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  1. Pseudomonas aeruginosa Possesses Two Putative Type I Signal Peptidases, LepB and PA1303, Each with Distinct Roles in Physiology and Virulence

    PubMed Central

    Rose, Ruth S.; Rangarajan, Minnie; Aduse-Opoku, Joseph; Hashim, Ahmed; Curtis, Michael A.

    2012-01-01

    Type I signal peptidases (SPases) cleave signal peptides from proteins during translocation across biological membranes and hence play a vital role in cellular physiology. SPase activity is also of fundamental importance to the pathogenesis of infection for many bacteria, including Pseudomonas aeruginosa, which utilizes a variety of secreted virulence factors, such as proteases and toxins. P. aeruginosa possesses two noncontiguous SPase homologues, LepB (PA0768) and PA1303, which share 43% amino acid identity. Reverse transcription (RT)-PCR showed that both proteases were expressed, while a FRET-based assay using a peptide based on the signal sequence cleavage region of the secreted LasB elastase showed that recombinant LepB and PA1303 enzymes were both active. LepB is positioned within a genetic locus that resembles the locus containing the extensively characterized SPase of E. coli and is of similar size and topology. It was also shown to be essential for viability and to have high sequence identity with SPases from other pseudomonads (≥78%). In contrast, PA1303, which is small for a Gram-negative SPase (20 kDa), was found to be dispensable. Mutation of PA1303 resulted in an altered protein secretion profile and increased N-butanoyl homoserine lactone production and influenced several quorum-sensing-controlled phenotypic traits, including swarming motility and the production of rhamnolipid and elastinolytic activity. The data indicate different cellular roles for these P. aeruginosa SPase paralogues; the role of PA1303 is integrated with the quorum-sensing cascade and includes the suppression of virulence factor secretion and virulence-associated phenotypes, while LepB is the primary SPase. PMID:22730125

  2. 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.

  3. Nominal Possession in Swahili: Its Role in Communication.

    ERIC Educational Resources Information Center

    Hawkinson, Annie K.

    This paper defines the grammatical role of a particle in Swahili in terms of the semantic information which it contributes to all utterances in which it occurs. The particle -A occurs in the syntactic configuration Noun 1 -A Noun 2 and has been traditionally described as reflecting relations of possession and attribution between the two nouns in…

  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.

  5. 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. PMID:25869594

  6. 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

  7. Strains of Burkholderia cenocepacia genomovar IIIA possessing the cblA gene that are distinct from ET12.

    PubMed

    Turton, Jane F; O'Brien, Emily; Megson, Brian; Kaufmann, Mary E; Pitt, Tyrone L

    2009-05-01

    Three strains of Burkholderia cenocepacia genomovar IIIA that were polymerase chain reaction positive for cblA, bcrA, and the epidemic strain marker, but were distinct from representatives of ET12 by pulsed-field gel electrophoresis, are described. One of these strains was shown to express cable pili by electron microscopy.

  8. [Possession of weapon and hunting license: the role of the physician].

    PubMed

    Manaouil, Cécile; Gignon, Maxime; Giboulet, Nicolas; Jardé, Olivier

    2012-01-01

    In France, the physician can inform the prefect that a patient, detaining weapon and followed for a pathology (psychiatric notably), is dangerous. Then, it comes back to the prefect to appreciate the appropriate measurements to take, notably to order the delivery of weapon and ammunitions. In France, the doctor can be solicited to establish the necessary medical certficates during requests of approval or acquisition and having guns for hunting and sports shooting, or to obtain the licence of hunting. The acquisition and the possession of certain weapon cannot be granted if the applicant is a protected person over 18, was or is hospitalized, without his consent, owing to mental disturbances or, is in a physical or psychical state apparently incompatible with the possession of weapon. But it appears that the access to this information by the prefects is made difficult by the absence of files centralizing these data. Question settles to institute an automated national file of hospitalizations under pressure, which could be consulted prior to the deliverance or the approval of possession of weapon for hunting and as sports shooting. In our opinion, this should be made, in a strictly supervised manner, through a sworn doctor, systematically solicited as part of the licence of hunting and licence of shooting, to liberate the family practitioners of an expertise role.

  9. Cytokinin-Specific Glycosyltransferases Possess Different Roles in Cytokinin Homeostasis Maintenance

    PubMed Central

    Šmehilová, Mária; Dobrůšková, Jana; Novák, Ondřej; Takáč, Tomáš; Galuszka, Petr

    2016-01-01

    Plant hormones cytokinins (CKs) are one of the major mediators of physiological responses throughout plant life span. Therefore, a proper homeostasis is maintained by regulation of their active levels. Besides degradation, CKs are deactivated by uridine diphosphate glycosyltransferases (UGTs). Physiologically, CKs active levels decline in senescing organs, providing a signal to nutrients that a shift to reproductive tissues has begun. In this work, we show CK glucosides distribution in Arabidopsis leaves during major developmental transition phases. Besides continuous accumulation of N-glucosides we detected sharp maximum of the glucosides in senescence. This is caused prevalently by N7-glucosides followed by N9-glucosides and specifically also by trans-zeatin-O-glucoside (tZOG). Interestingly, we observed a similar trend in response to exogenously applied CK. In Arabidopsis, only three UGTs deactivate CKs in vivo: UGT76C1, UGT76C2 and UGT85A1. We thereby show that UGT85A1 is specifically expressed in senescent leaves whereas UGT76C2 is activated rapidly in response to exogenously applied CK. To shed more light on the UGTs physiological roles, we performed a comparative study on UGTs loss-of-function mutants, characterizing a true ugt85a1-1 loss-of-function mutant for the first time. Although no altered phenotype was detected under standard condition we observed reduced chlorophyll degradation with increased anthocyanin accumulation in our experiment on detached leaves accompanied by senescence and stress related genes modulated expression. Among the mutants, ugt76c2 possessed extremely diminished CK N-glucosides levels whereas ugt76c1 showed some specificity toward cis-zeatin (cZ). Besides tZOG, a broader range of CK glucosides was decreased in ugt85a1-1. Performing CK metabolism gene expression profiling, we revealed that activation of CK degradation pathway serves as a general regulatory mechanism of disturbed CK homeostasis followed by decreased CK signaling in

  10. Cytokinin-Specific Glycosyltransferases Possess Different Roles in Cytokinin Homeostasis Maintenance

    PubMed Central

    Šmehilová, Mária; Dobrůšková, Jana; Novák, Ondřej; Takáč, Tomáš; Galuszka, Petr

    2016-01-01

    Plant hormones cytokinins (CKs) are one of the major mediators of physiological responses throughout plant life span. Therefore, a proper homeostasis is maintained by regulation of their active levels. Besides degradation, CKs are deactivated by uridine diphosphate glycosyltransferases (UGTs). Physiologically, CKs active levels decline in senescing organs, providing a signal to nutrients that a shift to reproductive tissues has begun. In this work, we show CK glucosides distribution in Arabidopsis leaves during major developmental transition phases. Besides continuous accumulation of N-glucosides we detected sharp maximum of the glucosides in senescence. This is caused prevalently by N7-glucosides followed by N9-glucosides and specifically also by trans-zeatin-O-glucoside (tZOG). Interestingly, we observed a similar trend in response to exogenously applied CK. In Arabidopsis, only three UGTs deactivate CKs in vivo: UGT76C1, UGT76C2 and UGT85A1. We thereby show that UGT85A1 is specifically expressed in senescent leaves whereas UGT76C2 is activated rapidly in response to exogenously applied CK. To shed more light on the UGTs physiological roles, we performed a comparative study on UGTs loss-of-function mutants, characterizing a true ugt85a1-1 loss-of-function mutant for the first time. Although no altered phenotype was detected under standard condition we observed reduced chlorophyll degradation with increased anthocyanin accumulation in our experiment on detached leaves accompanied by senescence and stress related genes modulated expression. Among the mutants, ugt76c2 possessed extremely diminished CK N-glucosides levels whereas ugt76c1 showed some specificity toward cis-zeatin (cZ). Besides tZOG, a broader range of CK glucosides was decreased in ugt85a1-1. Performing CK metabolism gene expression profiling, we revealed that activation of CK degradation pathway serves as a general regulatory mechanism of disturbed CK homeostasis followed by decreased CK signaling in

  11. Cytokinin-Specific Glycosyltransferases Possess Different Roles in Cytokinin Homeostasis Maintenance.

    PubMed

    Šmehilová, Mária; Dobrůšková, Jana; Novák, Ondřej; Takáč, Tomáš; Galuszka, Petr

    2016-01-01

    Plant hormones cytokinins (CKs) are one of the major mediators of physiological responses throughout plant life span. Therefore, a proper homeostasis is maintained by regulation of their active levels. Besides degradation, CKs are deactivated by uridine diphosphate glycosyltransferases (UGTs). Physiologically, CKs active levels decline in senescing organs, providing a signal to nutrients that a shift to reproductive tissues has begun. In this work, we show CK glucosides distribution in Arabidopsis leaves during major developmental transition phases. Besides continuous accumulation of N-glucosides we detected sharp maximum of the glucosides in senescence. This is caused prevalently by N7-glucosides followed by N9-glucosides and specifically also by trans-zeatin-O-glucoside (tZOG). Interestingly, we observed a similar trend in response to exogenously applied CK. In Arabidopsis, only three UGTs deactivate CKs in vivo: UGT76C1, UGT76C2 and UGT85A1. We thereby show that UGT85A1 is specifically expressed in senescent leaves whereas UGT76C2 is activated rapidly in response to exogenously applied CK. To shed more light on the UGTs physiological roles, we performed a comparative study on UGTs loss-of-function mutants, characterizing a true ugt85a1-1 loss-of-function mutant for the first time. Although no altered phenotype was detected under standard condition we observed reduced chlorophyll degradation with increased anthocyanin accumulation in our experiment on detached leaves accompanied by senescence and stress related genes modulated expression. Among the mutants, ugt76c2 possessed extremely diminished CK N-glucosides levels whereas ugt76c1 showed some specificity toward cis-zeatin (cZ). Besides tZOG, a broader range of CK glucosides was decreased in ugt85a1-1. Performing CK metabolism gene expression profiling, we revealed that activation of CK degradation pathway serves as a general regulatory mechanism of disturbed CK homeostasis followed by decreased CK signaling in

  12. How Risky Is Marijuana Possession? Considering the Role of Age, Race, and Gender

    ERIC Educational Resources Information Center

    Nguyen, Holly; Reuter, Peter

    2012-01-01

    Arrest rates per capita for possession of marijuana have increased threefold over the last 20 years and now constitute the largest single arrest offense category. Despite the increase in arrest numbers, rates of use have remained stable during much of the same period. This article presents the first estimates of the arrest probabilities for…

  13. Dynamic melody recognition: distinctiveness and the role of musical expertise.

    PubMed

    Bailes, Freya

    2010-07-01

    The hypothesis that melodies are recognized at moments when they exhibit a distinctive musical pattern was tested. In a melody recognition experiment, point-of-recognition (POR) data were gathered from 32 listeners (16 musicians and 16 nonmusicians) judging 120 melodies. A series of models of melody recognition were developed, resulting from a stepwise multiple regression of two classes of information relating to melodic familiarity and melodic distinctiveness. Melodic distinctiveness measures were assembled through statistical analyses of over 15,000 Western themes and melodies. A significant model, explaining 85% of the variance, entered measures primarily of timing distinctiveness and pitch distinctiveness, but excluding familiarity, as predictors of POR. Differences between nonmusician and musician models suggest a processing shift from momentary to accumulated information with increased exposure to music. Supplemental materials for this article may be downloaded from http://mc.psychonomic-journals.org/content/supplemental. PMID:20551343

  14. Two distinct roles of the yorkie/yap gene during homeostasis in the planarian Dugesia japonica.

    PubMed

    Hwang, Byulnim; An, Yang; Agata, Kiyokazu; Umesono, Yoshihiko

    2015-04-01

    Adult planarians possess somatic pluripotent stem cells called neoblasts that give rise to all missing cell types during regeneration and homeostasis. Recent studies revealed that the Yorkie (Yki)/Yes-associated protein (YAP) transcriptional coactivator family plays an important role in the regulation of tissue growth during development and regeneration, and therefore we investigated the role of a planarian yki-related gene (termed Djyki) during regeneration and homeostasis of the freshwater planarian Dugesia japonica. We found that knockdown of the function of Djyki by RNA interference (RNAi) downregulated neoblast proliferation and caused regeneration defects after amputation. In addition, Djyki RNAi caused edema during homeostasis. These seemingly distinct defects induced by Djyki RNAi were rescued by simultaneous RNAi of a planarian mats-related gene (termed Djmats), suggesting an important role of Djmats in the negative regulation of Djyki, in accordance with the conservation of the functional relationship of these two genes during the course of evolution. Interestingly, Djyki RNAi did not prevent normal protonephridial structure, suggesting that Djyki RNAi induced the edema phenotype without affecting the excretory system. Further analyses revealed that increased expression of the D. japonica gene DjaquaporinA (DjaqpA), which belongs to a large gene family that encodes a water channel protein for the regulation of transcellular water flow, promoted the induction of edema, but not defects in neoblast dynamics, in Djyki(RNAi) animals. Thus, we conclude that Djyki plays two distinct roles in the regulation of active proliferation of stem cells and in osmotic water transport across the body surface in D. japonica.

  15. Turning the tables of sex distinction in craniofacial identification: Why females possess thicker facial soft tissues than males, not vice versa.

    PubMed

    Stephan, Carl N; Preisler, Rory; Bulut, Ozgur; Bennett, Mike

    2016-10-01

    Males are universally reported to possess larger facial soft-tissue thickness (FSTT) than females, however, this observation oversimplifies the raw data yielding an underpowered assessment of FSTT sex-patterning where: differences are small (η(2)  < 5%) and inconsistent (females are routinely larger than males at the cheeks). Here we investigate body-size normalized data to assess whether more general and improved understanding of FSTT sex-variation in humans is possible. FSTTs were measured in 52 healthy living Australians aged 18 to 30 years using B-mode ultrasound. Participants' stature and body mass were also measured. Sex differences were calculated before and after normalization by the aforementioned body-composition variables. Methods were repeated in three other independent samples to evaluate reproducibility: 100 American Whites and 60 American Blacks measured by B-mode ultrasound; and 50 Turkish residents measured by regular supine CT. Compared to raw mean differences (F < M, by -6%), females displayed much thicker FSTTs than males when normalized for body mass (F > M, by +16%). Consequently, while the sexes share similar raw values, females possess much larger FSTTs for their relatively lighter bodies. The relative FSTT difference was 2.7× larger than the raw mean difference. Sex differences in FSTT are of larger magnitude and reversed direction in mass normalized data. Contrary to popular thought, females possess much larger FSTTs than males owing to their generically lighter bodies (-18 kg). These data patterns help explain why the pooling of sex-categorized FSTT does not jeopardize the sex-difference-it is encoded more strongly in terms relative to body mass. PMID:27324815

  16. 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

  17. Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function.

    PubMed

    Houston, B; Curry, B; Aitken, R J

    2015-06-01

    Reactive oxygen species (ROS) are known to play an important role in the regulation of human sperm function. In this study, we demonstrate for the first time that human spermatozoa possess interleukin-induced gene 1 (IL4I1), an l-amino acid oxidase (LAAO) which is capable of generating ROS on exposure to aromatic amino acids in the presence of oxygen. The preferred substrates were found to be phenylalanine and tryptophan while the enzyme was located in the acrosomal region and midpiece of these cells. In contrast to equine and bovine spermatozoa, enzyme activity was lost as soon as the spermatozoa became non-viable. On a cell-to-cell basis human spermatozoa were also shown to generate lower levels of hydrogen peroxide than their equine counterparts on exposure to phenylalanine. Stimulation of LAAO activity resulted in the induction of several hallmarks of capacitation including tyrosine phosphorylation of the sperm flagellum and concomitant activation of phospho-SRC expression. In addition, stimulation of LAAO resulted in an increase in the levels of acrosomal exocytosis in both the presence and absence of progesterone stimulation, via mechanisms that could be significantly reversed by the presence of catalase. As is often the case with free radical-mediated phenomena, prolonged exposure of human spermatozoa to phenylalanine resulted in the stimulation of apoptosis as indicated by significant increases in mitochondrial superoxide generation and the activation of intracellular caspases. These results confirm the existence of an LAAO in human spermatozoa with a potential role in driving the redox regulation of sperm capacitation and acrosomal exocytosis.

  18. 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.

  19. Distinct roles of PTCH2 splice variants in Hedgehog signalling.

    PubMed Central

    Rahnama, Fahimeh; Toftgård, Rune; Zaphiropoulos, Peter G

    2004-01-01

    The human PTCH2 gene is highly similar to PTCH1, a tumour suppressor gene frequently mutated in basal cell carcinoma and several other tumour types. PTCH1 is a transmembrane protein believed to inhibit another transmembrane protein SMO (Smoothened), which mediates HH (Hedgehog) signalling. In this study, we analysed the biological properties of several PTCH2 splice variants. An mRNA form that lacked the last exon was abundantly expressed in all tissues examined, in contrast with the one that included it. Moreover, a transcript lacking exon 9, which is a part of a conserved sterol-sensing domain, was identified in intestine, prostate and cerebellum. In ovary, spleen, testis, cerebellum and skin, an mRNA lacking both exons 9 and 10 could also be observed. The different PTCH2 isoforms localized in the cytoplasm were capable of internalizing the N-terminal fragment of Sonic HH (Shh-N). Additionally, the PTCH2 gene was found to be a target of HH signalling. PTCH2 promoter regulation assays demonstrated that only one of the PTCH2 variants could inhibit the activity of SHH-N, whereas none was capable of inhibiting the activated form of SMO (SMO-M2) and this contrasts with PTCH1. Despite the fact that the PTCH2 isoforms lacked the ability to inhibit SMO-M2 activity, all PTCH2 variants as well as PTCH1, on co-transfection with Smo, were able to change Smo localization from being largely dispersed in the cytoplasm to the juxtanuclear region. Furthermore, the PTCH2 isoforms and PTCH1 co-localized in doubly transfected cells and an interaction between them was confirmed using immunoprecipitation assays. Using Ptch1-/- mouse cells, it was shown that the PTCH2 variants and PTCH1 differentially act to reconstitute not only the SHH but also the Desert HH-dependent transcriptional response. We conclude that in spite of their structural similarities, the PTCH2 isoforms have distinct functional properties when compared with PTCH1. PMID:14613484

  20. Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins.

    PubMed

    Dixon, Shandee D; Huynh, Melanie M; Tamilselvam, Batcha; Spiegelman, Lindsey M; Son, Sophia B; Eshraghi, Aria; Blanke, Steven R; Bradley, Kenneth A

    2015-01-01

    Cytolethal distending toxins (CDTs) are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus. However, the molecular details and mechanism by which CDTs bind to host cells and exploit existing uptake and transport pathways to gain access to the nucleus are poorly understood. Here, we report that CdtA and CdtC subunits of CDTs derived from Haemophilus ducreyi (Hd-CDT) and enteropathogenic E. coli (Ec-CDT) are independently sufficient to support intoxication by their respective CdtB subunits. CdtA supported CdtB-mediated killing of T-cells and epithelial cells that was nearly as efficient as that observed with holotoxin. In contrast, the efficiency by which CdtC supported intoxication was dependent on the source of the toxin as well as the target cell type. Further, CdtC was found to alter the subcellular trafficking of Ec-CDT as determined by sensitivity to EGA, an inhibitor of endosomal trafficking, colocalization with markers of early and late endosomes, and the kinetics of DNA damage response. Finally, host cellular cholesterol was found to influence sensitivity to intoxication mediated by Ec-CdtA, revealing a role for cholesterol or cholesterol-rich membrane domains in intoxication mediated by this subunit. In summary, data presented here support a model in which CdtA and CdtC each bind distinct receptors on host cell surfaces that direct alternate intracellular uptake and/or trafficking pathways. PMID:26618479

  1. Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins

    PubMed Central

    Tamilselvam, Batcha; Spiegelman, Lindsey M.; Son, Sophia B.; Eshraghi, Aria; Blanke, Steven R.; Bradley, Kenneth A.

    2015-01-01

    Cytolethal distending toxins (CDTs) are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus. However, the molecular details and mechanism by which CDTs bind to host cells and exploit existing uptake and transport pathways to gain access to the nucleus are poorly understood. Here, we report that CdtA and CdtC subunits of CDTs derived from Haemophilus ducreyi (Hd-CDT) and enteropathogenic E. coli (Ec-CDT) are independently sufficient to support intoxication by their respective CdtB subunits. CdtA supported CdtB-mediated killing of T-cells and epithelial cells that was nearly as efficient as that observed with holotoxin. In contrast, the efficiency by which CdtC supported intoxication was dependent on the source of the toxin as well as the target cell type. Further, CdtC was found to alter the subcellular trafficking of Ec-CDT as determined by sensitivity to EGA, an inhibitor of endosomal trafficking, colocalization with markers of early and late endosomes, and the kinetics of DNA damage response. Finally, host cellular cholesterol was found to influence sensitivity to intoxication mediated by Ec-CdtA, revealing a role for cholesterol or cholesterol-rich membrane domains in intoxication mediated by this subunit. In summary, data presented here support a model in which CdtA and CdtC each bind distinct receptors on host cell surfaces that direct alternate intracellular uptake and/or trafficking pathways. PMID:26618479

  2. Distinct functional roles of amphibian (Xenopus laevis) colony-stimulating factor-1- and interleukin-34-derived macrophages

    PubMed Central

    Grayfer, Leon; Robert, Jacques

    2015-01-01

    Although Mϕ represent the most primordial immune cell subsets, the mechanisms governing their functional heterogeneity remain poorly defined. However, it is well established that the CSF-1 cytokine contributes to monopoiesis and to this heterogeneity, whereas the unrelated IL-34 also binds the CSF-1R toward poorly understood immunologic roles. To delineate the molecular and evolutionary basis behind vertebrate Mϕ functional heterogeneity, we performed comprehensive transcriptional and functional studies of amphibian (Xenopus laevis) BM (in vitro) and PER (in vivo) Mϕ derived by rXlCSF-1 and rXlIL-34. Our findings indicate that these amphibian cytokines promote morphologically and functionally distinct Mϕ populations. Mϕ induced by rXlCSF-1 possess more robust iNOS gene expression, are substantially more phagocytic, display greater NO responses, and exhibit enhanced bactericidal capacities. By contrast, rXlIL-34-derived Mϕ express greater levels of Arg-1 and NADPH oxidase components and possess greater respiratory burst responses. Most notably, whereas CSF-1 Mϕ are highly susceptible to the emerging FV3 ranavirus, rXlIL-34 Mϕ exhibit potent antiviral activity against this pathogen, which is dependent on reactive oxygen production. This work marks an advance in our understanding of the possible mechanisms governing vertebrate Mϕ functional heterogeneity. PMID:26136505

  3. Late Adolescent Girls' Relationships with Parents and Romantic Partner: The Distinct Role of Mothers and Fathers

    ERIC Educational Resources Information Center

    Scharf, Miri; Mayseless, Ofra

    2008-01-01

    The distinct role of mothers and fathers in shaping the quality of relationships with romantic partner was explored. One hundred and twenty 17-year old girls were observed during their senior year in high school with each of their parents during a Revealed differences task [Allen, J. P., Hauser, S. T., Bell, K. L., Boykin, K. A., & Tate, D. C.…

  4. Oxylipin Signaling: A Distinct Role for the Jasmonic Acid Precursor cis-(+)-12-Oxo-Phytodienoic Acid (cis-OPDA)

    PubMed Central

    Dave, Anuja; Graham, Ian A.

    2012-01-01

    Oxylipins are lipid-derived compounds, many of which act as signals in the plant response to biotic and abiotic stress. They include the phytohormone jasmonic acid (JA) and related jasmonate metabolites cis-(+)-12-oxo-phytodienoic acid (cis-OPDA), methyl jasmonate, and jasmonoyl-L-isoleucine (JA-Ile). Besides the defense response, jasmonates are involved in plant growth and development and regulate a range of processes including glandular trichome development, reproduction, root growth, and senescence. cis-OPDA is known to possess a signaling role distinct from JA-Ile. The non-enzymatically derived phytoprostanes are structurally similar to cis-OPDA and induce a common set of genes that are not responsive to JA in Arabidopsis thaliana. A novel role for cis-OPDA in seed germination regulation has recently been uncovered based on evidence from double mutants and feeding experiments showing that cis-OPDA interacts with abscisic acid (ABA), inhibits seed germination, and increases ABA INSENSITIVE5 (ABI5) protein abundance. Large amounts of cis-OPDA are esterified to galactolipids in A. thaliana and the resulting compounds, known as Arabidopsides, are thought to act as a rapidly available source of cis-OPDA. PMID:22645585

  5. Early- and late-born parvalbumin basket cell subpopulations exhibiting distinct regulation and roles in learning.

    PubMed

    Donato, Flavio; Chowdhury, Ananya; Lahr, Maria; Caroni, Pico

    2015-02-18

    Brain networks can support learning by promoting acquisition of task-relevant information or by adhering to validated rules, but the mechanisms involved are poorly understood. Upon learning, local inhibitory parvalbumin (PV)-expressing Basket cell networks can switch to opposite configurations that either favor or interfere with further learning, but how this opposite plasticity is induced and relates to distinct learning requirements has remained unclear. Here, we show that PV Basket cells consist of hitherto unrecognized subpopulations, with distinct schedules of neurogenesis, input connectivities, output target neurons, and roles in learning. Plasticity of hippocampal early-born PV neurons was recruited in rule consolidation, whereas plasticity of late-born PV neurons was recruited in new information acquisition. This involved regulation of early-born neuron plasticity specifically through excitation, and of late-born neuron plasticity specifically through inhibition. Therefore, opposite learning requirements are implemented by distinct local networks involving PV Basket cell subpopulations specifically regulated through inhibition or excitation.

  6. Phytochrome-Interacting Factors Have Both Shared and Distinct Biological Roles

    PubMed Central

    Jeong, Jinkil; Choi, Giltsu

    2013-01-01

    Phytochromes are plant photoreceptors that perceive red and far-red light. Upon the perception of light in Arabidopsis, light-activated phytochromes enter the nucleus and act on a set of interacting proteins, modulating their activities and thereby altering the expression levels of ∼10% of the organism’s entire gene complement. Phytochrome-interacting factors (PIFs) belonging to Arabidopsis basic helix-loop-helix (bHLH) subgroup 15 are key interacting proteins that play negative roles in light responses. Their activities are post-translationally countered by light-activated phytochromes, which promote the degradation of PIFs and directly or indirectly inhibit their binding to DNA. The PIFs share a high degree of similarity, but examinations of pif single and multiple mutants have indicated that they have shared and distinct functions in various developmental and physiological processes. These are believed to stem from differences in both intrinsic protein properties and their gene expression patterns. In an effort to clarify the basis of these shared and distinct functions, we compared recently published genome-wide ChIP data, developmental gene expression maps, and responses to various stimuli for the various PIFs. Based on our observations, we propose that the biological roles of PIFs stem from their shared and distinct DNA binding targets and specific gene expression patterns. PMID:23708772

  7. Distinct Roles of Central and Peripheral Prostaglandin E2 and EP Subtypes in Blood Pressure Regulation

    PubMed Central

    Yang, Tianxin; Du, Yaomin

    2012-01-01

    Prostaglandin E2 (PGE2) is a major prostanoid with a wide variety of biological activities. PGE2 can influence blood pressure (BP) both positively and negatively. In particular, centrally administered PGE2 induces hypertension whereas systemic administration of PGE2 produces a hypotensive effect. These physiologically opposing effects are generated by the existence of multiple EP receptors, namely EP1–4, which are G protein-coupled receptors with distinct signaling properties. This review highlights the distinct roles of PGE2 in BP regulation and the involvement of specific EP receptor subtypes. American Journal of Hypertension, advance online publication 14 June 2012; doi:10.1038/ajh.2012.67 PMID:22695507

  8. Role of codeposited impurities during growth. I. Explaining distinctive experimental morphology on Cu(0 0 1)

    NASA Astrophysics Data System (ADS)

    Hamouda, Ajmi Bh.; Sathiyanarayanan, Rajesh; Pimpinelli, Alberto; Einstein, T. L.

    2011-01-01

    A unified explanation of the physics underlying all the distinctive features of the growth instabilities observed on Cu vicinals has long eluded theorists. Recently, kinetic Monte Carlo studies showed that codeposition of impurities during growth could account for the key distinctive experimental observations [Hamouda , Phys. Rev. BPLRBAQ0556-280510.1103/PhysRevB.77.245430 77, 245430 (2008)]. To identify the responsible impurity atom, we compute the nearest-neighbor binding energies (ENN) and terrace diffusion barriers (Ed) for several candidate impurity atoms on Cu(0 0 1) using DFT-based VASP. Our calculations show that codeposition (with Cu) of midtransition elements, such as Fe, Mn, and W, could—in conjunction with substantial Ehrlich-Schwoebel barriers—cause the observed instabilities; when the experimental setup is considered, W emerges to be the most likely candidate. We discuss the role of impurities in nanostructuring of surfaces.

  9. Distinct physiological roles for the two L-asparaginase isozymes of Escherichia coli

    SciTech Connect

    Srikhanta, Yogitha N.; Atack, John M.; Beacham, Ifor R.; Jennings, Michael P.

    2013-07-05

    Highlights: •Escherichia coli contains two L-asparaginase isozymes with distinct localization, kinetics and regulation. •Mutant strains were used to examine the roles of these enzymes in L-asparagine utilization. •We report that L-asparaginase II permits growth on asparagine and glycerol under anaerobic conditions. •We propose that this enzyme is the first step in a co-regulated pathway leading to fumarate. •The pathway is regulated by anaerobiosis and cAMP and provides a terminal elector acceptor. -- Abstract: Escherichia coli expresses two L-asparaginase (EC 3.5.1.1) isozymes: L-asparaginse I, which is a low affinity, cytoplasmic enzyme that is expressed constitutively, and L-asparaginase II, a high affinity periplasmic enzyme that is under complex co-transcriptional regulation by both Fnr and Crp. The distinct localisation and regulation of these enzymes suggest different roles. To define these roles, a set of isogenic mutants was constructed that lacked either or both enzymes. Evidence is provided that L-asparaginase II, in contrast to L-asparaginase I, can be used in the provision of an anaerobic electron acceptor when using a non-fermentable carbon source in the presence of excess nitrogen.

  10. Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system.

    PubMed

    Nguyen, L K; Kulasiri, D

    2011-03-01

    Molecular fluctuations are known to affect dynamics of cellular systems in important ways. Studies aimed at understanding how molecular systems of certain regulatory architectures control noise therefore become essential. The interplay between feedback regulation and noise has been previously explored for cellular networks governed by a single negative feedback loop. However, similar issues within networks consisting of more complex regulatory structures remain elusive. The authors investigate how negative feedback loops manage noise within a biochemical cascade concurrently governed by multiple negative feedback loops, using the prokaryotic tryptophan (trp) operon system in Escherechia coli as the model system. To the authors knowledge, this is the first study of noise in the trp operon system. They show that the loops in the trp operon system possess distinct, even opposing, noise-controlling effects despite their seemingly analogous feedback structures. The enzyme inhibition loop, although controlling the last reaction of the cascade, was found to suppress noise not only for the tryptophan output but also for other upstream components. In contrast, the Repression (Rep) loop enhances noise for all systems components. Attenuation (Att) poses intermediate effects by attenuating noise for the upstream components but promoting noise for components downstream of its target. Regarding noise at the output tryptophan, Rep and Att can be categorised as noise-enhancing loops whereas Enzyme Inhibition as a noise-reducing loop. These findings suggest novel implications in how cellular systems with multiple feedback mechanisms control noise. [Includes supplementary material]. PMID:21405203

  11. Posterior Wnts Have Distinct Roles in Specification and Patterning of the Planarian Posterior Region.

    PubMed

    Sureda-Gómez, Miquel; Pascual-Carreras, Eudald; Adell, Teresa

    2015-11-05

    The wnt signaling pathway is an intercellular communication mechanism essential in cell-fate specification, tissue patterning and regional-identity specification. A βcatenin-dependent signal specifies the AP (Anteroposterior) axis of planarians, both during regeneration of new tissues and during normal homeostasis. Accordingly, four wnts (posterior wnts) are expressed in a nested manner in central and posterior regions of planarians. We have analyzed the specific role of each posterior wnt and the possible cooperation between them in specifying and patterning planarian central and posterior regions. We show that each posterior wnt exerts a distinct role during re-specification and maintenance of the central and posterior planarian regions, and that the integration of the different wnt signals (βcatenin dependent and independent) underlies the patterning of the AP axis from the central region to the tip of the tail. Based on these findings and data from the literature, we propose a model for patterning the planarian AP axis.

  12. Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

    PubMed

    Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

    2016-07-01

    Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. PMID:26693958

  13. Purified TPC Isoforms Form NAADP Receptors with Distinct Roles for Ca2+ Signaling and Endolysosomal Trafficking

    PubMed Central

    Ruas, Margarida; Rietdorf, Katja; Arredouani, Abdelilah; Davis, Lianne C.; Lloyd-Evans, Emyr; Koegel, Heidi; Funnell, Timothy M.; Morgan, Anthony J.; Ward, John A.; Watanabe, Keiko; Cheng, Xiaotong; Churchill, Grant C.; Zhu, Michael X.; Platt, Frances M.; Wessel, Gary M.; Parrington, John; Galione, Antony

    2010-01-01

    Summary Intracellular Ca2+ signals constitute key elements in signal transduction. Of the three major Ca2+ mobilizing messengers described, the most potent, nicotinic acid adenine dinucleotide phosphate (NAADP) is the least well understood in terms of its molecular targets [1]. Recently, we showed that heterologous expression of two-pore channel (TPC) proteins enhances NAADP-induced Ca2+ release, whereas the NAADP response was abolished in pancreatic beta cells from Tpcn2 gene knockout mice [2]. However, whether TPCs constitute native NAADP receptors is unclear. Here we show that immunopurified endogenous TPC complexes possess the hallmark properties ascribed to NAADP receptors, including nanomolar ligand affinity [3–5]. Our study also reveals important functional differences between the three TPC isoforms. Thus, TPC1 and TPC2 both mediate NAADP-induced Ca2+ release, but the subsequent amplification of this trigger Ca2+ by IP3Rs is more tightly coupled for TPC2. In contrast, TPC3 expression suppressed NAADP-induced Ca2+ release. Finally, increased TPC expression has dramatic and contrasting effects on endolysosomal structures and dynamics, implicating a role for NAADP in the regulation of vesicular trafficking. We propose that NAADP regulates endolysosomal Ca2+ storage and release via TPCs and coordinates endoplasmic reticulum Ca2+ release in a role that impacts on Ca2+ signaling in health and disease [6]. PMID:20346675

  14. 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

    1996-04-01

    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.

  15. Distinct Roles of Jasmonates and Aldehydes in Plant-Defense Responses

    PubMed Central

    Chehab, E. Wassim; Kaspi, Roy; Savchenko, Tatyana; Rowe, Heather; Negre-Zakharov, Florence; Kliebenstein, Dan; Dehesh, Katayoon

    2008-01-01

    Background Many inducible plant-defense responses are activated by jasmonates (JAs), C6-aldehydes, and their corresponding derivatives, produced by the two main competing branches of the oxylipin pathway, the allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches, respectively. In addition to competition for substrates, these branch-pathway-derived metabolites have substantial overlap in regulation of gene expression. Past experiments to define the role of C6-aldehydes in plant defense responses were biased towards the exogenous application of the synthetic metabolites or the use of genetic manipulation of HPL expression levels in plant genotypes with intact ability to produce the competing AOS-derived metabolites. To uncouple the roles of the C6-aldehydes and jasmonates in mediating direct and indirect plant-defense responses, we generated Arabidopsis genotypes lacking either one or both of these metabolites. These genotypes were subsequently challenged with a phloem-feeding insect (aphids: Myzus persicae), an insect herbivore (leafminers: Liriomyza trifolii), and two different necrotrophic fungal pathogens (Botrytis cinerea and Alternaria brassicicola). We also characterized the volatiles emitted by these plants upon aphid infestation or mechanical wounding and identified hexenyl acetate as the predominant compound in these volatile blends. Subsequently, we examined the signaling role of this compound in attracting the parasitoid wasp (Aphidius colemani), a natural enemy of aphids. Principal Findings This study conclusively establishes that jasmonates and C6-aldehydes play distinct roles in plant defense responses. The jasmonates are indispensable metabolites in mediating the activation of direct plant-defense responses, whereas the C6-aldehyes are not. On the other hand, hexenyl acetate, an acetylated C6-aldehyde, is the predominant wound-inducible volatile signal that mediates indirect defense responses by directing tritrophic (plant

  16. 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…

  17. Distinct spatiotemporal roles of hedgehog signalling during chick and mouse cranial base and axial skeleton development

    PubMed Central

    Balczerski, B.; Zakaria, S.; Tucker, A. S.; Borycki, A.G.; Koyama, E.; Pacifici, M.; Francis-West, P.

    2012-01-01

    The cranial base exerts a supportive role for the brain and includes the occipital, sphenoid and ethmoid bones that arise from cartilaginous precursors in the early embryo. As the occipital bone and the posterior part of the sphenoid are mesoderm derivatives that arise in close proximity to the notochord and floor plate, it has been assumed that their development, like the axial skeleton, is dependent on Sonic hedgehog (Shh) and modulation of bone morphogenetic protein (Bmp) signalling. Here we examined the development of the cranial base in chick and mouse embryos to compare the molecular signals that are required for chondrogenic induction in the trunk and head. We found that Shh signalling is required but the molecular network controlling cranial base development is distinct from that in the trunk. In the absence of Shh, the presumptive cranial base did not undergo chondrogenic commitment as determined by the loss of Sox9 expression and there was a decrease in cell survival. In contrast, induction of the otic capsule occurred normally demonstrating that induction of the cranial base is uncoupled from formation of the sensory capsules. Lastly, we found that the early cranial mesoderm is refractory to Shh signalling, likely accounting for why development of the cranial base occurs after the axial skeleton. Our data reveal that cranial and axial skeletal induction is controlled by conserved, yet spatiotemporally distinct mechanisms that co-ordinate development of the cranial base with that of the cranial musculature and the pharyngeal arches. PMID:23009899

  18. Compound-gene interaction mapping reveals distinct roles for Staphylococcus aureus teichoic acids

    PubMed Central

    Santa Maria, John P.; Sadaka, Ama; Moussa, Samir H.; Brown, Stephanie; Zhang, Yanjia J.; Rubin, Eric J.; Gilmore, Michael S.; Walker, Suzanne

    2014-01-01

    Staphylococcus aureus contains two distinct teichoic acid (TA) polymers, lipoteichoic acid (LTA) and wall teichoic acid (WTA), which are proposed to play redundant roles in regulating cell division. To gain insight into the underlying biology of S. aureus TAs, we used a small molecule inhibitor to screen a highly saturated transposon library for cellular factors that become essential when WTA is depleted. We constructed an interaction network connecting WTAs with genes involved in LTA synthesis, peptidoglycan synthesis, surface protein display, and D-alanine cell envelope modifications. Although LTAs and WTAs are synthetically lethal, we report that they do not have the same synthetic interactions with other cell envelope genes. For example, D-alanylation, a tailoring modification of both WTAs and LTAs, becomes essential when the former, but not the latter, are removed. Therefore, D-alanine–tailored LTAs are required for survival when WTAs are absent. Examination of terminal phenotoypes led to the unexpected discovery that cells lacking both LTAs and WTAs lose their ability to form Z rings and can no longer divide. We have concluded that the presence of either LTAs or WTAs on the cell surface is required for initiation of S. aureus cell division, but these polymers act as part of distinct cellular networks. PMID:25104751

  19. The condensin complexes play distinct roles to ensure normal chromosome morphogenesis during meiotic division in Arabidopsis.

    PubMed

    Smith, Sarah J; Osman, Kim; Franklin, F Christopher H

    2014-10-01

    Meiosis is a specialized cell division essential for sexual reproduction. During meiosis the chromosomes are highly organized, and correct chromosome architecture is required for faithful segregation of chromosomes at anaphase I and II. Condensin is involved in chromosome organization during meiotic and mitotic cell divisions. Three condensin subunits, AtSMC4 and the condensin I and II specific subunits AtCAP-D2 and AtCAP-D3, respectively, have been studied for their role in meiosis. This has revealed that both the condensin I and condensin II complexes are required to maintain normal structural integrity of the meiotic chromosomes during the two nuclear divisions. Their roles appear functionally distinct in that condensin I is required to maintain normal compaction of the centromeric repeats and 45S rDNA, whereas loss of condensin II was associated with extensive interchromosome connections at metaphase I. Depletion of condensin is also associated with a slight reduction in crossover formation, suggesting a role during meiotic prophase I. PMID:25065716

  20. Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization.

    PubMed

    Suzuki, Shigeki; Sreenath, Taduru; Haruyama, Naoto; Honeycutt, Cherlita; Terse, Anita; Cho, Andrew; Kohler, Thomas; Müller, Ralph; Goldberg, Michel; Kulkarni, Ashok B

    2009-05-01

    Dentin sialophosphoprotein (DSPP), a major non-collagenous matrix protein of odontoblasts, is proteolytically cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Our previous studies revealed that DSPP null mice display a phenotype similar to human autosomal dominant dentinogenesis imperfecta, in which teeth have widened predentin and irregular dentin mineralization resulting in sporadic unmineralized areas in dentin and frequent pulp exposure. Earlier in vitro studies suggested that DPP, but not DSP, plays a significant role in initiation and maturation of dentin mineralization. However, the precise in vivo roles of DSP and DPP are far from clear. Here we report the generation of DPPcKO mice, in which only DSP is expressed in a DSPP null background, resulting in a conditional DPP knockout. DPPcKO teeth show a partial rescue of the DSPP null phenotype with the restored predentin width, an absence of irregular unmineralized areas in dentin, and less frequent pulp exposure. Micro-computed tomography (micro-CT) analysis of DPPcKO molars further confirmed this partial rescue with a significant recovery in the dentin volume, but not in the dentin mineral density. These results indicate distinct roles of DSP and DPP in dentin mineralization, with DSP regulating initiation of dentin mineralization, and DPP being involved in the maturation of mineralized dentin.

  1. Distinct roles for Ste20-like kinase SLK in muscle function and regeneration

    PubMed Central

    2013-01-01

    Background Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood. Methods To gain further insights into the role of SLK in differentiated muscles, we expressed a kinase-inactive SLK from the human skeletal muscle actin promoter. Transgenic muscles were surveyed for potential defects. Standard histological procedures and cardiotoxin-induced regeneration assays we used to investigate the role of SLK in myogenesis and muscle repair. Results High levels of kinase-inactive SLK in muscle tissue produced an overall decrease in SLK activity in muscle tissue, resulting in altered muscle organization, reduced litter sizes, and reduced breeding capacity. The transgenic mice did not show any differences in fiber-type distribution but displayed enhanced regeneration capacity in vivo and more robust differentiation in vitro. Conclusions Our results show that SLK activity is required for optimal muscle development in the embryo and muscle physiology in the adult. However, reduced kinase activity during muscle repair enhances regeneration and differentiation. Together, these results suggest complex and distinct roles for SLK in muscle development and function. PMID:23815977

  2. The Inositol-3-Phosphate Synthase Biosynthetic Enzyme Has Distinct Catalytic and Metabolic Roles

    PubMed Central

    Frej, Anna D.; Clark, Jonathan; Le Roy, Caroline I.; Lilla, Sergio; Thomason, Peter A.; Otto, Grant P.; Churchill, Grant; Insall, Robert H.; Claus, Sandrine P.; Hawkins, Phillip; Stephens, Len

    2016-01-01

    Inositol levels, maintained by the biosynthetic enzyme inositol-3-phosphate synthase (Ino1), are altered in a range of disorders, including bipolar disorder and Alzheimer's disease. To date, most inositol studies have focused on the molecular and cellular effects of inositol depletion without considering Ino1 levels. Here we employ a simple eukaryote, Dictyostelium discoideum, to demonstrate distinct effects of loss of Ino1 and inositol depletion. We show that loss of Ino1 results in an inositol auxotrophy that can be rescued only partially by exogenous inositol. Removal of inositol supplementation from the ino1− mutant resulted in a rapid 56% reduction in inositol levels, triggering the induction of autophagy, reduced cytokinesis, and substrate adhesion. Inositol depletion also caused a dramatic generalized decrease in phosphoinositide levels that was rescued by inositol supplementation. However, loss of Ino1 triggered broad metabolic changes consistent with the induction of a catabolic state that was not rescued by inositol supplementation. These data suggest a metabolic role for Ino1 that is independent of inositol biosynthesis. To characterize this role, an Ino1 binding partner containing SEL1L1 domains (Q54IX5) and having homology to mammalian macromolecular complex adaptor proteins was identified. Our findings therefore identify a new role for Ino1, independent of inositol biosynthesis, with broad effects on cell metabolism. PMID:26951199

  3. Distinct roles of neuropilin 1 signaling for radial and tangential extension of callosal axons.

    PubMed

    Hatanaka, Yumiko; Matsumoto, Tomoko; Yanagawa, Yuchio; Fujisawa, Hajime; Murakami, Fujio; Masu, Masayuki

    2009-05-20

    Cortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate-shaped cells were located. DiI labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter. PMID:19296474

  4. Crystal Structures of the Viral Protease Npro Imply Distinct Roles for the Catalytic Water in Catalysis

    PubMed Central

    Zögg, Thomas; Sponring, Michael; Schindler, Sabrina; Koll, Maria; Schneider, Rainer; Brandstetter, Hans; Auer, Bernhard

    2013-01-01

    Summary Npro is a key effector protein of pestiviruses such as bovine viral diarrhea virus and abolishes host cell antiviral defense mechanisms. Synthesized as the N-terminal part of the viral polyprotein, Npro releases itself via an autoproteolytic cleavage, triggering its immunological functions. However, the mechanisms of its proteolytic action and its immune escape were unclear. Here, we present the crystal structures of Npro to 1.25 Å resolution. Structures of pre- and postcleavage intermediates identify three catalytically relevant elements. The trapping of the putative catalytic water reveals its distinct roles as a base, acid, and nucleophile. The presentation of the substrate further explains the enigmatic latency of the protease, ensuring a single in cis cleavage. Additionally, we identified a zinc-free, disulfide-linked conformation of the TRASH motif, an interaction hub of immune factors. The structure opens additional opportunities in utilizing Npro as an autocleaving fusion protein and as a pharmaceutical target. PMID:23643950

  5. Two Distinct Roles of Atlantic SSTs in ENSO Variability: North Tropical Atlantic SST and Atlantic Nino

    NASA Technical Reports Server (NTRS)

    Ham, Yoo-Geun; Kug, Jong-Seong; Park, Jong-Yeon

    2013-01-01

    Two distinct roles of the Atlantic sea surface temperatures (SSTs), namely, the North Tropical Atlantic (NTA) SST and the Atlantic Nino, on the El Nino-Southern Oscillation (ENSO) variability are investigated using the observational data from 1980 to 2010 and coupled model experiments. It appears that the NTA SST and the Atlantic Nino can be used as two independent predictors for predicting the development of ENSO events in the following season. Furthermore, they are likely to be linked to different types of El Nino events. Specifically, the NTA SST cooling during February, March, and April contributes to the central Pacific warming at the subsequent winter season, while the negative Atlantic Nino event during June, July, and August contributes to enhancing the eastern Pacific warming. The coupled model experiments support these results. With the aid of a lagged inverse relationship, the statistical forecast using two Atlantic indices can successfully predict various ENSO indices.

  6. Surface binding sites in amylase have distinct roles in recognition of starch structure motifs and degradation.

    PubMed

    Cockburn, Darrell; Nielsen, Morten M; Christiansen, Camilla; Andersen, Joakim M; Rannes, Julie B; Blennow, Andreas; Svensson, Birte

    2015-04-01

    Carbohydrate converting enzymes often possess extra substrate binding regions that enhance their activity. These can be found either on separate domains termed carbohydrate binding modules or as so-called surface binding sites (SBSs) situated on the catalytic domain. SBSs are common in starch degrading enzymes and critically important for their function. The affinity towards a variety of starch granules as well as soluble poly- and oligosaccharides of barley α-amylase 1 (AMY1) wild-type and mutants of two SBSs (SBS1 and SBS2) was investigated using Langmuir binding analysis, confocal laser scanning microscopy, affinity gel electrophoresis and surface plasmon resonance to unravel functional roles of the SBSs. SBS1 was critical for binding to different starch types as Kd increased by 7-62-fold or was not measurable upon mutation. By contrast SBS2 was particularly important for binding to soluble polysaccharides and oligosaccharides with α-1,6 linkages, suggesting that branch points are key structural elements in recognition by SBS2. Mutation at both SBS1 and SBS2 eliminated binding to all starch granule types tested. Taken together, the findings indicate that the two SBSs act in concert to localize AMY1 to the starch granule surface and that SBS2 works synergistically with the active site in the degradation of amylopectin.

  7. Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages.

    PubMed

    Papakonstanti, Evangelia A; Zwaenepoel, Olivier; Bilancio, Antonio; Burns, Emily; Nock, Gemma E; Houseman, Benjamin; Shokat, Kevan; Ridley, Anne J; Vanhaesebroeck, Bart

    2008-12-15

    The class IA isoforms of phosphoinositide 3-kinase (p110alpha, p110beta and p110delta) often have non-redundant functions in a given cell type. However, for reasons that are unclear, the role of a specific PI3K isoform can vary between cell types. Here, we compare the relative contributions of PI3K isoforms in primary and immortalised macrophages. In primary macrophages stimulated with the tyrosine kinase ligand colony-stimulating factor 1 (CSF1), all class IA PI3K isoforms participate in the regulation of Rac1, whereas p110delta selectively controls the activities of Akt, RhoA and PTEN, in addition to controlling proliferation and chemotaxis. The prominent role of p110delta in these cells correlates with it being the main PI3K isoform that is recruited to the activated CSF1 receptor (CSF1R). In immortalised BAC1.2F5 macrophages, however, the CSF1R also engages p110alpha, which takes up a more prominent role in CSF1R signalling, in processes including Akt phosphorylation and regulation of DNA synthesis. Cell migration, however, remains dependent mainly on p110delta. In other immortalised macrophage cell lines, such as IC-21 and J774.2, p110alpha also becomes more prominently involved in CSF1-induced Akt phosphorylation, at the expense of p110delta.These data show that PI3K isoforms can be differentially regulated in distinct cellular contexts, with the dominant role of the p110delta isoform in Akt phosphorylation and proliferation being lost upon cell immortalisation. These findings suggest that p110delta-selective PI3K inhibitors may be more effective in inflammation than in cancer. PMID:19033389

  8. Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis.

    PubMed

    Lai, Wen-Qi; Irwan, Anastasia Windy; Goh, Hong Heng; Melendez, Alirio J; McInnes, Iain B; Leung, Bernard P

    2009-08-01

    Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate (S1P). S1P plays a critical role in angiogenesis, inflammation, and various pathologic conditions. To date, two mammalian isoenzymes, SphK1 and SphK2, have been identified. Although both SphK1 and SphK2 share overall homology and produce the common product, S1P, it has been proposed they display different unique and separate functions. In this study, we examined the role of SphK1 and SphK2 in a murine collagen-induced arthritis model by down-regulating each isoenzyme via specific small interfering RNA (siRNA). Prophylactic i.p. administration of SphK1 siRNA significantly reduced the incidence, disease severity, and articular inflammation compared with control siRNA recipients. Treatment of SphK1 siRNA also down-regulated serum levels of S1P, IL-6, TNF-alpha, IFN-gamma, and IgG2a anti-collagen Ab. Ex vivo analysis demonstrated significant suppression of collagen-specific proinflammatory/Th1 cytokine (IL-6, TNF-alpha, IFN-gamma) release in SphK siRNA-treated mice. Interestingly, mice received with SphK2 siRNA develop more aggressive disease; higher serum levels of IL-6, TNF-alpha, and IFN-gamma; and proinflammatory cytokine production to collagen in vitro when compared with control siRNA recipients. Together, these results demonstrate the distinct immunomodulatory roles of SphK1 and SphK2 in the development of inflammatory arthritis by regulating the release of proinflammatory cytokines and T cell responses. These findings raise the possibility that drugs which specifically target SphK1 activity may play a beneficial role in the treatment of inflammatory arthritis.

  9. Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis

    PubMed Central

    Srinivasan, Prakash; Coppens, Isabelle; Jacobs-Lorena, Marcelo

    2009-01-01

    Invasion of host cells by the malaria parasite involves recognition and interaction with cell-surface receptors. A wide variety of parasite surface proteins participate in this process, most of which are specific to the parasite's particular invasive form. Upon entry, the parasite has to dissociate itself from the host-cell receptors. One mechanism by which it does so is by shedding its surface ligands using specific enzymes. Rhomboid belongs to a family of serine proteases that cleave cell-surface proteins within their transmembrane domains. Here we identify and partially characterize a Plasmodium berghei rhomboid protease (PbROM1) that plays distinct roles during parasite development. PbROM1 localizes to the surface of sporozoites after salivary gland invasion. In blood stage merozoites, PbROM1 localizes to the apical end where proteins involved in invasion are also present. Our genetic analysis suggests that PbROM1 functions in the invasive stages of parasite development. Whereas wild-type P. berghei is lethal to mice, animals infected with PbROM1 null mutants clear the parasites efficiently and develop long-lasting protective immunity. The results indicate that P. berghei Rhomboid 1 plays a nonessential but important role during parasite development and identify rhomboid proteases as potential targets for disease control. PMID:19148267

  10. Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis.

    PubMed

    van Dam, H; Castellazzi, M

    2001-04-30

    Jun : Fos and Jun : ATF complexes represent two classes of AP-1 dimers that (1) preferentially bind to either heptameric or octameric AP-1 binding sites, and (2) are differently regulated by cellular signaling pathways and oncogene products. To discriminate between the functions of Jun : Fos, Jun : ATF and Jun : Jun, mutants were developed that restrict the ability of Jun to dimerize either to itself, or to Fos(-like) or ATF(-like) partners. Introduction of these mutants in chicken embryo fibroblasts shows that Jun : Fra2 and Jun : ATF2 dimers play distinct, complementary roles in in vitro oncogenesis by inducing either anchorage independence or growth factor independence, respectively. v-Jun : ATF2 rather than v-Jun : Fra2 triggers the development of primary fibrosarcomas in the chicken wing. Genes encoding extracellular matrix components seem to constitute an important subset of v-Jun : ATF2-target genes. Repression of the matrix component SPARC by Jun is essential for the induction of fibrosarcomas. Avian primary cells transformed by either Jun : Fra2 or Jun : ATF2 thus provide powerful tools for the investigation of the downstream pathways involved in oncogenesis. Further genetic studies with Jun dimerization mutants will be required to be precise and extend the specific roles of the Jun : Fos and Jun : ATF dimers during cancer progression in avian and mammalian systems.

  11. Two distinct DNA binding modes guide dual roles Of a CRISPR-Cas protein complex

    PubMed Central

    Westra, Edze R.; Vlot, Marnix; Künne, Tim; Sobota, Małgorzata; Dekker, Cees; Brouns, Stan J.J.; Joo, Chirlmin

    2015-01-01

    SUMMARY Small RNA-guided protein complexes play an essential role in CRISPR-mediated immunity in prokaryotes. While these complexes initiate interference by flagging cognate invader DNA for destruction, recent evidence has implicated their involvement in new CRISPR memory formation, called priming, against mutated invader sequences. The mechanism by which the target recognition complex mediates these disparate responses—interference and priming—remains poorly understood. Using single-molecule FRET, we visualize how bona fide and mutated targets are differentially probed by E. coli Cascade. We observe that the recognition of bona fide targets is an ordered process that is tightly controlled for high fidelity. Mutated targets are recognized with low fidelity, which is featured by short-lived and PAM- and seed-independent binding by any segment of the crRNA. These dual roles of Cascade in immunity with distinct fidelities underpin CRISPR-Cas robustness, allowing for efficient degradation of bona fide targets and priming of mutated DNA targets. PMID:25752578

  12. Two distinct DNA binding modes guide dual roles of a CRISPR-Cas protein complex.

    PubMed

    Blosser, Timothy R; Loeff, Luuk; Westra, Edze R; Vlot, Marnix; Künne, Tim; Sobota, Małgorzata; Dekker, Cees; Brouns, Stan J J; Joo, Chirlmin

    2015-04-01

    Small RNA-guided protein complexes play an essential role in CRISPR-mediated immunity in prokaryotes. While these complexes initiate interference by flagging cognate invader DNA for destruction, recent evidence has implicated their involvement in new CRISPR memory formation, called priming, against mutated invader sequences. The mechanism by which the target recognition complex mediates these disparate responses-interference and priming-remains poorly understood. Using single-molecule FRET, we visualize how bona fide and mutated targets are differentially probed by E. coli Cascade. We observe that the recognition of bona fide targets is an ordered process that is tightly controlled for high fidelity. Mutated targets are recognized with low fidelity, which is featured by short-lived and PAM- and seed-independent binding by any segment of the crRNA. These dual roles of Cascade in immunity with distinct fidelities underpin CRISPR-Cas robustness, allowing for efficient degradation of bona fide targets and priming of mutated DNA targets.

  13. Distinct Roles for Intracellular and Extracellular Lipids in Hepatitis C Virus Infection

    PubMed Central

    Narayanan, Sowmya; Nieh, Albert H.; Kenwood, Brandon M.; Davis, Christine A.; Tosello-Trampont, Annie-Carole; Elich, Tedd D.; Breazeale, Steven D.; Ward, Eric; Anderson, Richard J.; Caldwell, Stephen H.; Hoehn, Kyle L.; Hahn, Young S.

    2016-01-01

    Hepatitis C is a chronic liver disease that contributes to progressive metabolic dysfunction. Infection of hepatocytes by hepatitis C virus (HCV) results in reprogramming of hepatic and serum lipids. However, the specific contribution of these distinct pools of lipids to HCV infection remains ill defined. In this study, we investigated the role of hepatic lipogenesis in HCV infection by targeting the rate-limiting step in this pathway, which is catalyzed by the acetyl-CoA carboxylase (ACC) enzymes. Using two structurally unrelated ACC inhibitors, we determined that blockade of lipogenesis resulted in reduced viral replication, assembly, and release. Supplementing exogenous lipids to cells treated with ACC inhibitors rescued HCV assembly with no effect on viral replication and release. Intriguingly, loss of viral RNA was not recapitulated at the protein level and addition of 2-bromopalmitate, a competitive inhibitor of protein palmitoylation, mirrored the effects of ACC inhibitors on reduced viral RNA without a concurrent loss in protein expression. These correlative results suggest that newly synthesized lipids may have a role in protein palmitoylation during HCV infection. PMID:27280294

  14. Distinct Roles of Muscle and Motoneuron LRP4 in Neuromuscular Junction Formation

    PubMed Central

    Wu, Haitao; Lu, Yisheng; Shen, Chengyong; Patel, Neil; Gan, Lin; Xiong, Wen C.; Mei, Lin

    2012-01-01

    SUMMARY Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act incis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of co-cultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin’s receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. PMID:22794264

  15. Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation.

    PubMed

    Wu, Haitao; Lu, Yisheng; Shen, Chengyong; Patel, Neil; Gan, Lin; Xiong, Wen C; Mei, Lin

    2012-07-12

    Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act in cis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of cocultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin's receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. PMID:22794264

  16. Separate and distinctive roles for Wnt5a in tongue, lingual tissue and taste papilla development.

    PubMed

    Liu, Hong-Xiang; Grosse, Ann S; Iwatsuki, Ken; Mishina, Yuji; Gumucio, Deborah L; Mistretta, Charlotte M

    2012-01-01

    Although canonical Wnt signaling is known to regulate taste papilla induction and numbers, roles for noncanonical Wnt pathways in tongue and taste papilla development have not been explored. With mutant mice and whole tongue organ cultures we demonstrate that Wnt5a protein and message are within anterior tongue mesenchyme across embryo stages from the initiation of tongue formation, through papilla placode appearance and taste papilla development. The Wnt5a mutant tongue is severely shortened, with an ankyloglossia, and lingual mesenchyme is disorganized. However, fungiform papilla morphology, number and innervation are preserved, as is expression of the papilla marker, Shh. These data demonstrate that the genetic regulation for tongue size and shape can be separated from that directing lingual papilla development. Preserved number of papillae in a shortened tongue results in an increased density of fungiform papillae in the mutant tongues. In tongue organ cultures, exogenous Wnt5a profoundly suppresses papilla formation and simultaneously decreases canonical Wnt signaling as measured by the TOPGAL reporter. These findings suggest that Wnt5a antagonizes canonical Wnt signaling to dictate papilla number and spacing. In all, distinctive roles for Wnt5a in tongue size, fungiform papilla patterning and development are shown and a necessary balance between non-canonical and canonical Wnt paths in regulating tongue growth and fungiform papillae is proposed in a model, through the Ror2 receptor. PMID:22024319

  17. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation

    PubMed Central

    Iwasaki, Hiromi; Somoza, Chamorro; Shigematsu, Hirokazu; Duprez, Estelle A.; Iwasaki-Arai, Junko; Mizuno, Shin-ichi; Arinobu, Yojiro; Geary, Kristin; Zhang, Pu; Dayaram, Tajhal; Fenyus, Maris L.; Elf, Shannon; Chan, Susan; Kastner, Philippe; Huettner, Claudia S.; Murray, Richard; Tenen, Daniel G.; Akashi, Koichi

    2005-01-01

    The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent “priming” of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages. PMID:15914556

  18. Picking sides: Distinct roles for CYP76M6 and -8 in rice oryzalexin biosynthesis

    PubMed Central

    Wu, Yisheng; Wang, Qiang; Hillwig, Matthew L.; Peters, Reuben J.

    2013-01-01

    Natural products biosynthesis often requires the action of multiple cytochromes P450 (CYPs), whose ability to introduce oxygen, increasing solubility, is critical for imparting biological activity. In previous investigations of rice diterpenoid biosynthesis, we have characterized CYPs that catalyze alternative hydroxylation of ent-sandaracopimaradiene, the precursor to the rice oryzalexin antibiotic phytoalexins. In particular, CYP76M5, -6 and -8 were all shown to carry out C7β-hydroxylation, while CYP701A8 catalyzes C3α-hydroxylation, with oxy groups found at both positions in oryzalexins A–D, suggesting that these may act consecutively in oryzalexin biosynthesis. Here we report that, although CYP701A8 only poorly reacts with 7β-hydroxy-ent-sandaracopimaradiene, CYP76M6 and -8 readily react with 3α-hydroxy-ent-sandaracopimaradiene. Notably, their activity yields distinct products, resulting from hydroxylation at C9β by CYP76M6 or C7β by CYP76M8, on different sides of the core tricyclic ring structure. Thus, CYP76M6 and -8 have distinct, non-redundant roles in orzyalexin biosynthesis. Moreover, the resulting 3α,7β- and 3α,9β- diols correspond to oryzalexins D and E, respectively. Accordingly, our results complete the functional identification of the biosynthetic pathway underlying the production of these bioactive phytoalexins. In addition, the altered regiochemistry catalyzed by CYP76M6 following C3α-hydroxylation has some implications for its active site configuration, offering further molecular insight. PMID:23795884

  19. Distinct roles for histone chaperones in the deposition of Htz1 in chromatin.

    PubMed

    Liu, Hongde; Zhu, Min; Mu, Yawen; Liu, Lingjie; Li, Guanghui; Wan, Yakun

    2014-01-01

    Histone variant Htz1 substitution for H2A plays important roles in diverse DNA transactions. Histone chaperones Chz1 and Nap1 (nucleosome assembly protein 1) are important for the deposition Htz1 into nucleosomes. In literatures, it was suggested that Chz1 is a Htz1-H2B-specific chaperone, and it is relatively unstructured in solution but it becomes structured in complex with the Htz1-H2B histone dimer. Nap1 (nucleosome assembly protein 1) can bind (H3-H4)2 tetramers, H2A-H2B dimers and Htz1-H2B dimers. Nap1 can bind H2A-H2B dimer in the cytoplasm and shuttles the dimer into the nucleus. Moreover, Nap1 functions in nucleosome assembly by competitively interacting with non-nucleosomal histone-DNA. However, the exact roles of these chaperones in assembling Htz1-containing nucleosome remain largely unknown. In this paper, we revealed that Chz1 does not show a physical interaction with chromatin. In contrast, Nap1 binds exactly at the genomic DNA that contains Htz1. Nap1 and Htz1 show a preferential interaction with AG-rich DNA sequences. Deletion of chz1 results in a significantly decreased binding of Htz1 in chromatin, whereas deletion of nap1 dramatically increases the association of Htz1 with chromatin. Furthermore, genome-wide nucleosome-mapping analysis revealed that nucleosome occupancy for Htz1p-bound genes decreases upon deleting htz1 or chz1, suggesting that Htz1 is required for nucleosome structure at the specific genome loci. All together, these results define the distinct roles for histone chaperones Chz1 and Nap1 to regulate Htz1 incorporation into chromatin. PMID:25338502

  20. Components of the Engulfment Machinery Have Distinct Roles in Corpse Processing

    PubMed Central

    Meehan, Tracy L.; Joudi, Tony F.; Timmons, Allison K.; Taylor, Jeffrey D.; Habib, Corey S.; Peterson, Jeanne S.; Emmanuel, Shanan; Franc, Nathalie C.; McCall, Kimberly

    2016-01-01

    Billions of cells die in our bodies on a daily basis and are engulfed by phagocytes. Engulfment, or phagocytosis, can be broken down into five basic steps: attraction of the phagocyte, recognition of the dying cell, internalization, phagosome maturation, and acidification. In this study, we focus on the last two steps, which can collectively be considered corpse processing, in which the engulfed material is degraded. We use the Drosophila ovarian follicle cells as a model for engulfment of apoptotic cells by epithelial cells. We show that engulfed material is processed using the canonical corpse processing pathway involving the small GTPases Rab5 and Rab7. The phagocytic receptor Draper is present on the phagocytic cup and on nascent, phosphatidylinositol 3-phosphate (PI(3)P)- and Rab7-positive phagosomes, whereas integrins are maintained on the cell surface during engulfment. Due to the difference in subcellular localization, we investigated the role of Draper, integrins, and downstream signaling components in corpse processing. We found that some proteins were required for internalization only, while others had defects in corpse processing as well. This suggests that several of the core engulfment proteins are required for distinct steps of engulfment. We also performed double mutant analysis and found that combined loss of draper and αPS3 still resulted in a small number of engulfed vesicles. Therefore, we investigated another known engulfment receptor, Crq. We found that loss of all three receptors did not inhibit engulfment any further, suggesting that Crq does not play a role in engulfment by the follicle cells. A more complete understanding of how the engulfment and corpse processing machinery interact may enable better understanding and treatment of diseases associated with defects in engulfment by epithelial cells. PMID:27347682

  1. The role of self-other distinction in understanding others' mental and emotional states: neurocognitive mechanisms in children and adults.

    PubMed

    Steinbeis, Nikolaus

    2016-01-19

    Social interactions come with the fundamental problem of trying to understand others' mental and affective states while under the overpowering influence of one's own concurrent thoughts and feelings. The ability to distinguish between simultaneous representations of others' current experiences as well as our own is crucial to navigate our complex social environments successfully. The developmental building blocks of this ability and how this is given rise to by functional and structural brain development remains poorly understood. In this review, I outline some of the key findings on the role of self-other distinction in understanding others' mental as well as emotional states in children and adults. I will begin by clarifying the crucial role for self-other distinction in avoiding egocentric attributions of one's own cognitive as well as affective states to others in adults and outline the underlying neural circuitry in overcoming such egocentricity. This will provide the basis for a discussion of the emergence of self-other distinction in early childhood as well as developmental changes therein throughout childhood and into adulthood. I will demonstrate that self-other distinction of cognitive and emotional states is already dissociable early in development. Concomitantly, I will show that processes of self-other distinction in cognitive and affective domains rely on adjacent but distinct neural circuitry each with unique connectivity profiles, presumably related to the nature of the distinction that needs to be made. PMID:26644593

  2. [Distinct roles of the direct and indirect pathways in the basal ganglia circuit mechanism].

    PubMed

    Morita, Makiko; Hikida, Takatoshi

    2015-11-01

    The basal ganglia are key neural substrates that control not only motor balance but also emotion, motivation, cognition, learning, and decision-making. Dysfunction of the basal ganglia leads to neurodegenerative diseases (e.g. Parkinson's disease and Huntington's disease) and psychiatric disorders (e.g. drug addiction, schizophrenia, and depression). In the basal ganglia circuit, there are two important pathways: the direct and indirect striatal pathways. Recently, new molecular techniques that activate or inactive selectively the direct or indirect pathway neurons have revealed the function of each pathway. Here we review the distinct roles of the direct and indirect striatal pathways in brain function and drug addiction. We have developed a reversible neurotransmission blocking technique, in which transmission of each pathway is selectively blocked by specific expression of transmission-blocking tetanus toxin, and revealed that the activation of D1 receptors in the direct pathway is critical for reward learning/cocaine addiction, and that the inactivation of D2 receptors is critical for aversive learning/learning flexibility. We propose a new circuit mechanism by which the dopaminergic input from the ventral tegmental area can switch the direct and indirect pathways in the nucleus accumbens. These basal ganglia circuit mechanisms will give us insights into the pathophysiology of mental diseases. PMID:26785520

  3. Distinct Roles of Chromatin Insulator Proteins in Control of the Drosophila Bithorax Complex.

    PubMed

    Savitsky, Mikhail; Kim, Maria; Kravchuk, Oksana; Schwartz, Yuri B

    2016-02-01

    Chromatin insulators are remarkable regulatory elements that can bring distant genomic sites together and block unscheduled enhancer-promoter communications. Insulators act via associated insulator proteins of two classes: sequence-specific DNA binding factors and "bridging" proteins. The latter are required to mediate interactions between distant insulator elements. Chromatin insulators are critical for correct expression of complex loci; however, their mode of action is poorly understood. Here, we use the Drosophila bithorax complex as a model to investigate the roles of the bridging proteins Cp190 and Mod(mdg4). The bithorax complex consists of three evolutionarily conserved homeotic genes Ubx, abd-A, and Abd-B, which specify anterior-posterior identity of the last thoracic and all abdominal segments of the fly. Looking at effects of CTCF, mod(mdg4), and Cp190 mutations on expression of the bithorax complex genes, we provide the first functional evidence that Mod(mdg4) acts in concert with the DNA binding insulator protein CTCF. We find that Mod(mdg4) and Cp190 are not redundant and may have distinct functional properties. We, for the first time, demonstrate that Cp190 is critical for correct regulation of the bithorax complex and show that Cp190 is required at an exceptionally strong Fub insulator to partition the bithorax complex into two topological domains.

  4. Distinct roles of Bazooka and Stardust in the specification of Drosophila photoreceptor membrane architecture.

    PubMed

    Hong, Yang; Ackerman, Larry; Jan, Lily Yeh; Jan, Yuh-Nung

    2003-10-28

    Photoreceptors form during Drosophila pupal development and acquire elaborate membrane structures, including the rhabdomeres and stalk membranes. Here, we show that the development of these cellular structures involves two distinct processes: the establishment of apical-basal polarity that requires Bazooka (Baz), and the regionalization of apical membrane into stalk membranes and rhabdomeres that requires Stardust (Sdt). In the absence of Baz, the apical-basal polarity is compromised in early pupal photoreceptors, and no identifiable apical membrane domain is formed. Sdt, in contrast, plays a more limited role in apical-basal polarity but is essential for the proper localization of transmembrane protein Crumbs (Crb), known to be required in the biogenesis of stalk membrane. Loss of Sdt causes strong defects in stalk membrane and rhabdomere resembling crb mutant phenotype. Thus, proteins required for establishing the early embryonic epithelial polarity are used later for the morphogenesis of photoreceptors, with Baz and Sdt functioning in different aspects of the formation of the apical-basal cellular architecture.

  5. Inalienable Possession in Mandarin.

    ERIC Educational Resources Information Center

    Kliffer, Michael D.

    Inalienable possession (iposs) in Mandarin Chinese has traditionally been thought restricted to associative (genitive) phrases where the possessor is juxtaposed to the possessum. In addition to such phrases, this analysis looks at five other possibilities where intrinsically relational nouns arise: zero anaphora; double subjects; passive of bodily…

  6. Btf and TRAP150 have distinct roles in regulating subcellular mRNA distribution

    PubMed Central

    Varia, Sapna; Potabathula, Divya; Deng, Zhihui; Bubulya, Athanasios; Bubulya, Paula A.

    2013-01-01

    Transcription of protein-coding genes in mammalian cells is coordinated with pre-mRNA processing as well as the assembly and nuclear export of mRNPs. Btf (BCLAF1) and TRAP150 (THRAP3) were previously reported to associate with in vitro spliced mRNPs and also as a part of the spliceosome, suggesting they are involved in pre-mRNA processing. Btf and TRAP150 are serine-arginine-rich (SR) proteins with significant sequence similarity, but the extent of their functional overlap is not yet clear. We show that both Btf and TRAP150 localize at a constitutively active β-tropomyosin (BTM) reporter minigene locus in mammalian cells. Both proteins also localize at a U2OS 2–6-3 reporter gene locus in a RNA polymerase II (RNAPII) transcription-dependent manner. While Btf and TRAP150 showed some overlap with reporter RNA and other pre-mRNA processing factors at transcription loci, they showed the most precise overlap with the exon junction complex (EJC) protein Magoh. Since EJC components have roles in nuclear export, we examined nuclear/cytoplasmic mRNA distribution after Btf or TRAP150 knockdown. Btf depletion caused an increase of β-tropomyosin minigene reporter transcripts in the cytoplasm as well as global increase of endogenous polyadenylated RNA in the cytoplasm, while TRAP150 depletion did not. We provide evidence that Btf has functions distinct from TRAP150 in regulating the subcellular distribution of mRNAs in human cells. PMID:23778535

  7. Ideas Exchange: Should School Districts Have a Specific Individual Designated as the Director or Coordinator for Physical Education? What Credentials Should One Possess to Be Effective in Such a Role?

    ERIC Educational Resources Information Center

    Kerekes, Jack; Chase, Melissa A.; Reiss, Carole B.; Fennel, Adam; Vulpis,Dominick; Magnotta, John; Arcadi, Mary; Siracuse, Robert M.; Christenson, Robert S.; Wright, Jim

    2010-01-01

    This article presents the opinions/ideas of professionals who were asked these questions: "Should school districts have a specific individual designated as the Director or Coordinator for Physical Education? What credentials should one possess to be effective in such a role?" The professionals contend that every school district needs to have a…

  8. Naming from definition: the role of feature type and feature distinctiveness.

    PubMed

    Marques, J Frederico

    2005-05-01

    The present paper evaluates the contribution of feature type and feature distinctiveness to naming of living and nonliving things using a naming from definition task. Normal subjects read verbal descriptions containing features varying in type (i.e., sensory vs. functional) and distinctiveness (i.e., distinct vs. shared) and were asked to name the concept described and to select the three features that most contributed to their answer. Main results showed that sensory features were selected more often than functional features to support naming living things and that, independent of feature type, more distinct features were selected to support naming more often than shared features. Results are discussed considering the implications for understanding naming and for neuropsychological evaluation. PMID:16104097

  9. Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making

    PubMed Central

    Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K.; Murphy, Gillian; Keeley, Sophie; Whone, Alan L.

    2012-01-01

    plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined. PMID:23114368

  10. The role of lithological contrasts in the formation of sinkholes: a Distinct Element Method modelling perspective

    NASA Astrophysics Data System (ADS)

    Al-Halbouni, Djamil; Holohan, Eoghan P.; Dahm, Torsten

    2015-04-01

    Sinkhole formation is a geological phenomenon resulting from dissolution and subrosion of rocks or sediments at depth, where large secondary pore space and cavities may develop, and from the eventual subsidence of the overburden. Although sinkholes may develop slowly as a natural process, their formation is often intensified by human activities. For instance, sinkhole hazard has intensified at the Dead Sea shoreline in the Middle East since the beginning of the recession of the Dead Sea level. Another example concerns sinkhole formation induced by solution mining of salt rock in the Lorraine district, France. Signs of precursors to collapse sinkholes have sometimes been indicated by monitoring studies, but are not well understood in terms of quantitative models. Here we report on a general, simplified approach to simulating sinkhole formation by using 2D Distinct Element Method (PFC2D) models comprising elastically bonded particles. The presence of bonds leads to elastic rock deformation under loading conditions and bond breakage may result in spontaneous formation of faults and cracks. Using different rheological parameters like Young's modulus, density, cohesion and friction coefficients, this method is able to simulate realistic rock layering contrasts. The dissolution or subrosion process leading to the formation of underground cavities is simulated via simple incremental particle deletion, whereby an arbitrary dissolution rate can be determined. Model structures preceding a sinkhole collapse, as well as precursory changes in density or porosity, are explicitly simulated and may be linked to measured geophysical parameters such as microseismicity, seismic velocity and electric conductivity. As well as examining precursory phenomena, we study the effect of lithological contrasts on (1) the geometry of sinkholes (diameter to depth ratio) and (2) the onset of collapse. Beside the formulation of general relations, we compare our simulations to well documented case

  11. Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

    PubMed

    Coulthard, Elizabeth J; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K; Murphy, Gillian; Keeley, Sophie; Whone, Alan L

    2012-12-01

    pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.

  12. The two subtype 1 somatostatin receptors of rainbow trout, Tsst1A and Tsst1B, possess both distinct and overlapping ligand binding and agonist-induced regulation features.

    PubMed

    Gong, Jun-Yang; Kittilson, Jeffrey D; Slagter, Barton J; Sheridan, Mark A

    2004-07-01

    In the present study, two isoforms of somatostatin receptor subtype one, previously obtained from the brain of rainbow trout, Tsst1A and Tsst1B, were stably transfected in the Chinese hamster ovary cell line (CHO-K1) and their binding properties were characterized. High affinity binding of somatostatin by expressed receptors was saturable and ligand selective. Both Tsst1A and Tsst1B preferentially bound peptides derived from preprosomatostatin I (PPSS I; e.g., SS-14-I) over those derived from PPSS II (containing Tyr7, Gly10-SS-14-I at their C-terminus; e.g., SS-25-II). The rank order of ligand affinities for Tsst1A was SS-28-I>SS-14-I>SS-26-I?SS-28-II>SS-14-II>SS-25-II. The rank order for Tsst1B was SS-14-I>SS-28-I>SS-26-1?SS-28-II>SS-25-II>SS-14-II. Agonist-induced regulation of Tsst1A and Tsst1B was also investigated. After 30 min of SS-14-I exposure, both Tsst1A and Tsst1B underwent rapid internalization; ca. 60% of membrane Tsst1A was internalized and only about 40% of membrane Tsst1B was internalized. Prolonged agonist exposure (up to 48 h) induced up-regulation of membrane-expressed Tsst1A, but had no effect on Tsst1B. These results indicate that Tsst1s display both distinct and overlapping ligand binding and agonist-induced regulation features. Such features may form the basis of ligand-selection and have important consequences on target organ responsiveness. PMID:15253878

  13. 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.

  14. Role of Importance and Distinctiveness of Semantic Features in People with Aphasia: A Replication Study

    ERIC Educational Resources Information Center

    Mason-Baughman, Mary Beth; Wallace, Sarah E.

    2014-01-01

    Previous studies suggest that people with aphasia have incomplete lexical-semantic representations with decreased low-importance distinctive (LID) feature knowledge. In addition, decreased LID feature knowledge correlates with ability to discriminate among semantically related words. The current study seeks to replicate and extend previous…

  15. 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. PMID:23269538

  16. On the roles of distinctiveness and semantic expectancies in episodic encoding of emotional words.

    PubMed

    Kamp, Siri-Maria; Potts, Geoffrey F; Donchin, Emanuel

    2015-12-01

    We examined the factors that contribute to enhanced recall for emotionally arousing words by analyzing behavioral performance, the P300 as an index of distinctiveness, and the N400 as an index of semantic expectancy violation in a modified Von Restorff paradigm. While their EEG was recorded, participants studied three list types (1) neutral words including one emotionally arousing isolate (either positive or negative), (2) arousing, negative words including one neutral isolate, or (3) arousing, positive words including one neutral isolate. Immediately after each list, free recall was tested. Negative, but not positive, words exhibited enhanced recall when presented as isolates in lists of neutral words and elicited a larger P300 for subsequently recalled than not-recalled words. This suggests that arousing, negative words stand out and that their distinctiveness contributes to their superior recall. Positive valence had an enhancing effect on recall only when the list contained mostly other positive words. Neutral isolates placed in either positive or negative lists elicited an N400, suggesting that semantic expectations developed in emotional word lists regardless of valence. However, semantic relatedness appeared to more strongly contribute to recall for positive than negative words. Our results suggest that distinctiveness and semantic relatedness contribute to episodic encoding of arousing words, but the impact of each factor depends on both a word's valence and its context.

  17. Distinctive Roles for Amygdalar CREB in Reconsolidation and Extinction of Fear Memory

    ERIC Educational Resources Information Center

    Tronson, Natalie C.; Wiseman, Shari L.; Neve, Rachael L.; Nestler, Eric J.; Olausson, Peter; Taylor, Jane R.

    2012-01-01

    Cyclic AMP response element binding protein (CREB) plays a critical role in fear memory formation. Here we determined the role of CREB selectively within the amygdala in reconsolidation and extinction of auditory fear. Viral overexpression of the inducible cAMP early repressor (ICER) or the dominant-negative mCREB, specifically within the lateral…

  18. Telomere dysfunction and cell survival: roles for distinctTIN2-containing complexes

    SciTech Connect

    Kim, Sahn-Ho; Davalos, Albert R.; Heo, Seok-Jin; Rodier, Francis; Beausejour, Christian; Kaminker, Patrick; Campisi, Judith

    2006-11-07

    Telomeres are maintained by three DNA binding proteins, TRF1, TRF2 and POT1, and several associated factors. One factor, TIN2, binds TRF1 and TRF2 directly and POT1 indirectly. These and two other proteins form a soluble complex that may be the core telomere-maintenance complex. It is not clear whether subcomplexes exist or function in vivo. Here, we provide evidence for two TIN2 subcomplexes with distinct functions in human cells. TIN2 ablation by RNA interference caused telomere uncapping and p53-independent cell death in all cells tested. However, we isolated two TIN2 complexes from cell lysates, each selectively sensitive to a TIN2 mutant (TIN2-13, TIN2-15C). In cells with wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere uncapping and eventual growth arrest. In cells lacking p53 function, TIN215C more than TIN2-13 caused genomic instability and cell death. Thus, TIN2 subcomplexes likely have distinct functions in telomere maintenance, and may provide selective targets for eliminating cells with mutant p53.

  19. Telomere dysfunction and cell survival: Roles for distinct TIN2-containing complexes

    SciTech Connect

    Kim, Sahn-ho; Davalos, Albert R.; Heo, Seok-Jin; Rodier, Francis; Zou, Ying; Beausejour, Christian; Kaminker, Patrick; Yannone, Steven M.; Campisi, Judith

    2007-10-02

    Telomeres are maintained by three DNA binding proteins (TRF1, TRF2 and POT1), and several associated factors. One factor, TIN2, binds TRF1 and TRF2 directly and POT1 indirectly. Along with two other proteins, TPP1 and hRap1, these form a soluble complex that may be the core telomere maintenance complex. It is not clear whether sub-complexes also exist in vivo. We provide evidence for two TIN2 sub-complexes with distinct functions in human cells. We isolated these two TIN2 sub-complexes from nuclear lysates of unperturbed cells and cells expressing TIN2 mutants TIN2-13, TIN2-15C, which cannot bind TRF2 or TRF1, respectively. In cells with wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere uncapping and eventual growth arrest. In cells lacking p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere dysfunction and cell death. Our findings suggest that distinct TIN2 complexes exist, and that TIN2-15C-sensitive subcomplexes are particularly important for cell survival in the absence of functional p53.

  20. Distinct Temporal Regulation of RET Isoform Internalization: Roles of Clathrin and AP2.

    PubMed

    Crupi, Mathieu J F; Yoganathan, Piriya; Bone, Leslie N; Lian, Eric; Fetz, Andrew; Antonescu, Costin N; Mulligan, Lois M

    2015-11-01

    The RET receptor tyrosine kinase (RTK) contributes to kidney and nervous system development, and is implicated in a number of human cancers. RET is expressed as two protein isoforms, RET9 and RET51, with distinct interactions and signaling properties that contribute to these processes. RET isoforms are internalized from the cell surface into endosomal compartments in response to glial cell line-derived neurotropic factor (GDNF) ligand stimulation but the specific mechanisms of RET trafficking remain to be elucidated. Here, we used total internal reflection fluorescence (TIRF) microscopy to demonstrate that RET internalization occurs primarily through clathrin coated pits (CCPs). Activated RET receptors colocalize with clathrin, but not caveolin. The RET51 isoform is rapidly and robustly recruited to CCPs upon GDNF stimulation, while RET9 recruitment occurs more slowly and is less pronounced. We showed that the clathrin-associated adaptor protein complex 2 (AP2) interacts directly with each RET isoform through its AP2 μ subunit, and is important for RET internalization. Our data establish that interactions with the AP2 complex promote RET receptor internalization via clathrin-mediated endocytosis but that RET9 and RET51 have distinct internalization kinetics that may contribute to differences in their biological functions. PMID:26304132

  1. Gremlin 2 regulates distinct roles of BMP and Endothelin 1 signaling in dorsoventral patterning of the facial skeleton

    PubMed Central

    Zuniga, Elizabeth; Rippen, Marie; Alexander, Courtney; Schilling, Thomas F.; Crump, J. Gage

    2011-01-01

    Patterning of the upper versus lower face involves generating distinct pre-skeletal identities along the dorsoventral (DV) axes of the pharyngeal arches. Whereas previous studies have shown roles for BMPs, Endothelin 1 (Edn1) and Jagged1b-Notch2 in DV patterning of the facial skeleton, how these pathways are integrated to generate different skeletal fates has remained unclear. Here, we show that BMP and Edn1 signaling have distinct roles in development of the ventral and intermediate skeletons, respectively, of the zebrafish face. Using transgenic gain-of-function approaches and cell-autonomy experiments, we find that BMPs strongly promote hand2 and msxe expression in ventral skeletal precursors, while Edn1 promotes the expression of nkx3.2 and three Dlx genes (dlx3b, dlx5a and dlx6a) in intermediate precursors. Furthermore, Edn1 and Jagged1b pattern the intermediate and dorsal facial skeletons in part by inducing the BMP antagonist Gremlin 2 (Grem2), which restricts BMP activity to the ventral-most face. We therefore propose a model in which later cross-inhibitory interactions between BMP and Edn1 signaling, in part mediated by Grem2, separate an initially homogenous ventral region into distinct ventral and intermediate skeletal precursor domains. PMID:22031546

  2. Possession in a New Language.

    ERIC Educational Resources Information Center

    Broeder, Peter

    1992-01-01

    Discusses a study on the untutored acquisition of possessive constructions in Dutch by two Turkish and two Moroccan adults during the first three years of their stay in the Netherlands. The focus is on the order of the owner and the possession in possessive constructions. (28 references) (JL)

  3. LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development.

    PubMed

    Byrd, Kevin M; Lough, Kendall J; Patel, Jeet H; Descovich, Carlos Patiño; Curtis, T Anthony; Williams, Scott E

    2016-08-01

    Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. PMID:27317810

  4. Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory.

    PubMed

    Gyurkó, M Dávid; Csermely, Péter; Sőti, Csaba; Steták, Attila

    2015-01-01

    The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans. PMID:26469632

  5. Microfluidic Investigation Reveals Distinct Roles for Actin Cytoskeleton and Myosin II Activity in Capillary Leukocyte Trafficking

    PubMed Central

    Gabriele, Sylvain; Benoliel, Anne-Marie; Bongrand, Pierre; Théodoly, Olivier

    2009-01-01

    Circulating leukocyte sequestration in pulmonary capillaries is arguably the initiating event of lung injury in acute respiratory distress syndrome. We present a microfluidic investigation of the roles of actin organization and myosin II activity during the different stages of leukocyte trafficking through narrow capillaries (entry, transit and shape relaxation) using specific drugs (latrunculin A, jasplakinolide, and blebbistatin). The deformation rate during entry reveals that cell stiffness depends strongly on F-actin organization and hardly on myosin II activity, supporting a microfilament role in leukocyte sequestration. In the transit stage, cell friction is influenced by stiffness, demonstrating that the actin network is not completely broken after a forced entry into a capillary. Conversely, membrane unfolding was independent of leukocyte stiffness. The surface area of sequestered leukocytes increased by up to 160% in the absence of myosin II activity, showing the major role of molecular motors in microvilli wrinkling and zipping. Finally, cell shape relaxation was largely independent of both actin organization and myosin II activity, whereas a deformed state was required for normal trafficking through capillary segments. PMID:19450501

  6. Contribution of mitochondria and endoplasmic reticulum dysfunction in insulin resistance: Distinct or interrelated roles?

    PubMed

    Rieusset, J

    2015-11-01

    Mitochondria and the endoplasmic reticulum (ER) regulate numerous cellular processes, and are critical contributors to cellular and whole-body homoeostasis. More important, mitochondrial dysfunction and ER stress are both closely associated with hepatic and skeletal muscle insulin resistance, thereby playing crucial roles in altered glucose homoeostasis in type 2 diabetes mellitus (T2DM). The accumulated evidence also suggests a potential interrelationship between alterations in both types of organelles, as mitochondrial dysfunction could participate in activation of the unfolded protein response, whereas ER stress could influence mitochondrial function. The fact that mitochondria and the ER are physically and functionally interconnected via mitochondria-associated membranes (MAMs) supports their interrelated roles in the pathophysiology of T2DM. However, the mechanisms that coordinate the interplay between mitochondrial dysfunction and ER stress, and its relevance to the control of glucose homoeostasis, are still unknown. This review evaluates the involvement of mitochondria and ER independently in the development of peripheral insulin resistance, as well as their potential roles in the disruption of organelle crosstalk at MAM interfaces in the alteration of insulin signalling.

  7. NFAT isoforms play distinct roles in TNFα-induced retinal leukostasis.

    PubMed

    Bretz, Colin A; Savage, Sara R; Capozzi, Megan E; Suarez, Sandra; Penn, John S

    2015-11-03

    The objective of this study was to determine the role of individual NFAT isoforms in TNFα-induced retinal leukostasis. To this end, human retinal microvascular endothelial cells (HRMEC) transfected with siRNA targeting individual NFAT isoforms were treated with TNFα, and qRT-PCR was used to examine the contribution of each isoform to the TNFα-induced upregulation of leukocyte adhesion proteins. This showed that NFATc1 siRNA increased ICAM1 expression, NFATc2 siRNA reduced CX3CL1, VCAM1, SELE, and ICAM1 expression, NFATc3 siRNA increased CX3CL1 and SELE expression, and NFATc4 siRNA reduced SELE expression. Transfected HRMEC monolayers were also treated with TNFα and assayed using a parallel plate flow chamber, and both NFATc2 and NFATc4 knockdown reduced TNFα-induced cell adhesion. The effect of isoform-specific knockdown on TNFα-induced cytokine production was also measured using protein ELISAs and conditioned cell culture medium, and showed that NFATc4 siRNA reduced CXCL10, CXCL11, and MCP-1 protein levels. Lastly, the CN/NFAT-signaling inhibitor INCA-6 was shown to reduce TNFα-induced retinal leukostasis in vivo. Together, these studies show a clear role for NFAT-signaling in TNFα-induced retinal leukostasis, and identify NFATc2 and NFATc4 as potentially valuable therapeutic targets for treating retinopathies in which TNFα plays a pathogenic role.

  8. NFAT isoforms play distinct roles in TNFα-induced retinal leukostasis

    PubMed Central

    Bretz, Colin A.; Savage, Sara R.; Capozzi, Megan E.; Suarez, Sandra; Penn, John S.

    2015-01-01

    The objective of this study was to determine the role of individual NFAT isoforms in TNFα-induced retinal leukostasis. To this end, human retinal microvascular endothelial cells (HRMEC) transfected with siRNA targeting individual NFAT isoforms were treated with TNFα, and qRT-PCR was used to examine the contribution of each isoform to the TNFα-induced upregulation of leukocyte adhesion proteins. This showed that NFATc1 siRNA increased ICAM1 expression, NFATc2 siRNA reduced CX3CL1, VCAM1, SELE, and ICAM1 expression, NFATc3 siRNA increased CX3CL1 and SELE expression, and NFATc4 siRNA reduced SELE expression. Transfected HRMEC monolayers were also treated with TNFα and assayed using a parallel plate flow chamber, and both NFATc2 and NFATc4 knockdown reduced TNFα-induced cell adhesion. The effect of isoform-specific knockdown on TNFα-induced cytokine production was also measured using protein ELISAs and conditioned cell culture medium, and showed that NFATc4 siRNA reduced CXCL10, CXCL11, and MCP-1 protein levels. Lastly, the CN/NFAT-signaling inhibitor INCA-6 was shown to reduce TNFα-induced retinal leukostasis in vivo. Together, these studies show a clear role for NFAT-signaling in TNFα-induced retinal leukostasis, and identify NFATc2 and NFATc4 as potentially valuable therapeutic targets for treating retinopathies in which TNFα plays a pathogenic role. PMID:26527057

  9. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation.

    PubMed

    Zeng, Huawei; Claycombe, Kate J; Reindl, Katie M

    2015-10-01

    Consumption of a high-fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk, while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer-preventive effects. To distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen), we examined the effects of physiologically relevant doses of butyrate (0.5-2 mmol/l) and DCA (0.05-0.3 mmol/l) on colon cell proliferation. We hypothesize that butyrate and DCA each modulates the cell cycle and apoptosis via common and distinct cellular signaling targets. In this study, we demonstrated that both butyrate and DCA inhibited cell proliferation by up to 89% and 92% and increased cell apoptosis rate by up to 3.1- and 4.5-fold, respectively. Cell cycle analyses revealed that butyrate led to an increase in G1 and G2 fractions with a concomitant drop in the S-phase fraction, but DCA induced an increase in only G1 fraction with a concomitant drop in the S-phase fraction when compared with the untreated cells. The examination of early cellular signaling revealed that DCA but not butyrate increased intracellular reactive oxygen species, genomic DNA breakage, the activation of ERK1/2, caspase-3 and PARP. In contrast, DCA decreased activated Rb protein level, and butyrate but not DCA increased p21 expression. Collectively, although both butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases tumor suppressor activation in cell cycle and apoptosis pathways.

  10. AAA+ proteases and their role in distinct stages along the Vibrio cholerae lifecycle.

    PubMed

    Pressler, Katharina; Vorkapic, Dina; Lichtenegger, Sabine; Malli, Gerald; Barilich, Benjamin P; Cakar, Fatih; Zingl, Franz G; Reidl, Joachim; Schild, Stefan

    2016-09-01

    The facultative human pathogen Vibrio cholerae has to adapt to different environmental conditions along its lifecycle by means of transcriptional, translational and post-translational regulation. This study provides a first comprehensive analysis regarding the contribution of the cytoplasmic AAA+ proteases Lon, ClpP and HslV to distinct features of V. cholerae behaviour, including biofilm formation, motility, cholera toxin expression and colonization fitness in the mouse model. While absence of HslV did not yield to any altered phenotype compared to wildtype, absence of Lon or ClpP resulted in significantly reduced colonization in vivo. In addition, a Δlon deletion mutant showed altered biofilm formation and increased motility, which could be correlated with higher expression of V. cholerae flagella gene class IV. Concordantly, we could show by immunoblot analysis, that Lon is the main protease responsible for proteolytic control of FliA, which is required for class IV flagella gene transcription, but also downregulates virulence gene expression. FliA becomes highly sensitive to proteolytic degradation in absence of its anti-sigma factor FlgM, a scenario reported to occur during mucosal penetration due to FlgM secretion through the broken flagellum. Our results confirm that the high stability of FliA in the absence of Lon results in less cholera toxin and toxin corgulated pilus production under virulence gene inducing conditions and in the presence of a damaged flagellum. Thus, the data presented herein provide a molecular explanation on how V. cholerae can achieve full expression of virulence genes during early stages of colonization, despite FliA getting liberated from the anti-sigma factor FlgM. PMID:27345492

  11. Distinct roles of left inferior frontal regions that explain individual differences in second language acquisition.

    PubMed

    Sakai, Kuniyoshi L; Nauchi, Arihito; Tatsuno, Yoshinori; Hirano, Kazuyoshi; Muraishi, Yukimasa; Kimura, Masakazu; Bostwick, Mike; Yusa, Noriaki

    2009-08-01

    Second language (L2) acquisition is more susceptible to environmental and idiosyncratic factors than first language acquisition. Here, we used functional magnetic resonance imaging for L2 learners of different ages of first exposure (mean: 12.6 and 5.6 years) in a formal school environment, and compared the cortical activations involved in processing English sentences containing either syntactic or spelling errors, where the testing ages and task performances of both groups were matched. We found novel activation patterns in two regions of the left inferior frontal gyrus (IFG) that correlated differentially with the performances of the late and early learners. Specifically, activations of the dorsal and ventral triangular part (F3t) of the left IFG correlated positively with the accuracy of the syntactic task for the late learners, whereas activations of the left ventral F3t correlated negatively with the accuracy for the early learners. In contrast, other cortical regions exhibited differential correlation patterns with the reaction times (RTs) of the syntactic task. Namely, activations of the orbital part (F3O) of the left IFG, as well as those of the left angular gyrus, correlated positively with the RTs for the late learners, whereas those activations correlated negatively with the RTs for the early learners. Moreover, the task-selective activation of the left F3O was maintained for both the late and early learners. These results explain individual differences in L2 acquisition, such that the acquisition of linguistic knowledge in L2 is subserved by at least two distinct inferior frontal regions of the left F3t and F3O.

  12. Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles

    PubMed Central

    Zhuang, Min; Wiita, Arun P.; O’Donoghue, Anthony J.; Knudsen, Giselle M.; Craik, Charles S.; Wells, James A.

    2016-01-01

    Proteases constitute the largest enzyme family, yet their biological roles are obscured by our rudimentary understanding of their cellular substrates. There are 12 human caspases that play crucial roles in inflammation and cell differentiation and drive the terminal stages of cell death. Recent N-terminomics technologies have begun to enumerate the diverse substrates individual caspases can cleave in complex cell lysates. It is clear that many caspases have shared substrates; however, few data exist about the catalytic efficiencies (kcat/KM) of these substrates, which is critical to understanding their true substrate preferences. In this study, we use quantitative MS to determine the catalytic efficiencies for hundreds of natural protease substrates in cellular lysate for two understudied members: caspase-2 and caspase-6. Most substrates are new, and the cleavage rates vary up to 500-fold. We compare the cleavage rates for common substrates with those found for caspase-3, caspase-7, and caspase-8, involved in apoptosis. There is little correlation in catalytic efficiencies among the five caspases, suggesting each has a unique set of preferred substrates, and thus more specialized roles than previously understood. We synthesized peptide substrates on the basis of protein cleavage sites and found similar catalytic efficiencies between the protein and peptide substrates. These data suggest the rates of proteolysis are dominated more by local primary sequence, and less by the tertiary protein fold. Our studies highlight that global quantitative rate analysis for posttranslational modification enzymes in complex milieus for native substrates is critical to better define their functions and relative sequence of events. PMID:27006500

  13. Explaining the link between objective and perceived differences in groups: The role of the belonging and distinctiveness motives.

    PubMed

    Ormiston, Margaret E

    2016-02-01

    Group diversity research often focuses on objective diversity, or the actual compositional attributes of the group (e.g., differences in sex or functional background), and its impact on group processes and performance. More recently, diversity researchers have called for consideration of group members' perceptions of diversity, or their subjective understanding of differences within their group, because these perceptions have important effects on group outcomes. In fact, research has indicated only a modest correlation between objective and perceived diversity. Although the subjective nature of group diversity has important implications for group outcomes, we are still unclear about why and when perceived diversity diverges from objective diversity. In this article, I examine the role of identity motives, or motives that guide self-definition, in shaping member's perceptions of themselves and their group's composition. I argue that group members want to balance their needs for belonging and distinctiveness, but high levels of objective differences make them feel too distinct whereas low levels of objective differences makes them feel too deindividuated. Individual differences in the need to belong and be distinct further influence the degree to which these motives are satisfied. In turn, when these motives are unsatisfied, they will affect members' perceptions of differences. The presented theory helps to explain the discrepancy between objective differences and members' perceptions of differences, and ultimately helps integrate opposing findings in the diversity literature.

  14. Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory.

    PubMed

    Okada, Kana; Nishizawa, Kayo; Kobayashi, Tomoko; Sakata, Shogo; Kobayashi, Kazuto

    2015-08-06

    Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer's disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.

  15. Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events.

    PubMed

    Farovik, Anja; Dupont, Laura M; Eichenbaum, Howard

    2010-01-01

    Previous studies have suggested that dorsal hippocampal areas CA3 and CA1 are both involved in representing sequences of events that compose unique episodes. However, it is uncertain whether the contribution of CA3 is restricted to spatial information, and it is unclear whether CA1 encodes order per se or contributes by an active maintenance of memories of sequential events. Here, we developed a new behavioral task that examines memory for the order of sequential nonspatial events presented as trial-unique odor pairings. When the interval between odors within a studied pair was brief (3 sec), bilateral dorsal CA3 lesions severely disrupted memory for their order, whereas dorsal CA1 lesions did not affect performance. However, when the inter-item interval was extended to 10 sec, CA1 lesions, as well as CA3 lesions, severely disrupted performance. These findings suggest that the role of CA3 in sequence memory is not limited to spatial information, but rather appears to be a fundamental property of CA3 function. In contrast, CA1 becomes involved when memories for events must be held or sequenced over long intervals. Thus, CA3 and CA1 are both involved in memory for sequential nonspatial events that compose unique experiences, and these areas play different roles that are distinguished by the duration of time that must be bridged between key events.

  16. Distinct Roles of SOM and VIP Interneurons during Cortical Up States

    PubMed Central

    Neske, Garrett T.; Connors, Barry W.

    2016-01-01

    During cortical network activity, recurrent synaptic excitation among pyramidal neurons is approximately balanced by synaptic inhibition, which is provided by a vast diversity of inhibitory interneurons. The relative contributions of different interneuron subtypes to inhibitory tone during cortical network activity is not well-understood. We previously showed that many of the major interneuron subtypes in mouse barrel cortex are highly active during Up states (Neske et al., 2015); while fast-spiking (FS), parvalbumin (PV)-positive cells were the most active interneuron subtype, many non-fast-spiking (NFS), PV-negative interneurons were as active or more active than neighboring pyramidal cells. This suggests that the NFS cells could play a role in maintaining or modulating Up states. Here, using optogenetic techniques, we further dissected the functional roles during Up states of two major NFS, PV-negative interneuron subtypes: somatostatin (SOM)-positive cells and vasoactive intestinal peptide (VIP)-positive cells. We found that while pyramidal cell excitability during Up states significantly increased when SOM cells were optogenetically silenced, VIP cells did not influence pyramidal cell excitability either upon optogenetic silencing or activation. VIP cells failed to contribute to Up states despite their ability to inhibit SOM cells strongly. We suggest that the contribution of VIP cells to the excitability of pyramidal cells may vary with cortical state. PMID:27507936

  17. Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory

    PubMed Central

    Okada, Kana; Nishizawa, Kayo; Kobayashi, Tomoko; Sakata, Shogo; Kobayashi, Kazuto

    2015-01-01

    Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer’s disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory. PMID:26246157

  18. Actin cap associated focal adhesions and their distinct role in cellular mechanosensing

    PubMed Central

    Kim, Dong-Hwee; Khatau, Shyam B.; Feng, Yunfeng; Walcott, Sam; Sun, Sean X.; Longmore, Gregory D.; Wirtz, Denis

    2012-01-01

    The ability for cells to sense and adapt to different physical microenvironments plays a critical role in development, immune responses, and cancer metastasis. Here we identify a small subset of focal adhesions that terminate fibers in the actin cap, a highly ordered filamentous actin structure that is anchored to the top of the nucleus by the LINC complexes; these differ from conventional focal adhesions in morphology, subcellular organization, movements, turnover dynamics, and response to biochemical stimuli. Actin cap associated focal adhesions (ACAFAs) dominate cell mechanosensing over a wide range of matrix stiffness, an ACAFA-specific function regulated by actomyosin contractility in the actin cap, while conventional focal adhesions are restrictively involved in mechanosensing for extremely soft substrates. These results establish the perinuclear actin cap and associated ACAFAs as major mediators of cellular mechanosensing and a critical element of the physical pathway that transduce mechanical cues all the way to the nucleus. PMID:22870384

  19. Distinct roles of multiple isoforms of CaMKII in signaling to the nucleus

    PubMed Central

    Ma, Huan; Li, Boxing; Tsien, Richard W.

    2015-01-01

    Long-lasting synaptic changes following information acquisition are critical steps for memory. In this process, long-term potentiation (LTP) is widely considered as one of the major cellular mechanisms modifying synaptic strength. It can be classified into early phase LTP (E-LTP) and late phase LTP (L-LTP) based on its duration. Using genetically modified mice, investigators have recognized the critical role of CaMKII in E-LTP and memory. However, its function in L-LTP, which is strongly dependent on gene transcription and protein synthesis, is still unclear. In this review, we discuss how different isoforms of CaMKII are coordinated to regulate gene expression in an activity-dependent manner, and thus contribute to L-LTP and memory. PMID:25700840

  20. The Drosophila Helicase Maleless (MLE) is Implicated in Functions Distinct From its Role in Dosage Compensation*

    PubMed Central

    Cugusi, Simona; Kallappagoudar, Satish; Ling, Huiping; Lucchesi, John C.

    2015-01-01

    Helicases are ubiquitous enzymes that unwind or remodel single or double-stranded nucleic acids, and that participate in a vast array of metabolic pathways. The ATP-dependent DEXH-box RNA/DNA helicase MLE was first identified as a core member of the chromatin remodeling MSL complex, responsible for dosage compensation in Drosophila males. Although this complex does not assemble in females, MLE is present. Given the multiplicity of functions attributed to its mammalian ortholog RNA helicase A, we have carried out an analysis for the purpose of determining whether MLE displays the same diversity. We have identified a number of different proteins that associate with MLE, implicating its role in specific pathways. We have documented this association in selected examples that include the spliceosome complex, heterogeneous Nuclear Ribonucleoproteins involved in RNA Processing and in Heterochromatin Protein 1 deposition, and the NuRD complex. PMID:25776889

  1. Distinct Roles of the Prefrontal and Posterior Parietal Cortices in Response Inhibition.

    PubMed

    Zhou, Xin; Qi, Xue-Lian; Constantinidis, Christos

    2016-03-29

    The dorsolateral prefrontal cortex and posterior parietal cortex have been implicated in the planning of movements and inhibition of inappropriate responses, though their precise roles in these functions are not known. To address this question, we trained monkeys to perform memory-guided saccade and anti-saccade tasks and compared neural responses in the same animals. A population of neurons with no motor responses was also activated by a stimulus appearing out of the receptive field and could therefore mediate vector inversion. These neurons were found almost exclusively in the prefrontal cortex. Prefrontal cortical activity better predicted the level of performance in the task. Representation of the saccade goal also peaked in the prefrontal cortex at a time that was predictive of reaction time. These results suggest that the prefrontal cortex is the primary site of vector inversion in the cerebral cortex and explain the importance of this area in response inhibition. PMID:26997283

  2. Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis

    PubMed Central

    Biswas, Uddipta; Hempel, Kai; Llano, Elena; Pendas, Alberto; Jessberger, Rolf

    2016-01-01

    Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1β, we generated Smc1β-/-Rec8-/- and Smc1β-/-Rad21L-/- mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1β complexes, SMC1α/RAD21 and to a small extent SMC1α/REC8 contribute to chromosome axis length. Removal of SMC1β and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1β-/-Rad21L-/- cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1α/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion. PMID:27792785

  3. A Vacuolar β-Glucosidase Homolog That Possesses Glucose-Conjugated Abscisic Acid Hydrolyzing Activity Plays an Important Role in Osmotic Stress Responses in Arabidopsis[W

    PubMed Central

    Xu, Zheng-Yi; Lee, Kwang Hee; Dong, Ting; Jeong, Jae Cheol; Jin, Jing Bo; Kanno, Yuri; Kim, Dae Heon; Kim, Soo Youn; Seo, Mitsunori; Bressan, Ray A.; Yun, Dae-Jin; Hwang, Inhwan

    2012-01-01

    The phytohormone abscisic acid (ABA) plays a critical role in various physiological processes, including adaptation to abiotic stresses. In Arabidopsis thaliana, ABA levels are increased both through de novo biosynthesis and via β-glucosidase homolog1 (BG1)-mediated hydrolysis of Glc-conjugated ABA (ABA-GE). However, it is not known how many different β-glucosidase proteins produce ABA from ABA-GE and how the multiple ABA production pathways are coordinated to increase ABA levels. Here, we report that a previously undiscovered β-glucosidase homolog, BG2, produced ABA by hydrolyzing ABA-GE and plays a role in osmotic stress response. BG2 localized to the vacuole as a high molecular weight complex and accumulated to high levels under dehydration stress. BG2 hydrolyzed ABA-GE to ABA in vitro. In addition, BG2 increased ABA levels in protoplasts upon application of exogenous ABA-GE. Overexpression of BG2 rescued the bg1 mutant phenotype, as observed for the overexpression of NCED3 in bg1 mutants. Multiple Arabidopsis bg2 alleles with a T-DNA insertion in BG2 were more sensitive to dehydration and NaCl stress, whereas BG2 overexpression resulted in enhanced resistance to dehydration and NaCl stress. Based on these observations, we propose that, in addition to the de novo biosynthesis, ABA is produced in multiple organelles by organelle-specific β-glucosidases in response to abiotic stresses. PMID:22582100

  4. Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.

    PubMed

    Poczobutt, Joanna M; De, Subhajyoti; Yadav, Vinod K; Nguyen, Teresa T; Li, Howard; Sippel, Trisha R; Weiser-Evans, Mary C M; Nemenoff, Raphael A

    2016-03-15

    Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and they alter their phenotype in response to local environmental cues. Whereas the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multimarker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and they suggest that distinct populations play specific roles in tumor progression. PMID:26873985

  5. Distinct Roles of Histone H3 and H2A Tails in Nucleosome Stability

    PubMed Central

    Li, Zhenhai; Kono, Hidetoshi

    2016-01-01

    Nucleosome breathing potentially increases the DNA exposure, which in turn recruits DNA-binding protein and regulates gene transcription. Numerous studies have shown the critical roles of N-terminal tails of histones H3 and H4 in gene expression; however, few studies have focused on the H2A C-terminal tail. Here we present thorough computational studies on a single nucleosome particle showing the linker DNA closing and opening, which is thought to be nucleosome breathing. With our simulation, the H2A C-terminal and H3 N-terminal tails were found to modulate the nucleosome conformation differently. The H2A C-terminal tail regulates nucleosome conformation by binding to linker DNA at different locations, whereas the H3 N-terminal tail regulates linker DNA by binding to it in different patterns. Further MD simulation on tail truncated structures corroborates this analysis. These findings replenish our understanding of the histone tail regulation mechanism on atomic level. PMID:27527579

  6. Evidence of a distinct lipid fraction in historical parchments: a potential role in degradation?

    PubMed

    Ghioni, C; Hiller, J C; Kennedy, C J; Aliev, A E; Odlyha, M; Boulton, M; Wess, T J

    2005-12-01

    Parchment, a biologically based material obtained from the processed hides of animals such as cattle and sheep, has been used for millennia as a writing medium. Although numerous studies have concentrated on the structure and degradation of collagen within parchment, little attention has been paid to noncollagenous components, such as lipids. In this study, we present the results of biochemical and structural analyses of historical and newly manufactured parchment to examine the potential role that lipid plays in parchment stability. The lipid fraction extracted from the parchments displayed different fatty acid compositions between historical and reference materials. Gas chromatography, small-angle X-ray scattering, and solid-state NMR were used to identify and investigate the lipid fraction from parchment samples and to study its contribution to collagen structure and degradation. We hypothesize that the origin of this lipid fraction is either intrinsic, attributable to incomplete fat removal in the manufacturing process, or extrinsic, attributable to microbiological attack on the proteinaceous component of parchments. Furthermore, we consider that the possible formation of protein-lipid complexes in parchment over the course of oxidative degradation may be mediated by reactive oxygen species formed by lipid peroxidation.

  7. The distinct role of performing euthanasia on depression and suicide in veterinarians.

    PubMed

    Tran, Lily; Crane, Monique F; Phillips, Jacqueline K

    2014-04-01

    Veterinarians are more likely to experience mood disorders and suicide than other occupational groups (Fritschi, Morrison, Shirangi & Day, 2009; Platt, Hawton, Simkin, & Mellanby, 2010). The performance of euthanasia has been implicated as contributing determinately to the prevalence of suicide risk and psychological distress in veterinarians (Bartram & Baldwin, 2008, 2010). In contrast, the application of psychological approaches would suggest a possible protective role for euthanasia administration. This paper is the first to investigate the association between euthanasia-administration frequency and depressed mood and suicide risk. A cross-sectional survey sampled 540 Australia-registered veterinarians (63.8% women), ranging in age from 23 to 74. Results revealed that the administration of objectionable euthanasia (i.e., euthanasia that the veterinarian disagreed with) was not related to our mental health variables. In contrast, overall euthanasia frequency had a weak positive linear relationship with depression. Moreover, overall euthanasia frequency moderated the impact of depression on suicide risk. The nature of this moderation suggested that average frequency per week of performing euthanasia attenuated the relationship between depressed mood and suicide risk. The implications of these findings and directions for further research are discussed. PMID:24635739

  8. Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain

    PubMed Central

    Mu, Yangling; Zhao, Chunmei; Toni, Nicolas; Yao, Jun; Gage, Fred H

    2015-01-01

    NMDA receptor (NMDAR)-dependent forms of synaptic plasticity are thought to underlie the assembly of developing neuronal circuits and to play a crucial role in learning and memory. It remains unclear how NMDAR might contribute to the wiring of adult-born granule cells (GCs). Here we demonstrate that nascent GCs lacking NMDARs but rescued from apoptosis by overexpressing the pro-survival protein Bcl2 were deficient in spine formation. Insufficient spinogenesis might be a general cause of cell death restricted within the NMDAR-dependent critical time window for GC survival. NMDAR loss also led to enhanced mushroom spine formation and synaptic AMPAR activity throughout the development of newborn GCs. Moreover, similar elevated synapse maturation in the absence of NMDARs was observed in neonate-generated GCs and CA1 pyramidal neurons. Together, these data suggest that NMDAR operates as a molecular monitor for controlling the activity-dependent establishment and maturation rate of synaptic connections between newborn neurons and others. DOI: http://dx.doi.org/10.7554/eLife.07871.001 PMID:26473971

  9. Distinct roles for GABA across multiple timescales in mammalian circadian timekeeping

    PubMed Central

    DeWoskin, Daniel; Myung, Jihwan; Belle, Mino D. C.; Piggins, Hugh D.; Takumi, Toru; Forger, Daniel B.

    2015-01-01

    The suprachiasmatic nuclei (SCN), the central circadian pacemakers in mammals, comprise a multiscale neuronal system that times daily events. We use recent advances in graphics processing unit computing to generate a multiscale model for the SCN that resolves cellular electrical activity down to the timescale of individual action potentials and the intracellular molecular events that generate circadian rhythms. We use the model to study the role of the neurotransmitter GABA in synchronizing circadian rhythms among individual SCN neurons, a topic of much debate in the circadian community. The model predicts that GABA signaling has two components: phasic (fast) and tonic (slow). Phasic GABA postsynaptic currents are released after action potentials, and can both increase or decrease firing rate, depending on their timing in the interspike interval, a modeling hypothesis we experimentally validate; this allows flexibility in the timing of circadian output signals. Phasic GABA, however, does not significantly affect molecular timekeeping. The tonic GABA signal is released when cells become very excited and depolarized; it changes the excitability of neurons in the network, can shift molecular rhythms, and affects SCN synchrony. We measure which neurons are excited or inhibited by GABA across the day and find GABA-excited neurons are synchronized by—and GABA-inhibited neurons repelled from—this tonic GABA signal, which modulates the synchrony in the SCN provided by other signaling molecules. Our mathematical model also provides an important tool for circadian research, and a model computational system for the many multiscale projects currently studying brain function. PMID:26130805

  10. Distinct Roles of Cytoskeletal Components in Immunological Synapse Formation and Directed Secretion

    PubMed Central

    Ueda, Hironori; Zhou, Jie; Xie, Jianming

    2015-01-01

    A hallmark of CD4+ T cell activation and immunological synapse (IS) formation is the migration of the microtubule organization center and associated organelles toward the APCs. In this study, we found that when murine CD4+ T cells were treated with a microtubule-destabilizing agent (vinblastine) after the formation of IS, the microtubule organization center dispersed and all of the major cellular organelles moved away from the IS. Cytokines were no longer directed toward the synapse but were randomly secreted in quantities similar to those seen in synaptic secretion. However, if the actin cytoskeleton was disrupted at the same time with cytochalasin D, the organelles did not shift away from the IS. These findings suggest that there is a complex interplay between the microtubules and actin cytoskeleton, where microtubules are important for directing particular cytokines into the synapse, but they are not involved in the amount of cytokines that are produced for at least 1 h after IS formation. In addition, we found that they play a critical role in mobilizing organelles to reorient toward the synapse during T cell activation and in stabilizing organelles against the force that is generated through actin polymerization so that they move toward the APCs. These findings show that there is a complex interplay between these major cytoskeletal components during synapse formation and maintenance. PMID:26392461

  11. Liver X Receptors (LXRs) Alpha and Beta Play Distinct Roles in the Mouse Epididymis.

    PubMed

    Whitfield, Marjorie; Ouvrier, Aurélia; Cadet, Rémi; Damon-Soubeyrand, Christelle; Guiton, Rachel; Janny, Laurent; Kocer, Ayhan; Marceau, Geoffroy; Pons-Rejraji, Hanae; Trousson, Amalia; Drevet, Joël R; Saez, Fabrice

    2016-03-01

    After its production in the testis, a spermatozoon has to undergo posttesticular maturation steps to become fully motile and fertile. The first step is epididymal maturation, during which immature spermatozoa are transformed into biochemically mature cells ready to proceed to the next step, capacitation, a physiological process occurring in the female genital tract. The biochemical transformations include modification of sperm lipid composition during epididymal transit, with significant changes in fatty acids, phospholipids, and sterols between the caput and the cauda epididymal spermatozoa. Although quantitative aspects of these changes are well documented for several mammalian species, molecular mechanisms governing these steps are poorly understood. Transgenic male mice invalidated for the two liver X receptors (LXRalpha and LXRbeta, nuclear oxysterol receptors regulating cholesterol and lipid metabolism) become sterile when aging, showing an epididymal phenotype. We used single-knockout-model mice to characterize the role of each LXR isoform during sperm maturation in the epididymis. We show here that although a certain redundancy exists in the functions of the two LXR isoforms, some physiological processes are more under the influence of only one of them. In both cases, aging males showed slight subfertility, associated with dyslipidemia, emphasizing the importance of lipid metabolism in relation with male fertility.

  12. Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions

    PubMed Central

    Goard, Michael J; Pho, Gerald N; Woodson, Jonathan; Sur, Mriganka

    2016-01-01

    Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution. DOI: http://dx.doi.org/10.7554/eLife.13764.001 PMID:27490481

  13. Distinct Roles of Bulbar Muscarinic and Nicotinic Receptors in Olfactory Discrimination Learning

    PubMed Central

    Devore, Sasha; de Almeida, Licurgo

    2014-01-01

    The olfactory bulb (OB) and piriform cortex receive dense cholinergic projections from the basal forebrain. Cholinergic modulation within the piriform cortex has long been proposed to serve important functions in olfactory learning and memory. We here investigate how olfactory discrimination learning is regulated by cholinergic modulation of the OB inputs to the piriform cortex. We examined rats' performance on a two-alternative choice odor discrimination task following local, bilateral blockade of cholinergic nicotinic and/or muscarinic receptors in the OB. Results demonstrate that acquisition, but not recall, of novel discrimination problems is impaired following blockade of OB cholinergic receptors, although the relative contribution of muscarinic and nicotinic receptors depends on task difficulty. Blocking muscarinic receptors impairs learning for nearly all odor sets, whereas blocking nicotinic receptors only affects performance for perceptually similar odors. This pattern of behavioral effects is consistent with predictions from a model of cholinergic modulation in the OB and piriform cortex (de Almeida et al., 2013). Model simulations suggest that muscarinic and nicotinic receptors may serve complementary roles in regulating coherence and sparseness of the OB network output, which in turn differentially regulate the strength and overlap in cortical odor representations. Overall, our results suggest that muscarinic receptor blockade results in a bona fide learning impairment that may arise because cortical neurons are activated less often. Behavioral impairment following nicotinic receptor blockade may not be due to the inability of the cortex to learn, but rather arises because the cortex is unable to resolve highly overlapping input patterns. PMID:25143606

  14. Distinct Behaviour of Sorafenib in Experimental Cachexia-Inducing Tumours: The Role of STAT3

    PubMed Central

    Busquets, Sílvia; López-Soriano, Francisco J.; Argilés, Josep M.

    2014-01-01

    The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC). The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways. PMID:25436606

  15. The distinctive roles of five different ARC genes in the chloroplast division process in Arabidopsis.

    PubMed

    Marrison, J L; Rutherford, S M; Robertson, E J; Lister, C; Dean, C; Leech, R M

    1999-06-01

    ARC (accumulation and replication of chloroplasts) genes control different aspects of the chloroplast division process in higher plants. In order to establish the hierarchy of the ARC genes in the chloroplast division process and to provide evidence for their specific roles, double mutants were constructed between arc11, arc6, arc5, arc3 and arc1 in all combinations and phenotypically analysed. arc11 is a new nuclear recessive mutant with 29 chloroplasts compared with 120 in wild type. All the phenotypes of the double mutants are unambiguous. ARC1 down-regulates proplastid division but is on a separate pathway from ARC3, ARC5, ARC6 and ARC11. ARC6 initiates both proplastid and chloroplast division. ARC3 controls the rate of chloroplast expansion and ARC11 the central positioning of the final division plane in chloroplast division. ARC5 facilitates separation of the two daughter chloroplasts. ARC5 maps to chromosome 3 and ARC11 and ARC6 map approximately 60 cM apart on chromosome 5.

  16. Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions.

    PubMed

    Goard, Michael J; Pho, Gerald N; Woodson, Jonathan; Sur, Mriganka

    2016-01-01

    Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution. PMID:27490481

  17. Distinct role of hydration water in protein misfolding and aggregation revealed by fluctuating thermodynamics analysis.

    PubMed

    Chong, Song-Ho; Ham, Sihyun

    2015-04-21

    decrease in solvation free energy, harnessing the monomer solvation free energy earned during the misfolding. The second step, where a compact dimer structure is formed, is driven by direct protein-protein interactions, but again it is accompanied by an increase in solvation free energy. The increased solvation free energy of the dimer will function as the driving force to recruit another Aβ protein in the approach stage of subsequent oligomerizations. The fluctuating thermodynamics analysis of the misfolding and dimerization of the Aβ protein indicates that the interaction of the protein with surrounding water plays a critical role in protein aggregation. Such a water-centric perspective is further corroborated by demonstrating that, for a large number of Aβ mutants and mutants of other protein systems, the change in the experimental aggregation propensity upon mutation has a significant correlation with the protein solvation free energy change. We also find striking discrimination between the positively and negatively charged residues on the protein surface by surrounding water molecules, which is shown to play a crucial role in determining the protein aggregation propensity. We argue that the protein total charge dictates such striking behavior of the surrounding water molecules. Our results provide new insights for understanding and predicting the protein aggregation propensity, thereby offering novel design principles for producing aggregation-resistant proteins for biotherapeutics.

  18. ATR and MKP1 play distinct roles in response to UV-B stress in Arabidopsis.

    PubMed

    González Besteiro, Marina A; Ulm, Roman

    2013-03-01

    Ultraviolet-B (UV-B) stress activates MAP kinases (MAPKs) MPK3 and MPK6 in Arabidopsis. MAPK activity must be tightly controlled in order to ensure an appropriate cellular outcome. MAPK phosphatases (MKPs) effectively control MAPKs by dephosphorylation of phosphothreonine and phosphotyrosine in their activation loops. Arabidopsis MKP1 is an important regulator of MPK3 and MPK6, and mkp1 knockout mutants are hypersensitive to UV-B stress, which is associated with reduced inactivation of MPK3 and MPK6. Here, we demonstrate that MPK3 and MPK6 are hyperactivated in response to UV-B in plants that are deficient in photorepair, suggesting that UV-damaged DNA is a trigger of MAPK signaling. This is not due to a block in replication, as, in contrast to atr, the mkp1 mutant is not hypersensitive to the replication-inhibiting drug hydroxyurea, hydroxyurea does not activate MPK3 and MPK6, and atr is not impaired in MPK3 and MPK6 activation in response to UV-B. We further show that mkp1 leaves and roots are UV-B hypersensitive, whereas atr is mainly affected at the root level. Tolerance to UV-B stress has been previously associated with stem cell removal and CYCB1;1 accumulation. Although UV-B-induced stem cell death and CYCB1;1 expression are not altered in mkp1 roots, CYCB1;1 expression is reduced in mkp1 leaves. We conclude that the MKP1 and ATR pathways operate in parallel, with primary roles for ATR in roots and MKP1 in leaves.

  19. Common and Distinct Roles of Juvenile Hormone Signaling Genes in Metamorphosis of Holometabolous and Hemimetabolous Insects

    PubMed Central

    Jindra, Marek

    2011-01-01

    Insect larvae metamorphose to winged and reproductive adults either directly (hemimetaboly) or through an intermediary pupal stage (holometaboly). In either case juvenile hormone (JH) prevents metamorphosis until a larva has attained an appropriate phase of development. In holometabolous insects, JH acts through its putative receptor Methoprene-tolerant (Met) to regulate Krüppel-homolog 1 (Kr-h1) and Broad-Complex (BR-C) genes. While Met and Kr-h1 prevent precocious metamorphosis in pre-final larval instars, BR-C specifies the pupal stage. How JH signaling operates in hemimetabolous insects is poorly understood. Here, we compare the function of Met, Kr-h1 and BR-C genes in the two types of insects. Using systemic RNAi in the hemimetabolous true bug, Pyrrhocoris apterus, we show that Met conveys the JH signal to prevent premature metamorphosis by maintaining high expression of Kr-h1. Knockdown of either Met or Kr-h1 (but not of BR-C) in penultimate-instar Pyrrhocoris larvae causes precocious development of adult color pattern, wings and genitalia. A natural fall of Kr-h1 expression in the last larval instar normally permits adult development, and treatment with an exogenous JH mimic methoprene at this time requires both Met and Kr-h1 to block the adult program and induce an extra larval instar. Met and Kr-h1 therefore serve as JH-dependent repressors of deleterious precocious metamorphic changes in both hemimetabolous and holometabolous juveniles, whereas BR-C has been recruited for a new role in specifying the holometabolous pupa. These results show that despite considerable evolutionary distance, insects with diverse developmental strategies employ a common-core JH signaling pathway to commit to adult morphogenesis. PMID:22174880

  20. Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles.

    PubMed

    Ang, Swee Kim; Zhang, Mengqi; Lodi, Tiziana; Lu, Hui

    2014-06-01

    Erv1 (essential for respiration and viability 1), is an essential component of the MIA (mitochondrial import and assembly) pathway, playing an important role in the oxidative folding of mitochondrial intermembrane space proteins. In the MIA pathway, Mia40, a thiol oxidoreductase with a CPC motif at its active site, oxidizes newly imported substrate proteins. Erv1 a FAD-dependent thiol oxidase, in turn reoxidizes Mia40 via its N-terminal Cys30-Cys33 shuttle disulfide. However, it is unclear how the two shuttle cysteine residues of Erv1 relay electrons from the Mia40 CPC motif to the Erv1 active-site Cys130-Cys133 disulfide. In the present study, using yeast genetic approaches we showed that both shuttle cysteine residues of Erv1 are required for cell growth. In organelle and in vitro studies confirmed that both shuttle cysteine residues were indeed required for import of MIA pathway substrates and Erv1 enzyme function to oxidize Mia40. Furthermore, our results revealed that the two shuttle cysteine residues of Erv1 are functionally distinct. Although Cys33 is essential for forming the intermediate disulfide Cys33-Cys130' and transferring electrons to the redox active-site directly, Cys30 plays two important roles: (i) dominantly interacts and receives electrons from the Mia40 CPC motif; and (ii) resolves the Erv1 Cys33-Cys130 intermediate disulfide. Taken together, we conclude that both shuttle cysteine residues are required for Erv1 function, and play complementary, but distinct, roles to ensure rapid turnover of active Erv1.

  1. Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles.

    PubMed

    Ang, Swee Kim; Zhang, Mengqi; Lodi, Tiziana; Lu, Hui

    2014-06-01

    Erv1 (essential for respiration and viability 1), is an essential component of the MIA (mitochondrial import and assembly) pathway, playing an important role in the oxidative folding of mitochondrial intermembrane space proteins. In the MIA pathway, Mia40, a thiol oxidoreductase with a CPC motif at its active site, oxidizes newly imported substrate proteins. Erv1 a FAD-dependent thiol oxidase, in turn reoxidizes Mia40 via its N-terminal Cys30-Cys33 shuttle disulfide. However, it is unclear how the two shuttle cysteine residues of Erv1 relay electrons from the Mia40 CPC motif to the Erv1 active-site Cys130-Cys133 disulfide. In the present study, using yeast genetic approaches we showed that both shuttle cysteine residues of Erv1 are required for cell growth. In organelle and in vitro studies confirmed that both shuttle cysteine residues were indeed required for import of MIA pathway substrates and Erv1 enzyme function to oxidize Mia40. Furthermore, our results revealed that the two shuttle cysteine residues of Erv1 are functionally distinct. Although Cys33 is essential for forming the intermediate disulfide Cys33-Cys130' and transferring electrons to the redox active-site directly, Cys30 plays two important roles: (i) dominantly interacts and receives electrons from the Mia40 CPC motif; and (ii) resolves the Erv1 Cys33-Cys130 intermediate disulfide. Taken together, we conclude that both shuttle cysteine residues are required for Erv1 function, and play complementary, but distinct, roles to ensure rapid turnover of active Erv1. PMID:24625320

  2. Distinct roles of the intraparietal sulcus and temporoparietal junction in attentional capture from distractor features: An individual differences approach.

    PubMed

    Painter, David R; Dux, Paul E; Mattingley, Jason B

    2015-07-01

    circuits underlying target and distractor capture, as well as distinct roles for the IPS and TPJ.

  3. Distinct roles of the intraparietal sulcus and temporoparietal junction in attentional capture from distractor features: An individual differences approach.

    PubMed

    Painter, David R; Dux, Paul E; Mattingley, Jason B

    2015-07-01

    circuits underlying target and distractor capture, as well as distinct roles for the IPS and TPJ. PMID:25724234

  4. Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity.

    PubMed

    Centonze, Diego; Grande, Cristina; Saulle, Emilia; Martin, Ana B; Gubellini, Paolo; Pavón, Nancy; Pisani, Antonio; Bernardi, Giorgio; Moratalla, Rosario; Calabresi, Paolo

    2003-09-17

    Stimulation of dopamine (DA) receptors in the striatum is essential for voluntary motor activity and for the generation of plasticity at corticostriatal synapses. In the present study, mice lacking DA D1 receptors have been used to investigate the involvement of the D1-like class (D1 and D5) of DA receptors in locomotion and corticostriatal long-term depression (LTD) and long-term potentiation (LTP). Our results suggest that D1 and D5 receptors exert distinct actions on both activity-dependent synaptic plasticity and spontaneous motor activity. Accordingly, the ablation of D1 receptors disrupted corticostriatal LTP, whereas pharmacological blockade of D5 receptors prevented LTD. On the other side, genetic ablation of D1 receptors increased locomotor activity, whereas the D1/D5 receptor antagonist SCH 23390 decreased motor activity in both control mice and mice lacking D1 receptors. Endogenous DA stimulated D1 and D5 receptors in distinct subtypes of striatal neurons to induce, respectively, LTP and LTD. In control mice, in fact, LTP was blocked by inhibiting the D1-protein kinase A pathway in the recorded spiny neuron, whereas the striatal nitric oxide-producing interneuron was presumably the neuronal subtype stimulated by D5 receptors during the induction phase of LTD. Understanding the role of DA receptors in striatal function is essential to gain insights into the neural bases of critical brain functions and of dramatic pathological conditions such as Parkinson's disease, schizophrenia, and drug addiction.

  5. Architectural proteins CTCF and cohesin have distinct roles in modulating the higher order structure and expression of the CFTR locus.

    PubMed

    Gosalia, Nehal; Neems, Daniel; Kerschner, Jenny L; Kosak, Steven T; Harris, Ann

    2014-09-01

    Higher order chromatin structures across the genome are maintained in part by the architectural proteins CCCTC binding factor (CTCF) and the cohesin complex, which co-localize at many sites across the genome. Here, we examine the role of these proteins in mediating chromatin structure at the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encompasses nearly 200 kb flanked by CTCF-binding enhancer-blocking insulator elements and is regulated by cell-type-specific intronic enhancers, which loop to the promoter in the active locus. SiRNA-mediated depletion of CTCF or the cohesin component, RAD21, showed that these two factors have distinct roles in regulating the higher order organization of CFTR. CTCF mediates the interactions between CTCF/cohesin binding sites, some of which have enhancer-blocking insulator activity. Cohesin shares this tethering role, but in addition stabilizes interactions between the promoter and cis-acting intronic elements including enhancers, which are also dependent on the forkhead box A1/A2 (FOXA1/A2) transcription factors (TFs). Disruption of the three-dimensional structure of the CFTR gene by depletion of CTCF or RAD21 increases gene expression, which is accompanied by alterations in histone modifications and TF occupancy across the locus, and causes internalization of the gene from the nuclear periphery. PMID:25081205

  6. Spatially distinct roles of class Ia PI3K isoforms in the development and maintenance of PTEN hamartoma tumor syndrome

    PubMed Central

    Wang, Qi; Von, Thanh; Bronson, Roderick; Ruan, Minzi; Mu, Wenxia; Huang, Alan; Maira, Sauveur-Michel; Zhao, Jean J.

    2013-01-01

    PTEN hamartoma tumor syndrome (PHTS) comprises a collection of genetic disorders associated with germline mutations in the tumor suppressor gene PTEN. Therapeutic options and preventative measures for PHTS are limited. Using both genetically engineered mouse models and pharmacological PI3K isoform-selective inhibitors, we found that the roles of PI3K isoforms are spatially distinct in the skin: While p110α is responsible for the sustained survival of suprabasal cells of the epidermis in the absence of PTEN, p110β is important for the hyperproliferation of basal cells in PHTS. Furthermore, we identified a differential expression pattern of p110α and p110β in basal and suprabasal keratinocytes as well as differential PI3K regulation by upstream signals in the basal and suprabasal compartments of the epidermis, providing a potential molecular mechanism underlying the specific roles of PI3K isoforms in the epidermis. Finally, we demonstrate that combined inhibition of both PI3K isoforms prevents the development of PHTS and also reverses skin hamartomas that have reached advanced stages in mice. Together, these results not only advance our overall understanding of the diverse roles of PI3K isoforms, but also have the potential for meaningful translation via the clinical utilization of PI3K inhibitors for both prevention and therapy in PHTS patients. PMID:23873941

  7. Structural Characterization of Minor Ampullate Spidroin Domains and Their Distinct Roles in Fibroin Solubility and Fiber Formation

    PubMed Central

    Gao, Zhenwei; Lin, Zhi; Huang, Weidong; Lai, Chong Cheong; Fan, Jing-song; Yang, Daiwen

    2013-01-01

    Spider silk is protein fibers with extraordinary mechanical properties. Up to now, it is still poorly understood how silk proteins are kept in a soluble form before spinning into fibers and how the protein molecules are aligned orderly to form fibers. Minor ampullate spidroin is one of the seven types of silk proteins, which consists of four types of domains: N-terminal domain, C-terminal domain (CTD), repetitive domain (RP) and linker domain (LK). Here we report the tertiary structure of CTD and secondary structures of RP and LK in aqueous solution, and their roles in protein stability, solubility and fiber formation. The stability and solubility of individual domains are dramatically different and can be explained by their distinct structures. For the tri-domain miniature fibroin, RP-LK-CTDMi, the three domains have no or weak interactions with one another at low protein concentrations (<1 mg/ml). The CTD in RP-LK-CTDMi is very stable and soluble, but it cannot stabilize the entire protein against chemical and thermal denaturation while it can keep the entire tri-domain in a highly water-soluble state. In the presence of shear force, protein aggregation is greatly accelerated and the aggregation rate is determined by the stability of folded domains and solubility of the disordered domains. Only the tri-domain RP-LK-CTDMi could form silk-like fibers, indicating that all three domains play distinct roles in fiber formation: LK as a nucleation site for assembly of protein molecules, RP for assistance of the assembly and CTD for regulating alignment of the assembled molecules. PMID:23418525

  8. Four Isoforms of Arabidopsis 4-Coumarate:CoA Ligase Have Overlapping yet Distinct Roles in Phenylpropanoid Metabolism1[OPEN

    PubMed Central

    Kim, Jeong Im

    2015-01-01

    The biosynthesis of lignin, flavonoids, and hydroxycinnamoyl esters share the first three enzymatic steps of the phenylpropanoid pathway. The last shared step is catalyzed by 4-coumarate:CoA ligase (4CL), which generates p-coumaroyl CoA and caffeoyl CoA from their respective acids. Four isoforms of 4CL have been identified in Arabidopsis (Arabidopsis thaliana). Phylogenetic analysis reveals that 4CL1, 4CL2, and 4CL4 are more closely related to each other than to 4CL3, suggesting that the two groups may serve different biological functions. Promoter-GUS analysis shows that 4CL1 and 4CL2 are expressed in lignifying cells. In contrast, 4CL3 is expressed in a broad range of cell types, and 4CL3 has acquired a distinct role in flavonoid metabolism. Sinapoylmalate, the major hydroxycinnamoyl ester found in Arabidopsis, is greatly reduced in the 4cl1 4cl3 mutant, showing that 4CL1 and 4CL3 function redundantly in its biosynthesis. 4CL1 accounts for the majority of the total 4CL activity, and loss of 4CL1 leads to reduction in lignin content but no growth defect. The 4cl1 4cl2 and 4cl1 4cl2 4cl3 mutants are both dwarf but do not have further reduced lignin than the 4cl1 mutant, indicating that either 4CL1 or 4CL2 is required for normal plant growth. Although 4CL4 has a limited expression profile, it does make a modest contribution to lignin biosynthesis. Together, these data show that the four isoforms of 4CL in Arabidopsis have overlapping yet distinct roles in phenylpropanoid metabolism. PMID:26491147

  9. pRB and E2F4 play distinct cell-intrinsic roles in fetal erythropoiesis.

    PubMed

    Zhang, Jing; Lee, Eunice Y; Liu, Yangang; Berman, Seth D; Lodish, Harvey F; Lees, Jacqueline A

    2010-01-15

    The retinoblastoma tumor suppressor protein pRB functions, at least in part, by directly binding to and modulating the activity of the E2F transcription factors. Previous studies have shown that both E2F4 and pRB play important roles in fetal erythropoiesis. Given that these two proteins interact directly we investigated the overlap of E2F4 and pRB function in this process by analyzing E2f4(-/-), conditional Rb knockout (Rb(1lox/1lox)), and compound E2f4(-/-);Rb(1lox/1lox) embryos. At E15.5 E2f4(-/-) and Rb(1lox/1lox) fetal erythroid cells display distinct abnormalities in their differentiation profiles. When cultured in vitro, both E2f4(-/-) and Rb(1lox/1lox) erythroid cells show defects in cell cycle progression. Surprisingly, analysis of cell cycle profiling suggests that E2F4 and pRB control cell cycle exit through different mechanisms. Moreover, only pRB, but not E2F4, promotes cell survival in erythroid cells. We observed an additive rather than a synergistic impact upon the erythroid defects in the compound E2f4(-/-);Rb(1lox/1lox) embryos. We further found that fetal liver macrophage development is largely normal regardless of genotype. Taken together, our results show that E2F4 and pRB play independent cell-intrinsic roles in fetal erythropoiesis.

  10. Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection.

    PubMed

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

    2004-12-01

    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) alpha in this infection is unknown. Here we report that C57BL/6 mice deficient in TNF (B6.TNF(-/-)) or LT alpha (B6.LT alpha(-/-)) 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 LT alpha and TNF regulated the migration of leukocytes into the sinusoidal area of the infected liver, their roles were distinct. LT alpha was essential for migration of leukocytes from periportal areas, an event consistent with LT alpha-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. LT alpha 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 LT alpha-deficient infected mice. These results demonstrate that both LT alpha and TNF are required for control of L. donovani infection in noncompensatory ways. PMID:15579454

  11. MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination.

    PubMed

    Bhattacharjee, Sonali; Osman, Fekret; Feeney, Laura; Lorenz, Alexander; Bryer, Claire; Whitby, Matthew C

    2013-09-11

    The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important functions in vertebrate cells. First, they are components of the constitutive centromere-associated network, aiding kinetochore assembly and function. Second, they work with the FANCM DNA translocase to promote DNA repair. However, it has been unclear whether there is crosstalk between these roles. We show that Mhf1 and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA repair/recombination and localizing to centromeres to promote chromosome segregation. Importantly, these functions are distinct, with the former being dependent on their interaction with the FANCM orthologue Fml1 and the latter not. Together with Fml1, they play a second role in aiding chromosome segregation by processing sister chromatid junctions. However, a failure of this activity does not manifest dramatically increased levels of chromosome missegregation due to the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions before the end of mitosis.

  12. Distinct Roles of Apolipoproteins A1 and E in the Modulation of High-Density Lipoprotein Composition and Function.

    PubMed

    Filou, Serafoula; Lhomme, Marie; Karavia, Eleni A; Kalogeropoulou, Christina; Theodoropoulos, Vassilis; Zvintzou, Evangelia; Sakellaropoulos, George C; Petropoulou, Peristera-Ioanna; Constantinou, Caterina; Kontush, Anatol; Kypreos, Kyriakos E

    2016-07-12

    In addition to high-density lipoprotein cholesterol (HDL-C) levels, HDL quality also appears to be very important for atheroprotection. Analysis of various clinical paradigms suggests that the lipid and apolipoprotein composition of HDL defines its size, shape, and functions and may determine its beneficial effects on human health. Previously, we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E (Apoe) is also capable of promoting the de novo biogenesis of HDL with the participation of ATP binding cassette A lipid transporter member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase (Lcat), in a manner independent of a functional Apoa1. Here, we performed a comparative analysis of the functions of these HDL subpopulations. Specifically, Apoe and Apoa1 double-deficient (Apoe(-/-) × Apoa1(-/-)) mice were infected with APOA1- or APOE3-expressing adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical and physicochemical methods. Western blot and lipidomic analyses indicated significant differences in the apolipoprotein and lipid composition of the two HDL species. Moreover APOE3-HDL presented a markedly reduced antioxidant potential and Abcg1-mediated cholesterol efflux capacity. Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production of TNFα in RAW264.7 cells, suggesting that the anti-inflammatory effects of APOA1 are dependent on APOE expression. Taken together, our data indicate that APOA1 and APOE3 recruit different apolipoproteins and lipids on the HDL particle, leading to structurally and functionally distinct HDL subpopulations. The distinct role of these two apolipoproteins in the modulation of HDL functionality may pave the way toward the development of novel pharmaceuticals that aim to improve HDL functionality. PMID:27332083

  13. Distinct roles for mammalian target of rapamycin complexes in the fibroblast response to transforming growth factor-beta.

    PubMed

    Rahimi, Rod A; Andrianifahanana, Mahefatiana; Wilkes, Mark C; Edens, Maryanne; Kottom, Theodore J; Blenis, John; Leof, Edward B

    2009-01-01

    Transforming growth factor-beta (TGF-beta) promotes a multitude of diverse biological processes, including growth arrest of epithelial cells and proliferation of fibroblasts. Although the TGF-beta signaling pathways that promote inhibition of epithelial cell growth are well characterized, less is known about the mechanisms mediating the positive response to this growth factor. Given that TGF-beta has been shown to promote fibrotic diseases and desmoplasia, identifying the fibroblast-specific TGF-beta signaling pathways is critical. Here, we investigate the role of mammalian target of rapamycin (mTOR), a known effector of phosphatidylinositol 3-kinase (PI3K) and promoter of cell growth, in the fibroblast response to TGF-beta. We show that TGF-beta activates mTOR complex 1 (mTORC1) in fibroblasts but not epithelial cells via a PI3K-Akt-TSC2-dependent pathway. Rapamycin, the pharmacologic inhibitor of mTOR, prevents TGF-beta-mediated anchorage-independent growth without affecting TGF-beta transcriptional responses or extracellular matrix protein induction. In addition to mTORC1, we also examined the role of mTORC2 in TGF-beta action. mTORC2 promotes TGF-beta-induced morphologic transformation and is required for TGF-beta-induced Akt S473 phosphorylation but not mTORC1 activation. Interestingly, both mTOR complexes are necessary for TGF-beta-mediated growth in soft agar. These results define distinct and overlapping roles for mTORC1 and mTORC2 in the fibroblast response to TGF-beta and suggest that inhibitors of mTOR signaling may be useful in treating fibrotic processes, such as desmoplasia. PMID:19117990

  14. Distinct Roles of the DmNav and DSC1 Channels in the Action of DDT and Pyrethroids

    PubMed Central

    Rinkevich, Frank D.; Du, Yuzhe; Tolinski, Josh; Ueda, Atsushi; Wu, Chun-Fang; Zhorov, Boris S.; Dong, Ke

    2015-01-01

    Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called DmNav), there is a sodium channel-like cation channel called DSC1 (Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNav (parats) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNav and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNav/DSC1 double mutant line by introducing a parats1 allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNav variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNav channel. Furthermore, we found that I265N-mediated pyrethroid resistance in parats1 mutant flies was almost completely abolished in parats1;DSC1−/− double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w1118A), and the parats1;DSC1−/− double mutant flies were even more resistant to DDT compared to the DSC1 knockout or parats1 mutant. Our findings revealed distinct roles of the DmNav and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance. PMID:25687544

  15. Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.

    PubMed

    Rinkevich, Frank D; Du, Yuzhe; Tolinski, Josh; Ueda, Atsushi; Wu, Chun-Fang; Zhorov, Boris S; Dong, Ke

    2015-03-01

    Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called DmNav), there is a sodium channel-like cation channel called DSC1 (Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNav (para(ts)) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNav and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNav/DSC1 double mutant line by introducing a para(ts1) allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNav variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNav channel. Furthermore, we found that I265N-mediated pyrethroid resistance in para(ts1) mutant flies was almost completely abolished in para(ts1);DSC1(-/-) double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w(1118A)), and the para(ts1);DSC1(-/-) double mutant flies were even more resistant to DDT compared to the DSC1 knockout or para(ts1) mutant. Our findings revealed distinct roles of the DmNav and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance. PMID:25687544

  16. Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.

    PubMed

    Rinkevich, Frank D; Du, Yuzhe; Tolinski, Josh; Ueda, Atsushi; Wu, Chun-Fang; Zhorov, Boris S; Dong, Ke

    2015-03-01

    Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called DmNav), there is a sodium channel-like cation channel called DSC1 (Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNav (para(ts)) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNav and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNav/DSC1 double mutant line by introducing a para(ts1) allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNav variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNav channel. Furthermore, we found that I265N-mediated pyrethroid resistance in para(ts1) mutant flies was almost completely abolished in para(ts1);DSC1(-/-) double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w(1118A)), and the para(ts1);DSC1(-/-) double mutant flies were even more resistant to DDT compared to the DSC1 knockout or para(ts1) mutant. Our findings revealed distinct roles of the DmNav and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance.

  17. The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics.

    PubMed

    Zhou, Zhen; Wang, Xiaohui; Liu, Hao-Yang; Zou, Xiaoqin; Li, Min; Hwang, Tzyh-Chang

    2006-10-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC (ATP binding cassette) transporter family, is a chloride channel whose activity is controlled by protein kinase-dependent phosphorylation. Opening and closing (gating) of the phosphorylated CFTR is coupled to ATP binding and hydrolysis at CFTR's two nucleotide binding domains (NBD1 and NBD2). Recent studies present evidence that the open channel conformation reflects a head-to-tail dimerization of CFTR's two NBDs as seen in the NBDs of other ABC transporters (Vergani et al., 2005). Whether these two ATP binding sites play an equivalent role in the dynamics of NBD dimerization, and thus in gating CFTR channels, remains unsettled. Based on the crystal structures of NBDs, sequence alignment, and homology modeling, we have identified two critical aromatic amino acids (W401 in NBD1 and Y1219 in NBD2) that coordinate the adenine ring of the bound ATP. Conversion of the W401 residue to glycine (W401G) has little effect on the sensitivity of the opening rate to [ATP], but the same mutation at the Y1219 residue dramatically lowers the apparent affinity for ATP by >50-fold, suggesting distinct roles of these two ATP binding sites in channel opening. The W401G mutation, however, shortens the open time constant. Energetic analysis of our data suggests that the free energy of ATP binding at NBD1, but not at NBD2, contributes significantly to the energetics of the open state. This kinetic and energetic asymmetry of CFTR's two NBDs suggests an asymmetric motion of the NBDs during channel gating. Opening of the channel is initiated by ATP binding at the NBD2 site, whereas separation of the NBD dimer at the NBD1 site constitutes the rate-limiting step in channel closing.

  18. Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation.

    PubMed

    Flajollet, Sébastien; Lefebvre, Bruno; Rachez, Christophe; Lefebvre, Philippe

    2006-07-21

    Retinoic acid receptors (RARs) are the molecular relays of retinoid action on transcription, cellular differentiation and apoptosis. Transcriptional activation of retinoid-regulated promoters requires the dismissal of corepressors and the recruitment of coactivators to promoter-bound RAR. RARs recruit in vitro a plethora of coactivators whose actual contribution to retinoid-induced transcription is poorly characterized in vivo. Embryonal carcinoma P19 cells, which are highly sensitive to retinoids, were depleted from archetypical coactivators by RNAi. SRC1-deficient P19 cells showed severely compromised retinoid-induced responses, in agreement with the supposed role of SRC1 as a RAR coactivator. Unexpectedly, Med1/TRAP220/DRIP205-depleted cells exhibited an exacerbated response to retinoids, both in terms transcriptional responses and of cellular differentiation. Med1 depletion affected TFIIH and cdk9 detection at the prototypical retinoid-regulated RARbeta2 promoter, and favored a higher RNA polymerase II detection in transcribed regions of the RARbeta2 gene. Furthermore, the nature of the ligand impacted strongly on the ability of RARs to interact with a given coactivator and to activate transcription in intact cells. Thus RAR accomplishes transcriptional activation as a function of the ligand structure, by recruiting regulatory complexes which control distinct molecular events at retinoid-regulated promoters.

  19. Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota.

    PubMed

    Carissimo, Guillaume; Pondeville, Emilie; McFarlane, Melanie; Dietrich, Isabelle; Mitri, Christian; Bischoff, Emmanuel; Antoniewski, Christophe; Bourgouin, Catherine; Failloux, Anna-Bella; Kohl, Alain; Vernick, Kenneth D

    2015-01-13

    Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. The risk associated with these viruses is increasing worldwide, including new emergence in Europe and the Americas. Anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o'nyong-nyong virus, whereas Aedes mosquitoes transmit many. Anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. Here, we determine the antiviral immune pathways of the Anopheles gambiae midgut, the initial site of viral infection after an infective blood meal. We compare them with the responses of the post-midgut systemic compartment, which is the site of the subsequent disseminated viral infection. Normal viral infection of the midgut requires bacterial flora and is inhibited by the activities of immune deficiency (Imd), JAK/STAT, and Leu-rich repeat immune factors. We show that the exogenous siRNA pathway, thought of as the canonical mosquito antiviral pathway, plays no detectable role in antiviral defense in the midgut but only protects later in the systemic compartment. These results alter the prevailing antiviral paradigm by describing distinct protective mechanisms in different body compartments and infection stages. Importantly, the presence of the midgut bacterial flora is required for full viral infectivity to Anopheles, in contrast to malaria infection, where the presence of the midgut bacterial flora is required for protection against infection. Thus, the enteric flora controls a reciprocal protection tradeoff in the vector for resistance to different human pathogens.

  20. The Distinct Role of the Amygdala, Superior Colliculus and Pulvinar in Processing of Central and Peripheral Snakes

    PubMed Central

    Almeida, Inês; Soares, Sandra C.; Castelo-Branco, Miguel

    2015-01-01

    pulvinar. Conclusion These results show that subcortical structures containing foveal representations such as the amygdala, pulvinar and superior colliculus play distinct roles in the central and peripheral processing of snake shapes. Our findings suggest multiple phylogenetic fingerprints in the responses of subcortical structures to fear-relevant stimuli. PMID:26075614

  1. Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota

    PubMed Central

    Carissimo, Guillaume; Pondeville, Emilie; McFarlane, Melanie; Dietrich, Isabelle; Mitri, Christian; Bischoff, Emmanuel; Antoniewski, Christophe; Bourgouin, Catherine; Failloux, Anna-Bella; Kohl, Alain; Vernick, Kenneth D.

    2015-01-01

    Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. The risk associated with these viruses is increasing worldwide, including new emergence in Europe and the Americas. Anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o’nyong-nyong virus, whereas Aedes mosquitoes transmit many. Anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. Here, we determine the antiviral immune pathways of the Anopheles gambiae midgut, the initial site of viral infection after an infective blood meal. We compare them with the responses of the post-midgut systemic compartment, which is the site of the subsequent disseminated viral infection. Normal viral infection of the midgut requires bacterial flora and is inhibited by the activities of immune deficiency (Imd), JAK/STAT, and Leu-rich repeat immune factors. We show that the exogenous siRNA pathway, thought of as the canonical mosquito antiviral pathway, plays no detectable role in antiviral defense in the midgut but only protects later in the systemic compartment. These results alter the prevailing antiviral paradigm by describing distinct protective mechanisms in different body compartments and infection stages. Importantly, the presence of the midgut bacterial flora is required for full viral infectivity to Anopheles, in contrast to malaria infection, where the presence of the midgut bacterial flora is required for protection against infection. Thus, the enteric flora controls a reciprocal protection tradeoff in the vector for resistance to different human pathogens. PMID:25548172

  2. Phosphatidylinositol 3-kinase and 4-kinase have distinct roles in intracellular trafficking of cellulose synthase complexes in Arabidopsis thaliana.

    PubMed

    Fujimoto, Masaru; Suda, Yasuyuki; Vernhettes, Samantha; Nakano, Akihiko; Ueda, Takashi

    2015-02-01

    The oriented deposition of cellulose microfibrils in the plant cell wall plays a crucial role in various plant functions such as cell growth, organ formation and defense responses. Cellulose is synthesized by cellulose synthase complexes (CSCs) embedded in the plasma membrane (PM), which comprise the cellulose synthases (CESAs). The abundance and localization of CSCs at the PM should be strictly controlled for precise regulation of cellulose deposition, which strongly depends on the membrane trafficking system. However, the mechanism of the intracellular transport of CSCs is still poorly understood. In this study, we explored requirements for phosphoinositides (PIs) in CESA trafficking by analyzing the effects of inhibitors of PI synthesis in Arabidopsis thaliana expressing green fluorescent protein-tagged CESA3 (GFP-CESA3). We found that a shift to a sucrose-free condition accelerated re-localization of PM-localized GFP-CESA3 into the periphery of the Golgi apparatus via the clathrin-enriched trans-Golgi network (TGN). Treatment with wortmannin (Wm), an inhibitor of phosphatidylinositol 3- (PI3K) and 4- (PI4K) kinases, and phenylarsine oxide (PAO), a more specific inhibitor for PI4K, inhibited internalization of GFP-CESA3 from the PM. In contrast, treatment with LY294002, which impairs the PI3K activity, did not exert such an inhibitory effect on the sequestration of GFP-CESA3, but caused a predominant accumulation of GFP-CESA3 at the ring-shaped periphery of the Golgi apparatus, resulting in the removal of GFP-CESA3 from the PM. These results indicate that PIs are essential elements for localization and intracellular transport of CESA3 and that PI4K and PI3K are required for distinct steps in secretory and/or endocytic trafficking of CESA3. PMID:25516570

  3. PET imaging reveals distinctive roles for different regional adipose tissue depots in systemic glucose metabolism in nonobese humans.

    PubMed

    Ng, Jason M; Azuma, Koichiro; Kelley, Carol; Pencek, Richard; Radikova, Zofia; Laymon, Charles; Price, Julie; Goodpaster, Bret H; Kelley, David E

    2012-11-01

    Excess amounts of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue (AT) are associated with insulin resistance, even in normal-weight subjects. In contrast, gluteal-femoral AT (GFAT) is hypothesized to offer protection against insulin resistance. Dynamic PET imaging studies were undertaken to examine the contributions of both metabolic activity and size (volume) of these depots in systemic glucose metabolism. Nonobese, healthy volunteers (n = 15) underwent dynamic PET imaging uptake of [¹⁸F]FDG at a steady-state (20 mU·m⁻²·min⁻¹) insulin infusion. PET images of tissue [¹⁸F]FDG activity were coregistered with MRI to derive K values for insulin-stimulated rates of fractional glucose uptake within tissue. Adipose tissue volume was calculated from DEXA and MRI. VAT had significantly higher rates of fractional glucose uptake per volume than SAT (P < 0.05) or GFAT (P < 0.01). K(GFAT) correlated positively (r = 0.67, P < 0.01) with systemic insulin sensitivity [glucose disappearance rate (R(d))] and negatively with insulin-suppressed FFA (r = -0.71, P < 0.01). SAT (r = -0.70, P < 0.01) and VAT mass (r = -0.55, P < 0.05) correlated negatively with R(d), but GFAT mass did not. We conclude that rates of fractional glucose uptake within GFAT and VAT are significantly and positively associated with systemic insulin sensitivity in nonobese subjects. Furthermore, whereas SAT and VAT amounts are confirmed to relate to systemic insulin resistance, GFAT amount is not associated with insulin resistance. These dynamic PET imaging studies indicate that both quantity and quality of specific AT depots have distinct roles in systemic insulin resistance and may help explain the metabolically obese but normal-weight phenotype. PMID:22967498

  4. Activation of resting T cells: distinct roles of intact accessory cells, phorbol myristate acetate and interleukin 1

    SciTech Connect

    Davis, L.; Lipsky, P.E.

    1986-03-05

    The accessory cell (AC) signals involved in the activation of resting guinea pig T lymphocytes stimulated with mitogen (PHA), or the calcium ionophore, ionomycin (Ion) were examined. Activation of T cells was assessed by cell cycle analysis after acridine orange staining and /sup 3/H-thymidine incorporation. PHA-stimulated T cells depleted of all AC were unable to respond in the presence of phorbol myristate acetate (PMA), and/or interleukin 1 (IL 1). With suboptimal numbers of AC, PMA greatly augmented the number of T cells activated by PHA to enter and progress through the cell cycle, but only when present during the first few hours of culture. By contrast, IL 1 had little effect on the number of cells entering the cell cycle, although it enhanced S phase entry of the activated cells. IL 1 augmented DNA synthesis when added initially or later in culture. In contrast to the effects noted with PHA, PMA promoted activation and DNA synthesis of the majority of Ion stimulated cells in the complete absence of AC. IL 1 alone could not support Ion induced T cell activation although it enhanced T cell DNA synthesis in cultures stimulated by PMA and Ion. These studies indicate that intact AC, IL 1 and PMA-like signals play distinct roles in the progression of T cells through the initial cell cycle. Stimulation by Ion requires only PMA whereas PHA responses require intact AC and can be amplified by PMA. The major effect of IL 1 is to promote S phase entry of activated T cells.

  5. Wnt/β-catenin signaling plays a distinct role in methyl gallate-mediated inhibition of adipogenesis.

    PubMed

    Jeon, Miso; Rahman, Naimur; Kim, Yong-Sik

    2016-10-01

    The canonical Wnt/β-catenin signaling not only features in many developmental processes but also recently emerged as an attractive negative regulator of differentiation of preadipocytes into adipocytes. Here, we show that β-catenin signaling plays a distinct role in methyl gallate (MG)-mediated inhibition of 3T3-L1 adipocytes differentiation. We found that the expression of β-catenin decreased after adipogenic hormonal induction, whereas incubation of the differentiating cells with a physiological concentration of MG during adipogenic hormonal induction significantly prevented β-catenin degradation by activating Wnt signaling components such as Wnt1, Wnt10b, Fzd1, Fzd2, Lrp5, Lrp6, Dvl1, and Dvl2. Mechanistic experiments revealed that MG treatment during early adipocytic differentiation specifically inhibited degradation of β-catenin caused by phosphorylation at serine-33. In addition, MG treatment led to phosphorylation of GSK3β, which is one of β-catenin-degrading enzymes. Consequently, MG treatment facilitated translocation of the stabilized β-catenin from the cytoplasm to nucleus, and activates its target genes cyclin D1 and c-Myc. Furthermore, MG-induced stabilization of β-catenin suppresses PPARγ expression. Moreover, pharmacological activation or inhibition of β-catenin signaling during adipocytes differentiation decreased and increased, respectively, the level of the key adipogenic marker, PPARγ, and of its downstream targets, aP2 and adiponectin while MG treatment effectively reversed their expression level. Collectively, our data suggest that MG is a novel pharmacological stimulator of canonical Wnt/β-catenin signaling, and therefore represents a promising therapeutic agent in obesity. PMID:27592552

  6. Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains

    PubMed Central

    Grego-Bessa, Joaquim; Hildebrand, Jeffrey; Anderson, Kathryn V.

    2015-01-01

    The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ∼24 h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. PMID:25742799

  7. IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct Roles in Epithelial Cell Mucin Production

    PubMed Central

    Zhen, Guohua; Park, Sung Woo; Nguyenvu, Louis T.; Rodriguez, Madeleine W.; Barbeau, Rebecca; Paquet, Agnes C.; Erle, David J.

    2007-01-01

    Overproduction of mucus is a central feature of asthma. The cytokine, IL-13, epidermal growth factor receptor (EGFR), and transcription factor, FOXA2, have each been implicated in mucus production, but the mechanistic relationships between these molecules are not yet well understood. To address this, we established a primary normal human bronchial epithelial cell culture system with IL-13–induced mucus production and gene transcript expression changes similar to those seen in vivo in mice. IL-13 did not stimulate release of the EGFR ligand, transforming growth factor (TGF)-α. However, there was constitutive release of TGF-α from normal human bronchial epithelial cells, and inhibition of TGF-α or EGFR reduced both constitutive and IL-13–induced mucin production. Microarray analysis revealed that IL-13 and the EGFR pathway appear to have almost completely independent effects on transcript expression. IL-13 induced a relatively small set of transcripts, including several novel transcripts that might play a role in pathogenesis of allergic airway disease. In contrast, EGFR activity had extensive effects, including altered expression of many transcripts associated with cell metabolism, survival, transcription, and differentiation. One of the few common effects of IL-13 and EGFR signaling was decreased expression of FOXA2, which is known to prevent mucus production. We conclude that the IL-13 and EGFR pathways make critical but quite distinct contributions to gene regulation in airway epithelial cells, and that both pathways affect expression of the key transcription factor, FOXA2, a known regulator of mucus production. PMID:16980555

  8. Recognition of β–Calcineurin by the Domains of Calmodulin: Thermodynamic and Structural Evidence for Distinct Roles

    PubMed Central

    O’Donnell, Susan E.; Yu, Liping; Fowler, Andrew; Shea, Madeline A.

    2010-01-01

    Calcineurin (CaN, PP2B, PPP3), a heterodimeric Ca2+-calmodulin-dependent Ser/Thr phosphatase, regulates swimming in Paramecia, stress responses in yeast, and T-cell activation and cardiac hypertrophy in humans. Calcium binding to CaNB (the regulatory subunit) triggers conformational change in CaNA (the catalytic subunit). Two isoforms of CaNA (α, β) are both abundant in brain and heart and activated by calcium-saturated calmodulin (CaM). The individual contribution of each domain of CaM to regulation of calcineurin is not known. Hydrodynamic analyses of (Ca2+)4-CaM1-148 bound to βCaNp, a peptide representing its CaM-binding domain, indicated a 1:1 stoichiometry. βCaNp binding to CaM increased the affinity of calcium for the N- and C-domains equally, thus preserving intrinsic domain differences, and the preference of calcium for sites III and IV. The equilibrium constants for individual calcium-saturated CaM domains dissociating from βCaNp were ~1 μM. A limiting Kd ≤ 1 nM was measured directly for full-length CaM, while thermodynamic linkage analysis indicated that it was approximately 1 pM. βCaNp binding to 15N-(Ca2+)4-CaM1-148 monitored by 15N/1HN HSQC NMR showed that association perturbed the N-domain of CaM more than its C-domain. NMR resonance assignments of CaM and βCaNp, and interpretation of intermolecular NOEs observed in the 13C-edited and 12C-14N-filtered 3D NOESY spectrum indicated anti-parallel binding. The sole aromatic residue (Phe) located near the βCaNp C-terminus was in close contact with several residues of the N-domain of CaM outside the hydrophobic cleft. These structural and thermodynamic properties would permit the domains of CaM to have distinct physiological roles in regulating activation of βCaN. PMID:21287611

  9. Distinct Functions of Neutrophil in Cancer and Its Regulation

    PubMed Central

    Granot, Zvi; Jablonska, Jadwiga

    2015-01-01

    Neutrophils are the most abundant of all white blood cells in the human circulation and are usually associated with inflammation and with fighting infections. In recent years the role immune cells play in cancer has been a matter of increasing interest. In this context the function of neutrophils is controversial as neutrophils were shown to possess both tumor promoting and tumor limiting properties. Here we provide an up-to-date review of the pro- and antitumor properties neutrophils possess as well as the environmental cues that regulate these distinct functions. PMID:26648665

  10. 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. PMID:22746214

  11. 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.

  12. The Distinct Roles of Sociometric and Perceived Popularity in Friendship: Implications for Adolescent Depressive Affect and Self-Esteem

    ERIC Educational Resources Information Center

    Litwack, Scott D.; Aikins, Julie Wargo; Cillessen, Antonius H. N.

    2012-01-01

    The primary goal of this study was to examine the similarities and distinctions between two types of popularity, sociometric and perceived, in their associations with friendship characteristics and how they in turn are related to depressive affect and self-esteem. Among 245 eighth graders, sociometric popularity was associated with a greater…

  13. 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...) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.33 Possession limit. No person shall...

  14. Exploring the effects of icon characteristics on user performance: the role of icon concreteness, complexity, and distinctiveness.

    PubMed

    McDougall, S J; de Bruijn, O; Curry, M B

    2000-12-01

    Because icons, signs, and symbols are now widely used to communicate information, it is essential for system designers to know what makes them easy to use and interpret. The authors report a series of studies that examine characteristics considered central to icon usability. After quantifying the properties of icon concreteness, complexity, and discriminability, the authors assessed each property's effects on user performance when user experience, task demands, and presentation context were systematically varied. Findings indicated that the effects of icon concreteness were primarily associated with the initial grasp of meaning, whereas complexity effects were found to persist longer and to be associated with search efficacy. The effects of icon distinctiveness were complex, but distinctiveness was enhanced by using both semantic and visual contrasts. The implications of these findings for interface design are discussed. PMID:11218339

  15. Members of the gibberellin receptor gene family GID1 (GIBBERELLIN INSENSITIVE DWARF1) play distinct roles during Lepidium sativum and Arabidopsis thaliana seed germination

    PubMed Central

    Voegele, Antje; Linkies, Ada; Müller, Kerstin; Leubner-Metzger, Gerhard

    2011-01-01

    Germination of endospermic seeds is partly regulated by the micropylar endosperm, which acts as constraint to radicle protrusion. Gibberellin (GA) signalling pathways control coat-dormancy release, endosperm weakening, and organ expansion during seed germination. Three GIBBERELLIN INSENSITIVE DWARF1 (GID1) GA receptors are known in Arabidopsis thaliana: GID1a, GID1b, and GID1c. Molecular phylogenetic analysis of angiosperm GID1s reveals that they cluster into two eudicot (GID1ac, GID1b) groups and one monocot group. Eudicots have at least one gene from each of the two groups, indicating that the different GID1 receptors fulfil distinct roles during plant development. A comparative Brassicaceae approach was used, in which gid1 mutant and whole-seed transcript analyses in Arabidopsis were combined with seed-tissue-specific analyses of its close relative Lepidium sativum (garden cress), for which three GID1 orthologues were cloned. GA signalling via the GID1ac receptors is required for Arabidopsis seed germination, GID1b cannot compensate for the impaired germination of the gid1agid1c mutant. Transcript expression patterns differed temporarily, spatially, and hormonally, with GID1b being distinct from GID1ac in both species. Endosperm weakening is mediated, at least in part, through GA-induced genes encoding cell-wall-modifying proteins. A suppression subtraction hybridization (SSH) cDNA library enriched for sequences that are highly expressed during early germination in the micropylar endosperm contained expansins and xyloglucan endo-transglycosylases/hydrolases (XTHs). Their transcript expression patterns in both species strongly suggest that they are regulated by distinct GID1-mediated GA signalling pathways. The GID1ac and GID1b pathways seem to fulfil distinct regulatory roles during Brassicaceae seed germination and seem to control their downstream targets distinctly. PMID:21778177

  16. Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections

    PubMed Central

    Balan, Murugabaskar; Tseng, Hsiang-Chi; McElrath, Constance; Smirnov, Sergey V.; Peng, Jianya; Yasukawa, Linda L.; Durbin, Russell K.; Durbin, Joan E.; Greenberg, Harry B.; Kotenko, Sergei V.

    2016-01-01

    Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets

  17. Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections.

    PubMed

    Lin, Jian-Da; Feng, Ningguo; Sen, Adrish; Balan, Murugabaskar; Tseng, Hsiang-Chi; McElrath, Constance; Smirnov, Sergey V; Peng, Jianya; Yasukawa, Linda L; Durbin, Russell K; Durbin, Joan E; Greenberg, Harry B; Kotenko, Sergei V

    2016-04-01

    Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets

  18. Distinct pharmacology of rat and human histamine H3 receptors: role of two amino acids in the third transmembrane domain

    PubMed Central

    Ligneau, X; Morisset, S; Tardivel-Lacombe, J; Gbahou, F; Ganellin, C R; Stark, H; Schunack, W; Schwartz, J -C; Arrang, J -M

    2000-01-01

    Starting from the sequence of the human histamine H3 receptor (hH3R) cDNA, we have cloned the corresponding rat cDNA. Whereas the two deduced proteins show 93.5% overall homology and differ only by five amino acid residues at the level of the transmembrane domains (TMs), some ligands displayed distinct affinities. Thioperamide and ciproxifan were about 10 fold more potent at the rat than at the human receptor, whereas FUB 349 displayed a reverse preference. Histamine, (R)α-methylhistamine, proxyfan or clobenpropit were nearly equipotent at H3 receptors of both species. The inverse discrimination patterns of ciproxifan and FUB 349 were partially changed by mutation of one amino acid (V122A), and fully abolished by mutation of two amino acids (A119T and V122A), in TM3 of the rH3R located in the vicinity of Asp114 purported to salt-link the ammonium group of histamine. Therefore, these two residues appear to be responsible for the distinct pharmacology of the H3R in the two species. PMID:11090094

  19. Are you upset? Distinct roles for orbitofrontal and lateral prefrontal cortex in detecting and distinguishing facial expressions of emotion.

    PubMed

    Tsuchida, Ami; Fellows, Lesley K

    2012-12-01

    Navigating our complex social world requires effective processing of subtle emotional signals, such as those conveyed by facial expressions. Failure to do so may underlie some of the disabling social-emotional deficits common in a range of neuropsychiatric and neurological conditions. Prefrontal cortex (PFC) has long been implicated in these processes, but the particular contributions of subregions within PFC remain unclear. We used a sensitive facial emotion rating task in patients with focal lesions to different regions within PFC to identify distinct contributions of 2 prefrontal regions to recognizing emotions from facial expressions. A combination of region-of-interest and voxel-based lesion-symptom mapping established that damage to ventromedial PFC impaired the detection of subtle facial expressions of emotion. Such patients had difficulty distinguishing emotional from neutral expressions. In contrast, patients with left ventrolateral PFC were able to detect the presence of emotional signals but had difficulty discriminating between specific emotions. These effects were regionally specific: Dorsomedial prefrontal damage had no effect on either aspect of emotion recognition. These findings suggest that separable processes relying critically on distinct regions within PFC responsible, on the one hand, for detecting emotional signals from facial expressions and, on the other, for correctly classifying such signals. PMID:22223852

  20. Cellular dynamics of regeneration reveals role of two distinct Pax7 stem cell populations in larval zebrafish muscle repair

    PubMed Central

    Pipalia, Tapan G.; Koth, Jana; Roy, Shukolpa D.; Hammond, Christina L.; Kawakami, Koichi

    2016-01-01

    ABSTRACT Heterogeneity of stem cells or their niches is likely to influence tissue regeneration. Here we reveal stem/precursor cell diversity during wound repair in larval zebrafish somitic body muscle using time-lapse 3D confocal microscopy on reporter lines. Skeletal muscle with incision wounds rapidly regenerates both slow and fast muscle fibre types. A swift immune response is followed by an increase in cells at the wound site, many of which express the muscle stem cell marker Pax7. Pax7+ cells proliferate and then undergo terminal differentiation involving Myogenin accumulation and subsequent loss of Pax7 followed by elongation and fusion to repair fast muscle fibres. Analysis of pax7a and pax7b transgenic reporter fish reveals that cells expressing each of the duplicated pax7 genes are distinctly localised in uninjured larvae. Cells marked by pax7a only or by both pax7a and pax7b enter the wound rapidly and contribute to muscle wound repair, but each behaves differently. Low numbers of pax7a-only cells form nascent fibres. Time-lapse microscopy revealed that the more numerous pax7b-marked cells frequently fuse to pre-existing fibres, contributing more strongly than pax7a-only cells to repair of damaged fibres. pax7b-marked cells are more often present in rows of aligned cells that are observed to fuse into a single fibre, but more rarely contribute to nascent regenerated fibres. Ablation of a substantial portion of nitroreductase-expressing pax7b cells with metronidazole prior to wounding triggered rapid pax7a-only cell accumulation, but this neither inhibited nor augmented pax7a-only cell-derived myogenesis and thus altered the cellular repair dynamics during wound healing. Moreover, pax7a-only cells did not regenerate pax7b cells, suggesting a lineage distinction. We propose a modified founder cell and fusion-competent cell model in which pax7a-only cells initiate fibre formation and pax7b cells contribute to fibre growth. This newly discovered cellular

  1. The two different isoforms of the RSC chromatin remodeling complex play distinct roles in DNA damage responses.

    PubMed

    Chambers, Anna L; Brownlee, Peter M; Durley, Samuel C; Beacham, Tracey; Kent, Nicholas A; Downs, Jessica A

    2012-01-01

    The RSC chromatin remodeling complex has been implicated in contributing to DNA double-strand break (DSB) repair in a number of studies. Both survival and levels of H2A phosphorylation in response to damage are reduced in the absence of RSC. Importantly, there is evidence for two isoforms of this complex, defined by the presence of either Rsc1 or Rsc2. Here, we investigated whether the two isoforms of RSC provide distinct contributions to DNA damage responses. First, we established that the two isoforms of RSC differ in the presence of Rsc1 or Rsc2 but otherwise have the same subunit composition. We found that both rsc1 and rsc2 mutant strains have intact DNA damage-induced checkpoint activity and transcriptional induction. In addition, both strains show reduced non-homologous end joining activity and have a similar spectrum of DSB repair junctions, suggesting perhaps that the two complexes provide the same functions. However, the hypersensitivity of a rsc1 strain cannot be complemented with an extra copy of RSC2, and likewise, the hypersensitivity of the rsc2 strain remains unchanged when an additional copy of RSC1 is present, indicating that the two proteins are unable to functionally compensate for one another in DNA damage responses. Rsc1, but not Rsc2, is required for nucleosome sliding flanking a DNA DSB. Interestingly, while swapping the domains from Rsc1 into the Rsc2 protein does not compromise hypersensitivity to DNA damage suggesting they are functionally interchangeable, the BAH domain from Rsc1 confers upon Rsc2 the ability to remodel chromatin at a DNA break. These data demonstrate that, despite the similarity between Rsc1 and Rsc2, the two different isoforms of RSC provide distinct functions in DNA damage responses, and that at least part of the functional specificity is dictated by the BAH domains.

  2. Male homosexuality and spirit possession in Brazil.

    PubMed

    Fry, P

    1985-01-01

    This paper examines the relationship between male homosexuality and the Afro-Brazilian possession cults in Belém do Parà. After a discussion of the literature follows a description of the cults' beliefs, rites and social organization. Male sex roles are then discussed and the two categories, bicha and man, analyzed. It is noted that there is no term which is equivalent to the western category of "homosexual" in this taxonomic system. After putting forward folk explanations for the presence of many bichas in the cults, an analysis is put forward of the social rewards available to bichas within these cults, and the structural relationship between homosexuality and these regions in terms of their congruent marginality vis-à-vis "normal society." PMID:4093598

  3. Transnational Geographies of Academic Distinction: The Role of Social Capital in the Recognition and Evaluation of "Overseas" Credentials

    ERIC Educational Resources Information Center

    Waters, Johanna L.

    2009-01-01

    This paper examines the role of specific and place-based social capital in the recognition and evaluation of international credentials. Whilst research on labour market segmentation has contributed towards an understanding of the spatial variability of the value of human capital, very little attention has been paid to the ways in which the…

  4. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Atlantic Herring Fishery § 648.204 Possession restrictions. (a) A vessel must be issued and possess a valid limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring from any herring management area in the EEZ, provided that the area has not been closed due to...

  5. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Atlantic Herring Fishery § 648.204 Possession restrictions. (a) A vessel must be issued and possess a valid limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring from any herring management area in the EEZ, provided that the area has not been closed due to...

  6. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Atlantic Herring Fishery § 648.204 Possession restrictions. (a) A vessel must be issued and possess a valid limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring from any herring management area in the EEZ, provided that the area has not been closed due to...

  7. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Atlantic Herring Fishery § 648.204 Possession restrictions. (a) A vessel must be issued and possess a valid limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring from any herring management area in the EEZ, provided that the area has not been closed due to...

  8. 50 CFR 648.125 - Possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... moratorium permit are subject to this possession limit. The owner, operator, and crew of a charter or party... a charter boat. This possession limit may be adjusted pursuant to the procedures in § 648.120. (b.... Compliance with the daily possession limit will be determined by dividing the number of scup on board by...

  9. Histone H3 K79 methylation states play distinct roles in UV-induced sister chromatid exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae

    PubMed Central

    Rossodivita, Alyssa A.; Boudoures, Anna L.; Mecoli, Jonathan P.; Steenkiste, Elizabeth M.; Karl, Andrea L.; Vines, Eudora M.; Cole, Arron M.; Ansbro, Megan R.; Thompson, Jeffrey S.

    2014-01-01

    Histone post-translational modifications have been shown to contribute to DNA damage repair. Prior studies have suggested that specific H3K79 methylation states play distinct roles in the response to UV-induced DNA damage. To evaluate these observations, we examined the effect of altered H3K79 methylation patterns on UV-induced G1/S checkpoint response and sister chromatid exchange (SCE). We found that the di- and trimethylated states both contribute to activation of the G1/S checkpoint to varying degrees, depending on the synchronization method, although methylation is not required for checkpoint in response to high levels of UV damage. In contrast, UV-induced SCE is largely a product of the trimethylated state, which influences the usage of gene conversion versus popout mechanisms. Regulation of H3K79 methylation by H2BK123 ubiquitylation is important for both checkpoint function and SCE. H3K79 methylation is not required for the repair of double-stranded breaks caused by transient HO endonuclease expression, but does play a modest role in survival from continuous exposure. The overall results provide evidence for the participation of H3K79 methylation in UV-induced recombination repair and checkpoint activation, and further indicate that the di- and trimethylation states play distinct roles in these DNA damage response pathways. PMID:24748660

  10. Distinct role of Arabidopsis mitochondrial P-type pentatricopeptide repeat protein-modulating editing protein, PPME, in nad1 RNA editing

    PubMed Central

    Leu, Kuan-Chieh; Hsieh, Ming-Hsiun; Wang, Huei-Jing; Hsieh, Hsu-Liang

    2016-01-01

    ABSTRACT The mitochondrion is an important power generator in most eukaryotic cells. To preserve its function, many essential nuclear-encoded factors play specific roles in mitochondrial RNA metabolic processes, including RNA editing. RNA editing consists of post-transcriptional deamination, which alters specific nucleotides in transcripts to mediate gene expression. In plant cells, many pentatricopeptide repeat proteins (PPRs) participate in diverse organellar RNA metabolic processes, but only PLS-type PPRs are involved in RNA editing. Here, we report a P-type PPR protein from Arabidopsis thaliana, P-type PPR-Modulating Editing (PPME), which has a distinct role in mitochondrial nad1 RNA editing via RNA binding activity. In the homozygous ppme mutant, cytosine (C)-to-uracil (U) conversions at both the nad1-898 and 937 sites were abolished, disrupting Arg300-to-Trp300 and Pro313-to-Ser313 amino acid changes in the mitochondrial NAD1 protein. NAD1 is a critical component of mitochondrial respiration complex I; its activity is severely reduced in the homozygous ppme mutant, resulting in significantly altered growth and development. Both abolished RNA editing and defective complex I activity were completely rescued by CaMV 35S promoter- and PPME native promoter-driven PPME genomic fragments tagged with GFP in a homozygous ppme background. Our experimental results demonstrate a distinct role of a P-type PPR protein, PPME, in RNA editing in plant organelles. PMID:27149614

  11. Distinct sensitivities to phosphate deprivation suggest that RGF peptides play disparate roles in Arabidopsis thaliana root development.

    PubMed

    Cederholm, Heidi M; Benfey, Philip N

    2015-08-01

    Growing agricultural demands in the face of impending inorganic phosphate (Pi) shortages underscore a need for a better understanding of plant development under conditions of Pi deprivation. Pi is an essential nutrient that is a major component of fertilizer. Plants have evolved strategies to improve the acquisition of this nutrient by altering root development under shortage conditions. We show that signaling peptides thought to act redundantly in Arabidopsis thaliana development have distinct functions in response to Pi deprivation. Using microscopy and confocal imaging, roots were analyzed for growth rate and cellular composition. Using expression microarrays, genes influencing development in response to phosphate deprivation were identified. ROOT GROWTH FACTOR1 (RGF1) and RGF2 influenced different aspects of root development under conditions of Pi deprivation. We found that RGF2 influenced the longitudinal growth rate in the primary root in response to Pi deprivation, whereas RGF1 affected circumferential cell number in the root meristem. These data suggest that the mechanisms controlling adaptive development can depend on disparate functions of genes thought to act redundantly, thus elucidating new functions for important developmental regulators.

  12. Vacuolar Nicotianamine Has Critical and Distinct Roles under Iron Deficiency and for Zinc Sequestration in Arabidopsis[C][W

    PubMed Central

    Haydon, Michael J.; Kawachi, Miki; Wirtz, Markus; Hillmer, Stefan; Hell, Rüdiger; Krämer, Ute

    2012-01-01

    The essential micronutrients Fe and Zn often limit plant growth but are toxic in excess. Arabidopsis thaliana ZINC-INDUCED FACILITATOR1 (ZIF1) is a vacuolar membrane major facilitator superfamily protein required for basal Zn tolerance. Here, we show that overexpression of ZIF1 enhances the partitioning into vacuoles of the low molecular mass metal chelator nicotianamine and leads to pronounced nicotianamine accumulation in roots, accompanied by vacuolar buildup of Zn. Heterologous ZIF1 protein localizes to vacuolar membranes and enhances nicotianamine contents of yeast cells engineered to synthesize nicotianamine, without complementing a Zn-hypersensitive mutant that additionally lacks vacuolar membrane Zn2+/H+ antiport activity. Retention in roots of Zn, but not of Fe, is enhanced in ZIF1 overexpressors at the expense of the shoots. Furthermore, these lines exhibit impaired intercellular Fe movement in leaves and constitutive Fe deficiency symptoms, thus phenocopying nicotianamine biosynthesis mutants. Hence, perturbing the subcellular distribution of the chelator nicotianamine has profound, yet distinct, effects on Zn and Fe with respect to their subcellular and interorgan partitioning. The zif1 mutant is also hypersensitive to Fe deficiency, even in media lacking added Zn. Therefore, accurate levels of ZIF1 expression are critical for both Zn and Fe homeostasis. This will help to advance the biofortification of crops. PMID:22374397

  13. Pivotal and distinct role for Plasmodium actin capping protein alpha during blood infection of the malaria parasite.

    PubMed

    Ganter, Markus; Rizopoulos, Zaira; Schüler, Herwig; Matuschewski, Kai

    2015-04-01

    Accurate regulation of microfilament dynamics is central to cell growth, motility and response to environmental stimuli. Stabilizing and depolymerizing proteins control the steady-state levels of filamentous (F-) actin. Capping protein (CP) binds to free barbed ends, thereby arresting microfilament growth and restraining elongation to remaining free barbed ends. In all CPs characterized to date, alpha and beta subunits form the active heterodimer. Here, we show in a eukaryotic parasitic cell that the two CP subunits can be functionally separated. Unlike the beta subunit, the CP alpha subunit of the apicomplexan parasite Plasmodium is refractory to targeted gene deletion during blood infection in the mammalian host. Combinatorial complementation of Plasmodium berghei CP genes with the orthologs from Plasmodium falciparum verified distinct activities of CP alpha and CP alpha/beta during parasite life cycle progression. Recombinant Plasmodium CP alpha could be produced in Escherichia coli in the absence of the beta subunit and the protein displayed F-actin capping activity. Thus, the functional separation of two CP subunits in a parasitic eukaryotic cell and the F-actin capping activity of CP alpha expand the repertoire of microfilament regulatory mechanisms assigned to CPs.

  14. Critical but Distinct Roles for the Pleckstrin Homology and Cysteine-Rich Domains as Positive Modulators of Vav2 Signaling and Transformation

    PubMed Central

    Booden, Michelle A.; Campbell, Sharon L.; Der, Channing J.

    2002-01-01

    Vav2, like all Dbl family proteins, possesses tandem Dbl homology (DH) and pleckstrin homology (PH) domains and functions as a guanine nucleotide exchange factor for Rho family GTPases. Whereas the PH domain is a critical positive regulator of DH domain function for a majority of Dbl family proteins, the PH domains of the related Vav and Vav3 proteins are dispensable for DH domain activity. Instead, Vav proteins contain a cysteine-rich domain (CRD) critical for DH domain function. We evaluated the contribution of the PH domain and the CRD to Vav2 guanine nucleotide exchange, signaling, and transforming activity. Unexpectedly, we found that mutations of the PH domain impaired Vav2 signaling, transforming activity, and membrane association. However, these mutations do not influence exchange activity on Rac and only slightly affect exchange on RhoA and Cdc42. We also found that the CRD was critical for the exchange activity in vitro and contributed to Vav2 membrane localization. Finally, we found that phosphoinositol 3-kinase activation synergistically enhanced Vav2 transforming and signaling activity by stimulating exchange activity but not membrane association. In conclusion, the PH domain and CRD are mechanistically distinct, positive modulators of Vav2 DH domain function in vivo. PMID:11909943

  15. Drp2 and Periaxin form Cajal Bands with Dystroglycan but have Distinct Roles in Schwann Cell Growth

    PubMed Central

    Sherman, Diane L.; Wu, Lai Man N.; Grove, Matthew; Gillespie, C. Stewart; Brophy, Peter J.

    2012-01-01

    Cajal bands are cytoplasmic channels flanked by appositions where the abaxonal surface of Schwann cell myelin apposes and adheres to the overlying plasma membrane. These appositions contain a dystroglycan complex that includes periaxin and dystrophin-related protein 2 (Drp2). Loss of periaxin disrupts appositions and Cajal bands in Schwann cells and causes a severe demyelinating neuropathy in mouse and man. Here we have investigated the role of mouse Drp2 in apposition assembly and Cajal band function and compared it to periaxin. We show that Periaxin and Drp2 are not only both required to form appositions, but they must also interact. Periaxin-Drp2 interaction is also required for Drp2 phosphorylation but phosphorylation is not required for the assembly of appositions. Drp2 loss causes corresponding increases in Dystrophin family members, utrophin and dystrophin Dp116 though dystroglycan remains unchanged. We also show that all dystroglycan complexes in Schwann cells utilise the uncleaved form of β-dystroglycan. Drp2-null Schwann cells have disrupted appositions and Cajal bands, and they undergoe focal hypermyelination and concomitant demyelination. Nevertheless, they do not have the short internodal lengths and associated reduced nerve conduction velocity seen in the absence of periaxin, showing that periaxin regulates Schwann cell elongation independent of its role in the dystroglycan complex. We conclude that the primary role of the dystroglycan complex in appositions is to stabilize and limit the radial growth of myelin. PMID:22764250

  16. IRE1/bZIP60-Mediated Unfolded Protein Response Plays Distinct Roles in Plant Immunity and Abiotic Stress Responses

    PubMed Central

    Blanco, Francisca; Boatwright, Jon Lucas; Moreno, Ignacio; Jordan, Melissa R.; Chen, Yani; Brandizzi, Federica; Dong, Xinnian

    2012-01-01

    Endoplasmic reticulum (ER)-mediated protein secretion and quality control have been shown to play an important role in immune responses in both animals and plants. In mammals, the ER membrane-located IRE1 kinase/endoribonuclease, a key regulator of unfolded protein response (UPR), is required for plasma cell development to accommodate massive secretion of immunoglobulins. Plant cells can secrete the so-called pathogenesis-related (PR) proteins with antimicrobial activities upon pathogen challenge. However, whether IRE1 plays any role in plant immunity is not known. Arabidopsis thaliana has two copies of IRE1, IRE1a and IRE1b. Here, we show that both IRE1a and IRE1b are transcriptionally induced during chemically-induced ER stress, bacterial pathogen infection and treatment with the immune signal salicylic acid (SA). However, we found that IRE1a plays a predominant role in the secretion of PR proteins upon SA treatment. Consequently, the ire1a mutant plants show enhanced susceptibility to a bacterial pathogen and are deficient in establishing systemic acquired resistance (SAR), whereas ire1b is unaffected in these responses. We further demonstrate that the immune deficiency in ire1a is due to a defect in SA- and pathogen-triggered, IRE1-mediated cytoplasmic splicing of the bZIP60 mRNA, which encodes a transcription factor involved in the expression of UPR-responsive genes. Consistently, IRE1a is preferentially required for bZIP60 splicing upon pathogen infection, while IRE1b plays a major role in bZIP60 processing upon Tunicamycin (Tm)-induced stress. We also show that SA-dependent induction of UPR-responsive genes is altered in the bzip60 mutant resulting in a moderate susceptibility to a bacterial pathogen. These results indicate that the IRE1/bZIP60 branch of UPR is a part of the plant response to pathogens for which the two Arabidopsis IRE1 isoforms play only partially overlapping roles and that IRE1 has both bZIP60-dependent and bZIP60-independent functions in

  17. Male-specific Fruitless isoforms have different regulatory roles conferred by distinct zinc finger DNA binding domains

    PubMed Central

    2013-01-01

    Background Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (FruM). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. Results By over-expressing individual FruM isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three FruM isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of FruM isoforms, including many annotated with neuronal functions. By determining the binding sites of individual FruM isoforms using SELEX we demonstrate that the distinct zinc finger domain of each FruM isoforms confers different DNA binding specificities. A genome-wide search for these binding site sequences finds that the gene sets identified as induced by over-expression of FruM isoforms in males are enriched for genes that contain the binding sites. An analysis of the chromosomal distribution of genes downstream of FruM shows that those that are induced and repressed in males are highly enriched and depleted on the X chromosome, respectively. Conclusions This study elucidates the different regulatory and DNA binding activities of three FruM isoforms on a genome-wide scale and identifies genes regulated by these isoforms. These results add to our understanding of sex chromosome biology and further support the hypothesis that in some cell-types genes with male-biased expression are enriched on the X chromosome. PMID:24074028

  18. Two alternatively spliced isoforms of the Arabidopsis SR45 protein have distinct roles during normal plant development.

    PubMed

    Zhang, Xiao-Ning; Mount, Stephen M

    2009-07-01

    The serine-arginine-rich (SR) proteins constitute a conserved family of pre-mRNA splicing factors. In Arabidopsis (Arabidopsis thaliana), they are encoded by 19 genes, most of which are themselves alternatively spliced. In the case of SR45, the use of alternative 3' splice sites 21 nucleotides apart generates two alternatively spliced isoforms. Isoform 1 (SR45.1) has an insertion relative to isoform 2 (SR45.2) that replaces a single arginine with eight amino acids (TSPQRKTG). The biological implications of SR45 alternative splicing have been unclear. A previously described loss-of-function mutant affecting both isoforms, sr45-1, shows several developmental defects, including defects in petal development and root growth. We found that the SR45 promoter is highly active in regions with actively growing and dividing cells. We also tested the ability of each SR45 isoform to complement the sr45-1 mutant by overexpression of isoform-specific green fluorescent protein (GFP) fusion proteins. As expected, transgenic plants overexpressing either isoform displayed both nuclear speckles and GFP fluorescence throughout the nucleoplasm. We found that SR45.1-GFP complements the flower petal phenotype, but not the root growth phenotype. Conversely, SR45.2-GFP complements root growth but not floral morphology. Mutation of a predicted phosphorylation site within the alternatively spliced segment, SR45.1-S219A-GFP, does not affect complementation. However, a double mutation affecting both serine-219 and the adjacent threonine-218 (SR45.1-T218A + S219A-GFP) behaves like isoform 2, complementing the root but not the floral phenotype. In conclusion, our study provides evidence that the two alternatively spliced isoforms of SR45 have distinct biological functions. PMID:19403727

  19. Distinct role of spatial frequency in dissociative reading of ideograms and phonograms: an fMRI study.

    PubMed

    Horie, Shizuka; Yamasaki, Takao; Okamoto, Tsuyoshi; Kan, Shigeyuki; Ogata, Katsuya; Miyauchi, Satoru; Tobimatsu, Shozo

    2012-11-01

    It has been proposed that distinct neural circuits are activated by reading Japanese ideograms (Kanji) and phonograms (Kana). By measuring high-density event-related potentials, we recently reported that spatial frequency (SF) information is responsible for the dissociation between Kanji and Kana reading. In particular, we found close links between Kana and low SF (LSF) information and between Kanji and high SF (HSF) information. However, it remains unclear which brain regions contribute to this dissociation. To determine this, we performed functional magnetic resonance imaging while presenting unfiltered or spatially filtered Kanji and Kana word stimuli to healthy native Japanese subjects. Fourier analysis revealed that Kanji and Kana stimuli were characterized by HSF and LSF information, respectively. When presented with either type of unfiltered stimulus (Kanji or Kana), the bilateral inferior temporal (IT, BA 37) regions were activated compared to the resting condition. Kana but not Kanji reading also activated the bilateral inferior parietal lobules (IPL, BA 40). When we compared Kanji and Kana reading directly, the left IT region was significantly activated by Kanji reading, while significant activation of the left IPL was observed during Kana reading. In response to filtered HSF stimuli, the Kanji reading minus Kana reading comparison revealed significant activation of the left IT region but not the left IPL. Conversely, significant activation of the left IPL but not the left IT region occurred in the Kana reading minus Kanji reading comparison for filtered LSF stimuli. These results suggest that Kanji and Kana engage a relatively overlapping network, within which the left IT is more involved in Kanji processing, while the left IPL contributes more to Kana processing. The preferential engagements of these brain regions could reflect the close links between Kana and LSF information, and between Kanji and HSF information. Therefore, this study provides further

  20. VEGF and thrombin induce MKP-1 through distinct signaling pathways: role for MKP-1 in endothelial cell migration.

    PubMed

    Kinney, Corttrell M; Chandrasekharan, Unni M; Mavrakis, Lori; DiCorleto, Paul E

    2008-01-01

    We have previously reported that MAPK phosphatase-1 (MKP-1/CL100) is a thrombin-responsive gene in endothelial cells (ECs). We now show that VEGF is another efficacious activator of MKP-1 expression in human umbilical vein ECs. VEGF-A and VEGF-E maximally induced MKP-1 expression in ECs; however, the other VEGF subtypes had no effect. Using specific neutralizing antibodies, we determined that VEGF induced MKP-1 specifically through VEGF receptor 2 (VEGFR-2), leading to the downstream activation of JNK. The VEGF-A(165) isoform stimulated MKP-1 expression, whereas the VEGF-A(162) isoform induced the gene to a lesser extent, and the VEGF-A(121) isoform had no effect. Furthermore, specific blocking antibodies against neuropilins, VEGFR-2 coreceptors, blocked MKP-1 induction. A Src kinase inhibitor (PP1) completely blocked both VEGF- and thrombin-induced MKP-1 expression. A dominant negative approach revealed that Src kinase was required for VEGF-induced MKP-1 expression, whereas Fyn kinase was critical for thrombin-induced MKP-1 expression. Moreover, VEGF-induced MKP-1 expression required JNK, whereas ERK was critical for thrombin-induced MKP-1 expression. In ECs treated with short interfering (si)RNA targeting MKP-1, JNK, ERK, and p38 phosphorylation were prolonged following VEGF stimulation. An ex vivo aortic angiogenesis assay revealed a reduction in VEGF- and thrombin-induced sprout outgrowth in segments from MKP-1-null mice versus wild-type controls. MKP-1 siRNA also significantly reduced VEGF-induced EC migration using a transwell assay system. Overall, these results demonstrate distinct MAPK signaling pathways for thrombin versus VEGF induction of MKP-1 in ECs and point to the importance of MKP-1 induction in VEGF-stimulated EC migration. PMID:18003751

  1. Conditional Deletion of Fgfr1 in the Proximal and Distal Tubule Identifies Distinct Roles in Phosphate and Calcium Transport

    PubMed Central

    Han, Xiaobin; Yang, Jiancheng; Li, Linqiang; Huang, Jinsong; King, Gwendalyn; Quarles, L. Darryl

    2016-01-01

    A postnatal role of fibroblast growth factor receptor-1 (FGFR1) in the kidney is suggested by its binding to α-Klotho to form an obligate receptor for the hormone fibroblast growth factor-23 (FGF-23). FGFR1 is expressed in both the proximal and distal renal tubular segments, but its tubular specific functions are unclear. In this study, we crossed Fgfr1flox/flox mice with either gamma-glutamyltransferase-Cre (γGT-Cre) or kidney specific-Cre (Ksp-Cre) mice to selectively create proximal tubule (PT) and distal tubule (DT) Fgfr1 conditional knockout mice (designated Fgfr1PT-cKO and Fgfr1DT-cKO, respectively). Fgfr1PT-cKO mice exhibited an increase in sodium-dependent phosphate co-transporter expression, hyperphosphatemia, and refractoriness to the phosphaturic actions of FGF-23, consistent with a direct role of FGFR1 in mediating the proximal tubular phosphate responses to FGF-23. In contrast, Fgfr1DT-cKO mice unexpectedly developed hypercalciuria, secondary elevations of parathyroid hormone (PTH), hypophosphatemia and enhanced urinary phosphate excretion. Fgfr1PT-cKO mice also developed a curly tail/spina bifida-like skeletal phenotype, whereas Fgfr1DT-cKO mice developed renal tubular micro-calcifications and reductions in cortical bone thickness. Thus, FGFR1 has dual functions to directly regulate proximal and distal tubule phosphate and calcium reabsorption, indicating a physiological role of FGFR1 signaling in both phosphate and calcium homeostasis. PMID:26839958

  2. Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.

    PubMed

    Manduca, Antonia; Morena, Maria; Campolongo, Patrizia; Servadio, Michela; Palmery, Maura; Trabace, Luigia; Hill, Matthew N; Vanderschuren, Louk J M J; Cuomo, Vincenzo; Trezza, Viviana

    2015-08-01

    To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats. JZL195, administered at the dose of 0.01mg/kg, increased social play behavior, that is the most characteristic social activity displayed by adolescent rats, and increased social interaction in adult animals. At both ages, these behavioral effects were antagonized by the CB1 cannabinoid receptor antagonist SR141716A and were associated with increased brain levels of 2-AG, but not AEA. Conversely, at the dose of 1mg/kg, JZL195 decreased general social exploration in adolescent rats without affecting social play behavior, and induced anxiogenic-like effects in the elevated plus-maze test both in adolescent and adult animals. These effects, mediated by activation of CB1 cannabinoid receptors, were paralleled by simultaneous increase in AEA and 2-AG levels in adolescent rats, and by an increase of only 2-AG levels in adult animals. These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes.

  3. Transcription Factors Pcr1 and Atf1 Have Distinct Roles in Stress- and Sty1-Dependent Gene Regulation▿ †

    PubMed Central

    Sansó, Miriam; Gogol, Madelaine; Ayté, José; Seidel, Chris; Hidalgo, Elena

    2008-01-01

    The mitogen-activated protein kinase Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. Upon stress activation, Sty1 reversibly accumulates in the nucleus, where it stimulates gene expression via the Atf1 transcription factor. The Atf1 protein forms a heterodimer with Pcr1, but the specific role of this association is controversial. We have carried out a comparative analysis of strains lacking these proteins individually. We demonstrate that Atf1 and Pcr1 have similar but not identical roles in S. pombe, since cells lacking Pcr1 do not share all the phenotypes reported for Δatf1 cells. Northern blot and microarray analyses demonstrate that the responses to specific stresses of cells lacking either Pcr1 or Atf1 do not fully overlap, and even though most Atf1-dependent genes induced by osmotic stress are also Pcr1 dependent, a subset of genes require only the presence of Atf1 for their induction. Whereas binding of Atf1 to most stress-dependent genes requires the presence of Pcr1, we demonstrate here that Atf1 can bind to the Pcr1-independent promoters in a Δpcr1 strain in vivo. Furthermore, these analyses show that both proteins have a global repressive effect on stress-dependent and stress-independent genes. PMID:18375616

  4. Distinct roles of the Y1 and Y2 receptors on neuropeptide Y-induced sensitization to sedation.

    PubMed

    Naveilhan, P; Canals, J M; Arenas, E; Ernfors, P

    2001-09-01

    Intracranial injection of neuropeptide Y (NPY) increases the sensitivity to sodium pentobarbital and ketamin sedation and has similar properties as GABA agonists on sleep. Mice sensitive to sedation have increased levels of NPY in many brain regions and Y1(-/-) mice show a marked resistance to barbiturates. Here we characterized the role of the NPY Y receptors in anesthetic-induced sedation. We show that Y1 and Y2, but not Y5, receptors participate in the modulation of sedation. Administration of a Y1 agonist increased the sodium pentobarbital-induced sedation and Y1(-/-) mice were less sensitive to this anesthetic. However, Y2(-/-) mice display increased sensitivity, showing that Y2 modulates GABAergic induced sedation both pharmacologically and physiologically and has a functionally opposing role to the Y1 receptor. Analysis of Y1(-/-)/Y2(-/-) double mutant mice show that increased sensitivity by Y1 occurs independent of the Y2 receptor, while the decreased sensitivity mediated by Y2 depend on an intact Y1 receptor. In contrast to sodium pentobarbital, both Y1 and Y2 receptors increase the sensitivity in a collaborative fashion to NMDA antagonist-induced sedation. These data demonstrate the physiological and pharmacological impact of the Y1 and Y2 receptors on sedation.

  5. Transcription factors Pcr1 and Atf1 have distinct roles in stress- and Sty1-dependent gene regulation.

    PubMed

    Sansó, Miriam; Gogol, Madelaine; Ayté, José; Seidel, Chris; Hidalgo, Elena

    2008-05-01

    The mitogen-activated protein kinase Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. Upon stress activation, Sty1 reversibly accumulates in the nucleus, where it stimulates gene expression via the Atf1 transcription factor. The Atf1 protein forms a heterodimer with Pcr1, but the specific role of this association is controversial. We have carried out a comparative analysis of strains lacking these proteins individually. We demonstrate that Atf1 and Pcr1 have similar but not identical roles in S. pombe, since cells lacking Pcr1 do not share all the phenotypes reported for Deltaatf1 cells. Northern blot and microarray analyses demonstrate that the responses to specific stresses of cells lacking either Pcr1 or Atf1 do not fully overlap, and even though most Atf1-dependent genes induced by osmotic stress are also Pcr1 dependent, a subset of genes require only the presence of Atf1 for their induction. Whereas binding of Atf1 to most stress-dependent genes requires the presence of Pcr1, we demonstrate here that Atf1 can bind to the Pcr1-independent promoters in a Deltapcr1 strain in vivo. Furthermore, these analyses show that both proteins have a global repressive effect on stress-dependent and stress-independent genes. PMID:18375616

  6. Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination.

    PubMed

    Yousif, Ashraf S; Stanlie, Andre; Begum, Nasim A; Honjo, Tasuku

    2014-10-01

    Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair complex, is required for CSR. The role of UNG in CSR and SHM is extremely controversial. AID deficiency in mice abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR-specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote non-homologous end joining during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, can be attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end joining during CSR.

  7. Functional connectivity delineates distinct roles of the inferior frontal cortex and pre-supplementary motor area in stop signal inhibition

    PubMed Central

    Duann, Jeng-Ren; Ide, Jaime S.; Luo, Xi; Li, Chiang-shan Ray

    2009-01-01

    The neural basis of motor response inhibition has drawn considerable attention in recent imaging literature. Many studies have employed the go/no-go or stop signal task to examine the neural processes underlying motor response inhibition. In particular, showing greater activity during no-go (stop) as compared to go trials and during stop success as compared to stop error trials, the right inferior prefrontal cortex (IFC) has been suggested by numerous studies as the cortical area mediating response inhibition. Many of these same studies as well as others have also implicated the pre-supplementary motor area (preSMA) in this process, in accord with a function of the medial prefrontal cortex in goal-directed action. Here we employed connectivity analyses to delineate the roles of IFC and preSMA during stop signal inhibition. Specifically, we hypothesized that, as an integral part of the ventral attention system, the IFC responds to a stop signal and expedites the stop process in the preSMA, the primary site of motor response inhibition. This hypothesis predicted that preSMA and primary motor cortex would show functional interconnectivity via the basal ganglia circuitry to mediate response execution or inhibition, whereas the IFC would influence the basal ganglia circuitry via connectivity with preSMA. The results of Granger causality analyses in 57 participants confirmed this hypothesis. Furthermore, psychophysiological interaction showed that, as compared to stop errors, stop successes evoked greater effective connectivity between the IFC and preSMA, providing additional support for this hypothesis. These new findings provided evidence critically differentiating the roles of IFC and preSMA during stop signal inhibition and have important implications for our understanding of the component processes of inhibitory control. PMID:19675251

  8. Distinct roles of highly conserved charged residues at the MotA-FliG interface in bacterial flagellar motor rotation.

    PubMed

    Morimoto, Yusuke V; Nakamura, Shuichi; Hiraoka, Koichi D; Namba, Keiichi; Minamino, Tohru

    2013-02-01

    Electrostatic interactions between the stator protein MotA and the rotor protein FliG are important for bacterial flagellar motor rotation. Arg90 and Glu98 of MotA are required not only for torque generation but also for stator assembly around the rotor, but their actual roles remain unknown. Here we analyzed the roles of functionally important charged residues at the MotA-FliG interface in motor performance. About 75% of the motA(R90E) cells and 45% of the motA(E98K) cells showed no fluorescent spots of green fluorescent protein (GFP)-MotB, indicating reduced efficiency of stator assembly around the rotor. The FliG(D289K) and FliG(R281V) mutations, which restore the motility of the motA(R90E) and motA(E98K) mutants, respectively, showed reduced numbers and intensity of GFP-MotB spots as well. The FliG(D289K) mutation significantly recovered the localization of GFP-MotB to the motor in the motA(R90E) mutant, whereas the FliG(R281V) mutation did not recover the GFP-MotB localization in the motA(E98K) mutant. These results suggest that the MotA-Arg90-FliG-Asp289 interaction is critical for the proper positioning of the stators around the rotor, whereas the MotA-Glu98-FliG-Arg281 interaction is more important for torque generation. PMID:23161029

  9. Bone marrow ablation demonstrates that excess endogenous parathyroid hormone plays distinct roles in trabecular and cortical bone.

    PubMed

    Yan, Jun; Sun, Weiwei; Zhang, Jing; Goltzman, David; Miao, Dengshun

    2012-07-01

    Mice null for Cyp27b1, which encodes the 25-hydroxyvitamin D-1α-hydroxylase [1α(OH)ase(-/-) mice], lack 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and have hypocalcemia and high parathyroid hormone (PTH) secretion. Intermittent, exogenous PTH is anabolic for bone. To determine the effect of the chronic excess endogenous PTH on osteogenesis and bone turnover, bone marrow ablations (BMX) were performed in tibiae and femurs of 6-week-old 1α(OH)ase(-/-) mice and in wild-type (WT) controls. Newly formed bone tissue was analyzed at 1, 2, and 3 weeks after BMX. BMX did not alter the higher levels of PTH in 1α(OH)ase(-/-) mice. In the marrow cavity, trabecular volume, osteoblast number, alkaline phosphatase-positive areas, type I collagen-positive areas, bone formation-related genes, and protein expression levels all increased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. Osteoclast numbers and surface and ratio of RANKL/OPG-relative mRNA levels decreased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. In the cortex, alkaline phosphatase-positive osteoblasts and osteoclast numbers increased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. These results demonstrate that chronic excess endogenous PTH exerts an anabolic role in trabecular bone by stimulating osteogenic cells and reducing bone resorption, but plays a catabolic role in cortical bone by enhancing bone turnover with an increase in resorption. PMID:22640808

  10. The Not4 E3 Ligase and CCR4 Deadenylase Play Distinct Roles in Protein Quality Control

    PubMed Central

    Halter, David; Collart, Martine A.; Panasenko, Olesya O.

    2014-01-01

    Eukaryotic cells control their proteome by regulating protein production and protein clearance. Protein production is determined to a large extent by mRNA levels, whereas protein degradation depends mostly upon the proteasome. Dysfunction of the proteasome leads to the accumulation of non-functional proteins that can aggregate, be toxic for the cell, and, in extreme cases, lead to cell death. mRNA levels are controlled by their rates of synthesis and degradation. Recent evidence indicates that these rates have oppositely co-evolved to ensure appropriate mRNA levels. This opposite co-evolution has been correlated with the mutations in the Ccr4-Not complex. Consistently, the deadenylation enzymes responsible for the rate-limiting step in eukaryotic mRNA degradation, Caf1 and Ccr4, are subunits of the Ccr4-Not complex. Another subunit of this complex is a RING E3 ligase, Not4. It is essential for cellular protein solubility and has been proposed to be involved in co-translational quality control. An open question has been whether this role of Not4 resides strictly in the regulation of the deadenylation module of the Ccr4-Not complex. However, Not4 is important for proper assembly of the proteasome, and the Ccr4-Not complex may have multiple functional modules that participate in protein quality control in different ways. In this work we studied how the functions of the Caf1/Ccr4 and Not4 modules are connected. We concluded that Not4 plays a role in protein quality control independently of the Ccr4 deadenylase, and that it is involved in clearance of aberrant proteins at least in part via the proteasome. PMID:24465968

  11. Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus

    PubMed Central

    Renaud, Tom M.; Meloni, Alessandra; Casu, Carla; Crielaard, Bart J.; Bystrom, Laura M.; Greenberg-Kushnir, Noa; Sasu, Barbra J.; Cooke, Keegan S.; Rivella, Stefano

    2014-01-01

    Anemia of inflammation (AI) is commonly observed in chronic inflammatory states and may hinder patient recovery and survival. Induction of hepcidin, mediated by interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several translational studies have been directed at neutralizing hepcidin overexpression as a therapeutic strategy against AI. However, additional hepcidin-independent mechanisms contribute to AI, which are likely mediated by a direct effect of inflammatory cytokines on erythropoiesis. In this study, we used wild-type, hepcidin knockout (Hamp-KO) and interleukin 6 knockout (IL-6-KO) mice as models of AI. AI was induced with heat-killed Brucella abortus (BA). The distinct roles of iron metabolism and inflammation triggered by interleukin 6 and hepcidin were investigated. BA-treated wild-type mice showed increased expression of hepcidin and inflammatory cytokines, as well as transitory suppression of erythropoiesis and shortened red blood cell lifespan, all of which contributed to the severe anemia of these mice. In contrast, BA-treated Hamp-KO or IL-6-KO mice showed milder anemia and faster recovery compared with normal mice. Moreover, they exhibited different patterns in the development and resolution of anemia, supporting the notion that interleukin 6 and hepcidin play distinct roles in modulating erythropoiesis in AI. PMID:24357729

  12. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

    PubMed

    Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

    2016-01-01

    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment. PMID:27605249

  13. Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin.

    PubMed

    Letra-Vilela, Ricardo; Sánchez-Sánchez, Ana María; Rocha, Ana Maia; Martin, Vanesa; Branco-Santos, Joana; Puente-Moncada, Noelia; Santa-Marta, Mariana; Outeiro, Tiago Fleming; Antolín, Isaac; Rodriguez, Carmen; Herrera, Federico

    2016-10-15

    Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine. PMID:27402602

  14. Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

    PubMed

    Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

    2015-07-01

    The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation.

  15. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain

    PubMed Central

    Labuz, Dominika; Celik, Melih Ö.; Zimmer, Andreas; Machelska, Halina

    2016-01-01

    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment. PMID:27605249

  16. Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin.

    PubMed

    Letra-Vilela, Ricardo; Sánchez-Sánchez, Ana María; Rocha, Ana Maia; Martin, Vanesa; Branco-Santos, Joana; Puente-Moncada, Noelia; Santa-Marta, Mariana; Outeiro, Tiago Fleming; Antolín, Isaac; Rodriguez, Carmen; Herrera, Federico

    2016-10-15

    Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine.

  17. Two distinct domains of Flo8 activator mediates its role in transcriptional activation and the physical interaction with Mss11.

    PubMed

    Kim, Hye Young; Lee, Sung Bae; Kang, Hyen Sam; Oh, Goo Taeg; Kim, TaeSoo

    2014-06-27

    Flo8 is a transcriptional activator essential for the inducible expression of a set of target genes such as STA1, FLO11, and FLO1 encoding an extracellular glucoamylase and two cell surface proteins, respectively. However, the molecular mechanism of Flo8-mediated transcriptional activation remains largely elusive. By generating serial deletion constructs, we revealed here that a novel transcriptional activation domain on its extreme C-terminal region plays a crucial role in activating transcription. On the other hand, the N-terminal LisH motif of Flo8 appears to be required for its physical interaction with another transcriptional activator, Mss11, for their cooperative transcriptional regulation of the shared targets. Additionally, GST pull-down experiments uncovered that Flo8 and Mss11 can directly form either a heterodimer or a homodimer capable of binding to DNA, and we also showed that this formed complex of two activators interacts functionally and physically with the Swi/Snf complex. Collectively, our findings provide valuable clues for understanding the molecular mechanism of Flo8-mediated transcriptional control of multiple targets. PMID:24813990

  18. Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer

    PubMed Central

    Walker, Sarah R.; Xiang, Michael; Frank, David A.

    2013-01-01

    The transcription factors STAT3 and STAT5 play important roles in the regulation of mammary gland function during pregnancy, lactation, and involution. Given that STAT3 and STAT5 regulate genes involved in proliferation and survival, it is not surprising that inappropriate activation of STAT3 and STAT5 occurs commonly in breast cancer. Although these proteins are structurally similar, they have divergent and opposing effects on gene expression and cellular phenotype. Notably, when STAT5 and STAT3 are activated simultaneously, STAT5 has a dominant effect, and leads to decreased proliferation and increased sensitivity to cell death. Similarly, in breast cancer, activation of both STAT5 and STAT3 is associated with longer patient survival than activation of STAT3 alone. Pharmacological inhibitors of STAT3 and STAT5 are being developed for cancer therapy, though understanding the activation state and functional interaction of STAT3 and STAT5 in a patient's tumor may be critical for the optimal use of this strategy. PMID:23531638

  19. Nitrate isotopes unveil distinct seasonal N-sources and the critical role of crop residues in groundwater contamination

    NASA Astrophysics Data System (ADS)

    Savard, Martine M.; Somers, George; Smirnoff, Anna; Paradis, Daniel; van Bochove, Eric; Liao, Shawna

    2010-02-01

    SummaryGlobally, fertilizers are identified as principle sources of nitrate in waters of intensely cultivated areas. Here this general concept is appraised on a seasonal basis over a two year period, under temperate climatic conditions. Water ( δ2H and δ18O) and nitrate ( δ15N and δ18O) isotopes in surface water and groundwater suggest that freshwater is acting as a transport vector conducting nitrate from agricultural soils to groundwater and ultimately to surface water. Measured nitrate isotopes of organic and inorganic fertilizers and of nitrate in groundwater are used to constrain a conceptual apportionment model quantifying the relative seasonal N contributions in an area of intense potato production. Source inputs differ strongly between the growing (summer and fall) and non-growing (winter and spring) periods. Chemical fertilizers and soil organic matter equally dominate and contribute to the growing period load, whereas soil organic matter dominates the non-growing period load, and accounts for over half of the overall annual nitrogen charge. These findings reveal the magnitude of nitrogen cycling by soil organic matter, and point to the benefits of controlling the timing of its nitrate release from this organic material. We conclude that strategies to attenuate contamination by nitrate in waters of temperate climate row-cropping regions must consider nitrogen cycling by soil organic matter, including the crucial role of crop residues throughout both the growing and non-growing seasons.

  20. Two distinct domains of Flo8 activator mediates its role in transcriptional activation and the physical interaction with Mss11.

    PubMed

    Kim, Hye Young; Lee, Sung Bae; Kang, Hyen Sam; Oh, Goo Taeg; Kim, TaeSoo

    2014-06-27

    Flo8 is a transcriptional activator essential for the inducible expression of a set of target genes such as STA1, FLO11, and FLO1 encoding an extracellular glucoamylase and two cell surface proteins, respectively. However, the molecular mechanism of Flo8-mediated transcriptional activation remains largely elusive. By generating serial deletion constructs, we revealed here that a novel transcriptional activation domain on its extreme C-terminal region plays a crucial role in activating transcription. On the other hand, the N-terminal LisH motif of Flo8 appears to be required for its physical interaction with another transcriptional activator, Mss11, for their cooperative transcriptional regulation of the shared targets. Additionally, GST pull-down experiments uncovered that Flo8 and Mss11 can directly form either a heterodimer or a homodimer capable of binding to DNA, and we also showed that this formed complex of two activators interacts functionally and physically with the Swi/Snf complex. Collectively, our findings provide valuable clues for understanding the molecular mechanism of Flo8-mediated transcriptional control of multiple targets.

  1. Secreted Phospholipases A2 Are Intestinal Stem Cell Niche Factors with Distinct Roles in Homeostasis, Inflammation, and Cancer.

    PubMed

    Schewe, Matthias; Franken, Patrick F; Sacchetti, Andrea; Schmitt, Mark; Joosten, Rosalie; Böttcher, René; van Royen, Martin E; Jeammet, Louise; Payré, Christine; Scott, Patricia M; Webb, Nancy R; Gelb, Michael; Cormier, Robert T; Lambeau, Gérard; Fodde, Riccardo

    2016-07-01

    The intestinal stem cell niche provides cues that actively maintain gut homeostasis. Dysregulation of these cues may compromise intestinal regeneration upon tissue insult and/or promote tumor growth. Here, we identify secreted phospholipases A2 (sPLA2s) as stem cell niche factors with context-dependent functions in the digestive tract. We show that group IIA sPLA2, a known genetic modifier of mouse intestinal tumorigenesis, is expressed by Paneth cells in the small intestine, while group X sPLA2 is expressed by Paneth/goblet-like cells in the colon. During homeostasis, group IIA/X sPLA2s inhibit Wnt signaling through intracellular activation of Yap1. However, upon inflammation they are secreted into the intestinal lumen, where they promote prostaglandin synthesis and Wnt signaling. Genetic ablation of both sPLA2s improves recovery from inflammation but increases colon cancer susceptibility due to release of their homeostatic Wnt-inhibitory role. This "trade-off" effect suggests sPLA2s have important functions as genetic modifiers of inflammation and colon cancer. PMID:27292189

  2. Distinct roles for the p53-like transcription factor XprG and autophagy genes in the response to starvation.

    PubMed

    Katz, Margaret E; Buckland, Rebecca; Hunter, Cameron C; Todd, Richard B

    2015-10-01

    Autophagy and autolysis are two cannibalistic pathways which allow filamentous fungi to obtain nutrients once environmental nutrient sources are exhausted. In Aspergillus nidulans, the effects of mutations in two key autophagy genes, atgA, the ATG1 ortholog, and atgH, the ATG8 ortholog, were compared with mutations in xprG, which encodes a transcriptional activator that plays a key role in autolysis. The anti-fungal drug rapamycin induces autophagy in a range of organisms. Mutations in atgA and atgH did not alter sensitivity to rapamycin, which inhibits growth and asexual spore production (conidiation), indicating that autophagy is not required for rapamycin sensitivity in A. nidulans. In contrast, inhibition of conidiation by rapamcyin was partially suppressed by the xprG1 gain-of-function mutation, indicating that XprG acts in the pathway(s) affected by rapamycin. It was anticipated that the absence of an intact autophagy pathway would accelerate the response to starvation. However, extracellular and intracellular protease production in response to carbon or nitrogen starvation was not increased in the atgAΔ and atgHΔ mutants, and the onset of autolysis was not accelerated. Compared to wild-type strains and the xprGΔ and xprG1 mutants, conidiation of the autophagy mutants was reduced in carbon- or nitrogen-limiting conditions but not during growth on nutrient-sufficient medium. Nuclear localization of the global nitrogen regulator AreA in response to nitrogen starvation was blocked in the xprG2 loss-of-function mutant, but not in the atgHΔ mutant. Conversely, the atgAΔ mutation but not the xprGΔ mutation prevented vacuolar accumulation of GFP-AtgH, a hallmark of autophagy. These results indicate that in A. nidulans there is little interaction between autophagy and autolysis and the two pathways are activated in parallel during starvation.

  3. Predominant Expression of Hybrid N-Glycans Has Distinct Cellular Roles Relative to Complex and Oligomannose N-Glycans

    PubMed Central

    Hall, M. Kristen; Weidner, Douglas A.; Zhu, Yong; Dayal, Sahil; Whitman, Austin A.; Schwalbe, Ruth A.

    2016-01-01

    Glycosylation modulates growth, maintenance, and stress signaling processes. Consequently, altered N-glycosylation is associated with reduced fitness and disease. Therefore, expanding our understanding of N-glycans in altering biological processes is of utmost interest. Herein, clustered regularly interspaced short palindromic repeats/caspase9 (CRISPR/Cas9) technology was employed to engineer a glycosylation mutant Chinese Hamster Ovary (CHO) cell line, K16, which expresses predominantly hybrid type N-glycans. This newly engineered cell line enabled us to compare N-glycan effects on cellular properties of hybrid type N-glycans, to the well-established Pro−5 and Lec1 cell lines, which express complex and oligomannose types of N-glycans, respectively. Lectin binding studies revealed the predominant N-glycan expressed in K16 is hybrid type. Cell dissociation and migration assays demonstrated the greatest strength of cell–cell adhesion and fastest migratory rates for oligomannose N-glycans, and these properties decreased as oligomannose type were converted to hybrid type, and further decreased upon conversion to complex type. Next, we examined the roles of three general types of N-glycans on ectopic expression of E-cadherin, a cell–cell adhesion protein. Microscopy revealed more functional E-cadherin at the cell–cell border when N-glycans were oligomannose and these levels decreased as the oligomannose N-glycans were processed to hybrid and then to complex. Thus, we provide evidence that all three general types of N-glycans impact plasma membrane architecture and cellular properties. PMID:27304954

  4. Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice

    SciTech Connect

    Simian, Marina; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Shyamala, Gopalan

    2009-05-11

    Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics. We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGF{beta}1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography. The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGF{beta}1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice. These data

  5. 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…

  6. 50 CFR 648.25 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession restrictions. 648.25 Section 648.25 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... Atlantic Mackerel, Squid, and Butterfish Fisheries § 648.25 Possession restrictions. (a) Atlantic...

  7. 50 CFR 648.204 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Atlantic Herring Fishery § 648.204 Possession restrictions. (a) A vessel must be issued a valid limited access herring permit to fish for, possess, or land more than 6,600 lb (3 mt) of Atlantic herring from or in the EEZ from any herring management area, provided that the area has not been closed due to...

  8. 50 CFR 648.145 - Possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Management Measures for the Black Sea Bass Fishery § 648.145 Possession limit. (a) No person shall possess more than 25 black sea bass, in, or harvested from the EEZ, unless that person is the owner or operator of a fishing vessel issued a black...

  9. 50 CFR 648.105 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... crew of a charter or party boat issued a summer flounder moratorium permit are subject to the... boat, or more than three crew members for a charter boat. This possession limit may be adjusted... possession limit with more than one person on board may be pooled in one or more containers. Compliance...

  10. The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling

    PubMed Central

    Kunttas-Tatli, Ezgi; Von Kleeck, Ryan A.; Greaves, Bradford D.; Vinson, David; Roberts, David M.; McCartney, Brooke M.

    2015-01-01

    The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC’s tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation–based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function. PMID:26446838

  11. The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling.

    PubMed

    Kunttas-Tatli, Ezgi; Von Kleeck, Ryan A; Greaves, Bradford D; Vinson, David; Roberts, David M; McCartney, Brooke M

    2015-12-01

    The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC's tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation-based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function.

  12. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo.

    PubMed Central

    von Andrian, U H; Chambers, J D; McEvoy, L M; Bargatze, R F; Arfors, K E; Butcher, E C

    1991-01-01

    The lectin homing receptor LECAM-1 (LAM-1, Leu8) and the beta 2 integrins, particularly Mac-1 (CD11b/CD18), participate in leukocyte-endothelial cell interactions in inflammation. LECAM-1 is rapidly shed while Mac-1 expression is dramatically increased upon neutrophil activation, suggesting functionally distinct roles for these molecules. Using intravital video microscopy, we have compared the effect of antibodies against LECAM-1 and CD18 on leukocyte interactions with rabbit mesenteric venules. Anti-LECAM-1 monoclonal antibody and its Fab fragments inhibited initial reversible leukocyte rolling along the vascular wall. Anti-CD18 monoclonal antibody had no effect on rolling but prevented subsequent firm attachment of leukocytes to venular endothelium. These results support a two-step model of leukocyte-endothelial cell interactions: reversible rolling mediated in part by LECAM-1 facilitates leukocyte recruitment by the local microenvironment and precedes activation-dependent firm attachment involving beta 2 integrins. Images PMID:1715568

  13. Signals involved in T cell activation. II. Distinct roles of intact accessory cells, phorbol esters, and interleukin 1 in activation and cell cycle progression of resting T lymphocytes

    SciTech Connect

    Davis, L.; Lipsky, P.E.

    1986-05-15

    The signals involved in the initiation of mitogen-induced activation of resting guinea pig T cells were examined. The combination of phytohemagglutinin (PHA) and 4..beta..-phorbol 12-myristate 13-acetate (PMA) stimulated DNA synthesis by accessory cell (AC)-depleted T cells cultured at high density, but the use of low density cultures indicated that intact AC were absolutely necessary for PHA-stimulated T cell DNA synthesis even in the presence of PMA, interleukin 1 (IL 1), or interleukin 2 (IL 2). In contrast, AC-depleted T cells were able to respond to the combination of the calcium ionophore, ionomycin, and PMA regardless of the cell density at which they were cultured. Results of cell cycle analysis support the conclusion that intact AC, IL 1, and a PMA-like signal play distinct roles in the progression of mitogen stimulated T cells through the first round of the cell cycle.

  14. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model

    PubMed Central

    Chen, Song; Wang, Chenran; Yeo, Syn; Liang, Chun-Chi; Okamoto, Takako; Sun, Shaogang; Wen, Jian; Guan, Jun-Lin

    2016-01-01

    Autophagy is an evolutionarily conserved cellular process controlled through a set of essential autophagy genes (Atgs). However, there is increasing evidence that most, if not all, Atgs also possess functions independent of their requirement in canonical autophagy, making it difficult to distinguish the contributions of autophagy-dependent or -independent functions of a particular Atg to various biological processes. To distinguish these functions for FIP200 (FAK family-interacting protein of 200 kDa), an Atg in autophagy induction, we examined FIP200 interaction with its autophagy partner, Atg13. We found that residues 582–585 (LQFL) in FIP200 are required for interaction with Atg13, and mutation of these residues to AAAA (designated the FIP200-4A mutant) abolished its canonical autophagy function in vitro. Furthermore, we created a FIP200-4A mutant knock-in mouse model and found that specifically blocking FIP200 interaction with Atg13 abolishes autophagy in vivo, providing direct support for the essential role of the ULK1/Atg13/FIP200/Atg101 complex in the process beyond previous studies relying on the complete knockout of individual components. Analysis of the new mouse model showed that nonautophagic functions of FIP200 are sufficient to fully support embryogenesis by maintaining a protective role in TNFα-induced apoptosis. However, FIP200-mediated canonical autophagy is required to support neonatal survival and tumor cell growth. These studies provide the first genetic evidence linking an Atg's autophagy and nonautophagic functions to different biological processes in vivo. PMID:27013233

  15. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model.

    PubMed

    Chen, Song; Wang, Chenran; Yeo, Syn; Liang, Chun-Chi; Okamoto, Takako; Sun, Shaogang; Wen, Jian; Guan, Jun-Lin

    2016-04-01

    Autophagy is an evolutionarily conserved cellular process controlled through a set of essential autophagy genes (Atgs). However, there is increasing evidence that most, if not all, Atgs also possess functions independent of their requirement in canonical autophagy, making it difficult to distinguish the contributions of autophagy-dependent or -independent functions of a particular Atg to various biological processes. To distinguish these functions for FIP200 (FAK family-interacting protein of 200 kDa), an Atg in autophagy induction, we examined FIP200 interaction with its autophagy partner, Atg13. We found that residues 582-585 (LQFL) in FIP200 are required for interaction with Atg13, and mutation of these residues to AAAA (designated the FIP200-4A mutant) abolished its canonical autophagy function in vitro. Furthermore, we created a FIP200-4A mutant knock-in mouse model and found that specifically blocking FIP200 interaction with Atg13 abolishes autophagy in vivo, providing direct support for the essential role of the ULK1/Atg13/FIP200/Atg101 complex in the process beyond previous studies relying on the complete knockout of individual components. Analysis of the new mouse model showed that nonautophagic functions of FIP200 are sufficient to fully support embryogenesis by maintaining a protective role in TNFα-induced apoptosis. However, FIP200-mediated canonical autophagy is required to support neonatal survival and tumor cell growth. These studies provide the first genetic evidence linking an Atg's autophagy and nonautophagic functions to different biological processes in vivo.

  16. 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

  17. Multiple personality in India: comparison with hysterical possession state.

    PubMed

    Varma, V K; Bouri, M; Wig, N N

    1981-01-01

    This article reports probably the first case of multiple personality from India and compares and contrasts it with the hysterical possession syndrome. Attention is drawn to the apparent rarity of multiple personality in contrast to the great prevalence of the possession syndrome in India (and other underdeveloped societies), while the reverse applies to Western Europe and North America. It is postulated that the disparity of frequency between the two manifestations of personal-identity disturbance derives from certain basic cultural differences. It is argued that polytheism and belief in reincarnation and spirits may be related to the possession syndrome, whereas high social approval of deliberate role-playing may foster the multiple personality syndrome.

  18. Decriminalizing Possession of All Controlled Substances.

    ERIC Educational Resources Information Center

    Kurzman, Marc G.

    1978-01-01

    Excerpts from the Minnesota Bar Association's Blue Ribbon Committee report of findings and recommendations, with regard to dealing with possession of heroin and other controlled substances, are presented here. (Author/DS)

  19. Mexico decriminalizes small-scale drug possession.

    PubMed

    2009-12-01

    On 20 August 2009, the Mexican government adopted legislation decriminalizing possession of small amounts of drugs. According to the new law, possession amounts for "personal and immediate use"--defined as up to half a gram of cocaine, five grams of marijuana, 50 milligrams of heroin, 40 milligrams of methamphetamine and 0.015 milligrams of LSD--will not lead to criminal prosecution. PMID:20225507

  20. Possession of cannabis legal for now.

    PubMed

    Betteridge, Glenn

    2003-04-01

    In two recent rulings the Ontario Court of Justice threw out charges of possession of cannabis contrary to section 4(I) of the Controlled Drugs and Substances Act (CDSA). The courts found that the accused in each case had been charged with an offence not known to law. Parliament never re-enacted the CDSA section prohibiting simple possession of cannabis (marijuana) after it was struck down by the Ontario Court of Appeal in the Parker case. PMID:12924322

  1. Haemophilus ducreyi RpoE and CpxRA Appear To Play Distinct yet Complementary Roles in Regulation of Envelope-Related Functions

    PubMed Central

    Gangaiah, Dharanesh; Zhang, Xinjun; Baker, Beth; Fortney, Kate R.; Liu, Yunlong; Munson, Robert S.

    2014-01-01

    Haemophilus ducreyi causes the sexually transmitted disease chancroid and a chronic limb ulceration syndrome in children. In humans, H. ducreyi is found in an abscess and overcomes a hostile environment to establish infection. To sense and respond to membrane stress, bacteria utilize two-component systems (TCSs) and extracytoplasmic function (ECF) sigma factors. We previously showed that activation of CpxRA, the only intact TCS in H. ducreyi, does not regulate homologues of envelope protein folding factors but does downregulate genes encoding envelope-localized proteins, including many virulence determinants. H. ducreyi also harbors a homologue of RpoE, which is the only ECF sigma factor in the organism. To potentially understand how H. ducreyi responds to membrane stress, here we defined RpoE-dependent genes using transcriptome sequencing (RNA-Seq). We identified 180 RpoE-dependent genes, of which 98% were upregulated; a major set of these genes encodes homologues of envelope maintenance and repair factors. We also identified and validated a putative RpoE promoter consensus sequence, which was enriched in the majority of RpoE-dependent targets. Comparison of RpoE-dependent genes to those controlled by CpxR showed that each transcription factor regulated a distinct set of genes. Given that RpoE activated a large number of genes encoding envelope maintenance and repair factors and that CpxRA represses genes encoding envelope-localized proteins, these data suggest that RpoE and CpxRA appear to play distinct yet complementary roles in regulating envelope homeostasis in H. ducreyi. PMID:25201944

  2. Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses

    PubMed Central

    Jacobson, David A; Mendez, Felipe; Thompson, Michael; Torres, Jacqueline; Cochet, Olivia; Philipson, Louis H

    2010-01-01

    Glucose-induced β-cell action potential (AP) repolarization is regulated by potassium efflux through voltage gated (Kv) and calcium activated (KCa) potassium channels. Thus, ablation of the primary Kv channel of the β-cell, Kv2.1, causes increased AP duration. However, Kv2.1−/− islet electrical activity still remains sensitive to the potassium channel inhibitor tetraethylammonium. Therefore, we utilized Kv2.1−/− islets to characterize Kv and KCa channels and their respective roles in modulating the β-cell AP. The remaining Kv current present in Kv2.1−/−β-cells is inhibited with 5 μm CP 339818. Inhibition of the remaining Kv current in Kv2.1−/− mouse β-cells increased AP firing frequency by 39.6% but did not significantly enhance glucose stimulated insulin secretion (GSIS). The modest regulation of islet AP frequency by CP 339818 implicates other K+ channels, possibly KCa channels, in regulating AP repolarization. Blockade of the KCa channel BK with slotoxin increased β-cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased β-cell AP amplitude by 30.6%. Interestingly, the KCa channel SK significantly contributes to Kv2.1−/− mouse islet AP repolarization. Inhibition of SK channels decreased AP firing frequency by 66% and increased AP duration by 67% only when Kv2.1 is ablated or inhibited and enhanced GSIS by 2.7-fold. Human islets also express SK3 channels and their β-cell AP frequency is significantly accelerated by 4.8-fold with apamin. These results uncover important repolarizing roles for both Kv and KCa channels and identify distinct roles for SK channel activity in regulating calcium- versus sodium-dependent AP firing. PMID:20643768

  3. Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion.

    PubMed

    Singh, Rajesh K; Mizuno, Koichi; Wasmeier, Christina; Wavre-Shapton, Silene T; Recchi, Chiara; Catz, Sergio D; Futter, Clare; Tolmachova, Tanya; Hume, Alistair N; Seabra, Miguel C

    2013-02-01

    Mediator release from mast cells is a critical step in allergic and inflammatory disease. However, the processes regulating the latter stages of granule release are yet to be fully understood. Rab27 small GTPases regulate release of secretory lysosomes in a variety of cells, including mast cell granules. In the present study, using murine bone marrow-derived mast cells (BMMC) from Rab27-deficient mutant mice, we found that, in contrast to Rab27b, Rab27a primarily plays an inhibitory role in regulating degranulation. Immunofluorescence analysis revealed that resting Rab27a-deficient (ashen) BMMCs display abnormal cortical F-actin distribution. Actin disassembly prior to IgE cross-linking increased wild-type BMMC secretion to ashen levels, suggesting that changes in the integrity of cortical F-actin underlie the ashen phenotype. Comparison of the secretory impairment of Rab27b knockout and Rab27a/b double knockout BMMCs highlighted a secondary positive role for Rab27a in enhancing degranulation. Rab27 is known to interact with actin via its effectors melanophilin (Mlph) and myosin Va (MyoVa) in other cell types. To better understand the differing roles of Rab27 proteins, we analysed the secretory phenotype of BMMCs derived from mice lacking Rab27 effector proteins. These experiments revealed that the phenotype of BMMCs deficient in Mlph (leaden) and BMMCs deficient in MyoVa (dilute) resembles the hyper-secretion of ashen BMMCs, while Munc13-4-deficient (jinx) BMMCs phenocopy the Rab27b knockout and double Rab27a/b knockout secretory impairment. We conclude that Rab27a and Rab27b regulate distinct steps in the BMMC degranulation pathway, with Rab27a/Mlph/MyoVa regulating cortical actin stability upstream of Rab27a/b/Munc13-4-dependent granule exocytosis.

  4. 22 CFR 72.15 - Action when possession is impractical.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Action when possession is impractical. 72.15....15 Action when possession is impractical. (a) A consular officer should not take physical possession... take physical possession....

  5. Syntactic Constraints on the Expression of Possession in Spanish.

    ERIC Educational Resources Information Center

    Kempchinsky, Paula

    1992-01-01

    In a discussion of possessives in Spanish, it is shown that three morphosyntactic constructs are systematically linked. The possessive dative construction, inalienable possession and nonrestrictive adjectives, and inalienable possession with subjects are examined. (25 references) (LB)

  6. Distinct and opposite roles for SH2 and SH3 domains of v-src in embryo survival and hemangiosarcoma formation.

    PubMed

    Morgan, John C; Majors, John E; Galileo, Deni S

    2005-01-01

    The cellular proto-oncogene c-src is thought to be involved in formation, progression, and metastasis of a variety of tumor cell types, although its exact role during tumor cell genesis is not well defined. v-src, the viral oncogene counterpart of c-src, causes metastatic sarcomas, hemorrhagic disease, and hemangiosarcomas in chicken embryos and, thus, can be used as a constitutively activated form of src for experimentally-induced tumorigenesis. Here, we used retroviral vectors to express wild-type v-src or SH2 or SH3 domain-deleted forms (DeltaSH2 or DeltaSH3) to determine if different pathogenic effects resulted. Vectors were injected into early chick embryo midbrain ventricles and embryos were sacrificed at various ages up to embryonic day (E) 18. Retroviral expression of all forms of v-src resulted in transformation of pial connective tissue cells into large, rounded abnormal-appearing cells. Surprisingly, all forms of v-src were lethal. The v-src retrovirus was lethal and killed most embryos by E15 with the development of hemangiosarcomas over the injection site between E10-E12. The DeltaSH3 retrovirus was the most deadly, killing most embryos by E12, however, it never resulted in hemangiosarcoma formation. The DeltaSH2 retrovirus injected embryos survived longer than v-src or DeltaSH3 embryos, and some of these embryos also developed large hemangiosarcomas over the injection site between E13 and E18. These results demonstrate that the src SH2 domain is required to be fully lethal, whereas the presence of the SH3 domain attenuated lethality. Furthermore, the formation of hemangiosarcomas absolutely required the presence of the src SH3 domain and to some extent required the SH2 domain. This implicates distinct and opposite roles for SH2 and SH3 domains of src and their cellular binding partners in tumorigenesis and hemorrhagic disease.

  7. Distinct and Redundant Roles of the Two MYST Histone Acetyltransferases Esa1 and Sas2 in Cell Growth and Morphogenesis of Candida albicans

    PubMed Central

    Wang, Xiongjun; Chang, Peng; Ding, Jianping

    2013-01-01

    Candida albicans is associated with humans, as both a harmless commensal organism and a pathogen. Adaption to human body temperature is extremely important for its growth and morphogenesis. Saccharomyces cerevisiae Esa1, a member of the MYST family HATs (histone acetyltransferases) and the catalytic subunit of the NuA4 complex, and its homologues in other eukaryotes have been shown to be essential for cell growth. To investigate the functional roles of two MYST family HATs, Esa1 and Sas2 in C. albicans, we deleted ESA1 and SAS2 in the C. albicans genome and performed cell growth analyses. Our results demonstrated that C. albicans Esa1 is not essential for general growth but is essential for filamentous growth. The esa1/esa1 mutant cells exhibited sensitivity to thermal, genotoxic, and oxidative stresses but tolerance to cold, osmotic, and cell wall stresses. In contrast, the sas2/sas2 mutant adapted to growth at higher temperatures and promoted filament formation at lower temperatures, resembling the phenotype of a C. albicans strain overexpressing ESA1. Cells with deletions of both ESA1 and SAS2 were inviable, reflecting the functional redundancy in cell growth. C. albicans Esa1 and Sas2 have distinct and synergistic effects on histone acetylation at H4K5, H4K12, and H4K16. Esa1 contributes mainly to acetylation of H4K5 and H4K12, whereas Sas2 contributes to acetylation of H4K16. Our findings suggest that C. albicans Esa1 and Sas2 play opposite roles in cell growth and morphogenesis and contribute coordinately to histone acetylation and gene regulation. PMID:23355007

  8. 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

  9. 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.

  10. Genome-Wide Occupancy of SREBP1 and Its Partners NFY and SP1 Reveals Novel Functional Roles and Combinatorial Regulation of Distinct Classes of Genes

    PubMed Central

    Reed, Brian D.; Charos, Alexandra E.; Szekely, Anna M.; Weissman, Sherman M.; Snyder, Michael

    2008-01-01

    The sterol regulatory element-binding protein (SREBP) family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding partners NFY and SP1 in a human hepatocyte cell line using chromatin immunoprecipitation combined with genome tiling arrays (ChIP-chip). We find that SREBP1 occupies the promoters of 1,141 target genes involved in diverse biological pathways, including novel targets with roles in lipid metabolism and insulin signaling. We also identify a conserved SREBP1 DNA-binding motif in SREBP1 target promoters, and we demonstrate that many SREBP1 target genes are transcriptionally activated by treatment with insulin and glucose using gene expression microarrays. Finally, we show that SREBP1 cooperates extensively with NFY and SP1 throughout the genome and that unique combinations of these factors target distinct functional pathways. Our results provide insight into the regulatory circuitry in which SREBP1 and its network partners coordinate a complex transcriptional response in the liver with cues from the diet. PMID:18654640

  11. 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.

  12. Expression patterns suggest that despite considerable functional redundancy, galectin-4 and -6 play distinct roles in normal and damaged mouse digestive tract.

    PubMed

    Houzelstein, Denis; Reyes-Gomez, Edouard; Maurer, Marie; Netter, Pierre; Higuet, Dominique

    2013-05-01

    The galectin-4 protein is mostly expressed in the digestive tract and is associated with lipid raft stabilization, protein apical trafficking, wound healing, and inflammation. While most mammalian species, including humans, have a single Lgals4 gene, some mice have two paralogues: Lgals4 and Lgals6. So far, their significant similarities have hindered the analysis of their respective expression and function. We took advantage of two antibodies that discriminate between the galectin-4 and galectin-6 proteins to document their patterns of expression in the normal and the dextran sodium sulfate (DSS)-damaged digestive tract in the mouse. In the normal digestive tract, their pattern of expression from tongue to colon is quite similar, which suggests functional redundancy. However, the presence of galectin-4, but not galectin-6, in the lamina propria of the DSS-damaged colon, its association with luminal colonic bacteria, and differences in subcellular localization of these proteins suggest that they also have distinct roles in the normal and the damaged mouse digestive tract. Our results provide a rare example of ancestral and derived functions evolving after tandem gene duplication.

  13. The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.

    PubMed

    Sato, Hiroyasu; Taketomi, Yoshitaka; Ushida, Ayako; Isogai, Yuki; Kojima, Takumi; Hirabayashi, Tetsuya; Miki, Yoshimi; Yamamoto, Kei; Nishito, Yasumasa; Kobayashi, Tetsuyuki; Ikeda, Kazutaka; Taguchi, Ryo; Hara, Shuntaro; Ida, Satoshi; Miyamoto, Yuji; Watanabe, Masayuki; Baba, Hideo; Miyata, Keishi; Oike, Yuichi; Gelb, Michael H; Murakami, Makoto

    2014-07-01

    Metabolic disorders, including obesity and insulin resistance, have their basis in dysregulated lipid metabolism and low-grade inflammation. In a microarray search of unique lipase-related genes whose expressions are associated with obesity, we found that two secreted phospholipase A2s (sPLA2s), PLA2G5 and PLA2G2E, were robustly induced in adipocytes of obese mice. Analyses of Pla2g5(-/-) and Pla2g2e(-/-) mice revealed distinct roles of these sPLA2s in diet-induced obesity. PLA2G5 hydrolyzed phosphatidylcholine in fat-overladen low-density lipoprotein to release unsaturated fatty acids, which prevented palmitate-induced M1 macrophage polarization. As such, PLA2G5 tipped the immune balance toward an M2 state, thereby counteracting adipose tissue inflammation, insulin resistance, hyperlipidemia, and obesity. PLA2G2E altered minor lipoprotein phospholipids, phosphatidylserine and phosphatidylethanolamine, and moderately facilitated lipid accumulation in adipose tissue and liver. Collectively, the identification of "metabolic sPLA2s" adds this gene family to a growing list of lipolytic enzymes that act as metabolic coordinators.

  14. Membrane binding and endoplasmic reticulum retention sequences of rotavirus VP7 are distinct: role of carboxy-terminal and other residues in membrane binding.

    PubMed

    Clarke, M L; Lockett, L J; Both, G W

    1995-10-01

    The sequences responsible for binding rotavirus glycoprotein VP7 to the membrane of the endoplasmic reticulum (ER) have not been identified. Here we show that the sequences which promote membrane binding in vitro are distinct from the N-terminal sequences which promote retention of VP7 in the ER in vivo. The role of the C-terminal region in membrane binding was also examined by using truncation mutants. Membrane binding in vitro was reduced but not abolished by removing up to 102 residues from the C terminus. The data suggest that the last 36 residues of VP7 may be present in the membrane or translocation pore, possibly with the C terminus protruding into the cytoplasm, since these residues contribute to, but do not account for, membrane binding. Surprisingly, modified forms of VP7 which are secreted from transfected cells showed the same membrane-binding properties in vitro as the protein retained in the ER membrane. Thus, secreted VP7 may not be present as a soluble polypeptide in the ER. A model to explain these results is presented. Previously published data are consistent with the idea that the highly conserved C terminus of nascent VP7 could have a cytoplasmic orientation which is important for assembly of mature virus particles. PMID:7666548

  15. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

    Two experiments were carried out to study the role of gender category in evaluations of face distinctiveness. In Experiment 1, participants had to evaluate the distinctiveness and the femininity-masculinity of real or artificial composite faces. The composite faces were created by blending either faces of the same gender (sexed composite faces,…

  16. 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... Atlantic Mackerel, squid, and butterfish framework adjustments to management measures. (a) Within season... the Atlantic Mackerel, Squid, and Butterfish FMP if it finds that action is necessary to meet or...

  17. Commonalities of French and Mandarin Inalienable Possession.

    ERIC Educational Resources Information Center

    Kliffer, Michael D.

    1996-01-01

    Examines inalienable possession in French and Mandarin with the aim of bringing out typological affinities. In particular, two unresolved issues are re-examined: Haiman's Iconicity Hypothesis and the question of the protypical semantic categories of iposs. (32 references) (Author/CK)

  18. 50 CFR 648.164 - Possession restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., and crew of a charter or party boat issued a bluefish commercial permit are not subject to the... party boat and three for a charter boat. (b) Bluefish harvested by vessels subject to the possession limit with more than one person on board may be pooled in one or more containers. Compliance with...

  19. Analyses of GA20ox- and GID1-over-expressing aspen suggest that gibberellins play two distinct roles in wood formation.

    PubMed

    Mauriat, Mélanie; Moritz, Thomas

    2009-06-01

    Gibberellins (GAs) are involved in many aspects of plant development, including shoot growth, flowering and wood formation. Increased levels of bioactive GAs are known to induce xylogenesis and xylem fiber elongation in aspen. However, there is currently little information on the response pathway(s) that mediate GA effects on wood formation. Here we characterize an important element of the GA pathway in hybrid aspen: the GA receptor, GID1. Four orthologs of GID1 were identified in Populus tremula x P. tremuloides (PttGID1.1-1.4). These were functional when expressed in Arabidopsis thaliana, and appear to present a degree of sub-functionalization in hybrid aspen. PttGID1.1 and PttGID1.3 were over-expressed in independent lines of hybrid aspen using either the 35S promoter or a xylem-specific promoter (LMX5). The 35S:PttGID1 over-expressors shared several phenotypic traits previously described in 35S:AtGA20ox1 over-expressors, including rapid growth, increased elongation, and increased xylogenesis. However, their xylem fibers were not elongated, unlike those of 35S:AtGA20ox1 plants. Similar differences in the xylem fiber phenotype were observed when PttGID1.1, PttGID1.3 or AtGA20ox1 were expressed under the control of the LMX5 promoter, suggesting either that PttGID1.1 and PttGID1.3 play no role in fiber elongation or that GA homeostasis is strongly controlled when GA signaling is altered. Our data suggest that GAs are required in two distinct wood-formation processes that have tissue-specific signaling pathways: xylogenesis, as mediated by GA signaling in the cambium, and fiber elongation in the developing xylem.

  20. Possession Versus Position: Strategic Evaluation in AFL.

    PubMed

    O'Shaughnessy, Darren M

    2006-01-01

    In sports like Australian Rules football and soccer, teams must battle to achieve possession of the ball in sufficient space to make optimal use of it. Ultimately the teams need to score, and to do that the ball must be brought into the area in front of goal - the place where the defence usually concentrates on shutting down space and opportunity time. Coaches would like to quantify the trade-offs between contested play in good positions and uncontested play in less promising positions, in order to inform their decision-making about where to put their players, and when to gamble on sending the ball to a contest rather than simply maintain possession. To evaluate football strategies, Champion Data has collected the on-ground locations of all 350,000 possessions and stoppages in the past two seasons of AFL (2004, 2005). By following each chain of play through to the next score, we can now reliably estimate the scoreboard "equity "of possessing the ball at any location, and measure the effect of having sufficient time to dispose of it effectively. As expected, winning the ball under physical pressure (through a "hard ball get") is far more difficult to convert into a score than winning it via a mark. We also analyse some equity gradients to show how getting the ball 20 metres closer to goal is much more important in certain areas of the ground than in others. We conclude by looking at the choices faced by players in possession wanting to maximise their likelihood of success. Key PointsEquity analysis provides a way of estimating the net value of actions on the sporting field.Combined with spatial data analysis, the relative merits of gaining position or maintaining possession can be judged.The advantage of having time and space to use the ball is measured in terms of scoreboard value, and is found to vary with field position.Each sport has identifiable areas of the field with high equity gradients, meaning that it is most important to gain territory there.

  1. 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

  2. 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.

  3. 50 CFR 648.295 - Recreational possession limit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Recreational possession limit. 648.295... Measures for the Tilefish Fishery § 648.295 Recreational possession limit. Any person fishing from a vessel... possession limit....

  4. 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)

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Possession of used liquor... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS ALCOHOL BEVERAGE DEALERS Reuse and Possession of Used Liquor Bottles § 31.203 Possession of used liquor bottles. The possession of used liquor bottles by any...

  6. 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... possessions. Whenever reference is made to the territories and possessions of the United States in this..., said territories and possessions shall be deemed to include only the Virgin Islands of the...

  7. 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... (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.35 Field possession limit. No...

  8. 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...

  9. 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...

  10. 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...

  11. 50 CFR 20.38 - Possession of live birds.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 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...

  12. 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...

  13. Planctomycetes do possess a peptidoglycan cell wall

    PubMed Central

    Jeske, Olga; Schüler, Margarete; Schumann, Peter; Schneider, Alexander; Boedeker, Christian; Jogler, Mareike; Bollschweiler, Daniel; Rohde, Manfred; Mayer, Christoph; Engelhardt, Harald; Spring, Stefan; Jogler, Christian

    2015-01-01

    Most bacteria contain a peptidoglycan (PG) cell wall, which is critical for maintenance of shape and important for cell division. In contrast, Planctomycetes have been proposed to produce a proteinaceous cell wall devoid of PG. The apparent absence of PG has been used as an argument for the putative planctomycetal ancestry of all bacterial lineages. Here we show, employing multiple bioinformatic methods, that planctomycetal genomes encode proteins required for PG synthesis. Furthermore, we biochemically demonstrate the presence of the sugar and the peptide components of PG in Planctomycetes. In addition, light and electron microscopic experiments reveal planctomycetal PG sacculi that are susceptible to lysozyme treatment. Finally, cryo-electron tomography demonstrates that Planctomycetes possess a typical PG cell wall and that their cellular architecture is thus more similar to that of other Gram-negative bacteria. Our findings shed new light on the cellular architecture and cell division of the maverick Planctomycetes. PMID:25964217

  14. [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. PMID:1192724

  15. 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 and furnishings, works of art, and book and wine collections, unless such items are of such...

  16. 22 CFR 72.14 - Nominal possession; property not normally taken into physical possession.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 and furnishings, works of art, and book and wine collections, unless such items are of such...

  17. China English: Its Distinctive Features

    ERIC Educational Resources Information Center

    Yang, Wei-dong; Dai, Wei-ping

    2011-01-01

    This paper attempts to expound that China English boasting its own distinctive features on the levels of phonology, words, sentences and discourse has been playing an irreplaceable role in intercultural activities, though still in its infancy and in the process of developing and perfecting itself, and it now makes every effort to move towards…

  18. A case of possessive state with onset influenced by 'door-to-door' sales.

    PubMed

    Satoh, S; Obata, S; Seno, E; Okada, T; Morita, N; Saito, T; Yoshikawa, M; Yamagami, A

    1996-12-01

    Recently in Japan, 'door-to-door sales' has become of concern because it has created numerous legal and social problems. In this paper, a 47 year old dissociative trance disorder case who presented with possession by God is discussed. Specific types of door-to-door sales is known to use superstition and folk beliefs as tools to lure customers. In this particular case, these religious factors seemed to have played an important role in the precipitation of the disorder and its presentation. In addition, the brain-washing environment observed in video lectures used in door-to-door sales seemed to play an important role in the development of the possessive state. We also performed social psychiatric analysis of the occurrence of the possessive state in a city area, which has been considered to develop within traditional culture. Phenomenological classification by one of the authors was useful for diagnosing underlying disorders in the possessive state.

  19. 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…

  20. Zinc ion acts as a cofactor for serine/threonine kinase MST3 and has a distinct role in autophosphorylation of MST3.

    PubMed

    Lu, Te-Jung; Huang, Chi-Ying F; Yuan, Chiun-Jye; Lee, Yuan-Chii; Leu, Tzeng-Horng; Chang, Wen-Chang; Lu, Te-Ling; Jeng, Wen-Yih; Lai, Ming-Derg

    2005-06-01

    We examined the metal ion cofactor preference for MST3 (mammalian Ste20-like kinase 3) of the Ste20 serine/threonine kinase family. Four metal ions (Mg(+2), Mn(+2), Zn(2+), and Co(2+)) activate endogenous, exogenous, and baculovirus-expressed recombinant MST3 within the physiological concentration range. In contrast, Fe(+2) and Ca(+2) do not function as MST3 cofactors. Mn(2+), Co(2+), and Mg(2+)-dependent autophosphorylation of MST3 is mainly on threonine residue while Zn(2+)-stimulated MST3 autophosphorylation is on both serine and threonine residues. The distinct autophosphorylation pattern on MST3 suggests that MST3 may exert various types of kinase reactions depending on the type of metal ion cofactor used. To our knowledge, this is the first report showing Zn(2+) as the metal ion cofactor of a recombinant serine/threonine kinase.

  1. Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and C. elegans

    PubMed Central

    George, Manju; Ying, GuoGuang; Rainey, Mark A; Solomon, Aharon; Parikh, Pankit T; Gao, Qingshen; Band, Vimla; Band, Hamid

    2007-01-01

    Background The four highly homologous human EHD proteins (EHD1-4) form a distinct subfamily of the Eps15 homology domain-containing protein family and are thought to regulate endocytic recycling. Certain members of this family have been studied in different cellular contexts; however, a lack of concurrent analyses of all four proteins has impeded an appreciation of their redundant versus distinct functions. Results Here, we analyzed the four EHD proteins both in mammalian cells and in a cross-species complementation assay using a C. elegans mutant lacking the EHD ortholog RME-1. We show that all human EHD proteins rescue the vacuolated intestinal phenotype of C. elegans rme-1 mutant, are simultaneously expressed in a panel of mammalian cell lines and tissues tested, and variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker. Small interfering RNA (siRNA) knock-down of EHD1, 2 and 4, and expression of dominant-negative EH domain deletion mutants showed that loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded transferrin exit from the endocytic recycling compartment. EH domain deletion mutants of EHD1 and 3 but not 2 or 4, induced a striking perinuclear clustering of co-transfected Rab11. Knock-down analyses indicated that EHD1 and 2 regulate the exit of cargo from the recycling endosome while EHD4, similar to that reported for EHD3 (Naslavsky et al. (2006) Mol. Biol. Cell 17, 163), regulates transport from the early endosome to the recycling endosome. Conclusion Altogether, our studies suggest that concurrently expressed human EHD proteins perform shared as well as discrete functions in the endocytic recycling pathway and lay a foundation for future studies to identify and characterize the molecular pathways involved. PMID:17233914

  2. Demonic possession and the historical construction of melancholy and hysteria.

    PubMed

    Westerink, Herman

    2014-09-01

    Contrary to the often-voiced opinion that the birth of modern psychiatry should be regarded as a victory of enlightened science and rationality over outdated religious beliefs and ecclesiastical authority, it is argued in this article that the emergence of medical and psychiatric approaches to pathology in modernity takes place in the context of intensified religious life and mutual rivalry between the various religious denominations. Notably the two main types of demonological possession appearing in the context of Protestant and Catholic religious life, theological reflections and pastoral practices play a major role in the conceptualizations of melancholy and hysteria. The heritage of this can be viewed in the works of psychiatrists such as Charcot and Kraepelin, and also in Freud's psychoanalysis.

  3. 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,...

  4. 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,...

  5. 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... 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...

  6. 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...

  7. 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... 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...

  8. 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... 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...

  9. 50 CFR 648.235 - Possession and landing restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession and landing restrictions. 648... Measures for the Spiny Dogfish Fishery § 648.235 Possession and landing restrictions. (a) Quota Period 1... calendar day. (c) Regulations governing the harvest, possession, landing, purchase, and sale of shark...

  10. 5 CFR 930.111 - State license in possession.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false State license in possession. 930.111... Operators § 930.111 State license in possession. An operator or incidental operator will have a State license in his or her possession at all times while driving a Government-owned or -leased motor vehicle...

  11. 50 CFR 20.39 - Termination of possession.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Termination of possession. 20.39 Section... (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.39 Termination of...

  12. 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... OF THE TREASURY CUSTOMS RELATIONS WITH CANADA AND MEXICO Baggage § 123.62 Baggage in possession of traveler. For baggage arriving in the actual possession of a traveler, his declaration shall be accepted...

  13. 27 CFR 31.202 - Possession of refilled liquor bottles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Possession of refilled... TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS ALCOHOL BEVERAGE DEALERS Reuse and Possession of Used Liquor Bottles § 31.202 Possession of refilled liquor bottles. No person who sells, or offers for...

  14. 32 CFR 552.120 - Possession and control.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Possession and control. 552.120 Section 552.120 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND... Explosives-Fort Lewis, Washington § 552.120 Possession and control. (a) Possession of weapons on the post...

  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... ASSISTANCE AND REAL PROPERTY ACQUISITION POLICIES Regulations and Procedures § 1306.3 Surrender of possession. Possession of real property will not be taken until the owner has been paid the agreed purchase price or...

  16. 32 CFR 507.12 - Possession and wearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Possession and wearing. 507.12 Section 507.12... Possession and wearing. (a) The wearing of any decoration, service medal, badge, service ribbon, lapel button... possession by a person of any of the articles prescribed in § 507.8 of this part is authorized provided...

  17. 24 CFR 27.45 - Transfer of title and possession.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Transfer of title and possession... Foreclosure of Multifamily Mortgages § 27.45 Transfer of title and possession. (a) If the Secretary is the....20, any commercial tenant and any residential tenant remaining in possession after the expiration...

  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...

  19. 32 CFR 538.3 - Restrictions on possession and use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Restrictions on possession and use. 538.3 Section 538.3 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY CLAIMS AND ACCOUNTS MILITARY PAYMENT CERTIFICATES § 538.3 Restrictions on possession and use. (a) Possession or use...

  20. 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...

  1. 20 CFR 404.1093 - Possession of the United States.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Possession of the United States. 404.1093... Income § 404.1093 Possession of the United States. In using the exclusions from gross income provided under section 931 of the Code (relating to income from sources within possessions of the United...

  2. New Women's Suitcases: The Possessive-Adjective Switch.

    ERIC Educational Resources Information Center

    Seymour, Deborah Mandelbaum

    An analysis of the structure of possessive-adjective phrases (e.g., "women's new suitcases, new women's suitcases") in English looks at some data that appear to conflict with the intuitive order of S-structure possessives preceding adjectives. A solution to this apparent anomaly is proposed: it is not the compounding of possessive-noun combination…

  3. Distinct linear and non-linear trajectories of reward and punishment reversal learning during development: relevance for dopamine's role in adolescent decision making.

    PubMed

    van der Schaaf, Marieke E; Warmerdam, Eveline; Crone, Eveline A; Cools, Roshan

    2011-10-01

    Abnormalities in value-based decision making during adolescence have often been attributed to non-linear, inverted-U shaped development of reward-related processes. This hypothesis is strengthened by functional imaging work revealing an inverted-U shaped relationship between age and reward-related activity in the striatum. However, behavioural studies have mostly reported linear rather than non-linear increases in reward-related performance. In the present study, we investigated the mechanisms underlying the development of reward- and punishment-related processing across four age groups using a reversal learning task previously shown to depend on striatal dopamine. We demonstrate both linear and non-linear age effects on distinct components of reversal learning. Specifically, results revealed a linear shift with age in terms of valence-dependent reversal learning, with children exhibiting better punishment than reward reversal learning, adults exhibiting better reward than punishment reversal learning and adolescents exhibiting an intermediate performance pattern. In addition, we also observed a non-linear, inverted-U shaped relationship between age and valence-independent reversal learning, which was due to aberrant ability of adolescents to update behaviour in response to negative performance feedback. These findings indicate that the (linear or nonlinear) nature of the relationship between age and reward learning depends on the type of reward learning under study.

  4. ALL2, a Homologue of ALL1, Has a Distinct Role in Regulating pH Homeostasis in the Pathogen Cryptococcus neoformans

    PubMed Central

    Jain, Neena; Bouklas, Tejas; Gupta, Anjali; Varshney, Avanish K.; Orner, Erika P.

    2015-01-01

    Cryptococcus neoformans is a facultative intracellular fungal pathogen that has a polysaccharide capsule and causes life-threatening meningoencephalitis. Its capsule, as well as its ability to survive in the acidic environment of the phagolysosome, contributes to the pathogen's resilience in the host environment. Previously, we reported that downregulation of allergen 1 (ALL1) results in the secretion of a shorter, more viscous exopolysaccharide with less branching and structural complexity, as well as altered iron homeostasis. Now, we report on a homologous coregulated gene, allergen 2 (ALL2). ALL2's function was characterized by generating null mutants in C. neoformans. In contrast to ALL1, loss of ALL2 attenuated virulence in the pulmonary infection model. The all2Δ mutant shed a less viscous exopolysaccharide and exhibited higher sensitivity to hydrogen peroxide than the wild type, and as a result, the all2Δ mutant was more resistant to macrophage-mediated killing. Transcriptome analysis further supported the distinct function of these two genes. Unlike ALL1's involvement in iron homeostasis, we now present data on ALL2's unique function in maintaining intracellular pH in low-pH conditions. Thus, our data highlight that C. neoformans, a human-pathogenic basidiomycete, has evolved a unique set of virulence-associated genes that contributes to its resilience in the human niche. PMID:26597983

  5. Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system.

    PubMed

    Zonta, Barbara; Tait, Steven; Melrose, Shona; Anderson, Heather; Harroch, Sheila; Higginson, Jennifer; Sherman, Diane L; Brophy, Peter J

    2008-06-30

    Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes of Ranvier. Myelin-forming oligodendrocytes in the central nervous system (CNS) induce the clustering of sodium channels into nodal complexes flanked by paranodal axoglial junctions. However, the molecular mechanisms for nodal complex assembly in the CNS are unknown. Two isoforms of Neurofascin, neuronal Nfasc186 and glial Nfasc155, are components of the nodal and paranodal complexes, respectively. Neurofascin-null mice have disrupted nodal and paranodal complexes. We show that transgenic Nfasc186 can rescue the nodal complex when expressed in Nfasc(-/-) mice in the absence of the Nfasc155-Caspr-Contactin adhesion complex. Reconstitution of the axoglial adhesion complex by expressing transgenic Nfasc155 in oligodendrocytes also rescues the nodal complex independently of Nfasc186. Furthermore, the Nfasc155 adhesion complex has an additional function in promoting the migration of myelinating processes along CNS axons. We propose that glial and neuronal Neurofascins have distinct functions in the assembly of the CNS node of Ranvier. PMID:18573915

  6. Comparative Analysis of kdp and ktr Mutants Reveals Distinct Roles of the Potassium Transporters in the Model Cyanobacterium Synechocystis sp. Strain PCC 6803

    PubMed Central

    Nanatani, Kei; Shijuku, Toshiaki; Takano, Yousuke; Zulkifli, Lalu; Yamazaki, Tomoko; Tominaga, Akira; Souma, Satoshi; Onai, Kiyoshi; Morishita, Megumi; Ishiura, Masahiro; Hagemann, Martin; Suzuki, Iwane; Maruyama, Hisataka; Arai, Fumihito

    2014-01-01

    Photoautotrophic bacteria have developed mechanisms to maintain K+ homeostasis under conditions of changing ionic concentrations in the environment. Synechocystis sp. strain PCC 6803 contains genes encoding a well-characterized Ktr-type K+ uptake transporter (Ktr) and a putative ATP-dependent transporter specific for K+ (Kdp). The contributions of each of these K+ transport systems to cellular K+ homeostasis have not yet been defined conclusively. To verify the functionality of Kdp, kdp genes were expressed in Escherichia coli, where Kdp conferred K+ uptake, albeit with lower rates than were conferred by Ktr. An on-chip microfluidic device enabled monitoring of the biphasic initial volume recovery of single Synechocystis cells after hyperosmotic shock. Here, Ktr functioned as the primary K+ uptake system during the first recovery phase, whereas Kdp did not contribute significantly. The expression of the kdp operon in Synechocystis was induced by extracellular K+ depletion. Correspondingly, Kdp-mediated K+ uptake supported Synechocystis cell growth with trace amounts of external potassium. This induction of kdp expression depended on two adjacent genes, hik20 and rre19, encoding a putative two-component system. The circadian expression of kdp and ktr peaked at subjective dawn, which may support the acquisition of K+ required for the regular diurnal photosynthetic metabolism. These results indicate that Kdp contributes to the maintenance of a basal intracellular K+ concentration under conditions of limited K+ in natural environments, whereas Ktr mediates fast potassium movements in the presence of greater K+ availability. Through their distinct activities, both Ktr and Kdp coordinate the responses of Synechocystis to changes in K+ levels under fluctuating environmental conditions. PMID:25313394

  7. Co-immunoprecipitation with Tau Isoform-specific Antibodies Reveals Distinct Protein Interactions and Highlights a Putative Role for 2N Tau in Disease*

    PubMed Central

    Liu, Chang; Song, Xiaomin; Nisbet, Rebecca

    2016-01-01

    Alternative splicing generates multiple isoforms of the microtubule-associated protein Tau, but little is known about their specific function. In the adult mouse brain, three Tau isoforms are expressed that contain either 0, 1, or 2 N-terminal inserts (0N, 1N, and 2N). We generated Tau isoform-specific antibodies and performed co-immunoprecipitations followed by tandem mass tag multiplexed quantitative mass spectrometry. We identified novel Tau-interacting proteins of which one-half comprised membrane-bound proteins, localized to the plasma membrane, mitochondria, and other organelles. Tau was also found to interact with proteins involved in presynaptic signal transduction. MetaCore analysis revealed one major Tau interaction cluster that contained 33 Tau pulldown proteins. To explore the pathways in which these proteins are involved, we conducted an ingenuity pathway analysis that revealed two significant overlapping pathways, “cell-to-cell signaling and interaction” and “neurological disease.” The functional enrichment tool DAVID showed that in particular the 2N Tau-interacting proteins were specifically associated with neurological disease. Finally, for a subset of Tau interactions (apolipoprotein A1 (apoA1), apoE, mitochondrial creatine kinase U-type, β-synuclein, synaptogyrin-3, synaptophysin, syntaxin 1B, synaptotagmin, and synapsin 1), we performed reverse co-immunoprecipitations, confirming the preferential interaction of specific isoforms. For example, apoA1 displayed a 5-fold preference for the interaction with 2N, whereas β-synuclein showed preference for 0N. Remarkably, a reverse immunoprecipitation with apoA1 detected only the 2N isoform. This highlights distinct protein interactions of the different Tau isoforms, suggesting that they execute different functions in brain tissue. PMID:26861879

  8. Proteinase-activated receptors 1 and 2 and the regulation of porcine coronary artery contractility: a role for distinct tyrosine kinase pathways

    PubMed Central

    El-Daly, Mahmoud; Saifeddine, Mahmoud; Mihara, Koichiro; Ramachandran, Rithwik; Triggle, Christopher R; Hollenberg, Morley D

    2014-01-01

    Background and Purpose Because angiotensin-II-mediated porcine coronary artery (PCA) vasoconstriction is blocked by protein tyrosine kinase (PYK) inhibitors, we hypothesized that proteinase-activated receptors (PARs), known to regulate vascular tension, like angiotensin-II, would also cause PCA contractions via PYK-dependent signalling pathways. Experimental Approach Contractions of intact and endothelium-free isolated PCA rings, stimulated by PAR1/PAR2-activating peptides, angiotensin-II, PGF2α, EGF, PDGF and KCl, were monitored with/without multiple signalling pathway inhibitors, including AG-tyrphostins AG18 (non-specific PYKs), AG1478 (EGF-receptor kinase), AG1296 (PDGF receptor kinase), PP1 (Src kinase), U0126 and PD98059 (MEK/MAPKinase kinase), indomethacin/SC-560/NS-398 (COX-1/2) and L-NAME (NOS). Key Results AG18 inhibited the contractions induced by all the agonists except KCl, whereas U0126 attenuated contractions induced by PAR1/PAR2 agonists, EGF and angiotensin-II, but not by PGF2α, the COX-produced metabolites of arachidonate and KCl. PP1 only affected the responses to PAR1/PAR2-activating peptides and angiotensin-II. The EGF-kinase inhibitor, AG1478, attenuated contractions initiated by the PARs (PAR2 >> PAR1) and EGF itself, but not by angiotensin-II, PGF2α or KCl. COX-1/2 inhibitors blocked the contractions induced by all the agonists, except KCl and PGF2α. Conclusion and Implications PAR1/2-mediated contractions of the PCA are dependent on Src and MAPKinase and, in part, involve EGF-receptor-kinase transactivation and the generation of a COX-derived contractile agonist. However, the PYK signalling pathways used by PARs are distinct from each other and from those triggered by angiotensin-II and EGF. These signalling pathways may be therapeutic targets for managing coagulation-proteinase-induced coronary vasospasm. PMID:24506284

  9. Distinct roles for miR-1 and miR-133a in the proliferation and differentiation of rhabdomyosarcoma cells.

    PubMed

    Rao, Prakash K; Missiaglia, Edoardo; Shields, Lauren; Hyde, Greg; Yuan, Bingbing; Shepherd, Christopher J; Shipley, Janet; Lodish, Harvey F

    2010-09-01

    Rhabdomyosarcoma is the most common soft tissue sarcoma in the pediatric population. As this tumor has an undifferentiated myogenic phenotype, agents that promote differentiation hold particular promise as part of a novel therapeutic approach to combat this type of cancer. In this report, we focus on the contribution of two microRNAs (miRNAs) in rhabdomyosarcomas. Levels of miR-1 and miR-133a are drastically reduced in representative cell lines from each major rhabdomyosarcoma subtype (embryonal and alveolar). Introduction of miR-1 and miR-133a into an embryonal rhabdomyosarcoma-derived cell line is cytostatic, thereby suggesting a tumor suppressor-like role for these myogenic miRNAs. Transcriptional profiling of cells after miR-1 and miR-133a expression reveals that miR-1 (but not miR-133a) exerts a strong promyogenic influence on these poorly differentiated tumor cells. We identify mRNAs that are down-regulated by these miRNAs and propose roles for miR-1 and miR-133a in repressing isoforms of genes that are normally not expressed in muscle. Finally, we show that mRNA targets of miR-1 and miR-133a are up-regulated in rhabdomyosarcomas, suggesting a causative role for these miRNAs in the development of rhabdomyosarcomas. More important, these results point to the promise of enhancing rhabdomyosarcoma therapy using miRNAs as agents that mediate cytostasis and promote muscle differentiation.

  10. Distinct roles of NF-{kappa}B p50 in the regulation of acetaminophen-induced inflammatory mediator production and hepatotoxicity

    SciTech Connect

    Dambach, Donna M.; Durham, Stephen K.; Laskin, Jeffrey D.; Laskin, Debra L. . E-mail: laskin@eohsi.rutgers.edu

    2006-03-01

    Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. In addition to inducing direct cellular damage, oxidants can activate transcription factors including NF-{kappa}B, which regulate the production of inflammatory mediators implicated in hepatotoxicity. Here, we investigated the role of APAP-induced oxidative stress and NF-{kappa}B in inflammatory mediator production. Treatment of mice with APAP (300 mg/kg, i.p.) resulted in centrilobular hepatic necrosis and increased serum aminotransferase levels. This was correlated with depletion of hepatic glutathione and CuZn superoxide dismutase (SOD). APAP administration also increased expression of the proinflammatory mediators, interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF{alpha}), macrophage chemotactic protein-1 (MCP-1), and KC/gro, and the anti-inflammatory cytokine, interleukin-10 (IL-10). Pretreatment of mice with the antioxidant, N-acetylcysteine (NAC) prevented APAP-induced depletion of glutathione and CuZnSOD, as well as hepatotoxicity. NAC also abrogated APAP-induced increases in TNF{alpha}, KC/gro, and IL-10, but augmented expression of the anti-inflammatory cytokines interleukin-4 (IL-4) and transforming growth factor-{beta} (TGF{beta}). No effects were observed on IL-1{beta} or MCP-1 expression. To determine if NF-{kappa}B plays a role in regulating mediator production, we used transgenic mice with a targeted disruption of the gene for NF-{kappa}B p50. As observed with NAC pretreatment, the loss of NF-{kappa}B p50 was associated with decreased ability of APAP to upregulate TNF{alpha}, KC/gro, and IL-10 expression and increased expression of IL-4 and TGF{beta}. However, in contrast to NAC pretreatment, the loss of p50 had no effect on APAP-induced hepatotoxicity. These data demonstrate that APAP-induced cytokine expression in the liver is influenced by oxidative stress and that this is dependent, in part, on NF-{kappa}B. However, NF-{kappa}B p50

  11. Distinct roles of L- and T-type voltage-dependent Ca2+ channels in regulation of lymphatic vessel contractile activity.

    PubMed

    Lee, Stewart; Roizes, Simon; von der Weid, Pierre-Yves

    2014-12-15

    Lymph drainage maintains tissue fluid homeostasis and facilitates immune response. It is promoted by phasic contractions of collecting lymphatic vessels through which lymph is propelled back into the blood circulation. This rhythmic contractile activity (i.e. lymphatic pumping) increases in rate with increase in luminal pressure and relies on activation of nifedipine-sensitive voltage-dependent Ca(2+) channels (VDCCs). Despite their importance, these channels have not been characterized in lymphatic vessels. We used pressure- and wire-myography as well as intracellular microelectrode electrophysiology to characterize the pharmacological and electrophysiological properties of L-type and T-type VDCCs in rat mesenteric lymphatic vessels and evaluated their particular role in the regulation of lymphatic pumping by stretch. We complemented our study with PCR and confocal immunofluorescence imaging to investigate the expression and localization of these channels in lymphatic vessels. Our data suggest a delineating role of VDCCs in stretch-induced lymphatic vessel contractions, as the stretch-induced increase in force of lymphatic vessel contractions was significantly attenuated in the presence of L-type VDCC blockers nifedipine and diltiazem, while the stretch-induced increase in contraction frequency was significantly decreased by the T-type VDCC blockers mibefradil and nickel. The latter effect was correlated with a hyperpolarization. We propose that activation of T-type VDCCs depolarizes membrane potential, regulating the frequency of lymphatic contractions via opening of L-type VDCCs, which drive the strength of contractions.

  12. Distinct and Redundant Roles of Protein Tyrosine Phosphatases Ptp1 and Ptp2 in Governing the Differentiation and Pathogenicity of Cryptococcus neoformans

    PubMed Central

    Lee, Kyung-Tae; Byun, Hyo-Jeong; Jung, Kwang-Woo; Hong, Joohyeon; Cheong, Eunji

    2014-01-01

    Protein tyrosine phosphatases (PTPs) serve as key negative-feedback regulators of mitogen-activated protein kinase (MAPK) signaling cascades. However, their roles and regulatory mechanisms in human fungal pathogens remain elusive. In this study, we characterized the functions of two PTPs, Ptp1 and Ptp2, in Cryptococcus neoformans, which causes fatal meningoencephalitis. PTP1 and PTP2 were found to be stress-inducible genes, which were controlled by the MAPK Hog1 and the transcription factor Atf1. Ptp2 suppressed the hyperphosphorylation of Hog1 and was involved in mediating vegetative growth, sexual differentiation, stress responses, antifungal drug resistance, and virulence factor regulation through the negative-feedback loop of the HOG pathway. In contrast, Ptp1 was not essential for Hog1 regulation, despite its Hog1-dependent induction. However, in the absence of Ptp2, Ptp1 served as a complementary PTP to control some stress responses. In differentiation, Ptp1 acted as a negative regulator, but in a Hog1- and Cpk1-independent manner. Additionally, Ptp1 and Ptp2 localized to the cytosol but were enriched in the nucleus during the stress response, affecting the transient nuclear localization of Hog1. Finally, Ptp1 and Ptp2 played minor and major roles, respectively, in the virulence of C. neoformans. Taken together, our data suggested that PTPs could be exploited as novel antifungal targets. PMID:24728196

  13. Toll-like receptors recognize distinct proteinase-resistant glycoconjugates in Campylobacter jejuni and Escherichia coli.

    PubMed

    Phongsisay, Vongsavanh; Hara, Hiromitsu; Fujimoto, Shuji

    2015-03-01

    Campylobacter jejuni causes gastroenteritis and autoimmune neuropathy Guillain-Barré syndrome. The mechanism by which C. jejuni infection results in such the hyperimmunity is not completely understood. Host immunity plays an important role in the disease pathogenesis; however, little is known how immune system recognizes this human pathogen. In this study, we report that Toll-like receptors recognize distinct proteinase K-resistant glycoconjugates in C. jejuni and Escherichia coli. Lipopolysaccharide is solely proteinase-resistant glycoconjugate in E. coli. In contrast, C. jejuni possesses at least five different components that are resistant to proteinase digestion and are capable of inducing NF-κB activation through TLR2 and TLR4. Possession of multiple activators of Toll-like receptors may be the unique strategy of C. jejuni to trigger hyperimmunity.

  14. The NS5A-binding heat shock proteins HSC70 and HSP70 play distinct roles in the hepatitis C viral life cycle

    PubMed Central

    Khachatoorian, Ronik; Ganapathy, Ekambaram; Ahmadieh, Yasaman; Wheatley, Nicole; Sundberg, Christopher; Jung, Chun-Ling; Arumugaswami, Vaithilingaraja; Raychaudhuri, Santanu; Dasgupta, Asim; French, Samuel W.

    2014-01-01

    We previously identified HSP70 and HSC70 in complex with NS5A in a proteomic screen. Here, coimmunoprecipitation studies confirmed NS5A/HSC70 complex formation during infection, and immunofluorescence studies showed NS5A and HSC70 to colocalize. Unlike HSP70, HSC70 knockdown did not decrease viral protein levels. Rather, intracellular infectious virion assembly was significantly impaired by HSC70 knockdown. We also discovered that both HSC70 nucleotide binding and substrate binding domains directly bind NS5A whereas only the HSP70 nucleotide binding domain does. Knockdown of both HSC70 and HSP70 demonstrated an additive reduction in virus production. This data suggests that HSC70 and HSP70 play discrete roles in the viral life cycle. Investigation of these different functions may facilitate developing of novel strategies that target host proteins to treat HCV infection. PMID:24725938

  15. Distinctive expression patterns of Hedgehog pathway genes in the Ciona intestinalis larva: implications for a role of Hedgehog signaling in postembryonic development and chordate evolution.

    PubMed

    Islam, A F M Tariqul; Moly, Pricila Khan; Miyamoto, Yuki; Kusakabe, Takehiro G

    2010-02-01

    Members of the Hedgehog (Hh) family are soluble ligands that orchestrate a wide spectrum of developmental processes ranging from left-right axis determination of the embryo to tissue patterning and organogenesis. Tunicates, including ascidians, are the closest relatives of vertebrates, and elucidation of Hh signaling in ascidians should provide an important clue towards better understanding the role of this pathway in development. In previous studies, expression patterns of genes encoding Hh and its downstream factor Gli have been examined up to the tailbud stage in the ascidian embryo, but their expression in the larva has not been reported. Here we show the spatial expression patterns of hedgehog (Ci-hh1, Ci-hh2), patched (Ci-ptc), smoothened (Ci-smo), and Gli (Ci-Gli) orthologs in larvae of the ascidian Ciona intestinalis. The expression patterns of Ci-hh2 and Ci-Gli dramatically change during the period between the late tailbud embryo and the swimming larva. At the larval stage, expression of Ci-Gli was found in a central part of the endoderm and in the visceral ganglion, while Ci-hh2 was expressed in two discrete endodermal regions, anteriorly and posteriorly adjacent to the cells expressing Gli. The expression patterns of these genes suggest that the Hh ligand controls postembryonic development of the endoderm and the central nervous system. Expression of a gene encoding Hh in the anterior and/or pharyngeal endoderm is probably an ancient chordate character; diversification of regulation and targets of the Hh signaling in this region may have played a major role in the evolution of chordate body structures.

  16. Distinct Roles of the Active-site Mg2+ Ligands, Asp882 and Asp705, of DNA Polymerase I (Klenow Fragment) during the Prechemistry Conformational Transitions*

    PubMed Central

    Bermek, Oya; Grindley, Nigel D. F.; Joyce, Catherine M.

    2011-01-01

    DNA polymerases catalyze the incorporation of deoxynucleoside triphosphates into a growing DNA chain using a pair of Mg2+ ions, coordinated at the active site by two invariant aspartates, whose removal by mutation typically reduces the polymerase activity to barely detectable levels. Using two stopped-flow fluorescence assays that we developed previously, we have investigated the role of the carboxylate ligands, Asp705 and Asp882, of DNA polymerase I (Klenow fragment) in the early prechemistry steps that prepare the active site for catalysis. We find that neither carboxylate is required for an early conformational transition, reported by a 2-aminopurine probe, that takes place in the open ternary complex after binding of the complementary dNTP. However, the subsequent fingers-closing step requires Asp882; this step converts the open ternary complex into the closed conformation, creating the active-site geometry required for catalysis. Crystal structures indicate that the Asp882 position changes very little during fingers-closing; this side chain may therefore serve as an anchor point to receive the dNTP-associated metal ion as the nucleotide is delivered into the active site. The Asp705 carboxylate is not required until after the fingers-closing step, and we suggest that its role is to facilitate the entry of the second Mg2+ into the active site. The two early prechemistry steps that we have studied take place normally at very low Mg2+ concentrations, although higher concentrations are needed for covalent nucleotide addition, consistent with the second metal ion entering the ternary complex after fingers-closing. PMID:21084297

  17. The role of subcellular distribution of cadmium and phytochelatins in the generation of distinct phenotypes of AtPCS1- and CePCS3-expressing tobacco.

    PubMed

    Wojas, Sylwia; Ruszczyńska, Anna; Bulska, Ewa; Clemens, Stephan; Antosiewicz, Danuta Maria

    2010-08-15

    Exposure to Cd2+ leads to activation of phytochelatin synthase (PCS) and the formation of phytochelatins (PCs) in the cytosol. Binding of Cd by PCs and the subsequent transport of PC-Cd complexes to the vacuole are essential for Cd tolerance. Attempts to improve Cd detoxification by PCS overexpression have resulted in contrasting plant phenotypes, ranging from enhanced Cd tolerance to Cd hypersensitivity. In the present paper, changes in the subcellular phytochelatin, glutathione, gamma-glutamylcysteine and cadmium vacuolar and cytosolic distribution underlying these phenotypes were examined. Cadmium and PCs levels were determined in protoplasts and vacuoles isolated from leaves of Nicotiana tabacum expressing either of two phytochelatin synthase genes, AtPCS1 and CePCS (differing in their level of Cd tolerance; being Cd hypersensitive or more Cd-tolerant as compared to wild-type plants, respectively). We showed that Cd hypersensitivity of AtPCS1-expressing tobacco results from a significant decrease in both the cytosolic and vacuolar pool of PCs, indicating a decreased cadmium detoxification capacity. By contrast, enhanced Cd tolerance of CePCS plants was accompanied by an increased cytosolic and vacuolar SH of PC/Cd ratio, suggesting more efficient Cd detoxification. Surprisingly, the substantially reduced level of PCs did not influence Cd accumulation in vacuoles of AtPCS1-transformed tobacco (relative to the wild-type), which suggests the important role of mechanisms other than PC-Cd transport in Cd translocation to the vacuole. Our data suggest that the key role of the PCs in Cd tolerance is temporary binding of Cd2+ in the cytosol, and contrary to the current view, their contribution to cadmium sequestration seems to be less important.

  18. Overlapping and Distinct Role of CXCR7-SDF-1/ITAC and CXCR4-SDF-1 Axes in Regulating Metastatic Behavior of Human Rhabdomyosarcomas

    PubMed Central

    Grymula, Katarzyna; Tarnowski, Maciej; Wysoczynski, Marcin; Drukala, Justyna; Barr, Frederic G.; Ratajczak, Janina; Kucia, Magdalena; Ratajczak, Mariusz Z

    2010-01-01

    We have demonstrated that the α-chemokine stromal-derived factor (SDF)-1-CXCR4 axis plays an important role in rhabdomyosarcoma (RMS) metastasis. With the recent descriptionof CXCR7, a new receptor for SDF-1 that also binds the interferon-inducible T-cell alpha chemoattractant (ITAC) chemokine, we became interested in the role of the CXCR7-SDF-1/ITAC axis in RMS progression. To address this issue, we evaluated 6 highly metastatic alveolar (A)RMS and 3 less metastatic embryonal (E)RMS cell lines and found that all these cell lines express CXCR7. While CXCR4 was expressed at a much higher level by highly metastatic ARMS lines, CXCR7 was present at a high level on ERMS lines. We also noticed that CXCR7 expression on RMS cells was downregulated in hypoxic conditions. More importantly, the CXCR7 receptor on RMS cell lines was functional after stimulation with ITAC and SDF-1 as evidenced by mitogen-activated protein kinase (MAPK)p42/44 and AKT phosphorylation as well as CXCR7 internalization, chemotaxis, cell motility, and adhesion assays. Similarly to CXCR4, signaling from activated CXCR7 was not associated with increased RMS proliferation or cell survival. Moreover, CXCR7+ RMS cells responded to SDF-1 and I-TAC in the presence of CXCR4 antagonists (T140, AMD3100). Furthermore, while intravenous injection of RMS cells with overexpressed CXCR7 resulted in increased seeding efficiency of tumor cells to bone marrow, CXCR7 downregulation showed the opposite effect. In conclusion, the CXCR7-SDF-1/ITAC axis is involved in the progression of RMS; targeting of the CXCR4-SDF-1 axis alone without simultaneous blockage of CXCR7 will be an inefficient strategy for inhibiting SDF-1-mediated pro-metastatic responses of RMS cells. PMID:20162608

  19. Distinct Roles of Ser-764 and Lys-773 at the N Terminus of von Willebrand Factor in Complex Assembly with Coagulation Factor VIII*

    PubMed Central

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G.; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766–Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764–Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. PMID:23168412

  20. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    PubMed

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-01

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. PMID:23168412

  1. Mycoplasma pulmonis possesses a novel chemoattractant for B lymphocytes.

    PubMed Central

    Ross, S E; Simecka, J W; Gambill, G P; Davis, J K; Cassell, G H

    1992-01-01

    Mycoplasma pulmonis causes chronic murine respiratory mycoplasmosis, which is characterized by extensive peribronchial and perivascular infiltration of mononuclear cells, including B lymphocytes. B-lymphocyte recruitment into sites of inflammation is presently poorly understood but must involve directed chemotaxis of these cells in response to some external recruitment stimulus. In these studies, picogram amounts of M. pulmonis membrane protein were found to possess potent chemoattractant activity for resting rat B lymphocytes. This report is the first description of a bacterially derived chemoattractant for B lymphocytes and offers a unique opportunity to study regulation of B-lymphocyte recruitment to a site of chronic pulmonary inflammation. Furthermore, M. pulmonis membrane activation of fresh rat serum was found to produce a potent stimulus for recruitment of peritoneal and alveolar macrophages. M. pulmonis-mediated recruitment of lymphocytes and macrophages may play a significant role in the pathogenesis of murine respiratory mycoplasmosis, a role in which organisms on the bronchiolar epithelial surfaces may release proteins which can directly or indirectly promote chemotaxis of inflammatory cells from the circulation. PMID:1730502

  2. Superoxide Dismutases, SOD1 and SOD2, Play a Distinct Role in the Fat Body during Pupation in Silkworm Bombyx mori

    PubMed Central

    Nojima, Yosui; Ito, Katsuhiko; Ono, Hiromasa; Nakazato, Takeru; Bono, Hidemasa; Yokoyama, Takeshi; Sato, Ryoichi; Suetsugu, Yoshitaka; Nakamura, Yuki; Yamamoto, Kimiko; Satoh, Jun-ichi; Tabunoki, Hiroko; Fugo, Hajime

    2015-01-01

    One way that aerobic biological systems counteract the generation of reactive oxygen species (ROS) is with superoxide dismutase proteins SOD1 and SOD2 that metabolize superoxide radicals to molecular oxygen and hydrogen peroxide or scavenge oxygen radicals produced by the extensive oxidation-reduction and electron-transport reactions that occur in mitochondria. We characterized SOD1 and SOD2 of Bombyx mori isolated from the fat body of larvae. Immunological analysis demonstrated the presence of BmSOD1 and BmSOD2 in the silk gland, midgut, fat body, Malpighian tubules, testis and ovary from larvae to adults. We found that BmSOD2 had a unique expression pattern in the fat body through the fifth instar larval developmental stage. The anti-oxidative functions of BmSOD1 and BmSOD2 were assessed by exposing larvae to insecticide rotenone or vasodilator isosorbide dinitrate, which is an ROS generator in BmN4 cells; however, exposure to these compounds had no effect on the expression levels of either BmSOD protein. Next, we investigated the physiological role of BmSOD1 and BmSOD2 under environmental oxidative stress, applied through whole-body UV irradiation and assayed using quantitative RT-PCR, immunoblotting and microarray analysis. The mRNA expression level of both BmSOD1 and BmSOD2 was markedly increased but protein expression level was increased only slightly. To examine the differences in mRNA and protein level due to UV irradiation intensity, we performed microarray analysis. Gene set enrichment analysis revealed that genes in the insulin signaling pathway and PPAR signaling pathway were significantly up-regulated after 6 and 12 hours of UV irradiation. Taken together, the activities of BmSOD1 and BmSOD2 may be related to the response to UV irradiation stress in B. mori. These results suggest that BmSOD1 and BmSOD2 modulate environmental oxidative stress in the cell and have a specific role in fat body of B. mori during pupation. PMID:25714339

  3. The distinct roles of anion transporters Slc26a3 (DRA) and Slc26a6 (PAT-1) in fluid and electrolyte absorption in the murine small intestine.

    PubMed

    Xia, Weiliang; Yu, Qin; Riederer, Brigitte; Singh, Anurag Kumar; Engelhardt, Regina; Yeruva, Sunil; Song, Penghong; Tian, De-An; Soleiman, Manoocher; Seidler, Ursula

    2014-08-01

    The mixing of gastric and pancreatic juice subjects the jejunum to unique ionic conditions with high luminal CO2 tension and HCO3 − concentration. We investigated the role of the small intestinal apical anion exchangers PAT-1 (Slc26a6) and DRA (Slc26a3) in basal and CO2/HCO3 −-stimulated jejunal fluid absorption. Single pass perfusion of jejunal segments was performed in anaesthetised wild type (WT) as well as in mice deficient in DRA, PAT-1, Na+/H+ exchanger 3 (NHE3) or NHE2, and in carbonic anhydrase II (CAII). Unbuffered saline (pH 7.4) perfusion of WT jejunum resulted in fluid absorption and acidification of the effluent. DRA-deficient jejunum absorbed less fluid than WT, and acidified the effluent more strongly, consistent with its action as a Cl−/HCO3 − exchanger. PAT-1-deficient jejunum also absorbed less fluid but resulted in less effluent acidification. Switching the luminal solution to a 5 % CO2/HCO3 − buffered solution (pH 7.4), resulted in a decrease in jejunal enterocyte pHi in all genotypes, an increase in luminal surface pH and a strong increase in fluid absorption in a PAT-1- and NHE3- but not DRA-, CAII, or NHE2-dependent fashion. Even in the absence of luminal Cl−, luminal CO2/HCO3 − augmented fluid absorption in WT, CAII, NHE2- or DRA-deficient, but not in PAT-1- or NHE3-deficient mice, indicating the likelihood that PAT-1 serves to import HCO3 − and NHE3 serves to import Na+ under these circumstances. The results suggest that PAT-1 plays an important role in jejunal Na+HCO3 – reabsorption, while DRA absorbs Cl− and exports HCO3 − in a partly CAII-dependent fashion. Both PAT-1 and DRA significantly contribute to intestinal fluid absorption and enterocyte acid/base balance but are activated by different ion gradients.

  4. Superoxide dismutases, SOD1 and SOD2, play a distinct role in the fat body during pupation in silkworm Bombyx mori.

    PubMed

    Nojima, Yosui; Ito, Katsuhiko; Ono, Hiromasa; Nakazato, Takeru; Bono, Hidemasa; Yokoyama, Takeshi; Sato, Ryoichi; Suetsugu, Yoshitaka; Nakamura, Yuki; Yamamoto, Kimiko; Satoh, Jun-ichi; Tabunoki, Hiroko; Fugo, Hajime

    2015-01-01

    One way that aerobic biological systems counteract the generation of reactive oxygen species (ROS) is with superoxide dismutase proteins SOD1 and SOD2 that metabolize superoxide radicals to molecular oxygen and hydrogen peroxide or scavenge oxygen radicals produced by the extensive oxidation-reduction and electron-transport reactions that occur in mitochondria. We characterized SOD1 and SOD2 of Bombyx mori isolated from the fat body of larvae. Immunological analysis demonstrated the presence of BmSOD1 and BmSOD2 in the silk gland, midgut, fat body, Malpighian tubules, testis and ovary from larvae to adults. We found that BmSOD2 had a unique expression pattern in the fat body through the fifth instar larval developmental stage. The anti-oxidative functions of BmSOD1 and BmSOD2 were assessed by exposing larvae to insecticide rotenone or vasodilator isosorbide dinitrate, which is an ROS generator in BmN4 cells; however, exposure to these compounds had no effect on the expression levels of either BmSOD protein. Next, we investigated the physiological role of BmSOD1 and BmSOD2 under environmental oxidative stress, applied through whole-body UV irradiation and assayed using quantitative RT-PCR, immunoblotting and microarray analysis. The mRNA expression level of both BmSOD1 and BmSOD2 was markedly increased but protein expression level was increased only slightly. To examine the differences in mRNA and protein level due to UV irradiation intensity, we performed microarray analysis. Gene set enrichment analysis revealed that genes in the insulin signaling pathway and PPAR signaling pathway were significantly up-regulated after 6 and 12 hours of UV irradiation. Taken together, the activities of BmSOD1 and BmSOD2 may be related to the response to UV irradiation stress in B. mori. These results suggest that BmSOD1 and BmSOD2 modulate environmental oxidative stress in the cell and have a specific role in fat body of B. mori during pupation. PMID:25714339

  5. Analysis of Drosophila p8 and p52 mutants reveals distinct roles for the maintenance of TFIIH stability and male germ cell differentiation

    PubMed Central

    Cruz-Becerra, Grisel; Juárez, Mandy; Valadez-Graham, Viviana

    2016-01-01

    Eukaryotic gene expression is activated by factors that interact within complex machinery to initiate transcription. An important component of this machinery is the DNA repair/transcription factor TFIIH. Mutations in TFIIH result in three human syndromes: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Transcription and DNA repair defects have been linked to some clinical features of these syndromes. However, how mutations in TFIIH affect specific developmental programmes, allowing organisms to develop with particular phenotypes, is not well understood. Here, we show that mutations in the p52 and p8 subunits of TFIIH have a moderate effect on the gene expression programme in the Drosophila testis, causing germ cell differentiation arrest in meiosis, but no Polycomb enrichment at the promoter of the affected differentiation genes, supporting recent data that disagree with the current Polycomb-mediated repression model for regulating gene expression in the testis. Moreover, we found that TFIIH stability is not compromised in p8 subunit-depleted testes that show transcriptional defects, highlighting the role of p8 in transcription. Therefore, this study reveals how defects in TFIIH affect a specific cell differentiation programme and contributes to understanding the specific syndrome manifestations in TFIIH-afflicted patients. PMID:27805905

  6. Overlapping and Distinct Roles of Aspergillus fumigatus UDP-glucose 4-Epimerases in Galactose Metabolism and the Synthesis of Galactose-containing Cell Wall Polysaccharides*

    PubMed Central

    Lee, Mark J.; Gravelat, Fabrice N.; Cerone, Robert P.; Baptista, Stefanie D.; Campoli, Paolo V.; Choe, Se-In; Kravtsov, Ilia; Vinogradov, Evgeny; Creuzenet, Carole; Liu, Hong; Berghuis, Albert M.; Latgé, Jean-Paul; Filler, Scott G.; Fontaine, Thierry; Sheppard, Donald C.

    2014-01-01

    The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis. PMID:24257745

  7. Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis

    PubMed Central

    Amiya, Takeru; Nakamoto, Nobuhiro; Chu, Po-sung; Teratani, Toshiaki; Nakajima, Hideaki; Fukuchi, Yumi; Taniki, Nobuhito; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Ebinuma, Hirotoshi; Kanai, Takanori

    2016-01-01

    The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9+ inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9+Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11blowF4/80high hepatic-resident Mφs were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9+Mφs were firmly replaced by donors, indicating that CCR9+Mφs originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU+CCR9+Mφs with a proliferative potential were detected specifically in the inflamed liver, and in vitro study revealed that BM-derived CD11b+ cells co-cultured with hepatic stellate cells (HSCs) or stimulated with retinoic acids could acquire CCR9 with antigen-presenting ability. Collectively, our study demonstrates that inflammatory Mφs originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury. PMID:27725760

  8. Distinct roles for extracellular-signal-regulated protein kinase (ERK) mitogen-activated protein kinases and phosphatidylinositol 3-kinase in the regulation of Mcl-1 synthesis.

    PubMed Central

    Schubert, K M; Duronio, V

    2001-01-01

    Alterations in the expression of various Bcl-2 family members may act as one means by which a cell's survival may be regulated. The mechanism by which cytokines regulate expression of Bcl-2 family members was examined in the haemopoietic cell line TF-1. Cytokine-induced Mcl-1 protein expression was shown to be controlled through a pathway dependent upon phosphatidylinositol 3-kinase (PI 3-kinase). The cytokine-induced increase in mRNA transcription was not dependent upon PI 3-kinase, thus dissociating the immediate-early transcription factors responsible for Mcl-1 transcription from the PI 3-kinase signalling pathway. In contrast, Mcl-1 mRNA levels were dependent upon MEK [mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated protein kinase kinase] activation, suggesting a role for the Ras/MEK/MAPK pathway in Mcl-1 transcription. Activation of PI 3-kinase was shown to be necessary to stimulate Mcl-1 protein translation. This was not due to any effect on prolonging the half-life of the protein. Finally, the lipid second messenger ceramide was shown to cause a reduction in Mcl-1 protein translation, probably via its ability to inhibit protein kinase B activation, providing further clues regarding the death-inducing effect of this lipid. PMID:11368774

  9. The Plexin PLX-2 and the Ephrin EFN-4 Have Distinct Roles in MAB-20/Semaphorin 2A Signaling in Caenorhabditis elegans Morphogenesis

    PubMed Central

    Nakao, Fumi; Hudson, Martin L.; Suzuki, Motoshi; Peckler, Zachary; Kurokawa, Rie; Liu, Zhicen; Gengyo-Ando, Keiko; Nukazuka, Akira; Fujii, Takashi; Suto, Fumikazu; Shibata, Yukimasa; Shioi, Go; Fujisawa, Hajime; Mitani, Shohei; Chisholm, Andrew D.; Takagi, Shin

    2007-01-01

    Semaphorins are extracellular proteins that regulate axon guidance and morphogenesis by interacting with a variety of cell surface receptors. Most semaphorins interact with plexin-containing receptor complexes, although some interact with non-plexin receptors. Class 2 semaphorins are secreted molecules that control axon guidance and epidermal morphogenesis in Drosophila and Caenorhabditis elegans. We show that the C. elegans class 2 semaphorin MAB-20 binds the plexin PLX-2. plx-2 mutations enhance the phenotypes of hypomorphic mab-20 alleles but not those of mab-20 null alleles, indicating that plx-2 and mab-20 act in a common pathway. Both mab-20 and plx-2 mutations affect epidermal morphogenesis during embryonic and in postembryonic development. In both contexts, plx-2 null mutant phenotypes are much less severe than mab-20 null phenotypes, indicating that PLX-2 is not essential for MAB-20 signaling. Mutations in the ephrin efn-4 do not synergize with mab-20, indicating that EFN-4 may act in MAB-20 signaling. EFN-4 and PLX-2 are coexpressed in the late embryonic epidermis where they play redundant roles in MAB-20-dependent cell sorting. PMID:17507686

  10. Overlapping and distinct roles of Aspergillus fumigatus UDP-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides.

    PubMed

    Lee, Mark J; Gravelat, Fabrice N; Cerone, Robert P; Baptista, Stefanie D; Campoli, Paolo V; Choe, Se-In; Kravtsov, Ilia; Vinogradov, Evgeny; Creuzenet, Carole; Liu, Hong; Berghuis, Albert M; Latgé, Jean-Paul; Filler, Scott G; Fontaine, Thierry; Sheppard, Donald C

    2014-01-17

    The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis.

  11. EFO1 and EFO2, encoding putative WD-domain proteins, have overlapping and distinct roles in the regulation of vegetative development and flowering of Arabidopsis.

    PubMed

    Wang, Wuyi; Yang, Dennis; Feldmann, Kenneth A

    2011-01-01

    From screening a population of Arabidopsis overexpression lines, two Arabidopsis genes were identified, EFO1 (early flowering by overexpression 1) and EFO2, that confer early flowering when overexpressed. The two genes encode putative WD-domain proteins which share high sequence similarity and constitute a small subfamily. Interestingly, the efo2-1 loss-of-function mutant also flowered earlier in short days and slightly earlier in long days than the wild type, while no flowering-time or morphological differences were observed in efo1-1 relative to the wild type. In addition, the efo2-1 mutation perturbed hypocotyl elongation, leaf expansion and formation, and stem elongation. EFO1 and EFO2 are both regulated by the circadian clock. Expression and genetic analyses revealed that EFO2 suppresses flowering largely through the action of CONSTANS (CO) and flowering locus T (FT), suggesting that EFO2 is a negative regulator of photoperiodic flowering. The growth defects in efo2-1 were augmented in efo1 efo2, but the induction of FT in the double mutant was comparable to that in efo2-1. Thus, while EFO2 acts as a floral repressor, EFO1 may not be directly involved in flowering, but the two genes do have overlapping roles in regulating other developmental processes. EFO1 and EFO2 may function collectively to serve as one of the converging points where the signals of growth and flowering intersect. PMID:21242318

  12. The genetic and structural basis of two distinct terminal side branch residues in stewartan and amylovoran exopolysaccharides and their potential role in host adaptation.

    PubMed

    Wang, Xiaolei; Yang, Fan; von Bodman, Susanne B

    2012-01-01

    Stewartan and amylovoran exopolysaccharide (EPS) produced by the plant pathogenic bacteria Pantoea stewartii and Erwinia amylovora are virulence factors in the cause of Stewart's vascular wilt and fire blight. The biosynthesis of amylovoran and stewartan is encoded by a set of homologous operons that have been partially characterized, although some annotations are solely on the basis of sequence homology. The major distinguishing features of these two EPS forms are the presence of a terminal pyruvate in amylovoran and glucose in stewartan, even though the gene systems to account for both are conserved and present in each bacterium. This study explores the genetic, structural and functional differences of amylovoran and stewartan, and their potential role in host adaptation. We report that the pyruvyl transferase gene in P. stewartii is non-functional, while the terminal glucosyl transferase is catalytically active. Conversely, in E. amylovora, the homologous glucosyl transferase activity appears to be relatively ineffective, while the pyruvyl transferase function predominates. We also show that the terminally pyruvylated versus glucosylated EPS require specific repeating unit translocases (Wzx). We discuss the evolutionary, functional and biological implications of the terminally pyruvylated and glucosylated polymers and their potential contribution to plant and insect host adaptation.

  13. Arabidopsis cytosolic acyl-CoA-binding proteins ACBP4, ACBP5 and ACBP6 have overlapping but distinct roles in seed development

    PubMed Central

    Hsiao, An-Shan; Haslam, Richard P.; Michaelson, Louise V.; Liao, Pan; Chen, Qin-Fang; Sooriyaarachchi, Sanjeewani; Mowbray, Sherry L.; Napier, Johnathan A.; Tanner, Julian A.; Chye, Mee-Len

    2014-01-01

    Eukaryotic cytosolic ACBPs (acyl-CoA-binding proteins) bind acyl-CoA esters and maintain a cytosolic acyl-CoA pool, but the thermodynamics of their protein–lipid interactions and physiological relevance in plants are not well understood. Arabidopsis has three cytosolic ACBPs which have been identified as AtACBP4, AtACBP5 and AtACBP6, and microarray data indicated that all of them are expressed in seeds; AtACBP4 is expressed in early embryogenesis, whereas AtACBP5 is expressed later. ITC (isothermal titration calorimetry) in combination with transgenic Arabidopsis lines were used to investigate the roles of these three ACBPs from Arabidopsis thaliana. The dissociation constants, stoichiometry and enthalpy change of AtACBP interactions with various acyl-CoA esters were determined using ITC. Strong binding of recombinant (r) AtACBP6 with long-chain acyl-CoA (C16- to C18-CoA) esters was observed with dissociation constants in the nanomolar range. However, the affinity of rAtACBP4 and rAtACBP5 to these acyl-CoA esters was much weaker (dissociation constants in the micromolar range), suggesting that they interact with acyl-CoA esters differently from rAtACBP6. When transgenic Arabidopsis expressing AtACBP6pro::GUS was generated, strong GUS (β-glucuronidase) expression in cotyledonary-staged embryos and seedlings prompted us to measure the acyl-CoA contents of the acbp6 mutant. This mutant accumulated higher levels of C18:1-CoA and C18:1- and C18:2-CoAs in cotyledonary-staged embryos and seedlings, respectively, in comparison with the wild type. The acbp4acbp5acbp6 mutant showed the lightest seed weight and highest sensitivity to abscisic acid during germination, suggesting their physiological functions in seeds. PMID:25423293

  14. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

    PubMed

    Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

    2015-12-01

    Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

  15. LHCBM1 and LHCBM2/7 Polypeptides, Components of Major LHCII Complex, Have Distinct Functional Roles in Photosynthetic Antenna System of Chlamydomonas reinhardtii*

    PubMed Central

    Ferrante, Paola; Ballottari, Matteo; Bonente, Giulia; Giuliano, Giovanni; Bassi, Roberto

    2012-01-01

    The photosystem II antenna of Chlamydomonas reinhardtii is composed of monomeric and trimeric complexes, the latter encoded by LHCBM genes. We employed artificial microRNA technology to specifically silence the LHCBM2 and LHCBM7 genes, encoding identical mature polypeptides, and the LHCBM1 gene. As a control, we studied the npq5 mutant, deficient in the LHCBM1 protein. The organization of LHCII complexes, functional antenna size, capacity for photoprotection, thermal energy dissipation and state transitions, and resistance to reactive oxygen species was studied in the various genotypes. Silencing of the LHCBM2/7 genes resulted in a decrease of an LHCII protein with an apparent molecular mass of 22 kDa, whereas silencing/lack of LHCBM1 caused the decrease/disappearance of a 23-kDa protein. A decrease in the abundance of trimeric LHCII complexes and in functional antenna size was observed in both LHCBM2/7 and LHCBM1 knockouts. In agreement with previous data, depletion of LHCBM1 decreased the capacity for excess energy dissipation but not the ability to perform state transitions. The opposite was true for LHCBM2/7, implying that this polypeptide has a different functional role from LHCBM1. The abundance of LHCBM1 and LHCBM2/7 is in both cases correlated with resistance to superoxide anion, whereas only LHCBM1 is also involved in singlet oxygen scavenging. These results suggest that different LHCBM components have well defined, non-redundant functions despite their high homology, implying that engineering of LHCBM proteins can be an effective strategy for manipulating the light harvesting system of Chlamydomonas reinhardtii. PMID:22431727

  16. Structural analysis and mutant growth properties reveal distinctive enzymatic and cellular roles for the three major L-alanine transaminases of Escherichia coli.

    PubMed

    Peña-Soler, Esther; Fernandez, Francisco J; López-Estepa, Miguel; Garces, Fernando; Richardson, Andrew J; Quintana, Juan F; Rudd, Kenneth E; Coll, Miquel; Vega, M Cristina

    2014-01-01

    In order to maintain proper cellular function, the metabolism of the bacterial microbiota presents several mechanisms oriented to keep a correctly balanced amino acid pool. Central components of these mechanisms are enzymes with alanine transaminase activity, pyridoxal 5'-phosphate-dependent enzymes that interconvert alanine and pyruvate, thereby allowing the precise control of alanine and glutamate concentrations, two of the most abundant amino acids in the cellular amino acid pool. Here we report the 2.11-Å crystal structure of full-length AlaA from the model organism Escherichia coli, a major bacterial alanine aminotransferase, and compare its overall structure and active site composition with detailed atomic models of two other bacterial enzymes capable of catalyzing this reaction in vivo, AlaC and valine-pyruvate aminotransferase (AvtA). Apart from a narrow entry channel to the active site, a feature of this new crystal structure is the role of an active site loop that closes in upon binding of substrate-mimicking molecules, and which has only been previously reported in a plant enzyme. Comparison of the available structures indicates that beyond superficial differences, alanine aminotransferases of diverse phylogenetic origins share a universal reaction mechanism that depends on an array of highly conserved amino acid residues and is similarly regulated by various unrelated motifs. Despite this unifying mechanism and regulation, growth competition experiments demonstrate that AlaA, AlaC and AvtA are not freely exchangeable in vivo, suggesting that their functional repertoire is not completely redundant thus providing an explanation for their independent evolutionary conservation.

  17. Distinct roles for insulin and insulin-like growth factor-1 receptors in pancreatic beta-cell glucose sensing revealed by RNA silencing.

    PubMed Central

    Da Silva Xavier, Gabriela; Qian, Qingwen; Cullen, Peter J; Rutter, Guy A

    2004-01-01

    The importance of the insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF-1R) for glucose-regulated insulin secretion and gene expression in pancreatic islet beta-cells is at present unresolved. Here, we have used small interfering RNAs (siRNAs) to silence the expression of each receptor selectively in clonal MIN6 beta-cells. Reduction of IR levels by >90% completely inhibited glucose (30 mM compared with 3 mM)-induced insulin secretion, but had no effect on depolarization-stimulated secretion. IR depletion also blocked the accumulation of preproinsulin (PPI), pancreatic duodenum homoeobox-1 (PDX-1) and glucokinase (GK) mRNAs at elevated glucose concentrations, as assessed by quantitative real-time PCR analysis (TaqMan). Similarly, depletion of IGF-1R inhibited glucose-induced insulin secretion but, in contrast with the effects of IR silencing, had little impact on the regulation of gene expression by glucose. Moreover, loss of IGF-1R, but not IR, markedly inhibited glucose-stimulated increases in cytosolic and mitochondrial ATP, suggesting a role for IGF-1R in the maintenance of oxidative metabolism and in the generation of mitochondrial coupling factors. RNA silencing thus represents a useful tool for the efficient and selective inactivation of receptor tyrosine kinases in isolated beta-cells. By inhibiting glucose-stimulated insulin secretion through the inactivation of IGF-1R, this approach also demonstrates the existence of insulin-independent mechanisms whereby elevated glucose concentrations regulate PPI, PDX-1 and GK gene expression in beta-cells. PMID:14563207

  18. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

    PubMed Central

    Parker, Andrew; Cross, Sally H.; Jackson, Ian J.; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R.; Brown, Steve D. M.

    2015-01-01

    ABSTRACT Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. PMID:26542706

  19. Tobacco bZIP transcription factor TGA2.2 and related factor TGA2.1 have distinct roles in plant defense responses and plant development.

    PubMed

    Thurow, Corinna; Schiermeyer, Andreas; Krawczyk, Stefanie; Butterbrodt, Thomas; Nickolov, Kaloian; Gatz, Christiane

    2005-10-01

    Salicylic acid (SA) is a crucial internal signaling molecule needed for the induction of plant defense responses upon attack of a variety of pathogens. Basic leucine zipper transcription factors of the TGA family bind to activating sequence-1 (as-1)-like elements which are SA-responsive cis elements found in promoters of 'immediate early' and 'late' SA-inducible genes. TGA2.2 constitutes the main component of tobacco as-1-binding factor-1 (ASF-1). TGA2.1, which differs from TGA2.2 by being able to activate transcription in yeast, constitutes a minor fraction of the complex. Both proteins interact with NPR1, a protein essential for SA inducibility of 'late' genes. Here we demonstrate using dsRNAi mediated gene silencing that reducing the amount of TGA2.2 and TGA2.1 correlates with a significant decrease in ASF-1 activity and with a decreased inducibility of both 'immediate early' and 'late' genes. In contrast, reducing the amount of TGA2.1 alone had no effect on the expression of these target genes suggesting that TGA2.1 is dispensable for SA-inducible gene expression from the as-1 element. Expression of a TGA2.2 mutant unable to form heterodimers with the endogenous pool of TGA factors led to reduced SA-inducibility of 'immediate early' gene Nt103, indicating that the native leucine zipper is important for the protein to act positively on transcription. Plants with reduced amounts of TGA2.1 developed petal like stamens indicating a regulatory role of TGA2.1 in defining organ identity in tobacco flowers. A model is suggested that unifies conflicting results on the function of tobacco TGA factors with respect to activation of the 'late' PR-1a promoter.

  20. Distinct catalytic activity and in vivo roles of the ExoIII and EndoIV AP endonucleases from Sulfolobus islandicus.

    PubMed

    Yan, Zhou; Huang, Qihong; Ni, Jinfeng; Shen, Yulong

    2016-09-01

    AP endonuclease cleaves the phosphodiester bond 5'- to the AP (apurinic or apyrimidinic) sites and is one of the major enzymes involved in base excision repair. So far, the properties of several archaeal AP endonuclease homologues have been characterized in vitro, but little is known about their functions in vivo. Herein, we report on the biochemical and genetic analysis of two AP endonucleases, SisExoIII and SisEndoIV, from the hyperthermophilic crenarchaeon Sulfolobus islandicus REY15A. Both SisExoIII and SisEndoIV exhibit AP endonuclease activity, but neither of them has 3'-5' exonuclease activity. SisExoIII and SisEndoIV have similar K M values on the substrate containing an AP site, but the latter cleaves the AP substrate at a dramatically higher catalytic rate than the former. Unlike other AP endonucleases identified in archaea, SisExoIII and SisEndoIV do not exhibit any cleavage activity on DNA having oxidative damage (8-oxo-dG) or uracil. Genetic analysis revealed that neither gene is essential for cell viability, and the growth of ∆SiRe_2666 (endoIV), ∆SiRe_0100 (exoIII), and ∆SiRe_0100∆SiRe_2666 is not affected under normal growth conditions. However, ∆SiRe_2666 exhibits higher sensitivity to the alkylating agent methyl methanesulfonate (MMS) than ∆SiRe_0100. Over-expression of SiRe_0100 can partially complement the sensitivity of ∆SiRe_2666 to MMS, suggesting a backup role of SisExoIII in AP site processing in vivo. Intriguingly, over-expression of SisEndoIV renders the strain more sensitive to MMS than the control. Taken together, we conclude that SisEndoIV, but not SisExoIII, is the main AP endonuclease that participates directly in base excision repair in S. islandicus. PMID:27457080

  1. The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter.

    PubMed

    Martin, Luc J; Tremblay, Jacques J

    2009-02-01

    The steroidogenic acute regulatory protein plays an essential role in steroid biosynthesis in steroidogenic cells. It is involved in the transport of cholesterol through the mitochondrial membrane where the first step of steroidogenesis occurs. Star gene expression in testicular Leydig cells is regulated by the pituitary LH through the cAMP signaling pathway. So far, several transcription factors have been implicated in the regulation of Star promoter activity in these cells. These include the nuclear receptors NUR77 and SF1, AP-1 family members (particularly c-JUN), GATA4, C/EBPbeta, DLX5/6, and CREB. Some of these factors were also shown to act in a cooperative manner to further enhance Star promoter activity. Here, we report that NUR77 and c-JUN have additive effects on the Star promoter. These effects were abolished only when both elements, NUR77 at -95 bp and AP-1 at -78 bp, were mutated. Consistent with this, in vitro co-immunoprecipitation revealed that NUR77 and c-JUN interact and that this interaction is mediated through part of the ligand binding domain of NUR77. Furthermore, we found that SF1 could cooperate with c-JUN on the mouse Star promoter but this cooperation involved different regulatory elements. Collectively, our data not only provide new insights into the molecular mechanisms that control mouse Star transcription in Leydig cells but also reveal a novel mechanism for the regulation of NR4A1-dependent genes in tissues where NUR77 and c-JUN factors are co-expressed.

  2. Distinct Roles of the Repeat-Containing Regions and Effector Domains of the Vibrio vulnificus Multifunctional-Autoprocessing Repeats-in-Toxin (MARTX) Toxin

    PubMed Central

    Kim, Byoung Sik; Gavin, Hannah E.

    2015-01-01

    ABSTRACT Vibrio vulnificus is a seafood-borne pathogen that destroys the intestinal epithelium, leading to rapid bacterial dissemination and death. The most important virulence factor is the multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin comprised of effector domains in the center region flanked by long repeat-containing regions which are well conserved among MARTX toxins and predicted to translocate effector domains. Here, we examined the role of the repeat-containing regions using a modified V. vulnificus MARTX (MARTXVv) toxin generated by replacing all the internal effector domains with β-lactamase (Bla). Bla activity was detected in secretions from the bacterium and also in the cytosol of intoxicated epithelial cells. The modified MARTXVv toxin without effector domains retained its necrotic activity but lost its cell-rounding activity. Further, deletion of the carboxyl-terminal repeat-containing region blocked toxin secretion from the bacterium. Deletion of the amino-terminal repeat-containing region had no effect on secretion but completely abolished translocation and necrosis. Neither secretion nor translocation was affected by enzymatically inactivating the cysteine protease domain of the toxin. These data demonstrate that the amino-terminal and carboxyl-terminal repeat-containing regions of the MARTXVv toxin are necessary and sufficient for the delivery of effector domains and epithelial cell lysis in vitro but that effector domains are required for other cytopathic functions. Furthermore, Ca2+-dependent secretion of the modified MARTXVv toxin suggests that nonclassical RTX-like repeats found in the carboxyl-terminal repeat-containing region are functionally similar to classical RTX repeats found in other RTX proteins. PMID:25827415

  3. 1. FRONT FACADE (Photograph of photograph in possession of Turner ...

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

    1. FRONT FACADE (Photograph of photograph in possession of Turner Associates and Nicholas Satterlee Associates, Washington, DC, 1973.) - 1 & 2 Logan Circle (House), Washington, District of Columbia, DC

  4. 27 CFR 31.202 - Possession of refilled liquor bottles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... liquor bottles. 31.202 Section 31.202 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Liquor Bottles § 31.202 Possession of refilled liquor bottles. No person who sells, or offers for sale, distilled spirits, or agent or employee of such person, shall: (a) Possess any liquor bottle in which...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 person... circumstances: (a) The owner or occupant of any premises on which the used bottles have been lawfully...

  6. 12 CFR 558.1 - Procedure upon taking possession.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Procedure upon taking possession. 558.1 Section 558.1 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY POSSESSION BY CONSERVATORS AND RECEIVERS FOR FEDERAL AND STATE SAVINGS ASSOCIATIONS § 558.1 Procedure upon taking...

  7. 25 CFR 11.452 - Possession of a controlled substance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... unlawful for a person to knowingly or intentionally possess any controlled substance listed in 21 CFR Part... by 21 CFR 1308.21 through 1308.35, as amended; or (3) The provisions of 42 U.S.C. 1996a (regarding... 25 Indians 1 2010-04-01 2010-04-01 false Possession of a controlled substance. 11.452 Section...

  8. 24 CFR 27.117 - Transfer of title and possession.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Transfer of title and possession. 27.117 Section 27.117 Housing and Urban Development Office of the Secretary, Department of Housing... Foreclosure of Single Family Mortgages § 27.117 Transfer of title and possession. (a) If the Secretary is...

  9. An Interpretive Approach to Inalienable Possession in French.

    ERIC Educational Resources Information Center

    Herschensohn, Julia

    The Lexicalist-interpretive approach to inalienable possession adopted in this paper proposes that body parts are generated with either the article (the unmarked determiner) or the possessive adjective (the marked determiner). The unmarked body part is codesignate with the indirect object; in the case of pseudo-transitives--a clearly delimited…

  10. 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

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  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. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Atlantic coastal port, including ports in the Gulf of Mexico and Caribbean Sea, must have all fins and... 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...

  1. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Atlantic coastal port, including ports in the Gulf of Mexico and Caribbean Sea, must have all fins and... 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...

  2. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Atlantic coastal port, including ports in the Gulf of Mexico and Caribbean Sea, must have all fins and... 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...

  3. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Atlantic coastal port, including ports in the Gulf of Mexico and Caribbean Sea, must have all fins and... 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...

  4. 50 CFR 635.30 - Possession at sea and landing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Atlantic coastal port, including ports in the Gulf of Mexico and Caribbean Sea, must have all fins and... 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....

  5. 22 CFR 72.15 - Action when possession is impractical.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Action when possession is impractical. 72.15 Section 72.15 Foreign Relations DEPARTMENT OF STATE PROTECTION AND WELFARE OF AMERICANS, THEIR PROPERTY....15 Action when possession is impractical. (a) A consular officer should not take physical...

  6. 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…

  7. 45 CFR 670.6 - Prior possession exception.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Prior possession exception. 670.6 Section 670.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION CONSERVATION OF ANTARCTIC ANIMALS AND PLANTS Prohibited Acts, Exceptions § 670.6 Prior possession exception....

  8. Histone deacetylase 4 possesses intrinsic nuclear import and export signals.

    PubMed

    Wang, A H; Yang, X J

    2001-09-01

    Nucleocytoplasmic trafficking of histone deacetylase 4 (HDAC4) plays an important role in regulating its function, and binding of 14-3-3 proteins is necessary for its cytoplasmic retention. Here, we report the identification of nuclear import and export sequences of HDAC4. While its N-terminal 118 residues modulate the nuclear localization, residues 244 to 279 constitute an authentic, strong nuclear localization signal. Mutational analysis of this signal revealed that three arginine-lysine clusters are necessary for its nuclear import activity. As for nuclear export, leucine-rich sequences located in the middle part of HDAC4 do not function as nuclear export signals. By contrast, a hydrophobic motif (MXXLXVXV) located at the C-terminal end serves as a nuclear export signal that is necessary for cytoplasmic retention of HDAC4. This motif is required for CRM1-mediated nuclear export of HDAC4. Furthermore, binding of 14-3-3 proteins promotes cytoplasmic localization of HDAC4 by both inhibiting its nuclear import and stimulating its nuclear export. Unlike wild-type HDAC4, a point mutant with abrogated MEF2-binding ability remains cytoplasmic upon exogenous expression of MEF2C, supporting the notion that direct MEF2 binding targets HDAC4 to the nucleus. Therefore, HDAC4 possesses intrinsic nuclear import and export signals for its dynamic nucleocytoplasmic shuttling, and association with 14-3-3 and MEF2 proteins affects such shuttling and thus directs HDAC4 to the cytoplasm and the nucleus, respectively.

  9. 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.

  10. 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. PMID:21667381

  11. Dissociative trance disorder: clinical and Rorschach findings in ten persons reporting demon possession and treated by exorcism.

    PubMed

    Ferracuti, S; Sacco, R; Lazzari, R

    1996-06-01

    Although dissociative trance disorders, especially possession disorder, are probably more common than is usually though, precise clinical data are lacking. Ten persons undergoing exorcisms for devil trance possession state were studied with the Dissociative Disorders Diagnostic Schedule and the Rorschach test. These persons had many traits in common with dissociative identity disorder patients. They were overwhelmed by paranormal experiences. Despite claiming possession by a demon, most of them managed to maintain normal social functioning. Rorschach findings showed that these persons had a complex personality organization: Some of them displayed a tendency to oversimplify stimulus perception whereas others seemed more committed to psychological complexity. Most had severe impairment of reality testing, and 6 of the participants had an extratensive coping stile. In this group of persons reporting demon possession, dissociative trance disorder seems to be a distinct clinical manifestation of a dissociative continuum, sharing some features with dissociative identity disorder.

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

    PubMed

    Woessner, Warren D; Chadwick, Robin A

    2014-11-01

    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. PMID:25237144

  13. A VICTIM OF AN EPIDEMIC OF POSSESSION SYNDROME

    PubMed Central

    Chandrashekar, C. R.

    1981-01-01

    SUMMARY A case of young man who got possessed by a god and two spirits alternatively is reported. He was one of the four victims of an epidemic of possession by two spirits (Mohini). The epidemic occurred following the prediction that the two women who committed suicide, would become Mohinis and liaunt adult men. It appeared that the strong belief and expectation in the local culture made the index person who was otherwise well adjusted in life to get possessed. The implication of this finding is discussed. PMID:22058566

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 10. Photocopy of a measured drawing (original in the possession ...

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

    10. Photocopy of a measured drawing (original in the possession of the Kunstakademiets, Copenhagen, Denmark; catalogued under the 'Vestindienstudier', 1961) ELEVATIONS AND SECTIONS OF TWO SECOND-FLOOR DOORS - Kompagnigade 51 (House), 51 Company Street, Christiansted, St. Croix, VI

  2. 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

  3. 2. Photocopy of photograph (Original in possession of Woodstock Historical ...

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

    2. Photocopy of photograph (Original in possession of Woodstock Historical Society) date unknown. Reproduced by permission. LOOKING NORTH TOWARDS GEORGE PERKINS MARSH HISTORICAL LANDMARK - Elm Street Bridge, Spanning Ottauquechee River, Woodstock, Windsor County, VT

  4. 3. Photocopy of photograph (Original in possession of Woodstock Historical ...

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

    3. Photocopy of photograph (Original in possession of Woodstock Historical Society) date unknown. Reproduced by permission. LOOKING NORTH TOWARD GEORGE PERKINS MARSH NATIONAL HISTORICAL LANDMARK - Elm Street Bridge, Spanning Ottauquechee River, Woodstock, Windsor County, VT

  5. Isolation and synthesis of polyoxygenated dibenzofurans possessing biological activity.

    PubMed

    Love, Brian E

    2015-06-01

    Reports from the past ten years describing the isolation and/or synthesis of bioactive dibenzofurans possessing three or more oxygen-containing substituents are reviewed. Dibenzofuranoquinones are included in the review.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  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. WEST ELEVATION IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 280, Sylvan Drive, Rock Island, Rock Island County, IL

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Photographic copy of photograph (circa 1927) (original print in possession ...

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

    Photographic copy of photograph (circa 1927) (original print in possession of Brunner and Brunner, Architect and Engineers, Inc., St. Joseph, Missouri) VIEW OF SOUTHEAST CORNER - Old City Auditorium, 404-424 North Fourth Street, Saint Joseph, Buchanan County, MO

  10. Photocopy of photograph (original print in possession of Brunner and ...

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

    Photocopy of photograph (original print in possession of Brunner and Brunner, Architect and Engineers, Inc., St. Joseph, Missouri). Photographer unknown. VIEW OF EAST FRONT BEFORE ALTERATIONS - Old City Auditorium, 404-424 North Fourth Street, Saint Joseph, Buchanan County, MO

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 42. Photocopy of bridge drawing, 1923 (original in possession of ...

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

    42. Photocopy of bridge drawing, 1923 (original in possession of Wilkes-Barre City Engineer's Office) ALTERNATE DESIGN - South Street Bridge, Spans Pennsylvania Avenue, Wilkes-Barre Boulevard, Pocono Northeast Railroad, Wilkes-Barre, Luzerne 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). FINAL INSPECTION - 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). OLIVING - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  4. 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

  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). LARGE HOLE-OPENING - 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). DRILLING - 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). MACHINE SHOP - Turtle Mountain Ordnance Plant, 213 First Street Northwest, Rolla, Rolette County, ND

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. First possession, history, and young children's ownership judgments.

    PubMed

    Friedman, Ori; Van de Vondervoort, Julia W; Defeyter, Margaret A; Neary, Karen R

    2013-01-01

    It is impossible to perceive who owns an object; this must be inferred. One way that children make such inferences is through a first possession bias--when two agents each use an object, children judge the object belongs to the one who used it first. Two experiments show that this bias does not result from children directly inferring ownership from first possession; the experiments instead support an alternative account according to which the first possession bias reflects children's historical reasoning. In Experiment 1, eighty-five 3- to 5-year-olds only based inferences on first possession when it was informative about the past. In Experiment 2, thirty-two 5-year-olds based ownership judgments on testimony about past contact, while disregarding testimony about future contact.

  16. The concept possession hypothesis of self-consciousness.

    PubMed

    Savanah, Stephane

    2012-06-01

    This paper presents the hypothesis that concept possession is sufficient and necessary for self-consciousness. If this is true it provides a yardstick for gauging the validity of different research paradigms in which claims for self-consciousness in animals or human infants are made: a convincing demonstration of concept possession in a research subject, such as a display of inferential reasoning, may be taken as conclusive evidence of self-consciousness. Intuitively, there appears to be a correlation between intelligence in animals (which presupposes concept possession) and the existence of self-consciousness. I present three discussions to support the hypothesis: an analogy between perception and conception, where both are self-specifying; an argument that any web of concepts will always include the self-concept; and a fresh interpretation of Bermũdez (1998) showing how his theory of non-conceptual content provides strong support for the concept possession hypothesis.

  17. 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

  18. 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

  19. 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

  20. 10. Photocopy of negative (original in possession of Chiricahua National ...

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

    10. Photocopy of negative (original in possession of Chiricahua National Monument), photographer unknown, c.1910 JA HU STAFFORD AND YOUNGEST DAUGHTER IN FRONT OF WEST SIDE OF CABIN - Faraway Ranch, Stafford-Riggs Cabin, Willcox, Cochise County, AZ

  1. 20. Photograph of line drawing in possession of Engineering Plans ...

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

    20. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. SOUTH ELEVATION, 1964. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  2. 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. FIRST FLOOR PLAN, 1936. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  3. 19. Photograph of line drawing in possession of Engineering Plans ...

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

    19. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. NORTH ELEVATION, 1964. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  4. 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. SOUTH AND EAST ELEVATIONS. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  5. 17. Photograph of line drawing in possession of Engineering Plans ...

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

    17. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. SECOND FLOOR PLAN, 1936. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  6. 12. Photograph of a photograph in possession of Rock Island ...

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

    12. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. COMMANDING OFFICER'S OFFICE, FIRST FLOOR. DATED 1898. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  7. 18. Photograph of line drawing in possession of Engineering Plans ...

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

    18. Photograph of line drawing in possession of Engineering Plans and Services Division, Rock Island Arsenal. WEST AND EAST ELEVATIONS, 1964. - Rock Island Arsenal, Building No. 360, Gillespie Avenue between Rodman Avenue & North Avenue, Rock Island, Rock Island County, IL

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 15. Photocopy of photograph (original in the possession of the ...

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

    15. Photocopy of photograph (original in the possession of the Cooper County Court) Photographer Lloyd Grotjan (1987). ORIGINAL BLUEPRINT OF NORTH END APPROACH STRUCTURE - Roberts Bluff Bridge, .5 mile East of Blackwater, Blackwater, Cooper County, MO

  18. 13. Photocopy of photograph (original in the possession of the ...

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

    13. Photocopy of photograph (original in the possession of the Cooper County Court) Photographer Lloyd Grotjan (1987). VIEW OF MAIN SPAN PROPOSAL - Roberts Bluff Bridge, .5 mile East of Blackwater, Blackwater, Cooper County, MO

  19. 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)

  20. 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

  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. 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

  3. 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

  4. 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

  5. 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

  6. 14. Photocopy of photograph (original print in possession of George ...

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

    14. Photocopy of photograph (original print in possession of George Pavlica, Bovey, MN) 1913, photographer unknown, cityscape with tower in background - Bovey Water Tower, Eighth Avenue & T.H. 169, Bovey, Itasca County, MN

  7. Photographic copy of the original (1896) architectural drawing in possession ...

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

    Photographic copy of the original (1896) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. Details for two country rooms, third floor. - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  8. Photographic copy of the original (1896) architectural drawing in possession ...

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

    Photographic copy of the original (1896) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. Details of Fifth Street entrance, staircase, elevator. - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  9. Photographic copy of the original (1896) architectural drawing in possession ...

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

    Photographic copy of the original (1896) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. West elevation. - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  10. Photographic copy of the original (1896) architectural drawing in possession ...

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

    Photographic copy of the original (1896) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. Rear (southern) elevation). - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  11. Photographic copy of the original (1934) architectural drawing in possession ...

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

    Photographic copy of the original (1934) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. Fifth Street (north) elevation and south (west) elevation - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  12. Photographic copy of the original (1896) architectural drawing in possession ...

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

    Photographic copy of the original (1896) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. North elevation of Fifth Street. - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  13. Photographic copy of the original (1934) architectural drawing in possession ...

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

    Photographic copy of the original (1934) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. Rear (south) elevation. - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  14. Photographic copy of the original (1896) architectural drawing in possession ...

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

    Photographic copy of the original (1896) architectural drawing in possession of U.S. Postal Service, Pueblo, Colorado. East elevation on Main Street. - Pueblo Federal Building & Post Office, 421 North Main Street, Pueblo, Pueblo County, CO

  15. 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

  16. 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, UNDATED. - Rock Island Arsenal, Building No. 4, Terrace Avenue between Gillespie & East Avenues, Rock Island, Rock Island County, IL

  17. 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. PLAN, UNDATED. - Rock Island Arsenal, Building No. 64, Rodman Avenue between Second & Third Streets, Rock Island, Rock Island County, IL

  18. 50 CFR 648.52 - Possession and landing limits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., or possess more than 50 bu (17.6 hL) of in-shell scallops shoreward of the VMS Demarcation Line. Such....2 hL) of in-shell scallops seaward of the VMS demarcation line on a properly declared IFQ scallop... vessel may possess up to 50 bu (17.6 hL) of in-shell scallops seaward of the VMS demarcation line on...

  19. 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

  20. Escherichia coli K-12 possesses multiple cryptic but functional chaperone-usher fimbriae with distinct surface specificities.

    PubMed

    Korea, Charalampia-Georgia; Badouraly, Réana; Prevost, Marie-Christine; Ghigo, Jean-Marc; Beloin, Christophe

    2010-07-01

    Commensal and pathogenic Escherichia coli adherence to host and environmental surfaces is mediated by a variety of adhesins. Although extensively studied as a model bacterium, 34% of the genes in the E. coli K-12 genome have no known function. We hypothesized that some of them may correspond to functional adhesins. We characterized E. coli K-12 ycb, ybg, yfc, yad, yra, sfm and yeh operons, which display sequence and organizational homologies to type 1 fimbriae exported by the chaperone/usher pathway. We showed that, although these operons are poorly expressed under laboratory conditions, six of them are nevertheless functional when expressed, and promote adhesion to abiotic and/or epithelial cell surfaces. While the studied fimbriae display different binding specificities, we obtained evidence of synergy/interference with other adhesins such as Ag43 or type 1 fimbriae. We showed that their expression is under the negative control of H-NS and, except for yad, subjected to cAMP receptor protein-mediated activation and carbon catabolite repression. These results therefore demonstrate that ycb, yfc, yad, yra, sfm and yeh operons encode cryptic but functional fimbriae adhesins whose expression following environmental modifications could contribute to E. coli's ability to adhere to and colonize a wide diversity of surfaces in its various ecological niches.

  1. To do, to have, or to share? Valuing experiences over material possessions depends on the involvement of others.

    PubMed

    Caprariello, Peter A; Reis, Harry T

    2013-02-01

    Recent evidence indicates that spending discretionary money with the intention of acquiring life experiences-events that one lives through-makes people happier than spending money with the intention of acquiring material possessions-tangible objects that one obtains and possesses. We propose and show that experiences are more likely to be shared with others, whereas material possessions are more prone to solitary use and that this distinction may account for their differential effects on happiness. In 4 studies, we present evidence demonstrating that the inclusion of others is a key dimension of how people derive happiness from discretionary spending. These studies showed that when the social-solitary and experiential-material dimensions were considered simultaneously, social discretionary spending was favored over solitary discretionary spending, whereas experiences showed no happiness-producing advantage relative to possessions. Furthermore, whereas spending money on socially shared experiences was valued more than spending money on either experiences enacted alone or material possessions, solitary experiences were no more valued than material possessions. Together, these results extend and clarify the basic findings of prior research and add to growing evidence that the social context of experiences is critical for their effects on happiness.

  2. Tourette's syndrome: from demonic possession and psychoanalysis to the discovery of gene.

    PubMed

    Germiniani, Francisco M B; Miranda, Anna Paula P; Ferenczy, Peter; Munhoz, Renato P; Teive, Hélio A G

    2012-07-01

    In this paper we make a brief historical review of the hypothesis concerning the etiology of Tourette's syndrome (TS), focusing on varying trends over time: at first, its presumed relation to witchcraft and demonic possessions, followed by the psychoanalytical theory, which attributed TS to a masturbatory equivalent. Then, progressing to modern time, to the immunological theory and finally the advent of genetics and their role in the etiology of TS.

  3. Tourette's syndrome: from demonic possession and psychoanalysis to the discovery of gene.

    PubMed

    Germiniani, Francisco M B; Miranda, Anna Paula P; Ferenczy, Peter; Munhoz, Renato P; Teive, Hélio A G

    2012-07-01

    In this paper we make a brief historical review of the hypothesis concerning the etiology of Tourette's syndrome (TS), focusing on varying trends over time: at first, its presumed relation to witchcraft and demonic possessions, followed by the psychoanalytical theory, which attributed TS to a masturbatory equivalent. Then, progressing to modern time, to the immunological theory and finally the advent of genetics and their role in the etiology of TS. PMID:22836463

  4. First possession: an assumption guiding inferences about who owns what.

    PubMed

    Friedman, Ori

    2008-04-01

    How do we determine who owns what? This article reports evidence indicating that we typically assume that the first person who possesses an object is its owner. In Experiments 1 and 2, participants read cartoons in which two children each take a turn playing with a toy. Participants selected the character who first possessed the toy when judging who owned it, but not when judging which character liked it more. In Experiment 3, participants read stories based on the Pierson v. Post (1805) property law case. In line with the appellate court's ruling in that case, participants selected the character who first captured and possessed an animal as its owner over another character who had pursued it earlier. Together, these findings provide evidence for an assumption that specifically guides our reasoning about ownership and that may lead everyday intuitions about property to be generally consistent with property law.

  5. 29. Photocopy of photograph (original slide in possession of the ...

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

    29. Photocopy of photograph (original slide in possession of the Preservation Society of Charleston, Charleston, South Carolina; Collection of Dr. and Mrs. E. L. Powers, Charleston, South Carolina) Photographer unknown, Christmas 1935 DETAIL, FIRST FLOOR, SOUTH ROOM, MANTELPIECE AND CHIMNEY BREAST, LOOKING WEST - 8 Court House Square (House), Charleston, Charleston County, SC

  6. 41. Photocopy of photograph (original photograph in possession of Sacramento ...

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

    41. Photocopy of photograph (original photograph in possession of Sacramento Archives and Museum Collection Center, Sacramento, California) Original photographer and year unknown. A WHEAT FIELD ON THE NATOMAS LANDS. - Reclamation District 1000, Northwest Sacramento County & southwest Sutter County, bisected by State Highway No. 99, Sacramento, Sacramento County, CA

  7. 9. Photograph of a photograph in possession of Rock Island ...

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

    9. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SECOND FLOOR, EAST WING. MOTORIZED MACHINING EQUIPMENT USED IN MANUFACTURE OF MACHINE GUN PARTS. SHOWN IN THE FOREGROUND IS A PRATT & WHITNEY VERTICAL MILLING MACHINE. DATED JANUARY 21, 1943. - Rock Island Arsenal, Building No. 68, Rodman Avenue between Fourth Street & East Avenue, Rock Island, Rock Island County, IL

  8. 1. Photographic copy of photograph, in possession of SCIP Office, ...

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

    1. Photographic copy of photograph, in possession of SCIP Office, Coolidge, AZ. No date, circa 1940. Photographer unknown. HEADQUARTERS OFFICE, 205 W. ROOSEVELT, COOLIDGE, AZ. - San Carlos Irrigation Project, San Carlos Irrigation Project Headquarters, 205 West Roosevelt, Coolidge, Pinal County, AZ

  9. 16. Photocopy of drawing (Original in the possession of Richard ...

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

    16. Photocopy of drawing (Original in the possession of Richard F. McCann, F.A.I.A., Seattle, WA) B. Marcus Priteca, Architect, Date unknown SUB-BASEMENT FLOOR PLAN (Negative is 4' x 5') - Pantages Theatre & Jones Building, 901-909 Broadway, Tacoma, Pierce County, WA

  10. 50 CFR 648.106 - Summer flounder possession restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... flounder are filleted into single (butterfly) fillets, each fillet is deemed to be from one whole summer... trawl vessels issued a permit under § 648.4(a)(3) that fish with or possess nets or pieces of net on... for inspection in standard 100-lb (45.3-kg) totes or fish boxes having a liquid capacity of 18.2...

  11. 50 CFR 648.106 - Summer flounder possession restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... flounder are filleted into single (butterfly) fillets, each fillet is deemed to be from one whole summer... trawl vessels issued a permit under § 648.4(a)(3) that fish with or possess nets or pieces of net on... for inspection in standard 100-lb (45.3-kg) totes or fish boxes having a liquid capacity of 18.2...

  12. 50 CFR 648.106 - Summer flounder possession restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... flounder are filleted into single (butterfly) fillets, each fillet is deemed to be from one whole summer... trawl vessels issued a permit under § 648.4(a)(3) that fish with or possess nets or pieces of net on... for inspection in standard 100-lb (45.3-kg) totes or fish boxes having a liquid capacity of 18.2...

  13. Cherished Possessions: A New England Legacy. Educator's Resource Guide.

    ERIC Educational Resources Information Center

    Peters, Amy L.

    The exhibition, "Cherished Possessions: A New England Legacy," consists of approximately 200 objects drawn from the Society for the Preservation of New England Antiquities collection of fine and decorative arts. Each item in the exhibition has been selected for its ability to tell a story and to place the history of that item within the larger…

  14. 14. Photocopy of photograph (original negative in the possession of ...

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

    14. Photocopy of photograph (original negative in the possession of the Allen County Museum, Ebesole Studio Glass Plate Negative Collection, circa 1900), photographer unknown VIEW SOUTHEAST SHOWING HOLLAND BLOCK BUILDING AND ANNEX - Holland Block Annex, 112-116 East High Street, Lima, Allen County, OH

  15. 13. Photocopy of photograph (original photocopy in the possession of ...

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

    13. Photocopy of photograph (original photocopy in the possession of the Allen County Museum, circa 1900), photographer unknown VIEW SOUTHEAST SHOWING HOLLAND BLOCK BUILDING AND ANNEX DURING A PARADE FOR THE GRAND ARMY OF THE REPUBLIC - Holland Block Annex, 112-116 East High Street, Lima, Allen County, OH

  16. 15. Photocopy of photograph (original photocopy in the possession of ...

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

    15. Photocopy of photograph (original photocopy in the possession of the Allen County Museum, circa 1930), photographer unknown VIEW OF THE HOLLAND BUILDING AND ANNEX FOLLOWING THE 1929 FIRE - Holland Block Annex, 112-116 East High Street, Lima, Allen County, OH

  17. 23. Photocopy of drawing (original in possession of Naval Surface ...

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

    23. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL, FAN HOUSING ASSEMBLY, 1952 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  18. 14. Photocopy of drawing (original in possession of Naval Surface ...

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

    14. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL, FRAMING PLAN, TOP AND BOTTOM, 1941 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  19. 15. Photocopy of drawing (original in possession of Naval Surface ...

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

    15. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL, ELEVATIONS E-E TO H-H AND SECTIONS, 1941 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  20. 20. Photocopy of drawing (original in possession of Naval Surface ...

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

    20. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL FIRST FLOOR PLANS AND DETAILS, 1948 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD