* mutant proteins were tested in vitro for the ability to bind to the FNR consensus DNA site in a gel retardation assay under aerobic conditions. At the concentration of protein tested, only extracts which contained FNR* mutant proteins with amino acid substitutions at position 154 showed significant DNA binding. The three position-154 FNR* mutant proteins could be further distinguished from the other mutant proteins by analysis of the in vivo phenotypes of FNR* proteins containing amino acid substitutions at either of two essential cysteine residues. In the presence of oxygen, FNR* mutant proteins with amino acid substitutions at position 154 were the least affected when either Cys-23 or Cys-122 was substituted for Ser. On the basis of these in vivo and in vitro analyses, FNR* mutant proteins appear to segregate into at least two classes. Thus, it appears that each class of FNR* substitutions alters the normal pathway of FNR activation in response to oxygen deprivation by a different mechanism. PMID:7608069

  15. Distinctive expression patterns of hypoxia-inducible factor-1α and endothelial nitric oxide synthase following hypergravity exposure

    PubMed Central

    Yoon, Gun; Oh, Choong Sik; Kim, Hyun-Soo

    2016-01-01

    This study was designed to examine the expression of hypoxia-inducible factor-1α (HIF-1α) and the level and activity of endothelial nitric oxide synthase (eNOS) in the hearts and livers of mice exposed to hypergravity. Hypergravity-induced hypoxia and the subsequent post-exposure reoxygenation significantly increased cardiac HIF-1α levels. Furthermore, the levels and activity of cardiac eNOS also showed significant increase immediately following hypergravity exposure and during the reoxygenation period. In contrast, the expression of phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) showed significant elevation only during the reoxygenation period. These data raise the possibility that the increase in cardiac HIF-1α expression induced by reoxygenation involves a cascade of signaling events, including activation of the Akt and ERK pathways. In the liver, HIF-1α expression was significantly increased immediately after hypergravity exposure, indicating that hypergravity exposure to causes hepatocellular hypoxia. The hypergravity-exposed livers showed significantly higher eNOS immunoreactivity than did those of control mice. Consistent with these results, significant increases in eNOS activity and nitrate/nitrite levels were also observed. These findings suggest that hypergravity-induced hypoxia plays a significant role in the upregulation of hepatic eNOS. PMID:27191892

  16. Neurofibroma-associated growth factors activate a distinct signaling network to alter the function of neurofibromin-deficient endothelial cells.

    PubMed

    Munchhof, Amy M; Li, Fang; White, Hilary A; Mead, Laura E; Krier, Theresa R; Fenoglio, Amy; Li, Xiaohong; Yuan, Jin; Yang, Feng-Chun; Ingram, David A

    2006-06-01

    Genetic inactivation of tumor suppressor genes initiates human cancers. However, interaction of accessory cells with the tumor-initiating cell within the microenvironment is often required for tumor progression. This paradigm is relevant to understanding neurofibroma development in neurofibromatosis type I patients. Somatic inactivation of the Nf1 tumor suppressor gene, which encodes neurofibromin, is necessary but not sufficient to initiate neurofibroma development. In contrast, neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1+/-) microenvironment. Neurofibromas are highly vascularized, and recent studies suggest that Nf1+/- mice have increased angiogenesis in vivo. However, the function of neurofibromin in human endothelial cells (ECs) and the biochemical mechanism by which neurofibromin regulates neoangiogenesis are not known. Utilizing Nf1+/- mice, primary human ECs and endothelial progenitor cells harvested from NF1 patients, we identified a discrete Ras effector pathway, which alters the proliferation and migration of neurofibromin-deficient ECs in response to neurofibroma-derived growth factors both in vitro and in vivo. Thus, these studies identify a unique biochemical pathway in Nf1+/- ECs as a potential therapeutic target in the neurofibroma microenvironment.

  17. Actin depolymerizing factors ADF7 and ADF10 play distinct roles during pollen development and pollen tube growth.

    PubMed

    Daher, Firas Bou; Geitmann, Anja

    2012-07-01

    An important player in actin remodeling is the actin depolymerizing factor (ADF) which increases actin filament treadmilling rates. Previously, we had prepared fluorescent protein fusions of two Arabidopsis pollen specific ADFs, ADF7 and ADF10. These had enabled us to determine the temporal expression patterns and subcellular localization of these proteins during male gametophyte development. Here we generated stable transformants containing both chimeric genes allowing for simultaneous imaging and direct comparison. One of the striking differences between the two proteins was the localization profile in the growing pollen tube apex. Whereas ADF10 was associated with the filamentous actin array forming the subapical actin fringe, ADF7 was present in the same cytoplasmic region, but in diffuse form. This suggests that ADF7 is involved in the high actin turnover that is likely to occur in the fringe by continuously and efficiently depolymerizing filamentous actin and supplying monomeric actin to the advancing end of the fringe. The possibility to visualize both of these pollen-specific ADFs simultaneously opens avenues for future research into the regulatory function of actin binding proteins in pollen.

  18. Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions

    SciTech Connect

    Irminger, J.C.; Rosen, K.M.; Humble, R.E.; Villa-Komaroff, L.

    1987-09-01

    The authors have used RNA from human hypothalamus as template for the production of cDNAs encoding insulin-like growth factor II (IGF-II). The prohormone coding sequence of brain IGF-II RNA is identical to that found in liver; however, the 5' untranslated sequence of the brain cDNA has no homology to the 5' untranslated sequence of the previously reported liver cDNAs. By using hybridization to specific probes as well as a method based on the properties of RNase H, they found that the human IGF-II gene has at least three exons that encode alternative 5' untranslated regions and that are expressed in a tissue-specific manner. A probe specific to the brain cDNA 5' untranslated region hybridizes to a 6.0-kilobase transcript present in placenta, hypothalamus, adrenal gland, kidney, Wilms tumor, and a pheochromocytoma. The 5' untranslated sequence of the brain cDNA does not hybridize to a 5.3-kilobase transcript found in liver or to a 5.0-kb transcript found in pheochromocytoma. By using RNase H to specifically fragment the IGF-II transcripts into 3' and 5' fragments, they found that the RNAs vary in size due to differences in the 5' end but not the 3' end.

  19. Chelating agents exert distinct effects on biofilm formation in Staphylococcus aureus depending on strain background: role for clumping factor B

    PubMed Central

    Abraham, Nabil M.; Lamlertthon, Supaporn; Fowler, Vance G.

    2012-01-01

    Staphylococcus aureus is a leading cause of catheter infections, and biofilm formation plays a key role in the pathogenesis. Metal ion chelators inhibit bacterial biofilm formation and viability, making them attractive candidates as components in catheter lock solutions. The goal of this study was to characterize further the effect of chelators on biofilm formation. The effect of the calcium chelators ethylene glycol tetraacetic acid (EGTA) and trisodium citrate (TSC) on biofilm formation by 30 S. aureus strains was tested. The response to subinhibitory doses of EGTA and TSC varied dramatically depending on strain variation. In some strains, the chelators prevented biofilm formation, in others they had no effect, and they actually enhanced biofilm formation in others. The molecular basis for this phenotypic variability was investigated using two related strains: Newman, in which biofilm formation was inhibited by chelators, and 10833, which formed strong biofilms in the presence of chelators. It was found that deletion of the gene encoding the surface adhesin clumping factor B (clfB) completely eliminated chelator-induced biofilm formation in strain 10833. The role of ClfB in biofilm formation activity in chelators was confirmed in additional strains. It was concluded that biofilm-forming ability varies strikingly depending on strain background, and that ClfB is involved in biofilm formation in the presence EGTA and citrate. These results suggest that subinhibitory doses of chelating agents in catheter lock solutions may actually augment biofilm formation in certain strains of S. aureus, and emphasize the importance of using these agents appropriately so that inhibitory doses are achieved consistently. PMID:22516131

  20. 137Cs Inter-Plant Concentration Ratios Provide a Predictive Tool for Coral Atolls with Distinct Benefits Over Transfer Factors

    SciTech Connect

    Robison, W L; Hamilton, T F; Bogen, K; Corado, C L; Kehl, S R

    2007-07-17

    Inter-plant concentration ratios (IPCR), [Bq g{sup -1} {sup 137}Cs in coral atoll tree food-crops/Bq g{sup -1} {sup 137}Cs in leaves of native plant species whose roots share a common soil volume], can replace transfer factors (TF) to predict {sup 137}Cs concentration in tree food-crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact tree roots naturally integrate 137Cs over large volumes of soil. Root absorption of {sup 137}Cs replaces large-scale, expensive soil sampling schemes to reduce variability in {sup 137}Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log normally distributed (LND) with geometric standard deviation (GSD) = 1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSD's of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD = 1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10 to 20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples.

  1. (137)Cs inter-plant concentration ratios provide a predictive tool for coral atolls with distinct benefits over transfer factors.

    PubMed

    Robison, William L; Hamilton, Terry F; Bogen, Kenneth T; Conrado, Cynthia L; Kehl, Steven R

    2008-01-01

    Inter-plant concentration ratios (IPCR) [Bqg(-1)(137)Cs in coral atoll tree food crops/Bqg(-1)(137)Cs in leaves of native plant species whose roots share a common soil volume] can replace transfer factors (TF) to predict (137)Cs concentration in tree food crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact that tree roots naturally integrate (137)Cs over large volumes of soil. Root absorption of (137)Cs replaces large-scale, expensive soil sampling schemes to reduce variability in (137)Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log-normally distributed (LND) with geometric standard deviation (GSD)=1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSDs of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD=1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10-20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples.

  2. Chemical profiles of two pheromone glands are differentially regulated by distinct mating factors in honey bee queens (Apis mellifera L.).

    PubMed

    Niño, Elina L; Malka, Osnat; Hefetz, Abraham; Tarpy, David R; Grozinger, Christina M

    2013-01-01

    Pheromones mediate social interactions among individuals in a wide variety of species, from yeast to mammals. In social insects such as honey bees, pheromone communication systems can be extraordinarily complex and serve to coordinate behaviors among many individuals. One of the primary mediators of social behavior and organization in honey bee colonies is queen pheromone, which is produced by multiple glands. The types and quantities of chemicals produced differ significantly between virgin and mated queens, and recent studies have suggested that, in newly mated queens, insemination volume or quantity can affect pheromone production. Here, we examine the long-term impact of different factors involved during queen insemination on the chemical composition of the mandibular and Dufour's glands, two of the major sources of queen pheromone. Our results demonstrate that carbon dioxide (an anesthetic used in instrumental insemination), physical manipulation of genital tract (presumably mimicking the act of copulation), insemination substance (saline vs. semen), and insemination volume (1 vs. 8 µl) all have long-term effects on mandibular gland chemical profiles. In contrast, Dufour's gland chemical profiles were changed only upon insemination and were not influenced by exposure to carbon dioxide, manipulation, insemination substance or volume. These results suggest that the chemical contents of these two glands are regulated by different neuro-physiological mechanisms. Furthermore, workers responded differently to the different mandibular gland extracts in a choice assay. Although these studies must be validated in naturally mated queens of varying mating quality, our results suggest that while the chemical composition of Dufour's gland is associated with mating status, that of the mandibular glands is associated with both mating status and insemination success. Thus, the queen appears to be signaling both status and reproductive quality to the workers, which may impact

  3. Traumatic Experience and Somatoform Dissociation Among Spirit Possession Practitioners in the Dominican Republic.

    PubMed

    Schaffler, Yvonne; Cardeña, Etzel; Reijman, Sophie; Haluza, Daniela

    2016-03-01

    Recent studies in African contexts have revealed a strong association between spirit possession and severe trauma, with inclusion into a possession cult serving at times a therapeutic function. Research on spirit possession in the Dominican Republic has so far not included quantitative studies of trauma and dissociation. This study evaluated demographic variables, somatoform dissociative symptoms, and potentially traumatizing events in the Dominican Republic with a group of Vodou practitioners that either do or do not experience spirit possession. Inter-group comparisons revealed that in contrast to non-possessed participants (n = 38), those experiencing spirit possession (n = 47) reported greater somatoform dissociation, more problems with sleep, and previous exposure to mortal danger such as assaults, accidents, or diseases. The two groups did not differ significantly in other types of trauma. The best predictor variable for group classification was somatoform dissociation, although those items could also reflect the experience of followers during a possession episode. A factor analysis across variables resulted in three factors: having to take responsibility early on in life and taking on a professional spiritual role; traumatic events and pain; and distress/dissociation. In comparison with the non-possessed individuals, the possessed ones did not seem to overall have a remarkably more severe story of trauma and seemed to derive economic gains from possession practice.

  4. Misregulation of AUXIN RESPONSE FACTOR 8 Underlies the Developmental Abnormalities Caused by Three Distinct Viral Silencing Suppressors in Arabidopsis

    PubMed Central

    Jay, Florence; Wang, Yu; Yu, Agnès; Taconnat, Ludivine; Pelletier, Sandra; Colot, Vincent; Renou, Jean-Pierre; Voinnet, Olivier

    2011-01-01

    In Arabidopsis, micro (mi)RNAs and trans-acting (ta-si)RNAs synthesized directly or indirectly through the DICER-LIKE-1 (DCL1) ribonuclease have roles in patterning and hormonal responses, while DCL2,3,4-dependent small-interfering (si)RNAs are mainly involved in silencing of transposable elements and antiviral defense. Viral suppressors of RNA silencing (VSRs) produced by phytoviruses to counter plant defense may perturb plant developmental programs because of the collision of their inhibitory effects with the regulatory action of endogenous miRNAs and ta-siRNAs. This could explain the similar developmental aberrations displayed by Arabidopsis miRNA/ta-siRNA pathway mutants, including dcl1, and by some VSR-expressing plants. Nonetheless, the molecular bases for these morphological aberrations have remained mysterious, and their contribution to viral disease symptoms/virulence unexplored. The extent of VSR inhibitory actions to other types of endogenous small RNAs remains also unclear. Here, we present an in-depth analysis of transgenic Arabidopsis expressing constitutively HcPro, P19 and P15, three unrelated VSRs. We show that VSR expression has comparable, yet modest effects on known miRNA and ta-siRNA target RNA levels, similar to those observed using an hypomorphic dcl1 mutation. However, by combining results of transcriptome studies with deep-sequencing data from immuno-precipitated small RNAs, additional, novel endogenous targets of miRNA and ta-siRNA were identified, unraveling an unsuspected complexity in the origin and scope-of-action of these molecules. Other stringent analyses pinpointed misregulation of the miR167 target AUXIN RESPONSE FACTOR 8 (ARF8) as a major cause for the developmental aberrations exhibited by VSR transgenic plants, but also for the phenotypes induced during normal viral infection caused by the HcPro-encoding Turnip mosaic virus (TuMV). Neither RNA silencing, its suppression by VSRs, nor the virulence/accumulation of TuMV was

  5. Control of fibroblast growth factor (FGF) 7- and FGF1-induced mitogenesis and downstream signaling by distinct heparin octasaccharide motifs.

    PubMed

    Luo, Yongde; Ye, Sheng; Kan, Mikio; McKeehan, Wallace L

    2006-07-28

    Variation in length, disaccharide composition, and sulfation of heparan sulfate (HS) affects fibroblast growth factor (FGF) signaling. However, it is unclear whether the specific distribution of groups within oligosaccharides or random variations in charge density underlies the effects. Recently we showed that a mixture of undersulfated octasaccharides exhibiting 7 and 8 sulfates (7,8-S-OctaF7) generated from heparin had the highest affinity for FGF7 monitored by salt resistance (>0.60 M salt) of octasaccharide-FGF7 complexes. 7,8-S-OctaF7 also had the highest specific activity for formation of a complex with dimeric FGFR2IIIb competent to bind FGF7. Here we show that when endogenous HS was inhibited by chlorate treatment, 7,8-S-OctaF7 specifically supported FGF7-stimulated DNA synthesis and downstream signaling in FGFR2IIIb-expressing mouse keratinocytes. It failed to support FGF1 signaling in both HS-deficient mouse keratinocytes and 3T3 fibroblasts. In contrast, abundant, more highly sulfated and heterogenous mixtures of octasaccharides with lower affinity (0.30-0.60 M salt) for FGF7 supported FGF1-induced signaling in both cell types. In contrast to the two-component 7,8-S-OctaF7 mixture from FGF7, the high affinity octasaccharide fraction from FGF1 was a heterogeneous mixture with components ranging from 8 to 12 sulfates with 11-S-octasaccharides the most abundant. The high affinity fraction exhibited similar properties to the lower affinity fractions from both FGF1 and FGF7. Octasaccharide mixtures eluting from FGF1 between 0.30 and 0.60 M and above 0.60 M salt were nearly equal in support of FGF1 signaling in fibroblasts and keratinocytes. Both were deficient in support of FGF7-induced signaling in keratinocytes. The results show that both variations in overall charge density and specific distribution of charged groups within HS motifs exhibit FGF-specific control over formation of FGF-HS-FGFR complexes and downstream signaling.

  6. L-alanine-glyoxylate aminotransferase II of rat kidney and liver mitochondria possesses cysteine S-conjugate beta-lyase activity: a contributing factor to the nephrotoxicity/hepatotoxicity of halogenated alkenes?

    PubMed Central

    Cooper, Arthur J L; Krasnikov, Boris F; Okuno, Etsuo; Jeitner, Thomas M

    2003-01-01

    Several halogenated alkenes are metabolized in part to cysteine S-conjugates, which are mitochondrial toxicants of kidney and, to a lesser extent, other organs. Toxicity is due to cysteine S-conjugate beta-lyases, which convert the cysteine S-conjugate into pyruvate, ammonia and a reactive sulphur-containing fragment. A section of the human population is exposed to halogenated alkenes. To understand the health effects of such exposure, it is important to identify cysteine S-conjugate beta-lyases that contribute to mitochondrial damage. Mitochondrial aspartate aminotransferase [Cooper, Bruschi, Iriarte and Martinez-Carrion (2002) Biochem. J. 368, 253-261] and mitochondrial branched-chain aminotransferase [Cooper, Bruschi, Conway and Hutson (2003) Biochem. Pharmacol. 65, 181-192] exhibit beta-lyase activity toward S -(1,2-dichlorovinyl)-L-cysteine (the cysteine S-conjugate of trichloroethylene) and S -(1,1,2,2-tetrafluoroethyl)-L-cysteine (the cysteine S-conjugate of tetrafluoroethylene). Turnover leads to eventual inactivation of these enzymes. Here we report that mitochondrial L-alanine-glyoxylate aminotransferase II, which, in the rat, is most active in kidney, catalyses cysteine S-conjugate beta-lyase reactions with S -(1,1,2,2-tetrafluoroethyl)-L-cysteine, S -(1,2-dichlorovinyl)-L-cysteine and S -(benzothiazolyl-L-cysteine); turnover leads to inactivation. Previous workers showed that the reactive-sulphur-containing fragment released from S -(1,1,2,2-tetrafluoroethyl)-L-cysteine and S -(1,2-dichlorovinyl)-L-cysteine is toxic by acting as a thioacylating agent - particularly of lysine residues in nearby proteins. Toxicity, however, may also involve 'self-inactivation' of key enzymes. The present findings suggest that alanine-glyoxylate aminotransferase II may be an important factor in the well-established targeting of rat kidney mitochondria by toxic halogenated cysteine S-conjugates. Previous reports suggest that alanine-glyoxylate aminotransferase II is absent

  7. 50 CFR 20.38 - Possession of live birds.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.38 Possession of live birds. Every migratory game bird wounded by hunting and reduced to possession by the hunter shall be immediately killed...

  8. Persistent influenza C virus possesses distinct functional properties due to a modified HEF glycoprotein.

    PubMed

    Marschall, M; Herrler, G; Böswald, C; Foerst, G; Meier-Ewert, H

    1994-09-01

    A model of long term viral persistence has been established by selecting a spontaneous mutant strain of influenza C/Ann Arbor/1/50 virus in a permanent carrier culture of MDCK cells. Infectivity and cell tropism are mainly determined by the multifunctional viral membrane glycoprotein (HEF). HEF analysis was aimed at identifying a putative correlation between sequence and function, i.e. receptor binding, enzymatic activity, antigenicity and rate of infection. The current experimental picture is summarized by the following findings: (i) C/Ann Arbor/1/50 persistent virus carries a modified receptor-binding sequence, (ii) receptor-binding activity is altered, as indicated by a higher efficiency in recognizing low amounts of the receptor determinant N-acetyl-9-O-acetylneuraminic acid, (iii) direct attachment to cell surfaces differs from that of wild-type virus, as measured by slower kinetics of viral elution, (iv) receptor-destroying enzymatic activity is diminished, (v) characteristic features of virion surface morphology are altered or unstable, (vi) persistent-type HEF epitopes are distinguishable by monoclonal antibodies from wild-type and (vii) viral infectivity is intensified for cells bearing a low number of receptors. The sum of these changes highlights a structurally and functionally modified HEF glycoprotein that allows long term viral persistence. In order to clarify which of the described points are required for the persistent viral phenotype, a working concept is presented.

  9. Stimulation of the human intercellular adhesion molecule-1 promoter by interleukin-6 and interferon-gamma involves binding of distinct factors to a palindromic response element.

    PubMed

    Caldenhoven, E; Coffer, P; Yuan, J; Van de Stolpe, A; Horn, F; Kruijer, W; Van der Saag, P T

    1994-08-19

    Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein that promotes adhesion in immunological and inflammatory reactions. ICAM-1 is expressed on cells of many lineages and is induced by interleukin-6 (IL-6) and interferon-gamma (IFN-gamma). Functional analysis of ICAM-1 promoter-luciferase constructs in HepG2 cells enabled us to identify a region between -110 and -37 mediating IL-6 and IFN-gamma responsiveness and containing a palindromic IL-6/IFN-gamma response element (pIRE). Site-directed mutagenesis of key nucleotides in the ICAM-1 pIRE abolished the effect of both IL-6 and IFN-gamma stimulation, while this pIRE element was sufficient to confer IL-6 and IFN-gamma responsiveness to a heterologous promoter. We further show by gel retardation analysis that distinct nuclear factors induced by both IL-6 or IFN-gamma specifically bind to this pIRE. Furthermore, treatment with IL-6 results in the formation of multiple complexes while IFN-gamma induces a single binding complex, both in HepG2 and monocytic U937 cells. Differentiation of U937 cells by exposure to 12-O-tetradecanoyl phorbol-13-acetate abolishes response to IL-6 but not IFN-gamma. Supershift data utilizing the ICAM-1 pIRE revealed that IFN-gamma and IL-6 both induce a factor antigenically related to IFN-gamma activation factor. We further provide data suggesting that IL-6 additionally activates an ICAM-1 pIRE binding factor related to the previously described acute-phase response factor in disparate cell types. We therefore conclude that the activation of these related nuclear factors by IL-6 and IFN-gamma is important in the regulation of ICAM-1 gene expression.

  10. Weapon Possession Among College Students: A Study From a Midwestern University.

    PubMed

    Jang, Hyunseok; Kang, Ji Hyon; Dierenfeldt, Rick; Lindsteadt, Greg

    2015-10-01

    Weapon possession on college campuses causes great concern, but there remains a lack of research examining the determinants of this phenomenon. Previous studies addressing weapon possession have primarily focused on either K-12 or the general adult population. Unlike previous studies, this study examined the weapon possession among college students using data collected from a mid-sized university in Missouri, and 451 students participated. Weapon possession and other theoretical factors were measured through the self-administered survey. Logistical regression analysis revealed that weapon socialization was the most significant factor in predicting student weapon carrying. Also, gender and age were significant factors in explaining campus-based weapon possession. This research has a limitation with generalizability because the data were collected from only a single university with convenient sampling. Future studies need to cover a wider range of college students from a variety of different universities with random sampling. © The Author(s) 2014.

  11. Distinctions among agency, communion, and unmitigated agency and communion according to the interpersonal circumplex, Five-factor model, and social-emotional correlates.

    PubMed

    Ghaed, Shiva G; Gallo, Linda C

    2006-02-01

    In this study, we examined common measures of agency (AG), communion (CM), and unmitigated agency (UA) and unmitigated communion (UC) using the interpersonal circumplex and Five-factor models (FFM) as conceptual frameworks. AG aligned with interpersonal dominance in circumplex space and related positively to conscientiousness and inversely to neuroticism. CM corresponded with interpersonal affiliation and related positively to conscientiousness. UA was consistent with hostile-dominance and related to lower conscientiousness and higher neuroticism. UC related to friendly submission but was not strongly represented in the circumplex and did not relate to the FFM. Each construct showed distinct social-emotional correlates. These findings support the convergent and divergent properties of the constructs but suggest that additional attention to the conceptual definition and measurement of UC is warranted.

  12. Binding of transcription factor GabR to DNA requires recognition of DNA shape at a location distinct from its cognate binding site.

    PubMed

    Al-Zyoud, Walid A; Hynson, Robert M G; Ganuelas, Lorraine A; Coster, Adelle C F; Duff, Anthony P; Baker, Matthew A B; Stewart, Alastair G; Giannoulatou, Eleni; Ho, Joshua W K; Gaus, Katharina; Liu, Dali; Lee, Lawrence K; Böcking, Till

    2016-02-18

    Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding. In silico predictions suggest that the bridging DNA sequence is likely to be bendable in one direction and kinetic analysis of mutant DNA sequences with biolayer interferometry, allowed the independent quantification of the relative contribution of DNA base and shape recognition in the GabR-DNA interaction. These indicate that the two cognate binding sites as well as the bendability of the DNA sequence in between these sites are required to form a stable complex. The mechanism of GabR-DNA interaction provides an example where the correct shape of DNA, at a clearly distinct location from the cognate binding site, is required for transcription factor binding and has implications for bioinformatics searches for novel binding sites. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Afr1p regulates the Saccharomyces cerevisiae alpha-factor receptor by a mechanism that is distinct from receptor phosphorylation and endocytosis.

    PubMed Central

    Davis, C; Dube, P; Konopka, J B

    1998-01-01

    The alpha-factor pheromone receptor activates a G protein signaling pathway that induces the conjugation of the yeast Saccharomyces cerevisiae. Our previous studies identified AFR1 as a gene that regulates this signaling pathway because overexpression of AFR1 promoted resistance to alpha-factor. AFR1 also showed an interesting genetic relationship with the alpha-factor receptor gene, STE2, suggesting that the receptor is regulated by Afr1p. To investigate the mechanism of this regulation, we tested AFR1 for a role in the two processes that are known to regulate receptor signaling: phosphorylation and down-regulation of ligand-bound receptors by endocytosis. AFR1 overexpression diminished signaling in a strain that lacks the C-terminal phosphorylation sites of the receptor, indicating that AFR1 acts independently of phosphorylation. The effects of AFR1 overexpression were weaker in strains that were defective in receptor endocytosis. However, AFR1 overexpression did not detectably influence receptor endocytosis or the stability of the receptor protein. Instead, gene dosage studies showed that the effects of AFR1 overexpression on signaling were inversely proportional to the number of receptors. These results indicate that AFR1 acts independently of endocytosis, and that the weaker effects of AFR1 in strains that are defective in receptor endocytosis were probably an indirect consequence of their increased receptor number caused by the failure of receptors to undergo ligand-stimulated endocytosis. Analysis of the ligand binding properties of the receptor showed that AFR1 overexpression did not alter the number of cell-surface receptors or the affinity for alpha-factor. Thus, Afr1p prevents alpha-factor receptors from activating G protein signaling by a mechanism that is distinct from other known pathways. PMID:9504911

  14. Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system.

    PubMed

    van der Lee, Robin; Szklarczyk, Radek; Smeitink, Jan; Smeets, Hubert J M; Huynen, Martijn A; Vogel, Rutger

    2015-09-15

    Transcriptional control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study we performed RNA sequencing of two control and two complex I-deficient patient cell lines cultured in the presence of compounds that perturb mitochondrial metabolism: chloramphenicol, AICAR, or resveratrol. We combined this with a comprehensive analysis of mitochondrial and nuclear gene expression patterns, co-expression calculations and transcription factor binding sites. Our analyses show that subsets of mitochondrial OXPHOS genes respond opposingly to chloramphenicol and AICAR, whereas the response of nuclear OXPHOS genes is less consistent between cell lines and treatments. Across all samples nuclear OXPHOS genes have a significantly higher co-expression with each other than with other genes, including those encoding mitochondrial proteins. We found no evidence for complex-specific mRNA expression regulation: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of nuclear genes for OXPHOS subunits versus assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of novel candidates (ELK1, KLF7, SP4, EHF, ZNF143, and TEL2). OXPHOS genes share an expression program distinct from other genes

  15. Detailed Analysis of Clinicopathologic Factors Demonstrate Distinct Difference in Outcome and Prognostic Factors Between Surgically Treated HPV-Positive and Negative Oropharyngeal Cancer

    PubMed Central

    Iyer, N. Gopalakrishna; Dogan, Snjezana; Palmer, Frank; Rahmati, Rahmatullah; Nixon, Iain J.; Lee, Nancy; Patel, Snehal G.; Shah, Jatin P.; Ganly, Ian

    2016-01-01

    Background Oropharyngeal cancers (OPC) secondary to human papillomavirus (HPV) infections likely represent a completely different disease compared with conventional head and neck cancers. Our objective was to analyze a surgically treated cohort to determine predictors of outcome in HPV-positive versus HPV-negative patients. Methods HPV positivity was inferred based on p16-immunohistochemistry. Data was available for 201 patients with OPC treated with surgical resection with/without adjuvant radiotherapy between 1985 and 2005. Subsite distribution was: 66 (33 %) tonsil, 46 (23 %) soft palate, and 89 (44 %) tongue base. Patients were classified into low-, intermediate-, and high-risk groups based on p16 status and smoking history. Outcomes stratified by p16 status and risk groups were determined by the Kaplan–Meier method. Factors predictive of outcome were determined by univariate and multivariate analyses. Results In this cohort, 30 % had locally advanced disease (pT3/T4) and 71 % had nodal metastasis. The 5-year overall (OS), disease-specific, and recurrence-free survival rates were 60, 76, and 66 %, respectively. There were 22 % low-, 34 % intermediate-, and 44 % high-risk patients. Patients who were p16-positive had better survival compared with p16-negative (OS, 74 vs. 44 %; p < .001). Similarly, low-risk group patients had a better survival compared with intermediate- and high-risk groups (OS, 76, 68, 45 %, respectively, p < .001). Independent predictors of survival in p16-negative patients included margin status, lymphovascular invasion, pN status, and extracapsular spread. In contrast, none of these were predictive in p16-positive patients. Conclusions Surgically treated patients with p16-positive OPC have superior survival compared with p16-negative patients. Outcomes in p16-positive and p16-negative OPC are determined by different prognostic factors supporting the notion that these are very different diseases. These should be incorporated into future

  16. Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

    PubMed Central

    Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

    2012-01-01

    Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

  17. A distinct basic fibroblast growth factor (FGF-2)/FGF receptor interaction distinguishes urokinase-type plasminogen activator induction from mitogenicity in endothelial cells.

    PubMed Central

    Rusnati, M; Dell'Era, P; Urbinati, C; Tanghetti, E; Massardi, M L; Nagamine, Y; Monti, E; Presta, M

    1996-01-01

    Basic fibroblast growth factor (FGF-2) induces cell proliferation and urokinase-type plasminogen activator (uPA) production in fetal bovine aortic endothelial GM 7373 cells. In the present paper we investigated the role of the interaction of FGF-2 with tyrosine-kinase (TK) FGF receptors (FGFRs) in mediating uPA up-regulation in these cells. The results show that FGF-2 antagonists suramin, protamine, heparin, the synthetic peptide FGF-2(112-155), and a soluble form of FGFR-1 do not inhibit FGF-2-mediated uPA up-regulation at concentrations that affect growth factor binding to cell surface receptors and mitogenic activity. In contrast, tyrosine phosphorylation inhibitors and overexpression of a dominant negative TK- mutant of FGFR-1 abolish the uPA-inducing activity of FGF-2, indicating that FGFR and its TK activity are essential in mediating uPA induction. Accordingly, FGF-2 induces uPA up-regulation in Chinese hamster ovary cells transfected with wild-type FGFR-1, -2, -3, or -4 but not with TK- FGFR-1 mutant. Small unilamellar phosphatidyl choline:cholesterol vesicles loaded with FGF-2 increased uPA production in GM 7373 cells in the absence of a mitogenic response. Liposome-encapsulated FGF-2 showed a limited but significant capacity, relative to free FGF-2, to interact with FGFR both at 4 degrees C and 37 degrees C and to be internalized within the cell. uPA up-regulation by liposome-encapsulated FGF-2 was quenched by neutralizing anti-FGF-2 antibodies, indicating that the activity of liposome-delivered FGF-2 is mediated by an extracellular action of the growth factor. Taken together, the data indicate that a distinct interaction of FGF-2 with FGFR, quantitatively and/or qualitatively different from the one that leads to mitogenicity, is responsible for the uPA-inducing activity of the growth factor. Images PMID:8868466

  18. Cherished Possessions and Adaptation of Older People to Nursing Homes.

    ERIC Educational Resources Information Center

    Wapner, Seymour; And Others

    1990-01-01

    Examined cherished possessions and adaptation to nursing home of 100 nursing home residents. Findings showed those with possessions were better adapted; possessions served functions of historical continuity, comfort, and belongingness; and more women than men had cherished possessions. (Author/PVV)

  19. 50 CFR 20.38 - Possession of live birds.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Possession of live birds. 20.38 Section 20... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.38 Possession of live birds. Every migratory game bird wounded by hunting and reduced to possession by the hunter shall be immediately killed...

  20. 50 CFR 20.38 - Possession of live birds.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Possession of live birds. 20.38 Section 20... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.38 Possession of live birds. Every migratory game bird wounded by hunting and reduced to possession by the hunter shall be immediately killed...

  1. 50 CFR 20.38 - Possession of live birds.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Possession of live birds. 20.38 Section 20... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.38 Possession of live birds. Every migratory game bird wounded by hunting and reduced to possession by the hunter shall be immediately killed...

  2. 50 CFR 20.38 - Possession of live birds.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Possession of live birds. 20.38 Section 20... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.38 Possession of live birds. Every migratory game bird wounded by hunting and reduced to possession by the hunter shall be immediately killed...

  3. [The phenomenon of possession. Conception and experiences of possession in youth].

    PubMed

    Bron, B

    1975-01-01

    In the last few years, a trend to the multiplication of experiences of possession has been observed in young people. On the basis of four typical examples, the author examines this phenomenon in the light of the psychiatric, psychoanalytic and theological understanding of possession. It involves mostly young people, who do not have hysterical fits or psychotic episodes during spiritualist practices but who specially tend to take a strong interest in occultism, who very often consume drugs and have contacts with groups in which the interest for demonology plays an important part.

  4. Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions.

    PubMed

    Wang, Qian; Polimanti, Renato; Kranzler, Henry R; Farrer, Lindsay A; Zhao, Hongyu; Gelernter, Joel

    2017-01-01

    Schizophrenia (SZ) and HIV infection are serious disorders with a complex phenotypic relationship. Observational studies have described their comorbidity; their genetic correlation is not well studied. We performed extensive analysis in search of common genetic factors for SZ and HIV, and their relationship with risky sexual behavior (RSB). Summary statistics from genome-wide association studies of HIV infection and schizophrenia were obtained and 2379 European Americans were genotyped and assessed for RSB score. Genetic relationships between traits were analyzed in three ways: linkage disequilibrium (LD) score regression to estimate genetic correlation; GPA (Genetic analysis incorporating Pleiotropy and Annotation) to test pleiotropy and identify pleiotropic loci; polygenic risk scores (PRS) of SZ and HIV to predict RSB using linear regression. We found significant pleiotropy (p = 5.31E - 28) and a positive genetic correlation (cor = 0.17, p = 0.002) for SZ and HIV infection. Pleiotropic SNPs with opposite effect directions (antagonistic) and SNPs with the same effect direction (synergistic) were enriched for distinctly different biological functions. SZ PRS computed with antagonistically pleiotropic SNPs consistently predicted RSB score with nominal significance, but SZ PRS based on either synergistically pleiotropic SNPs or all SNPs did not predict RSB. The epidemiologic correlation between schizophrenia and HIV can partly be explained by overlapping genetic risk factors, which are related to risky sexual behavior.

  5. Corynebacterium glutamicum possesses β-N-acetylglucosaminidase.

    PubMed

    Matano, Christian; Kolkenbrock, Stephan; Hamer, Stefanie N; Sgobba, Elvira; Moerschbacher, Bruno M; Wendisch, Volker F

    2016-08-05

    In Gram-positive Corynebacterium glutamicum and other members of the suborder Corynebacterianeae, which includes mycobacteria, cell elongation and peptidoglycan biosynthesis is mainly due to polar growth. C. glutamicum lacks an uptake system for the peptidoglycan constituent N-acetylglucosamine (GlcNAc), but is able to catabolize GlcNAc-6-phosphate. Due to its importance in white biotechnology and in order to ensure more sustainable processes based on non-food renewables and to reduce feedstock costs, C. glutamicum strains have previously been engineered to produce amino acids from GlcNAc. GlcNAc also is a constituent of chitin, but it is unknown if C. glutamicum possesses chitinolytic enzymes. Chitin was shown here not to be growth substrate for C. glutamicum. However, its genome encodes a putative N-acetylglucosaminidase. The nagA 2 gene product was active as β-N-acetylglucosaminidase with 0.27 mM 4-nitrophenyl N,N'-diacetyl-β-D-chitobioside as substrate supporting half-maximal activity. NagA2 was secreted into the culture medium when overproduced with TAT and Sec dependent signal peptides, while it remained cytoplasmic when overproduced without signal peptide. Heterologous expression of exochitinase gene chiB from Serratia marcescens resulted in chitinolytic activity and ChiB secretion was enhanced when a signal peptide from C. glutamicum was used. Colloidal chitin did not support growth of a strain secreting exochitinase ChiB and β-N-acetylglucosaminidase NagA2. C. glutamicum possesses β-N-acetylglucosaminidase. In the wild type, β-N-acetylglucosaminidase activity was too low to be detected. However, overproduction of the enzyme fused to TAT or Sec signal peptides led to secretion of active β-N-acetylglucosaminidase. The finding that concomitant secretion of endogenous NagA2 and exochitinase ChiB from S. marcescens did not entail growth with colloidal chitin as sole or combined carbon source, may indicate the requirement for higher or additional enzyme

  6. Transcription Factor STE12α Has Distinct Roles in Morphogenesis, Virulence, and Ecological Fitness of the Primary Pathogenic Yeast Cryptococcus gattii†

    PubMed Central

    Ren, Ping; Springer, Deborah J.; Behr, Melissa J.; Samsonoff, William A.; Chaturvedi, Sudha; Chaturvedi, Vishnu

    2006-01-01

    Cryptococcus gattii is a primary pathogenic yeast, increasingly important in public health, but factors responsible for its host predilection and geographical distribution remain largely unknown. We have characterized C. gattii STE12α to probe its role in biology and pathogenesis because this transcription factor has been linked to virulence in many human and plant pathogenic fungi. A full-length STE12α gene was cloned by colony hybridization and sequenced using primer walk and 3′ rapid amplification of cDNA ends strategies, and a ste12αΔ gene knockout mutant was created by URA5 insertion at the homologous site. A semiquantitative analysis revealed delayed and poor mating in ste12αΔ mutant; this defect was not reversed by exogenous cyclic AMP. C. gattii parent and mutant strains showed robust haploid fruiting. Among putative virulence factors tested, the laccase transcript and enzymatic activity were down regulated in the ste12αΔ mutant, with diminished production of melanin. However, capsule, superoxide dismutase, phospholipase, and urease were unaffected. Similarly, Ste12 deficiency did not cause any auxotrophy, assimilation defects, or sensitivity to a large panel of chemicals and antifungals. The ste12αΔ mutant was markedly attenuated in virulence in both BALB/c and A/Jcr mice models of meningoencephalitis, and it also exhibited significant in vivo growth reduction and was highly susceptible to in vitro killing by human neutrophils (polymorphonuclear leukocytes). In tests designed to simulate the C. gattii natural habitat, the ste12αΔ mutant was poorly pigmented on wood agar prepared from two tree species and showed poor survival and multiplication in wood blocks. Thus, STE12α plays distinct roles in C. gattii morphogenesis, virulence, and ecological fitness. PMID:16835451

  7. 22 CFR 72.14 - Nominal possession; property not normally taken into physical possession.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... possession. (a) When a consular officer take articles of a decedent's personal property from a foreign... Department discharging the consular officer of any responsibility for the articles transferred. (b) A... effects; (2) Motor vehicles, airplanes or watercraft; (3) Toiletries, such as toothpaste or razors; (4...

  8. Firearm possession among adolescents presenting to an urban emergency department for assault.

    PubMed

    Carter, Patrick M; Walton, Maureen A; Newton, Manya F; Clery, Michael; Whiteside, Lauren K; Zimmerman, Marc A; Cunningham, Rebecca M

    2013-08-01

    Firearm violence is a leading cause of death among youth. The objectives of this study were (1) determine firearm possession rates and associated correlates among youth seeking care for assault in an emergency department (ED); (2) understand differences in risk factors for youth with firearm possession; and (3) identify firearm possession characteristics in this population: type, reason for possession, and source of firearms. Youth (14 to 24 years old) presenting to a Level 1 ED with assault were administered a computerized screening survey. Validated instruments were administered, measuring demographics, firearm rates and characteristics, attitudes toward aggression, substance use, and previous violence history. Among 689 assault-injured youth, 23% reported firearm possession in the past 6 months. Only 17% of those reporting firearm possession obtained the gun from a legal source; 22% reported ownership of highly lethal automatic/semiautomatic weapons and 37.1% reported having a firearm for protection. Logistic regression analysis identified significant correlates of firearm possession, including male gender, higher socioeconomic status, illicit drug use, recent serious fight, and retaliatory attitudes. ED assault-injured youth had high rates of firearm possession (23.1%), most of which were not obtained from legal sources. Youth with firearm possession were more likely to have been in a recent serious fight, and to endorse aggressive attitudes that increase their risk for retaliatory violence. Future prevention efforts should focus on minimizing illegal firearm access among high-risk youth, nonviolent alternatives to retaliatory violence, and substance use prevention.

  9. Predicting distinct organization of transcription factor binding sites on the promoter regions: a new genome-based approach to expand human embryonic stem cell regulatory network.

    PubMed

    Hosseinpour, Batool; Bakhtiarizadeh, Mohammad Reza; Khosravi, Pegah; Ebrahimie, Esmaeil

    2013-12-01

    Self-proliferation and differentiation into distinct cell types have been made stem cell as a promising target for regenerative medicine. Several key genes can regulate self-renewal and pluripotency of embryonic stem cells (hESCs). They work together and build a transcriptional hierarchy. Coexpression and coregulation of genes control by common regulatory elements on the promoter regions. Consequently, distinct organization and combination of transcription factor binding sites (TFBSs modules) on promoter regions, in view of order and distance, lead to a common specific expression pattern within a set of genes. To gain insights into transcriptional regulation of hESCs, we selected promoter regions of eleven common expressed hESC genes including SOX2, LIN28, STAT3, NANOG, LEFTB, TDGF1, POU5F1, FOXD3, TERF1, REX1 and GDF3 to predict activating regulatory modules on promoters and discover key corresponding transcription factors. Then, promoter regions in human genome were explored for modules and 328 genes containing the same modules were detected. Using microarray data, we verified that 102 of 328 genes commonly upregulate in hESCs. Also, using output data of DNA-protein interaction assays, we found that 42 of all predicted genes are targets of SOX2, NANOG and POU5F1. Additionally, a protein interaction network of hESC genes was constructed based on biological processes, and interestingly, 126 downregulated genes along with upregulated ones identified by promoter analysis were predicted in the network. Based on the results, we suggest that the identified genes, coregulating with common hESC genes, represent a novel approach for gene discovery based on whole genome promoter analysis irrespective of gene expression. Altogether, promoter profiling can be used to expand hESC transcriptional regulatory circuitry by analysis of shared functional sequences between genes. This approach provides a clear image on underlying regulatory mechanism of gene expression profile and

  10. Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites.

    PubMed Central

    Toniatti, C; Demartis, A; Monaci, P; Nicosia, A; Ciliberto, G

    1990-01-01

    The promoter region of the human C-reactive protein (CRP) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL-6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF-1/LF-B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF-1 site is used as competitor. However, HNF-1 is not the intranuclear mediator of IL-6 because synthetic promoters formed by multimerized copies of different HNF-1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF-1 is capable of trans-activating transcription from the wild-type CRP promoter but not from mutants which have lost the ability to bind HNF-1. Moreover, the level of trans-activation observed with the natural promoter containing both HNF-1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF-1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 7. PMID:2265613

  11. Human marrow megakaryocyte differentiation: multiparameter correlative analysis identifies von Willebrand factor as a sensitive and distinctive marker for early (2N and 4N) megakaryocytes.

    PubMed

    Tomer, Aaron

    2004-11-01

    Human megakaryocyte differentiation and maturation were studied in fresh marrow aspirates by using multiparameter flow cytometric correlative analysis. The expression of glycoprotein (GP)IIb/IIIa, GPIIIa, GPIb, and CD36 correlated directly with cell size and ploidy (r > 0.97); however, GPIb acquisition was relatively slow. von Willebrand factor (VWF) is robustly expressed by early (2N and 4N) megakaryocytes, enabling their complete resolution from the other marrow cells at a level superior to that achieved with GPIIb/IIIa. Expression of myeloid CD45 and immunoglobulin G (IgG)-FcgammaRII receptor (CDw32) increased with megakaryocyte maturation and contrasted with the declining expression of HLA-DR (negative in platelets). Interleukin-6 receptor expression in megakaryocytes was higher than in other marrow cells. By using the time-of-flight technique, the diameter of the megakaryocyte population was 37 +/- 4 microm (mean +/- 1 SD) compared with 14 +/- 2 microm for the total marrow cells, ranging from 21 +/- 4 microm for 2N cells to 56 +/- 8 microm for 64N cells. Cell size directly correlated with cell DNA (r = 0.98). Receptor density of GPIIb/IIIa and GPIb decreased with the transition from 2N to 4N cells, then reached maximum at 32N cells. In conclusion, the present methods are useful for studying in vivo human megakaryocytopoiesis in normal and altered states. The expression of VWF is a sensitive and distinctive marker for the identification of young marrow megakaryocytes.

  12. Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus

    SciTech Connect

    Sorensen, Karina Dalsgaard; Sorensen, Annette Balle; Quintanilla-Martinez, Leticia; Kunder, Sandra; Schmidt, Joerg; Pedersen, Finn Skou . E-mail: fsp@mb.au.dk

    2005-04-10

    Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity.

  13. Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells.

    PubMed

    Danzer, Steve C; McNamara, James O

    2004-12-15

    Hippocampal dentate granule cells directly excite and indirectly inhibit CA3 pyramidal cells via distinct presynaptic terminal specializations of their mossy fiber axons. This mossy fiber pathway contains the highest concentration of brain-derived neurotrophic factor (BDNF) in the CNS, yet whether BDNF is positioned to regulate the excitatory and/or inhibitory pathways is unknown. To localize BDNF, confocal microscopy of green fluorescent protein transgenic mice was combined with BDNF immunohistochemistry. Approximately half of presynaptic granule cell-CA3 pyramidal cell contacts were found to contain BDNF. Moreover, enhanced neuronal activity virtually doubled the percentage of BDNF-immunoreactive terminals contacting CA3 pyramidal cells. To our surprise, BDNF was also found in mossy fiber terminals contacting inhibitory neurons. These studies demonstrate that mossy fiber BDNF is poised to regulate both direct excitatory and indirect feedforward inhibitory inputs to CA3 pyramdal cells and reveal that seizure activity increases the pool of BDNF-expressing granule cell presynaptic terminals contacting CA3 pyramidal cells.

  14. Joint and distinct risk factors associated with micro- and macrovascular complications in a cohort of type 2 diabetic patients cared through disease management.

    PubMed

    Ciardullo, Anna V; Daghio, M Monica; Bevini, Massimo; Feltri, Gaetano; Novi, Doriano; Fattori, Giuseppe; Borsari, Silvana; Donato, Carlo Di

    2010-12-01

    We analysed the risk factors associated with diabetic complications in the cohort of patients assisted by a type 2 diabetes mellitus (T2DM) shared-care program. We analysed registry data from 16,136 T2DM patients. Of them, 4,781 had microangiopathy, 3,469 CV events. They were 70.5 ± 17.1 years old, 50% were male, disease duration 13.3 ± 7.8 years, BMI 28.7 ± 4.9 kg/m², HbA1c 7.08 ± 1.23%, FBG 134.7 ± 35.7 mg/dl, 2hPPBG 163.9 ± 47.8 mg/dl, 12.5% smokers. Cholesterol 202.5 ± 37.6 mg/dl, HDL 51.4 ± 20.4 mg/dl, LDL 126.5 ± 36.0 mg/dl, triglyceride 146.2 ± 72.4 mg/dl, SBP 137.8 ± 14.2 mmHg, DBP 80.7 ± 10.8 mmHg, 10-year CV risk score 13.7 ± 9.1; 70.4% had no microangiopathy-i.e. renal, retinal, peripheral nerve disease-and 78.5% of patients had no CV events. Age-adjusted risk factors associated with diabetic complications were male gender, HbA1c, 2hPPBG, HDL, and triglyceride. FBG and SBP were associated with microangiopathy, whereas smoking with cardiovascular events. Optimal targets were reached in: FBG 17%, 2hPPBG 8%, HbA1c 21%, cholesterol 17%, HDL 8%, LDL 5%, triglyceride 20%, SBP 13%, DBP 30%. Drug profiles showed 13% using metformin, 28% sulphonilureas, 26% bitherapy, 4% insulin; 12% statins, 16% anti-platelets, 27% anti-hypertensives, 2% anti-coagulants. T2DM patients showed an acceptable CV risk profile. Joint risk factors for diabetic complications were male gender, HbA1c, 2hPPBG, HDL, and triglyceride. Distinct risk factors were FBG and SBP for micro- and smoking for macrovascular disease. A targeted-to-treat approach needs more attention in the care of T2DM patients.

  15. Cultural variations in interpretation of postnatal illness: Jinn possession amongst Muslim communities.

    PubMed

    Hanely, Jane; Brown, Amy

    2014-04-01

    Maternal experience of emotional and physical disturbance during the postnatal period is a worldwide occurrence but may be interpreted differently according to cultural background. Little is known about different expressions and treatment of cultural phenomena during the postnatal period such as the affliction of Jinn possession in Arabic cultures. Jinn are considered to be evil spirits, which cause emotional and physical distress at times of vulnerability such as the postnatal period. The aim of this paper was to explore maternal experience of Jinn possession and draw parallels with Western interpretations of postnatal illness. Ten women in an Arabian Gulf state who had recently given birth and identified themselves as having Jinn possession were interviewed as to their experiences of Jinn possession. Mothers described the Jinn as evil spirits who cause symptoms such as sadness, anxiety and physical malaise during the postnatal period. Numerous risk factors for possession emerged such as lack of familial support, poverty and a traumatic birth. Clear parallels emerged between Western concepts of postnatal illness and Jinn possession. Mothers in Muslim cultures may experience Jinn possession during the postnatal period, which reflects similar symptoms and aetiology to Western concepts of postnatal illness. With increasing multiculturalism in the UK, understanding the origins and perception of Jinn possession is important for health professionals working in Muslim communities here.

  16. Possession Zone as a Performance Indicator in Football. The Game of the Best Teams

    PubMed Central

    Casal, Claudio A.; Maneiro, Rubén; Ardá, Toni; Marí, Francisco J.; Losada, José L.

    2017-01-01

    Possession time in football has been widely discussed in research but few studies have analyzed the importance of the field area in which possession occurs. The objective of this study was to identify the existence of significant differences in the field zone of ball possession between successful and unsuccessful teams and to acknowledge if the match status modulates the possession model. To this end, 2,284 attacks were analyzed corresponding to the matches in the final phase of the UEFA Euro 2016 France, recording possession time and field zone in which possession occurred. Video recordings of matches were analyzed and coded post-event using notational analysis. We have found that successful offensive game patterns are different from unsuccessful ones. Specifically, field zone in which major possession occurs changes significantly between successful and unsuccessful teams (x2 = 15.72, p < 0.05) and through Welch’s T significant differences were detected in possession time between successful and unsuccessful teams (H = 24.289, p < 0.001). The former are characterized by longer possession times, preferably in the middle offensive zone, on the other hand, unsuccessful teams have shorter possession times and preferably on the middle defensive zone. Logistic regression also allowed us to identify that greater possession in the middle offensive zone is a good indicator of success in the offensive game, allowing us to predict a greater chance of victory in the match. Specifically, every time the teams achieve possession in the middle offensive zone, the chance of winning the match will increase 1.72 times and, the probability of winning the match making longer possessions in the middle offensive zone is 44.25%. Applying the Kruskal–Wallis test we have also been able to verify how match status modulates the teams possession time, specifically, when teams are winning they have longer possessions x2 = 92.628, p = 0.011. Results obtained are expected to help gain more

  17. The clinical characteristics of possession disorder among 20 Chinese patients in the Hebei province of China.

    PubMed

    Gaw, A C; Ding, Q; Levine, R E; Gaw, H

    1998-03-01

    This paper describes the clinical characteristics of 20 hospitalized psychiatric patients in the Hebei province of China who believed they were possessed. A structured interview focused on clinical characteristics associated with possession phenomena was developed and administered to 20 patients at eight hospitals in the province. All patients had been given the Chinese diagnosis of yi-ping (hysteria) by Chinese physicians before being recruited for the study. The subjects' mean age was 37 years. Most were women from rural areas with little education. Major events reported to precede possession included interpersonal conflicts, subjectively meaningful circumstances, illness, and death of an individual or dreaming of a deceased individual. Possessing agents were thought to be spirits of deceased individuals, deities, animals, and devils. Twenty percent of subjects reported multiple possessions. The initial experience of possession typically came on acutely and often became a chronic relapsing illness. Almost all subjects manifested the two symptoms of loss of control over their actions and acting differently. They frequently showed loss of awareness of surroundings, loss of personal identity, inability to distinguish reality from fantasy, change in tone of voice, and loss of perceived sensitivity to pain. Preliminary findings indicate that the disorder is a syndrome with distinct clinical characteristics that adheres most closely to the DSM-IV diagnosis of dissociative trance disorder under the category of dissociative disorder not otherwise specified.

  18. 31 CFR 0.215 - Possession of weapons and explosives.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Possession of weapons and explosives... OF THE TREASURY EMPLOYEE RULES OF CONDUCT Rules of Conduct § 0.215 Possession of weapons and explosives. (a) Employees shall not possess firearms, explosives, or other dangerous or deadly weapons...

  19. 50 CFR 648.145 - Black sea bass possession limit.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Black sea bass possession limit. 648.145... Measures for the Black Sea Bass Fishery § 648.145 Black sea bass possession limit. (a) During the recreational fishing season specified at § 648.146, no person shall possess more than 15 black sea bass in, or...

  20. 50 CFR 648.145 - Black sea bass possession limit.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Black sea bass possession limit. 648.145... Measures for the Black Sea Bass Fishery § 648.145 Black sea bass possession limit. (a) During the recreational fishing season specified at § 648.146, no person shall possess more than 20 black sea bass in, or...

  1. 50 CFR 648.145 - Black sea bass possession limit.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Black sea bass possession limit. 648.145... Measures for the Black Sea Bass Fishery § 648.145 Black sea bass possession limit. (a) From January 1 through February 28, no person shall possess more than 15 black sea bass in, or harvested from, the EEZ...

  2. 31 CFR 0.215 - Possession of weapons and explosives.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Possession of weapons and explosives... explosives. (a) Employees shall not possess firearms, explosives, or other dangerous or deadly weapons... paragraph (a) of this section does not apply to employees who are required to possess weapons or explosives...

  3. 46 CFR 308.504 - Definition of territories and possessions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Definition of territories and possessions. 308.504... RISK INSURANCE War Risk Cargo Insurance I-Introduction § 308.504 Definition of territories and possessions. Whenever reference is made to the territories and possessions of the United States in this...

  4. 50 CFR 20.39 - Termination of possession.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.39 Termination of possession. Subject to all other requirements of this part, the possession of birds taken by any hunter shall be... consigned for transport by the Postal Service or a common carrier to some person other than the hunter. ...

  5. 50 CFR 20.35 - Field possession limit.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Field possession limit. 20.35 Section 20.35 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.35 Field possession limit. No...

  6. 50 CFR 20.35 - Field possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Field possession limit. 20.35 Section 20.35 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.35 Field possession limit. No...

  7. 50 CFR 20.35 - Field possession limit.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Field possession limit. 20.35 Section 20.35 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.35 Field possession limit. No...

  8. 50 CFR 20.35 - Field possession limit.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Field possession limit. 20.35 Section 20.35 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.35 Field possession limit. No...

  9. 50 CFR 20.35 - Field possession limit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Field possession limit. 20.35 Section 20.35 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.35 Field possession limit. No...

  10. 31 CFR 0.215 - Possession of weapons and explosives.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Possession of weapons and explosives... OF THE TREASURY EMPLOYEE RULES OF CONDUCT Rules of Conduct § 0.215 Possession of weapons and explosives. (a) Employees shall not possess firearms, explosives, or other dangerous or deadly...

  11. 31 CFR 0.215 - Possession of weapons and explosives.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Possession of weapons and explosives... OF THE TREASURY EMPLOYEE RULES OF CONDUCT Rules of Conduct § 0.215 Possession of weapons and explosives. (a) Employees shall not possess firearms, explosives, or other dangerous or deadly...

  12. 31 CFR 0.215 - Possession of weapons and explosives.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Possession of weapons and explosives... OF THE TREASURY EMPLOYEE RULES OF CONDUCT Rules of Conduct § 0.215 Possession of weapons and explosives. (a) Employees shall not possess firearms, explosives, or other dangerous or deadly...

  13. 50 CFR 622.277 - Bag and possession limits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ATLANTIC Dolphin and Wahoo Fishery Off the Atlantic States § 622.277 Bag and possession limits. Section 622.11(a) provides the general applicability for bag and possession limits. (a) Atlantic dolphin and wahoo. Bag and possession limits are as follows: (1) Dolphin—10, not to exceed 60 per vessel,...

  14. 50 CFR 622.277 - Bag and possession limits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ATLANTIC Dolphin and Wahoo Fishery Off the Atlantic States § 622.277 Bag and possession limits. Section 622.11(a) provides the general applicability for bag and possession limits. (a) Atlantic dolphin and wahoo. Bag and possession limits are as follows: (1) Dolphin—10, not to exceed 60 per vessel,...

  15. Interleukin-6 and leukemia inhibitory factor induction of JunB is regulated by distinct cell type-specific cis-acting elements.

    PubMed

    Sjin, R M; Lord, K A; Abdollahi, A; Hoffman, B; Liebermann, D A

    1999-10-01

    Interleukin (IL)-6 plays an important role in a wide range of biological activities, including differentiation of murine M1 myeloid leukemic cells into mature macrophages. At the onset of M1 differentiation, a set of myeloid differentiation primary response (MyD) genes are induced, including the proto-oncogene for JunB. In order to examine the molecular nature of the mechanisms by which IL-6 activates the immediate early expression of MyD genes, JunB was used as a paradigm. A novel IL-6 response element, -65/-52 IL-6RE, to which a 100-kDa protein complex is bound, has been identified on the JunB promoter. Leukemia inhibitory factor (LIF)-induced activation of JunB in M1 cells was also mediated via the -65/-52 IL-6RE. The STAT3 and CRE-like binding sites of the JunB promoter, identified as IL-6-responsive elements in HepG2 liver cells were found, however, to play no role in JunB inducibility by IL-6 in M1 myeloid cells. Conversely, the -65/-52 IL-6RE is shown not to be necessary for JunB inducibility by IL-6 or LIF in liver cells. It appears, therefore, that immediate early activation of JunB is regulated differently in M1 myeloid cells than in HepG2 liver cells. This indicates that distinct cis-acting control elements participate in cell type-specific induction of JunB by members of the IL-6 cytokine superfamily.

  16. Common and distinct functions of Arabidopsis class A1 and A2 heat shock factors in diverse abiotic stress responses and development.

    PubMed

    Liu, Hsiang-chin; Charng, Yee-yung

    2013-09-01

    There are 21 heat shock factor (HSF) homologs in Arabidopsis (Arabidopsis thaliana), of which members of class A1 (HSFA1a/HSFA1b/HSFA1d/HSFA1e) play the major role in activating the transcription of heat-induced genes, including HSFA2. Once induced, HSFA2 becomes the dominant HSF and is able to form heterooligomeric complexes with HSFA1. However, whether HSFA2 could function independently as a transcription regulator in the absence of the HSFA1s was undetermined. To address this question, we introduced a Cauliflower mosaic virus 35S promoter:HSFA2 construct into hsfa1a/hsfa1b/hsfa1d/hsfa1e quadruple knockout (QK) and wild-type (Wt) backgrounds to yield transgenic lines A2QK and A2Wt, respectively. Constitutive expression of HSFA2 rescued the developmental defects of the QK mutant and promoted callus formation in A2QK, but not in A2Wt, after heat treatment. Transcriptome analysis showed that heat stress response genes are differentially regulated by the HSFA1s and HSFA2; the genes involved in metabolism and redox homeostasis are preferentially regulated by HSFA2, while HSFA1-preferring genes are enriched in transcription function. Ectopic expression of HSFA2 complemented the defects of QK in tolerance to different heat stress regimes, and to hydrogen peroxide, but not to salt and osmotic stresses. Furthermore, we showed that HSFA1a/HSFA1b/HSFA1d are involved in thermotolerance to mild heat stress at temperatures as low as 27°C. We also noticed subfunctionalization of the four Arabidopsis A1-type HSFs in diverse abiotic stress responses. Overall, this study reveals the overlapping and distinct functions of class A1 and A2 HSFs and may enable more precise use of HSFs in engineering stress tolerance in the future.

  17. Distinct Splice Variants of Dynamin-related Protein 1 Differentially Utilize Mitochondrial Fission Factor as an Effector of Cooperative GTPase Activity*

    PubMed Central

    Macdonald, Patrick J.; Francy, Christopher A.; Stepanyants, Natalia; Lehman, Lance; Baglio, Anthony; Mears, Jason A.; Qi, Xin; Ramachandran, Rajesh

    2016-01-01

    Multiple isoforms of the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) arise from the alternative splicing of its single gene-encoded pre-mRNA transcript. Among these, the longer Drp1 isoforms, expressed selectively in neurons, bear unique polypeptide sequences within their GTPase and variable domains, known as the A-insert and the B-insert, respectively. Their functions remain unresolved. A comparison of the various biochemical and biophysical properties of the neuronally expressed isoforms with that of the ubiquitously expressed, and shortest, Drp1 isoform (Drp1-short) has revealed the effect of these inserts on Drp1 function. Utilizing various biochemical, biophysical, and cellular approaches, we find that the A- and B-inserts distinctly alter the oligomerization propensity of Drp1 in solution as well as the preferred curvature of helical Drp1 self-assembly on membranes. Consequently, these sequences also suppress Drp1 cooperative GTPase activity. Mitochondrial fission factor (Mff), a tail-anchored membrane protein of the mitochondrial outer membrane that recruits Drp1 to sites of ensuing fission, differentially stimulates the disparate Drp1 isoforms and alleviates the autoinhibitory effect imposed by these sequences on Drp1 function. Moreover, the differential stimulatory effects of Mff on Drp1 isoforms are dependent on the mitochondrial lipid, cardiolipin (CL). Although Mff stimulation of the intrinsically cooperative Drp1-short isoform is relatively modest, CL-independent, and even counter-productive at high CL concentrations, Mff stimulation of the much less cooperative longest Drp1 isoform (Drp1-long) is robust and occurs synergistically with increasing CL content. Thus, membrane-anchored Mff differentially regulates various Drp1 isoforms by functioning as an allosteric effector of cooperative GTPase activity. PMID:26578513

  18. Distinct Splice Variants of Dynamin-related Protein 1 Differentially Utilize Mitochondrial Fission Factor as an Effector of Cooperative GTPase Activity.

    PubMed

    Macdonald, Patrick J; Francy, Christopher A; Stepanyants, Natalia; Lehman, Lance; Baglio, Anthony; Mears, Jason A; Qi, Xin; Ramachandran, Rajesh

    2016-01-01

    Multiple isoforms of the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) arise from the alternative splicing of its single gene-encoded pre-mRNA transcript. Among these, the longer Drp1 isoforms, expressed selectively in neurons, bear unique polypeptide sequences within their GTPase and variable domains, known as the A-insert and the B-insert, respectively. Their functions remain unresolved. A comparison of the various biochemical and biophysical properties of the neuronally expressed isoforms with that of the ubiquitously expressed, and shortest, Drp1 isoform (Drp1-short) has revealed the effect of these inserts on Drp1 function. Utilizing various biochemical, biophysical, and cellular approaches, we find that the A- and B-inserts distinctly alter the oligomerization propensity of Drp1 in solution as well as the preferred curvature of helical Drp1 self-assembly on membranes. Consequently, these sequences also suppress Drp1 cooperative GTPase activity. Mitochondrial fission factor (Mff), a tail-anchored membrane protein of the mitochondrial outer membrane that recruits Drp1 to sites of ensuing fission, differentially stimulates the disparate Drp1 isoforms and alleviates the autoinhibitory effect imposed by these sequences on Drp1 function. Moreover, the differential stimulatory effects of Mff on Drp1 isoforms are dependent on the mitochondrial lipid, cardiolipin (CL). Although Mff stimulation of the intrinsically cooperative Drp1-short isoform is relatively modest, CL-independent, and even counter-productive at high CL concentrations, Mff stimulation of the much less cooperative longest Drp1 isoform (Drp1-long) is robust and occurs synergistically with increasing CL content. Thus, membrane-anchored Mff differentially regulates various Drp1 isoforms by functioning as an allosteric effector of cooperative GTPase activity.

  19. Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms

    PubMed Central

    Ara, Anjuman; Love, Robin P.; Chelico, Linda

    2014-01-01

    The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif (virus infectivity factor) deficient HIV-1 virions to differing degrees by deaminating cytosines to uracils in single-stranded (−)HIV-1 DNA. Upon replication of the (−)DNA to (+)DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils, thereby inducing C/G→T/A mutations that can functionally inactivate HIV-1. Although both APOBEC3F and APOBEC3G are expressed in cell types HIV-1 infects and are suppressed by Vif, there has been no prior biochemical analysis of APOBEC3F, in contrast to APOBEC3G. Using synthetic DNA substrates, we characterized APOBEC3F and found that similar to APOBEC3G; it is a processive enzyme and can deaminate at least two cytosines in a single enzyme-substrate encounter. However, APOBEC3F scanning movement is distinct from APOBEC3G, and relies on jumping rather than both jumping and sliding. APOBEC3F jumping movements were also different from APOBEC3G. The lack of sliding movement from APOBEC3F is due to an 190NPM192 motif, since insertion of this motif into APOBEC3G decreases its sliding movements. The APOBEC3G NPM mutant induced significantly less mutations in comparison to wild-type APOBEC3G in an in vitro model HIV-1 replication assay and single-cycle infectivity assay, indicating that differences in DNA scanning were relevant to restriction of HIV-1. Conversely, mutation of the APOBEC3F 191Pro to 191Gly enables APOBEC3F sliding movements to occur. Although APOBEC3F 190NGM192 could slide, the enzyme did not induce more mutagenesis than wild-type APOBEC3F, demonstrating that the unique jumping mechanism of APOBEC3F abrogates the influence of sliding on mutagenesis. Overall, we demonstrate key differences in the impact of APOBEC3F- and APOBEC3G-induced mutagenesis on HIV-1 that supports a model in which both the processive DNA scanning mechanism and preferred deamination motif (APOBEC3F, 5

  20. Dissociative trance and spirit possession: Challenges for cultures in transition.

    PubMed

    Bhavsar, Vishal; Ventriglio, Antonio; Bhugra, Dinesh

    2016-12-01

    The cross-cultural validity of dissociative possession and trance disorders is a matter of some debate, limiting research and meaningful interpretation of prevalence data. Intimate to these concerns is the status of spirit possession categories studied in the social sciences, particularly anthropology. These two categories are phenomenologically related and display similar epidemiological associations. In India, dissociative and conversion disorders are fairly common in clinical settings. There is no doubt that there are true cultural variations in possession and trance disorders. A new framework may enable clinicians to better understand possession states and spirit possession. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

  1. β-Arrestin1 and Distinct CXCR4 Structures Are Required for Stromal Derived Factor-1 to Downregulate CXCR4 Cell-Surface Levels in Neuroblastoma

    PubMed Central

    Clift, Ian C.; Bamidele, Adebowale O.; Rodriguez-Ramirez, Christie; Kremer, Kimberly N.

    2014-01-01

    CXC chemokine receptor 4 (CXCR4) is a G protein–coupled receptor (GPCR) located on the cell surface that signals upon binding the chemokine stromal derived factor-1 (SDF-1; also called CXCL 12). CXCR4 promotes neuroblastoma proliferation and chemotaxis. CXCR4 expression negatively correlates with prognosis and drives neuroblastoma growth and metastasis in mouse models. All functions of CXCR4 require its expression on the cell surface, yet the molecular mechanisms that regulate CXCR4 cell-surface levels in neuroblastoma are poorly understood. We characterized CXCR4 cell-surface regulation in the related SH-SY5Y and SK-N-SH human neuroblastoma cell lines. SDF-1 treatment caused rapid down-modulation of CXCR4 in SH-SY5Y cells. Pharmacologic activation of protein kinase C similarly reduced CXCR4, but via a distinct mechanism. Analysis of CXCR4 mutants delineated two CXCR4 regions required for SDF-1 treatment to decrease cell-surface CXCR4 in neuroblastoma cells: the isoleucine-leucine motif at residues 328 and 329 and residues 343–352. In contrast, and unlike CXCR4 regulation in other cell types, serines 324, 325, 338, and 339 were not required. Arrestin proteins can bind and regulate GPCR cell-surface expression, often functioning together with kinases such as G protein–coupled receptor kinase 2 (GRK2). Using SK-N-SH cells which are naturally deficient in β-arrestin1, we showed that β-arrestin1 is required for the CXCR4 343–352 region to modulate CXCR4 cell-surface expression following treatment with SDF-1. Moreover, GRK2 overexpression enhanced CXCR4 internalization, via a mechanism requiring both β-arrestin1 expression and the 343–352 region. Together, these results characterize CXCR4 structural domains and β-arrestin1 as critical regulators of CXCR4 cell-surface expression in neuroblastoma. β-Arrestin1 levels may therefore influence the CXCR4-driven metastasis of neuroblastoma as well as prognosis. PMID:24452472

  2. Investigating the link between gun possession and gun assault.

    PubMed

    Branas, Charles C; Richmond, Therese S; Culhane, Dennis P; Ten Have, Thomas R; Wiebe, Douglas J

    2009-11-01

    We investigated the possible relationship between being shot in an assault and possession of a gun at the time. We enrolled 677 case participants that had been shot in an assault and 684 population-based control participants within Philadelphia, PA, from 2003 to 2006. We adjusted odds ratios for confounding variables. After adjustment, individuals in possession of a gun were 4.46 (P < .05) times more likely to be shot in an assault than those not in possession. Among gun assaults where the victim had at least some chance to resist, this adjusted odds ratio increased to 5.45 (P < .05). On average, guns did not protect those who possessed them from being shot in an assault. Although successful defensive gun uses occur each year, the probability of success may be low for civilian gun users in urban areas. Such users should reconsider their possession of guns or, at least, understand that regular possession necessitates careful safety countermeasures.

  3. Developing of Library for Proofs of Data Possession in Charm

    DTIC Science & Technology

    2013-06-01

    Provable data possession at untrusted stores ,” in Proc. of the 14th ACM Conf. on Comput. and...is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Provable Data Possession (PDP) is a cryptographic tool for auditing big... Provable Data Possession (PDP) is a cryptographic tool for auditing big data on a storage server or in the cloud. The goal of PDP is to efficiently

  4. The pursuit of optimal distinctiveness and consumer preferences.

    PubMed

    He, Lingnan; Cong, Feng; Liu, Yanping; Zhou, Xinyue

    2010-10-01

    This article investigates the effect of optimal distinctiveness on consumer product consumption. The authors argue that consumers acquire and display material possessions to restore their optimal levels of distinctiveness. Results showed that placing consumers in a state of low distinctiveness increased desire to acquire distinctive products, whereas perceptions of high distinctiveness reduced desire to acquire such products. Consumers' desire for distinctiveness-related products held true for various consumer choices, including willingness to pay more for limited-edition products and preference for unpopular gifts. This finding has implications for understanding consumer choice in expressing identity.

  5. Firearm Possession Among Adolescents Presenting to an Urban Emergency Department for Assault

    PubMed Central

    Walton, Maureen A.; Newton, Manya F.; Clery, Michael; Whiteside, Lauren K.; Zimmerman, Marc A.; Cunningham, Rebecca M.

    2013-01-01

    BACKGROUND AND OBJECTIVES: Firearm violence is a leading cause of death among youth. The objectives of this study were (1) determine firearm possession rates and associated correlates among youth seeking care for assault in an emergency department (ED); (2) understand differences in risk factors for youth with firearm possession; and (3) identify firearm possession characteristics in this population: type, reason for possession, and source of firearms. METHODS: Youth (14 to 24 years old) presenting to a Level 1 ED with assault were administered a computerized screening survey. Validated instruments were administered, measuring demographics, firearm rates and characteristics, attitudes toward aggression, substance use, and previous violence history. RESULTS: Among 689 assault-injured youth, 23% reported firearm possession in the past 6 months. Only 17% of those reporting firearm possession obtained the gun from a legal source; 22% reported ownership of highly lethal automatic/semiautomatic weapons and 37.1% reported having a firearm for protection. Logistic regression analysis identified significant correlates of firearm possession, including male gender, higher socioeconomic status, illicit drug use, recent serious fight, and retaliatory attitudes. CONCLUSIONS: ED assault-injured youth had high rates of firearm possession (23.1%), most of which were not obtained from legal sources. Youth with firearm possession were more likely to have been in a recent serious fight, and to endorse aggressive attitudes that increase their risk for retaliatory violence. Future prevention efforts should focus on minimizing illegal firearm access among high-risk youth, nonviolent alternatives to retaliatory violence, and substance use prevention. PMID:23837181

  6. Roots from distinct plant developmental stages are capable of rapidly selecting their own microbiome without the influence of environmental and soil edaphic factors

    USDA-ARS?s Scientific Manuscript database

    Soil microbes live in close association with plants and are crucial for plant health and fitness. Recent literature revealed that specific microbes were cultured at distinct developmental stages of Arabidopsis. It is not clear how fast the roots, depending on their developmental stage, can alter the...

  7. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Possession at sea and landing. 635.30....30 Possession at sea and landing. (a) Atlantic tunas. Persons that own or operate a fishing vessel... taken from its management unit or a sailfish taken shoreward of the outer boundary of the EEZ or lands...

  8. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Possession at sea and landing. 635.30....30 Possession at sea and landing. (a) Atlantic tunas. Persons that own or operate a fishing vessel... taken from its management unit or a sailfish taken shoreward of the outer boundary of the EEZ or lands...

  9. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession at sea and landing. 635.30....30 Possession at sea and landing. Link to an amendment published at 75 FR 57702, Sept. 22, 2010. (a... marlin taken from its management unit or a sailfish taken shoreward of the outer boundary of the EEZ...

  10. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... taken from its management unit or a sailfish taken shoreward of the outer boundary of the EEZ or lands a... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Possession at sea and landing. 635.30....30 Possession at sea and landing. (a) Atlantic tunas. Persons that own or operate a fishing...

  11. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... taken from its management unit or a sailfish taken shoreward of the outer boundary of the EEZ or lands a... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Possession at sea and landing. 635.30....30 Possession at sea and landing. (a) Atlantic tunas. Persons that own or operate a fishing...

  12. 50 CFR 648.40 - Prohibition on possession.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Atlantic Salmon § 648.40 Prohibition on possession. (a) Incidental catch. All Atlantic salmon caught... maximum probability of survival. (b) Presumption. The possession of Atlantic salmon is prima facie evidence that such Atlantic salmon were taken in violation of this regulation. Evidence that such fish...

  13. 50 CFR 648.40 - Prohibition on possession.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Atlantic Salmon § 648.40 Prohibition on possession. (a) Incidental catch. All Atlantic salmon caught... maximum probability of survival. (b) Presumption. The possession of Atlantic salmon is prima facie evidence that such Atlantic salmon were taken in violation of this regulation. Evidence that such fish...

  14. 50 CFR 648.40 - Prohibition on possession.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Atlantic Salmon § 648.40 Prohibition on possession. (a) Incidental catch. All Atlantic salmon caught... maximum probability of survival. (b) Presumption. The possession of Atlantic salmon is prima facie evidence that such Atlantic salmon were taken in violation of this regulation. Evidence that such fish...

  15. 50 CFR 648.40 - Prohibition on possession.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Atlantic Salmon § 648.40 Prohibition on possession. (a) Incidental catch. All Atlantic salmon caught... maximum probability of survival. (b) Presumption. The possession of Atlantic salmon is prima facie evidence that such Atlantic salmon were taken in violation of this regulation. Evidence that such fish...

  16. 50 CFR 648.40 - Prohibition on possession.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Atlantic Salmon § 648.40 Prohibition on possession. (a) Incidental catch. All Atlantic salmon caught... maximum probability of survival. (b) Presumption. The possession of Atlantic salmon is prima facie evidence that such Atlantic salmon were taken in violation of this regulation. Evidence that such fish...

  17. 50 CFR 648.235 - Possession and landing restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Measures for the Spiny Dogfish Fishery § 648.235 Possession and landing restrictions. (a) Quota Period 1. From May 1 through October 31, vessels issued a valid Federal spiny dogfish permit specified under § 648.4(a)(11) may: (1) Possess up to 3,000 lb (1.36 mt) of spiny dogfish per trip; and (2) Land only...

  18. 50 CFR 648.235 - Possession and landing restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Measures for the Spiny Dogfish Fishery § 648.235 Possession and landing restrictions. Link to an amendment... a valid Federal spiny dogfish permit specified under § 648.4(a)(11) may: (1) Possess up to 3,000 lb (1.36 mt) of spiny dogfish per trip; and (2) Land only one trip of spiny dogfish per calendar day. (b...

  19. Parental contributions to adolescents' possessions and educational expenses: gender differences.

    PubMed

    Peters, J F

    1991-01-01

    This study explored adolescent gender differences in possessions and parental financial assistance. Eight common adolescent possessions were analyzed, as well as expected parental contributions to their children's postsecondary education. The issues of gender inequality in the home and gender differences in the process of adolescent independence are addressed.

  20. Pre-Posed Possessive Constructions in Russian and Polish

    ERIC Educational Resources Information Center

    Houle, Erik Richard

    2013-01-01

    In Contemporary Standard Russian (CSR) and Contemporary Standard Polish (CSP) nominal possession is conveyed by means of the adnominal genitive. In this construction the dependent follows the noun it modifies and is marked morphologically for possession in the genitive case. The head noun is marked morphologically for any one of the six…

  1. The Meaning of Cherished Personal Possessions for the Elderly

    ERIC Educational Resources Information Center

    Sherman, Edmund; Newman, Evelyn S.

    1977-01-01

    In this exploratory study, 94 elderly persons, in seven senior service centers and one nursing home, were interviewed to identify and ascertain the meaning of cherished possessions in later years. Lack of cherished possessions was associated with low life satisfaction scores, a suggested indicator of poor adjustment to old age. (Author)

  2. 27 CFR 31.203 - Possession of used liquor bottles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... recycling or reclaiming the glass or other approved liquor bottle material. (26 U.S.C. 5301) ... bottles. 31.203 Section 31.203 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Bottles § 31.203 Possession of used liquor bottles. The possession of used liquor bottles by any...

  3. 27 CFR 31.203 - Possession of used liquor bottles.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... recycling or reclaiming the glass or other approved liquor bottle material. (26 U.S.C. 5301) ... bottles. 31.203 Section 31.203 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Bottles § 31.203 Possession of used liquor bottles. The possession of used liquor bottles by any...

  4. 27 CFR 31.203 - Possession of used liquor bottles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... recycling or reclaiming the glass or other approved liquor bottle material. (26 U.S.C. 5301) ... bottles. 31.203 Section 31.203 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Bottles § 31.203 Possession of used liquor bottles. The possession of used liquor bottles by any...

  5. 27 CFR 31.203 - Possession of used liquor bottles.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... recycling or reclaiming the glass or other approved liquor bottle material. (26 U.S.C. 5301) ... bottles. 31.203 Section 31.203 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Bottles § 31.203 Possession of used liquor bottles. The possession of used liquor bottles by any...

  6. 27 CFR 31.203 - Possession of used liquor bottles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... recycling or reclaiming the glass or other approved liquor bottle material. (26 U.S.C. 5301) ... bottles. 31.203 Section 31.203 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Bottles § 31.203 Possession of used liquor bottles. The possession of used liquor bottles by any...

  7. The Relationship between Social Capital and Weapon Possession on Campus

    ERIC Educational Resources Information Center

    Messer, Rachel H.; Bradley, Kristopher I.; Calvi, Jessica L.; Kennison, Shelia M.

    2012-01-01

    The present research focused on the problem of how college officials might be able to predict weapon possession on college campuses. We hypothesized that measures of social capital (i.e., trust and participation in society) may be useful in identifying individuals who are likely to possess weapons on campuses. Prior research has shown that those…

  8. 50 CFR 640.23 - Bag/possession limits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management... daily bag or possession limit for spiny lobster in or from the EEZ off the southern Atlantic states... fishing season specified in § 640.20(b)(1), the daily bag or possession limit of spiny lobster in or...

  9. 50 CFR 640.23 - Bag/possession limits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management... daily bag or possession limit for spiny lobster in or from the EEZ off the southern Atlantic states... fishing season specified in § 640.20(b)(1), the daily bag or possession limit of spiny lobster in or...

  10. 50 CFR 640.23 - Bag/possession limits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management... daily bag or possession limit for spiny lobster in or from the EEZ off the southern Atlantic states... fishing season specified in § 640.20(b)(1), the daily bag or possession limit of spiny lobster in or...

  11. 18 CFR 1306.3 - Surrender of possession.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Surrender of possession. 1306.3 Section 1306.3 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION POLICIES Regulations and Procedures § 1306.3 Surrender of possession...

  12. 18 CFR 1306.3 - Surrender of possession.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Surrender of possession. 1306.3 Section 1306.3 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION POLICIES Regulations and Procedures § 1306.3 Surrender of possession...

  13. 18 CFR 1306.3 - Surrender of possession.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Surrender of possession. 1306.3 Section 1306.3 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION POLICIES Regulations and Procedures § 1306.3 Surrender of possession...

  14. 18 CFR 1306.3 - Surrender of possession.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Surrender of possession. 1306.3 Section 1306.3 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION POLICIES Regulations and Procedures § 1306.3 Surrender of possession...

  15. 18 CFR 1306.3 - Surrender of possession.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Surrender of possession. 1306.3 Section 1306.3 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION POLICIES Regulations and Procedures § 1306.3 Surrender of possession...

  16. Whose? L2-English Speakers' Possessive Pronoun Gender Errors

    ERIC Educational Resources Information Center

    Anton-Mendez, Ines

    2011-01-01

    This article reports the results of an experiment on production of "his/her" in English as a second language (L2) by proficient native speakers of Italian, Spanish, and Dutch. In Dutch and English, 3rd person singular possessive pronouns agree in gender with their antecedents, in Italian and Spanish possessives in general agree with the noun they…

  17. 19 CFR 123.62 - Baggage in possession of traveler.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Baggage in possession of traveler. 123.62 Section 123.62 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... traveler. For baggage arriving in the actual possession of a traveler, his declaration shall be accepted in...

  18. The Relationship between Social Capital and Weapon Possession on Campus

    ERIC Educational Resources Information Center

    Messer, Rachel H.; Bradley, Kristopher I.; Calvi, Jessica L.; Kennison, Shelia M.

    2012-01-01

    The present research focused on the problem of how college officials might be able to predict weapon possession on college campuses. We hypothesized that measures of social capital (i.e., trust and participation in society) may be useful in identifying individuals who are likely to possess weapons on campuses. Prior research has shown that those…

  19. Pre-Posed Possessive Constructions in Russian and Polish

    ERIC Educational Resources Information Center

    Houle, Erik Richard

    2013-01-01

    In Contemporary Standard Russian (CSR) and Contemporary Standard Polish (CSP) nominal possession is conveyed by means of the adnominal genitive. In this construction the dependent follows the noun it modifies and is marked morphologically for possession in the genitive case. The head noun is marked morphologically for any one of the six…

  20. 32 CFR 552.120 - Possession and control.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Explosives-Fort Lewis, Washington § 552.120 Possession and control. (a) Possession of weapons on the post by... Lewis. Prior coordination for the use of ranges will be made through the Range Control Officer or Range... privately owned weapons by either military or civilian personnel is prohibited while on the Fort Lewis...

  1. 50 CFR 648.94 - Monkfish possession and landing restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... = 191). A vessel may not possess heads only without possessing the equivalent weight of tails allowed by... (head on and gutted), or any combination of the three provided the weight of monkfish heads on board does not exceed 1.91 times the weight of monkfish tails on board. When any combination of tails, and...

  2. 9. Photocopy of 1845 manuscript (original in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photocopy of 1845 manuscript (original in the possession of the Metropolitan Museum of Art, New York City, N.Y.; photocopy in the possession of the Onondaga Historical Association) ENTRY IN A. J. DAVIS' (ARCHITECT) ACCOUNT BOOK, SHOWING SKETCH OF WEST ELEVATION AND FIRST LEVEL PLAN, AND SCHEDULE OF TEN DRAWINGS - Sedgewick House, 742 James Street, Syracuse, Onondaga County, NY

  3. Creating Distinctiveness: Lessons from Uncommon Colleges and Universities. ERIC Digest.

    ERIC Educational Resources Information Center

    Townsend, Barbara K.; And Others

    This brief report summarizes a longer document with the same title. Distinctive colleges and universities possess a unifying theme or vision that is expressed in all their activities. They also usually respond to newly emerging societal or community needs unmet by existing schools of higher education. Distinctiveness, however, can limit the…

  4. Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster

    PubMed Central

    Valentino, Michael D.; McGuire, Abigail Manson; Rosch, Jason W.; Bispo, Paulo J. M.; Burnham, Corinna; Sanfilippo, Christine M.; Carter, Robert A.; Zegans, Michael E.; Beall, Bernard; Earl, Ashlee M.; Tuomanen, Elaine I.; Morris, Timothy W.; Haas, Wolfgang; Gilmore, Michael S.

    2014-01-01

    Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the US. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with other unencapsulated nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not been described in encapsulated pneumococci. These findings suggest that the unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis strategy substantially different from that described for S. pneumoniae at other infection sites. PMID:25388376

  5. Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster.

    PubMed

    Valentino, Michael D; McGuire, Abigail Manson; Rosch, Jason W; Bispo, Paulo J M; Burnham, Corinna; Sanfilippo, Christine M; Carter, Robert A; Zegans, Michael E; Beall, Bernard; Earl, Ashlee M; Tuomanen, Elaine I; Morris, Timothy W; Haas, Wolfgang; Gilmore, Michael S

    2014-11-12

    Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the United States. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with other unencapsulated nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not been described in encapsulated pneumococci. These findings suggest that the unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis strategy substantially different from that described for S. pneumoniae at other infection sites.

  6. Possession experiences in dissociative identity disorder: a preliminary study.

    PubMed

    Ross, Colin A

    2011-01-01

    Dissociative trance disorder, which includes possession experiences, was introduced as a provisional diagnosis requiring further study in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Consideration is now being given to including possession experiences within dissociative identity disorder (DID) in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), which is due to be published in 2013. In order to provide empirical data relevant to the relationship between DID and possession states, I analyzed data on the prevalence of trance, possession states, sleepwalking, and paranormal experiences in 3 large samples: patients with DID from North America; psychiatric outpatients from Shanghai, China; and a general population sample from Winnipeg, Canada. Trance, sleepwalking, paranormal, and possession experiences were much more common in the DID patients than in the 2 comparison samples. The study is preliminary and exploratory in nature because the samples were not matched in any way.

  7. Determinants of possession of the ball in soccer.

    PubMed

    Lago, Carlos; Martín, Rafael

    2007-07-01

    In research on the importance of the possession of the ball in soccer, little attention has been paid to its determinants. Using data from 170 matches of the 2003 - 2004 Spanish Soccer League, we explain why differences in the possession of the ball among teams are so great. In particular, four variables are examined: evolving match status (i.e. whether the team is winning, losing or drawing), venue (i.e. playing at home or away), and the identities of the team and the opponent in each match. Results of linear regression analysis show that these four variables are statistically significant and together explain most of the variance in possession. In short, home teams have more possession than away teams, teams have more possession when they are losing matches than when winning or drawing, and the identity of the opponent matters - the worse the opponent, the greater the possession of the ball. Combinations of these variables could be used to develop a model that predicts possession in soccer.

  8. Gun possession among American youth: a discovery-based approach to understand gun violence.

    PubMed

    Ruggles, Kelly V; Rajan, Sonali

    2014-01-01

    To apply discovery-based computational methods to nationally representative data from the Centers for Disease Control and Preventions' Youth Risk Behavior Surveillance System to better understand and visualize the behavioral factors associated with gun possession among adolescent youth. Our study uncovered the multidimensional nature of gun possession across nearly five million unique data points over a ten year period (2001-2011). Specifically, we automated odds ratio calculations for 55 risk behaviors to assemble a comprehensive table of associations for every behavior combination. Downstream analyses included the hierarchical clustering of risk behaviors based on their association "fingerprint" to 1) visualize and assess which behaviors frequently co-occur and 2) evaluate which risk behaviors are consistently found to be associated with gun possession. From these analyses, we identified more than 40 behavioral factors, including heroin use, using snuff on school property, having been injured in a fight, and having been a victim of sexual violence, that have and continue to be strongly associated with gun possession. Additionally, we identified six behavioral clusters based on association similarities: 1) physical activity and nutrition; 2) disordered eating, suicide and sexual violence; 3) weapon carrying and physical safety; 4) alcohol, marijuana and cigarette use; 5) drug use on school property and 6) overall drug use. Use of computational methodologies identified multiple risk behaviors, beyond more commonly discussed indicators of poor mental health, that are associated with gun possession among youth. Implications for prevention efforts and future interdisciplinary work applying computational methods to behavioral science data are described.

  9. Pathologic von Willebrand factor degradation with a left ventricular assist device occurs via two distinct mechanisms: mechanical demolition and enzymatic cleavage.

    PubMed

    Bartoli, Carlo R; Restle, David J; Zhang, David M; Acker, Michael A; Atluri, Pavan

    2015-01-01

    Bleeding is an important source of morbidity in patients with a left ventricular assist device. Evidence suggests a major role for von Willebrand factor. However, limited data exist to explain the mechanism(s) of von Willebrand factor degradation during left ventricular assist device support. We investigated whether left ventricular assist device-related shear stress and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13, the von Willebrand factor protease) altered von Willebrand factor metabolism. Whole blood was collected from patients (n = 8) with a left ventricular assist device. von Willebrand factor multimers and degradation fragments were characterized with electrophoresis and immunoblotting. To investigate mechanisms, an in vitro model was developed to generate the supraphysiologic shear stress of a continuous-flow left ventricular assist device. Normal human blood (n = 8) was cycled in a laboratory vortexer (∼2400 rpm, shear stress ∼175 dyne/cm(2), 4 hours) to reproduce the pathologic degradation of von Willebrand factor that occurs during left ventricular assist device support. To investigate the specific mechanistic roles of shear stress and ADAMTS-13 in von Willebrand factor degradation, purified von Willebrand factor protein ± ADAMTS-13 protease were exposed to supraphysiologic shear stress in the vortexer. von Willebrand factor multimers and 11 von Willebrand factor degradation fragments were characterized with electrophoresis and immunoblotting. Left ventricular assist device support reduced large von Willebrand factor multimers and significantly increased 10/11 von Willebrand factor degradation fragments (P < .05). Normal human blood exposed to supraphysiologic shear stress in the vortexer demonstrated the same profile of von Willebrand factor degradation fragments as in a patient with a left ventricular assist device. Supraphysiologic shear stress alone caused modest mechanical demolition of

  10. Must an inventor "possess" an invention to patent it?

    PubMed

    Woessner, Warren D; Chadwick, Robin A

    2014-09-18

    The requirements for patenting inventions relating to biotechnology have become increasingly strict and complicated in recent years. Despite early patent rulings that there is no need for an inventor to "reduce to practice" an invention, the courts are now ruling that an inventor must "possess" his or her invention before filing for patent. This review discusses what such "possession" may mean and describes decisions in which courts have found that an inventor has met or failed the possession test before filing for patent protection. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  11. Possession syndrome at high altitude ( 4575 m/15000 ft ).

    PubMed

    Khan, I D; Sahni, A K

    2013-01-01

    In a first of its kind, a 20 year old Hindu, highlander, working girl presented with abnormal behavior, unrelenting symptoms, had limited benefit by usual treatment and was diagnosed as possession syndrome. Exorcism offered symptomatic relief. The girl resumed normal activities with no recurrence in a 12 month follow up. Possession syndrome is explained in both medical and theological perspectives. Modern medicine associates it with a mental illness though True Possession syndrome without associated mental illness has been reported. Theological perspective can be amalgamated with current scientific theory and practice, thereby complimenting existing concepts.

  12. Does Possession of Apolipoprotein E[superscript E]4 Benefit Cognitive Function in Healthy Young Adults?

    ERIC Educational Resources Information Center

    Bunce, David; Anstey, Kaarin J.; Burns, Richard; Christensen, Helen; Easteal, Simon

    2011-01-01

    There is considerable evidence that the apolipoprotein E (APOE)[superscript E]4 allele is associated with cognitive deficits in older persons, and is a risk factor for dementia. However, it has recently been suggested that possession of the [superscript E]4 allele may benefit cognition in early adulthood. We tested this possibility in 5445…

  13. The Impact of World Knowledge on the Processing of Mandarin Possessive Reflexive "Zijide"

    ERIC Educational Resources Information Center

    Li, Rui; Zhang, Zhiyi; Ni, Chuanbin

    2017-01-01

    It has long been considered that the Mandarin possessive reflexive "zijide" can be either locally bound or long distance bound, leading to ambiguity where it fails to exclusively refer back to either long distance binding NP or the local NP. In addition to syntactic factors such as the local versus long distance division, the present…

  14. Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor.

    PubMed

    Arsenijevic, Y; Weiss, S

    1998-03-15

    Insulin-like growth factor-I (IGF-I) has been reported previously to promote the proliferation, survival, and maturation of sympathetic neuroblasts, the genesis of retinal neurons, and the survival of CNS projection and motor neurons. Here we asked whether IGF-I could promote the in vitro differentiation of postmitotic mammalian CNS neuronal precursors derived from multipotent epidermal growth factor (EGF)-responsive stem cells. In the absence of IGF-I, virtually no neurons were present in cultured stem cell progeny, whereas IGF-I increased neuron number by eight- to 40-fold. Brief exposures (2 hr) to IGF-I were sufficient to allow for neuronal differentiation without affecting proliferation or survival. IGF-I actions could be mimicked by insulin and IGF-II at concentrations that correspond to the pharmacology of the IGF-I receptor, the latter for which the mRNA was detected in undifferentiated stem cell progeny. Although ineffectual alone at low concentrations (10 nM) that would activate its own receptor, insulin was able to potentiate the actions of IGF-I by acting on mitotically active neural precursors. When neuronal precursor differentiation by IGF-I was examined in relation to brain-derived neurotrophic factor (BDNF), two important observations were made: (1) BDNF could potentiate the differentiating actions of IGF-I plus insulin, and (2) BDNF could act on a separate population of precursors that did not require IGF-I plus insulin for differentiation. Taken together, these results suggest that IGF-I and BDNF may act together or sequentially to promote neuronal precursor differentiation.

  15. 20. Photocopy of negative (original in possession of WACC), photographer ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photocopy of negative (original in possession of WACC), photographer unknown, c.1920's BOY WITH DEER STANDING IN EAST YARD OF MAIN HOUSE WITH WELL AND SCREENED PORCH PICTURED IN LEFT BACKGROUND - Faraway Ranch, Willcox, Cochise County, AZ

  16. 9. Photocopy of drawing (Original in possession of National Archives ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photocopy of drawing (Original in possession of National Archives and Record Service, Record Group 92) Delineator unknown, Date unknown FIRST FLOOR PLAN - Omaha Quartermaster Depot Historic District, Twenty-second & Woolworth Streets, Omaha, Douglas County, NE

  17. 10. Photocopy of drawing (Original in possession of National Archives ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photocopy of drawing (Original in possession of National Archives and Record Service, Record Group 92) Delineator unknown, Date unknown SECOND FLOOR PLAN - Omaha Quartermaster Depot Historic District, Twenty-second & Woolworth Streets, Omaha, Douglas County, NE

  18. 8. Photocopy of drawing (Original in possession of National Archives ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Photocopy of drawing (Original in possession of National Archives and Record Service, Record Group 92) Delineator unknown, Date unknown BASEMENT FLOOR PLAN - Omaha Quartermaster Depot Historic District, Twenty-second & Woolworth Streets, Omaha, Douglas County, NE

  19. 10. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Signal Corps, USA, 1945 INTERIOR VIEW OF PIER SHED - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

  20. 17. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Signal Corps, USA, 1947 VIEW OF PIER 4 AND PIER 5-BROOKLYN ARMY BASE TERMINAL - Brooklyn Army Supply Base, Pier 4, Brooklyn, Kings County, NY

  1. 8. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Signal Corp, USA, 1946 VIEW OF PIERS 2, 3, AND 4-BROOKLYN ARMY BASE TERMINAL - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

  2. 18. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Signal Corps, USA, 1933 VIEW OF EAST (FRONT) ELEVATION-PIER 4 - Brooklyn Army Supply Base, Pier 4, Brooklyn, Kings County, NY

  3. 22. Photocopy of construction drawing (original in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Photocopy of construction drawing (original in the possession of the Public Service Company of Colorado, Denver Colorado) Engineering Department, The Central Colorado Power Co., 1909 HEADWORKS - Shoshone Hydroelectric Plant Complex, 60111 U.S. Highway 6, Garfield County, CO

  4. The epistemological significance of possession entering the DSM.

    PubMed

    Stephenson, Craig

    2015-09-01

    The discourse of the American Psychiatric Association's DSM reflects the inherently dialogic or contradictory nature of its stated mandate to demonstrate both 'nosological completeness' and cultural 'inclusiveness'. Psychiatry employs the dialogic discourse of the DSM in a one-sided, positivistic manner by identifying what it considers universal mental disease entities stripped of their cultural context. In 1992 the editors of the Diagnostic and Statistical Manual of Mental Disorders proposed to introduce possession into their revisions. A survey of the discussions about introducing 'possession' as a dissociative disorder to be listed in the DSM-IV indicates a missed epistemological break. Subsequently the editors of the DSM-5 politically 'recuperated' possession into its official discourse, without acknowledging the anarchic challenges that possession presents to psychiatry as a cultural practice.

  5. 1. Photocopy of a measured drawing (original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Photocopy of a measured drawing (original in the possession of the Kunstakademiets (Royal Academy of Fine Arts), Copenhagen, Denmark, 1961) EAST (FRONT) ELEVATION - Richmond Prison, Keeper's House, Richmond, St. Croix, VI

  6. 23. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. VERTICAL WESTINGHOUSE GENERATORS IN 1919 ADDITION. DATED FEBRUARY 19, 1919. - Rock Island Arsenal, Building No. 160, Sylvan Drive, Rock Island, Rock Island County, IL

  7. 6. Photocopy of photograph (Original print in possession of the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of photograph (Original print in possession of the Division of Mechanical and Civil Engineering, Smithsonian Institute) SIMILAR BRIDGE IN FRAMINGHAM MASSACHUSETTS - Elm Street Bridge, Spanning Ottauquechee River, Woodstock, Windsor County, VT

  8. 7. Photocopy of photograph (original in possession of the Division ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photocopy of photograph (original in possession of the Division of Mechanical and Civil Engineering, Smithsonian Institute) PARKER TRUSS BRIDGE IN MAINE - Elm Street Bridge, Spanning Ottauquechee River, Woodstock, Windsor County, VT

  9. Constitutional Law: Right of Privacy--Possession of Marijuana

    ERIC Educational Resources Information Center

    Rohrer, David E.

    1976-01-01

    The Alaska Supreme Court in Ravin v. State accepted the defendant's contention that the prohibition of possession of marihuana infringed on his constitutional right to privacy. The significance of the case is discussed. (LBH)

  10. 50 CFR 622.38 - Bag and possession limits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Reef Fish Resources of the Gulf of Mexico § 622.38 Bag and possession limits. (a) Additional applicability provisions...

  11. 4. Photocopy of measured drawing (original in possession of Trinity ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of measured drawing (original in possession of Trinity Episcopal Cathedral) Edward Tuckerman Potter, architect ca. 1867 WEST FACADE, ELEVATION - Grace Episcopal Cathedral, 1121 Main Street, Davenport, Scott County, IA

  12. 5. Photocopy of measured drawing (original in possession of Trinity ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of measured drawing (original in possession of Trinity Episcopal Cathedral) Edward Tuckerman Potter, architect ca. 1867 CROSS SECTION, LOOKING NORTH - Grace Episcopal Cathedral, 1121 Main Street, Davenport, Scott County, IA

  13. 7. Photocopy of photograph, original negative in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photocopy of photograph, original negative in the possession of John R. Morison, Peterborough, New Hampshire. Photographer unknown circa June, 1887. PILE DRIVER BUILDING TEMPORARY RAIL TRESTLE - Rulo Bridge, Spanning Missouri River, Rulo, Richardson County, NE

  14. Vowel Polarization and Third Person Possessed Endings in Eskimo

    ERIC Educational Resources Information Center

    Koo, Jang H.

    1974-01-01

    In Eskimo there are two different underlying representations on the phonological level for the possessive and transitive constructions, but confusion has resulted from the fact that these have been treated identically. (CK)

  15. 38. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) SECOND FLOOR PLAN, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  16. 44. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) TRANSVERSE SECTION, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  17. 51. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) NORTH AND WEST ELEVATION, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  18. 46. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) GROUND FLOOR PLAN, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  19. 35. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) TRANSVERSE SECTION, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  20. 61. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    61. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) TYPICAL EXTERIOR WALL SECTIONS (REVISED), 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  1. 39. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) WEST ELEVATION, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  2. 42. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) SECTION THROUGH WEST (FREMONT AVENUE) WING, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  3. 50. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    50. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) DOOR AND WINDOW DETAILS, OTHER MILLWORK DETAILS, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  4. 55. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    55. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) GROUND AND FIRST FLOOR PLANS, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  5. 33. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) EAST ELEVATION, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  6. 56. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    56. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) SECOND FLOOR, ROOF AND CEILING FRAMING PLANS, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  7. 53. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) EXTERIOR DETAILS, WALL SECTION, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  8. 49. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) ROOF AND ATTIC PLAN, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  9. 32. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. Photocopy of architectural drawing (original print in the possession of the Minneapolis Special School District No. 1) SOUTH ELEVATION, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  10. 36. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) FOUNDATION PLAN, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  11. 34. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) NORTH ELEVATION, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  12. 37. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    37. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) FIRST FLOOR PLAN, 1897 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  13. 40. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    40. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) WEST ELEVATION, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  14. 59. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    59. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) ROOF TRUSSES, MISCELLANEOUS DETAILS, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  15. 47. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) FIRST FLOOR PLAN, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  16. 52. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) EAST ELEVATION, CROSS SECTION, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  17. 43. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) LONGITUDINAL SECTION THROUGH AUDITORIUM; COURT ELEVATION, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  18. 58. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    58. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) MISCELLANEOUS DETAILS, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  19. 57. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    57. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) SECOND FLOOR AND ROFF PLANS, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  20. 60. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    60. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) FLAT, 1916 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  1. 48. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    48. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) SECOND FLOOR PLAN, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  2. 41. Photocopy of architectural drawing (original print in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. Photocopy of architectural drawing (original print in the possession of Minneapolis Special School District No. 1) WEST ELEVATION, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  3. 54. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    54. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) FOUNDATION AND FIRST FLOOR FRAMING PLANS, 1916, ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  4. 45. Photocopy of architectural drawing (original print in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. Photocopy of architectural drawing (original print in possession of Minneapolis Special School District No. 1) FOUNDATION PLAN, 1909 ADDITION - Frederika Bremer Intermediate School, 1214 Lowry Avenue North, Minneapolis, Hennepin County, MN

  5. Photographic copy of photograph (original print in possession of William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph (original print in possession of William Langer Jewel Bearing Plant, Rolla, North Dakota). MACHINE SHOP - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  6. Photographic copy of photograph (original print in possession of William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph (original print in possession of William Langer Jewel Bearing Plant, Rolla, North Dakota). LARGE HOLE-OPENING - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  7. Photographic copy of photograph (original print in possession of William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph (original print in possession of William Langer Jewel Bearing Plant, Rolla, North Dakota). FINAL INSPECTION - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  8. 7. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Photographer unknown, circa 1983) OVERALL VIEW OF THE BROOKLYN ARMY TERMINAL, LOOKING NORTHEAST - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

  9. 32 CFR 507.12 - Possession and wearing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... is subject to punishment as prescribed in the statutes referred to in § 507.5 of this part. (b) Mere... such possession is not used to defraud or misrepresent the identification or status of the individual...

  10. 24. Photocopy of photograph (original in possession of Chiricahua National ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Photocopy of photograph (original in possession of Chiricahua National Monument), photographer unknown, c.1938 LILLIAN AND ED RIGGS IN FRONT OF RANCH HOUSE WITH ANNA MARIE POWERS - Faraway Ranch, Willcox, Cochise County, AZ

  11. 8. Photocopy of photograph (original photograph in possession of Coronado ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Photocopy of photograph (original photograph in possession of Coronado Historical Association). Photographer Unknown, circa 1922. HEILMAN VILLAS FROM ORANGE AVENUE - Heilman Villas, 706-720 Orange Avenue & 1060-1090 Seventh Street, Coronado, San Diego County, CA

  12. 4. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. LOOKING NORTH AFTER ADDITION OF CONICAL ROOF. ORIGINALLY PUBLISHED 1887. - Rock Island Arsenal, Building No. 53, North Avenue North of Midpoint, Rock Island, Rock Island County, IL

  13. 10. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. INTERIOR, LOOKING WEST. DATED OCTOBER 2, 1945. - Rock Island Arsenal, Building No. 138, Second Avenue between South Avenue & Ramsey Street, Rock Island, Rock Island County, IL

  14. 8. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH ELEVATON IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 68, Rodman Avenue between Fourth Street & East Avenue, Rock Island, Rock Island County, IL

  15. 6. photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. ELEVATIONS AND PLANS FOR POWDER BARREL RACK, 1889. - Rock Island Arsenal, Building No. 280, Sylvan Drive, Rock Island, Rock Island County, IL

  16. 5. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. PLAN, ELEVATION, AND SECTION, 1874; TRACING, 1935. - Rock Island Arsenal, Building No. 53, North Avenue North of Midpoint, Rock Island, Rock Island County, IL

  17. 6. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. ELEVATIONS, 1871. - Rock Island Arsenal, Building No. 105, South Avenue between Gillespie Avenue & Second Street, Rock Island, Rock Island County, IL

  18. 11. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. ELEVATION AND DETAILS, UNDATED. - Rock Island Arsenal, Building No. 138, Second Avenue between South Avenue & Ramsey Street, Rock Island, Rock Island County, IL

  19. 5. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. PLAN, UNDATED. - Rock Island Arsenal, Building No. 105, South Avenue between Gillespie Avenue & Second Street, Rock Island, Rock Island County, IL

  20. 5. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. INTERIOR AFTER REMODELING INTO OFFICE SPACE. DATED FEBRUARY 13, 1943. - Rock Island Arsenal, Building No. 67, Rodman Avenue & Fourth Street, Rock Island, Rock Island County, IL

  1. 4. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH AND WEST ELEVATIONS. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 108, Rodman Avenue between Third & Fourth Streets, Rock Island, Rock Island County, IL

  2. 13. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. BASEMENT PLAN, 1920. - Rock Island Arsenal, Building No. 90, East Avenue between North Avenue & King Drive, Rock Island, Rock Island County, IL

  3. 4. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH ELEVATION IN UNALTERED CONDITION. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 109, Rodman Avenue & Fourth Street, Rock Island, Rock Island County, IL

  4. 9. Photograph of photograph in possession of Rock Island Arsenal ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photograph of photograph in possession of Rock Island Arsenal Historical Office. WEST AND NORTH ELEVATIONS. ORIGINALLY PUBLISHED 1887. - Rock Island Arsenal, Building No. 90, East Avenue between North Avenue & King Drive, Rock Island, Rock Island County, IL

  5. 10. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH AND WEST ELEVATIONS IN UNALTERED CONDITION. DATED APRIL 18, 1941. - Rock Island Arsenal, Building No. 56, North Avenue & East Avenue, Rock Island, Rock Island County, IL

  6. 5. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. WEST ELEVATION IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 280, Sylvan Drive, Rock Island, Rock Island County, IL

  7. 15. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. SECOND FLOOR PLAN, 1920. - Rock Island Arsenal, Building No. 90, East Avenue between North Avenue & King Drive, Rock Island, Rock Island County, IL

  8. 10. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. FRONT ELEVATION, 1873. - Rock Island Arsenal, Building No. 225, Rodman Avenue between Flagler Street & Gillespie Avenue, Rock Island, Rock Island County, IL

  9. 3. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH ELEVATION IN UNALTERED CONDITION. DATED MARCH 19, 1945. - Rock Island Arsenal, Building No. 61, Rodman Avenue & First Street, Rock Island, Rock Island County, IL

  10. 14. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. FIRST FLOOR PLAN, 1920. - Rock Island Arsenal, Building No. 90, East Avenue between North Avenue & King Drive, Rock Island, Rock Island County, IL

  11. 3. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH ELEVATION IN UNALTERED CONDITION. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 103, Rodman Avenue & First Street, Rock Island, Rock Island County, IL

  12. 7. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH AND EAST ELEVATIONS. DATED MARCH 19, 1945. - Rock Island Arsenal, Building No. 62, Rodman Avenue between First & Second Streets, Rock Island, Rock Island County, IL

  13. 11. Photograph of a photograph in possession of Rock Island ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. BASEMENT, SHOWING ORIGINAL OPEN INTERIOR PLAN. DATED APRIL 7, 1942. - Rock Island Arsenal, Building No. 56, North Avenue & East Avenue, Rock Island, Rock Island County, IL

  14. 16. Photograph of line drawing in possession of Engineering Plans ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. ATTIC PLAN, 1920. - Rock Island Arsenal, Building No. 90, East Avenue between North Avenue & King Drive, Rock Island, Rock Island County, IL

  15. 24. Photocopy of construction drawing (original in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Photocopy of construction drawing (original in the possession of the Public Service Company of Colorado, Denver Colorado) Lewis E. Ashbaugh, Engineer, 1908 POWER HOUSE ARRANGEMENT - Shoshone Hydroelectric Plant Complex, 60111 U.S. Highway 6, Garfield County, CO

  16. 20. Photocopy of construction drawing (original in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photocopy of construction drawing (original in the possession of the Public Service Company of Colorado, Denver Colorado) Albert Carr, Engineer, 1908 GLENWOOD POWER CANAL AND PIPELINE - Shoshone Hydroelectric Plant Complex, 60111 U.S. Highway 6, Garfield County, CO

  17. 3. Photocopy of photograph, original print in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photocopy of photograph, original print in the possession of John R. Morison, Peterborough, New Hampshire. Photographer unknown, circa 1887. JAMES HOWARD TRANSFER STEAMER USED FOR CONSTRUCTION - Cairo Bridge, Spanning Ohio River, Cairo, Alexander County, IL

  18. 9. Photocopy of plan (original plan in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photocopy of plan (original plan in the possession of the City of Spokane, Department of Public Works) DETAIL OF FRAMEWORK FOR ARCH CENTERING - Washington Street Bridge, Spanning Spokane River at Washington Street, Spokane, Spokane County, WA

  19. 39. Photocopy of bridge drawing, 1923 (original in possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. Photocopy of bridge drawing, 1923 (original in possession of Wilkes-Barre City Engineer's Office) STRESS SHEET TRUSS SPANS - South Street Bridge, Spans Pennsylvania Avenue, Wilkes-Barre Boulevard, Pocono Northeast Railroad, Wilkes-Barre, Luzerne County, PA

  20. 26. Photocopy of drawing (original in possession of Allegany County, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. Photocopy of drawing (original in possession of Allegany County, Cumberland, MD) HEADER BUILDING, ELEVATIONS OF WEST SIDE ON COL LINE AH AND AP, 1920 - Kelly-Springfield Tire Plant, Factory Building, 701 Kelly Road, Cumberland, Allegany County, MD

  1. Photograph of original drawing (original in possession of National Passenger ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of original drawing (original in possession of National Passenger Railroad Corporation). Canopy Plans, Sections, and Details (n.d.) - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  2. Photographic copy of photograph (original print in possession of William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph (original print in possession of William Langer Jewel Bearing Plant, Rolla, North Dakota). PASTING JEWEL BLANKS, PREPARATION FOR DRILLING. - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  3. Photographic copy of photograph (original print in possession of William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph (original print in possession of William Langer Jewel Bearing Plant, Rolla, North Dakota). DRILLING - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  4. Photograph of line drawing in possession of Engineering Plans and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. MAP OF ROCK ISLAND ARSENAL, 1919, REVISED 1938 - Rock Island Arsenal, Rock Island, Rock Island County, IL

  5. 6. Photograph of an architectural drawing in possession of Engineering ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photograph of an architectural drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. ELEVATION, 1874. DELINEATOR: W. OTTO GRONEN. - Rock Island Arsenal, Building No. 321, Rodman Avenue & Rock Island Avenue, Rock Island, Rock Island County, IL

  6. 5. Photocopy of measured drawing (original drawing in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of measured drawing (original drawing in the possession of the Rigsarkivet (Royal Archives), Copenhagen, Denmark) Lieutenant Giellerup, delineator, May 1829 PLAN PROPOSED ALTERATIONS OF SECOND FLOOR OF GOVERNMENT HOUSE - Government House, King Street, Christiansted, St. Croix, VI

  7. 4. Photocopy of measured drawing (original drawing in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of measured drawing (original drawing in the possession of the Rigsarkivet (Royal Archives), Copenhagen, Denmark) Lieutenant Giellerup, delineator, May 1829 PROPOSED ALTERATIONS OF GOVERNMENT HOUSE - Government House, King Street, Christiansted, St. Croix, VI

  8. 6. Photocopy of measured drawing (original drawing in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of measured drawing (original drawing in the possession of the Rigsarkivet (Royal Archives), Copenhagen, Denmark) Ludvig Schellerup, architect, August 1864 PLAN OF GOVERNMENT HOUSE - Government House, King Street, Christiansted, St. Croix, VI

  9. 20 CFR 404.1093 - Possession of the United States.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment... figuring your net earnings from self-employment, the term possession of the United States shall be deemed...

  10. Photographic copy of photograph (original print in possession of William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph (original print in possession of William Langer Jewel Bearing Plant, Rolla, North Dakota). OLIVING - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  11. 20 CFR 404.1093 - Possession of the United States.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment... figuring your net earnings from self-employment, the term possession of the United States shall be deemed...

  12. 20 CFR 404.1093 - Possession of the United States.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment... figuring your net earnings from self-employment, the term possession of the United States shall be deemed...

  13. 20 CFR 404.1093 - Possession of the United States.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment... figuring your net earnings from self-employment, the term possession of the United States shall be deemed...

  14. 20 CFR 404.1093 - Possession of the United States.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment... figuring your net earnings from self-employment, the term possession of the United States shall be deemed...

  15. 25. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. John C. Trautwine, architect and engineer, circa December 1833. PLAN OF THE BASEMENT - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  16. 30. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    30. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Thomas U. Walter, architect, November 25, 1833. PLAN OF THIRD STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  17. 22. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. William Strickland, architect, circa December 1833. SECOND STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  18. 33. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Walter F. Price, architect, June 5, 1913. PROPOSED COVERED PASSAGES FOR THE PENNSYLVANIA HOSPITAL - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  19. 31. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Thomas U. Walter, architect, November 25, 1833. FRONT ELEVATION - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  20. 18. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Samuel H. Kneass, architect, January 1834. PLAN OF THE PRINCIPAL STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  1. 17. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Samuel H. Kneass, architect, January 1834. PLAN OF THE BASEMENT STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  2. 19. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Samuel H. Kneass, architect, January 1834. PLAN OF THE THIRD STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  3. 21. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. William Strickland, architect, circa December 1833. BASEMENT STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  4. 23. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. William Strickland, architect, circa December 1833. THIRD STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  5. 14. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. John Haviland, architect, December 1833. PLAN OF THE PRINCIPAL FLOOR - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  6. 29. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Thomas U. Walter, architect, November 25, 1833. PLAN OF PRINCIPAL STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  7. 28. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Thomas U. Walter, architect, November 25, 1833. PLAN OF BASEMENT STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  8. 20. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. Samuel H. Kneass, architect, January 1834. PINE STREET FRONT - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  9. 24. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. William Strickland, architect, circa December 1833. NORTH FRONT - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  10. 15. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. John Haviland, architect, December 1833. ELEVATION OF THE NORTH OR PRINCIPAL FRONT - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  11. 27. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. John C. Trautwine, architect and engineer, circa December 1833. NORTH FRONT and EAST & WEST FRONTS - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  12. 26. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. John C. Trautwine, architect and engineer, circa December 1833. PLAN OF THE PRINCIPAL STORY - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  13. 16. Photograph of architectural competition drawing; original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. Photograph of architectural competition drawing; original in the possession of the Pennsylvania Hospital. John Haviland, architect, December 1833. LONGITUDINAL SECTION FROM EAST TO WEST - Pennsylvania Hospital, Eighth & Ninth, Pine & Spruce Streets, Philadelphia, Philadelphia County, PA

  14. 13. Photocopy of photograph (original photograph in possession of Butt ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. Photocopy of photograph (original photograph in possession of Butt Booth). Photograph dated ca. 1908. VIEW SOUTH SHOWING ATTACHED OXEN AND ENGINE SHEDS - Baker-Booth Blacksmith Shop, Lear Hill Road, West of Route 10, Goshen, Sullivan County, NH

  15. 1. Photograph of line drawing in possession of the Watervliet ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Photograph of line drawing in possession of the Watervliet Arsenal Museum, New York. 'VILLAGE OF WEST TROY EMBRACING WATER VLIET' BY S. A. BEERS, 1845. - Watervliet Arsenal, South Broadway, Watervliet, Albany County, NY

  16. 2. Photocopy of negative (original in possession of Western Archeological ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Photocopy of negative (original in possession of Western Archeological and Conservation Center (WACC), Tucson, Arizona), photographer unknown, undated CHILDREN POISED AT EDGE OF FILLED SWIMMING POOL - Faraway Ranch, Swimming Pool, Willcox, Cochise County, AZ

  17. 10. Photocopy of a measured drawing in possession of the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Photocopy of a measured drawing in possession of the Kunstakademiets (Royal Danish Academy of Fine Arts), Copenhagen, Denmark, 1961 Photographer unknown RAADETSGADE (STREET) (EAST) ELEVATION - Dronningensgade 32 (House), 32 Queen Street, Charlotte Amalie, St. Thomas, VI

  18. 6. Photocopy of a measured drawing in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of a measured drawing in the possession of the Kunstakademiets (Royal Academy of Fine Arts), Copenhagen, Denmark, 1961 EAST (RAADETSGADE) ELEVATION - Dronningensgade 8B (House), 8B Queen Street, Charlotte Amalie, St. Thomas, VI

  19. 1. Photocopy of a measured drawing (original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Photocopy of a measured drawing (original in the possession of the Kunstakademiets (Royal Academy of Fine Arts), Copenhagen, Denmark, 1961) PLANS OF FIRST AND SECOND FLOORS - Dronningensgade 2 (House), 2 Queen Street, Charlotte Amalie, St. Thomas, VI

  20. 5. Photocopy of a measured drawing (original in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of a measured drawing (original in the possession of the Kunstakademiets (Royal Academy of Fine Arts), Copenhagen, Denmark, 1961) ELEVATION (END) FACING WIMMELSKAFTSGADE - Dronningensgade 8B (House), 8B Queen Street, Charlotte Amalie, St. Thomas, VI

  1. 6. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Topo-Metrics, Inc, 1992. Aerial view of the Brooklyn Army Terminal - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

  2. 9. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Photographer and date unknown VIEW BETWEEN PIERS 2 AND 3, LOOKING FROM WAREHOUSE ROOF - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

  3. 20. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photocopy of photograph (original in possession of NYC Economic Development Corp.) US Army photograph, 1949 VIEW SOUTH ELEVATION, OUTER END-PIER 4 - Brooklyn Army Supply Base, Pier 4, Brooklyn, Kings County, NY

  4. 12. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Photocopy of photograph (original in possession of NYC Economic Development Corp.) US Army Photograph, 1952 VIEW OF TEST HOLES BETWEEN PIERS - Brooklyn Army Supply Base, Pier 2, Brooklyn, Kings County, NY

  5. 19. Photocopy of photograph (original in possession of NYC Economic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photocopy of photograph (original in possession of NYC Economic Development Corp.) Photographer and date unknown PIER 4 CONNECTING BRIDGE AND WAREHOUSE A - Brooklyn Army Supply Base, Pier 4, Brooklyn, Kings County, NY

  6. Photocopy of drawing (original in possession of Allegany County, Cumberland, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing (original in possession of Allegany County, Cumberland, MD) CEMENT HOUSE FLOOR PLAN, 1942 - Kelly-Springfield Tire Plant, Cement House, 701 Kelly Road, Cumberland, Allegany County, MD

  7. 3. Photographic copy of map, dated October 1932, in possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photographic copy of map, dated October 1932, in possession of San Carlos Irrigation and Drainage District. U.S. Indian Irrigation Service. PICACHO RESERVOI - San Carlos Irrigation Project, Picacho Resevoir, South of Gila River, Coolidge, Pinal County, AZ

  8. 6. Photocopy of photograph (original print in possession of Western ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of photograph (original print in possession of Western Archaeologial and Conservation Center (WACC), Tucson, Arizona), photographer unknown, undated AERIAL VIEW OF FARAWAY RANCH AND VICINITY - Faraway Ranch, Willcox, Cochise County, AZ

  9. 5. Photocopy of negative (original in possession of Western Archeological ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of negative (original in possession of Western Archeological and Conservation Center (WACC), Tucson, Arizona), photographer unknown, undated BARN AND CORRAL LOOKING NORTHEAST - Faraway Ranch, Barn & Tool Shed, Willcox, Cochise County, AZ

  10. 34. Photocopy of photograph (original in possession of Western Archeological ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. Photocopy of photograph (original in possession of Western Archeological and Conservation Center, (WACC), Tucson, Arizona), photographer unknown, c.1910 MAIN HOUSE - Faraway Ranch, Erickson-Riggs Ranch House, State Highway 181, Willcox, Cochise County, AZ

  11. 4. Photocopy of photograph (original in possession of Western Archeological ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of photograph (original in possession of Western Archeological and Conservation Center (WACC), Tucson, Arizona), photographer unknown, undated NEIL ERICKSON WORKING OUTSIDE OFFICE/GARAGE WHEN IT WAS NEW - Faraway Ranch, Office-Garage, Willcox, Cochise County, AZ

  12. 16. Photographic copy of drawing, dated September 1924, in possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. Photographic copy of drawing, dated September 1924, in possession of San Carlos Irrigation Project. United States Indian Service, Irrigation. PIMA LATERAL HEADWORKS, RADIAL GATES - San Carlos Irrigation Project, Pima Lateral, Main Canal at Sacaton Dam, Coolidge, Pinal County, AZ

  13. 9. Photocopy of Charles H. Parkers Patent (Original in possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photocopy of Charles H. Parkers Patent (Original in possession of United States Patent Office) PATENT DRAWING OF C. H. PARKER TRUSS BRIDGE - Elm Street Bridge, Spanning Ottauquechee River, Woodstock, Windsor County, VT

  14. 15. Photocopy of drawing (original in the possession of the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Photocopy of drawing (original in the possession of the Archives Collection, Syracuse Univerity) Photographer and date unknown PROPOSED DESIGN BY W. L. WOOLETT, ARCHITECT, SHOWING FRONT ELEVATION - Syracuse University, Hall of Languages, Syracuse University Campus, Syracuse, Onondaga County, NY

  15. 19. Photocopy of blackline print in possession of Mrs. William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photocopy of blackline print in possession of Mrs. William L. Reno. Original drawing by George Locke Howe, Architect 1938. 'SECOND FLOOR PLAN' - Mr. & Mrs. Charles Collier House, 6080 Leesburg Pike, Falls Church, Falls Church, VA

  16. 22. Photocopy of blackline print in possession of Mrs. William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Photocopy of blackline print in possession of Mrs. William L. Reno. Original drawing by George Locke Howe, Architect 1938. 'NORTH EAST ELEVATION' - Mr. & Mrs. Charles Collier House, 6080 Leesburg Pike, Falls Church, Falls Church, VA

  17. 20. Photocopy of blackline print in possession of Mrs. William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photocopy of blackline print in possession of Mrs. William L. Reno. Original drawing by George Locke Howe, Architect 1938. 'SOUTH WEST ELEVATION' - Mr. & Mrs. Charles Collier House, 6080 Leesburg Pike, Falls Church, Falls Church, VA

  18. 18. Photocopy of blackline print in possession of Mrs. William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photocopy of blackline print in possession of Mrs. William L. Reno. Original drawing by George Locke Howe, Architect 1938. 'FIRST FLOOR PLAN' - Mr. & Mrs. Charles Collier House, 6080 Leesburg Pike, Falls Church, Falls Church, VA

  19. 36. Photocopy of photograph (original in possession of Chiricahua National ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. Photocopy of photograph (original in possession of Chiricahua National Monument), photographer unknown, c.1915 EMMA ERICKSON AND MRS. COLLINS ON BALCONY OF RANCH HOUSE - Faraway Ranch, Erickson-Riggs Ranch House, State Highway 181, Willcox, Cochise County, AZ

  20. 23. Photocopy of blackline print in possession of Mrs. William ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. Photocopy of blackline print in possession of Mrs. William L. Reno. Original drawing by George Locke Howe, Architect 1938. SHEET OF SECTIONS AND ROOM ELEVATIONS - Mr. & Mrs. Charles Collier House, 6080 Leesburg Pike, Falls Church, Falls Church, VA

  1. 12. Photocopy of sketch (original in possession of WACC) George ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Photocopy of sketch (original in possession of WACC) George Dunn, photographer, 1892 'ORIGINAL HOME OF MR. AND MRS. NEIL ERICKSON IN BONITA CANYON ABOUT 1892' - Faraway Ranch, Willcox, Cochise County, AZ

  2. 5. Photocopy of drawing (original in possession of Allegany County, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of drawing (original in possession of Allegany County, Cumberland, MD) FIRST FLOOR PLAN, BOILER AND POWER HOUSE, 1922 - Kelly-Springfield Tire Plant, Power House, 701 Kelly Road, Cumberland, Allegany County, MD

  3. 28. Photocopy of drawing (original in possession of Allegany County, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Photocopy of drawing (original in possession of Allegany County, Cumberland, MD) FACTORY BUILDING, PLAN OF FLOOR B, MACHINERY LAYOUT, 1943, NOTE INFILLED COURTS - Kelly-Springfield Tire Plant, Factory Building, 701 Kelly Road, Cumberland, Allegany County, MD

  4. Photocopy of drawing (original In possession of Allegany County, Cumberland, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing (original In possession of Allegany County, Cumberland, MD) WELL WATER RESERVOIR, 1926 - Kelly-Springfield Tire Plant, Cooling Tower, 701 Kelly Road, Cumberland, Allegany County, MD

  5. 25. Photocopy of drawing (original in possession of Allegany County, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Photocopy of drawing (original in possession of Allegany County, Cumberland, MD) COURT 4, SECTION BETWEEN COLS. 51 AND 52, LOOKING NORTH, NOTE MONITOR WINDOW, 1920 - Kelly-Springfield Tire Plant, Factory Building, 701 Kelly Road, Cumberland, Allegany County, MD

  6. 27. Photocopy of drawing (original in possession of Allegany County, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. Photocopy of drawing (original in possession of Allegany County, Cumberland, MD) FACTORY BUILDING, PLAN OF FLOOR B, 1928, NOTE OPEN COURTS - Kelly-Springfield Tire Plant, Factory Building, 701 Kelly Road, Cumberland, Allegany County, MD

  7. Constitutional Law: Right of Privacy--Possession of Marijuana

    ERIC Educational Resources Information Center

    Rohrer, David E.

    1976-01-01

    The Alaska Supreme Court in Ravin v. State accepted the defendant's contention that the prohibition of possession of marihuana infringed on his constitutional right to privacy. The significance of the case is discussed. (LBH)

  8. 9. Photocopy of drawing (original in possession of Naval Surface ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL COMPLEX, SCHEMATIC, UNDATED - Naval Surface Warfare Center, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  9. Photocopy of photograph (original photograph in possession of Atlanta Housing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of photograph (original photograph in possession of Atlanta Housing Authority, Atlanta GA). Photographer unknown, circa 1940. VIEW OF APARTMENT INTERIOR. - Techwood Homes (Public Housing), Bounded by North Avenue, Parker Street, William Street & Lovejoy Street, Atlanta, Fulton County, GA

  10. 2. Photocopy of measured drawing (original drawing in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Photocopy of measured drawing (original drawing in the possession of Beinecke Rare Books Library, Yale University) Henry Austin, architect, 1850 NORTHEAST ELEVATION - Moses Yale Beach House, 86 North Main Street, Wallingford, New Haven County, CT

  11. 1. Photocopy of measured drawing (original drawing in the possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Photocopy of measured drawing (original drawing in the possession of Beinecke Rare Books Library, Yale University) Henry Austin, architect, 1850 SOUTHEAST (FRONT) ELEVATION - Moses Yale Beach House, 86 North Main Street, Wallingford, New Haven County, CT

  12. 15. Photographic copy of floor plan, not dated, in possession ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Photographic copy of floor plan, not dated, in possession of Selfridge Base Museum, Mt. Clemens, Michigan. - Selfridge Field, Building No. 1050, Northwest corner of Doolittle Avenue & D Street; Harrison Township, Mount Clemens, Macomb County, MI

  13. 4. Photocopy of negative (original in possession of Western Archeological ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of negative (original in possession of Western Archeological and Conservation Center (WACC), Tucson, Arizona), photographer unknown, c.1920's RARE VIEW OF BUNKHOUSE LOOKING SOUTHEAST - Faraway Ranch, Guest Quarters-Bunkhouse, Willcox, Cochise County, AZ

  14. 39. Photocopy of photograph (original in possession of WACC), photographer ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. Photocopy of photograph (original in possession of WACC), photographer unknown, c.1930's GUEST DINING ROOM WITH TABLE LAID FOR GUESTS - Faraway Ranch, Erickson-Riggs Ranch House, State Highway 181, Willcox, Cochise County, AZ

  15. 6. Photocopy of photograph, original negative in the possession of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of photograph, original negative in the possession of John R. Morison, Peterborough, New Hampshire. Photographer unknown circa June, 1887. AIR CHAMBER AND PNEUMATIC PUMP ABOARD THE STEAMER JOHN BERTRAM - Rulo Bridge, Spanning Missouri River, Rulo, Richardson County, NE

  16. 32 CFR 507.12 - Possession and wearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Possession and wearing. (a) The wearing of any decoration, service medal, badge, service ribbon, lapel button... medal, badge, service ribbon, lapel button, or insignia to misrepresent the identification or status of...

  17. Investigating the Link Between Gun Possession and Gun Assault

    PubMed Central

    Richmond, Therese S.; Culhane, Dennis P.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2009-01-01

    Objectives. We investigated the possible relationship between being shot in an assault and possession of a gun at the time. Methods. We enrolled 677 case participants that had been shot in an assault and 684 population-based control participants within Philadelphia, PA, from 2003 to 2006. We adjusted odds ratios for confounding variables. Results. After adjustment, individuals in possession of a gun were 4.46 (P < .05) times more likely to be shot in an assault than those not in possession. Among gun assaults where the victim had at least some chance to resist, this adjusted odds ratio increased to 5.45 (P < .05). Conclusions. On average, guns did not protect those who possessed them from being shot in an assault. Although successful defensive gun uses occur each year, the probability of success may be low for civilian gun users in urban areas. Such users should reconsider their possession of guns or, at least, understand that regular possession necessitates careful safety countermeasures. PMID:19762675

  18. Regulation of energy metabolism by the extracytoplasmic function (ECF) s factors of Arcobacter butzleri

    USDA-ARS?s Scientific Manuscript database

    The extracytoplasmic function (ECF) s factors are fundamental for bacterial adaptation to distinct environments and for survival under different stress conditions. The emerging pathogen Arcobacter butzleri possesses seven putative pairs of s/anti-s factors belonging to the ECF family. Here, we repor...

  19. Incidence and risk factors for breast cancer subtypes in three distinct South-East Asian ethnic groups: Chinese, Malay and natives of Sarawak, Malaysia.

    PubMed

    Devi, C R Beena; Tang, Tieng Swee; Corbex, Marilys

    2012-12-15

    We determined the incidences of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) subtypes among breast cancer cases in Sarawak, Malaysia and their correlation with various risk factors in the three ethnic groups: Chinese, Malay and native. Subtype status was ascertained for 1,034 cases of female breast cancer (93% of all cases diagnosed since 2003), and the age-standardized incidence rates (ASRs) of each subtype were inferred. Case-case comparisons across subtypes were performed for reproductive risk factors. We found 48% luminal A (ER+/PR+/HER2-), 29% triple-negative (ER-/PR-/HER2-), 12% triple-positive (ER+/PR+/HER2+) and 11% HER2-overexpressing (ER-/PR-/HER2+) subtypes, with ASRs of 10.6, 6.0, 2.8 and 2.8 per 100,000, respectively. The proportions of subtypes and ASRs differed significantly by ethnic groups: HER2-positive cases were more frequent in Malays (29%; 95% CI [23;35]) than Chinese (22%; [19;26] and natives (21%; [16;26]); triple-negative cases were less frequent among Chinese (23%; [20;27]) than Malays (33%; [27;39]) and natives (37%; [31;43]). The results of the case-case comparison were in accordance with those observed in western case series. Some uncommon associations, such as between triple-negative subtype and older age at menopause (OR, 1.59; p < 0.05), were found. The triple-negative and HER2+ subtypes predominate in our region, with significant differences among ethnic groups. Our results support the idea that the risk factors for different subtypes vary markedly. Westernized populations are more likely to have factors that increase the risk for the luminal A type, while risk factors for the triple-negative type are more frequent in local populations. Copyright © 2012 UICC.

  20. Distinct roles of the polarity factors Boi1 and Boi2 in the control of exocytosis and abscission in budding yeast.

    PubMed

    Masgrau, Aina; Battola, Andrea; Sanmartin, Trinidad; Pryszcz, Leszek P; Gabaldón, Toni; Mendoza, Manuel

    2017-09-13

    Boi1 and Boi2 (Boi1/2) are budding yeast plasma membrane proteins that function in polarized growth, and in cytokinesis inhibition in response to chromosome bridges via the NoCut abscission checkpoint. How Boi1/2 act in these two distinct processes is not understood. We demonstrate that Boi1/2 are required for a late step in the fusion of secretory vesicles with the plasma membrane of the growing bud. Cells lacking Boi1/2 accumulate secretory vesicles and are defective in bud growth. In contrast, Boi2 is specifically required for abscission inhibition in cells with chromatin bridges. The SH3 domain of Boi2, which is dispensable for bud growth and targets Boi2 to the site of abscission, is necessary and sufficient for abscission inhibition. Gain of function of the exocyst, a conserved protein complex involved in tethering of exocytic vesicles to the plasma membrane, rescued secretion and bud growth defects in boi mutant cells, and abrogated NoCut checkpoint function. Thus, Boi2 functions redundantly with Boi1 to promote the fusion of secretory vesicles with the plasma membrane at sites of polarized growth, and acts as an abscission inhibitor during cytokinesis in response to chromatin bridges. © 2017 by The American Society for Cell Biology.