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Sample records for ngtrf1 reveals unique

  1. Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not shared by other old world arenaviruses.

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    Hadar Israeli

    2017-04-01

    Full Text Available Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.

  2. Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.

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    Taiga Miyazaki

    2013-01-01

    Full Text Available Proper protein folding in the endoplasmic reticulum (ER is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR, is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata.

  3. The complete genome sequence of Bacillus velezensis strain GH1-13 reveals agriculturally beneficial properties and a unique plasmid.

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    Kim, Sang Yoon; Song, Hajin; Sang, Mee Kyung; Weon, Hang-Yeon; Song, Jaekyeong

    2017-10-10

    The bacterial strain Bacillus velezensis GH1-13, isolated from rice paddy soil in Korea, has been shown to promote plant growth and have strong antagonistic activities against pathogens. Here, we report the complete genome sequence of GH1-13, revealing that it possesses a single 4,071,980-bp circular chromosome with 46.2% GC-content. The chromosome encodes 3,930 genes, and we have also identified a unique plasmid in the strain that encodes a further 104 genes (71,628bp and 31.7% GC-content). The genome was found to contain various enzyme-encoding operons, including indole-3-acetic acid (IAA) biosynthesis proteins, 2,3-butanediol dehydrogenase, various non-ribosomal peptide synthetases, and several polyketide synthases. These properties are responsible for the promotion of plant growth and the biosynthesis of secondary metabolites. They therefore have multiple beneficial effects that could be applied to agriculture. Through curing, we found that the unique plasmid of GH1-13 has important roles in the production of phytohormones, such as IAA, and in shaping phenotypic and physiological characteristics. The plasmid therefore likely influences the biological activities of GH1-13. The complete genome sequence of B. velezensis GH1-13 contributes to our understanding of this beneficial strain and will encourage research into its development for agricultural or biotechnological applications, enhancing productivity and crop quality. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures.

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    Moon Young Lee

    Full Text Available Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC, which serve as slow-wave electrical pacemakers for gastrointestinal (GI smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

  5. Revealing a steroid receptor ligand as a unique PPAR[gamma] agonist

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    Lin, Shengchen; Han, Ying; Shi, Yuzhe; Rong, Hui; Zheng, Songyang; Jin, Shikan; Lin, Shu-Yong; Lin, Sheng-Cai; Li, Yong (Pitt); (Xiamen)

    2012-06-28

    Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPAR{gamma} agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPAR{gamma} target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPAR{gamma} ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPAR{gamma} ligands in the treatment of insulin resistance.

  6. "1"8F-FDG PET reveals unique features of large vessel inflammation in patients with Takayasu's arteritis

    International Nuclear Information System (INIS)

    Incerti, Elena; Fallanca, Federico; Alongi, Pierpaolo; Gianolli, Luigi; Picchio, Maria; Tombetti, Enrico; Sartorelli, Silvia; Sabbadini, Maria Grazia; Manfredi, Angelo A.; Baldissera, Elena M.; Tombolini, Elisabetta; Papa, Maurizio; De Cobelli, Francesco; Mason, Justin C.

    2017-01-01

    The object of this study was to assess whether "1"8F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu's arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions <4 mm thick. We studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUV_m_a_x), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated. Increased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUV_m_a_x values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUV_m_a_x in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria. PET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potential confounder. Prospective

  7. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.

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    Xiao, Gang; Chan, Lai N; Klemm, Lars; Braas, Daniel; Chen, Zhengshan; Geng, Huimin; Zhang, Qiuyi Chen; Aghajanirefah, Ali; Cosgun, Kadriye Nehir; Sadras, Teresa; Lee, Jaewoong; Mirzapoiazova, Tamara; Salgia, Ravi; Ernst, Thomas; Hochhaus, Andreas; Jumaa, Hassan; Jiang, Xiaoyan; Weinstock, David M; Graeber, Thomas G; Müschen, Markus

    2018-04-05

    B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1. Reflecting B-cell-specific transcriptional PPP-repression, glucose carbon utilization in B cells is heavily skewed in favor of glycolysis resulting in lack of PPP-dependent antioxidant protection. These findings reveal a gatekeeper function of the PPP in a broad range of B cell malignancies that can be efficiently targeted by small molecule inhibition of PP2A and G6PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. 4.0-A resolution cryo-EM structure of the mammalian chaperonin TRiC/CCT reveals its unique subunit arrangement.

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    Cong, Yao; Baker, Matthew L; Jakana, Joanita; Woolford, David; Miller, Erik J; Reissmann, Stefanie; Kumar, Ramya N; Redding-Johanson, Alyssa M; Batth, Tanveer S; Mukhopadhyay, Aindrila; Ludtke, Steven J; Frydman, Judith; Chiu, Wah

    2010-03-16

    The essential double-ring eukaryotic chaperonin TRiC/CCT (TCP1-ring complex or chaperonin containing TCP1) assists the folding of approximately 5-10% of the cellular proteome. Many TRiC substrates cannot be folded by other chaperonins from prokaryotes or archaea. These unique folding properties are likely linked to TRiC's unique heterooligomeric subunit organization, whereby each ring consists of eight different paralogous subunits in an arrangement that remains uncertain. Using single particle cryo-EM without imposing symmetry, we determined the mammalian TRiC structure at 4.7-A resolution. This revealed the existence of a 2-fold axis between its two rings resulting in two homotypic subunit interactions across the rings. A subsequent 2-fold symmetrized map yielded a 4.0-A resolution structure that evinces the densities of a large fraction of side chains, loops, and insertions. These features permitted unambiguous identification of all eight individual subunits, despite their sequence similarity. Independent biochemical near-neighbor analysis supports our cryo-EM derived TRiC subunit arrangement. We obtained a Calpha backbone model for each subunit from an initial homology model refined against the cryo-EM density. A subsequently optimized atomic model for a subunit showed approximately 95% of the main chain dihedral angles in the allowable regions of the Ramachandran plot. The determination of the TRiC subunit arrangement opens the way to understand its unique function and mechanism. In particular, an unevenly distributed positively charged wall lining the closed folding chamber of TRiC differs strikingly from that of prokaryotic and archaeal chaperonins. These interior surface chemical properties likely play an important role in TRiC's cellular substrate specificity.

  9. Identification and genetic characterization of unique HIV-1 A1/C recombinant strain in South Africa.

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    Musyoki, Andrew M; Rakgole, Johnny N; Selabe, Gloria; Mphahlele, Jeffrey

    2015-03-01

    HIV isolates from South Africa are predominantly subtype C. Sporadic isolation of non-C strains has been reported mainly in cosmopolitan cities. HIV isolate j51 was recovered from a rural South African heterosexual female aged 51 years. Near full length amplification of the genome was attempted using PCR with primers targeting overlapping segments of the HIV genome. Analysis of 5593 bp (gag to vpu) at a bootstrap value greater than 70% found that all but the vpu gene was HIV-1 subtype A1. The vpu gene was assigned HIV-1 subtype C. The recombination breaking point was estimated at position 6035+/- 15 bp with reference to the beginning of the HXB2 reference strain. Isolate j51 revealed a unique genome constellation to previously reported recombinant strains with parental A/C backbones from South Africa though a common recombination with subtype C within the vpu gene. Identification of recombinant strains supports continued surveillance of HIV genetic diversity.

  10. Salivary gland proteome analysis reveals modulation of anopheline unique proteins in insensitive acetylcholinesterase resistant Anopheles gambiae mosquitoes.

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    Sylvie Cornelie

    Full Text Available Insensitive acetylcholinesterase resistance due to a mutation in the acetylcholinesterase (ace encoding ace-1 gene confers cross-resistance to organophosphate and carbamate insecticides in Anopheles gambiae populations from Central and West Africa. This mutation is associated with a strong genetic cost revealed through alterations of some life history traits but little is known about the physiological and behavioural changes in insects bearing the ace-1(R allele. Comparative analysis of the salivary gland contents between An. gambiae susceptible and ace-1(R resistant strains was carried out to charaterize factors that could be involved in modifications of blood meal process, trophic behaviour or pathogen interaction in the insecticide-resistant mosquitoes. Differential analysis of the salivary gland protein profiles revealed differences in abundance for several proteins, two of them showing major differences between the two strains. These two proteins identified as saglin and TRIO are salivary gland-1 related proteins, a family unique to anopheline mosquitoes, one of them playing a crucial role in salivary gland invasion by Plasmodium falciparum sporozoites. Differential expression of two other proteins previously identified in the Anopheles sialome was also observed. The differentially regulated proteins are involved in pathogen invasion, blood feeding process, and protection against oxidation, relevant steps in the outcome of malaria infection. Further functional studies and insect behaviour experiments would confirm the impact of the modification of the sialome composition on blood feeding and pathogen transmission abilities of the resistant mosquitoes. The data supports the hypothesis of alterations linked to insecticide resistance in the biology of the primary vector of human malaria in Africa.

  11. Uranium(VI) coordination polymers with pyromellitate ligand: Unique 1D channel structures and diverse fluorescence

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    Zhang, Yingjie, E-mail: yzx@ansto.gov.au [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Bhadbhade, Mohan [Mark Wainwright Analytical Centre, University of New South Wales, Kensington, NSW 2052 (Australia); Karatchevtseva, Inna [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Price, Jason R. [Australian Synchrotron, 800 Blackburn Road, Clayton, VIC 3168 (Australia); Liu, Hao [Centre for Clean Energy Technology, School of Chemistry and Forensic Science, University of Technology Sydney, PO Box 123, Broadway, Sydney, NSW 2007 (Australia); Zhang, Zhaoming; Kong, Linggen [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Čejka, Jiří [Department of Mineralogy, National Museum, Václavské náměstí, 68, Prague 1, 115 79-CZ (Czech Republic); Lu, Kim; Lumpkin, Gregory R. [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia)

    2015-03-15

    Three new coordination polymers of uranium(VI) with pyromellitic acid (H{sub 4}btca) have been synthesized and structurally characterized. (ED)[(UO{sub 2})(btca)]·(DMSO)·3H{sub 2}O (1) (ED=ethylenediammonium; DMSO=dimethylsulfoxide) has a lamellar structure with intercalation of ED and DMSO. (NH{sub 4}){sub 2}[(UO{sub 2}){sub 6}O{sub 2}(OH){sub 6}(btca)]·~6H{sub 2}O (2) has a 3D framework built from 7-fold coordinated uranyl trinuclear units and btca ligands with 1D diamond-shaped channels (~8.5 Å×~8.6 Å). [(UO{sub 2}){sub 2}(H{sub 2}O)(btca)]·4H{sub 2}O (3) has a 3D network constructed by two types of 7-fold coordinated uranium polyhedron. The unique μ{sub 5}-coordination mode of btca in 3 enables the formation of 1D olive-shaped large channels (~4.5 Å×~19 Å). Vibrational modes, thermal stabilities and fluorescence properties have been investigated. - Graphical abstract: Table of content: three new uranium(VI) coordination polymers with pyromellitic acid (H{sub 4}btca) have been synthesized via room temperature and hydrothermal synthesis methods, and structurally characterized. Two to three dimensional (3D) frameworks are revealed. All 3D frameworks have unique 1D large channels. Their vibrational modes, thermal stabilities and photoluminescence properties have been investigated. - Highlights: • Three new coordination polymers of U(VI) with pyromellitic acid (H{sub 4}btca). • Structures from a 2D layer to 3D frameworks with unique 1D channels. • Unusual µ{sub 5}-(η{sub 1}:η{sub 2}:η{sub 1}:η{sub 2:}η{sub 1}) coordination mode of btca ligand. • Vibrational modes, thermal stabilities and luminescent properties reported.

  12. Secondary metabolites from the unique bamboo, Melocanna baccifera.

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    Govindan, Balaji; Johnson, Anil John; Viswanathan, Gayathri; Ramaswamy, Venkataraman; Koshy, Konnath Chacko; Baby, Sabulal

    2018-02-15

    Phytochemistry of fruits and leaves of the unique bamboo Melocanna baccifera resulted in the isolation of 27 secondary metabolites, including 4-Oxabicyclo[3.2.2]nona-1(7),5,8-triene and Verbacine. Biological activity studies of Verbacine revealed it as an inhibitor of acetylcholinesterase and as cytotoxic against C6 cancer cells.

  13. Phylogenetic analysis of canine distemper virus in South America clade 1 reveals unique molecular signatures of the local epidemic.

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    Fischer, Cristine D B; Gräf, Tiago; Ikuta, Nilo; Lehmann, Fernanda K M; Passos, Daniel T; Makiejczuk, Aline; Silveira, Marcos A T; Fonseca, André S K; Canal, Cláudio W; Lunge, Vagner R

    2016-07-01

    Canine distemper virus (CDV) is a highly contagious pathogen for domestic dogs and several wild carnivore species. In Brazil, natural infection of CDV in dogs is very high due to the large non-vaccinated dog population, a scenario that calls for new studies on the molecular epidemiology. This study investigates the phylodynamics and amino-acid signatures of CDV epidemic in South America by analyzing a large dataset compiled from publicly available sequences and also by collecting new samples from Brazil. A population of 175 dogs with canine distemper (CD) signs was sampled, from which 89 were positive for CDV, generating 42 new CDV sequences. Phylogenetic analysis of the new and publicly available sequences revealed that Brazilian sequences mainly clustered in South America 1 (SA1) clade, which has its origin estimated to the late 1980's. The reconstruction of the demographic history in SA1 clade showed an epidemic expanding until the recent years, doubling in size every nine years. SA1 clade epidemic distinguished from the world CDV epidemic by the emergence of the R580Q strain, a very rare and potentially detrimental substitution in the viral genome. The R580Q substitution was estimated to have happened in one single evolutionary step in the epidemic history in SA1 clade, emerging shortly after introduction to the continent. Moreover, a high prevalence (11.9%) of the Y549H mutation was observed among the domestic dogs sampled here. This finding was associated (p<0.05) with outcome-death and higher frequency in mixed-breed dogs, the later being an indicator of a continuous exchange of CDV strains circulating among wild carnivores and domestic dogs. The results reported here highlight the diversity of the worldwide CDV epidemic and reveal local features that can be valuable for combating the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

    Science.gov (United States)

    Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

    2018-01-01

    Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma

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    Totoki, Yasushi; Yoshida, Akihiko; Hosoda, Fumie; Nakamura, Hiromi; Hama, Natsuko; Ogura, Koichi; Yoshida, Aki; Fujiwara, Tomohiro; Arai, Yasuhito; Toguchida, Junya; Tsuda, Hitoshi; Miyano, Satoru; Kawai, Akira

    2014-01-01

    Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors. PMID:25024164

  16. A High-Resolution Crystal Structure of a Psychrohalophilic α-Carbonic Anhydrase from Photobacterium profundum Reveals a Unique Dimer Interface.

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    Vijayakumar Somalinga

    Full Text Available Bacterial α-carbonic anhydrases (α-CA are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α-CA (PprCA reveals that the protein is a heterogeneous mix of monomers and dimers. Furthermore, an "in-gel" carbonic anhydrase activity assay, also known as protonography, revealed two distinct bands corresponding to monomeric and dimeric forms of PprCA that are catalytically active. The crystal structure of PprCA was determined in its native form and reveals a highly conserved "knot-topology" that is characteristic of α-CA's. Similar to other bacterial α-CA's, PprCA also crystallized as a dimer. Furthermore, dimer interface analysis revealed the presence of a chloride ion (Cl- in the interface which is unique to PprCA and has not been observed in any other α-CA's characterized so far. Molecular dynamics simulation and chloride ion occupancy analysis shows 100% occupancy for the Cl- ion in the dimer interface. Zinc coordinating triple histidine residues, substrate binding hydrophobic patch residues, and the hydrophilic proton wire residues are highly conserved in PprCA and are identical to other well-studied α-CA's.

  17. Structure of the large terminase from a hyperthermophilic virus reveals a unique mechanism for oligomerization and ATP hydrolysis.

    Science.gov (United States)

    Xu, Rui-Gang; Jenkins, Huw T; Antson, Alfred A; Greive, Sandra J

    2017-12-15

    The crystal structure of the large terminase from the Geobacillus stearothermophilus bacteriophage D6E shows a unique relative orientation of the N-terminal adenosine triphosphatase (ATPase) and C-terminal nuclease domains. This monomeric 'initiation' state with the two domains 'locked' together is stabilized via a conserved C-terminal arm, which may interact with the portal protein during motor assembly, as predicted for several bacteriophages. Further work supports the formation of an active oligomeric state: (i) AUC data demonstrate the presence of oligomers; (ii) mutational analysis reveals a trans-arginine finger, R158, indispensable for ATP hydrolysis; (iii) the location of this arginine is conserved with the HerA/FtsK ATPase superfamily; (iv) a molecular docking model of the pentamer is compatible with the location of the identified arginine finger. However, this pentameric model is structurally incompatible with the monomeric 'initiation' state and is supported by the observed increase in kcat of ATP hydrolysis, from 7.8 ± 0.1 min-1 to 457.7 ± 9.2 min-1 upon removal of the C-terminal nuclease domain. Taken together, these structural, biophysical and biochemical data suggest a model where transition from the 'initiation' state into a catalytically competent pentameric state, is accompanied by substantial domain rearrangements, triggered by the removal of the C-terminal arm from the ATPase active site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. The unique N-terminal zinc finger of synaptotagmin-like protein 4 reveals FYVE structure.

    Science.gov (United States)

    Miyamoto, Kazuhide; Nakatani, Arisa; Saito, Kazuki

    2017-12-01

    Synaptotagmin-like protein 4 (Slp4), expressed in human platelets, is associated with dense granule release. Slp4 is comprised of the N-terminal zinc finger, Slp homology domain, and C2 domains. We synthesized a compact construct (the Slp4N peptide) corresponding to the Slp4 N-terminal zinc finger. Herein, we have determined the solution structure of the Slp4N peptide by nuclear magnetic resonance (NMR). Furthermore, experimental, chemical modification of Cys residues revealed that the Slp4N peptide binds two zinc atoms to mediate proper folding. NMR data showed that eight Cys residues coordinate zinc atoms in a cross-brace fashion. The Simple Modular Architecture Research Tool database predicted the structure of Slp4N as a RING finger. However, the actual structure of the Slp4N peptide adopts a unique C 4 C 4 -type FYVE fold and is distinct from a RING fold. To create an artificial RING finger (ARF) with specific ubiquitin-conjugating enzyme (E2)-binding capability, cross-brace structures with eight zinc-ligating residues are needed as the scaffold. The cross-brace structure of the Slp4N peptide could be utilized as the scaffold for the design of ARFs. © 2017 The Protein Society.

  19. Runtime analysis of the (1+1) EA on computing unique input output sequences

    DEFF Research Database (Denmark)

    Lehre, Per Kristian; Yao, Xin

    2010-01-01

    Computing unique input output (UIO) sequences is a fundamental and hard problem in conformance testing of finite state machines (FSM). Previous experimental research has shown that evolutionary algorithms (EAs) can be applied successfully to find UIOs for some FSMs. However, before EAs can...... in the theoretical analysis, and the variability of the runtime. The numerical results fit well with the theoretical results, even for small problem instance sizes. Together, these results provide a first theoretical characterisation of the potential and limitations of the (1 + 1) EA on the problem of computing UIOs....

  20. Molecular Evolutionary Characterization of a V1R Subfamily Unique to Strepsirrhine Primates

    Science.gov (United States)

    Yoder, Anne D.; Chan, Lauren M.; dos Reis, Mario; Larsen, Peter A.; Campbell, C. Ryan; Rasoloarison, Rodin; Barrett, Meredith; Roos, Christian; Kappeler, Peter; Bielawski, Joseph; Yang, Ziheng

    2014-01-01

    Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1Rstrep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1Rstrep-α and V1Rstrep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1Rstrep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available. PMID:24398377

  1. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  2. Breaking down pluripotency in the porcine embryo reveals both a premature and reticent stem cell state in the inner cell mass and unique expression profiles of the naive and primed stem cell states.

    Science.gov (United States)

    Hall, Vanessa Jane; Hyttel, Poul

    2014-09-01

    To date, it has been difficult to establish bona fide porcine embryonic stem cells (pESC) and stable induced pluripotent stem cells. Reasons for this remain unclear, but they may depend on inappropriate culture conditions. This study reports the most insights to date on genes expressed in the pluripotent cells of the porcine embryo, namely the inner cell mass (ICM), the trophectoderm-covered epiblast (EPI), and the embryonic disc epiblast (ED). Specifically, we reveal that the early porcine ICM represents a premature state of pluripotency due to lack of translation of key pluripotent proteins, and the late ICM enters a transient, reticent pluripotent state which lacks expression of most genes associated with pluripotency. We describe a unique expression profile of the porcine EPI, reflecting the naive stem cell state, including expression of OCT4, NANOG, CRIPTO, and SSEA-1; weak expression of NrOB1 and REX1; but very limited expression of genes in classical pathways involved in regulating pluripotency. The porcine ED, reflecting the primed stem cell state, can be characterized by the expression of OCT4, NANOG, SOX2, KLF4, cMYC, REX1, CRIPTO, and KLF2. Further cell culture experiments using inhibitors against FGF, JAK/STAT, BMP, WNT, and NODAL pathways on cell cultures derived from day 5 and 10 embryos reveal the importance of FGF, JAK/STAT, and BMP signaling in maintaining cell proliferation of pESCs in vitro. Together, this article provides new insights into the regulation of pluripotency, revealing unique stem cell states in the different porcine stem cell populations derived from the early developing embryo.

  3. Scissors and unique-parity modes of M1 excitation in deformed nuclei

    International Nuclear Information System (INIS)

    Otsuka, T.

    1989-01-01

    In this paper the possible modes of M1 excitation in deformed even-even nuclei are studied in terms of the particle-number-conserved Nilsson + BCS formalism with the standard parameters. The spurious motion with respect to the rotation is removed. In addition to the Scissors mode, the Unique-Parity Spin and Normal-Parity Spin modes are suggested, although the latter may be fragmented to a large extent. The Scissors mode carries most of the orbital strength, while the others the spin strength. The proton Unique-Parity (i.e. Oh 11/12 ) Spin mode for 164 Dy is obtained just below Ex = 3 MeV with B(M1) ∼ 0.2 μ 2 N ) in the sum rule limit. This is in a good agreement to the recent experimental data

  4. Light and electron microscopy of the European beaver (Castor fiber) stomach reveal unique morphological features with possible general biological significance.

    Science.gov (United States)

    Ziółkowska, Natalia; Lewczuk, Bogdan; Petryński, Wojciech; Palkowska, Katarzyna; Prusik, Magdalena; Targońska, Krystyna; Giżejewski, Zygmunt; Przybylska-Gornowicz, Barbara

    2014-01-01

    Anatomical, histological, and ultrastructural studies of the European beaver stomach revealed several unique morphological features. The prominent attribute of its gross morphology was the cardiogastric gland (CGG), located near the oesophageal entrance. Light microscopy showed that the CGG was formed by invaginations of the mucosa into the submucosa, which contained densely packed proper gastric glands comprised primarily of parietal and chief cells. Mucous neck cells represented beaver stomach was the presence of specific mucus with a thickness up to 950 µm (in frozen, unfixed sections) that coated the mucosa. Our observations suggest that the formation of this mucus is complex and includes the secretory granule accumulation in the cytoplasm of pit cells, the granule aggregation inside cells, and the incorporation of degenerating cells into the mucus.

  5. Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

    Science.gov (United States)

    Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

    2017-03-01

    In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The MB2 gene family of Plasmodium species has a unique combination of S1 and GTP-binding domains

    Directory of Open Access Journals (Sweden)

    Ogunjumo Oluwasanmi

    2004-06-01

    Full Text Available Abstract Background Identification and characterization of novel Plasmodium gene families is necessary for developing new anti-malarial therapeutics. The products of the Plasmodium falciparum gene, MB2, were shown previously to have a stage-specific pattern of subcellular localization and proteolytic processing. Results Genes homologous to MB2 were identified in five additional parasite species, P. knowlesi, P. gallinaceum, P. berghei, P. yoelii, and P. chabaudi. Sequence comparisons among the MB2 gene products reveal amino acid conservation of structural features, including putative S1 and GTP-binding domains, and putative signal peptides and nuclear localization signals. Conclusions The combination of domains is unique to this gene family and indicates that MB2 genes comprise a novel family and therefore may be a good target for drug development.

  7. The MB2 gene family of Plasmodium species has a unique combination of S1 and GTP-binding domains

    Science.gov (United States)

    Romero, Lisa C; Nguyen, Thanh V; Deville, Benoit; Ogunjumo, Oluwasanmi; James, Anthony A

    2004-01-01

    Background Identification and characterization of novel Plasmodium gene families is necessary for developing new anti-malarial therapeutics. The products of the Plasmodium falciparum gene, MB2, were shown previously to have a stage-specific pattern of subcellular localization and proteolytic processing. Results Genes homologous to MB2 were identified in five additional parasite species, P. knowlesi, P. gallinaceum, P. berghei, P. yoelii, and P. chabaudi. Sequence comparisons among the MB2 gene products reveal amino acid conservation of structural features, including putative S1 and GTP-binding domains, and putative signal peptides and nuclear localization signals. Conclusions The combination of domains is unique to this gene family and indicates that MB2 genes comprise a novel family and therefore may be a good target for drug development. PMID:15222903

  8. Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.

    Science.gov (United States)

    Zarate, Yuri A; Lichty, Angie W; Champion, Kristen J; Clarkson, L Kate; Holden, Kenton R; Matheus, M Gisele

    2014-08-01

    Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused by gain-of-function germline mutations affecting components of the Ras-MAPK pathway. The authors present the case of a 6-year-old male with Noonan syndrome, Chiari malformation type I, shunted benign external hydrocephalus in infancy, and unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene was identified. The patient underwent brain magnetic resonance imaging, computed tomography angiography, and magnetic resonance angiography to further clarify the nature of his abnormal brain vasculature. The authors compared his findings to the few cases of Noonan syndrome reported with cerebrovascular pathology. © The Author(s) 2013.

  9. Transcriptome analysis of the digestive system of a wood-feeding termite (Coptotermes formosanus) revealed a unique mechanism for effective biomass degradation.

    Science.gov (United States)

    Geng, Alei; Cheng, Yanbing; Wang, Yongli; Zhu, Daochen; Le, Yilin; Wu, Jian; Xie, Rongrong; Yuan, Joshua S; Sun, Jianzhong

    2018-01-01

    Wood-feeding termite, Coptotermes formosanus Shiraki, represents a highly efficient system for biomass deconstruction and utilization. However, the detailed mechanisms of lignin modification and carbohydrate degradation in this system are still largely elusive. In order to reveal the inherent mechanisms for efficient biomass degradation, four different organs (salivary glands, foregut, midgut, and hindgut) within a complete digestive system of a lower termite, C. formosanus , were dissected and collected. Comparative transcriptomics was carried out to analyze these organs using high-throughput RNA sequencing. A total of 71,117 unigenes were successfully assembled, and the comparative transcriptome analyses revealed significant differential distributions of GH (glycosyl hydrolase) genes and auxiliary redox enzyme genes in different digestive organs. Among the GH genes in the salivary glands, the most abundant were GH9, GH22, and GH1 genes. The corresponding enzymes may have secreted into the foregut and midgut to initiate the hydrolysis of biomass and to achieve a lignin-carbohydrate co-deconstruction system. As the most diverse GH families, GH7 and GH5 were primarily identified from the symbiotic protists in the hindgut. These enzymes could play a synergistic role with the endogenous enzymes from the host termite for biomass degradation. Moreover, twelve out of fourteen genes coding auxiliary redox enzymes from the host termite origin were induced by the feeding of lignin-rich diets. This indicated that these genes may be involved in lignin component deconstruction with its redox network during biomass pretreatment. These findings demonstrate that the termite digestive system synergized the hydrolysis and redox reactions in a programmatic process, through different parts of its gut system, to achieve a maximized utilization of carbohydrates. The detailed unique mechanisms identified from the termite digestive system may provide new insights for advanced design of

  10. Plutonium uniqueness

    International Nuclear Information System (INIS)

    Silver, G.L.

    1984-01-01

    A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

  11. Neurog1 Genetic Inducible Fate Mapping (GIFM) Reveals the Existence of Complex Spatiotemporal Cyto-Architectures in the Developing Cerebellum.

    Science.gov (United States)

    Obana, Edwin A; Lundell, Travis G; Yi, Kevin J; Radomski, Kryslaine L; Zhou, Qiong; Doughty, Martin L

    2015-06-01

    Neurog1 is a pro-neural basic helix-loop-helix (bHLH) transcription factor expressed in progenitor cells located in the ventricular zone and subsequently the presumptive white matter tracts of the developing mouse cerebellum. We used genetic inducible fate mapping (GIFM) with a transgenic Neurog1-CreER allele to characterize the contributions of Neurog1 lineages to cerebellar circuit formation in mice. GIFM reveals Neurog1-expressing progenitors are fate-mapped to become Purkinje cells and all GABAergic interneuron cell types of the cerebellar cortex but not glia. The spatiotemporal sequence of GIFM is unique to each neuronal cell type. GIFM on embryonic days (E) 10.5 to E12.5 labels Purkinje cells with different medial-lateral settling patterns depending on the day of tamoxifen delivery. GIFM on E11.5 to P7 labels interneurons and the timing of tamoxifen administration correlates with the final inside-to-outside resting position of GABAergic interneurons in the cerebellar cortex. Proliferative status and long-term BrdU retention of GIFM lineages reveals Purkinje cells express Neurog1 around the time they become post-mitotic. In contrast, GIFM labels mitotic and post-mitotic interneurons. Neurog1-CreER GIFM reveals a correlation between the timing of Neurog1 expression and the spatial organization of GABAergic neurons in the cerebellar cortex with possible implications for cerebellar circuit assembly.

  12. Top-down proteomics reveals a unique protein S-thiolation switch in Salmonella Typimurium in response to infection-like conditions

    Energy Technology Data Exchange (ETDEWEB)

    Ansong, Charles; Wu, Si; Meng, Da; Liu, Xiaowen; Brewer, Heather M.; Kaiser, Brooke LD; Nakayasu, Ernesto S.; Cort, John R.; Pevzner, Pavel A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.; Pasa-Tolic, Ljiljana

    2013-06-18

    Characterization of the mature protein complement in cells is crucial for a better understanding of cellular processes on a systems-wide scale. Bottom-up proteomic approaches often lead to loss of critical information about an endogenous protein’s actual state due to post translational modifications (PTMs) and other processes. Top-down approaches that involve analysis of the intact protein can address this concern but present significant analytical challenges related to the separation quality needed, measurement sensitivity, and speed that result in low throughput and limited coverage. Here we used single-dimension ultra high pressure liquid chromatography mass spectrometry to investigate the comprehensive ‘intact’ proteome of the Gram negative bacterial pathogen Salmonella Typhimurium. Top-down proteomics analysis revealed 563 unique proteins including 1665 proteoforms generated by PTMs, representing the largest microbial top-down dataset reported to date. Our analysis not only confirmed several previously recognized aspects of Salmonella biology and bacterial PTMs in general, but also revealed several novel biological insights. Of particular interest was differential utilization of the protein S-thiolation forms S-glutathionylation and S-cysteinylation in response to infection-like conditions versus basal conditions, which was corroborated by changes in corresponding biosynthetic pathways. This differential utilization highlights underlying metabolic mechanisms that modulate changes in cellular signaling, and represents to our knowledge the first report of S-cysteinylation in Gram negative bacteria. The demonstrated utility of our simple proteome-wide intact protein level measurement strategy for gaining biological insight should promote broader adoption and applications of top-down proteomics approaches.

  13. An integrated Drosophila model system reveals unique properties for F14512, a novel polyamine-containing anticancer drug that targets topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Sonia Chelouah

    Full Text Available F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to ensure the preferential uptake of F14512 by cancer cells, strong interaction with DNA and potent inhibition of topoisomerase II (Topo II. The antitumor activity of F14512 in human tumor models is significantly higher than that of other epipodophyllotoxins in spite of a lower induction of DNA breakage. Hence, the demonstrated superiority of F14512 over other Topo II poisons might not result solely from its preferential uptake by cancer cells, but could also be due to unique effects on Topo II interactions with DNA. To further dissect the mechanism of action of F14512, we used Drosophila melanogaster mutants whose genetic background leads to an easily scored phenotype that is sensitive to changes in Topo II activity and/or localization. F14512 has antiproliferative properties in Drosophila cells and stabilizes ternary Topo II/DNA cleavable complexes at unique sites located in moderately repeated sequences, suggesting that the drug specifically targets a select and limited subset of genomic sequences. Feeding F14512 to developing mutant Drosophila larvae led to the recovery of flies expressing a striking phenotype, "Eye wide shut," where one eye is replaced by a first thoracic segment. Other recovered F14512-induced gain- and loss-of-function phenotypes similarly correspond to precise genetic dysfunctions. These complex in vivo results obtained in a whole developing organism can be reconciled with known genetic anomalies and constitute a remarkable instance of specific alterations of gene expression by ingestion of a drug. "Drosophila-based anticancer pharmacology" hence reveals unique properties for F14512, demonstrating the usefulness of an assay system that provides a low-cost, rapid and effective complement to mammalian models and permits the elucidation of fundamental mechanisms of

  14. Analysis of the cytochrome c oxidase subunit 1 (COX1) gene reveals the unique evolution of the giant panda.

    Science.gov (United States)

    Hu, Yao-Dong; Pang, Hui-Zhong; Li, De-Sheng; Ling, Shan-Shan; Lan, Dan; Wang, Ye; Zhu, Yun; Li, Di-Yan; Wei, Rong-Ping; Zhang, He-Min; Wang, Cheng-Dong

    2016-11-05

    As the rate-limiting enzyme of the mitochondrial respiratory chain, cytochrome c oxidase (COX) plays a crucial role in biological metabolism. "Living fossil" giant panda (Ailuropoda melanoleuca) is well-known for its special bamboo diet. In an effort to explore functional variation of COX1 in the energy metabolism behind giant panda's low-energy bamboo diet, we looked at genetic variation of COX1 gene in giant panda, and tested for its selection effect. In 1545 base pairs of the gene from 15 samples, 9 positions were variable and 1 mutation leaded to an amino acid sequence change. COX1 gene produces six haplotypes, nucleotide (pi), haplotype diversity (Hd). In addition, the average number of nucleotide differences (k) is 0.001629±0.001036, 0.8083±0.0694 and 2.517, respectively. Also, dN/dS ratio is significantly below 1. These results indicated that giant panda had a low population genetic diversity, and an obvious purifying selection of the COX1 gene which reduces synthesis of ATP determines giant panda's low-energy bamboo diet. Phylogenetic trees based on the COX1 gene were constructed to demonstrate that giant panda is the sister group of other Ursidae. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Unique Organization of the Nuclear Envelope in the Post-natal Quiescent Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Arantxa Cebrián-Silla

    2017-07-01

    Full Text Available Neural stem cells (B1 astrocytes; NSCs in the adult ventricular-subventricular-zone (V-SVZ originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS, reported in certain lymphocytes and some cancer cells. Using molecular markers, [3H]thymidine birth-dating, and Ara-C, we found that B1 cells with ELCS correspond to quiescent NSCs. ELCS begin forming in embryonic radial glia cells and represent a specific nuclear compartment containing particular epigenetic modifications and telomeres. These results reveal a unique nuclear compartment in quiescent NSCs, which is useful for identifying these primary progenitors and study their gene regulation.

  16. The dengue vector Aedes aegypti contains a functional high mobility group box 1 (HMGB1 protein with a unique regulatory C-terminus.

    Directory of Open Access Journals (Sweden)

    Fabio Schneider Ribeiro

    Full Text Available The mosquito Aedes aegypti can spread the dengue, chikungunya and yellow fever viruses. Thus, the search for key molecules involved in the mosquito survival represents today a promising vector control strategy. High Mobility Group Box (HMGB proteins are essential nuclear factors that maintain the high-order structure of chromatin, keeping eukaryotic cells viable. Outside the nucleus, secreted HMGB proteins could alert the innate immune system to foreign antigens and trigger the initiation of host defenses. In this work, we cloned and functionally characterized the HMGB1 protein from Aedes aegypti (AaHMGB1. The AaHMGB1 protein typically consists of two HMG-box DNA binding domains and an acidic C-terminus. Interestingly, AaHMGB1 contains a unique alanine/glutamine-rich (AQ-rich C-terminal region that seems to be exclusive of dipteran HMGB proteins. AaHMGB1 is localized to the cell nucleus, mainly associated with heterochromatin. Circular dichroism analyses of AaHMGB1 or the C-terminal truncated proteins revealed α-helical structures. We showed that AaHMGB1 can effectively bind and change the topology of DNA, and that the AQ-rich and the C-terminal acidic regions can modulate its ability to promote DNA supercoiling, as well as its preference to bind supercoiled DNA. AaHMGB1 is phosphorylated by PKA and PKC, but not by CK2. Importantly, phosphorylation of AaHMGB1 by PKA or PKC completely abolishes its DNA bending activity. Thus, our study shows that a functional HMGB1 protein occurs in Aedes aegypt and we provide the first description of a HMGB1 protein containing an AQ-rich regulatory C-terminus.

  17. Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.

    LENUS (Irish Health Repository)

    Moreau, Isabelle

    2012-02-03

    BACKGROUND: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1\\/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free. The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms. RESULTS: A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin\\/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction. CONCLUSION: In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.

  18. Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a nonforensic sample.

    Science.gov (United States)

    Yoder, Keith J; Porges, Eric C; Decety, Jean

    2015-04-01

    Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self-Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. © 2014 Wiley Periodicals, Inc.

  19. A Unique Late Triassic Dinosauromorph Assemblage Reveals Dinosaur Ancestral Anatomy and Diet.

    Science.gov (United States)

    Cabreira, Sergio Furtado; Kellner, Alexander Wilhelm Armin; Dias-da-Silva, Sérgio; Roberto da Silva, Lúcio; Bronzati, Mario; Marsola, Júlio Cesar de Almeida; Müller, Rodrigo Temp; Bittencourt, Jonathas de Souza; Batista, Brunna Jul'Armando; Raugust, Tiago; Carrilho, Rodrigo; Brodt, André; Langer, Max Cardoso

    2016-11-21

    Dinosauromorpha includes dinosaurs and other much less diverse dinosaur precursors of Triassic age, such as lagerpetids [1]. Joint occurrences of these taxa with dinosaurs are rare but more common during the latest part of that period (Norian-Rhaetian, 228-201 million years ago [mya]) [2, 3]. In contrast, the new lagerpetid and saurischian dinosaur described here were unearthed from one of the oldest rock units with dinosaur fossils worldwide, the Carnian (237-228 mya) Santa Maria Formation of south Brazil [4], a record only matched in age by much more fragmentary remains from Argentina [5]. This is the first time nearly complete dinosaur and non-dinosaur dinosauromorph remains are found together in the same excavation, clearly showing that these animals were contemporaries since the first stages of dinosaur evolution. The new lagerpetid preserves the first skull, scapular and forelimb elements, plus associated vertebrae, known for the group, revealing how dinosaurs acquired several of their typical anatomical traits. Furthermore, a novel phylogenetic analysis shows the new dinosaur as the most basal Sauropodomorpha. Its plesiomorphic teeth, strictly adapted to faunivory, provide crucial data to infer the feeding behavior of the first dinosaurs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Mechanistic Insights into the Unique Role of Copper in CO2 Electroreduction Reactions.

    Science.gov (United States)

    Liu, Shan Ping; Zhao, Ming; Gao, Wang; Jiang, Qing

    2017-01-20

    Cu demonstrates a unique capability towards CO 2 electroreduction that can close the anthropogenic carbon cycle; however, its reaction mechanism remains elusive, owing to the obscurity of the solid-liquid interface on Cu surfaces where electrochemical reactions occur. Using a genetic algorithm method in addition to density functional theory, we explicitly identify the configuration of a water bilayer on Cu(2 11) and build electrochemical models. These enable us to reveal a mechanistic picture for CO 2 electroreduction, finding the key intermediates CCO* for the C 2 H 4 pathway and CH* for the CH 4 pathway, which rationalize a series of experimental observations. Furthermore, we find that the interplay between the Cu surfaces, carbon monomers, and water network (but not the binding of CO*) essentially determine the unique capability of Cu towards CO 2 electroreduction, proposing a new and effective descriptor for exploiting optimal catalysts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Unique Chiral Interpenetrating d-f Heterometallic MOFs as Luminescent Sensors.

    Science.gov (United States)

    Wu, Zhi-Lei; Dong, Jie; Ni, Wei-Yan; Zhang, Bo-Wen; Cui, Jian-Zhong; Zhao, Bin

    2015-06-01

    One novel three-dimensional (3D) 3d-4f metal-organic framework (MOF), [TbZn(L)(CO3)2(H2O)]n (1) [HL = 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine], has been successfully synthesized and structurally characterized. Structural analysis shows that compound 1 features a unique chiral interpenetrating 3D framework for the first time. The resulting crystals of 1 are composed of enantiomers 1a (P41) and 1b (P43), as was clearly confirmed by the crystal structure and the corresponding circular dichroism (CD) analyses of eight randomly selected crystals. The investigations on CD spectra based on every single crystal clearly assigned the Cotton effect signals. The powder X-ray diffraction measurement of 1 after being immersed in common solvents reveals that 1 possess excellent solvent stability. Furthermore, luminescent studies imply that 1 displays highly selective luminescent sensing of aldehydes, such as formol, acetaldehyde, and propanal.

  2. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De

    2017-05-09

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  3. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De; Zhang, Zhen; Hadjichristidis, Nikolaos

    2017-01-01

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  4. Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Trevor E. Angell

    2018-03-01

    Full Text Available Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients. Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4 have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma. Adverse effects of these immune checkpoint inhibitors include immune-related adverse events (irAE, of which one of the most common is autoimmune thyroiditis. Though thyroiditis is increasingly recognized, there are no reports of the pathological findings that occur in immunotherapy-induced thyroiditis. We present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features. A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab (PD-1 antagonist plus ipilimumab (CTLA-4 antagonist therapy. A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells, lymphocytes and CD163-positive histiocytes. This case reports cytopathologic features found in immune checkpoint inhibitor related thyroiditis. These appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.

  5. Skipper genome sheds light on unique phenotypic traits and phylogeny.

    Science.gov (United States)

    Cong, Qian; Borek, Dominika; Otwinowski, Zbyszek; Grishin, Nick V

    2015-08-27

    Butterflies and moths are emerging as model organisms in genetics and evolutionary studies. The family Hesperiidae (skippers) was traditionally viewed as a sister to other butterflies based on its moth-like morphology and darting flight habits with fast wing beats. However, DNA studies suggest that the family Papilionidae (swallowtails) may be the sister to other butterflies including skippers. The moth-like features and the controversial position of skippers in Lepidoptera phylogeny make them valuable targets for comparative genomics. We obtained the 310 Mb draft genome of the Clouded Skipper (Lerema accius) from a wild-caught specimen using a cost-effective strategy that overcomes the high (1.6 %) heterozygosity problem. Comparative analysis of Lerema accius and the highly heterozygous genome of Papilio glaucus revealed differences in patterns of SNP distribution, but similarities in functions of genes that are enriched in non-synonymous SNPs. Comparison of Lepidoptera genomes revealed possible molecular bases for unique traits of skippers: a duplication of electron transport chain components could result in efficient energy supply for their rapid flight; a diversified family of predicted cellulases might allow them to feed on cellulose-enriched grasses; an expansion of pheromone-binding proteins and enzymes for pheromone synthesis implies a more efficient mate-recognition system, which compensates for the lack of clear visual cues due to the similarities in wing colors and patterns of many species of skippers. Phylogenetic analysis of several Lepidoptera genomes suggested that the position of Hesperiidae remains uncertain as the tree topology varied depending on the evolutionary model. Completion of the first genome from the family Hesperiidae allowed comparative analyses with other Lepidoptera that revealed potential genetic bases for the unique phenotypic traits of skippers. This work lays the foundation for future experimental studies of skippers and

  6. A rice gid1 suppressor mutant reveals that gibberellin is not always required for interaction between its receptor, GID1, and DELLA proteins.

    Science.gov (United States)

    Yamamoto, Yuko; Hirai, Takaaki; Yamamoto, Eiji; Kawamura, Mayuko; Sato, Tomomi; Kitano, Hidemi; Matsuoka, Makoto; Ueguchi-Tanaka, Miyako

    2010-11-01

    To investigate gibberellin (GA) signaling using the rice (Oryza sativa) GA receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) mutant gid1-8, we isolated a suppressor mutant, Suppressor of gid1-1 (Sgd-1). Sgd-1 is an intragenic mutant containing the original gid1-8 mutation (L45F) and an additional amino acid substitution (P99S) in the loop region. GID1(P99S) interacts with the rice DELLA protein SLENDER RICE1 (SLR1), even in the absence of GA. Substitution of the 99th Pro with other amino acids revealed that substitution with Ala (P99A) caused the highest level of GA-independent interaction. Physicochemical analysis using surface plasmon resonance revealed that GID1(P99A) has smaller K(a) (association) and K(d) (dissociation) values for GA(4) than does wild-type GID1. This suggests that the GID1(P99A) lid is at least partially closed, resulting in both GA-independent and GA-hypersensitive interactions with SLR1. One of the three Arabidopsis thaliana GID1s, At GID1b, can also interact with DELLA proteins in the absence of GA, so we investigated whether GA-independent interaction of At GID1b depends on a mechanism similar to that of rice GID1(P99A). Substitution of the loop region or a few amino acids of At GID1b with those of At GID1a diminished its GA-independent interaction with GAI while maintaining the GA-dependent interaction. Soybean (Glycine max) and Brassica napus also have GID1s similar to At GID1b, indicating that these unique GID1s occur in various dicots and may have important functions in these plants.

  7. A new approach to the analysis of Type 1 non-uniqueness of the ITS-90 above 0 °C

    Science.gov (United States)

    Gaita, Sonia; Bonnier, Georges

    2018-04-01

    The Type 1 non-uniqueness (NU-1) is the difference between interpolated values at the same temperature in the resistance thermometer subranges of the International Temperature Scale of 1990 (ITS-90) that overlap. The paper argues for a method of evaluating the NU-1 at a given temperature which considers all subranges of the Scale that contain the respective temperature, not only combinations of two, and it proposes mathematical models to determine the values of NU-1 for temperatures above 0 °C. The paper demonstrates that NU-1 is not the right contributor to the uncertainty associated with the realisation of the ITS-90. Therefore, a new concept of Correction for the Type 1 non-uniqueness of the Scale, CNU-1, is introduced and its mathematical model is established. Also, the estimate of CNU-1 and its standard uncertainty are defined and they are assessed through statistical analysis. The values of standard uncertainty determined by the novel methodology do not exceed 0.26 mK and they are smaller than the values given in the specific Guides developed by the Consultative Committee for Thermometry. The proposed models allow authors to single out and analyse the factors that generate Type 1 non-uniqueness of the Scale and influence its value.

  8. Functional profiles reveal unique ecological roles of various biological soil crust organisms

    Science.gov (United States)

    Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

    2011-01-01

    1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

  9. Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2008-12-01

    Full Text Available Abstract Background Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

  10. Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation

    International Nuclear Information System (INIS)

    Miller, Mitchell D.; Aravind, L.; Bakolitsa, Constantina; Rife, Christopher L.; Carlton, Dennis; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structure of the first representative of DUF364 family reveals a combination of enolase N-terminal-like and C-terminal Rossmann-like folds. Analysis of the interdomain cleft combined with sequence and genome context conservation among homologs, suggests a unique catalytic site likely involved in the synthesis of a flavin or pterin derivative. The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

  11. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

    Science.gov (United States)

    Merrick, B Alex; Phadke, Dhiral P; Auerbach, Scott S; Mav, Deepak; Stiegelmeyer, Suzy M; Shah, Ruchir R; Tice, Raymond R

    2013-01-01

    Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the

  12. The liberal illusion of uniqueness.

    Science.gov (United States)

    Stern, Chadly; West, Tessa V; Schmitt, Peter G

    2014-01-01

    In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed.

  13. Structural and biochemical analysis of a unique phosphatase from Bdellovibrio bacteriovorus reveals its structural and functional relationship with the protein tyrosine phosphatase class of phytase.

    Directory of Open Access Journals (Sweden)

    Robert J Gruninger

    Full Text Available Bdellovibrio bacteriovorus is an unusual δ-proteobacterium that invades and preys on other Gram-negative bacteria and is of potential interest as a whole cell therapeutic against pathogens of man, animals and crops. PTPs (protein tyrosine phosphatases are an important class of enzyme involved in desphosphorylating a variety of substrates, often with implications in cell signaling. The B. bacteriovorus open reading frame Bd1204 is predicted to encode a PTP of unknown function. Bd1204 is both structurally and mechanistically related to the PTP-like phytase (PTPLP class of enzymes and possesses a number of unique properties not observed in any other PTPLPs characterized to date. Bd1204 does not display catalytic activity against some common protein tyrosine phosphatase substrates but is highly specific for hydrolysis of phosphomonoester bonds of inositol hexakisphosphate. The structure reveals that Bd1204 has the smallest and least electropositive active site of all characterized PTPLPs to date yet possesses a unique substrate specificity characterized by a strict preference for inositol hexakisphosphate. These two active site features are believed to be the most significant contributors to the specificity of phytate degrading enzymes. We speculate that Bd1204 may be involved in phosphate acquisition outside of prey.

  14. MiAMP1, a novel protein from macadamia integrifolia adopts a greek key β-barrel fold unique amongst plant antimicrobial proteins

    International Nuclear Information System (INIS)

    McManus, A.M.; Nielsen, K.J.; Craik, D.J.; Marcus, J.P.; Harrison, S.J.; Green, J.L.; Manners, J.M.

    1999-01-01

    Full text: MiAMP1 is a recently discovered 76 amino acid, highly basic protein from the nut kernel of Macadamia integrifolia which possesses no sequence homology to any known protein. A study of its antimicrobial activity revealed that it inhibited the growth of several microbial plant pathogens in vitro but had no effect on mammalian or plant cells. For these reasons, MiAMP1 is considered to be a potentially useful tool for the genetic engineering of disease resistance in transgenic crop plants and for the design of new fungicides. The three-dimensional structure of MiAMP1 was determined through homonuclear and heteronuclear ( 15 N) 2D NMR spectroscopy and subsequent simulated annealing calculations. MiAMP1 is made up of eight β-strands which are arranged in two Greek key motifs. These Greek key motifs associate to form a Greek key β-barrel. This structure is unique amongst plant antimicrobial proteins and forms a new class which we term the β-Barrelins. Interestingly, the structure of MiAMP1 bears remarkable similarity to a yeast killer toxin from Williopsis mrakii. The structural similarity of MiAMP1 and WmKT, which originate from plant and fungal phyla respectively, may reflect a similar mode of action

  15. Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

    Science.gov (United States)

    Battaglia, Manuela; Anderson, Mark S; Buckner, Jane H; Geyer, Susan M; Gottlieb, Peter A; Kay, Thomas W H; Lernmark, Åke; Muller, Sarah; Pugliese, Alberto; Roep, Bart O; Greenbaum, Carla J; Peakman, Mark

    2017-11-01

    Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.

  16. Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Pejchal, Robert; Walker, Laura M.; Stanfield, Robyn L.; Phogat, Sanjay K.; Koff, Wayne C.; Poignard, Pascal; Burton, Dennis R.; Wilson, Ian A. (Scripps); (IAVI)

    2010-11-15

    Development of an effective vaccine against HIV-1 will likely require elicitation of broad and potent neutralizing antibodies against the trimeric surface envelope glycoprotein (Env). Monoclonal antibodies (mAbs) PG9 and PG16 neutralize {approx}80% of HIV-1 isolates across all clades with extraordinary potency and target novel epitopes preferentially expressed on Env trimers. As these neutralization properties are ideal for a vaccine-elicited antibody response to HIV-1, their structural basis was investigated. The crystal structure of the antigen-binding fragment (Fab) of PG16 at 2.5 {angstrom} resolution revealed its unusually long, 28-residue, complementarity determining region (CDR) H3 forms a unique, stable subdomain that towers above the antibody surface. A 7-residue 'specificity loop' on the 'hammerhead' subdomain was identified that, when transplanted from PG16 to PG9 and vice versa, accounted for differences in the fine specificity and neutralization of these two mAbs. The PG16 electron density maps also revealed that a CDR H3 tyrosine was sulfated, which was confirmed for both PG9 (doubly) and PG16 (singly) by mass spectral analysis. We further showed that tyrosine sulfation plays a role in binding and neutralization. An N-linked glycan modification is observed in the variable light chain, but not required for antigen recognition. Further, the crystal structure of the PG9 light chain at 3.0 {angstrom} facilitated homology modeling to support the presence of these unusual features in PG9. Thus, PG9 and PG16 use unique structural features to mediate potent neutralization of HIV-1 that may be of utility in antibody engineering and for high-affinity recognition of a variety of therapeutic targets.

  17. Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

    Science.gov (United States)

    Sun, Ji; MacKinnon, Roderick

    2017-06-01

    KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

    Directory of Open Access Journals (Sweden)

    Daniel A Rauch

    Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  19. A Rice gid1 Suppressor Mutant Reveals That Gibberellin Is Not Always Required for Interaction between Its Receptor, GID1, and DELLA Proteins[W][OA

    Science.gov (United States)

    Yamamoto, Yuko; Hirai, Takaaki; Yamamoto, Eiji; Kawamura, Mayuko; Sato, Tomomi; Kitano, Hidemi; Matsuoka, Makoto; Ueguchi-Tanaka, Miyako

    2010-01-01

    To investigate gibberellin (GA) signaling using the rice (Oryza sativa) GA receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) mutant gid1-8, we isolated a suppressor mutant, Suppressor of gid1-1 (Sgd-1). Sgd-1 is an intragenic mutant containing the original gid1-8 mutation (L45F) and an additional amino acid substitution (P99S) in the loop region. GID1P99S interacts with the rice DELLA protein SLENDER RICE1 (SLR1), even in the absence of GA. Substitution of the 99th Pro with other amino acids revealed that substitution with Ala (P99A) caused the highest level of GA-independent interaction. Physicochemical analysis using surface plasmon resonance revealed that GID1P99A has smaller Ka (association) and Kd (dissociation) values for GA4 than does wild-type GID1. This suggests that the GID1P99A lid is at least partially closed, resulting in both GA-independent and GA-hypersensitive interactions with SLR1. One of the three Arabidopsis thaliana GID1s, At GID1b, can also interact with DELLA proteins in the absence of GA, so we investigated whether GA-independent interaction of At GID1b depends on a mechanism similar to that of rice GID1P99A. Substitution of the loop region or a few amino acids of At GID1b with those of At GID1a diminished its GA-independent interaction with GAI while maintaining the GA-dependent interaction. Soybean (Glycine max) and Brassica napus also have GID1s similar to At GID1b, indicating that these unique GID1s occur in various dicots and may have important functions in these plants. PMID:21098733

  20. Tibialis Posterior Tenosynovitis: A Unique Musculoskeletal Manifestation of Gout.

    Science.gov (United States)

    Shupper, Peter; Stitik, Todd P

    2018-02-01

    Extra-articular manifestations of gout can present in several ways, including tenosynovitis. We present a rare case of acute tibialis posterior gouty tenosynovitis. An 82-year-old man with a history of well-controlled gout presented with acute onset of left ankle pain, occurring without inciting event. The medial ankle was slightly erythematous with moderate dorsal-medial swelling and mild dorsal-lateral swelling, with severe tenderness to palpation over the medial retro-malleolar region. Range of motion and manual muscle testing were pain limited throughout. Ultrasound examination revealed a left posterior tibialis tendon sheath tenosynovitis with effusion and overlying soft tissue edema. Tendon sheath aspirate revealed sodium urate crystals and a white blood cell count of 6400/μL. Tendon sheath injection with a mixture of 1% lidocaine and dexamethasone 4 mg resulted in symptom resolution. Repeat ultrasound examination demonstrated no evidence of tibialis posterior tendon sheath effusion. This case is unique not only because acute gouty posterior tibialis tenosynovitis is very rare, particularly in a normouricemic individual, but also because the sonographic evidence of gouty infiltration into the posterior tibialis tendon and overlying subcutaneous tissue considerably aided in arriving at the correct diagnosis in a timely manner.

  1. Uniqueness theorems in linear elasticity

    CERN Document Server

    Knops, Robin John

    1971-01-01

    The classical result for uniqueness in elasticity theory is due to Kirchhoff. It states that the standard mixed boundary value problem for a homogeneous isotropic linear elastic material in equilibrium and occupying a bounded three-dimensional region of space possesses at most one solution in the classical sense, provided the Lame and shear moduli, A and J1 respectively, obey the inequalities (3 A + 2 J1) > 0 and J1>O. In linear elastodynamics the analogous result, due to Neumann, is that the initial-mixed boundary value problem possesses at most one solution provided the elastic moduli satisfy the same set of inequalities as in Kirchhoffs theorem. Most standard textbooks on the linear theory of elasticity mention only these two classical criteria for uniqueness and neglect altogether the abundant literature which has appeared since the original publications of Kirchhoff. To remedy this deficiency it seems appropriate to attempt a coherent description ofthe various contributions made to the study of uniquenes...

  2. Comparative genome and transcriptome analysis reveals distinctive surface characteristics and unique physiological potentials of Pseudomonas aeruginosa ATCC 27853

    KAUST Repository

    Cao, Huiluo

    2017-06-12

    Pseudomonas aeruginosa ATCC 27853 was isolated from a hospital blood specimen in 1971 and has been widely used as a model strain to survey antibiotics susceptibilities, biofilm development, and metabolic activities of Pseudomonas spp.. Although four draft genomes of P. aeruginosa ATCC 27853 have been sequenced, the complete genome of this strain is still lacking, hindering a comprehensive understanding of its physiology and functional genome.Here we sequenced and assembled the complete genome of P. aeruginosa ATCC 27853 using the Pacific Biosciences SMRT (PacBio) technology and Illumina sequencing platform. We found that accessory genes of ATCC 27853 including prophages and genomic islands (GIs) mainly contribute to the difference between P. aeruginosa ATCC 27853 and other P. aeruginosa strains. Seven prophages were identified within the genome of P. aeruginosa ATCC 27853. Of the predicted 25 GIs, three contain genes that encode monoxoygenases, dioxygenases and hydrolases that could be involved in the metabolism of aromatic compounds. Surveying virulence-related genes revealed that a series of genes that encode the B-band O-antigen of LPS are lacking in ATCC 27853. Distinctive SNPs in genes of cellular adhesion proteins such as type IV pili and flagella biosynthesis were also observed in this strain. Colony morphology analysis confirmed an enhanced biofilm formation capability of ATCC 27853 on solid agar surface compared to Pseudomonas aeruginosa PAO1. We then performed transcriptome analysis of ATCC 27853 and PAO1 using RNA-seq and compared the expression of orthologous genes to understand the functional genome and the genomic details underlying the distinctive colony morphogenesis. These analyses revealed an increased expression of genes involved in cellular adhesion and biofilm maturation such as type IV pili, exopolysaccharide and electron transport chain components in ATCC 27853 compared with PAO1. In addition, distinctive expression profiles of the

  3. Trinuclear Lanthanoid Complexes of 1,3,5-Triamino-1,3,5-trideoxy-cis-inositol with a Unique, Sandwich-Type Cage Structure(1).

    Science.gov (United States)

    Hedinger, Roman; Ghisletta, Michele; Hegetschweiler, Kaspar; Tóth, Eva; Merbach, André E.; Sessoli, Roberta; Gatteschi, Dante; Gramlich, Volker

    1998-12-28

    A variety of trinuclear complexes [M(3)(H(-)(3)L)(2)](3+) [M = Y, La, Eu, Gd, Dy; L = 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci) and 1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol (tdci)] was prepared as solid materials of the composition M(3)(H(-)(3)L)(2)X(3).pH(2)O.qEtOH (X = Cl, NO(3); 2.5 1)/n, a = 10.294(3) Å, b = 15.494(5) Å, c = 19.994(6) Å, beta = 95.36(2) degrees, Z = 4 for C(12)Cl(3)Gd(3)H(42)N(6)O(15). The two complexes exhibited a unique, sandwich-type cage structure, where the two triply deprotonated taci ligands encapsulate an equilateral triangle of the three metal centers. The metal cations are coordinated to the equatorial, terminal amino groups and are bridged by the axial &mgr;(2)-alkoxo groups. The coordination spheres are completed by additional peripheral ligands such as H(2)O or Cl(-) counterions. The coordination number of the metal cations is 8. Magnetic susceptibility measurements of the Gd complex revealed very weak antiferromagnetic coupling interactions between the three Gd centers. Complex formation and species distribution in aqueous solution was investigated by potentiometry and pD-dependent NMR spectroscopy. An exclusive formation of the [Eu(3)(H(-)(3)taci)(2)](3+) unit in solution was found in the range 7

  4. Unique Path Partitions

    DEFF Research Database (Denmark)

    Bessenrodt, Christine; Olsson, Jørn Børling; Sellers, James A.

    2013-01-01

    We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions.......We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions....

  5. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

    Directory of Open Access Journals (Sweden)

    B Alex Merrick

    Full Text Available Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1, a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL. Paired-end reads were mapped to the rat genome (Rn4 with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005 compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c

  6. The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.

    Science.gov (United States)

    Lucato, Christina M; Halls, Michelle L; Ooms, Lisa M; Liu, Heng-Jia; Mitchell, Christina A; Whisstock, James C; Ellisdon, Andrew M

    2015-08-21

    The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Recurrent intussusception, coeliac disease and cholelithiasis: A unique combination

    Directory of Open Access Journals (Sweden)

    Sinha C

    2007-01-01

    Full Text Available Authors report an 11-month-old female child, who presented with recurrent episodes of colicky abdominal pain and diarrhea. An abdominal ultrasound revealed small bowel intussusception. She was also noted to have a thick walled gall bladder and a solitary gallstone. Further investigations confirmed the diagnosis of coeliac disease. The combination of small bowel intussusception, coeliac disease and cholelithiasis is unique and has not been reported in the literature.

  8. Molecular epidemiology of HIV-1 among the HIV infected people of Manipur, Northeastern India: Emergence of unique recombinant forms.

    Science.gov (United States)

    Sharma, Adhikarimayum Lakhikumar; Singh, Thiyam Ramsing; Devi, Khuraijam Ranjana; Singh, Lisam Shanjukumar

    2017-06-01

    According to the Joint National Programme on HIV/AIDS (UNAIDS), the northeastern region of India has the highest HIV prevalence in the country. This study was conducted to determine the current HIV-1 molecular epidemiology of Manipur, a state in northeast India. Blood samples from HIV-1 seropositive subjects were collected between June 2011 and February 2014. The partial regions of HIV-1 genes; pol and tat-vpu-env were independently amplified, sequenced, analyzed, and genotyped. Based on all sequences generated from 110 samples using pol and/or tat-vpu-env gene, the overall HIV-1 genotypes distribution of Manipur was as follows: 65.45% (72/110) subtype C, 32.73% (36/110) unique recombinant forms (URFs), and 1.82% (2/110) subtype B. The distribution of HIV-1 genotypes among the risk groups was: heterosexual: 58.33% (35/60) subtype C, 38.33% (23/60) URFs, and 3.34% (2/60) subtype B; intravenous drug users (IDUs): 85.36% (35/41) subtype C, 9.76% (4/41) URFs, and 4.88% (2/41) subtype B; mother to child (MTC): 50% (3/6) URFs and 50% (3/6) subtype C and blood transfusion: 100% (3/3) subtype C. The findings for the first time revealed the emergence of URFs of HIV-1 in Manipur which is predominant among the sexual and MTC risk groups as compared to IDUs. Taking together, this study illustrated that Manipur is the "recombinant hotspot of HIV" of India. The results will provide the clinical importance for continuous monitoring of HIV-infections in order to design appropriate prevention measures to limit the spread of new HIV infections. © 2016 Wiley Periodicals, Inc.

  9. Uniqueness and non-uniqueness of semigroups generated by singular diffusion operators

    CERN Document Server

    Eberle, Andreas

    1999-01-01

    This book addresses both probabilists working on diffusion processes and analysts interested in linear parabolic partial differential equations with singular coefficients. The central question discussed is whether a given diffusion operator, i.e., a second order linear differential operator without zeroth order term, which is a priori defined on test functions over some (finite or infinite dimensional) state space only, uniquely determines a strongly continuous semigroup on a corresponding weighted Lp space. Particular emphasis is placed on phenomena causing non-uniqueness, as well as on the relation between different notions of uniqueness appearing in analytic and probabilistic contexts.

  10. NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Joshua M. Baughman

    2016-07-01

    Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

  11. Hydrogen/deuterium exchange mass spectrometry and computational modeling reveal a discontinuous epitope of an antibody/TL1A Interaction.

    Science.gov (United States)

    Huang, Richard Y-C; Krystek, Stanley R; Felix, Nathan; Graziano, Robert F; Srinivasan, Mohan; Pashine, Achal; Chen, Guodong

    2018-01-01

    TL1A, a tumor necrosis factor-like cytokine, is a ligand for the death domain receptor DR3. TL1A, upon binding to DR3, can stimulate lymphocytes and trigger secretion of proinflammatory cytokines. Therefore, blockade of TL1A/DR3 interaction may be a potential therapeutic strategy for autoimmune and inflammatory diseases. Recently, the anti-TL1A monoclonal antibody 1 (mAb1) with a strong potency in blocking the TL1A/DR3 interaction was identified. Here, we report on the use of hydrogen/deuterium exchange mass spectrometry (HDX-MS) to obtain molecular-level details of mAb1's binding epitope on TL1A. HDX coupled with electron-transfer dissociation MS provided residue-level epitope information. The HDX dataset, in combination with solvent accessible surface area (SASA) analysis and computational modeling, revealed a discontinuous epitope within the predicted interaction interface of TL1A and DR3. The epitope regions span a distance within the approximate size of the variable domains of mAb1's heavy and light chains, indicating it uses a unique mechanism of action to block the TL1A/DR3 interaction.

  12. Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host.

    Directory of Open Access Journals (Sweden)

    Roman Leontovyč

    2016-02-01

    Full Text Available To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts' immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation, peptidases (cathepsins and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes.

  13. [Uniqueness seeking behavior as a self-verification: an alternative approach to the study of uniqueness].

    Science.gov (United States)

    Yamaoka, S

    1995-06-01

    Uniqueness theory explains that extremely high perceived similarity between self and others evokes negative emotional reactions and causes uniqueness seeking behavior. However, the theory conceptualizes similarity so ambiguously that it appears to suffer from low predictive validity. The purpose of the current article is to propose an alternative explanation of uniqueness seeking behavior. It posits that perceived uniqueness deprivation is a threat to self-concepts, and therefore causes self-verification behavior. Two levels of self verification are conceived: one based on personal categorization and the other on social categorization. The present approach regards uniqueness seeking behavior as the personal-level self verification. To test these propositions, a 2 (very high or moderate similarity information) x 2 (with or without outgroup information) x 2 (high or low need for uniqueness) between-subject factorial-design experiment was conducted with 95 university students. Results supported the self-verification approach, and were discussed in terms of effects of uniqueness deprivation, levels of self-categorization, and individual differences in need for uniqueness.

  14. [Family of ribosomal proteins S1 contains unique conservative domain].

    Science.gov (United States)

    Deriusheva, E I; Machulin, A V; Selivanova, O M; Serdiuk, I N

    2010-01-01

    Different representatives of bacteria have different number of amino acid residues in the ribosomal proteins S1. This number varies from 111 (Spiroplasma kunkelii) to 863 a.a. (Treponema pallidum). Traditionally and for lack of this protein three-dimensional structure, its architecture is represented as repeating S1 domains. Number of these domains depends on the protein's length. Domain's quantity and its boundaries data are contained in the specialized databases, such as SMART, Pfam and PROSITE. However, for the same object these data may be very different. For search of domain's quantity and its boundaries, new approach, based on the analysis of dicted secondary structure (PsiPred), was used. This approach allowed us to reveal structural domains in amino acid sequences of S1 proteins and at that number varied from one to six. Alignment of S1 proteins, containing different domain's number, with the S1 RNAbinding domain of Escherichia coli PNPase elicited a fact that in family of ribosomal proteins SI one domain has maximal homology with S1 domain from PNPase. This conservative domain migrates along polypeptide chain and locates in proteins, containing different domain's number, according to specified pattern. In this domain as well in the S1 domain from PNPase, residues Phe-19, Phe-22, His-34, Asp-64 and Arg-68 are clustered on the surface and formed RNA binding site.

  15. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals.

    Science.gov (United States)

    Elfaki, Tayseer Elamin Mohamed; Arndts, Kathrin; Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A; Atti El Mekki, Misk El Yemen A; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E

    2016-05-01

    In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4-85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to

  16. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals.

    Directory of Open Access Journals (Sweden)

    Tayseer Elamin Mohamed Elfaki

    2016-05-01

    Full Text Available In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity.This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4-85 years old from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+, n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+ and n = 61 people who were infection-free (Sm uninf. Immunoepidemiological findings were further investigated using two binary multivariable regression analysis.Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis.Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers

  17. The unique architecture and function of cellulose-interacting proteins in oomycetes revealed by genomic and structural analyses

    Directory of Open Access Journals (Sweden)

    Larroque Mathieu

    2012-11-01

    provides insight into the evolution and biological roles of CBM1-containing proteins from oomycetes. We show that while CBM1s from fungi and oomycetes are similar, they team up with different protein domains, either in proteins implicated in the degradation of plant cell wall components in the case of fungi or in proteins involved in adhesion to polysaccharidic substrates in the case of oomycetes. This work highlighted the unique role and evolution of CBM1 proteins in oomycete among the Stramenopile lineage.

  18. Unique growth strategy in the Earth's first trees revealed in silicified fossil trunks from China.

    Science.gov (United States)

    Xu, Hong-He; Berry, Christopher M; Stein, William E; Wang, Yi; Tang, Peng; Fu, Qiang

    2017-11-07

    Cladoxylopsida included the earliest large trees that formed critical components of globally transformative pioneering forest ecosystems in the Mid- and early Late Devonian (ca. 393-372 Ma). Well-known cladoxylopsid fossils include the up to ∼1-m-diameter sandstone casts known as Eospermatopteris from Middle Devonian strata of New York State. Cladoxylopsid trunk structure comprised a more-or-less distinct cylinder of numerous separate cauline xylem strands connected internally with a network of medullary xylem strands and, near the base, externally with downward-growing roots, all embedded within parenchyma. However, the means by which this complex vascular system was able to grow to a large diameter is unknown. We demonstrate-based on exceptional, up to ∼70-cm-diameter silicified fossil trunks with extensive preservation of cellular anatomy from the early Late Devonian (Frasnian, ca. 374 Ma) of Xinjiang, China-that trunk expansion is associated with a cylindrical zone of diffuse secondary growth within ground and cortical parenchyma and with production of a large amount of wood containing both rays and growth increments concentrically around individual xylem strands by normal cambia. The xylem system accommodates expansion by tearing of individual strand interconnections during secondary development. This mode of growth seems indeterminate, capable of producing trees of large size and, despite some unique features, invites comparison with secondary development in some living monocots. Understanding the structure and growth of cladoxylopsids informs analysis of canopy competition within early forests with the potential to drive global processes. Published under the PNAS license.

  19. Structural Characterization of Maize SIRK1 Kinase Domain Reveals an Unusual Architecture of the Activation Segment

    Directory of Open Access Journals (Sweden)

    Bruno Aquino

    2017-05-01

    Full Text Available Kinases are primary regulators of plant metabolism and excellent targets for plant breeding. However, most kinases, including the abundant receptor-like kinases (RLK, have no assigned role. SIRK1 is a leucine-rich repeat receptor-like kinase (LRR-RLK, the largest family of RLK. In Arabidopsis thaliana, SIRK1 (AtSIRK1 is phosphorylated after sucrose is resupplied to sucrose-starved seedlings and it modulates the sugar response by phosphorylating several substrates. In maize, the ZmSIRK1 expression is altered in response to drought stress. In neither Arabidopsis nor in maize has the function of SIRK1 been completely elucidated. As a first step toward the biochemical characterization of ZmSIRK1, we obtained its recombinant kinase domain, demonstrated that it binds AMP-PNP, a non-hydrolysable ATP-analog, and solved the structure of ZmSIRK1- AMP-PNP co-crystal. The ZmSIRK1 crystal structure revealed a unique conformation for the activation segment. In an attempt to find inhibitors for ZmSIRK1, we screened a focused small molecule library and identified six compounds that stabilized ZmSIRK1 against thermal melt. ITC analysis confirmed that three of these compounds bound to ZmSIRK1 with low micromolar affinity. Solving the 3D structure of ZmSIRK1-AMP-PNP co-crystal provided information on the molecular mechanism of ZmSIRK1 activity. Furthermore, the identification of small molecules that bind this kinase can serve as initial backbone for development of new potent and selective ZmSIRK1 antagonists.

  20. Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains.

    Science.gov (United States)

    Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika

    2015-03-18

    Kefir has a long tradition in human nutrition due to its presupposed health promoting effects. To investigate the potential contribution of bioactive peptides to the physiological effects of kefir, comprehensive analysis of the peptide profile was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano-ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified, mainly released from β-casein, followed by αS1-, κ-, and αS2-casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk indicating that the fermentation step does not only increase the proteolytic activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the composition of the peptide fraction. The influence of the microflora was determined by analyzing kefir produced from traditional kefir grains or commercial starter culture. Kefir from starter culture featured 230 peptide sequences and showed a significantly, 1.4-fold higher proteolytic activity than kefir from kefir grains with 127 peptides. A match of 97 peptides in both varieties indicates the presence of a typical kefir peptide profile that is not influenced by the individual composition of the microflora. Sixteen of the newly identified peptides were previously described as bioactive, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid, mineral binding, antioxidant, and antithrombotic effects. The present study describes a comprehensive peptide profile of kefir comprising 257 sequences. The peptide list was used to identify 16 bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral binding, antimicrobial, immunomodulating and opioid activity in kefir. Furthermore, it was shown that a majority of the kefir peptides were not endogenously present in the raw material milk, but were released from milk caseins by proteases of the microbiota and are therefore specific for the product. Consequently, the proteolytic activity and the

  1. Systems Signatures Reveal Unique Remission-path of Type 2 Diabetes Following Roux-en-Y Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Li, Qing-Run; Wang, Zi-Ming; Wewer Albrechtsen, Nicolai J

    2018-01-01

    metabolites and proteins of 10 normal glucose-tolerant obese (NO) and 9 diabetic obese (DO) patients before and 1-week, 3-months, 1-year after RYGB. 146 proteins and 128 metabolites from both NO and DO groups at all four stages were selected for further analysis. By analyzing a set of bi....... The principal component analyses (PCA) revealed that the edge states of the post-RYGB NO subjects were significantly different from those of the post-RYGB DO patients. Particularly, the time-dependent changes of the molecular hub-networks differed between DO and NO groups after RYGB. In conclusion......-molecular associations among the corresponding network of the subjects with our newly developed computational method, we defined the represented physiological states (called the edge-states that reflect the interactions among the bio-molecules), and the related molecular networks of NO and DO patients, respectively...

  2. Complete genome sequence of Brachyspira intermedia reveals unique genomic features in Brachyspira species and phage-mediated horizontal gene transfer

    Science.gov (United States)

    2011-01-01

    Background Brachyspira spp. colonize the intestines of some mammalian and avian species and show different degrees of enteropathogenicity. Brachyspira intermedia can cause production losses in chickens and strain PWS/AT now becomes the fourth genome to be completed in the genus Brachyspira. Results 15 classes of unique and shared genes were analyzed in B. intermedia, B. murdochii, B. hyodysenteriae and B. pilosicoli. The largest number of unique genes was found in B. intermedia and B. murdochii. This indicates the presence of larger pan-genomes. In general, hypothetical protein annotations are overrepresented among the unique genes. A 3.2 kb plasmid was found in B. intermedia strain PWS/AT. The plasmid was also present in the B. murdochii strain but not in nine other Brachyspira isolates. Within the Brachyspira genomes, genes had been translocated and also frequently switched between leading and lagging strands, a process that can be followed by different AT-skews in the third positions of synonymous codons. We also found evidence that bacteriophages were being remodeled and genes incorporated into them. Conclusions The accessory gene pool shapes species-specific traits. It is also influenced by reductive genome evolution and horizontal gene transfer. Gene-transfer events can cross both species and genus boundaries and bacteriophages appear to play an important role in this process. A mechanism for horizontal gene transfer appears to be gene translocations leading to remodeling of bacteriophages in combination with broad tropism. PMID:21816042

  3. Mcph1-deficient mice reveal a role for MCPH1 in otitis media.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    Full Text Available Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a (/tm1a mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a (/tm1a mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a (/tm1a mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a (/tm1a mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media.

  4. Uniquely Strongly Clean Group Rings

    Institute of Scientific and Technical Information of China (English)

    WANG XIU-LAN

    2012-01-01

    A ring R is called clean if every element is the sum of an idempotent and a unit,and R is called uniquely strongly clean (USC for short) if every element is uniquely the sum of an idempotent and a unit that commute.In this article,some conditions on a ring R and a group G such that RG is clean are given.It is also shown that if G is a locally finite group,then the group ring RG is USC if and only if R is USC,and G is a 2-group.The left uniquely exchange group ring,as a middle ring of the uniquely clean ring and the USC ring,does not possess this property,and so does the uniquely exchange group ring.

  5. Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

    Science.gov (United States)

    Pridmore, Ralph W

    2013-01-01

    This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors) but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral) functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure) hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique) over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0) in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones.) Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

  6. Structural characterization of the bacterial proteasome homolog BPH reveals a tetradecameric double-ring complex with unique inner cavity properties.

    Science.gov (United States)

    Fuchs, Adrian C D; Maldoner, Lorena; Hipp, Katharina; Hartmann, Marcus D; Martin, Jörg

    2018-01-19

    Eukaryotic and archaeal proteasomes are paradigms for self-compartmentalizing proteases. To a large extent, their function requires interplay with hexameric ATPases associated with diverse cellular activities (AAA+) that act as substrate unfoldases. Bacteria have various types of self-compartmentalizing proteases; in addition to the proteasome itself, these include the proteasome homolog HslV, which functions together with the AAA+ HslU; the ClpP protease with its partner AAA+ ClpX; and Anbu, a recently characterized ancestral proteasome variant. Previous bioinformatic analysis has revealed a novel bacterial member of the proteasome family Betaproteobacteria proteasome homolog (BPH). Using cluster analysis, we here affirmed that BPH evolutionarily descends from HslV. Crystal structures of the Thiobacillus denitrificans and Cupriavidus metallidurans BPHs disclosed a homo-oligomeric double-ring architecture in which the active sites face the interior of the cylinder. Using small-angle X-ray scattering (SAXS) and electron microscopy averaging, we found that BPH forms tetradecamers in solution, unlike the dodecamers seen in HslV. Although the highly acidic inner surface of BPH was in striking contrast to the cavity characteristics of the proteasome and HslV, a classical proteasomal reaction mechanism could be inferred from the covalent binding of the proteasome-specific inhibitor epoxomicin to BPH. A ligand-bound structure implied that the elongated BPH inner pore loop may be involved in substrate recognition. The apparent lack of a partner unfoldase and other unique features, such as Ser replacing Thr as the catalytic residue in certain BPH subfamilies, suggest a proteolytic function for BPH distinct from those of known bacterial self-compartmentalizing proteases. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Specially designed B4C/SnO2 nanocomposite for photocatalysis: traditional ceramic with unique properties

    Science.gov (United States)

    Singh, Paviter; Kaur, Gurpreet; Singh, Kulwinder; Singh, Bikramjeet; Kaur, Manpreet; Kaur, Manjot; Krishnan, Unni; Kumar, Manjeet; Bala, Rajni; Kumar, Akshay

    2018-02-01

    Boron carbide: A traditional ceramic material shows unique properties when explored in nano-range. Specially designed boron-based nanocomposite has been synthesized by reflux method. The addition of SnO2 in base matrix increases the defect states in boron carbide and shows unique catalytic properties. The calculated texture coefficient and Nelson-Riley factor show that the synthesized nanocomposite has large number of defect states. Also this composite is explored for the first time for catalysis degradation of industrial used dyes. The degradation analysis of industrial pollutants such as Novacron red Huntsman (NRH) and methylene blue (MB) dye reveals that the composite is an efficient catalyst. Degradation study shows that 1 g/L catalyst concentration of B4C/SnO2 degrades NRH and MB dye up to approximately 97.38 and 79.41%, respectively, in 20 min under sunlight irradiation. This water-insoluble catalyst can be recovered and reused.

  8. Within-culture variations of uniqueness: towards an integrative approach based on social status, gender, life contexts, and interpersonal comparison.

    Science.gov (United States)

    Causse, Elsa; Félonneau, Marie-Line

    2014-01-01

    Research on uniqueness is widely focused on cross-cultural comparisons and tends to postulate a certain form of within-culture homogeneity. Taking the opposite course of this classic posture, we aimed at testing an integrative approach enabling the study of within-culture variations of uniqueness. This approach considered different sources of variation: social status, gender, life contexts, and interpersonal comparison. Four hundred seventy-nine participants completed a measure based on descriptions of "self" and "other." Results showed important variations of uniqueness. An interaction between social status and life contexts revealed the expression of uniqueness in the low-status group. This study highlights the complexity of uniqueness that appears to be related to both cultural ideology and social hierarchy.

  9. Flexible and efficient genome tiling design with penalized uniqueness score

    Directory of Open Access Journals (Sweden)

    Du Yang

    2012-12-01

    Full Text Available Abstract Background As a powerful tool in whole genome analysis, tiling array has been widely used in the answering of many genomic questions. Now it could also serve as a capture device for the library preparation in the popular high throughput sequencing experiments. Thus, a flexible and efficient tiling array design approach is still needed and could assist in various types and scales of transcriptomic experiment. Results In this paper, we address issues and challenges in designing probes suitable for tiling array applications and targeted sequencing. In particular, we define the penalized uniqueness score, which serves as a controlling criterion to eliminate potential cross-hybridization, and a flexible tiling array design pipeline. Unlike BLAST or simple suffix array based methods, computing and using our uniqueness measurement can be more efficient for large scale design and require less memory. The parameters provided could assist in various types of genomic tiling task. In addition, using both commercial array data and experiment data we show, unlike previously claimed, that palindromic sequence exhibiting relatively lower uniqueness. Conclusions Our proposed penalized uniqueness score could serve as a better indicator for cross hybridization with higher sensitivity and specificity, giving more control of expected array quality. The flexible tiling design algorithm incorporating the penalized uniqueness score was shown to give higher coverage and resolution. The package to calculate the penalized uniqueness score and the described probe selection algorithm are implemented as a Perl program, which is freely available at http://www1.fbn-dummerstorf.de/en/forschung/fbs/fb3/paper/2012-yang-1/OTAD.v1.1.tar.gz.

  10. Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

    Directory of Open Access Journals (Sweden)

    Ralph W Pridmore

    Full Text Available This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0 in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones. Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

  11. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates

    DEFF Research Database (Denmark)

    Hoffman, Nolan J; Parker, Benjamin L; Chaudhuri, Rima

    2015-01-01

    -intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given...

  12. On uniqueness in evolution quasivariational inequalities

    Czech Academy of Sciences Publication Activity Database

    Brokate, M.; Krejčí, Pavel; Schnabel, H.

    2004-01-01

    Roč. 11, č. 1 (2004), s. 111-130 ISSN 0944-6532 Institutional research plan: CEZ:AV0Z1019905 Keywords : evolution quasivariational inequality * uniqueness * sweeping process Subject RIV: BA - General Mathematics Impact factor: 0.425, year: 2004 http://www.heldermann-verlag.de/jca/jca11/jca0386.pdf

  13. Rationality, irrationality and escalating behavior in lowest unique bid auctions.

    Science.gov (United States)

    Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A N

    2012-01-01

    Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions--lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of "bid space". The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets.

  14. Comparative transcriptional profiling of 3 murine models of SLE nephritis reveals both unique and shared regulatory networks.

    Directory of Open Access Journals (Sweden)

    Ramalingam Bethunaickan

    Full Text Available To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease.Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR.955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss.These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune-mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis.

  15. Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency.

    Science.gov (United States)

    Moradi, Sharif; Sharifi-Zarchi, Ali; Ahmadi, Amirhossein; Mollamohammadi, Sepideh; Stubenvoll, Alexander; Günther, Stefan; Salekdeh, Ghasem Hosseini; Asgari, Sassan; Braun, Thomas; Baharvand, Hossein

    2017-12-12

    Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the "miRNome" of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most "ground-state miRNAs" are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the Dlk1-Dio3 locus (miR-541-5p, miR-410-3p, and miR-381-3p) promoted pluripotency via inhibition of multi-lineage differentiation and stimulation of self-renewal. Overall, our results demonstrate that ground-state pluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. A unique SUMO-2-interacting motif within LANA is essential for KSHV latency.

    Directory of Open Access Journals (Sweden)

    Qiliang Cai

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV stabilizes hypoxia-inducible factor α (HIF-1α during latent infection, and HIF-1α reactivates lytic replication under hypoxic stress. However, the mechanism utilized by KSHV to block lytic reactivation with the accumulation of HIF-1α in latency remains unclear. Here, we report that LANA encoded by KSHV contains a unique SUMO-interacting motif (LANA(SIM which is specific for interaction with SUMO-2 and facilitates LANA SUMOylation at lysine 1140. Proteomic and co-immunoprecipitation analysis further reveal that the SUMO-2 modified transcription repressor KAP1 is a critical factor recruited by LANA(SIM. Deletion of LANA(SIM led to functional loss of both LANA-mediated viral episome maintenance and lytic gene silencing. Moreover, hypoxia reduced KAP1 SUMOylation and resulted in dissociation of both KAP1 and Sin3A repressors from LANA(SIM-associated complex. Therefore, the LANA(SIM motif plays an essential role in KSHV latency and is a potential drug target against KSHV-associated cancers.

  17. Sufficient conditions for uniqueness of the weak value

    International Nuclear Information System (INIS)

    Dressel, J; Jordan, A N

    2012-01-01

    We review and clarify the sufficient conditions for uniquely defining the generalized weak value as the weak limit of a conditioned average using the contextual values formalism introduced in Dressel, Agarwal and Jordan (2010 Phys. Rev. Lett. http://dx.doi.org/10.1103/PhysRevLett.104.240401). We also respond to criticism of our work by Parrott (arXiv:1105.4188v1) concerning a proposed counter-example to the uniqueness of the definition of the generalized weak value. The counter-example does not satisfy our prescription in the case of an underspecified measurement context. We show that when the contextual values formalism is properly applied to this example, a natural interpretation of the measurement emerges and the unique definition in the weak limit holds. We also prove a theorem regarding the uniqueness of the definition under our sufficient conditions for the general case. Finally, a second proposed counter-example by Parrott (arXiv:1105.4188v6) is shown not to satisfy the sufficiency conditions for the provided theorem. (paper)

  18. Concentration and mindfulness meditations: unique forms of consciousness?

    Science.gov (United States)

    Dunn, B R; Hartigan, J A; Mikulas, W L

    1999-09-01

    Electroencephalographic (EEG) recordings from 19 scalp recording sites were used to differentiate among two posited unique forms of mediation, concentration and mindfulness, and a normal relaxation control condition. Analyzes of all traditional frequency bandwidth data (i.e., delta 1-3 Hz; theta, 4-7 Hz; alpha, 8-12 Hz; beta 1, 13-25 Hz; beta 2, 26-32 Hz) showed strong mean amplitude frequency differences between the two meditation conditions and relaxation over numerous cortical sites. Furthermore, significant differences were obtained between concentration and mindfulness states at all bandwidths. Taken together, our results suggest that concentration and mindfulness "meditations" may be unique forms of consciousness and are not merely degrees of a state of relaxation.

  19. Cancer: Unique to Older Adults

    Science.gov (United States)

    ... A to Z › Cancer › Unique to Older Adults Font size A A A Print Share Glossary Unique ... group with other older people with the same type of cancer. Researchers have found that support groups ...

  20. MoMuLV-ts-1: A Unique Mouse Model of Retrovirus-Induced Lymphoma Transmitted by Breast Milk

    Directory of Open Access Journals (Sweden)

    J. Chakraborty

    2011-01-01

    Full Text Available Our laboratory has developed a murine model of lymphoma via breast milk transmission of MoMuLV-ts-1 (Moloney murine leukemia virus-temperature sensitive mutant-1. Uninfected offspring suckled from infected surrogate mothers become infected and develop lymphoma. Multiple gene integration sites of ts-1 into the infected mouse genome including tacc3, aurka, ndel1, tpx2, p53, and rhamm were identified, and mRNA expressions were quantitated. These genes produce centrosomal proteins, which may be involved in abnormal chromosomal segregation leading to aneuploidy or multiploidy, thus causing lymphoma. Since there is no report to date on this retroviral model leading to centrosomal abnormality, and causing lymphoma development, this is a valuable and unique model to study the centrosomal involvement in lymphomagenesis.

  1. Proteomics approach to identify unique xylem sap proteins in Pierce's disease-tolerant Vitis species.

    Science.gov (United States)

    Basha, Sheikh M; Mazhar, Hifza; Vasanthaiah, Hemanth K N

    2010-03-01

    Pierce's disease (PD) is a destructive bacterial disease of grapes caused by Xylella fastidiosa which is xylem-confined. The tolerance level to this disease varies among Vitis species. Our research was aimed at identifying unique xylem sap proteins present in PD-tolerant Vitis species. The results showed wide variation in the xylem sap protein composition, where a set of polypeptides with pI between 4.5 and 4.7 and M(r) of 31 kDa were present in abundant amount in muscadine (Vitis rotundifolia, PD-tolerant), in reduced levels in Florida hybrid bunch (Vitis spp., PD-tolerant) and absent in bunch grapes (Vitis vinifera, PD-susceptible). Liquid chromatography/mass spectrometry/mass spectrometry analysis of these proteins revealed their similarity to beta-1, 3-glucanase, peroxidase, and a subunit of oxygen-evolving enhancer protein 1, which are known to play role in defense and oxygen generation. In addition, the amount of free amino acids and soluble sugars was found to be significantly lower in xylem sap of muscadine genotypes compared to V. vinifera genotypes, indicating that the higher nutritional value of bunch grape sap may be more suitable for Xylella growth. These data suggest that the presence of these unique proteins in xylem sap is vital for PD tolerance in muscadine and Florida hybrid bunch grapes.

  2. Photo-Elicitation and Visual Semiotics: A Unique Methodology for Studying Inclusion for Children with Disabilities

    Science.gov (United States)

    Stockall, Nancy

    2013-01-01

    The methodology in this paper discusses the use of photographs as an elicitation strategy that can reveal the thinking processes of participants in a qualitatively rich manner. Photo-elicitation techniques combined with a Piercian semiotic perspective offer a unique method for creating a frame of action for later participant analysis. Illustrative…

  3. High-resolution deep sequencing reveals biodiversity, population structure, and persistence of HIV-1 quasispecies within host ecosystems

    Directory of Open Access Journals (Sweden)

    Yin Li

    2012-12-01

    Full Text Available Abstract Background Deep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment. While extensively applied to microbiome studies, population genetics studies of viruses are limited. To define the scope of HIV-1 population biodiversity within infected individuals, a suite of phylogenetic and population genetic algorithms was applied to HIV-1 envelope hypervariable domain 3 (Env V3 within peripheral blood mononuclear cells from a group of perinatally HIV-1 subtype B infected, therapy-naïve children. Results Biodiversity of HIV-1 Env V3 quasispecies ranged from about 70 to 270 unique sequence clusters across individuals. Viral population structure was organized into a limited number of clusters that included the dominant variants combined with multiple clusters of low frequency variants. Next generation viral quasispecies evolved from low frequency variants at earlier time points through multiple non-synonymous changes in lineages within the evolutionary landscape. Minor V3 variants detected as long as four years after infection co-localized in phylogenetic reconstructions with early transmitting viruses or with subsequent plasma virus circulating two years later. Conclusions Deep sequencing defines HIV-1 population complexity and structure, reveals the ebb and flow of dominant and rare viral variants in the host ecosystem, and identifies an evolutionary record of low-frequency cell-associated viral V3 variants that persist for years. Bioinformatics pipeline developed for HIV-1 can be applied for biodiversity studies of virome populations in human, animal, or plant ecosystems.

  4. Uniqueness in time measurement

    International Nuclear Information System (INIS)

    Lorenzen, P.

    1981-01-01

    According to P. Janich a clock is defined as an apparatus in which a point ( hand ) is moving uniformly on a straight line ( path ). For the definition of uniformly first the scaling (as a constant ratio of velocities) is defined without clocks. Thereafter the uniqueness of the time measurement can be proved using the prove of scaling of all clocks. But the uniqueness can be defined without scaling, as it is pointed out here. (orig.) [de

  5. Seafloor massive sulfide deposits support unique megafaunal assemblages: Implications for seabed mining and conservation.

    Science.gov (United States)

    Boschen, Rachel E; Rowden, Ashley A; Clark, Malcolm R; Pallentin, Arne; Gardner, Jonathan P A

    2016-04-01

    Mining of seafloor massive sulfides (SMS) is imminent, but the ecology of assemblages at SMS deposits is poorly known. Proposed conservation strategies include protected areas to preserve biodiversity at risk from mining impacts. Determining site suitability requires biological characterisation of the mine site and protected area(s). Video survey of a proposed mine site and protected area off New Zealand revealed unique megafaunal assemblages at the mine site. Significant relationships were identified between assemblage structure and environmental conditions, including hydrothermal features. Unique assemblages occurred at both active and inactive chimneys and are particularly at risk from mining-related impacts. The occurrence of unique assemblages at the mine site suggests that the proposed protected area is insufficient alone and should instead form part of a network. These results provide support for including hydrothermally active and inactive features within networks of protected areas and emphasise the need for quantitative survey data of proposed sites. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Rationality, irrationality and escalating behavior in lowest unique bid auctions.

    Directory of Open Access Journals (Sweden)

    Filippo Radicchi

    Full Text Available Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions--lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of "bid space". The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets.

  7. Rationality, Irrationality and Escalating Behavior in Lowest Unique Bid Auctions

    Science.gov (United States)

    Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A. N.

    2012-01-01

    Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions – lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of “bid space”. The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets. PMID:22279553

  8. {sup 18}F-FDG PET reveals unique features of large vessel inflammation in patients with Takayasu's arteritis

    Energy Technology Data Exchange (ETDEWEB)

    Incerti, Elena; Fallanca, Federico; Alongi, Pierpaolo; Gianolli, Luigi; Picchio, Maria [IRCCS San Raffaele Scientific Institute, Unit of Nuclear Medicine, Milan (Italy); Tombetti, Enrico; Sartorelli, Silvia; Sabbadini, Maria Grazia; Manfredi, Angelo A. [Vita-Salute San Raffaele University, Milan (Italy); IRCCS San Raffaele Scientific Institute, Unit of Internal Medicine and Clinical Immunology, Milan (Italy); Baldissera, Elena M. [IRCCS San Raffaele Scientific Institute, Unit of Internal Medicine and Clinical Immunology, Milan (Italy); Tombolini, Elisabetta [Vita-Salute San Raffaele University, Milan (Italy); Papa, Maurizio [IRCCS San Raffaele Scientific Institute, Department of Radiology, Milan (Italy); De Cobelli, Francesco [Vita-Salute San Raffaele University, Milan (Italy); IRCCS San Raffaele Scientific Institute, Department of Radiology, Milan (Italy); Mason, Justin C. [Imperial College London and Imperial College Healthcare NHS Trust, Vascular Science and Rheumatology, London (United Kingdom)

    2017-07-15

    The object of this study was to assess whether {sup 18}F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu's arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions <4 mm thick. We studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUV{sub max}), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated. Increased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUV{sub max} values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUV{sub max} in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria. PET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potential confounder

  9. Modularity, comparative cognition and human uniqueness.

    Science.gov (United States)

    Shettleworth, Sara J

    2012-10-05

    Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research.

  10. Dynamic karyotype evolution and unique sex determination systems in Leptidea wood white butterflies.

    Science.gov (United States)

    Šíchová, Jindra; Voleníková, Anna; Dincă, Vlad; Nguyen, Petr; Vila, Roger; Sahara, Ken; Marec, František

    2015-05-19

    Chromosomal rearrangements have the potential to limit the rate and pattern of gene flow within and between species and thus play a direct role in promoting and maintaining speciation. Wood white butterflies of the genus Leptidea are excellent models to study the role of chromosome rearrangements in speciation because they show karyotype variability not only among but also within species. In this work, we investigated genome architecture of three cryptic Leptidea species (L. juvernica, L. sinapis and L. reali) by standard and molecular cytogenetic techniques in order to reveal causes of the karyotype variability. Chromosome numbers ranged from 2n = 85 to 91 in L. juvernica and 2n = 69 to 73 in L. sinapis (both from Czech populations) to 2n = 51 to 55 in L. reali (Spanish population). We observed significant differences in chromosome numbers and localization of cytogenetic markers (rDNA and H3 histone genes) within the offspring of individual females. Using FISH with the (TTAGG) n telomeric probe we also documented the presence of multiple chromosome fusions and/or fissions and other complex rearrangements. Thus, the intraspecific karyotype variability is likely due to irregular chromosome segregation of multivalent meiotic configurations. The analysis of female meiotic chromosomes by GISH and CGH revealed multiple sex chromosomes: W1W2W3Z1Z2Z3Z4 in L. juvernica, W1W2W3Z1Z2Z3 in L. sinapis and W1W2W3W4Z1Z2Z3Z4 in L. reali. Our results suggest a dynamic karyotype evolution and point to the role of chromosomal rearrangements in the speciation of Leptidea butterflies. Moreover, our study revealed a curious sex determination system with 3-4 W and 3-4 Z chromosomes, which is unique in the Lepidoptera and which could also have played a role in the speciation process of the three Leptidea species.

  11. Integrated analysis of breast cancer cell lines reveals unique signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.; Laderoute, Keith R.; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L.; Laquerre, Sylvie; Jackson, Jeffrey R.; Wooster, Richard F.; Kuo, Wen-Lin; Gray, Joe W.; Spellman, Paul T.

    2009-03-31

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  12. Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

    Science.gov (United States)

    Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

    2009-01-01

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  13. Father involvement: Identifying and predicting family members' shared and unique perceptions.

    Science.gov (United States)

    Dyer, W Justin; Day, Randal D; Harper, James M

    2014-08-01

    Father involvement research has typically not recognized that reports of involvement contain at least two components: 1 reflecting a view of father involvement that is broadly recognized in the family, and another reflecting each reporter's unique perceptions. Using a longitudinal sample of 302 families, this study provides a first examination of shared and unique views of father involvement (engagement and warmth) from the perspectives of fathers, children, and mothers. This study also identifies influences on these shared and unique perspectives. Father involvement reports were obtained when the child was 12 and 14 years old. Mother reports overlapped more with the shared view than father or child reports. This suggests the mother's view may be more in line with broadly recognized father involvement. Regarding antecedents, for fathers' unique view, a compensatory model partially explains results; that is, negative aspects of family life were positively associated with fathers' unique view. Children's unique view of engagement may partially reflect a sentiment override with father antisocial behaviors being predictive. Mothers' unique view of engagement was predicted by father and mother work hours and her unique view of warmth was predicted by depression and maternal gatekeeping. Taken, together finding suggests a far more nuanced view of father involvement should be considered.

  14. Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

    Science.gov (United States)

    Singletary, Sean T.; Cook, Anthony K.; Hobbs, Janet L.; Pollock, Jennifer S.; Inscho, Edward W.

    2014-01-01

    Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of S1P (0.001–10 μM) evoked concentration-dependent vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. After administration of 10 μM S1P, the diameter of afferent arterioles decreased to 35%±5% of the control diameter, whereas the diameters of interlobular and arcuate arteries declined to 50%±12% and 68%±6% of the control diameter, respectively. Notably, efferent arterioles did not respond to S1P. The S1P receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction. Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P-mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P-mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats reduced renal blood flow dose dependently. Western blotting and immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated preglomerular microvessels and microvascular smooth muscle cells. These data demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction via activation of S1P1 and/or S1P2 receptors, partially via L-type voltage-dependent calcium channels. Accordingly, S1P may have a novel function in regulating afferent arteriolar resistance under physiologic conditions. PMID:24578134

  15. A study of Huntington disease-like syndromes in black South African patients reveals a single SCA2 mutation and a unique distribution of normal alleles across five repeat loci.

    Science.gov (United States)

    Baine, Fiona K; Peerbhai, Nabeelah; Krause, Amanda

    2018-07-15

    Huntington disease (HD) is a progressive neurodegenerative disease, characterised by a triad of movement disorder, emotional and behavioural disturbances and cognitive impairment. The underlying cause is an expanded CAG repeat in the huntingtin gene. For a small proportion of patients presenting with HD-like symptoms, the mutation in this gene is not identified and they are said to have a HD "phenocopy". South Africa has the highest number of recorded cases of an African-specific phenocopy, Huntington disease-like 2 (HDL2), caused by a repeat expansion in the junctophilin-3 gene. However, a significant proportion of black patients with clinical symptoms suggestive of HD still test negative for HD and HDL2. This study thus aimed to investigate five other loci associated with HD phenocopy syndromes - ATN1, ATXN2, ATXN7, TBP and C9orf72. In a sample of patients in whom HD and HDL2 had been excluded, a single expansion was identified in the ATXN2 gene, confirming a diagnosis of Spinocerebellar ataxia 2. The results indicate that common repeat expansion disorders do not contribute significantly to the HD-like phenotype in black South African patients. Importantly, allele sizing reveals unique distributions of normal repeat lengths across the associated loci in the African population studied. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Crystal structure of human importin-α1 (Rch1, revealing a potential autoinhibition mode involving homodimerization.

    Directory of Open Access Journals (Sweden)

    Hideyuki Miyatake

    Full Text Available In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB-truncated human importin-α1 (ΔIBB-h-importin-α1 at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.

  17. Nature inspired capacitive sensor with unique and unclonable characteristic

    Science.gov (United States)

    Karuthedath, C. B.; Schwesinger, N.

    2018-02-01

    Background of this paper is the development of sensors showing a nature like characteristic. The sensor is able to detect excitations on inertia bases and operates capacitive. It consists of a miniaturized interdigitated electrode structure on a printed circuit board, a flexible and conductive membrane of PDMS located in a certain distance above and a certain number of steel balls fixed on top of the membrane. The steel ball distribution is random and the conductivity of the membrane is not homogeneous across the membrane. Due to this double random distribution, no sensor equals the other, although the external geometry is equal. The overall size of the sensor is 4.7mm x 4.7mm x 1.7mm. Tilt, acceleration or magnetic fields are capable of causing forces on the steel balls and therefore relative movements between the membrane and the electrode structures. Due to this movement, capacity changes of the arrangement are measurable. This paper describes besides the fabrication of conductive membranes the preparation of regarding sensors. Process technology makes cloning of the sensors impossible. Although all process steps are suited for mass production, no sensor equals the other. Measurements with these sensors prove that each sensor reacts differently to the same excitation. Calculations of the Intra-Concordance-Coefficient show the similarity of the sensors for equal excitations. On the other hand, the maximum Inter-Concordance-Coefficient reveals the differences of such sensors very clearly. Such a characteristic, i.e. equal reaction to equal excitation and an output of significantly different signals allows considering each sensor as a unique device. The sensors obviously behave like receptors in natural organisms. These unusual properties of uniqueness and impossibility to clone make the sensors very interesting for highly secure identification demands. In combination with a very simple measurement procedure, the sensors are an attractive hardware base for

  18. A unique dual activity amino acid hydroxylase in Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Gaskell

    Full Text Available The genome of the protozoan parasite Toxoplasma gondii was found to contain two genes encoding tyrosine hydroxylase; that produces L-DOPA. The encoded enzymes metabolize phenylalanine as well as tyrosine with substrate preference for tyrosine. Thus the enzymes catabolize phenylalanine to tyrosine and tyrosine to L-DOPA. The catalytic domain descriptive of this class of enzymes is conserved with the parasite enzyme and exhibits similar kinetic properties to metazoan tyrosine hydroxylases, but contains a unique N-terminal extension with a signal sequence motif. One of the genes, TgAaaH1, is constitutively expressed while the other gene, TgAaaH2, is induced during formation of the bradyzoites of the cyst stages of the life cycle. This is the first description of an aromatic amino acid hydroxylase in an apicomplexan parasite. Extensive searching of apicomplexan genome sequences revealed an ortholog in Neospora caninum but not in Eimeria, Cryptosporidium, Theileria, or Plasmodium. Possible role(s of these bi-functional enzymes during host infection are discussed.

  19. Generating unique IDs from patient identification data using security models

    Directory of Open Access Journals (Sweden)

    Emad A Mohammed

    2016-01-01

    Full Text Available Background: The use of electronic health records (EHRs has continued to increase within healthcare systems in the developed and developing nations. EHRs allow for increased patient safety, grant patients easier access to their medical records, and offer a wealth of data to researchers. However, various bioethical, financial, logistical, and information security considerations must be addressed while transitioning to an EHR system. The need to encrypt private patient information for data sharing is one of the foremost challenges faced by health information technology. Method: We describe the usage of the message digest-5 (MD5 and secure hashing algorithm (SHA as methods for encrypting electronic medical data. In particular, we present an application of the MD5 and SHA-1 algorithms in encrypting a composite message from private patient information. Results: The results show that the composite message can be used to create a unique one-way encrypted ID per patient record that can be used for data sharing. Conclusion: The described software tool can be used to share patient EMRs between practitioners without revealing patients identifiable data.

  20. Generating unique IDs from patient identification data using security models.

    Science.gov (United States)

    Mohammed, Emad A; Slack, Jonathan C; Naugler, Christopher T

    2016-01-01

    The use of electronic health records (EHRs) has continued to increase within healthcare systems in the developed and developing nations. EHRs allow for increased patient safety, grant patients easier access to their medical records, and offer a wealth of data to researchers. However, various bioethical, financial, logistical, and information security considerations must be addressed while transitioning to an EHR system. The need to encrypt private patient information for data sharing is one of the foremost challenges faced by health information technology. We describe the usage of the message digest-5 (MD5) and secure hashing algorithm (SHA) as methods for encrypting electronic medical data. In particular, we present an application of the MD5 and SHA-1 algorithms in encrypting a composite message from private patient information. The results show that the composite message can be used to create a unique one-way encrypted ID per patient record that can be used for data sharing. The described software tool can be used to share patient EMRs between practitioners without revealing patients identifiable data.

  1. Crystal structure of Aquifex aeolicus gene product Aq1627: a putative phosphoglucosamine mutase reveals a unique C-terminal end-to-end disulfide linkage.

    Science.gov (United States)

    Sridharan, Upasana; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Kumarevel, Thirumananseri; Ponnuraj, Karthe

    2017-06-27

    The Aq1627 gene from Aquifex aeolicus, a hyperthermophilic bacterium has been cloned and overexpressed in Escherichia coli. The protein was purified to homogeneity and its X-ray crystal structure was determined to 1.3 Å resolution using multiple wavelength anomalous dispersion phasing. The structural and sequence analysis of Aq1627 is suggestive of a putative phosphoglucosamine mutase. The structural features of Aq1627 further indicate that it could belong to a new subclass of the phosphoglucosamine mutase family. Aq1627 structure contains a unique C-terminal end-to-end disulfide bond, which links two monomers and this structural information can be used in protein engineering to make proteins more stable in different applications.

  2. Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Wusheng

    2012-01-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC, the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB, normal differentiated squamous epithelium (ND, and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and

  3. Computational topology and the Unique Games Conjecture

    OpenAIRE

    Grochow, Joshua A.; Tucker-Foltz, Jamie

    2018-01-01

    Covering spaces of graphs have long been useful for studying expanders (as "graph lifts") and unique games (as the "label-extended graph"). In this paper we advocate for the thesis that there is a much deeper relationship between computational topology and the Unique Games Conjecture. Our starting point is Linial's 2005 observation that the only known problems whose inapproximability is equivalent to the Unique Games Conjecture - Unique Games and Max-2Lin - are instances of Maximum Section of...

  4. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    2007-11-01

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  5. Unique self-assembly properties of a bridge-shaped protein dimer with quantum dots

    International Nuclear Information System (INIS)

    Wang, Jianhao; Jiang, Pengju; Gao, Liqian; Yu, Yongsheng; Lu, Yao; Qiu, Lin; Wang, Cheli; Xia, Jiang

    2013-01-01

    How protein–protein interaction affects protein–nanoparticle self-assembly is the key to the understanding of biomolecular coating of nanoparticle in biological fluids. However, the relationship between protein shape and its interaction with nanoparticles is still under-exploited because of lack of a well-conceived binding system and a method to detect the subtle change in the protein–nanoparticle assemblies. Noticing this unresolved need, we cloned and expressed a His-tagged SpeA protein that adopts a bridge-shaped dimer structure, and utilized a high-resolution capillary electrophoresis method to monitor assembly formation between the protein and quantum dots (QDs, 5 nm in diameter). We observed that the bridge-shaped structure rendered a low SpeA:QD stoichiometry at saturation. Also, close monitoring of imidazole (Im) displacement of surface-bound protein revealed a unique two-step process. High-concentration Im could displace surface-bound SpeA protein and form a transient QD–protein intermediate, through a kinetically controlled displacement process. An affinity-driven equilibrium step then followed, resulting in re-assembling of the QD–protein complex in about 1 h. Through a temporarily formed intermediate, Im causes a rearrangement of His-tagged proteins on the surface. Thus, our work showcases that the synergistic interplay between QD–His-tag interaction and protein–protein interaction can result in unique properties of protein–nanoparticle assembly for the first time

  6. Unique self-assembly properties of a bridge-shaped protein dimer with quantum dots

    Science.gov (United States)

    Wang, Jianhao; Jiang, Pengju; Gao, Liqian; Yu, Yongsheng; Lu, Yao; Qiu, Lin; Wang, Cheli; Xia, Jiang

    2013-09-01

    How protein-protein interaction affects protein-nanoparticle self-assembly is the key to the understanding of biomolecular coating of nanoparticle in biological fluids. However, the relationship between protein shape and its interaction with nanoparticles is still under-exploited because of lack of a well-conceived binding system and a method to detect the subtle change in the protein-nanoparticle assemblies. Noticing this unresolved need, we cloned and expressed a His-tagged SpeA protein that adopts a bridge-shaped dimer structure, and utilized a high-resolution capillary electrophoresis method to monitor assembly formation between the protein and quantum dots (QDs, 5 nm in diameter). We observed that the bridge-shaped structure rendered a low SpeA:QD stoichiometry at saturation. Also, close monitoring of imidazole (Im) displacement of surface-bound protein revealed a unique two-step process. High-concentration Im could displace surface-bound SpeA protein and form a transient QD-protein intermediate, through a kinetically controlled displacement process. An affinity-driven equilibrium step then followed, resulting in re-assembling of the QD-protein complex in about 1 h. Through a temporarily formed intermediate, Im causes a rearrangement of His-tagged proteins on the surface. Thus, our work showcases that the synergistic interplay between QD-His-tag interaction and protein-protein interaction can result in unique properties of protein-nanoparticle assembly for the first time.

  7. Couple-level Minority Stress: An Examination of Same-sex Couples' Unique Experiences.

    Science.gov (United States)

    Frost, David M; LeBlanc, Allen J; de Vries, Brian; Alston-Stepnitz, Eli; Stephenson, Rob; Woodyatt, Cory

    2017-12-01

    Social stress resulting from stigma, prejudice, and discrimination-"minority stress"-negatively impacts sexual minority individuals' health and relational well-being. The present study examined how being in a same-sex couple can result in exposure to unique minority stressors not accounted for at the individual level. Relationship timeline interviews were conducted with 120 same-sex couples equally distributed across two study sites (Atlanta and San Francisco), gender (male and female), and relationship duration (at least six months but less than three years, at least three years but less than seven years, and seven or more years). Directed content analyses identified 17 unique couple-level minority stressors experienced within nine distinct social contexts. Analyses also revealed experiences of dyadic minority stress processes (stress discrepancies and stress contagion). These findings can be useful in future efforts to better understand and address the cumulative impact of minority stress on relational well-being and individual health.

  8. A unique case of craniopagus twins: considerations and challenges for dental rehabilitation.

    Science.gov (United States)

    Campbell, Karen M

    2013-01-01

    The purpose of this case report was to describe oral findings and outline challenges and considerations for general anesthetic (GA) and dental management of 4-year-old female craniopagus (cranially conjoined) twins, at high risk for medical comorbidity, who presented for treatment of severe early childhood caries. This hospital-based procedure required good interdisciplinary communication, cooperation, and presurgical planning to address unique challenges and ensure positive postoperative outcomes. Two separate anesthesia teams delivered GA simultaneously to each twin. To minimize anesthetic exposure, two pediatric dental teams completed dental care concurrently. Extensive plaque accumulation and unusual "mirror-image" caries distribution were attributed to frequency and postural pooling during feeding. The rehabilitation objective was to provide definitive dental management, minimizing future need for dental retreatment under GA. Two-month follow-up revealed intact dental restorations, good oral hygiene, and weight gain. For these unique twins however, the challenge of long-term oral health maintenance remains.

  9. Evidence for a unique PTSD construct represented by PTSD's D1-D3 symptoms.

    Science.gov (United States)

    Elhai, Jon D; Biehn, Tracey L; Armour, Cherie; Klopper, Jessica J; Frueh, B Christopher; Palmieri, Patrick A

    2011-04-01

    Two models of posttraumatic stress disorder (PTSD) have received the most empirical support in confirmatory factor analytic studies: King, Leskin, King, and Weathers' (1998) Emotional Numbing model of reexperiencing, avoidance, emotional numbing and hyperarousal; and Simms, Watson, and Doebbeling's (2002) Dysphoria model of reexperiencing, avoidance, dysphoria and hyperarousal. These models only differ in placement of three PTSD symptoms: sleep problems (D1), irritability (D2), and concentration problems (D3). In the present study, we recruited 252 women victims of domestic violence and tested whether there is empirical support to separate these three PTSD symptoms into a fifth factor, while retaining the Emotional Numbing and Dysphoria models' remaining four factors. Confirmatory factor analytic findings demonstrated that separating the three symptoms into a separate factor significantly enhanced model fit for the Emotional Numbing and Dysphoria models. These three symptoms may represent a unique latent construct. Implications are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks

    DEFF Research Database (Denmark)

    Huang, Hongda; Strømme, Caroline B; Saredi, Giulia

    2015-01-01

    During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase......, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required...... for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling...

  11. A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks.

    Science.gov (United States)

    Huang, Hongda; Strømme, Caroline B; Saredi, Giulia; Hödl, Martina; Strandsby, Anne; González-Aguilera, Cristina; Chen, Shoudeng; Groth, Anja; Patel, Dinshaw J

    2015-08-01

    During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling histones genome wide during DNA replication.

  12. Heart Failure: Unique to Older Adults

    Science.gov (United States)

    ... to Z › Heart Failure › Unique to Older Adults Font size A A A Print Share Glossary Unique ... will suffer from depression at some point. This type of severe depression is more serious than the ...

  13. Putative in vitro expressed gene fragments unique to Mycobacterium avium subspecies para tuberculosis

    DEFF Research Database (Denmark)

    Nielsen, Kirstine Klitgaard; Ahrens, Peter

    2002-01-01

    By a suppression subtractive hybridization based method, nine novel Mycobacterium avium subsp. para tuberculosis (M. para tuberculosis) fragments of between 318 and 596 bp have been identified and characterized. Database search revealed little or no similarity with other mycobacteria. The uniquen......By a suppression subtractive hybridization based method, nine novel Mycobacterium avium subsp. para tuberculosis (M. para tuberculosis) fragments of between 318 and 596 bp have been identified and characterized. Database search revealed little or no similarity with other mycobacteria....... The uniqueness and diagnostic potential of seven of these fragments in relation to M. paratuberculosis closest relative Mycobacterium avium subsp. avium (M. avium) was confirmed by species-specific PCR and Southern blot. Furthermore, RT-PCR indicated that eight of the nine fragments originate from areas...

  14. King Lear Reveals the Tragic Pattern of Shakespeare

    Directory of Open Access Journals (Sweden)

    Salim Eflih Al-Ibia

    2017-04-01

    Full Text Available Rather than focusing on the obvious traditions of evaluating Shakespearean tragic heroes, this paper presents a groundbreaking approach to unfold the pattern William Shakespeare follows as he designed his unique characters. This pattern applies to most, if not all, Shakespearean tragic heroes. I argue that Shakespeare himself reveals a great portion of this pattern on the tongue of Lear as the latter disowns Goneril and Regan promising to have “such revenges on [them] both” in King Lear. Lear’s threats bestow four unique aspects that apply not only to his character but they also apply to Shakespearean tragic heroes. Lear’s speech tells us that he is determined to have an awful type of revenge on his daughters. However, the very same speech tells us that he seems uncertain about the method through which he should carry out this revenge. Lear does not express any type of remorse as he pursues his vengeful plans nor should he aim at amnesty. He also admits his own madness as he closes his revealing speech. This research develops these facts about Lear to unfold the unique pattern Shakespeare follows as he portrayed his major tragic figures. This pattern is examined, described and analyzed in King Lear, Othello, and Hamlet. We will find out that the pattern suggested in this study helps us better understand Shakespeare’s tragedies and enables us to provide better explanations for some controversial scenes in the tragedies discussed.

  15. Creativity and technical innovation: spatial ability's unique role.

    Science.gov (United States)

    Kell, Harrison J; Lubinski, David; Benbow, Camilla P; Steiger, James H

    2013-09-01

    In the late 1970s, 563 intellectually talented 13-year-olds (identified by the SAT as in the top 0.5% of ability) were assessed on spatial ability. More than 30 years later, the present study evaluated whether spatial ability provided incremental validity (beyond the SAT's mathematical and verbal reasoning subtests) for differentially predicting which of these individuals had patents and three classes of refereed publications. A two-step discriminant-function analysis revealed that the SAT subtests jointly accounted for 10.8% of the variance among these outcomes (p development of creativity, beyond the roles played by the abilities traditionally measured in educational selection, counseling, and industrial-organizational psychology. Spatial ability plays a key and unique role in structuring many important psychological phenomena and should be examined more broadly across the applied and basic psychological sciences.

  16. Unique Case Reports Associated with Ovarian Failure: Necessity of Two Intact X Chromosomes

    Directory of Open Access Journals (Sweden)

    Lakshmi Rao Kandukuri

    2012-01-01

    Full Text Available Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30–40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months with low level of oestrogen and raised level of Luteinizing Hormone (LH and Follicle Stimulating Hormone (FSH > 20 IU/l occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22 and q28 and (mos,45XO/46,X+ringX involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.

  17. Touch and You’re Trapp(cked: Quantifying the Uniqueness of Touch Gestures for Tracking

    Directory of Open Access Journals (Sweden)

    Masood Rahat

    2018-04-01

    Full Text Available We argue that touch-based gestures on touch-screen devices enable the threat of a form of persistent and ubiquitous tracking which we call touch-based tracking. Touch-based tracking goes beyond the tracking of virtual identities and has the potential for cross-device tracking as well as identifying multiple users using the same device. We demonstrate the likelihood of touch-based tracking by focusing on touch gestures widely used to interact with touch devices such as swipes and taps.. Our objective is to quantify and measure the information carried by touch-based gestures which may lead to tracking users. For this purpose, we develop an information theoretic method that measures the amount of information about users leaked by gestures when modelled as feature vectors. Our methodology allows us to evaluate the information leaked by individual features of gestures, samples of gestures, as well as samples of combinations of gestures. Through our purpose-built app, called TouchTrack, we gather gesture samples from 89 users, and demonstrate that touch gestures contain sufficient information to uniquely identify and track users. Our results show that writing samples (on a touch pad can reveal 73.7% of information (when measured in bits, and left swipes can reveal up to 68.6% of information. Combining different combinations of gestures results in higher uniqueness, with the combination of keystrokes, swipes and writing revealing up to 98.5% of information about users. We further show that, through our methodology, we can correctly re-identify returning users with a success rate of more than 90%.

  18. α-Diazo-β-ketonitriles: uniquely reactive substrates for arene and alkene cyclopropanation.

    Science.gov (United States)

    Nani, Roger R; Reisman, Sarah E

    2013-05-15

    An investigation of the intramolecular cyclopropanation reactions of α-diazo-β-ketonitriles is reported. These studies reveal that α-diazo-β-ketonitriles exhibit unique reactivity in their ability to undergo arene cyclopropanation reactions; other similar acceptor-acceptor-substituted diazo substrates instead produce mixtures of C-H insertion and dimerization products. α-Diazo-β-ketonitriles also undergo highly efficient intramolecular cyclopropanation of tri- and tetrasubstituted alkenes. In addition, the α-cyano-α-ketocyclopropane products are demonstrated to serve as substrates for SN2, SN2', and aldehyde cycloaddition reactions.

  19. Cyp1a reporter zebrafish reveals target tissues for dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kun-Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Park, Hye-Jeong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Jin Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Suhyun [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Williams, Darren R. [New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Kim, Myeong-Kyu [Department of Neurology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jung, Young Do [Department of Biochemistry, Chonnam National University Medical School, Gwangju (Korea, Republic of); Teraoka, Hiroki [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Park, Hae-Chul [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Choy, Hyon E., E-mail: hyonchoy@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Shin, Boo Ahn, E-mail: bashin@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Choi, Seok-Yong, E-mail: zebrafish@chonnam.ac.kr [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of)

    2013-06-15

    Highlights: •2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic anthropogenic substance ever identified. •Transgenic cyp1a reporter zebrafish reveals target tissues for TCDD. •The retinal bipolar cells, otic vesicle, lateral line, pancreas, cloaca and pectoral fin bud are novel targets in zebrafish for TCDD. •Our findings will further understanding of human health risks by TCDD. -- Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

  20. Unique specification of Yang-Mills solutions

    International Nuclear Information System (INIS)

    Campbell, W.B.; Joseph, D.W.; Morgan, T.A.

    1980-01-01

    Screened time-independent cylindrically-symmetric solutions of Yang-Mills equations are given which show that the source does not uniquely determine the field. However, these particular solutions suggest a natural way of uniquely specifying solutions in terms of a physical realization of a symmetry group. (orig.)

  1. Determining hydraulic parameters of a karst aquifer using unique ...

    African Journals Online (AJOL)

    2014-07-15

    Jul 15, 2014 ... 1 Faculty of Natural Sciences, Potchefstroom Campus, North-West University, ... a first-ever attempt to utilise various sets of unique historical data ..... Even though the aquifer shows characteristics of all major ...... Earth Sci.

  2. Identification of Alternative Splice Variants Using Unique Tryptic Peptide Sequences for Database Searches.

    Science.gov (United States)

    Tran, Trung T; Bollineni, Ravi C; Strozynski, Margarita; Koehler, Christian J; Thiede, Bernd

    2017-07-07

    Alternative splicing is a mechanism in eukaryotes by which different forms of mRNAs are generated from the same gene. Identification of alternative splice variants requires the identification of peptides specific for alternative splice forms. For this purpose, we generated a human database that contains only unique tryptic peptides specific for alternative splice forms from Swiss-Prot entries. Using this database allows an easy access to splice variant-specific peptide sequences that match to MS data. Furthermore, we combined this database without alternative splice variant-1-specific peptides with human Swiss-Prot. This combined database can be used as a general database for searching of LC-MS data. LC-MS data derived from in-solution digests of two different cell lines (LNCaP, HeLa) and phosphoproteomics studies were analyzed using these two databases. Several nonalternative splice variant-1-specific peptides were found in both cell lines, and some of them seemed to be cell-line-specific. Control and apoptotic phosphoproteomes from Jurkat T cells revealed several nonalternative splice variant-1-specific peptides, and some of them showed clear quantitative differences between the two states.

  3. Unique Prokaryotic Consortia in Geochemically Distinct Sediments from Red Sea Atlantis II and Discovery Deep Brine Pools

    Science.gov (United States)

    Siam, Rania; Mustafa, Ghada A.; Sharaf, Hazem; Moustafa, Ahmed; Ramadan, Adham R.; Antunes, Andre; Bajic, Vladimir B.; Stingl, Uli; Marsis, Nardine G. R.; Coolen, Marco J. L.; Sogin, Mitchell; Ferreira, Ari J. S.; Dorry, Hamza El

    2012-01-01

    The seafloor is a unique environment, which allows insights into how geochemical processes affect the diversity of biological life. Among its diverse ecosystems are deep-sea brine pools - water bodies characterized by a unique combination of extreme conditions. The ‘polyextremophiles’ that constitute the microbial assemblage of these deep hot brines have not been comprehensively studied. We report a comparative taxonomic analysis of the prokaryotic communities of the sediments directly below the Red Sea brine pools, namely, Atlantis II, Discovery, Chain Deep, and an adjacent brine-influenced site. Analyses of sediment samples and high-throughput pyrosequencing of PCR-amplified environmental 16S ribosomal RNA genes (16S rDNA) revealed that one sulfur (S)-rich Atlantis II and one nitrogen (N)-rich Discovery Deep section contained distinct microbial populations that differed from those found in the other sediment samples examined. Proteobacteria, Actinobacteria, Cyanobacteria, Deferribacteres, and Euryarchaeota were the most abundant bacterial and archaeal phyla in both the S- and N-rich sections. Relative abundance-based hierarchical clustering of the 16S rDNA pyrotags assigned to major taxonomic groups allowed us to categorize the archaeal and bacterial communities into three major and distinct groups; group I was unique to the S-rich Atlantis II section (ATII-1), group II was characteristic for the N-rich Discovery sample (DD-1), and group III reflected the composition of the remaining sediments. Many of the groups detected in the S-rich Atlantis II section are likely to play a dominant role in the cycling of methane and sulfur due to their phylogenetic affiliations with bacteria and archaea involved in anaerobic methane oxidation and sulfate reduction. PMID:22916172

  4. Unique prokaryotic consortia in geochemically distinct sediments from Red Sea Atlantis II and discovery deep brine pools.

    Directory of Open Access Journals (Sweden)

    Rania Siam

    Full Text Available The seafloor is a unique environment, which allows insights into how geochemical processes affect the diversity of biological life. Among its diverse ecosystems are deep-sea brine pools - water bodies characterized by a unique combination of extreme conditions. The 'polyextremophiles' that constitute the microbial assemblage of these deep hot brines have not been comprehensively studied. We report a comparative taxonomic analysis of the prokaryotic communities of the sediments directly below the Red Sea brine pools, namely, Atlantis II, Discovery, Chain Deep, and an adjacent brine-influenced site. Analyses of sediment samples and high-throughput pyrosequencing of PCR-amplified environmental 16S ribosomal RNA genes (16S rDNA revealed that one sulfur (S-rich Atlantis II and one nitrogen (N-rich Discovery Deep section contained distinct microbial populations that differed from those found in the other sediment samples examined. Proteobacteria, Actinobacteria, Cyanobacteria, Deferribacteres, and Euryarchaeota were the most abundant bacterial and archaeal phyla in both the S- and N-rich sections. Relative abundance-based hierarchical clustering of the 16S rDNA pyrotags assigned to major taxonomic groups allowed us to categorize the archaeal and bacterial communities into three major and distinct groups; group I was unique to the S-rich Atlantis II section (ATII-1, group II was characteristic for the N-rich Discovery sample (DD-1, and group III reflected the composition of the remaining sediments. Many of the groups detected in the S-rich Atlantis II section are likely to play a dominant role in the cycling of methane and sulfur due to their phylogenetic affiliations with bacteria and archaea involved in anaerobic methane oxidation and sulfate reduction.

  5. Unique prokaryotic consortia in geochemically distinct sediments from Red Sea Atlantis II and discovery deep brine pools.

    KAUST Repository

    Siam, Rania

    2012-08-20

    The seafloor is a unique environment, which allows insights into how geochemical processes affect the diversity of biological life. Among its diverse ecosystems are deep-sea brine pools - water bodies characterized by a unique combination of extreme conditions. The \\'polyextremophiles\\' that constitute the microbial assemblage of these deep hot brines have not been comprehensively studied. We report a comparative taxonomic analysis of the prokaryotic communities of the sediments directly below the Red Sea brine pools, namely, Atlantis II, Discovery, Chain Deep, and an adjacent brine-influenced site. Analyses of sediment samples and high-throughput pyrosequencing of PCR-amplified environmental 16S ribosomal RNA genes (16S rDNA) revealed that one sulfur (S)-rich Atlantis II and one nitrogen (N)-rich Discovery Deep section contained distinct microbial populations that differed from those found in the other sediment samples examined. Proteobacteria, Actinobacteria, Cyanobacteria, Deferribacteres, and Euryarchaeota were the most abundant bacterial and archaeal phyla in both the S- and N-rich sections. Relative abundance-based hierarchical clustering of the 16S rDNA pyrotags assigned to major taxonomic groups allowed us to categorize the archaeal and bacterial communities into three major and distinct groups; group I was unique to the S-rich Atlantis II section (ATII-1), group II was characteristic for the N-rich Discovery sample (DD-1), and group III reflected the composition of the remaining sediments. Many of the groups detected in the S-rich Atlantis II section are likely to play a dominant role in the cycling of methane and sulfur due to their phylogenetic affiliations with bacteria and archaea involved in anaerobic methane oxidation and sulfate reduction.

  6. Crystal structure of Arabidopsis thaliana Dawdle forkhead-associated domain reveals a conserved phospho-threonine recognition cleft for dicer-like 1 binding.

    Science.gov (United States)

    Machida, Satoru; Yuan, Y Adam

    2013-07-01

    Dawdle (DDL) is a microRNA processing protein essential for the development of Arabidopsis. DDL contains a putative nuclear localization signal at its amino-terminus and forkhead-associated (FHA) domain at the carboxyl-terminus. Here, we report the crystal structure of the FHA domain of Arabidopsis Dawdle, determined by multiple-wavelength anomalous dispersion method at 1.7-Å resolution. DDL FHA structure displays a seven-stranded β-sandwich architecture that contains a unique structural motif comprising two long anti-parallel strands. Strikingly, crystal packing of the DDL FHA domain reveals that a glutamate residue from the symmetry-related DDL FHA domain, a structural mimic of the phospho-threonine, is specifically recognized by the structurally conserved phospho-threonine binding cleft. Consistently with the structural observations, co-immuno-precipitation experiments performed in Nicotiana benthamiana show that the DDL FHA domain co-immuno-precipitates with DCL1 fragments containing the predicted pThr+3(Ile/Val/Leu/Asp) motif. Taken together, we count the recognition of the target residue by the canonical binding cleft of the DDL FHA domain as the key molecular event to instate FHA domain-mediated protein-protein interaction in plant miRNA processing.

  7. Uniqueness of time-independent electromagnetic fields

    DEFF Research Database (Denmark)

    Karlsson, Per W.

    1974-01-01

    As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics......As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics...

  8. Changes in unique hues induced by chromatic surrounds.

    Science.gov (United States)

    Klauke, Susanne; Wachtler, Thomas

    2016-03-01

    A chromatic surround can have a strong influence on the perceived hue of a stimulus. We investigated whether chromatic induction has similar effects on the perception of colors that appear pure and unmixed (unique red, green, blue, and yellow) as on other colors. Subjects performed unique hue settings of stimuli in isoluminant surrounds of different chromaticities. Compared with the settings in a neutral gray surround, unique hue settings altered systematically with chromatic surrounds. The amount of induced hue shift depended on the difference between stimulus and surround hues, and was similar for unique hue settings as for settings of nonunique hues. Intraindividual variability in unique hue settings was roughly twice as high as for settings obtained in asymmetric matching experiments, which may reflect the presence of a reference stimulus in the matching task. Variabilities were also larger with chromatic surrounds than with neutral gray surrounds, for both unique hue settings and matching of nonunique hues. The results suggest that the neural representations underlying unique hue percepts are influenced by the same neural processing mechanisms as the percepts of other colors.

  9. Increasing Need for Uniqueness in Contemporary China: Empirical Evidence

    Directory of Open Access Journals (Sweden)

    Huajian Cai

    2018-05-01

    Full Text Available Past research has documented various cultural and psychological changes in contemporary China. In two studies, we examine how Chinese people’s need for uniqueness (NFU also has changed. In Study 1, we found a significant cross-generational increase in Chinese participants’ self-reported NFU. In Study 2, we sampled the names of Chinese newborn babies over the last five decades and found that parents have been increasingly likely to use unique characters to name their children. These findings suggest that the NFU has been rising in China, a historically collectivistic-oriented society. Theoretical and practical implications of our findings were discussed.

  10. Is Life Unique?

    Science.gov (United States)

    Abel, David L.

    2011-01-01

    Is life physicochemically unique? No. Is life unique? Yes. Life manifests innumerable formalisms that cannot be generated or explained by physicodynamics alone. Life pursues thousands of biofunctional goals, not the least of which is staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is largely directed by linear digital programming and by the Prescriptive Information (PI) instantiated particularly into physicodynamically indeterminate nucleotide sequencing. Epigenomic controls only compound the sophistication of these formalisms. Life employs representationalism through the use of symbol systems. Life manifests autonomy, homeostasis far from equilibrium in the harshest of environments, positive and negative feedback mechanisms, prevention and correction of its own errors, and organization of its components into Sustained Functional Systems (SFS). Chance and necessity—heat agitation and the cause-and-effect determinism of nature’s orderliness—cannot spawn formalisms such as mathematics, language, symbol systems, coding, decoding, logic, organization (not to be confused with mere self-ordering), integration of circuits, computational success, and the pursuit of functionality. All of these characteristics of life are formal, not physical. PMID:25382119

  11. RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus.

    Science.gov (United States)

    Grégoire, Catherine-Alexandra; Tobin, Stephanie; Goldenstein, Brianna L; Samarut, Éric; Leclerc, Andréanne; Aumont, Anne; Drapeau, Pierre; Fulton, Stephanie; Fernandes, Karl J L

    2018-01-01

    Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running's genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

  12. Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells

    Energy Technology Data Exchange (ETDEWEB)

    Abou-El-Ardat, Khalil, E-mail: kabouela@sckcen.be [Radiobiology Unit, Molecular and Cellular Biology, GKD Building, Studiecentrum voor Kernenergie - Centre d' Etude de l' Energie Nucleaire (SCK-CEN), Boeretang 200, 2400 Mol (Belgium); Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Universiteit Gent, 9000 Ghent (Belgium); Monsieurs, Pieter [Radiobiology Unit, Molecular and Cellular Biology, GKD Building, Studiecentrum voor Kernenergie - Centre d' Etude de l' Energie Nucleaire (SCK-CEN), Boeretang 200, 2400 Mol (Belgium); Anastasov, Natasa; Atkinson, Mike [Department of Radiation Sciences, Helmholtz Zentrum Muenchen, Munich (Germany); Derradji, Hanane [Radiobiology Unit, Molecular and Cellular Biology, GKD Building, Studiecentrum voor Kernenergie - Centre d' Etude de l' Energie Nucleaire (SCK-CEN), Boeretang 200, 2400 Mol (Belgium); De Meyer, Tim [Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Universiteit Gent, 9000 Ghent (Belgium); Department of Applied Mathematics, Biometrics and Process Control, Faculty of Bioscience Engineering, Universiteit Gent, 9000 Ghent (Belgium); Bekaert, Sofie [Clinical Research Center, Faculty for Medicine and Health Sciences, Universiteit Gent, 185 De Pintelaan, 9000 Ghent (Belgium); Van Criekinge, Wim [Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Universiteit Gent, 9000 Ghent (Belgium); and others

    2012-03-01

    The high doses of radiation received in the wake of the Chernobyl incident and the atomic bombing of Hiroshima and Nagasaki have been linked to the increased appearance of thyroid cancer in the children living in the vicinity of the site. However, the data gathered on the effect of low doses of radiation on the thyroid remain limited. We have examined the genome wide transcriptional response of a culture of TPC-1 human cell line of papillary thyroid carcinoma origin with a RET/PTC1 translocation to various doses (0.0625, 0.5, and 4 Gy) of X-rays and compared it to response of thyroids with a RET/PTC3 translocation and against wild-type mouse thyroids irradiated with the same doses using Affymetrix microarrays. We have found considerable overlap at a high dose of 4 Gy in both RET/PTC-positive systems but no common genes at 62.5 mGy. In addition, the response of RET/PTC-positive system at all doses was distinct from the response of wild-type thyroids with both systems signaling down different pathways. Analysis of the response of microRNAs in TPC-1 cells revealed a radiation-responsive signature of microRNAs in addition to dose-responsive microRNAs. Our results point to the fact that a low dose of X-rays seems to have a significant proliferative effect on normal thyroids. This observation should be studied further as opposed to its effect on RET/PTC-positive thyroids which was subtle, anti-proliferative and system-dependent.

  13. Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region

    DEFF Research Database (Denmark)

    Norberg, Peter; Olofsson, Sigvard; Tarp, Mads Agervig

    2007-01-01

    Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized for O-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed......-glycosylation not only for the two most commonly expressed N-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusively O-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin...

  14. Octacyanoniobate(IV)-based molecular magnets revealing 3D long-range order

    International Nuclear Information System (INIS)

    Pelka, R; Balanda, M; Pinkowicz, D; Drath, O; Nitek, W; Sieklucka, B; Rams, M; Majcher, A

    2011-01-01

    Isostructural series of chemical formula {[M II (pirazol) 4 ] 2 [Nb IV (CN) 8 ]· 4H 2 O} n (M II = Mn (1), Fe (2), Co (3), Ni (4)) has been obtained by the self-assembly technique. Its unique crystallographic structure consists in the formation of a 3D extended network of magnetic centers braced by geometrically identical cyanido bridges. Magnetic measurements reveal the transitions to the 3D order at temperatures 23.7, 8.3, 5.9, 13.4 K for 1, 2, 3, and 4, respectively. The character of order is demonstrated to be ferrimagnetic for 1 and 2 and ferromagnetic for 3 and 4. The mean-field approach is used to determine the corresponding exchange coupling constants. The observed interactions are discussed within the magnetic orbital model.

  15. Octacyanoniobate(IV)-based molecular magnets revealing 3D long-range order

    Science.gov (United States)

    Pełka, R.; Pinkowicz, D.; Drath, O.; Bałanda, M.; Rams, M.; Majcher, A.; Nitek, W.; Sieklucka, B.

    2011-07-01

    Isostructural series of chemical formula {[MII(pirazol)4]2[NbIV(CN)8]· 4H2O}n (MII = Mn (1), Fe (2), Co (3), Ni (4)) has been obtained by the self-assembly technique. Its unique crystallographic structure consists in the formation of a 3D extended network of magnetic centers braced by geometrically identical cyanido bridges. Magnetic measurements reveal the transitions to the 3D order at temperatures 23.7, 8.3, 5.9, 13.4 K for 1, 2, 3, and 4, respectively. The character of order is demonstrated to be ferrimagnetic for 1 and 2 and ferromagnetic for 3 and 4. The mean-field approach is used to determine the corresponding exchange coupling constants. The observed interactions are discussed within the magnetic orbital model.

  16. Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

    Science.gov (United States)

    Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

    2008-07-01

    A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

  17. Structures of Astromaterials Revealed by EBSD

    Science.gov (United States)

    Zolensky, M.

    2018-01-01

    Groups at the Johnson Space Center and the University of Tokyo have been using electron back-scattered diffraction (EBSD) to reveal the crystal structures of extraterrestrial minerals for many years. Even though we also routinely use transmission electron microscopy, synchrotron X-ray diffraction (SXRD), and conventional electron diffraction, we find that EBSD is the most powerful technique for crystal structure elucidation in many instances. In this talk I describe a few of the cases where we have found EBSD to provide crucial, unique information. See attachment.

  18. NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

    Science.gov (United States)

    Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong

    2015-11-10

    A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result

  19. Diversity and strain specificity of plant cell wall degrading enzymes revealed by the draft genome of Ruminococcus flavefaciens FD-1.

    Directory of Open Access Journals (Sweden)

    Margret E Berg Miller

    Full Text Available BACKGROUND: Ruminococcus flavefaciens is a predominant cellulolytic rumen bacterium, which forms a multi-enzyme cellulosome complex that could play an integral role in the ability of this bacterium to degrade plant cell wall polysaccharides. Identifying the major enzyme types involved in plant cell wall degradation is essential for gaining a better understanding of the cellulolytic capabilities of this organism as well as highlighting potential enzymes for application in improvement of livestock nutrition and for conversion of cellulosic biomass to liquid fuels. METHODOLOGY/PRINCIPAL FINDINGS: The R. flavefaciens FD-1 genome was sequenced to 29x-coverage, based on pulsed-field gel electrophoresis estimates (4.4 Mb, and assembled into 119 contigs providing 4,576,399 bp of unique sequence. As much as 87.1% of the genome encodes ORFs, tRNA, rRNAs, or repeats. The GC content was calculated at 45%. A total of 4,339 ORFs was detected with an average gene length of 918 bp. The cellulosome model for R. flavefaciens was further refined by sequence analysis, with at least 225 dockerin-containing ORFs, including previously characterized cohesin-containing scaffoldin molecules. These dockerin-containing ORFs encode a variety of catalytic modules including glycoside hydrolases (GHs, polysaccharide lyases, and carbohydrate esterases. Additionally, 56 ORFs encode proteins that contain carbohydrate-binding modules (CBMs. Functional microarray analysis of the genome revealed that 56 of the cellulosome-associated ORFs were up-regulated, 14 were down-regulated, 135 were unaffected, when R. flavefaciens FD-1 was grown on cellulose versus cellobiose. Three multi-modular xylanases (ORF01222, ORF03896, and ORF01315 exhibited the highest levels of up-regulation. CONCLUSIONS/SIGNIFICANCE: The genomic evidence indicates that R. flavefaciens FD-1 has the largest known number of fiber-degrading enzymes likely to be arranged in a cellulosome architecture. Functional

  20. Uniqueness and nonuniqueness for the porous medium equation with non linear boundary conditions

    OpenAIRE

    Cortazar, Carmen; Elgueta, Manuel; Rossi, Julio D.

    2003-01-01

    We study the uniqueness problem for nonnegative solutions of $u_t=\\Delta u^m$ in $\\Omega \\times [0,T)$, $-\\frac{\\partial u^m}{\\partial \\hat{n}}(x,t)=u^{\\lambda}(x,t)$ on $\\partial \\Omega \\times (0,T)$ and $u(x,0) \\equiv 0$ on $\\Omega$ where $m > 1$, $\\lambda \\ge 1$, and $\\Omega$ is a bounded domain with smooth boundary in $\\mathbf {R}^N$. We prove that the solution $u \\equiv 0$ is unique if and only if $2\\lambda \\geq m+1$.

  1. Unique Footprint in the scl1.3 Locus Affects Adhesion and Biofilm Formation of the Invasive M3-Type Group A Streptococcus.

    Science.gov (United States)

    Bachert, Beth A; Choi, Soo J; LaSala, Paul R; Harper, Tiffany I; McNitt, Dudley H; Boehm, Dylan T; Caswell, Clayton C; Ciborowski, Pawel; Keene, Douglas R; Flores, Anthony R; Musser, James M; Squeglia, Flavia; Marasco, Daniela; Berisio, Rita; Lukomski, Slawomir

    2016-01-01

    The streptococcal collagen-like proteins 1 and 2 (Scl1 and Scl2) are major surface adhesins that are ubiquitous among group A Streptococcus (GAS). Invasive M3-type strains, however, have evolved two unique conserved features in the scl1 locus: (i) an IS1548 element insertion in the scl1 promoter region and (ii) a nonsense mutation within the scl1 coding sequence. The scl1 transcript is drastically reduced in M3-type GAS, contrasting with a high transcription level of scl1 allele in invasive M1-type GAS. This leads to a lack of Scl1 expression in M3 strains. In contrast, while scl2 transcription and Scl2 production are elevated in M3 strains, M1 GAS lack Scl2 surface expression. M3-type strains were shown to have reduced biofilm formation on inanimate surfaces coated with cellular fibronectin and laminin, and in human skin equivalents. Repair of the nonsense mutation and restoration of Scl1 expression on M3-GAS cells, restores biofilm formation on cellular fibronectin and laminin coatings. Inactivation of scl1 in biofilm-capable M28 and M41 strains results in larger skin lesions in a mouse model, indicating that lack of Scl1 adhesin promotes bacterial spread over localized infection. These studies suggest the uniquely evolved scl1 locus in the M3-type strains, which prevents surface expression of the major Scl1 adhesin, contributed to the emergence of the invasive M3-type strains. Furthermore these studies provide insight into the molecular mechanisms mediating colonization, biofilm formation, and pathogenesis of group A streptococci.

  2. Unique footprint in the scl1.3 locus affects adhesion and biofilm formation of the invasive M3-type group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Beth Alexandra Bachert

    2016-08-01

    Full Text Available The streptococcal collagen-like proteins 1 and 2 (Scl1 and Scl2 are major surface adhesins that are ubiquitous among group A Streptococcus (GAS. Invasive M3-type strains, however, have evolved two unique conserved features in the scl1 locus: (i an IS1548 element insertion in the scl1 promoter region and (ii a nonsense mutation within the scl1 coding sequence. The scl1 transcript is drastically reduced in M3-type GAS, contrasting with a high transcription level of scl1 allele in invasive M1-type GAS. This leads to a lack of Scl1 expression in M3 strains. In contrast, while scl2 transcription and Scl2 production are elevated in M3 strains, M1 GAS lack Scl2 surface expression. M3-type strains were shown to have reduced biofilm formation on inanimate surfaces coated with cellular fibronectin and laminin, and in human skin equivalents. Repair of the nonsense mutation and restoration of Scl1 expression on M3-GAS cells, restores biofilm formation on cellular fibronectin and laminin coatings. Inactivation of scl1 in biofilm-capable M28 and M41 strains results in larger skin lesions in a mouse model, indicating that lack of Scl1 adhesin promotes bacterial spread over localized infection. These studies suggest the uniquely evolved scl1 locus in the M3-type strains, which prevents surface expression of the major Scl1 adhesin, contributed to the emergence of the invasive M3-type strains. Furthermore these studies provide insight into the molecular mechanisms mediating colonization, biofilm formation, and pathogenesis of group A streptococci.

  3. Unique Aspects of Cryptochrome in Chronobiology and Metabolism, Pancreatic β-Cell Dysfunction, and Regeneration: Research into Cysteine414-Alanine Mutant CRY1

    OpenAIRE

    Satoshi Okano

    2016-01-01

    Cryptochrome proteins (CRYs), which can bind noncovalently to cofactor (chromophore) flavin adenine dinucleotide (FAD), occur widely among organisms. CRYs play indispensable roles in the generation of circadian rhythm in mammals. Transgenic mice (Tg mice), ubiquitously expressing mouse CRY1 having a mutation in which cysteine414 (the zinc-binding site of CRY1) being replaced with alanine, display unique phenotypes in their circadian rhythms. Moreover, male Tg mice exhibit symptoms of diabetes...

  4. Structural characterization of Helicobacter pylori dethiobiotin synthetase reveals differences between family members

    Energy Technology Data Exchange (ETDEWEB)

    Porebski, Przemyslaw J.; Klimecka, Maria; Chruszcz, Maksymilian; Nicholls, Robert A.; Murzyn, Krzysztof; Cuff, Marianne E.; Xu, Xiaohui; Cymborowski, Marcin; Murshudov, Garib N.; Savchenko, Alexei; Edwards, Aled; Minor, Wladek (MCSG); (UV); (MRC)

    2012-07-11

    Dethiobiotin synthetase (DTBS) is involved in the biosynthesis of biotin in bacteria, fungi, and plants. As humans lack this pathway, DTBS is a promising antimicrobial drug target. We determined structures of DTBS from Helicobacter pylori (hpDTBS) bound with cofactors and a substrate analog, and described its unique characteristics relative to other DTBS proteins. Comparison with bacterial DTBS orthologs revealed considerable structural differences in nucleotide recognition. The C-terminal region of DTBS proteins, which contains two nucleotide-recognition motifs, differs greatly among DTBS proteins from different species. The structure of hpDTBS revealed that this protein is unique and does not contain a C-terminal region containing one of the motifs. The single nucleotide-binding motif in hpDTBS is similar to its counterpart in GTPases; however, isothermal titration calorimetry binding studies showed that hpDTBS has a strong preference for ATP. The structural determinants of ATP specificity were assessed with X-ray crystallographic studies of hpDTBS-ATP and hpDTBS-GTP complexes. The unique mode of nucleotide recognition in hpDTBS makes this protein a good target for H. pylori-specific inhibitors of the biotin synthesis pathway.

  5. Coexistence of uniquely ergodic subsystems of interval mapping

    International Nuclear Information System (INIS)

    Ye Xiangdong.

    1991-10-01

    The purpose of this paper is to show that uniquely ergodic subsystems of interval mapping also coexist in the same way as minimal sets do. To do this we give some notations in section 2. In section 3 we define D-function of a uniquely ergodic system and show its basic properties. We prove the coexistence of uniquely ergodic subsystems of interval mapping in section 4. Lastly we give the examples of uniquely ergodic systems with given D-functions in section 5. 27 refs

  6. A unique bivalent binding and inhibition mechanism by the yatapoxvirus interleukin 18 binding protein.

    Directory of Open Access Journals (Sweden)

    Brian Krumm

    Full Text Available Interleukin 18 (IL18 is a cytokine that plays an important role in inflammation as well as host defense against microbes. Mammals encode a soluble inhibitor of IL18 termed IL18 binding protein (IL18BP that modulates IL18 activity through a negative feedback mechanism. Many poxviruses encode homologous IL18BPs, which contribute to virulence. Previous structural and functional studies on IL18 and IL18BPs revealed an essential binding hot spot involving a lysine on IL18 and two aromatic residues on IL18BPs. The aromatic residues are conserved among the very diverse mammalian and poxviruses IL18BPs with the notable exception of yatapoxvirus IL18BPs, which lack a critical phenylalanine residue. To understand the mechanism by which yatapoxvirus IL18BPs neutralize IL18, we solved the crystal structure of the Yaba-Like Disease Virus (YLDV IL18BP and IL18 complex at 1.75 Å resolution. YLDV-IL18BP forms a disulfide bonded homo-dimer engaging IL18 in a 2∶2 stoichiometry, in contrast to the 11 complex of ectromelia virus (ECTV IL18BP and IL18. Disruption of the dimer interface resulted in a functional monomer, however with a 3-fold decrease in binding affinity. The overall architecture of the YLDV-IL18BP:IL18 complex is similar to that observed in the ECTV-IL18BP:IL18 complex, despite lacking the critical lysine-phenylalanine interaction. Through structural and mutagenesis studies, contact residues that are unique to the YLDV-IL18BP:IL18 binding interface were identified, including Q67, P116 of YLDV-IL18BP and Y1, S105 and D110 of IL18. Overall, our studies show that YLDV-IL18BP is unique among the diverse family of mammalian and poxvirus IL-18BPs in that it uses a bivalent binding mode and a unique set of interacting residues for binding IL18. However, despite this extensive divergence, YLDV-IL18BP binds to the same surface of IL18 used by other IL18BPs, suggesting that all IL18BPs use a conserved inhibitory mechanism by blocking a putative receptor

  7. Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development

    Directory of Open Access Journals (Sweden)

    Asrar Alam

    2014-01-01

    Full Text Available Metabolic enzymes have been known to carry out a variety of functions besides their normal housekeeping roles known as “moonlighting functions.” These functionalities arise from structural changes induced by posttranslational modifications and/or binding of interacting proteins. Glycolysis is the sole source of energy generation for malaria parasite Plasmodium falciparum, hence a potential pathway for therapeutic intervention. Crystal structures of several P. falciparum glycolytic enzymes have been solved, revealing that they exhibit unique structural differences from the respective host enzymes, which could be exploited for their selective targeting. In addition, these enzymes carry out many parasite-specific functions, which could be of potential interest to control parasite development and transmission. This review focuses on the moonlighting functions of P. falciparum glycolytic enzymes and unique structural differences and functional features of the parasite enzymes, which could be exploited for therapeutic and transmission blocking interventions against malaria.

  8. Essential Genes for In Vitro Growth of the Endophyte Herbaspirillum seropedicae SmR1 as Revealed by Transposon Insertion Site Sequencing.

    Science.gov (United States)

    Rosconi, Federico; de Vries, Stefan P W; Baig, Abiyad; Fabiano, Elena; Grant, Andrew J

    2016-11-15

    The interior of plants contains microorganisms (referred to as endophytes) that are distinct from those present at the root surface or in the surrounding soil. Herbaspirillum seropedicae strain SmR1, belonging to the betaproteobacteria, is an endophyte that colonizes crops, including rice, maize, sugarcane, and sorghum. Different approaches have revealed genes and pathways regulated during the interactions of H. seropedicae with its plant hosts. However, functional genomic analysis of transposon (Tn) mutants has been hampered by the lack of genetic tools. Here we successfully employed a combination of in vivo high-density mariner Tn mutagenesis and targeted Tn insertion site sequencing (Tn-seq) in H. seropedicae SmR1. The analysis of multiple gene-saturating Tn libraries revealed that 395 genes are essential for the growth of H. seropedicae SmR1 in tryptone-yeast extract medium. A comparative analysis with the Database of Essential Genes (DEG) showed that 25 genes are uniquely essential in H. seropedicae SmR1. The Tn mutagenesis protocol developed and the gene-saturating Tn libraries generated will facilitate elucidation of the genetic mechanisms of the H. seropedicae endophytic lifestyle. A focal point in the study of endophytes is the development of effective biofertilizers that could help to reduce the input of agrochemicals in croplands. Besides the ability to promote plant growth, a good biofertilizer should be successful in colonizing its host and competing against the native microbiota. By using a systematic Tn-based gene-inactivation strategy and massively parallel sequencing of Tn insertion sites (Tn-seq), it is possible to study the fitness of thousands of Tn mutants in a single experiment. We have applied the combination of these techniques to the plant-growth-promoting endophyte Herbaspirillum seropedicae SmR1. The Tn mutant libraries generated will enable studies into the genetic mechanisms of H. seropedicae-plant interactions. The approach that we

  9. Being and feeling unique: statistical deviance and psychological marginality.

    Science.gov (United States)

    Frable, D E

    1993-03-01

    Two studies tested the hypothesis that people with culturally stigmatized and concealable conditions (e.g., gays, epileptics, juvenile delinquents, and incest victims) would be more likely to feel unique than people with culturally valued or conspicuous conditions (e.g., the physically attractive, the intellectually gifted, the obese, and the facially scarred). In Study 1, culturally stigmatized individuals with concealable conditions were least likely to perceive consensus between their personal preferences and those of others. In Study 2, they were most likely to describe themselves as unique and to make these self-relevant decisions quickly. Marginality is a psychological reality, not just a statistical one, for those with stigmatized and concealable "master status" conditions.

  10. Non-unique Product Groups on Two Generators

    OpenAIRE

    Carter, William Paul

    2007-01-01

    The main purpose of this paper is to better understand groups that do not have the unique product property. In particular, the goal is to better understand Promislow's example, G, of such a group. In doing so, we will develop methods for generating examples of other sets that do not have the unique product property. With these methods we can show that there exists other distinct 14 element, square, non-unique product sets in G that are not inversions or translations. Also, this paper answers ...

  11. RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus

    Directory of Open Access Journals (Sweden)

    Catherine-Alexandra Grégoire

    2018-04-01

    Full Text Available Environmental enrichment (EE is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG, a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN, a locked disk (LD, or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running’s genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

  12. Association of GSTP1 gene polymorphisms with performance traits ...

    African Journals Online (AJOL)

    sony

    The genetic variants were determined by PCR-SSCP technique. Two unique SSCP patterns were observed in fragment 1, 3, 5 and 6 of GSTP1 gene. Sequence analysis with reference to GenBank. Acc. no AC_000186.1 revealed polymorphisms at position 210, 746, 2438, 2439, 2443, 2507, 2695 and insertions between ...

  13. Unique microstructure and excellent mechanical properties of ADI

    Directory of Open Access Journals (Sweden)

    Jincheng Liu

    2006-11-01

    Full Text Available Amongst the cast iron family, ADI has a unique microstructure and an excellent, optimised combination of mechanical properties. The main microstructure of ADI is ausferrite, which is a mixture ofextremely fine acicular ferrite and stable, high carbon austenite. There are two types of austenite in ADI:(1 the coarser and more equiaxed blocks of austenite between non-parallel acicular structures, which exist mainly in the last solidified area, and (2 the thin films of ustenite between the individual ferriteplatelets in the acicular structure. It is this unique microstructure, which gives ADI its excellent static and dynamic properties, and good low temperature impact toughness. The effect of microstructure on the mechanical properties is explained in more detail by examining the microstructure at the atomic scale. Considering the nanometer grain sizes, the unique microstructure, the excellent mechanical properties,good castability, (which enables near net shape components to be produced economically and in large volumes, and the fact that it can be 100% recycled, it is not overemphasized to call ADI a high-tech,nanometer and “green” material. ADI still has the potential to be further improved and its production and the number of applications for ADI will continue to grow, driven by the resultant cost savings over alternative materials.

  14. Tattoos and piercings: bodily expressions of uniqueness?

    Science.gov (United States)

    Tiggemann, Marika; Hopkins, Louise A

    2011-06-01

    The study aimed to investigate the motivations underlying the body modification practices of tattooing and piercing. There were 80 participants recruited from an Australian music store, who provided descriptions of their tattoos and piercings and completed measures of need for uniqueness, appearance investment and distinctive appearance investment. It was found that tattooed individuals scored significantly higher on need for uniqueness than non-tattooed individuals. Further, individuals with conventional ear piercings scored significantly lower on need for uniqueness than individuals with no piercings or with facial and body piercings. Neither appearance investment nor distinctive appearance investment differed significantly among tattoo or piercing status groups. Strength of identification with music was significantly correlated with number of tattoos, but not number of piercings. It was concluded that tattooing, but not body piercing, represents a bodily expression of uniqueness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    Science.gov (United States)

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  16. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  17. Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia

    International Nuclear Information System (INIS)

    Chen, C-C; You, J-Y; Gau, J-P; Huang, C-E; Chen, Y-Y; Tsai, Y-H; Chou, H-J; Lung, J; Yang, M-H

    2015-01-01

    Epithelial–mesenchymal transition (EMT) is a critical process for inducing stem-like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1, an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1, and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1. AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1-overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest that, in a subset of AML patients, Twist1 has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes

  18. Investigation of unique hue setting changes with ageing

    Institute of Scientific and Technical Information of China (English)

    Chenyang Fu; Kaida Xiao; Dimosthenis Karatzas; Sophie Wuerger

    2011-01-01

    Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n = 185) of colour-normal observers ranging from 18 to 75 years of age are assessed. Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions. Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed. Based on the chromatic (protan, deutan, tritan) thresholds and using scaled cone signals, we predict the unique hue changes with ageing. A dependency on age for unique red and unique yellow for predicted hue angle is found. We conclude that the chromatic sensitivity deteriorates significantly with age, whereas the appearance of unique hues is much less affected, remaining almost constant despite the known changes in the ocular media.%@@ Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n = 185) of colour-normal observers ranging from 18 to 75 years of age are assessed.Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions.Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed.

  19. Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan.

    Science.gov (United States)

    Nakayama, Hiroki; Tsukamoto, Katsura

    2018-04-17

    The approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0 days [interquartile range, 263.3-336.0]; 222.5 patients [66.0-454.3]) were significantly lower than those on non-orphan drugs (353.0 days [277.0-535.5]; 521.0 patients [303.5-814.5], respectively) (P < 0.001). Phase II, non-randomized and non-controlled designs were more frequently used in pivotal studies on orphan anticancer drugs (45.9%, 41.9% and 43.2%) than non-orphan drugs (17.2%, 14.1% and 14.1%, respectively). Response rate was more commonly used as a primary endpoint in pivotal studies on orphan anticancer drugs (48.6%) than non-orphan drugs (17.2%). Indications limited by molecular features, second or later treatment line, and accelerated approval in the United States were associated with the use of response rate in orphan anticancer drug studies. In conclusion, we demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.

  20. Marginal and happy? The need for uniqueness predicts the adjustment of marginal immigrants.

    Science.gov (United States)

    Debrosse, Régine; de la Sablonnière, Roxane; Rossignac-Milon, Maya

    2015-12-01

    Marginalization is often presented as the strategy associated with the worst adjustment for immigrants. This study identifies a critical variable that buffers marginal immigrants from the negative effects of marginalization on adjustment: The need for uniqueness. In three studies, we surveyed immigrants recruited on university campuses (n = 119, n = 116) and in the field (n = 61). Among marginal immigrants, a higher need for uniqueness predicted higher self-esteem (Study 1), affect (Study 2), and life satisfaction (Study 3), and marginally higher happiness (Study 2) and self-esteem (Study 3). No relationship between the need for uniqueness and adjustment was found among non-marginal immigrants. The adaptive value of the need for uniqueness for marginal immigrants is discussed. © 2015 The British Psychological Society.

  1. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody

    Directory of Open Access Journals (Sweden)

    Chandra Mohan Sharma

    2016-01-01

    Full Text Available Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes , limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies.Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome,cerebellar ataxia and palatal myoclonus.This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.

  2. Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.

    Science.gov (United States)

    Koch, Maximilian F; Harteis, Sabrina; Blank, Iris D; Pestel, Galina; Tietze, Lutz F; Ochsenfeld, Christian; Schneider, Sabine; Sieber, Stephan A

    2015-11-09

    Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial π-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The first venomous crustacean revealed by transcriptomics and functional morphology: remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin.

    Science.gov (United States)

    von Reumont, Björn M; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A

    2014-01-01

    Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.

  4. An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression

    Science.gov (United States)

    2017-10-01

    targeting of critical androgen receptor -604 coregulator interactions in prostate cancer . Nature communications 4, 1923, 605 doi:10.1038/ncomms2912 (2013...AWARD NUMBER: W81XWH-16-1-0474 TITLE: An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression PRINCIPAL INVESTIGATOR...14 Sep 2017 4. Title An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER

  5. RUCS: Rapid identification of PCR primers for unique core sequences

    DEFF Research Database (Denmark)

    Thomsen, Martin Christen Frølund; Hasman, Henrik; Westh, Henrik

    2017-01-01

    Designing PCR primers to target a specific selection of whole genome sequenced strains can be a long, arduous, and sometimes impractical task. Such tasks would benefit greatly from an automated tool to both identify unique targets, and to validate the vast number of potential primer pairs...... for the targets in silico . Here we present RUCS, a program that will find PCR primer pairs and probes for the unique core sequences of a positive genome dataset complement to a negative genome dataset. The resulting primer pairs and probes are in addition to simple selection also validated through a complex...... in silico PCR simulation. We compared our method, which identifies the unique core sequences, against an existing tool called ssGeneFinder, and found that our method was 6.5-20 times more sensitive. We used RUCS to design primer pairs that would target a set of genomes known to contain the mcr-1 colistin...

  6. A novel frequency analysis method for assessing K(ir)2.1 and Na (v)1.5 currents.

    Science.gov (United States)

    Rigby, J R; Poelzing, S

    2012-04-01

    Voltage clamping is an important tool for measuring individual currents from an electrically active cell. However, it is difficult to isolate individual currents without pharmacological or voltage inhibition. Herein, we present a technique that involves inserting a noise function into a standard voltage step protocol, which allows one to characterize the unique frequency response of an ion channel at different step potentials. Specifically, we compute the fast Fourier transform for a family of current traces at different step potentials for the inward rectifying potassium channel, K(ir)2.1, and the channel encoding the cardiac fast sodium current, Na(v)1.5. Each individual frequency magnitude, as a function of voltage step, is correlated to the peak current produced by each channel. The correlation coefficient vs. frequency relationship reveals that these two channels are associated with some unique frequencies with high absolute correlation. The individual IV relationship can then be recreated using only the unique frequencies with magnitudes of high absolute correlation. Thus, this study demonstrates that ion channels may exhibit unique frequency responses.

  7. Unique C-terminal region of Hap3 is required for methanol-regulated gene expression in the methylotrophic yeast Candida boidinii.

    Science.gov (United States)

    Oda, Saori; Yurimoto, Hiroya; Nitta, Nobuhisa; Sakai, Yasuyoshi

    2016-05-01

    The Hap complex of the methylotrophic yeast Candida boidinii was found to be required for methanol-regulated gene expression. In this study, we performed functional characterization of CbHap3p, one of the Hap complex components in C. boidinii. Sequence alignment of Hap3 proteins revealed the presence of a unique extended C-terminal region, which is not present in Hap3p from Saccharomyces cerevisiae (ScHap3p), but is found in Hap3p proteins of methylotrophic yeasts. Deletion of the C-terminal region of CbHap3p (Δ256-292 or Δ107-237) diminished activation of methanol-regulated genes and abolished the ability to grow on methanol, but did not affect nuclear localization or DNA-binding ability. However, deletion of the N-terminal region of CbHap3p (Δ1-20) led to not only a growth defect on methanol and a decreased level of methanol-regulated gene expression, but also impaired nuclear localization and binding to methanol-regulated gene promoters. We also revealed that CbHap3p could complement the growth defect of the Schap3Δ strain on glycerol, although ScHap3p could not complement the growth defect of a Cbhap3Δ strain on methanol. We conclude that the unique C-terminal region of CbHap3p contributes to maximum activation of methanol-regulated genes, whilst the N-terminal region is required for nuclear localization and binding to DNA.

  8. Uniqueness of non-linear ground states for fractional Laplacians in R

    DEFF Research Database (Denmark)

    Frank, Rupert L.; Lenzmann, Enno

    2013-01-01

    We prove uniqueness of ground state solutions Q = Q(|x|) ≥ 0 of the non-linear equation (−Δ)sQ+Q−Qα+1=0inR,where 0 fractional Laplacian in one dimension. In particular, we answer affirmatively an open question...... recently raised by Kenig–Martel–Robbiano and we generalize (by completely different techniques) the specific uniqueness result obtained by Amick and Toland for s=12 and α = 1 in [5] for the Benjamin–Ono equation. As a technical key result in this paper, we show that the associated linearized operator L...... + = (−Δ) s +1−(α+1)Q α is non-degenerate; i.e., its kernel satisfies ker L + = span{Q′}. This result about L + proves a spectral assumption, which plays a central role for the stability of solitary waves and blowup analysis for non-linear dispersive PDEs with fractional Laplacians, such as the generalized...

  9. Uniqueness conditions for finitely dependent random fields

    International Nuclear Information System (INIS)

    Dobrushin, R.L.; Pecherski, E.A.

    1981-01-01

    The authors consider a random field for which uniqueness and some additional conditions guaranteeing that the correlations between the variables of the field decrease rapidly enough with the distance between the values of the parameter occur. The main result of the paper states that in such a case uniqueness is true for any other field with transition probabilities sufficiently close to those of the original field. Then they apply this result to some ''degenerate'' classes of random fields for which one can check this condition of correlation to decay, and thus obtain some new conditions of uniqueness. (Auth.)

  10. Practical relevance of pattern uniqueness in forensic science.

    Science.gov (United States)

    Jayaprakash, Paul T

    2013-09-10

    Uniqueness being unprovable, it has recently been argued that individualization in forensic science is irrelevant and, probability, as applied for DNA profiles, should be applied for all identifications. Critiques against uniqueness have omitted physical matching, a realistic and tangible individualization that supports uniqueness. Describing case examples illustrating pattern matches including physical matching, it is indicated that individualizations are practically relevant for forensic science as they establish facts on a definitive basis providing firm leads benefitting criminal investigation. As a tenet of forensic identification, uniqueness forms a fundamental paradigm relevant for individualization. Evidence on the indeterministic and stochastic causal pathways of characteristics in patterns available in the related fields of science sufficiently supports the proposition of uniqueness. Characteristics involved in physical matching and matching achieved in patterned evidence existing in the state of nature are not events amenable for counting; instead these are ensemble of visible units occupying the entire pattern area stretching the probability of re-occurrence of a verisimilitude pattern into infinity offering epistemic support to uniqueness. Observational methods are as respectable as instrumental or statistical methods since they are capable of generating results that are tangible and obviously valid as in physical matching. Applying the probabilistic interpretation used for DNA profiles to the other patterns would be unbefitting since these two are disparate, the causal pathways of the events, the loci, in the manipulated DNA profiles being determinable. While uniqueness enables individualizations, it does not vouch for eliminating errors. Instead of dismissing uniqueness and individualization, accepting errors as human or system failures and seeking remedial measures would benefit forensic science practice and criminal investigation. Copyright © 2013

  11. Are common names becoming less common? The rise in uniqueness and individualism in Japan.

    Science.gov (United States)

    Ogihara, Yuji; Fujita, Hiroyo; Tominaga, Hitoshi; Ishigaki, Sho; Kashimoto, Takuya; Takahashi, Ayano; Toyohara, Kyoko; Uchida, Yukiko

    2015-01-01

    We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates) suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual's psyche and behavior outside the head; e.g., advertising) can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by pairing common

  12. Unique properties of Drosophila spermatocyte primary cilia

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Riparbelli

    2013-09-01

    The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT, maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol, a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.

  13. Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina.

    Directory of Open Access Journals (Sweden)

    Astrid Zayas-Santiago

    Full Text Available Müller cells, the principal glial cells of the vertebrate retina, are fundamental for the maintenance and function of neuronal cells. In most vertebrates, including humans, Müller cells abundantly express Kir4.1 inwardly rectifying potassium channels responsible for hyperpolarized membrane potential and for various vital functions such as potassium buffering and glutamate clearance; inter-species differences in Kir4.1 expression were, however, observed. Localization and function of potassium channels in Müller cells from the retina of crocodiles remain, hitherto, unknown.We studied retinae of the Spectacled caiman (Caiman crocodilus fuscus, endowed with both diurnal and nocturnal vision, by (i immunohistochemistry, (ii whole-cell voltage-clamp, and (iii fluorescent dye tracing to investigate K+ channel distribution and glia-to-neuron communications.Immunohistochemistry revealed that caiman Müller cells, similarly to other vertebrates, express vimentin, GFAP, S100β, and glutamine synthetase. In contrast, Kir4.1 channel protein was not found in Müller cells but was localized in photoreceptor cells. Instead, 2P-domain TASK-1 channels were expressed in Müller cells. Electrophysiological properties of enzymatically dissociated Müller cells without photoreceptors and isolated Müller cells with adhering photoreceptors were significantly different. This suggests ion coupling between Müller cells and photoreceptors in the caiman retina. Sulforhodamine-B injected into cones permeated to adhering Müller cells thus revealing a uni-directional dye coupling.Our data indicate that caiman Müller glial cells are unique among vertebrates studied so far by predominantly expressing TASK-1 rather than Kir4.1 K+ channels and by bi-directional ion and uni-directional dye coupling to photoreceptor cells. This coupling may play an important role in specific glia-neuron signaling pathways and in a new type of K+ buffering.

  14. Human uniqueness-self-interest and social cooperation.

    Science.gov (United States)

    Okada, Daijiro; Bingham, Paul M

    2008-07-21

    Humans are unique among all species of terrestrial history in both ecological dominance and individual properties. Many, or perhaps all, of the unique elements of this nonpareil status can be plausibly interpreted as evolutionary and strategic elements and consequences of the unprecedented intensity and scale of our social cooperation. Convincing explanation of this unique human social adaptation remains a central, unmet challenge to the scientific enterprise. We develop a hypothesis for the ancestral origin of expanded cooperative social behavior. Specifically, we present a game theoretic analysis demonstrating that a specific pattern of expanded social cooperation between conspecific individuals with conflicts of interest (including non-kin) can be strategically viable, but only in animals that possess a highly unusual capacity for conspecific violence (credible threat) having very specific properties that dramatically reduce the costs of coercive violence. The resulting reduced costs allow preemptive or compensated coercion to be an instantaneously self-interested behavior under diverse circumstances rather than in rare, idiosyncratic circumstances as in actors (animals) who do not have access to inexpensive coercive threat. Humans are apparently unique among terrestrial organisms in having evolved conspecific coercive capabilities that fulfill these stringent requirements. Thus, our results support the proposal that access to a novel capacity for projection of coercive threat might represent the essential initiating event for the evolution of a human-like pattern of social cooperation and the subsequent evolution of the diverse features of human uniqueness. Empirical evidence indicates that these constraints were, in fact, met only in our evolutionary lineage. The logic for the emergence of uniquely human cooperation suggested by our analysis apparently accounts simply for the human fossil record.

  15. Unique Aspects of Cryptochrome in Chronobiology and Metabolism, Pancreatic β-Cell Dysfunction, and Regeneration: Research into Cysteine414-Alanine Mutant CRY1

    Directory of Open Access Journals (Sweden)

    Satoshi Okano

    2016-01-01

    Full Text Available Cryptochrome proteins (CRYs, which can bind noncovalently to cofactor (chromophore flavin adenine dinucleotide (FAD, occur widely among organisms. CRYs play indispensable roles in the generation of circadian rhythm in mammals. Transgenic mice (Tg mice, ubiquitously expressing mouse CRY1 having a mutation in which cysteine414 (the zinc-binding site of CRY1 being replaced with alanine, display unique phenotypes in their circadian rhythms. Moreover, male Tg mice exhibit symptoms of diabetes characterized by beta-cell dysfunction, resembling human maturity onset diabetes of the young (MODY. The lowered proliferation of β-cells is a primary cause of age-dependent β-cell loss. Furthermore, unusually enlarged duct-like structures developed prominently in the Tg mice pancreases. The duct-like structures contained insulin-positive cells, suggesting neogenesis of β-cells in the Tg mice. This review, based mainly on the author’s investigation of the unique features of Tg mice, presents reported results and recent findings related to molecular processes associated with mammalian cryptochromes, especially their involvement in the regulation of metabolism. New information is described with emphasis on the aspects of islet architecture, pancreatic β-cell dysfunction, and regeneration.

  16. Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity.

    Science.gov (United States)

    Zhang, Peilan; Li, Kunhua; Yang, Guang; Xia, Changqing; Polston, Jane E; Li, Gengnan; Li, Shiwu; Lin, Zhao; Yang, Li-Jun; Bruner, Steven D; Ding, Yousong

    2017-08-22

    Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan-GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcβ1-4(Fucα1-3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αβα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel β-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment.

  17. Unique Action of Interleukin-18 on T Cells and Other Immune Cells

    Directory of Open Access Journals (Sweden)

    Kenji Nakanishi

    2018-04-01

    Full Text Available Interleukin (IL-18 was originally discovered as a factor that enhances interferon (IFN-γ production by anti-CD3-stimulated Th1 cells, particularly in association with IL-12. IL-12 is a cytokine that induces development of Th1 cells. IL-18 cannot induce Th1 cell development, but has the capacity to activate established Th1 cells to produce IFN-γ in the presence of IL-12. Thus, IL-18 is regarded as a proinflammatory cytokine that facilitates type 1 responses. However, in the absence of IL-12 but presence of IL-2, IL-18 stimulates natural killer cells, NKT cells, and even established Th1 cells to produce IL-3, IL-9, and IL-13. Thus, IL-18 also facilitates type 2 responses. This unique function of IL-18 contributes to infection-associated allergic diseases. Together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Thus, IL-18 also induces innate-type allergic inflammation. IL-18 belongs to the IL-1 family of cytokines, which share similar molecular structures, receptors structures, and signal transduction pathways. Nevertheless, IL-18 shows a unique function by binding to a specific receptor expressed on distinct types of cells. In this review article, I will focus on the unique features of IL-18 in lymphocytes, basophils, and mast cells, particularly in comparison with IL-33.

  18. Constructing Dense Graphs with Unique Hamiltonian Cycles

    Science.gov (United States)

    Lynch, Mark A. M.

    2012-01-01

    It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

  19. High-frequency microrheology reveals cytoskeleton dynamics in living cells

    Science.gov (United States)

    Rigato, Annafrancesca; Miyagi, Atsushi; Scheuring, Simon; Rico, Felix

    2017-08-01

    Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range--up to the frequency characterizing the molecular components--provides a mechanistic understanding of cell mechanics.

  20. Hausdorff dimension of unique beta expansions

    International Nuclear Information System (INIS)

    Kong, Derong; Li, Wenxia

    2015-01-01

    Given an integer N ⩾ 2 and a real number β > 1, let Γ β, N be the set of all x=∑ i=1 ∞ d i /β i with d i  ∈ {0, 1, ···, N − 1} for all i ⩾ 1. The infinite sequence (d i ) is called a β-expansion of x. Let U β,N be the set of all x's in Γ β,N which have unique β-expansions. We give explicit formula of the Hausdorff dimension of U β,N for β in any admissible interval [β L , β U ], where β L is a purely Parry number while β U is a transcendental number whose quasi-greedy expansion of 1 is related to the classical Thue–Morse sequence. This allows us to calculate the Hausdorff dimension of U β,N for almost every β > 1. In particular, this improves the main results of Gábor Kallós (1999, 2001). Moreover, we find that the dimension function f(β) = dim H U β,N fluctuates frequently for β ∈ (1, N). (paper)

  1. Detailed Molecular Epidemiologic Characterization of HIV-1 Infection in Bulgaria Reveals Broad Diversity and Evolving Phylodynamics

    Science.gov (United States)

    Ivanov, Ivailo Alexiev; Beshkov, Danail; Shankar, Anupama; Hanson, Debra L.; Paraskevis, Dimitrios; Georgieva, Viara; Karamacheva, Lyudmila; Taskov, Hristo; Varleva, Tonka; Elenkov, Ivaylo; Stoicheva, Mariana; Nikolova, Daniela; Switzer, William M.

    2013-01-01

    Limited information is available to describe the molecular epidemiology of HIV-1 in Bulgaria. To better understand the genetic diversity and the epidemiologic dynamics of HIV-1 we analyzed 125 new polymerase (pol) sequences from Bulgarians diagnosed through 2009 and 77 pol sequences available from our previous study from persons infected prior to 2007. Epidemiologic and demographic information was obtained from each participant and phylogenetic analysis was used to infer HIV-1 evolutionary histories. 120 (59.5%) persons were infected with one of five different HIV-1 subtypes (A1, B, C, F1 and H) and 63 (31.2%) persons were infected with one of six different circulating recombinant forms (CRFs; 01_AE, 02_AG, 04_cpx, 05_DF, 14_BG, and 36_cpx). We also for the first time identified infection with two different clusters of unique A-like and F-like sub-subtype variants in 12 persons (5.9%) and seven unique recombinant forms (3.5%), including a novel J/C recombinant. While subtype B was the major genotype identified and was more prevalent in MSM and increased between 2000–2005, most non-B subtypes were present in persons ≥45 years old. CRF01_AE was the most common non-B subtype and was higher in women and IDUs relative to other risk groups combined. Our results show that HIV-1 infection in Bulgaria reflects the shifting distribution of genotypes coincident with the changing epidemiology of the HIV-1 epidemic among different risk groups. Our data support increased public health interventions targeting IDUs and MSM. Furthermore, the substantial and increasing HIV-1 genetic heterogeneity, combined with fluctuating infection dynamics, highlights the importance of sustained and expanded surveillance to prevent and control HIV-1 infection in Bulgaria. PMID:23527245

  2. The γ Dor stars as revealed by Kepler: A key to reveal deep-layer rotation in A and F stars

    Directory of Open Access Journals (Sweden)

    Salmon S. J. A. J.

    2017-01-01

    Full Text Available The γ Dor pulsating stars present high-order gravity modes, which make them important targets in the intermediate-and low-mass main-sequence region of the Hertzsprung-Russell diagram. Whilst we have only access to rotation in the envelope of the Sun, the g modes of γ Dor stars can in principle deliver us constraints on the inner layers. With the puzzling discovery of unexpectedly low rotation rates in the core of red giants, the γ Dor stars appear now as unique targets to explore internal angular momentum transport in the progenitors of red giants. Yet, the γ Dor pulsations remain hard to detect from the ground for their periods are close to 1 day. While the CoRoT space mission first revealed intriguing frequency spectra, the almost uninterrupted 4-year photometry from the Kepler mission eventually shed a new light on them. It revealed regularities in the spectra, expected to bear signature of physical processes, including rotation, in the shear layers close to the convective core. We present here the first results of our effort to derive exploitable seismic diagnosis for mid- to fast rotators among γ Dor stars. We confirm their potential to explore the rotation history of this early phase of stellar evolution.

  3. Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.

    Science.gov (United States)

    Eswaran, Jeyanthy; Bernad, Antonio; Ligos, Jose M; Guinea, Barbara; Debreczeni, Judit E; Sobott, Frank; Parker, Sirlester A; Najmanovich, Rafael; Turk, Benjamin E; Knapp, Stefan

    2008-01-01

    The activation segment of protein kinases is structurally highly conserved and central to regulation of kinase activation. Here we report an atypical activation segment architecture in human MPSK1 comprising a beta sheet and a large alpha-helical insertion. Sequence comparisons suggested that similar activation segments exist in all members of the MPSK1 family and in MAST kinases. The consequence of this nonclassical activation segment on substrate recognition was studied using peptide library screens that revealed a preferred substrate sequence of X-X-P/V/I-phi-H/Y-T*-N/G-X-X-X (phi is an aliphatic residue). In addition, we identified the GTPase DRG1 as an MPSK1 interaction partner and specific substrate. The interaction domain in DRG1 was mapped to the N terminus, leading to recruitment and phosphorylation at Thr100 within the GTPase domain. The presented data reveal an atypical kinase structural motif and suggest a role of MPSK1 regulating DRG1, a GTPase involved in regulation of cellular growth.

  4. Ancient DNA and morphometric analysis reveal extinction and replacement of New Zealand's unique black swans.

    Science.gov (United States)

    Rawlence, Nicolas J; Kardamaki, Afroditi; Easton, Luke J; Tennyson, Alan J D; Scofield, R Paul; Waters, Jonathan M

    2017-07-26

    Prehistoric human impacts on megafaunal populations have dramatically reshaped ecosystems worldwide. However, the effects of human exploitation on smaller species, such as anatids (ducks, geese, and swans) are less clear. In this study we apply ancient DNA and osteological approaches to reassess the history of Australasia's iconic black swans ( Cygnus atratus ) including the palaeo-behaviour of prehistoric populations. Our study shows that at the time of human colonization, New Zealand housed a genetically, morphologically, and potentially ecologically distinct swan lineage ( C. sumnerensis , Poūwa), divergent from modern (Australian) C. atratus Morphological analyses indicate C. sumnerensis exhibited classic signs of the 'island rule' effect, being larger, and likely flight-reduced compared to C. atratus Our research reveals sudden extinction and replacement events within this anatid species complex, coinciding with recent human colonization of New Zealand. This research highlights the role of anthropogenic processes in rapidly reshaping island ecosystems and raises new questions for avian conservation, ecosystem re-wilding, and de-extinction. © 2017 The Author(s).

  5. Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes.

    Science.gov (United States)

    Kehr, Jan-Christoph; Gatte Picchi, Douglas; Dittmann, Elke

    2011-01-01

    Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially emphasize modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future.

  6. Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

    Directory of Open Access Journals (Sweden)

    Jan-Christoph Kehr

    2011-12-01

    Full Text Available Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially emphasize modular nonribosomal peptide synthetase (NRPS and polyketide synthase (PKS pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future.

  7. On the uniqueness of minimal coupling in higher-spin gauge theory

    International Nuclear Information System (INIS)

    Boulanger, Nicolas; Sundell, Per; Leclercq, Serge

    2008-01-01

    We address the uniqueness of the minimal couplings between higher-spin fields and gravity. These couplings are cubic vertices built from gauge non-invariant connections that induce non-abelian deformations of the gauge algebra. We show that Fradkin-Vasiliev's cubic 2-s-s vertex, which contains up to 2s-2 derivatives dressed by a cosmological constant Λ, has a limit where: (i) Λ → 0; (ii) the spin-2 Weyl tensor scales non-uniformly with s; and (iii) all lower-derivative couplings are scaled away. For s = 3 the limit yields the unique non-abelian spin 2-3-3 vertex found recently by two of the authors, thereby proving the uniqueness of the corresponding FV vertex. We extend the analysis to s = 4 and a class of spin 1-s-s vertices. The non-universality of the flat limit high-lightens not only the problematic aspects of higher-spin interactions with Λ = 0 but also the strongly coupled nature of the derivative expansion of the fully nonlinear higher-spin field equations with Λ≠0, wherein the standard minimal couplings mediated via the Lorentz connection are subleading at energy scales (|Λ|) 1/2 || E || M p . Finally, combining our results with those obtained by Metsaev, we give the complete list of all the manifestly covariant cubic couplings of the form 1-s-s and 2-s-s , in Minkowski background.

  8. Spherical Harmonics Reveal Standing EEG Waves and Long-Range Neural Synchronization during Non-REM Sleep

    OpenAIRE

    Sivakumar, Siddharth S.; Namath, Amalia G.; Galán, Roberto F.

    2016-01-01

    Previous work from our lab has demonstrated how the connectivity of brain circuits constrains the repertoire of activity patterns that those circuits can display. Specifically, we have shown that the principal components of spontaneous neural activity are uniquely determined by the underlying circuit connections, and that although the principal components do not uniquely resolve the circuit structure, they do reveal important features about it. Expanding upon this framework on a larger scale ...

  9. Using Quantum Confinement to Uniquely Identify Devices

    Science.gov (United States)

    Roberts, J.; Bagci, I. E.; Zawawi, M. A. M.; Sexton, J.; Hulbert, N.; Noori, Y. J.; Young, M. P.; Woodhead, C. S.; Missous, M.; Migliorato, M. A.; Roedig, U.; Young, R. J.

    2015-11-01

    Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.

  10. Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases.

    Science.gov (United States)

    Gruninger, Robert J; Cote, Chris; McAllister, Tim A; Abbott, D Wade

    2016-04-01

    Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. Enzymes targeting these esters represent promising biotools for increasing bioconversion efficiency. Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 42: , D490-D495]. We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. This provides a structure-based tool for predicting exolysis and endolysis in CE1. These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. © 2016 Authors; published by

  11. Novel criteria of uniqueness for signal reconstruction from phase

    NARCIS (Netherlands)

    Ma, C.

    1991-01-01

    An approach for ascertaining whether a signal is uniquely determined by its Fourier transform phase is proposed. It is shown that uniqueness corresponds to the nonsingularity of a matrix which can be formed from the finite-length real sequence. The criterion of uniqueness for reconstructing a

  12. Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes.

    Science.gov (United States)

    Zhang, Meiling; Chekan, Jonathan R; Dodd, Dylan; Hong, Pei-Ying; Radlinski, Lauren; Revindran, Vanessa; Nair, Satish K; Mackie, Roderick I; Cann, Isaac

    2014-09-02

    Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose-configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 Å), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 Å), and the CBM from its homolog in the Prevotella bryantii B14 Xyn10C (1.68 Å) reveal an unanticipated mode for ligand binding. A minimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health.

  13. Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes

    KAUST Repository

    Zhang, Meiling

    2014-08-18

    Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT-04215 and BACOVA-04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xy-lose- configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 Å), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 Å), and the CBM fromits homolog in the Prevotella bryantii B 14 Xyn10C (1.68 Å) reveal an unanticipated mode for ligand binding. Aminimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health.

  14. Octacyanoniobate(IV)-based molecular magnets revealing 3D long-range order

    Energy Technology Data Exchange (ETDEWEB)

    Pelka, R; Balanda, M [Institute of Physics PAN, Radzikowskiego 152, 31-342, Krakow (Poland); Pinkowicz, D; Drath, O; Nitek, W; Sieklucka, B [Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow (Poland); Rams, M; Majcher, A, E-mail: robert.pelka@ifj.edu.pl [Institute of Physics, Jagiellonian University, Reymonta 4, 30-059 Krakow (Poland)

    2011-07-06

    Isostructural series of chemical formula {l_brace}[M{sup II}(pirazol){sub 4}]{sub 2}[Nb{sup IV}(CN){sub 8}]{center_dot} 4H{sub 2}O{r_brace}{sub n} (M{sup II} = Mn (1), Fe (2), Co (3), Ni (4)) has been obtained by the self-assembly technique. Its unique crystallographic structure consists in the formation of a 3D extended network of magnetic centers braced by geometrically identical cyanido bridges. Magnetic measurements reveal the transitions to the 3D order at temperatures 23.7, 8.3, 5.9, 13.4 K for 1, 2, 3, and 4, respectively. The character of order is demonstrated to be ferrimagnetic for 1 and 2 and ferromagnetic for 3 and 4. The mean-field approach is used to determine the corresponding exchange coupling constants. The observed interactions are discussed within the magnetic orbital model.

  15. Veto players and equilibrium uniqueness in the Baron–Ferejohn model

    Czech Academy of Sciences Publication Activity Database

    Celik, Levent; Karabay, Bilgehan

    2016-01-01

    Roč. 81, č. 1 (2016), s. 33-52 ISSN 0040-5833 R&D Projects: GA ČR(CZ) GAP402/12/0666 Institutional support: PRVOUK-P23 Keywords : multilateral bargaining * equilibrium uniqueness * veto players Subject RIV: AH - Economics Impact factor: 0.606, year: 2016

  16. Effort towards symmetric removal and surface smoothening of 1.3-GHz niobium single-cell cavity in vertical electropolishing using a unique cathode

    Science.gov (United States)

    Chouhan, Vijay; Kato, Shigeki; Nii, Keisuke; Yamaguchi, Takanori; Sawabe, Motoaki; Hayano, Hitoshi; Ida, Yoshiaki

    2017-08-01

    A detailed study on vertical electropolishing (VEP) of a 1.3-GHz single-cell niobium coupon cavity, which contains six coupons and four viewports at different positions, is reported. The cavity was vertically electropolished using a conventional rod and three types of unique cathodes named as Ninja cathodes, which were designed to have four retractable blades made of either an insulator or a metal or a combination of both. This study reveals the effect of the cathodes and their rotation speed on uniformity in removal thickness and surface morphology at different positions inside the cavity. Removal thickness was measured at several positions of the cavity using an ultrasonic thickness gauge and the surface features of the coupons were examined by an optical microscope and a surface profiler. The Ninja cathode with partial metallic blades was found to be effective not only in reducing asymmetric removal, which is one of the major problems in VEP and might be caused by the accumulation of hydrogen (H2 ) gas bubbles on the top iris of the cavity, but also in yielding a smooth surface of the entire cavity. A higher rotation speed of the Ninja cathode prevents bubble accumulation on the upper iris, and might result in a viscous layer of similar thickness in the cavity cell. Moreover, a higher electric field at the equator owing to the proximity of partial metallic blades to the equator surface resulted in a smooth surface. The effects of H2 gas bubbles and stirring were also observed in lab EP experiments.

  17. Effort towards symmetric removal and surface smoothening of 1.3-GHz niobium single-cell cavity in vertical electropolishing using a unique cathode

    Directory of Open Access Journals (Sweden)

    Vijay Chouhan

    2017-08-01

    Full Text Available A detailed study on vertical electropolishing (VEP of a 1.3-GHz single-cell niobium coupon cavity, which contains six coupons and four viewports at different positions, is reported. The cavity was vertically electropolished using a conventional rod and three types of unique cathodes named as Ninja cathodes, which were designed to have four retractable blades made of either an insulator or a metal or a combination of both. This study reveals the effect of the cathodes and their rotation speed on uniformity in removal thickness and surface morphology at different positions inside the cavity. Removal thickness was measured at several positions of the cavity using an ultrasonic thickness gauge and the surface features of the coupons were examined by an optical microscope and a surface profiler. The Ninja cathode with partial metallic blades was found to be effective not only in reducing asymmetric removal, which is one of the major problems in VEP and might be caused by the accumulation of hydrogen (H_{2} gas bubbles on the top iris of the cavity, but also in yielding a smooth surface of the entire cavity. A higher rotation speed of the Ninja cathode prevents bubble accumulation on the upper iris, and might result in a viscous layer of similar thickness in the cavity cell. Moreover, a higher electric field at the equator owing to the proximity of partial metallic blades to the equator surface resulted in a smooth surface. The effects of H_{2} gas bubbles and stirring were also observed in lab EP experiments.

  18. EXISTENCE AND UNIQUENESS OF THE ENTROPY SOLUTION TO A NONLINEAR HYPERBOLIC EQUATION

    Institute of Scientific and Technical Information of China (English)

    R.EYMARD; T.Gallouёt; R.Herbin

    1995-01-01

    This work is concerned with the proof of the existence and uniqueness of the entropy weak solution to the following nonlinear hyperbolic equation: ut+div(vf(u)) = 0 in IRN×(0, T), with initial data u(-, 0) = u0(-) in IRN, where u0 ∈ L∞(IRN) is a given function, v is a divergence-free bounded fnnction of class C1 from IRN × [0, T] to IRN, and f is a 5motion of class C1 from IR to IR. It also gives a result of convergence of a numerical scheme for the discretization of this equation. The authors first show the existence of a “process” solution (which generalizes the concept of entropy weak solutions, and can be obtained by passing to the limit of solutions ofthe numerical scheme). The uniqueness of this entropy process solution is then proven; it isalso proven that the entropy process solution is in fact an entropy weak solution. Hence the existence and uniqueness of the entropy weak solution are proven.

  19. "That thing in New York": Impaired naming vs. preserved recognition of unique entities following an anterior temporal lobe lesion

    Directory of Open Access Journals (Sweden)

    Daniel Roberts

    2014-04-01

    Full Text Available Background Anterior temporal lobe (aTL damage often results in semantic impairment. As such, the contribution of this region to semantic processing has received considerable attention. Two theories exist to explain aTL function based on conflicting neuropsychological investigations. The first proposes bilateral aTLs form a “hub” implicated in multimodal semantics (for review see: Jefferies, 2013. The second assumes distinct functions. The left is thought to function as a repertoire for knowledge of entities with unique lexical-conceptual associations (for review: Ross & Olson, 2012. These items represent an extreme end of a continuum of semantic specificity spanning unique (e.g., Eiffel Tower over less specific (e.g., tower to nonspecific (e.g., landmark – often denoted by famous faces, landmarks and proper names. LaTL function, therefore, is to link semantics to language systems for naming, whilst RaTL is involved in familiarity and recognition (e.g., Eiffel Tower -> a building in Paris; Drane et al., 2013. Evidence for each theory has proceeded in parallel but there has been no attempt to directly test them in a patient (Simmons & Martin, 2009. The novelty of this study, therefore, was to determine whether LaTL lesions disproportionately affect unique entity naming vs. recognition. Method WRP, a 51year old right-handed male, three year post-HSVE has a LaTL lesion with destruction of the temporal pole, extending to medial temporal, amygdala and hippocampus and atypical connectivity particularly involving the uncinate fasciculas. There is no evidence of either cortical or white matter damage in the right hemisphere. Previous work with WRP revealed a mild/moderate category-specific semantic deficit (Roberts et al., 2012. This new study focuses on unique entity picture naming, recognition and word-to-picture matching (WPM. Results & Discussion As predicted, results (Table 1 show that WRP was severely impaired in naming different categories

  20. Uniqueness of the Fock representation of the Gowdy S1 x S2 and S3 models

    International Nuclear Information System (INIS)

    Cortez, Jeronimo; Marugan, Guillermo A Mena; Velhinho, Jose M

    2008-01-01

    After a suitable gauge fixing, the local gravitational degrees of freedom of the Gowdy S 1 x S 2 and S 3 cosmologies are encoded in an axisymmetric field on the sphere S 2 . Recently, it has been shown that a standard field parametrization of these reduced models admits no Fock quantization with a unitary dynamics. This lack of unitarity is surpassed by a convenient redefinition of the field and the choice of an adequate complex structure. The result is a Fock quantization where both the dynamics and the SO(3)-symmetries of the field equations are unitarily implemented. The present work proves that this Fock representation is in fact unique inasmuch as, up to equivalence, there exists no other possible choice of SO(3)-invariant complex structure leading to a unitary implementation of the time evolution

  1. Using principal component analysis to capture individual differences within a unified neuropsychological model of chronic post-stroke aphasia: Revealing the unique neural correlates of speech fluency, phonology and semantics.

    Science.gov (United States)

    Halai, Ajay D; Woollams, Anna M; Lambon Ralph, Matthew A

    2017-01-01

    Individual differences in the performance profiles of neuropsychologically-impaired patients are pervasive yet there is still no resolution on the best way to model and account for the variation in their behavioural impairments and the associated neural correlates. To date, researchers have generally taken one of three different approaches: a single-case study methodology in which each case is considered separately; a case-series design in which all individual patients from a small coherent group are examined and directly compared; or, group studies, in which a sample of cases are investigated as one group with the assumption that they are drawn from a homogenous category and that performance differences are of no interest. In recent research, we have developed a complementary alternative through the use of principal component analysis (PCA) of individual data from large patient cohorts. This data-driven approach not only generates a single unified model for the group as a whole (expressed in terms of the emergent principal components) but is also able to capture the individual differences between patients (in terms of their relative positions along the principal behavioural axes). We demonstrate the use of this approach by considering speech fluency, phonology and semantics in aphasia diagnosis and classification, as well as their unique neural correlates. PCA of the behavioural data from 31 patients with chronic post-stroke aphasia resulted in four statistically-independent behavioural components reflecting phonological, semantic, executive-cognitive and fluency abilities. Even after accounting for lesion volume, entering the four behavioural components simultaneously into a voxel-based correlational methodology (VBCM) analysis revealed that speech fluency (speech quanta) was uniquely correlated with left motor cortex and underlying white matter (including the anterior section of the arcuate fasciculus and the frontal aslant tract), phonological skills with

  2. Methanophosphagen: Unique cyclic pyrophosphate isolated from Methanobacterium thermoautotrophicum

    OpenAIRE

    Kanodia, Sushila; Roberts, Mary Fedarko

    1983-01-01

    A unique cyclic pyrophosphate compound has been detected at 10-12 mM intracellular concentration in Methanobacterium thermoautotrophicum by in vivo31P NMR. This compound has been extracted from cells and purified by anion-exchange chromatography. Studies with 1H, 13C, and 31P NMR and fast-atom-bombardment mass spectrometry have identified it as 2,3-cyclopyrophosphoglycerate, an intramolecularly cyclized pyrophosphate of 2,3-diphosphoglycerate. Chemical degradation to 2,3-diphosphoglycerate an...

  3. Diabetes: Unique to Older Adults

    Science.gov (United States)

    ... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

  4. Tissue-Specific Floral Transcriptome Analysis of the Sexually Deceptive Orchid Chiloglottis trapeziformis Provides Insights into the Biosynthesis and Regulation of Its Unique UV-B Dependent Floral Volatile, Chiloglottone 1

    Directory of Open Access Journals (Sweden)

    Darren C. J. Wong

    2017-07-01

    Full Text Available The Australian sexually deceptive orchid, Chiloglottis trapeziformis, employs a unique UV-B-dependent floral volatile, chiloglottone 1, for specific male wasp pollinator attraction. Chiloglottone 1 and related variants (2,5-dialkylcyclohexane-1,3-diones, represent a unique class of specialized metabolites presumed to be the product of cyclization between two fatty acid (FA precursors. However, the genes involved in the biosynthesis of precursors, intermediates, and transcriptional regulation remains to be discovered. Chiloglottone 1 production occurs in the aggregation of calli (callus on the labellum under continuous UV-B light. Therefore, deep sequencing, transcriptome assembly, and differential expression (DE analysis were performed across different tissue types and UV-B treatments. Transcripts expressed in the callus and labellum (∼23,000 transcripts were highly specialized and enriched for a diversity of known and novel metabolic pathways. DE analysis between chiloglottone-emitting callus versus the remainder of the labellum showed strong coordinated induction of entire FA biosynthesis and β-oxidation pathways including genes encoding Ketoacyl-ACP Synthase, Acyl-CoA Oxidase, and Multifunctional Protein. Phylogenetic analysis revealed potential gene duplicates with tissue-specific differential regulation including two Acyl-ACP Thioesterase B and a Ketoacyl-ACP Synthase genes. UV-B treatment induced the activation of UVR8-mediated signaling and large-scale transcriptome changes in both tissues, however, neither FA biosynthesis/β-oxidation nor other lipid metabolic pathways showed clear indications of concerted DE. Gene co-expression network analysis identified three callus-specific modules enriched with various lipid metabolism categories. These networks also highlight promising candidates involved in the cyclization of chiloglottone 1 intermediates (e.g., Bet v I and dimeric α,β barrel proteins and orchestrating regulation of precursor

  5. Uniqueness of the Fock quantization of the Gowdy T3 model

    International Nuclear Information System (INIS)

    Cortez, Jeronimo; Marugan, Guillermo A. Mena; Velhinho, Jose M.

    2007-01-01

    After its reduction by a gauge-fixing procedure, the family of linearly polarized Gowdy T 3 cosmologies admits a scalar field description whose evolution is governed by a Klein-Gordon type equation in a flat background in 1+1 dimensions with the spatial topology of S 1 , though in the presence of a time-dependent potential. The model is still subject to a homogeneous constraint, which generates S 1 -translations. Recently, a Fock quantization of this scalar field was introduced and shown to be unique under the requirements of unitarity of the dynamics and invariance under the gauge group of S 1 -translations. In this work, we extend and complete this uniqueness result by considering other possible scalar field descriptions, resulting from reasonable field reparametrizations of the induced metric of the reduced model. In the reduced phase space, these alternate descriptions can be obtained by means of a time-dependent scaling of the field, the inverse scaling of its canonical momentum, and the possible addition of a time-dependent, linear contribution of the field to this momentum. Demanding again unitarity of the field dynamics and invariance under the gauge group, we prove that the alternate canonical pairs of fieldlike variables admit a Fock representation if and only if the scaling of the field is constant in time. In this case, there exists essentially a unique Fock representation, provided by the quantization constructed by Corichi, Cortez, and Mena Marugan. In particular, our analysis shows that the scalar field description proposed by Pierri does not admit a Fock quantization with the above unitarity and invariance properties

  6. Unique Results and Lessons Learned From the TSS Missions

    Science.gov (United States)

    Stone, Nobie H.

    2016-01-01

    The Tethered Satellite System (TSS) Space Shuttle missions, TSS-1 in 1993 and TSS-1R in 1996, were the height of space tether technology development in the U.S. Altogether, the investment made by NASA and the Italian Space Agency (ASI) over the thirteen-year period of the TSS Program totaled approximately $400M-exclusive of the two Space Shuttle flights provided by NASA. Since those two pioneering missions, there have been several smaller tether flight experiments, but interest in this promising technology has waned within NASA as well as the DOD agencies. This is curious in view of the unique capabilities of space tether systems and the fact that they have been flight validated in earth orbit and shown to perform better than the preflight dynamic or electrodynamic theoretical predictions. While it is true that the TSS-1 and TSS-1R missions experienced technical difficulties, the causes of these early developmental problems are now known to have been engineering design flaws, material selection, and procedural issues that (1) are unrelated to the basic viability of space tether technology, and (2) can be readily corrected. The purpose of this paper is to review the dynamic and electrodynamic fundamentals of space tethers and the unique capabilities they afford (that are enabling to certain types of space missions); to elucidate the nature, cause, and solution of the early developmental problems; and to provide an update on progress made in development of the technology.

  7. Nuclear resonance scattering of synchrotron radiation as a unique electronic, structural and thermodynamic probe

    International Nuclear Information System (INIS)

    Alp, E. Ercan; Sturhahn, Wolfgang; Toellner, Thomas S.; Zhao, Jiyong; Leu, Bogdan M.

    2012-01-01

    Discovery of Moessbauer effect in a nuclear transition was a remarkable development. It revealed how long-lived nuclear states with relatively low energies in the kiloelectron volt (keV) region can be excited without recoil. This new effect had a unique feature involving a coupling between nuclear physics and solid-state physics, both in terms of physics and sociology. Physics coupling originates from the fact that recoilless emission and absorption or resonance is only possible if the requirement that nuclei have to be bound in a lattice with quantized vibrational states is fulfilled, and that the finite electron density on the nucleus couples to nuclear degrees of freedom leading to hyperfine interactions. thus, Moessbauer spectroscopy allows peering into solid-state effects using unique nuclear transitions. Sociological aspects of this coupling had been equally startling and fruitful. The interaction between diverse scientific communities, who learned to use Moessbauer spectroscopy proved to be very valuable. For example, biologists, geologists, chemists, physics, materials scientists, and archeologists, all sharing a common spectroscopic technique, also learned to appreciate the beauty and intricacies of each other's fields. As a laboratory-based technique, Moessbauer spectroscopy matured by the end of the 1970s. Further exciting developments took place when accelerator-based techniques were employed, like synchrotron radiation or 'in-beam'Moessbauer experiments with implanted radioactive ions. More recently, two Moessbauer spectrometers on the surface of the Mars kept the technique vibrant and viable up until present time. In this chapter, the authors look into some of the unique aspects of nuclear resonance excited with synchrotron radiation as a probe of condensed matter, including magnetism, valence, vibrations, and lattice dynamics, and review the development of nuclear resonance inelastic x-ray scattering (NRIXS) and synchrotron Moessbauer spectroscopy

  8. Might "Unique" Factors Be "Common"? On the Possibility of Indeterminate Common-Unique Covariances

    Science.gov (United States)

    Grayson, Dave

    2006-01-01

    The present paper shows that the usual factor analytic structured data dispersion matrix lambda psi lambda' + delta can readily arise from a set of scores y = lambda eta + epsilon, shere the "common" (eta) and "unique" (epsilon) factors have nonzero covariance: gamma = Cov epsilon,eta) is not equal to 0. Implications of this finding are discussed…

  9. Unique coexistence of dispersion stability and nanoparticle chemisorption in alkylamine/alkylacid encapsulated silver nanocolloids.

    Science.gov (United States)

    Aoshima, Keisuke; Hirakawa, Yuya; Togashi, Takanari; Kurihara, Masato; Arai, Shunto; Hasegawa, Tatsuo

    2018-04-17

    Surface encapsulation of metal nanoparticles (NPs) is fundamental to achieve sufficient dispersion stability of metal nanocolloids, or metal nanoink. However, the feature is incompatible with surface reactive nature of the metal NPs, although these features are both essential to realizing the functional applications into printed electronics technologies. Here we show that two different kinds of encapsulation for silver NPs (AgNPs) by alkylamine and alkylacid together are the key to achieve unique compatibility between the high dispersion stability as dense nanoclolloids and the AgNP chemisorption printing on activated patterned polymer surfaces. Advanced confocal dynamic light scattering study reveals that an additive trace amount of oleic acid is the critical parameter for controlling the dispersion and coagulative (or surface-reactive) characteristics of the silver nanocolloids. The composition of the disperse media is also important for obtaining highly concentrated but low-viscosity silver nanocolloids that show very stable dispersion. The results demonstrate that the high-resolution AgNP chemisorption printing is possible only by using unique silver nanocolloids composed of an exceptional balance of ligand formulation and dispersant composition.

  10. Screening the budding yeast genome reveals unique factors affecting K2 toxin susceptibility.

    Science.gov (United States)

    Servienė, Elena; Lukša, Juliana; Orentaitė, Irma; Lafontaine, Denis L J; Urbonavičius, Jaunius

    2012-01-01

    Understanding how biotoxins kill cells is of prime importance in biomedicine and the food industry. The budding yeast (S. cerevisiae) killers serve as a convenient model to study the activity of biotoxins consistently supplying with significant insights into the basic mechanisms of virus-host cell interactions and toxin entry into eukaryotic target cells. K1 and K2 toxins are active at the cell wall, leading to the disruption of the plasma membrane and subsequent cell death by ion leakage. K28 toxin is active in the cell nucleus, blocking DNA synthesis and cell cycle progression, thereby triggering apoptosis. Genome-wide screens in the budding yeast S. cerevisiae identified several hundred effectors of K1 and K28 toxins. Surprisingly, no such screen had been performed for K2 toxin, the most frequent killer toxin among industrial budding yeasts. We conducted several concurrent genome-wide screens in S. cerevisiae and identified 332 novel K2 toxin effectors. The effectors involved in K2 resistance and hypersensitivity largely map in distinct cellular pathways, including cell wall and plasma membrane structure/biogenesis and mitochondrial function for K2 resistance, and cell wall stress signaling and ion/pH homeostasis for K2 hypersensitivity. 70% of K2 effectors are different from those involved in K1 or K28 susceptibility. Our work demonstrates that despite the fact that K1 and K2 toxins share some aspects of their killing strategies, they largely rely on different sets of effectors. Since the vast majority of the host factors identified here is exclusively active towards K2, we conclude that cells have acquired a specific K2 toxin effectors set. Our work thus indicates that K1 and K2 have elaborated different biological pathways and provides a first step towards the detailed characterization of K2 mode of action.

  11. Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Ikemoto, Yu; Takayama, Yoshinaga; Fujii, Katsunori; Masuda, Mokuri; Kato, Chise; Hatsuse, Hiromi; Fujitani, Kazuko; Nagao, Kazuaki; Kameyama, Kohzoh; Ikehara, Hajime; Toyoda, Masashi; Umezawa, Akihiro; Miyashita, Toshiyuki

    2017-08-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterised by developmental defects and tumorigenesis, such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 ( PTCH1 ) gene. In this article, we seek to demonstrate a mosaicism containing double mutations in PTCH1 in an individual with NBCCS. A de novo germline mutation of PTCH1 (c.272delG) was detected in a 31-year-old woman with NBCCS. Gene analysis of two out of four induced pluripotent stem cell (iPSC) clones established from the patient unexpectedly revealed an additional mutation, c.274delT. Deep sequencing confirmed a low-prevalence somatic mutation (5.5%-15.6% depending on the tissue) identical to the one found in iPSC clones. This is the first case of mosaicism unequivocally demonstrated in NBCCS. Furthermore, the mosaicism is unique in that the patient carries one normal and two mutant alleles. Because these mutations are located in close proximity, reversion error is likely to be involved in this event rather than a spontaneous mutation. In addition, this study indicates that gene analysis of iPSC clones can contribute to the detection of mosaicism containing a minor population carrying a second mutation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity

    Science.gov (United States)

    Zhang, Peilan; Yang, Guang; Xia, Changqing; Polston, Jane E.; Li, Gengnan; Li, Shiwu; Lin, Zhao; Yang, Li-jun; Bruner, Steven D.

    2017-01-01

    Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan–GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus. Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcβ1–4(Fucα1–3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αβα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel β-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment. PMID:28784797

  13. Unique Approach to Dental Management of Children with Hearing Impairment.

    Science.gov (United States)

    Renahan, Navanith; Varma, R Balagopal; Kumaran, Parvathy; Xavier, Arun M

    2017-01-01

    The number of deaf children has dramatically increased in the past few decades. These children present to the pediatric dentist a unique set of challenges mostly pertaining to the establishment of communication with them. There have been very few attempts in the past to break down these challenges and formulate a strategy on how to manage them effectively. This is a case report of a child who was successfully managed using two different modes of communication. Finally, the advantages and disadvantages are mentioned, and a common strategy incorporating the positives of both the methods has been devised. Renahan N, Varma RB, Kumaran P, Xavier AM. Unique Approach to Dental Management of Children with Hearing Impairment. Int J Clin Pediatr Dent 2017;10(1):107-110.

  14. Carbon Catabolite Repression Regulates the Production of the Unique Volatile Sodorifen of Serratia plymuthica 4Rx13

    Directory of Open Access Journals (Sweden)

    Nancy Magnus

    2017-12-01

    Full Text Available Microorganisms are capable of synthesizing a plethora of secondary metabolites including the long-overlooked volatile organic compounds. Little knowledge has been accumulated regarding the regulation of the biosynthesis of such mVOCs. The emission of the unique compound sodorifen of Serratia plymuthica isolates was significantly reduced in minimal medium with glucose, while succinate elevated sodorifen release. The hypothesis of carbon catabolite repression (CCR acting as a major control entity on the synthesis of mVOCs was proven by genetic evidence. Central components of the typical CCR of Gram-negative bacteria such as the adenylate cyclase (CYA, the cAMP binding receptor protein (CRP, and the catabolite responsive element (CRE were removed by insertional mutagenesis. CYA, CRP, CRE1 mutants revealed a lower sodorifen release. Moreover, the emission potential of other S. plymuthica isolates was also evaluated.

  15. Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

    Science.gov (United States)

    Pan, Jie; Park, Thomas J; Cutz, Ernest; Yeger, Herman

    2014-01-01

    The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and

  16. A comparative antibody analysis of Pannexin1 expression in four rat brain regions reveals varying subcellular localizations

    Directory of Open Access Journals (Sweden)

    Angela C Cone

    2013-02-01

    Full Text Available Pannexin1 (Panx1 channels release cytosolic ATP in response to signaling pathways. Panx1 is highly expressed in the central nervous system. We used four antibodies with different Panx1 anti-peptide epitopes to analyze four regions of rat brain. These antibodies labeled the same bands in Western blots and had highly similar patterns of immunofluorescence in tissue culture cells expressing Panx1, but Western blots of brain lysates from Panx1 knockout and control mice showed different banding patterns. Localizations of Panx1 in brain slices were generated using automated wide-field mosaic confocal microscopy for imaging large regions of interest while retaining maximum resolution for examining cell populations and compartments. We compared Panx1 expression over the cerebellum, hippocampus with adjacent cortex, thalamus and olfactory bulb. While Panx1 localizes to the same neuronal cell types, subcellular localizations differ. Two antibodies with epitopes against the intracellular loop and one against the carboxy terminus preferentially labeled cell bodies, while an antibody raised against an N-terminal peptide highlighted neuronal processes more than cell bodies. These labeling patterns may be a reflection of different cellular and subcellular localizations of full-length and/or modified Panx1 channels where each antibody is highlighting unique or differentially accessible Panx1 populations. However, we cannot rule out that one or more of these antibodies have specificity issues. All data associated with experiments from these four antibodies are presented in a manner that allows them to be compared and our claims thoroughly evaluated, rather than eliminating results that were questionable. Each antibody is given a unique identifier through the NIF Antibody Registry that can be used to track usage of individual antibodies across papers and all image and metadata are made available in the public repository, the Cell Centered Database, for on

  17. The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

    Directory of Open Access Journals (Sweden)

    Maheswara Reddy Emani

    2015-03-01

    Full Text Available The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

  18. Is physical space unique or optional

    International Nuclear Information System (INIS)

    Ekstein, H.; Centre National de la Recherche Scientifique, 13 - Marseille

    1975-02-01

    There are two concepts of the physical space-time. One, S(F), is that of a fixed arena in which events take place. The other S(D), is that of a space-time shaped by events. The second depends on the state (initial conditions) or on the external field, the first does not. The main assertions of the present paper are: 1) the fixed space-time S(F) is neither incompatibles with nor made superfluous, by Einstein's theory. S(F) is experimentally explorable, unique, and probably identical with Minkowski space M. 2) The dynamical space S(D) is largely optional. It can be chosen to be M, but the natural choice is Einstein's pseudo-Riemanian manifold [fr

  19. Customization: Ideal Varieties, Product Uniqueness and Price Competition

    OpenAIRE

    Oksana Loginova; X. Henry Wang

    2009-01-01

    We study customization in the Hotelling model with two firms. In addition to providing ideal varieties, the perceived uniqueness of a customized product contributes independently to consumer utility. We show that only when consumer preferences for uniqueness are high customization occurs in equilibrium.

  20. Single crystal structure analyses of scheelite-powellite CaW1-xMoxO4 solidsolutions and unique occurrence in Jisyakuyama skarn deposits

    Science.gov (United States)

    Yamashita, K.; Yoshiasa, A.; Miyazaki, H.; Tokuda, M.; Tobase, T.; Isobe, H.; Nishiyama, T.; Sugiyama, K.; Miyawaki, R.

    2017-12-01

    Jisyakuyama skarn deposit, Fukuchi, Fukuoka, Japan, shows a simple occurrenceformed by penetration of hot water into limestone cracks. A unique occurrence of scheelite-powellite CaW1-xMoxO4 minerals is observed in the skarn deposit. Many syntheticexperiments for scheelite-powellite solid solutions have been reported as research onfluorescent materials. In this system it is known that a complete continuous solid solution isformed even at room temperature. In this study, we have carried out the chemical analyses,crystal structural refinements and detail description of occurrence on scheelite-powelliteminerals. We have also attempted synthesis of single crystal of solid solution in a widecomposition range. The chemical compositions were determined by JEOL scanningelectron microscope and EDS, INCA system. We have performed the crystal structurerefinements of the scheelite-powellite CaW1-xMoxO4 solid solutions (x=0.0-1.0) byRIGAKU single-crystal structure analysis system RAPID. The R and S values are around0.0s and 1.03. As the result of structural refinements of natural products and many solidsolutions, we confirm that most large natural single crystals have compositions at bothendmembers, and large solid solution crystals are rare. The lattice constants, interatomicdistances and other crystallographic parameters for the solid solution change uniquely withcomposition and it was confirmed as a continuous solid solution. Single crystals of scheeliteendmember + powellite endmember + solid solution with various compositions form anaggregate in the deposit (Figure 1). Crystal shapes of powellite and scheelite arehypidiomorphic and allotriomorphic, respectively. Many solid solution crystals areaccompanied by scheelite endmember and a compositional gap is observed betweenpowellite and solid-solution crystals. The presence of several penetration solutions withsignificantly different W and Mo contents may be assumed. This research can be expectedto lead to giving restrictive

  1. Low back pain at school: unique risk deriving from unsatisfactory grade in maths and school-type recommendation.

    Science.gov (United States)

    Erne, Cordula; Elfering, Achim

    2011-12-01

    Psychosocial stress and pain may relate to educational selection. At the end of primary school (International Standard Classification of Education: ISCED level 1) children are recommended for one of three performance-based lower secondary level types of school (ISCED level 2). The study examines the association of educational selection and other risk factors with pain in the upper back (UBP), lower back pain (LBP), peripheral (limb) pain (PP), and abdominal pain (AP). Teacher reports of unsatisfactory grades in mathematics, and official school-type recommendation are included as objective psychosocial risk factors. One hundred and ninety-two schoolchildren, aged between 10 and 13 from 11 classes of 7 schools in Switzerland participated in the cross-sectional study. In logistic regression analysis, predictor variables included age, sex, BMI, participation in sport, physical mobility, weight of satchel, hours of daily TV, video, and computer use, pupils' back pain reported by the mother and father, psychosocial strain, unsatisfactory grade in mathematics, and school-type recommendation. Analysis of pain drawings was highly reliable and revealed high prevalence rates of musculoskeletal pain in the last 4 weeks (UBP 15.3%, LBP 13:8%, PP 33.9%, AP 20.1%). Psychosocial risk factors were uniquely significant predictors of UBP (psychosocial strain), LBP (psychosocial strain, unsatisfactory grade in mathematics, school-type recommendation), and AP (school-type recommendation). In conclusion, selection in terms of educational school system was uniquely associated with LBP in schoolchildren. Stress caused by educational selection should be addressed in primary prevention of musculoskeletal pain in schoolchildren.

  2. Uniqueness of a pre-generator for $C_0$-semigroup on a general locally convex vector space

    OpenAIRE

    Lemle, Ludovic Dan; Wu, Liming

    2007-01-01

    The main purpose is to generalize a theorem of Arendt about uniqueness of $C_0$-semigroups from Banach space setting to the general locally convex vector spaces, more precisely, we show that cores are the only domains of uniqueness for $C_0$-semigroups on locally convex spaces. As an application, we find a necessary and sufficient condition for that the mass transport equation has one unique $L^1(\\R^d,dx)$ weak solution.

  3. Can facial uniqueness be inferred from impostor scores?

    NARCIS (Netherlands)

    Dutta, A.; Veldhuis, Raymond N.J.; Spreeuwers, Lieuwe Jan

    2013-01-01

    In Biometrics, facial uniqueness is commonly inferred from impostor similarity scores. In this paper, we show that such uniqueness measures are highly unstable in the presence of image quality variations like pose, noise and blur. We also experimentally demonstrate the instability of a recently

  4. Kosovo case: A unique arbitrariness

    Directory of Open Access Journals (Sweden)

    Nakarada Radmila

    2007-01-01

    Full Text Available The end of Cold war, contrary to expectations has brought new conflicts and forms of violence, new divisions and new relativizations of the international legal order. Taking as an example the endeavors to resolve the Kosovo conflict, the author attempts to indicate the broader implications of the international efforts to constitute an independent state on part of the territory of an existing sovereign state. The arguments used to justify the redefinition of the borders of the Serbian state without its consent, the moral, democratic, peace arguments, are reviewed. Particular attention is paid to the argument that Kosovo is a unique case and therefore unique rules should be applied. The author seeks to understand the deeper significance of these efforts, concluding that dismantling the present international legal order is not only a potential danger but a possible aim.

  5. Are common names becoming less common? The rise in uniqueness and individualism in Japan

    Directory of Open Access Journals (Sweden)

    Yuji eOgihara

    2015-10-01

    Full Text Available We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual’s psyche and behavior outside the head; e.g., advertising can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by

  6. Are common names becoming less common? The rise in uniqueness and individualism in Japan

    Science.gov (United States)

    Ogihara, Yuji; Fujita, Hiroyo; Tominaga, Hitoshi; Ishigaki, Sho; Kashimoto, Takuya; Takahashi, Ayano; Toyohara, Kyoko; Uchida, Yukiko

    2015-01-01

    We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates) suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual’s psyche and behavior outside the head; e.g., advertising) can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by pairing common

  7. Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 × 1 Nucleotide UU Internal Loop Conformations

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D. (Scripps)

    2012-03-27

    RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[{und UU}GGGC(C{und U}G){sub 3}GUCC]{sub 2}, refined to 2.20 and 1.52 {angstrom} resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 x 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 {angstrom} structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 x 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 x 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 {angstrom} structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 x 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 x 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.

  8. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

    Science.gov (United States)

    Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

    2016-01-01

    In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

  9. Systems-Level Annotation of a Metabolomics Data Set Reduces 25 000 Features to Fewer than 1000 Unique Metabolites.

    Science.gov (United States)

    Mahieu, Nathaniel G; Patti, Gary J

    2017-10-03

    When using liquid chromatography/mass spectrometry (LC/MS) to perform untargeted metabolomics, it is now routine to detect tens of thousands of features from biological samples. Poor understanding of the data, however, has complicated interpretation and masked the number of unique metabolites actually being measured in an experiment. Here we place an upper bound on the number of unique metabolites detected in Escherichia coli samples analyzed with one untargeted metabolomics method. We first group multiple features arising from the same analyte, which we call "degenerate features", using a context-driven annotation approach. Surprisingly, this analysis revealed thousands of previously unreported degeneracies that reduced the number of unique analytes to ∼2961. We then applied an orthogonal approach to remove nonbiological features from the data using the 13 C-based credentialing technology. This further reduced the number of unique analytes to less than 1000. Our 90% reduction in data is 5-fold greater than previously published studies. On the basis of the results, we propose an alternative approach to untargeted metabolomics that relies on thoroughly annotated reference data sets. To this end, we introduce the creDBle database ( http://creDBle.wustl.edu ), which contains accurate mass, retention time, and MS/MS fragmentation data as well as annotations of all credentialed features.

  10. Molecular genetic features of polyploidization and aneuploidization reveal unique patterns for genome duplication in diploid Malus.

    Directory of Open Access Journals (Sweden)

    Michael J Considine

    Full Text Available Polyploidization results in genome duplication and is an important step in evolution and speciation. The Malus genome confirmed that this genus was derived through auto-polyploidization, yet the genetic and meiotic mechanisms for polyploidization, particularly for aneuploidization, are unclear in this genus or other woody perennials. In fact the contribution of aneuploidization remains poorly understood throughout Plantae. We add to this knowledge by characterization of eupolyploidization and aneuploidization in 27,542 F₁ seedlings from seven diploid Malus populations using cytology and microsatellite markers. We provide the first evidence that aneuploidy exceeds eupolyploidy in the diploid crosses, suggesting aneuploidization is a leading cause of genome duplication. Gametes from diploid Malus had a unique combinational pattern; ova preserved euploidy exclusively, while spermatozoa presented both euploidy and aneuploidy. All non-reduced gametes were genetically heterozygous, indicating first-division restitution was the exclusive mode for Malus eupolyploidization and aneuploidization. Chromosome segregation pattern among aneuploids was non-uniform, however, certain chromosomes were associated for aneuploidization. This study is the first to provide molecular evidence for the contribution of heterozygous non-reduced gametes to fitness in polyploids and aneuploids. Aneuploidization can increase, while eupolyploidization may decrease genetic diversity in their newly established populations. Auto-triploidization is important for speciation in the extant Malus. The features of Malus polyploidization confer genetic stability and diversity, and present heterozygosity, heterosis and adaptability for evolutionary selection. A protocol using co-dominant markers was proposed for accelerating apple triploid breeding program. A path was postulated for evolution of numerically odd basic chromosomes. The model for Malus derivation was considerably revised

  11. Molecular genetic features of polyploidization and aneuploidization reveal unique patterns for genome duplication in diploid Malus.

    Science.gov (United States)

    Considine, Michael J; Wan, Yizhen; D'Antuono, Mario F; Zhou, Qian; Han, Mingyu; Gao, Hua; Wang, Man

    2012-01-01

    Polyploidization results in genome duplication and is an important step in evolution and speciation. The Malus genome confirmed that this genus was derived through auto-polyploidization, yet the genetic and meiotic mechanisms for polyploidization, particularly for aneuploidization, are unclear in this genus or other woody perennials. In fact the contribution of aneuploidization remains poorly understood throughout Plantae. We add to this knowledge by characterization of eupolyploidization and aneuploidization in 27,542 F₁ seedlings from seven diploid Malus populations using cytology and microsatellite markers. We provide the first evidence that aneuploidy exceeds eupolyploidy in the diploid crosses, suggesting aneuploidization is a leading cause of genome duplication. Gametes from diploid Malus had a unique combinational pattern; ova preserved euploidy exclusively, while spermatozoa presented both euploidy and aneuploidy. All non-reduced gametes were genetically heterozygous, indicating first-division restitution was the exclusive mode for Malus eupolyploidization and aneuploidization. Chromosome segregation pattern among aneuploids was non-uniform, however, certain chromosomes were associated for aneuploidization. This study is the first to provide molecular evidence for the contribution of heterozygous non-reduced gametes to fitness in polyploids and aneuploids. Aneuploidization can increase, while eupolyploidization may decrease genetic diversity in their newly established populations. Auto-triploidization is important for speciation in the extant Malus. The features of Malus polyploidization confer genetic stability and diversity, and present heterozygosity, heterosis and adaptability for evolutionary selection. A protocol using co-dominant markers was proposed for accelerating apple triploid breeding program. A path was postulated for evolution of numerically odd basic chromosomes. The model for Malus derivation was considerably revised. Impacts of

  12. Camelid genomes reveal evolution and adaptation to desert environments.

    Science.gov (United States)

    Wu, Huiguang; Guang, Xuanmin; Al-Fageeh, Mohamed B; Cao, Junwei; Pan, Shengkai; Zhou, Huanmin; Zhang, Li; Abutarboush, Mohammed H; Xing, Yanping; Xie, Zhiyuan; Alshanqeeti, Ali S; Zhang, Yanru; Yao, Qiulin; Al-Shomrani, Badr M; Zhang, Dong; Li, Jiang; Manee, Manee M; Yang, Zili; Yang, Linfeng; Liu, Yiyi; Zhang, Jilin; Altammami, Musaad A; Wang, Shenyuan; Yu, Lili; Zhang, Wenbin; Liu, Sanyang; Ba, La; Liu, Chunxia; Yang, Xukui; Meng, Fanhua; Wang, Shaowei; Li, Lu; Li, Erli; Li, Xueqiong; Wu, Kaifeng; Zhang, Shu; Wang, Junyi; Yin, Ye; Yang, Huanming; Al-Swailem, Abdulaziz M; Wang, Jun

    2014-10-21

    Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

  13. Programmable self-assembly of three-dimensional nanostructures from 10,000 unique components

    Science.gov (United States)

    Ong, Luvena L.; Hanikel, Nikita; Yaghi, Omar K.; Grun, Casey; Strauss, Maximilian T.; Bron, Patrick; Lai-Kee-Him, Josephine; Schueder, Florian; Wang, Bei; Wang, Pengfei; Kishi, Jocelyn Y.; Myhrvold, Cameron; Zhu, Allen; Jungmann, Ralf; Bellot, Gaetan; Ke, Yonggang; Yin, Peng

    2017-12-01

    Nucleic acids (DNA and RNA) are widely used to construct nanometre-scale structures with ever increasing complexity, with possible application in fields such as structural biology, biophysics, synthetic biology and photonics. The nanostructures are formed through one-pot self-assembly, with early kilodalton-scale examples containing typically tens of unique DNA strands. The introduction of DNA origami, which uses many staple strands to fold one long scaffold strand into a desired structure, has provided access to megadalton-scale nanostructures that contain hundreds of unique DNA strands. Even larger DNA origami structures are possible, but manufacturing and manipulating an increasingly long scaffold strand remains a challenge. An alternative and more readily scalable approach involves the assembly of DNA bricks, which each consist of four short binding domains arranged so that the bricks can interlock. This approach does not require a scaffold; instead, the short DNA brick strands self-assemble according to specific inter-brick interactions. First-generation bricks used to create three-dimensional structures are 32 nucleotides long, consisting of four eight-nucleotide binding domains. Protocols have been designed to direct the assembly of hundreds of distinct bricks into well formed structures, but attempts to create larger structures have encountered practical challenges and had limited success. Here we show that DNA bricks with longer, 13-nucleotide binding domains make it possible to self-assemble 0.1-1-gigadalton, three-dimensional nanostructures from tens of thousands of unique components, including a 0.5-gigadalton cuboid containing about 30,000 unique bricks and a 1-gigadalton rotationally symmetric tetramer. We also assembled a cuboid that contains around 10,000 bricks and about 20,000 uniquely addressable, 13-base-pair ‘voxels’ that serves as a molecular canvas for three-dimensional sculpting. Complex, user-prescribed, three-dimensional cavities can

  14. Unique Reversible Crystal-to-Crystal Phase Transition – Structural and Functional Properties of Fused Ladder Thienoarenes

    KAUST Repository

    Abe, Yuichiro

    2017-08-15

    Donor-acceptor type molecules based on fused ladder thienoarenes, indacenodithiophene (IDT) and dithienocyclopenta-thienothiophene (DTCTT), coupled with benzothiadiazole, are prepared and their solid-state structures are investigated. They display a rich variety of solid phases ranging from amorphous glass states to crystalline states, upon changes in the central aromatic core and side group structures. Most notably, the DTCTT-based derivatives showed reversible crystal-to-crystal phase transitions in heating and cooling cycles. Unlike what has been seen in π−conjugated molecules variable temperature XRD revealed that structural change occurs continuously during the transition. A columnar self-assembled structure with slip-stacked π−π interaction is proposed to be involved in the solid-state. This research provides the evidence of unique structural behavior of the DTCTT-based molecules through the detailed structural analysis. This unique structural transition paves the way for these materials to have self-healing of crystal defects, leading to improved optoelectronic properties.

  15. Unique Reversible Crystal-to-Crystal Phase Transition – Structural and Functional Properties of Fused Ladder Thienoarenes

    KAUST Repository

    Abe, Yuichiro; Savikhin, Victoria; Yin, Jun; Grimsdale, Andrew C.; Soci, Cesare; Toney, Michael F.; Lam, Yeng Ming

    2017-01-01

    Donor-acceptor type molecules based on fused ladder thienoarenes, indacenodithiophene (IDT) and dithienocyclopenta-thienothiophene (DTCTT), coupled with benzothiadiazole, are prepared and their solid-state structures are investigated. They display a rich variety of solid phases ranging from amorphous glass states to crystalline states, upon changes in the central aromatic core and side group structures. Most notably, the DTCTT-based derivatives showed reversible crystal-to-crystal phase transitions in heating and cooling cycles. Unlike what has been seen in π−conjugated molecules variable temperature XRD revealed that structural change occurs continuously during the transition. A columnar self-assembled structure with slip-stacked π−π interaction is proposed to be involved in the solid-state. This research provides the evidence of unique structural behavior of the DTCTT-based molecules through the detailed structural analysis. This unique structural transition paves the way for these materials to have self-healing of crystal defects, leading to improved optoelectronic properties.

  16. The scorpion toxin Bot IX is a potent member of the α-like family and has a unique N-terminal sequence extension.

    Science.gov (United States)

    Martin-Eauclaire, Marie-France; Salvatierra, Juan; Bosmans, Frank; Bougis, Pierre E

    2016-09-01

    We report the detailed chemical, immunological and pharmacological characterization of the α-toxin Bot IX from the Moroccan scorpion Buthus occitanus tunetanus venom. Bot IX, which consists of 70 amino acids, is a highly atypical toxin. It carries a unique N-terminal sequence extension and is highly lethal in mice. Voltage clamp recordings on oocytes expressing rat Nav1.2 or insect BgNav1 reveal that, similar to other α-like toxins, Bot IX inhibits fast inactivation of both variants. Moreover, Bot IX belongs to the same structural/immunological group as the α-like toxin Bot I. Remarkably, radioiodinated Bot IX competes efficiently with the classical α-toxin AaH II from Androctonus australis, and displays one of the highest affinities for Nav channels. © 2016 Federation of European Biochemical Societies.

  17. A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Jiazhang; Yu, Kaiwen; Fei, Xiaowen; Liu, Yao; Nakayasu, Ernesto S.; Piehowski, Paul D.; Shaw, Jared B.; Puvar, Kedar; Das, Chittaranjan; Liu, Xiaoyun; Luo, Zhao-Qing

    2017-05-12

    Ubiquitination regulates many aspects of host immunity and thus is a common target for infectious agents. Recent studies revealed that members of the SidE effector family of the bacterial pathogen Legionella pneumophila attacked several small GTPases associated with the endoplasmic reticulum by a novel ubiquitination mechanism that does not require the E1 and E2 enzymes of the host ubiquitination machinery. Following ubiquitin activation by ADP- ribosylation via a mono-ADP-ribosylation motif, ADP-ribosylated ubiquitin is cleaved by a phosphodiesterasedomainwithinSdeA,whichisconcomitantwiththelinkof phosphoribosylated ubiquitin to serine residues in the substrate. Here we demonstrate that the activity of SidEs is regulated by SidJ, another effector encoded by a gene situated in the locus coding for three members of the SidE family (SdeC, SdeB and SdeA). SidJ functions to remove ubiquitin from SidEs-modified substrates by cleaving the phosphodiester bond that links phosphoribosylated ubiquitin to protein substrates. Further, the deubiquitinase activity of SidJ is essential for its role in L. pneumophila infection. Finally, the activity of SidJ is required for efficiently reducing the abundance of ubiquitinated Rab33b in infected cells within a few hours after bacterial uptake. Our results establish SidJ as a deubiquitinase that functions to impose temporal regulation of the activity of the SidE effectors. The identification of SidJ may shed light on future study of signaling cascades mediated by this unique ubiquitination that also potentially regulates cellular processes in eukaryotic cells.

  18. Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

    Science.gov (United States)

    Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

    2018-05-21

    The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  19. A unique nuclear thermal rocket engine using a particle bed reactor

    Science.gov (United States)

    Culver, Donald W.; Dahl, Wayne B.; McIlwain, Melvin C.

    1992-01-01

    Aerojet Propulsion Division (APD) studied 75-klb thrust Nuclear Thermal Rocket Engines (NTRE) with particle bed reactors (PBR) for application to NASA's manned Mars mission and prepared a conceptual design description of a unique engine that best satisfied mission-defined propulsion requirements and customer criteria. This paper describes the selection of a sprint-type Mars transfer mission and its impact on propulsion system design and operation. It shows how our NTRE concept was developed from this information. The resulting, unusual engine design is short, lightweight, and capable of high specific impulse operation, all factors that decrease Earth to orbit launch costs. Many unusual features of the NTRE are discussed, including nozzle area ratio variation and nozzle closure for closed loop after cooling. Mission performance calculations reveal that other well known engine options do not support this mission.

  20. Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy

    Directory of Open Access Journals (Sweden)

    Daniel Sultanov

    2017-01-01

    Full Text Available DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose polymerase 1 increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer microscopy. PARP-1 binding to a double-strand break in the vicinity of a nucleosome results in a significant increase of the distance between the adjacent gyres of nucleosomal DNA. This partial uncoiling of the entire nucleosomal DNA occurs without apparent loss of histones and is reversed after poly(ADP-ribosylation of PARP-1. Thus PARP-1-nucleosome interactions result in reversible, partial uncoiling of the entire nucleosomal DNA.

  1. DECISIONS ET COMPETITIVITE SUR LE MARCHE UNIQUE EUROPEEN

    Directory of Open Access Journals (Sweden)

    Sirghi Nicoleta

    2008-05-01

    Full Text Available L’un des traits importants du marché unique européen, a comme source le męme énoncé du principal objectif de l’intégration européenne ainsi que: l’harmonisation des niveaux du développement des Etats Membres et l’augmentation du niveau de vie dans l’ensemble de la communauté. Pour le marché unique européen, cet aspect se traduit par une permanente et soutenue augmentation de la demande. Cet ouvrage présente au début une analyse des éléments spécifiques du marché européen. Ensuite on identifie les opportunités et les risques au niveau macroéconomique adjointes aux perspectives du marché unique européen. Comme fondement on présente des stratégies du développement réalisables au niveau microéconomique que puissent assurer l’augmentation du niveau sur la compétitivité des sociétés sur le marché unique européen.

  2. Real-Time PCR Assay for a Unique Chromosomal Sequence of Bacillus anthracis

    Science.gov (United States)

    2004-12-01

    13061 Neisseria lactamica .............................................................. 23970 Bacillus coagulans ...NEG Bacillus coagulane 7050 NEG NEG Bacillus cereus 13472 NEG NEG Bacillus licheniforms 12759 NEG NEG Bacillus cereus 13824 NEG NEG Bacillus ...Assay for a Unique Chromosomal Sequence of Bacillus anthracis Elizabeth Bode,1 William Hurtle,2† and David Norwood1* United States Army Medical

  3. Unique Physician Identification Number (UPIN) Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Unique Physician Identification Number (UPIN) Directory contains selected information on physicians, doctors of Osteopathy, limited licensed practitioners and...

  4. Unique case of esophageal rupture after a fall from height

    Directory of Open Access Journals (Sweden)

    van Berge Henegouwen Mark I

    2009-12-01

    Full Text Available Abstract Background Traumatic ruptures of the esophagus are relatively rare. This condition is associated with high morbidity and mortality. Most traumatic ruptures occur after motor vehicle accidents. Case Presentation We describe a unique case of a 23 year old woman that presented at our trauma resuscitation room after a fall from 8 meters. During physical examination there were no clinical signs of life-threatening injuries. She did however have a massive amount of subcutaneous emphysema of the chest and neck and pneumomediastinum. Flexible laryngoscopy revealed a lesion in the upper esophagus just below the level of the upper esophageal sphincter. Despite preventive administration of intravenous antibiotics and nutrition via a nasogastric tube, the patient developed a cervical abscess, which drained spontaneously. Normal diet was gradually resumed after 2.5 weeks and the patient was discharged in a reasonable condition 3 weeks after the accident. Conclusions This case report presents a high cervical esophageal rupture without associated local injuries after a fall from height.

  5. Landsat imagery: a unique resource

    Science.gov (United States)

    Miller, H.; Sexton, N.; Koontz, L.

    2011-01-01

    Landsat satellites provide high-quality, multi-spectral imagery of the surface of the Earth. These moderate-resolution, remotely sensed images are not just pictures, but contain many layers of data collected at different points along the visible and invisible light spectrum. These data can be manipulated to reveal what the Earth’s surface looks like, including what types of vegetation are present or how a natural disaster has impacted an area (Fig. 1).

  6. Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

    Directory of Open Access Journals (Sweden)

    Jie Pan

    Full Text Available The pulmonary neuroepithelial bodies (NEBs constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+ via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT, and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR, Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates. The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1 NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2 NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3 NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4 NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA and the neurogenic gene (MASH1 indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional

  7. Drosophila melanogaster Mounts a Unique Immune Response to the Rhabdovirus Sigma virus▿

    Science.gov (United States)

    Tsai, C. W.; McGraw, E. A.; Ammar, E.-D.; Dietzgen, R. G.; Hogenhout, S. A.

    2008-01-01

    Rhabdoviruses are important pathogens of humans, livestock, and plants that are often vectored by insects. Rhabdovirus particles have a characteristic bullet shape with a lipid envelope and surface-exposed transmembrane glycoproteins. Sigma virus (SIGMAV) is a member of the Rhabdoviridae and is a naturally occurring disease agent of Drosophila melanogaster. The infection is maintained in Drosophila populations through vertical transmission via germ cells. We report here the nature of the Drosophila innate immune response to SIGMAV infection as revealed by quantitative reverse transcription-PCR analysis of differentially expressed genes identified by microarray analysis. We have also compared and contrasted the immune response of the host with respect to two nonenveloped viruses, Drosophila C virus (DCV) and Drosophila X virus (DXV). We determined that SIGMAV infection upregulates expression of the peptidoglycan receptor protein genes PGRP-SB1 and PGRP-SD and the antimicrobial peptide (AMP) genes Diptericin-A, Attacin-A, Attacin-B, Cecropin-A1, and Drosocin. SIGMAV infection did not induce PGRP-SA and the AMP genes Drosomycin-B, Metchnikowin, and Defensin that are upregulated in DCV and/or DXV infections. Expression levels of the Toll and Imd signaling cascade genes are not significantly altered by SIGMAV infection. These results highlight shared and unique aspects of the Drosophila immune response to the three viruses and may shed light on the nature of the interaction with the host and the evolution of these associations. PMID:18378641

  8. The Phe105 Loop of Alix Bro1 Domain Plays a Key Role in HIV-1 Release

    Energy Technology Data Exchange (ETDEWEB)

    Sette, Paola; Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Snyder, Greg; Smith, Patrick; Xiao, Tsan Sam; Bouamr, Fadila (NIH)

    2011-12-07

    Alix and cellular paralogs HD-PTP and Brox contain N-terminal Bro1 domains that bind ESCRT-III CHMP4. In contrast to HD-PTP and Brox, expression of the Bro1 domain of Alix alleviates HIV-1 release defects that result from interrupted access to ESCRT. In an attempt to elucidate this functional discrepancy, we solved the crystal structures of the Bro1 domains of HD-PTP and Brox. They revealed typical 'boomerang' folds they share with the Bro1 Alix domain. However, they each contain unique structural features that may be relevant to their specific function(s). In particular, phenylalanine residue in position 105 (Phe105) of Alix belongs to a long loop that is unique to its Bro1 domain. Concurrently, mutation of Phe105 and surrounding residues at the tip of the loop compromise the function of Alix in HIV-1 budding without affecting its interactions with Gag or CHMP4. These studies identify a new functional determinant in the Bro1 domain of Alix.

  9. Plasmodium falciparum centromeres display a unique epigenetic makeup and cluster prior to and during schizogony.

    Science.gov (United States)

    Hoeijmakers, Wieteke A M; Flueck, Christian; Françoijs, Kees-Jan; Smits, Arne H; Wetzel, Johanna; Volz, Jennifer C; Cowman, Alan F; Voss, Till; Stunnenberg, Hendrik G; Bártfai, Richárd

    2012-09-01

    Centromeres are essential for the faithful transmission of chromosomes to the next generation, therefore being essential in all eukaryotic organisms. The centromeres of Plasmodium falciparum, the causative agent of the most severe form of malaria, have been broadly mapped on most chromosomes, but their epigenetic composition remained undefined. Here, we reveal that the centromeric histone variant PfCENH3 occupies a 4-4.5 kb region on each P. falciparum chromosome, which is devoid of pericentric heterochromatin but harbours another histone variant, PfH2A.Z. These CENH3 covered regions pinpoint the exact position of the centromere on all chromosomes and revealed that all centromeric regions have similar size and sequence composition. Immunofluorescence assay of PfCENH3 strongly suggests that P. falciparum centromeres cluster to a single nuclear location prior to and during mitosis and cytokinesis but dissociate soon after invasion. In summary, we reveal a dynamic association of Plasmodium centromeres, which bear a unique epigenetic signature and conform to a strict structure. These findings suggest that DNA-associated and epigenetic elements play an important role in centromere establishment in this important human pathogen. © 2012 Blackwell Publishing Ltd.

  10. New Examples of Torsion-Free Non-unique Product Groups

    OpenAIRE

    Carter, William

    2013-01-01

    We give an infinite family of torsion-free groups that do not satisfy the unique product property. For these examples, we also show that each group contains arbitrarily large sets whose square has no uniquely represented element.

  11. Uniqueness of Gibbs Measure for Models with Uncountable Set of Spin Values on a Cayley Tree

    International Nuclear Information System (INIS)

    Eshkabilov, Yu. Kh.; Haydarov, F. H.; Rozikov, U. A.

    2013-01-01

    We consider models with nearest-neighbor interactions and with the set [0, 1] of spin values, on a Cayley tree of order K ≥ 1. It is known that the ‘splitting Gibbs measures’ of the model can be described by solutions of a nonlinear integral equation. For arbitrary k ≥ 2 we find a sufficient condition under which the integral equation has unique solution, hence under the condition the corresponding model has unique splitting Gibbs measure.

  12. Unique Perspectives on a Transforming Energy Economy: 2014 Annual Report (Brochure)

    Energy Technology Data Exchange (ETDEWEB)

    Gossett, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-03-01

    What makes JISEA unique? Unique perspectives. This brochure highlights the unique perspectives provided by the Joint Institute for Strategic Energy Analysis through JISEA's recent accomplishments and the people behind them.

  13. PET-CT in the typification of unique pulmonary injuries

    International Nuclear Information System (INIS)

    Cobos, P.; San Roman, Jose L.; Dalurzo, L.

    2007-01-01

    The objective of this document is to evaluate the usefulness of the PET-CT for the characterization of the unique pulmonary injuries. Retrospective analysis was made to patients with unique pulmonary injuries who carried out a PET-CT in the Italian Hospital between May of 2003 - March of 2005. Those patients with pulmonary outlying nodule, or unique pulmonary mass that had pathological anatomy of injury or follow-up through a computed tomography of thorax made with an interval of time not minor at 2 years of the PET-CT were included [es

  14. Lattices with unique complements

    CERN Document Server

    Saliĭ, V N

    1988-01-01

    The class of uniquely complemented lattices properly contains all Boolean lattices. However, no explicit example of a non-Boolean lattice of this class has been found. In addition, the question of whether this class contains any complete non-Boolean lattices remains unanswered. This book focuses on these classical problems of lattice theory and the various attempts to solve them. Requiring no specialized knowledge, the book is directed at researchers and students interested in general algebra and mathematical logic.

  15. Structure determination of human Lck unique and SH3 domains by nuclear magnetic resonance spectroscopy

    Directory of Open Access Journals (Sweden)

    Willbold Dieter

    2003-05-01

    Full Text Available Abstract Background Protein tyrosine kinases are involved in signal transduction pathways that regulate cell growth, differentiation, activation and transformation. Human lymphocyte specific kinase (Lck is a 56 kDa protein involved in T-cell- and IL2-receptor signaling. Three-dimensional structures are known for SH3, SH2 and kinase domains of Lck as well as for other tyrosine kinases. No structure is known for the unique domain of any Src-type tyrosine kinase. Results Lck(1–120 comprising unique and SH3 domains was structurally investigated by nuclear magnetic resonance spectroscopy. We found the unique domain, in contrast to the SH3 part, to have basically no defined structural elements. The solution structure of the SH3 part could be determined with very high precision. It does not show significant differences to Lck SH3 in the absence of the unique domain. Minor differences were observed to the X-ray structure of Lck SH3. Conclusion The unique domain of Lck does not contain any defined structure elements in the absence of ligands and membranes. Presence of the unique domain is not relevant to the three-dimensional structure of the Lck SH3 domain.

  16. Common and unique elements of the ABA-regulated transcriptome of Arabidopsis guard cells

    Directory of Open Access Journals (Sweden)

    Zhao Zhixin

    2011-05-01

    Full Text Available Abstract Background In the presence of drought and other desiccating stresses, plants synthesize and redistribute the phytohormone abscisic acid (ABA. ABA promotes plant water conservation by acting on specialized cells in the leaf epidermis, guard cells, which border and regulate the apertures of stomatal pores through which transpirational water loss occurs. Following ABA exposure, solute uptake into guard cells is rapidly inhibited and solute loss is promoted, resulting in inhibition of stomatal opening and promotion of stomatal closure, with consequent plant water conservation. There is a wealth of information on the guard cell signaling mechanisms underlying these rapid ABA responses. To investigate ABA regulation of gene expression in guard cells in a systematic genome-wide manner, we analyzed data from global transcriptomes of guard cells generated with Affymetrix ATH1 microarrays, and compared these results to ABA regulation of gene expression in leaves and other tissues. Results The 1173 ABA-regulated genes of guard cells identified by our study share significant overlap with ABA-regulated genes of other tissues, and are associated with well-defined ABA-related promoter motifs such as ABREs and DREs. However, we also computationally identified a unique cis-acting motif, GTCGG, associated with ABA-induction of gene expression specifically in guard cells. In addition, approximately 300 genes showing ABA-regulation unique to this cell type were newly uncovered by our study. Within the ABA-regulated gene set of guard cells, we found that many of the genes known to encode ion transporters associated with stomatal opening are down-regulated by ABA, providing one mechanism for long-term maintenance of stomatal closure during drought. We also found examples of both negative and positive feedback in the transcriptional regulation by ABA of known ABA-signaling genes, particularly with regard to the PYR/PYL/RCAR class of soluble ABA receptors and

  17. Common and unique elements of the ABA-regulated transcriptome of Arabidopsis guard cells

    Science.gov (United States)

    2011-01-01

    Background In the presence of drought and other desiccating stresses, plants synthesize and redistribute the phytohormone abscisic acid (ABA). ABA promotes plant water conservation by acting on specialized cells in the leaf epidermis, guard cells, which border and regulate the apertures of stomatal pores through which transpirational water loss occurs. Following ABA exposure, solute uptake into guard cells is rapidly inhibited and solute loss is promoted, resulting in inhibition of stomatal opening and promotion of stomatal closure, with consequent plant water conservation. There is a wealth of information on the guard cell signaling mechanisms underlying these rapid ABA responses. To investigate ABA regulation of gene expression in guard cells in a systematic genome-wide manner, we analyzed data from global transcriptomes of guard cells generated with Affymetrix ATH1 microarrays, and compared these results to ABA regulation of gene expression in leaves and other tissues. Results The 1173 ABA-regulated genes of guard cells identified by our study share significant overlap with ABA-regulated genes of other tissues, and are associated with well-defined ABA-related promoter motifs such as ABREs and DREs. However, we also computationally identified a unique cis-acting motif, GTCGG, associated with ABA-induction of gene expression specifically in guard cells. In addition, approximately 300 genes showing ABA-regulation unique to this cell type were newly uncovered by our study. Within the ABA-regulated gene set of guard cells, we found that many of the genes known to encode ion transporters associated with stomatal opening are down-regulated by ABA, providing one mechanism for long-term maintenance of stomatal closure during drought. We also found examples of both negative and positive feedback in the transcriptional regulation by ABA of known ABA-signaling genes, particularly with regard to the PYR/PYL/RCAR class of soluble ABA receptors and their downstream targets

  18. Uniqueness of solutions for a mathematical model for magneto-viscoelastic flows

    Science.gov (United States)

    Schlömerkemper, A.; Žabenský, J.

    2018-06-01

    We investigate uniqueness of weak solutions for a system of partial differential equations capturing behavior of magnetoelastic materials. This system couples the Navier–Stokes equations with evolutionary equations for the deformation gradient and for the magnetization obtained from a special case of the micromagnetic energy. It turns out that the conditions on uniqueness coincide with those for the well-known Navier–Stokes equations in bounded domains: weak solutions are unique in two spatial dimensions, and weak solutions satisfying the Prodi–Serrin conditions are unique among all weak solutions in three dimensions. That is, we obtain the so-called weak-strong uniqueness result in three spatial dimensions.

  19. Revealing the Mind of the Sage: The Narrative Rhetoric of the "Chuang Tzu."

    Science.gov (United States)

    Kirkwood, William G.

    1992-01-01

    Argues that one of the formative texts of Taoism, the "Chuang Tzu," is worthy of study by rhetoric scholars because it reveals a unique approach to rhetoric in its attempt to disclose the mind of the sage not through logic but through intuition, and it shows how storytelling can acquaint people with previously unsuspected possibilities of thought…

  20. TIME SERIES ANALYSIS USING A UNIQUE MODEL OF TRANSFORMATION

    Directory of Open Access Journals (Sweden)

    Goran Klepac

    2007-12-01

    Full Text Available REFII1 model is an authorial mathematical model for time series data mining. The main purpose of that model is to automate time series analysis, through a unique transformation model of time series. An advantage of this approach of time series analysis is the linkage of different methods for time series analysis, linking traditional data mining tools in time series, and constructing new algorithms for analyzing time series. It is worth mentioning that REFII model is not a closed system, which means that we have a finite set of methods. At first, this is a model for transformation of values of time series, which prepares data used by different sets of methods based on the same model of transformation in a domain of problem space. REFII model gives a new approach in time series analysis based on a unique model of transformation, which is a base for all kind of time series analysis. The advantage of REFII model is its possible application in many different areas such as finance, medicine, voice recognition, face recognition and text mining.

  1. Common processes at unique volcanoes – a volcanological conundrum

    Directory of Open Access Journals (Sweden)

    Katharine eCashman

    2014-11-01

    Full Text Available An emerging challenge in modern volcanology is the apparent contradiction between the perception that every volcano is unique, and classification systems based on commonalities among volcano morphology and eruptive style. On the one hand, detailed studies of individual volcanoes show that a single volcano often exhibits similar patterns of behaviour over multiple eruptive episodes; this observation has led to the idea that each volcano has its own distinctive pattern of behaviour (or personality. In contrast, volcano classification schemes define eruption styles referenced to type volcanoes (e.g. Plinian, Strombolian, Vulcanian; this approach implicitly assumes that common processes underpin volcanic activity and can be used to predict the nature, extent and ensuing hazards of individual volcanoes. Actual volcanic eruptions, however, often include multiple styles, and type volcanoes may experience atypical eruptions (e.g., violent explosive eruptions of Kilauea, Hawaii1. The volcanological community is thus left with a fundamental conundrum that pits the uniqueness of individual volcanic systems against generalization of common processes. Addressing this challenge represents a major challenge to volcano research.

  2. Uniqueness of the electrostatic solution in Schwarzschild space

    International Nuclear Information System (INIS)

    Molnar, Pal G.; Elsaesser, Klaus

    2003-01-01

    In this Brief Report we give the proof that the solution of any static test charge distribution in Schwarzschild space is unique. In order to give the proof we derive the first Green's identity written with p-forms on (pseudo) Riemannian manifolds. Moreover, the proof of uniqueness can be shown for either any purely electric or purely magnetic field configuration. The spacetime geometry is not crucial for the proof

  3. Sleep, Internalizing Problems, and Social Withdrawal: Unique Associations in Clinic-Referred Youth With Elevated Sluggish Cognitive Tempo Symptoms.

    Science.gov (United States)

    Rondon, Ana T; Hilton, Dane C; Jarrett, Matthew A; Ollendick, Thomas H

    2018-02-01

    We compared clinic-referred youth with ADHD + sluggish cognitive tempo (SCT; n = 34), ADHD Only ( n = 108), and SCT Only ( n = 22) on demographics, co-occurring symptomatology, comorbid diagnoses, and social functioning. In total, 164 youth (age = 6-17 years, M = 9.97) and their parent(s) presented to an outpatient clinic for a psychoeducational assessment. Between-group analyses and regressions were used to examine study variables. SCT groups were older and exhibited more parent-reported internalizing problems, externalizing problems, sleep problems, and social withdrawal on the Child Behavior Checklist. No significant differences emerged between groups on the Teacher Report Form. Regression analyses involving multiple covariates revealed that SCT symptoms were uniquely related to social withdrawal but not general social problems. Based on parent report, SCT symptoms have a unique relationship with internalizing problems, sleep problems, and social withdrawal. Future research should explore correlates of SCT in youth using multiple informants.

  4. Genome sequencing and analysis reveals possible determinants of Staphylococcus aureus nasal carriage

    Directory of Open Access Journals (Sweden)

    Cole Alexander M

    2008-09-01

    Full Text Available Abstract Background Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown. Herein, we have set a genomic foundation for unraveling the bacterial determinants of nasal carriage in S. aureus. Results MLST analysis revealed no lineage specific differences between carrier and non-carrier strains suggesting a role for mobile genetic elements. We completely sequenced a model carrier isolate (D30 and a model non-carrier strain (930918-3 to identify differential gene content. Comparison revealed the presence of 84 genes unique to the carrier strain and strongly suggests a role for Type VII secretion systems in nasal carriage. These genes, along with a putative pathogenicity island (SaPIBov present uniquely in the carrier strains are likely important in affecting carriage. Further, PCR-based genotyping of other clinical isolates for a specific subset of these 84 genes raise the possibility of nasal carriage being caused by multiple gene sets. Conclusion Our data suggest that carriage is likely a heterogeneic phenotypic trait and implies a role for nucleotide level polymorphism in carriage. Complete genome level analyses of multiple carriage strains of S. aureus will be important in clarifying molecular determinants of S. aureus nasal carriage.

  5. Unique computer system for safeguards use

    International Nuclear Information System (INIS)

    Kuckertz, T.H.; Pratt, J.C.

    1981-01-01

    Microprocessors have been used to implement specialized scientific data processing systems since 1976. One such system, the LeCroy 3500, is presently being used by the Detection and Verification Group of the Energy Division at Los Alamos National Laboratory for a large variety of tasks involving measurement of various nuclear parameters associated with radioactive materials. The system is unique because it can do not only sophisticated pulse height and multi-scale analyses but also other analyses that are limited only by the availability fo CAMAC modules that would acquire data from exotic experiments. The system is also field portable which extends the range of experiments that it can control. Four applications of this system are described in this paper: (1) plutonium storage vault monitoring, (2) coded aperture image reconstruction, (3) spatial distribution of gamma radiation, and (4) nuclear waste management. 7 figures

  6. Global existence and uniqueness result for the diffusive Peterlin viscoelastic model

    Czech Academy of Sciences Publication Activity Database

    Medviďová-Lukáčová, M.; Mizerová, H.; Nečasová, Šárka

    2015-01-01

    Roč. 120, June (2015), s. 154-170 ISSN 0362-546X R&D Projects: GA ČR GA13-00522S Institutional support: RVO:67985840 Keywords : Peterlin viscoelastic model * existence * uniqueness Subject RIV: BA - General Mathematics Impact factor: 1.125, year: 2015 http://www.sciencedirect.com/science/article/pii/S0362546X1500070X

  7. Transcriptomic analysis of short-fruit 1 (sf1) reveals new insights into the variation of fruit-related traits in Cucumis sativus.

    Science.gov (United States)

    Wang, Lina; Cao, Chenxing; Zheng, Shuangshuang; Zhang, Haiyang; Liu, Panjing; Ge, Qian; Li, Jinrui; Ren, Zhonghai

    2017-06-07

    Fruit size is an important quality trait in different market classes of Cucumis sativus L., an economically important vegetable cultivated worldwide, but the genetic and molecular mechanisms that control fruit size are largely unknown. In this study, we isolated a natural cucumber mutant, short fruit 1 (sf1), caused by a single recessive Mendelian factor, from the North China-type inbred line CNS2. In addition to significantly decreased fruit length, other fruit-related phenotypic variations were also observed in sf1 compared to the wild-type (WT) phenotype, indicating that sf1 might have pleiotropic effects. Microscopic imaging showed that fruit cell size in sf1 was much larger than that in WT, suggesting that the short fruit phenotype in sf1 is caused by decreased cell number. Fine mapping revealed that sf1 was localized to a 174.3 kb region on chromosome 6. Similarly, SNP association analysis of bulked segregant RNA-Seq data showed increased SNP frequency in the same region of chromosome 6. In addition, transcriptomic analysis revealed that sf1 might control fruit length through the fine-tuning of cytokinin and auxin signalling, gibberellin biosynthesis and signal transduction in cucumber fruits. Overall, our results provide important information for further study of fruit length and other fruit-related features in cucumber.

  8. Uniqueness plots: A simple graphical tool for identifying poor peak fits in X-ray photoelectron spectroscopy

    International Nuclear Information System (INIS)

    Singh, Bhupinder; Diwan, Anubhav; Jain, Varun; Herrera-Gomez, Alberto; Terry, Jeff; Linford, Matthew R.

    2016-01-01

    Highlights: • Uniqueness plots are introduced as a new tool for identifying poor XPS peak fits. • Uniqueness plots are demonstrated on real XPS data sets. • A horizontal line in a uniqueness plot indicates a poor fit, i.e., fit parameter correlation. • A parabolic shape in a uniqueness plot indicates that a fit may be appropriate. - Abstract: Peak fitting is an essential part of X-ray photoelectron spectroscopy (XPS) narrow scan analysis, and the Literature contains both good and bad examples of peak fitting. A common cause of poor peak fitting is the inclusion of too many fit parameters, often without a sound chemical and/or physical basis for them, and/or the failure to reasonably constrain them. Under these conditions, fit parameters are often correlated, and therefore lacking in statistical meaning. Here we introduce the uniqueness plot as a simple graphical tool for identifying bad peak fits in XPS, i.e., fit parameter correlation. These plots are widely used in spectroscopic ellipsometry. We illustrate uniqueness plots with two data sets: a C 1s narrow scan from ozone-treated carbon nanotube forests and an Si 2p narrow scan from an air-oxidized silicon wafer. For each fit, we consider different numbers of parameters and constraints on them. As expected, the uniqueness plots are parabolic when fewer fit parameters and/or more constraints are applied. However, they fan out and eventually become horizontal lines as more unconstrained parameters are included in the fits. Uniqueness plots are generated by plotting the chi squared (χ 2 ) value for a fit vs. a systematically varied value of a parameter in the fit. The Abbe criterion is also considered as a figure of merit for uniqueness plots in the Supporting Information. We recommend that uniqueness plots be used by XPS practitioners for identifying inappropriate peak fits.

  9. Uniqueness plots: A simple graphical tool for identifying poor peak fits in X-ray photoelectron spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Bhupinder; Diwan, Anubhav; Jain, Varun [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84606 (United States); Herrera-Gomez, Alberto [CINVESTAV-Unidad Queretaro, Queretaro, 76230 (Mexico); Terry, Jeff [Department of Physics, Illinois Institute of Technology, Chicago, IL, 60616 (United States); Linford, Matthew R., E-mail: mrlinford@chem.byu.edu [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84606 (United States)

    2016-11-30

    Highlights: • Uniqueness plots are introduced as a new tool for identifying poor XPS peak fits. • Uniqueness plots are demonstrated on real XPS data sets. • A horizontal line in a uniqueness plot indicates a poor fit, i.e., fit parameter correlation. • A parabolic shape in a uniqueness plot indicates that a fit may be appropriate. - Abstract: Peak fitting is an essential part of X-ray photoelectron spectroscopy (XPS) narrow scan analysis, and the Literature contains both good and bad examples of peak fitting. A common cause of poor peak fitting is the inclusion of too many fit parameters, often without a sound chemical and/or physical basis for them, and/or the failure to reasonably constrain them. Under these conditions, fit parameters are often correlated, and therefore lacking in statistical meaning. Here we introduce the uniqueness plot as a simple graphical tool for identifying bad peak fits in XPS, i.e., fit parameter correlation. These plots are widely used in spectroscopic ellipsometry. We illustrate uniqueness plots with two data sets: a C 1s narrow scan from ozone-treated carbon nanotube forests and an Si 2p narrow scan from an air-oxidized silicon wafer. For each fit, we consider different numbers of parameters and constraints on them. As expected, the uniqueness plots are parabolic when fewer fit parameters and/or more constraints are applied. However, they fan out and eventually become horizontal lines as more unconstrained parameters are included in the fits. Uniqueness plots are generated by plotting the chi squared (χ{sup 2}) value for a fit vs. a systematically varied value of a parameter in the fit. The Abbe criterion is also considered as a figure of merit for uniqueness plots in the Supporting Information. We recommend that uniqueness plots be used by XPS practitioners for identifying inappropriate peak fits.

  10. Multiple floating metatarsals: a unique injury

    Directory of Open Access Journals (Sweden)

    Trikha Vivek

    2013-04-01

    Full Text Available 【Abstract】Concomitant dislocation of the tar-sometatarsal and metatarsophalangeal joints of foot is an extremely rare injury. Such injuries presenting in a single or adjacent dual rays have been described in few cases previously. We describe such an injury in adjacent three metatarsals of a polytrauma patient. These injuries are likely to be missed in the initial assessment of a polytrauma patient. These patients are at risk of an overlooked diagnosis but the consequences of missing this type of injury may be Vivek Trikha*, Tarun Goyal, Amit K Agarwal quite severe. This case is presented in view of its unique-ness along with possible mechanism of injury, the sequence of reduction and follow-up. Knowledge of such injury and its proper management may be useful to the trauma surgeons. Key words: Metatarsal bones; Metatarsophalangeal joint; Wounds and injuries

  11. On the Non-Uniqueness of Sediment Yield

    Science.gov (United States)

    Kim, J.; Ivanov, V. Y.; Fatichi, S.

    2014-12-01

    There has been ample experimental evidence that soil erosion does not necessarily occur at the same rate, given the same amount of rainfall or runoff. Such a non-unique phenomenon has been often referred to in literature as due to 'natural variability'. Our recent study hypothesized that uncertainties in the distribution and properties of a sediment layer can be a potential clue to one of the reasons of the non-unique sediment yield. Specifically, numerical experimentation with a sophisticated two-dimensional model showed that a deposited layer plays two conflicting roles: it can both increase and decrease soil erosion, given the same magnitude of runoff. The difference in erodibilities of the "original, intact soil layer" and the "deposited, loose soil layer" and the composition of soil particles in the underlying layers give rise to the non-uniqueness of the amount of eroded materials. In continuing efforts, we attempt to investigate this phenomenon using a comprehensive the Universal Soil Loss Erosion (USLE) database, that contains data on paired hillslopes that show a high degree of non-uniqueness in the response, even though the hillslopes exhibit the same topography, soil type, rainfall and meteorological forcings, and landuse. An underlying hypothesis of this study is that uncertainties in the distribution of soil substrate prior to a rainfall event lead to low predictability skill, i.e., a stochastically-varying outcome. A large number of simulation cases demonstrating the proposed hypothesis are conducted using a coupled numerical model, tRIBS-VEGGIE-FEaST (Triangulated irregular network - based Real time Integrated Basin Simulator- VEGetation Generator for Interactive Evolution -Flow Erosion and Sediment Transport).

  12. Classical many-particle systems with unique disordered ground states

    Science.gov (United States)

    Zhang, G.; Stillinger, F. H.; Torquato, S.

    2017-10-01

    Classical ground states (global energy-minimizing configurations) of many-particle systems are typically unique crystalline structures, implying zero enumeration entropy of distinct patterns (aside from trivial symmetry operations). By contrast, the few previously known disordered classical ground states of many-particle systems are all high-entropy (highly degenerate) states. Here we show computationally that our recently proposed "perfect-glass" many-particle model [Sci. Rep. 6, 36963 (2016), 10.1038/srep36963] possesses disordered classical ground states with a zero entropy: a highly counterintuitive situation . For all of the system sizes, parameters, and space dimensions that we have numerically investigated, the disordered ground states are unique such that they can always be superposed onto each other or their mirror image. At low energies, the density of states obtained from simulations matches those calculated from the harmonic approximation near a single ground state, further confirming ground-state uniqueness. Our discovery provides singular examples in which entropy and disorder are at odds with one another. The zero-entropy ground states provide a unique perspective on the celebrated Kauzmann-entropy crisis in which the extrapolated entropy of a supercooled liquid drops below that of the crystal. We expect that our disordered unique patterns to be of value in fields beyond glass physics, including applications in cryptography as pseudorandom functions with tunable computational complexity.

  13. The unique cysteine knot regulates the pleotropic hormone leptin.

    Directory of Open Access Journals (Sweden)

    Ellinor Haglund

    Full Text Available Leptin plays a key role in regulating energy intake/expenditure, metabolism and hypertension. It folds into a four-helix bundle that binds to the extracellular receptor to initiate signaling. Our work on leptin revealed a hidden complexity in the formation of a previously un-described, cysteine-knotted topology in leptin. We hypothesized that this unique topology could offer new mechanisms in regulating the protein activity. A combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function. Our results surprisingly show that the free energy landscape is conserved between knotted and unknotted protein, however the additional complexity added by the knot formation is structurally important. Native state analyses led to the discovery that the disulphide-bond plays an important role in receptor binding and thus mediate biological activity by local motions on distal receptor-binding sites, far removed from the disulphide-bridge. Thus, the disulphide-bridge appears to function as a point of tension that allows dissipation of stress at a distance in leptin.

  14. Unique physiology of host-parasite interactions in microsporidia infections.

    Science.gov (United States)

    Williams, Bryony A P

    2009-11-01

    Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.

  15. Accessibility of physical states and non-uniqueness of entanglement measure

    International Nuclear Information System (INIS)

    Morikoshi, Fumiaki; Santos, Marcelo Franca; Vedral, Vlatko

    2004-01-01

    Ordering physical states is the key to quantifying some physical property of the states uniquely. Bipartite pure entangled states are totally ordered under local operations and classical communication (LOCC) in the asymptotic limit and uniquely quantified by the well-known entropy of entanglement. However, we show that mixed entangled states are partially ordered under LOCC even in the asymptotic limit. Therefore, non-uniqueness of entanglement measure is understood on the basis of an operational notion of asymptotic convertibility

  16. Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires' disease.

    Directory of Open Access Journals (Sweden)

    Christel Cazalet

    2010-02-01

    Full Text Available Legionella pneumophila and L. longbeachae are two species of a large genus of bacteria that are ubiquitous in nature. L. pneumophila is mainly found in natural and artificial water circuits while L. longbeachae is mainly present in soil. Under the appropriate conditions both species are human pathogens, capable of causing a severe form of pneumonia termed Legionnaires' disease. Here we report the sequencing and analysis of four L. longbeachae genomes, one complete genome sequence of L. longbeachae strain NSW150 serogroup (Sg 1, and three draft genome sequences another belonging to Sg1 and two to Sg2. The genome organization and gene content of the four L. longbeachae genomes are highly conserved, indicating strong pressure for niche adaptation. Analysis and comparison of L. longbeachae strain NSW150 with L. pneumophila revealed common but also unexpected features specific to this pathogen. The interaction with host cells shows distinct features from L. pneumophila, as L. longbeachae possesses a unique repertoire of putative Dot/Icm type IV secretion system substrates, eukaryotic-like and eukaryotic domain proteins, and encodes additional secretion systems. However, analysis of the ability of a dotA mutant of L. longbeachae NSW150 to replicate in the Acanthamoeba castellanii and in a mouse lung infection model showed that the Dot/Icm type IV secretion system is also essential for the virulence of L. longbeachae. In contrast to L. pneumophila, L. longbeachae does not encode flagella, thereby providing a possible explanation for differences in mouse susceptibility to infection between the two pathogens. Furthermore, transcriptome analysis revealed that L. longbeachae has a less pronounced biphasic life cycle as compared to L. pneumophila, and genome analysis and electron microscopy suggested that L. longbeachae is encapsulated. These species-specific differences may account for the different environmental niches and disease epidemiology of these

  17. Avian papillomaviruses: the parrot Psittacus erithacus papillomavirus (PePV genome has a unique organization of the early protein region and is phylogenetically related to the chaffinch papillomavirus

    Directory of Open Access Journals (Sweden)

    Jenson A Bennett

    2002-07-01

    Full Text Available Abstract Background An avian papillomavirus genome has been cloned from a cutaneous exophytic papilloma from an African grey parrot (Psittacus erithacus. The nucleotide sequence, genome organization, and phylogenetic position of the Psittacus erithacus papillomavirus (PePV were determined. This PePV sequence represents the first complete avian papillomavirus genome defined. Results The PePV genome (7304 basepairs differs from other papillomaviruses, in that it has a unique organization of the early protein region lacking classical E6 and E7 open reading frames. Phylogenetic comparison of the PePV sequence with partial E1 and L1 sequences of the chaffinch (Fringilla coelebs papillomavirus (FPV reveals that these two avian papillomaviruses form a monophyletic cluster with a common branch that originates near the unresolved center of the papillomavirus evolutionary tree. Conclusions The PePV genome has a unique layout of the early protein region which represents a novel prototypic genomic organization for avian papillomaviruses. The close relationship between PePV and FPV, and between their Psittaciformes and Passeriformes hosts, supports the hypothesis that papillomaviruses have co-evolved and speciated together with their host species throughout evolution.

  18. Using the Theory of Planned Behavior to Identify Predictors of Oral Hygiene: A Collection of Unique Behaviors.

    Science.gov (United States)

    Brein, Daniel J; Fleenor, Thomas J; Kim, Soo-Woo; Krupat, Edward

    2016-03-01

    This study aims to identify predictors of performed oral hygiene behaviors (OHBs) based on the Theory of Planned Behavior (TPB), oral health knowledge, and demographic factors. Using a questionnaire, 381 participants in three general dental offices and one hospital dental department in York, Pennsylvania, were surveyed regarding performed OHB, attitudes, subjective norms, perceived behavioral control, oral health knowledge, income, age, and sex. Three unique elements of OHB were identified for analysis: brushing, interdental cleaning, and tongue cleaning. Regression analysis revealed that attitude was the strongest predictor of brushing behavior, followed by oral health knowledge, perceived behavior control, subjective norms, and income. Perceived behavior control was the strongest predictor of interdental cleaning, followed by increased age and attitude. Female sex was the strongest predictor of tongue cleaning, followed by subjective norms, decreased age, and perceived behavior control. Respectively, these three groups of predictive variables explained 22.5% of brushing behavior, 22.7% of interdental cleaning behavior, and 9.5% of tongue cleaning behavior. The present findings highlight the utility of viewing OHB as a set of unique behaviors with unique predictive variables and provide additional support for use of TPB in predicting OHB. Periodontal practitioners should consider the strong associations of attitude and perceived behavioral control with brushing and interdental cleaning behaviors when designing interventional efforts to improve patient home care.

  19. Unique type of isolated cardiac valvular amyloidosis

    Directory of Open Access Journals (Sweden)

    Reehana Salma

    2006-10-01

    Full Text Available Abstract Background Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. Case presentation A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. Conclusion Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis, and senile type(s. Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis.

  20. A generator for unique quantum random numbers based on vacuum states

    DEFF Research Database (Denmark)

    Gabriel, C.; Wittmann, C.; Sych, D.

    2010-01-01

    the purity of a continuous-variable quantum vacuum state to generate unique random numbers. We use the intrinsic randomness in measuring the quadratures of a mode in the lowest energy vacuum state, which cannot be correlated to any other state. The simplicity of our source, combined with its verifiably......Random numbers are a valuable component in diverse applications that range from simulations(1) over gambling to cryptography(2,3). The quest for true randomness in these applications has engendered a large variety of different proposals for producing random numbers based on the foundational...... unpredictability of quantum mechanics(4-11). However, most approaches do not consider that a potential adversary could have knowledge about the generated numbers, so the numbers are not verifiably random and unique(12-15). Here we present a simple experimental setup based on homodyne measurements that uses...

  1. Metabolomics reveals mycoplasma contamination interferes with the metabolism of PANC-1 cells.

    Science.gov (United States)

    Yu, Tao; Wang, Yongtao; Zhang, Huizhen; Johnson, Caroline H; Jiang, Yiming; Li, Xiangjun; Wu, Zeming; Liu, Tian; Krausz, Kristopher W; Yu, Aiming; Gonzalez, Frank J; Huang, Min; Bi, Huichang

    2016-06-01

    Mycoplasma contamination is a common problem in cell culture and can alter cellular functions. Since cell metabolism is either directly or indirectly involved in every aspect of cell function, it is important to detect changes to the cellular metabolome after mycoplasma infection. In this study, liquid chromatography mass spectrometry (LC/MS)-based metabolomics was used to investigate the effect of mycoplasma contamination on the cellular metabolism of human pancreatic carcinoma cells (PANC-1). Multivariate analysis demonstrated that mycoplasma contamination induced significant metabolic changes in PANC-1 cells. Twenty-three metabolites were identified and found to be involved in arginine and purine metabolism and energy supply. This study demonstrates that mycoplasma contamination significantly alters cellular metabolite levels, confirming the compelling need for routine checking of cell cultures for mycoplasma contamination, particularly when used for metabolomics studies. Graphical abstract Metabolomics reveals mycoplasma contamination changes the metabolome of PANC-1 cells.

  2. Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

    Science.gov (United States)

    Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

    2016-01-01

    The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

  3. Consciousness: a unique way of processing information.

    Science.gov (United States)

    Marchetti, Giorgio

    2018-02-08

    In this article, I argue that consciousness is a unique way of processing information, in that: it produces information, rather than purely transmitting it; the information it produces is meaningful for us; the meaning it has is always individuated. This uniqueness allows us to process information on the basis of our personal needs and ever-changing interactions with the environment, and consequently to act autonomously. Three main basic cognitive processes contribute to realize this unique way of information processing: the self, attention and working memory. The self, which is primarily expressed via the central and peripheral nervous systems, maps our body, the environment, and our relations with the environment. It is the primary means by which the complexity inherent to our composite structure is reduced into the "single voice" of a unique individual. It provides a reference system that (albeit evolving) is sufficiently stable to define the variations that will be used as the raw material for the construction of conscious information. Attention allows for the selection of those variations in the state of the self that are most relevant in the given situation. Attention originates and is deployed from a single locus inside our body, which represents the center of the self, around which all our conscious experiences are organized. Whatever is focused by attention appears in our consciousness as possessing a spatial quality defined by this center and the direction toward which attention is focused. In addition, attention determines two other features of conscious experience: periodicity and phenomenal quality. Self and attention are necessary but not sufficient for conscious information to be produced. Complex forms of conscious experiences, such as the various modes of givenness of conscious experience and the stream of consciousness, need a working memory mechanism to assemble the basic pieces of information selected by attention.

  4. Assessment of the Bacteriocinogenic Potential of Marine Bacteria Reveals Lichenicidin Production by Seaweed-Derived Bacillus spp.

    Directory of Open Access Journals (Sweden)

    Gillian E. Gardiner

    2012-10-01

    Full Text Available The objectives of this study were (1 to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2 to identify at least some of the bacteriocins produced, if any and (3 to determine if they are unique to the marine environment and/or novel. Fifteen Bacillus licheniformis or pumilus isolates with antimicrobial activity against at least one of the indicator bacteria used were recovered. Some, at least, of the antimicrobials produced were bacteriocins, as they were proteinaceous and the producers displayed immunity. Screening with PCR primers for known Bacillus bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored the bli04127 gene which encodes one of the peptides of the two-peptide lantibiotic lichenicidin. Production of both lichenicidin peptides was then confirmed by mass spectrometry. This is the first definitive proof of bacteriocin production by seaweed-derived bacteria. The authors acknowledge that the bacteriocin produced has previously been discovered and is not unique to the marine environment. However, the other marine isolates likely produce novel bacteriocins, as none harboured genes for known Bacillus bacteriocins.

  5. Restablished Accretion in Post-outburst Classical Novae Revealed by X-rays

    Science.gov (United States)

    Hernanz, Margarita; Ferri, Carlo; Sala, Glòria

    2009-05-01

    Classical novae are explosions on accreting white dwarfs (hereinafter WDs) in cataclysmic variables (hereinafter CVs) a hydrogen thermonuclear runaway on top of the WD is responsible for the outburst. X-rays provide a unique way to study the turn-off of H-burning, because super soft X-rays reveal the hot WD photosphere, but also to understand how accretion is established again in the binary system. Observations with XMM-Newton of some post-outburst novae have revealed such a process, but a coverage up to larger energies -as Simbol-X will provide- is fundamental to well understand the characteristics of the binary system and of the nova ejecta. We present a brief summary of our results up to now and prospects for the Simbol-X mission.

  6. On the uniqueness of the injective III1 factor

    DEFF Research Database (Denmark)

    Haagerup, U.

    2016-01-01

    We give a new proof of a theorem due to Alain Connes, that an injective factor N of type III1 with separable predual and with trivial bicentralizer is isomorphic to the Araki-Woods type III1 factor R∞. This, combined with the author's solution to the bicentralizer problem for injective III1 facto...

  7. Unique Structural Features of Influenza Virus H15 Hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Tzarum, Netanel; McBride, Ryan; Nycholat, Corwin M.; Peng, Wenjie; Paulson, James C.; Wilson, Ian A. (Scripps)

    2017-04-12

    Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite rare and, until recently, geographically restricted to wild shorebirds and waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150-loop (loop beginning at position 150) of the receptor-binding site common to this subgroup and a unique insertion in the 260-loop compared to any other subtype. Here, we show that the H15 HA has a high preference for avian receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than all other HAs due to a tilt and opening of the HA1 subunits of the head domain. The extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA surface and can contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have been shown to cause enhanced disease in mammalian models, further characterization and immune surveillance of H15 viruses are warranted.

    IMPORTANCEIn the last 2 decades, an apparent increase has been reported for cases of human infection by emerging avian influenza A virus subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that also include H7 and H10. H15 viruses have been restricted to Australia, but recent isolation of H15 viruses in western Siberia suggests that they could be spread more globally via the avian flyways that converge and emanate from this region. Here we report on characterization of the three-dimensional structure and receptor specificity of the H15 hemagglutinin, revealing distinct features and specificities that can

  8. Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow

    Directory of Open Access Journals (Sweden)

    Hilton Helen

    2010-05-01

    Full Text Available Abstract Background Vertebrates show clear asymmetry in left-right (L-R patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. Results A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1, as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM. LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. Conclusion Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make

  9. Chromosomal structures and repetitive sequences divergence in Cucumis species revealed by comparative cytogenetic mapping.

    Science.gov (United States)

    Zhang, Yunxia; Cheng, Chunyan; Li, Ji; Yang, Shuqiong; Wang, Yunzhu; Li, Ziang; Chen, Jinfeng; Lou, Qunfeng

    2015-09-25

    Differentiation and copy number of repetitive sequences affect directly chromosome structure which contributes to reproductive isolation and speciation. Comparative cytogenetic mapping has been verified an efficient tool to elucidate the differentiation and distribution of repetitive sequences in genome. In present study, the distinct chromosomal structures of five Cucumis species were revealed through genomic in situ hybridization (GISH) technique and comparative cytogenetic mapping of major satellite repeats. Chromosome structures of five Cucumis species were investigated using GISH and comparative mapping of specific satellites. Southern hybridization was employed to study the proliferation of satellites, whose structural characteristics were helpful for analyzing chromosome evolution. Preferential distribution of repetitive DNAs at the subtelomeric regions was found in C. sativus, C hystrix and C. metuliferus, while majority was positioned at the pericentromeric heterochromatin regions in C. melo and C. anguria. Further, comparative GISH (cGISH) through using genomic DNA of other species as probes revealed high homology of repeats between C. sativus and C. hystrix. Specific satellites including 45S rDNA, Type I/II, Type III, Type IV, CentM and telomeric repeat were then comparatively mapped in these species. Type I/II and Type IV produced bright signals at the subtelomeric regions of C. sativus and C. hystrix simultaneously, which might explain the significance of their amplification in the divergence of Cucumis subgenus from the ancient ancestor. Unique positioning of Type III and CentM only at the centromeric domains of C. sativus and C. melo, respectively, combining with unique southern bands, revealed rapid evolutionary patterns of centromeric DNA in Cucumis. Obvious interstitial telomeric repeats were observed in chromosomes 1 and 2 of C. sativus, which might provide evidence of the fusion hypothesis of chromosome evolution from x = 12 to x = 7 in

  10. Whole-exome sequencing reveals GPIHBP1 mutations in infantile colitis with severe hypertriglyceridemia.

    Science.gov (United States)

    Gonzaga-Jauregui, Claudia; Mir, Sabina; Penney, Samantha; Jhangiani, Shalini; Midgen, Craig; Finegold, Milton; Muzny, Donna M; Wang, Min; Bacino, Carlos A; Gibbs, Richard A; Lupski, James R; Kellermayer, Richard; Hanchard, Neil A

    2014-07-01

    Severe congenital hypertriglyceridemia (HTG) is a rare disorder caused by mutations in genes affecting lipoprotein lipase (LPL) activity. Here we report a 5-week-old Hispanic girl with severe HTG (12,031 mg/dL, normal limit 150 mg/dL) who presented with the unusual combination of lower gastrointestinal bleeding and milky plasma. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. After negative sequencing of the LPL gene, whole-exome sequencing revealed novel compound heterozygous mutations in GPIHBP1. Our study broadens the phenotype of GPIHBP1-associated HTG, reinforces the effectiveness of whole-exome sequencing in Mendelian diagnoses, and implicates triglycerides in gastrointestinal mucosal injury.

  11. Plastic-casting intrinsic-surface unique identifier (tag)

    International Nuclear Information System (INIS)

    Palm, R.G.; De Volpi, A.

    1995-04-01

    This report describes the development of an authenticated intrinsic-surf ace tagging method for unique- identification of controlled items. Although developed for control of items limited by an arms control treaty, this method has other potential applications to keep track of critical or high-value items. Each tag (unique-identifier) consists of the intrinsic, microscopic surface topography of a small designated area on a controlled item. It is implemented by making a baseline plastic casting of the designated tag area and usually placing a cover (for example, a bar-code label) over this area to protect the surface from environmental alteration. The plastic casting is returned to a laboratory and prepared for high-resolution scanning electron microscope imaging. Several images are digitized and stored for use as a standard for authentication of castings taken during future inspections. Authentication is determined by numerically comparing digital images. Commercially available hardware and software are used for this tag. Tag parameters are optimized, so unique casting images are obtained from original surfaces, and images obtained from attempted duplicate surfaces are detected. This optimization uses the modulation transfer function, a first principle of image analysis, to determine the parameters. Surface duplication experiments confirmed the optimization

  12. Formation of a unique cluster of G-quadruplex structures in the HIV-1 Nef coding region: implications for antiviral activity.

    Directory of Open Access Journals (Sweden)

    Rosalba Perrone

    Full Text Available G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis in vitro and in vivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment.

  13. Comparative fecal metagenomics unveils unique functional capacity of the swine gut

    Directory of Open Access Journals (Sweden)

    Martinson John

    2011-05-01

    Full Text Available Abstract Background Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available. Results Analysis of 637, 722 pyrosequencing reads (130 megabases generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and JGI IMG/M-ER pipelines. Taxonomic analysis of metagenomic reads indicated that swine fecal microbiomes were dominated by Firmicutes and Bacteroidetes phyla. At a finer phylogenetic resolution, Prevotella spp. dominated the swine fecal metagenome, while some genes associated with Treponema and Anareovibrio species were found to be exclusively within the pig fecal metagenomic sequences analyzed. Functional analysis revealed that carbohydrate metabolism was the most abundant SEED subsystem, representing 13% of the swine metagenome. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Virulence factors associated with antibiotic resistance genes with highest sequence homology to genes in Bacteroidetes, Clostridia, and Methanosarcina were numerous within the gene families unique to the swine fecal metagenomes. Other abundant proteins unique to the distal swine gut shared high sequence homology to putative carbohydrate membrane transporters. Conclusions The results from this metagenomic survey demonstrated the presence of genes associated with resistance to antibiotics and carbohydrate metabolism suggesting that the swine gut microbiome may be shaped by husbandry practices.

  14. Proteomics of Fusarium oxysporum race 1 and race 4 reveals enzymes involved in carbohydrate metabolism and ion transport that might play important roles in banana Fusarium wilt.

    Science.gov (United States)

    Sun, Yong; Yi, Xiaoping; Peng, Ming; Zeng, Huicai; Wang, Dan; Li, Bo; Tong, Zheng; Chang, Lili; Jin, Xiang; Wang, Xuchu

    2014-01-01

    Banana Fusarium wilt is a soil-spread fungal disease caused by Fusarium oxysporum. In China, the main virulence fungi in banana are F. oxysporum race 1 (F1, weak virulence) and race 4 (F4, strong virulence). To date, no proteomic analyses have compared the two races, but the difference in virulence between F1 and F4 might result from their differentially expressed proteins. Here we report the first comparative proteomics of F1 and F4 cultured under various conditions, and finally identify 99 protein species, which represent 59 unique proteins. These proteins are mainly involved in carbohydrate metabolism, post-translational modification, energy production, and inorganic ion transport. Bioinformatics analysis indicated that among the 46 proteins identified from F4 were several enzymes that might be important for virulence. Reverse transcription PCR analysis of the genes for 15 of the 56 proteins revealed that their transcriptional patterns were similar to their protein expression patterns. Taken together, these data suggest that proteins involved in carbohydrate metabolism and ion transport may be important in the pathogenesis of banana Fusarium wilt. Some enzymes such as catalase-peroxidase, galactosidase and chitinase might contribute to the strong virulence of F4. Overexpression or knockout of the genes for the F4-specific proteins will help us to further understand the molecular mechanism of Fusarium-induced banana wilt.

  15. Gallium a unique anti-resorptive agent in bone: Preclinical studies on its mechanisms of action

    International Nuclear Information System (INIS)

    Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R.; Jones, K.W.

    1990-01-01

    The discovery of gallium as a new and unique agent for the treatment of metabolic bone disorders was in part fortuitous. Gallium is an exciting new therapeutic agent for the treatment of pathologic states characterized by accelerated bone resorption. Compared to other therapeutic metal compounds containing platinum or germanium, gallium affects its antiresorptive action without any evidence of a cytotoxic effect on bone cells. Gallium is unique amongst all therapeutically available antiresorptive agents in that it favors bone formation. 18 refs., 1 fig

  16. HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression.

    Science.gov (United States)

    Keith, Brian; Johnson, Randall S; Simon, M Celeste

    2011-12-15

    Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.

  17. On the existence and uniqueness of minima and maxima on spheres of the integral functional of the calculus of variations

    Science.gov (United States)

    Ricceri, Biagio

    2006-12-01

    Given a bounded domain [Omega][subset of]Rn, we prove that if is a C1 function whose gradient is Lipschitzian in Rn+1 and non-zero at 0, then, for each r>0 small enough, the restriction of the integral functional to the sphere has a unique global minimum and a unique global maximum.

  18. Weeping dragon, a unique ornamenal citrus

    Science.gov (United States)

    ‘Weeping Dragon’ is a new ornamental citrus cultivar developed by intercrossing of two unusual and unique citrus types, Poncirus trifoliata cultivated variety (cv.) Flying Dragon, and Citrus sinensis cv. ‘Cipo’. This new hybrid cultivar combines strongly contorted and weeping growth traits in a smal...

  19. A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

    Directory of Open Access Journals (Sweden)

    Karen M Chisholm

    Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

  20. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Directory of Open Access Journals (Sweden)

    Alexander Zhyvoloup

    2017-07-01

    Full Text Available HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  1. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Science.gov (United States)

    Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

    2017-07-01

    HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  2. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

    DEFF Research Database (Denmark)

    Bultmann-Mellin, Insa; Conradi, Anne; Maul, Alexandra C

    2015-01-01

    Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been ...

  3. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, Jiapeng [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); Mouveaux, Thomas [Université Lille Nord de France, (France); Light, Samuel H.; Minasov, George; Anderson, Wayne F. [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); Tomavo, Stanislas [Université Lille Nord de France, (France); Ngô, Huân M., E-mail: h-ngo@northwestern.edu [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); BrainMicro LLC, 21 Pendleton Street, New Haven, CT 06511 (United States)

    2015-03-01

    The second crystal structure of a parasite protein preferentially enriched in the brain cyst of T. gondii has been solved at 2.75 Å resolution. Bradyzoite enolase 1 is reported to have differential functions as a glycolytic enzyme and a transcriptional regulator in bradyzoites. In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

  4. Holistic Leadership-Nursing's Unique Contribution to Healthcare.

    Science.gov (United States)

    Clarke, Pamela N; Bleich, Michael R

    2018-04-01

    This dialogue is focused on holistic leadership from the perspective of a well-known leader in nursing. He frames the changing healthcare environment and nursing's unique contribution on the interprofessional team.

  5. 48 CFR 52.211-7 - Alternatives to Government-unique standards.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Alternatives to Government... Government-unique standards. The offeror may propose voluntary consensus standards that meet the Government's... voluntary consensus standard instead of the Government-unique standard if it meets the Government's...

  6. A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Brandon K. Hadland

    2017-06-01

    Full Text Available Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs. However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes.

  7. Mutations in four glycosyl hydrolases reveal a highly coordinated pathway for rhodopsin biosynthesis and N-glycan trimming in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Erica E Rosenbaum

    2014-05-01

    Full Text Available As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II, α-mannosidase-IIb (α-Man-IIb, a β-N-acetylglucosaminidase called fused lobes (Fdl, and hexosaminidase 1 (Hexo1. We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights

  8. Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster

    Science.gov (United States)

    Rosenbaum, Erica E.; Vasiljevic, Eva; Brehm, Kimberley S.; Colley, Nansi Jo

    2014-01-01

    As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan) undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II), α-mannosidase-IIb (α-Man-IIb), a β-N-acetylglucosaminidase called fused lobes (Fdl), and hexosaminidase 1 (Hexo1). We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights into the

  9. UNiquant, a Program for Quantitative Proteomics Analysis Using Stable Isotope Labeling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xin; Tolmachev, Aleksey V.; Shen, Yulei; Liu, Miao; Huang, Lin; Zhang, Zhixin; Anderson, Gordon A.; Smith, Richard D.; Chan, Wing C.; Hinrichs, Steven; Fu, Kai; Ding, Shi-Jian

    2011-03-04

    We present UNiquant, a new software program for analyzing stable isotope labeling (SIL) based quantitative proteomics data. UNiquant surpassed the performance of two other platforms, MaxQuant and Mascot Distiller, using complex proteome mixtures having either known or unknown heavy/light ratios. UNiquant is compatible with a broad spectrum of search engines and SIL methods, providing outstanding peptide pair identification and accurate measurement of the relative peptide/protein abundance.

  10. Fluorescent Photo-conversion: A second chance to label unique cells.

    Science.gov (United States)

    Mellott, Adam J; Shinogle, Heather E; Moore, David S; Detamore, Michael S

    2015-03-01

    Not all cells behave uniformly after treatment in tissue engineering studies. In fact, some treated cells display no signs of treatment or show unique characteristics not consistent with other treated cells. What if the "unique" cells could be isolated from a treated population, and further studied? Photo-convertible reporter proteins, such as Dendra2 , allow for the ability to selectively identify unique cells with a secondary label within a primary labeled treated population. In the current study, select cells were identified and labeled through photo-conversion of Dendra2 -transfected human Wharton's Jelly cells (hWJCs) for the first time. Robust photo-conversion of green-to-red fluorescence was achieved consistently in arbitrarily selected cells, allowing for precise cell identification of select hWJCs. The current study demonstrates a method that offers investigators the opportunity to selectively label and identify unique cells within a treated population for further study or isolation from the treatment population. Photo-convertible reporter proteins, such as Dendra2 , offer the ability over non-photo-convertible reporter proteins, such as green fluorescent protein, to analyze unique individual cells within a treated population, which allows investigators to gain more meaningful information on how a treatment affects all cells within a target population.

  11. Executive Functions Contribute Uniquely to Reading Competence in Minority Youth

    Science.gov (United States)

    Jacobson, Lisa A.; Koriakin, Taylor; Lipkin, Paul; Boada, Richard; Frijters, Jan; Lovett, Maureen; Hill, Dina; Willcutt, Erik; Gottwald, Stephanie; Wolf, Maryanne; Bosson-Heenan, Joan; Gruen, Jeffrey R.; Mahone, E. Mark

    2018-01-01

    Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing “higher-level” or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty. PMID:26755569

  12. The unique character of traditional forest-related knowledge: threats and challenges ahead

    Science.gov (United States)

    Ronald L. Trosper; John A. Parrotta; Mauro Agnoletti; Vladimir Bocharnikov; Suzanne A. Feary; Monica Gabay; Christian Gamborg; Jesus García Latorre; Elisabeth Johann; Andrey Laletin; Hin Fui Lim; Alfred Oteng-Yeboah; Miguel A. Pinedo-Vasquez; P.S. Ramakrishnan; Yeo-Chang. Youn

    2012-01-01

    This chapter refl ects on the major fi ndings of the lead authors of this book regarding traditional forest-related knowledge (TFRK) using five criteria for distinguishing the unique character of traditional knowledge: (1) its attention to sustainability; (2) relationships to land; (3) identity; (4) reciprocity; and (5) limitations on market involvement. Following an...

  13. Girl with idiopathic childhood hypercalcemia reveals new disease-causing CYP24A1 mutation

    DEFF Research Database (Denmark)

    Madsen, Jens Otto Broby; Sauer, Sabrina; Beck, Bodo

    2018-01-01

    of a 21 months old girl initially hospitalized due to excessive consumption of water and behavioral difficulties. Blood tests showed hypercalcemia, borderline high vitamin-D levels, and renal ultrasound revealed medullary nephrocalcinosis. An abnormality within the vitamin-D metabolism was suspected......CONTEXT: Idiopathic Infantile Hypercalcemia (IHH) was associated with vitamin-D supplementation in the 1950's. 50 years later mutations in the CYP241A gene, involved in the degradation of vitamin-D, have been identified as being a part of the etiology. CASE DESCRIPTION: We hereby report a case...... and genetic testing was performed. This revealed the patient to be compound heterozygous for a common (p.E143del) and a novel (likely) disease-causing mutation (p.H83D) in the CYP24A1 gene. The hypercalcemia normalized after calcium depleted diet and discontinuation of vitamin-D supplementation. CONCLUSIONS...

  14. Microbial Communities and Their Predicted Metabolic Functions in Growth Laminae of a Unique Large Conical Mat from Lake Untersee, East Antarctica

    Directory of Open Access Journals (Sweden)

    Hyunmin Koo

    2017-08-01

    Full Text Available In this study, we report the distribution of microbial taxa and their predicted metabolic functions observed in the top (U1, middle (U2, and inner (U3 decadal growth laminae of a unique large conical microbial mat from perennially ice-covered Lake Untersee of East Antarctica, using NextGen sequencing of the 16S rRNA gene and bioinformatics tools. The results showed that the U1 lamina was dominated by cyanobacteria, specifically Phormidium sp., Leptolyngbya sp., and Pseudanabaena sp. The U2 and U3 laminae had high abundances of Actinobacteria, Verrucomicrobia, Proteobacteria, and Bacteroidetes. Closely related taxa within each abundant bacterial taxon found in each lamina were further differentiated at the highest taxonomic resolution using the oligotyping method. PICRUSt analysis, which determines predicted KEGG functional categories from the gene contents and abundances among microbial communities, revealed a high number of sequences belonging to carbon fixation, energy metabolism, cyanophycin, chlorophyll, and photosynthesis proteins in the U1 lamina. The functional predictions of the microbial communities in U2 and U3 represented signal transduction, membrane transport, zinc transport and amino acid-, carbohydrate-, and arsenic- metabolisms. The Nearest Sequenced Taxon Index (NSTI values processed through PICRUSt were 0.10, 0.13, and 0.11 for U1, U2, and U3 laminae, respectively. These values indicated a close correspondence with the reference microbial genome database, implying high confidence in the predicted metabolic functions of the microbial communities in each lamina. The distribution of microbial taxa observed in each lamina and their predicted metabolic functions provides additional insight into the complex microbial ecosystem at Lake Untersee, and lays the foundation for studies that will enhance our understanding of the mechanisms responsible for the formation of these unique mat structures and their evolutionary significance.

  15. Denture identification using unique identification authority of India barcode

    OpenAIRE

    Sudhindra Mahoorkar; Anoop Jain

    2013-01-01

    Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

  16. Denture identification using unique identification authority of India barcode.

    Science.gov (United States)

    Mahoorkar, Sudhindra; Jain, Anoop

    2013-01-01

    Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

  17. Comparative sequence analyses of the major quantitative trait locus phosphorus uptake 1 (Pup1) reveal a complex genetic structure.

    Science.gov (United States)

    Heuer, Sigrid; Lu, Xiaochun; Chin, Joong Hyoun; Tanaka, Juan Pariasca; Kanamori, Hiroyuki; Matsumoto, Takashi; De Leon, Teresa; Ulat, Victor Jun; Ismail, Abdelbagi M; Yano, Masahiro; Wissuwa, Matthias

    2009-06-01

    The phosphorus uptake 1 (Pup1) locus was identified as a major quantitative trait locus (QTL) for tolerance of phosphorus deficiency in rice. Near-isogenic lines with the Pup1 region from tolerant donor parent Kasalath typically show threefold higher phosphorus uptake and grain yield in phosphorus-deficient field trials than the intolerant parent Nipponbare. In this study, we report the fine mapping of the Pup1 locus to the long arm of chromosome 12 (15.31-15.47 Mb). Genes in the region were initially identified on the basis of the Nipponbare reference genome, but did not reveal any obvious candidate genes related to phosphorus uptake. Kasalath BAC clones were therefore sequenced and revealed a 278-kbp sequence significantly different from the syntenic regions in Nipponbare (145 kb) and in the indica reference genome of 93-11 (742 kbp). Size differences are caused by large insertions or deletions (INDELs), and an exceptionally large number of retrotransposon and transposon-related elements (TEs) present in all three sequences (45%-54%). About 46 kb of the Kasalath sequence did not align with the entire Nipponbare genome, and only three Nipponbare genes (fatty acid alpha-dioxygenase, dirigent protein and aspartic proteinase) are highly conserved in Kasalath. Two Nipponbare genes (expressed proteins) might have evolved by at least three TE integrations in an ancestor gene that is still present in Kasalath. Several predicted Kasalath genes are novel or unknown genes that are mainly located within INDEL regions. Our results highlight the importance of sequencing QTL regions in the respective donor parent, as important genes might not be present in the current reference genomes.

  18. Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites

    Directory of Open Access Journals (Sweden)

    Sibley L David

    2005-12-01

    Full Text Available Abstract Background The phylum Apicomplexa is an early-branching eukaryotic lineage that contains a number of important human and animal pathogens. Their complex life cycles and unique cytoskeletal features distinguish them from other model eukaryotes. Apicomplexans rely on actin-based motility for cell invasion, yet the regulation of this system remains largely unknown. Consequently, we focused our efforts on identifying actin-related proteins in the recently completed genomes of Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., and Theileria spp. Results Comparative genomic and phylogenetic studies of apicomplexan genomes reveals that most contain only a single conventional actin and yet they each have 8–10 additional actin-related proteins. Among these are a highly conserved Arp1 protein (likely part of a conserved dynactin complex, and Arp4 and Arp6 homologues (subunits of the chromatin-remodeling machinery. In contrast, apicomplexans lack canonical Arp2 or Arp3 proteins, suggesting they lost the Arp2/3 actin polymerization complex on their evolutionary path towards intracellular parasitism. Seven of these actin-like proteins (ALPs are novel to apicomplexans. They show no phylogenetic associations to the known Arp groups and likely serve functions specific to this important group of intracellular parasites. Conclusion The large diversity of actin-like proteins in apicomplexans suggests that the actin protein family has diverged to fulfill various roles in the unique biology of intracellular parasites. Conserved Arps likely participate in vesicular transport and gene expression, while apicomplexan-specific ALPs may control unique biological traits such as actin-based gliding motility.

  19. On the accuracy, uniqueness and implication of dimensionless accidental relations between fundamental constants

    International Nuclear Information System (INIS)

    Bahran, M.; Univ. of Oklahoma, Norman-OK,

    2002-01-01

    Ibrahim et al(1) found an accidental formula relating the gravitational coupling constant, the electromagnetic fine structure constant and the proton to electron mass ratio. This work comments on such relation, in particular it studies the accuracy, uniqueness and unification implication of such accidental relation.(author)

  20. Unique in the shopping mall: On the reidentifiability of credit card metadata

    DEFF Research Database (Denmark)

    de Montjoye, Yves-Alexandre; Radaelli, Laura; Singh, Vivek Kumar

    2015-01-01

    . We study 3 months of credit card records for 1.1 million people and show that four spatiotemporal points are enough to uniquely reidentify 90% of individuals. We show that knowing the price of a transaction increases the risk of reidentification by 22%, on average. Finally, we show that even data...... sets that provide coarse information at any or all of the dimensions provide little anonymity and that women are more reidentifiable than men in credit card metadata....

  1. C1q Nephropathy: The Unique Underrecognized Pathological Entity

    Directory of Open Access Journals (Sweden)

    Joe Devasahayam

    2015-01-01

    Full Text Available C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD, focal segmental glomerulosclerosis (FSGS, and proliferative glomerulonephritis. Clinical presentation is also diverse, and ranges from asymptomatic hematuria or proteinuria to frank nephritic or nephrotic syndrome in both children and adults. Hypertension and renal insufficiency at the time of diagnosis are common findings. Optimal treatment is not clear and is usually guided by the underlying light microscopic lesion. Corticosteroids are the mainstay of treatment, with immunosuppressive agents reserved for steroid resistant cases. The presence of nephrotic syndrome and FSGS appear to predict adverse outcomes as opposed to favorable outcomes in those with MCD. Further research is needed to establish C1q nephropathy as a universally recognized distinct clinical entity. In this paper, we discuss the current understanding of pathogenesis, histopathology, clinical features, therapeutic options, and outcomes of C1q nephropathy.

  2. Guide to good practices for operations aspects of unique processes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Aspects of Facility Chemistry and Unique Processes, Chapter XIII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing employee training and facility management programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Aspects of Unique Processes is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for all personnel to coordinate interrelated activities affecting unique processes.

  3. NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene

    International Nuclear Information System (INIS)

    Mattila, Henna; Schindler, Martin; Isotalo, Jarkko; Ikonen, Tarja; Vihinen, Mauno; Oja, Hannu; Tammela, Teuvo LJ; Wahlfors, Tiina; Schleutker, Johanna

    2011-01-01

    Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPCX1 at Xq27-q28, but due to the complex structure of the region, the susceptibility gene has not yet been identified. In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PC) patients and their healthy brothers were selected from a group of HPCX1-linked families. Expression analyses were done using Agilent 44 K oligoarrays, and selected genes were screened for mutations by direct sequencing. In addition, microRNA expression levels in the lymphoblastic cells were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to PC. Seventeen genes were selected for resequencing based on the NMD array, but no truncating mutations were found. The most interesting variant was MAGEC1 p.Met1?. An association was seen between the variant and unselected PC (OR = 2.35, 95% CI = 1.10-5.02) and HPC (OR = 3.38, 95% CI = 1.10-10.40). miRNA analysis revealed altogether 29 miRNAs with altered expression between the PC cases and controls. miRNA target analysis revealed that 12 of them also had possible target sites in the MAGEC1 gene. These miRNAs were selected for validation process including four miRNAs located in the X chromosome. The expressions of 14 miRNAs were validated in families that contributed to the significant signal differences in Agilent arrays. Further functional studies are needed to fully understand the possible contribution of these miRNAs and MAGEC1 start codon variant to PC

  4. Uniqueness of solution to a stationary boundary kinetic problem

    International Nuclear Information System (INIS)

    Zhykharsky, A.V.

    1992-01-01

    The paper treats the question of uniqueness of solution to the boundary kinetic problem. This analysis is based on the accurate solutions to the stationary one-dimensional boundary kinetic problem for the limited plasma system. In the paper a simplified problem statement is used (no account is taken of the external magnetic field, a simplest form of boundary conditions is accepted) which, however, covers all features of the problem considered. Omitting the details of the conclusion we will write a set of Vlasov stationary kinetic equations for the cases of plane, cylindrical and spherical geometry of the problem. (author) 1 ref

  5. Genetic Diversity among Rhizobium leguminosarum bv. Trifolii Strains Revealed by Allozyme and Restriction Fragment Length Polymorphism Analyses

    Science.gov (United States)

    Demezas, David H.; Reardon, Terry B.; Watson, John M.; Gibson, Alan H.

    1991-01-01

    Allozyme electrophoresis and restriction fragment length polymorphism (RFLP) analyses were used to examine the genetic diversity of a collection of 18 Rhizobium leguminosarum bv. trifolii, 1 R. leguminosarum bv. viciae, and 2 R. meliloti strains. Allozyme analysis at 28 loci revealed 16 electrophoretic types. The mean genetic distance between electrophoretic types of R. leguminosarum and R. meliloti was 0.83. Within R. leguminosarum, the single strain of bv. viciae differed at an average of 0.65 from strains of bv. trifolii, while electrophoretic types of bv. trifolii differed at a range of 0.23 to 0.62. Analysis of RFLPs around two chromosomal DNA probes also delineated 16 unique RFLP patterns and yielded genetic diversity similar to that revealed by the allozyme data. Analysis of RFLPs around three Sym (symbiotic) plasmid-derived probes demonstrated that the Sym plasmids reflect genetic divergence similar to that of their bacterial hosts. The large genetic distances between many strains precluded reliable estimates of their genetic relationships. PMID:16348600

  6. Peniciadametizine A, a Dithiodiketopiperazine with a Unique Spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] Skeleton, and a Related Analogue, Peniciadametizine B, from the Marine Sponge-Derived Fungus Penicillium adametzioides

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2015-06-01

    Full Text Available Peniciadametizine A (1; a new dithiodiketopiperazine derivative possessing a unique spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton, together with a highly oxygenated new analogue, peniciadametizine B (2; as well as two known compounds, brasiliamide A (3; and viridicatumtoxin (4, were isolated and identified from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge. The unambiguous assignment of the relative and absolute configuration for the spiro center C-2 of compound 1 was solved by the combination of NMR and ECD measurements with Density-Functional Theory (DFT conformational analysis and Time-Dependent Density-Functional Theory-Electronic Circular Dichroism (TDDFT-ECD calculations. The spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton of 1 has not been reported yet among natural products and the biosynthetic pathway for 1 and 2 was discussed. Compounds 1 and 2 showed inhibitory activity against the pathogenic fungus Alternaria brassicae.

  7. A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

    Science.gov (United States)

    Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

    2006-01-01

    The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

  8. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  9. Uniqueness plots: A simple graphical tool for identifying poor peak fits in X-ray photoelectron spectroscopy

    Science.gov (United States)

    Singh, Bhupinder; Diwan, Anubhav; Jain, Varun; Herrera-Gomez, Alberto; Terry, Jeff; Linford, Matthew R.

    2016-11-01

    Peak fitting is an essential part of X-ray photoelectron spectroscopy (XPS) narrow scan analysis, and the Literature contains both good and bad examples of peak fitting. A common cause of poor peak fitting is the inclusion of too many fit parameters, often without a sound chemical and/or physical basis for them, and/or the failure to reasonably constrain them. Under these conditions, fit parameters are often correlated, and therefore lacking in statistical meaning. Here we introduce the uniqueness plot as a simple graphical tool for identifying bad peak fits in XPS, i.e., fit parameter correlation. These plots are widely used in spectroscopic ellipsometry. We illustrate uniqueness plots with two data sets: a C 1s narrow scan from ozone-treated carbon nanotube forests and an Si 2p narrow scan from an air-oxidized silicon wafer. For each fit, we consider different numbers of parameters and constraints on them. As expected, the uniqueness plots are parabolic when fewer fit parameters and/or more constraints are applied. However, they fan out and eventually become horizontal lines as more unconstrained parameters are included in the fits. Uniqueness plots are generated by plotting the chi squared (χ2) value for a fit vs. a systematically varied value of a parameter in the fit. The Abbe criterion is also considered as a figure of merit for uniqueness plots in the Supporting Information. We recommend that uniqueness plots be used by XPS practitioners for identifying inappropriate peak fits.

  10. Revealing barriers and facilitators to use a new genetic test: comparison of three user involvement methods.

    Science.gov (United States)

    Rhebergen, Martijn D F; Visser, Maaike J; Verberk, Maarten M; Lenderink, Annet F; van Dijk, Frank J H; Kezic, Sanja; Hulshof, Carel T J

    2012-10-01

    We compared three common user involvement methods in revealing barriers and facilitators from intended users that might influence their use of a new genetic test. The study was part of the development of a new genetic test on the susceptibility to hand eczema for nurses. Eighty student nurses participated in five focus groups (n = 33), 15 interviews (n = 15) or questionnaires (n = 32). For each method, data were collected until saturation. We compared the mean number of items and relevant remarks that could influence the use of the genetic test obtained per method, divided by the number of participants in that method. Thematic content analysis was performed using MAXQDA software. The focus groups revealed 30 unique items compared to 29 in the interviews and 21 in the questionnaires. The interviews produced more items and relevant remarks per participant (1.9 and 8.4 pp) than focus groups (0.9 and 4.8 pp) or questionnaires (0.7 and 2.3 pp). All three involvement methods revealed relevant barriers and facilitators to use a new genetic test. Focus groups and interviews revealed substantially more items than questionnaires. Furthermore, this study suggests a preference for the use of interviews because the number of items per participant was higher than for focus groups and questionnaires. This conclusion may be valid for other genetic tests as well.

  11. The Uniqueness of Milton Friedman

    OpenAIRE

    J. Daniel Hammond

    2013-01-01

    That there is no Milton Friedman today is not a mystery; the mystery is how Milton Friedman could have been. The facts of Friedman’s biography make him unique among twentieth-century public figures. He had extensive knowledge and expertise in mathematics and statistics. Yet he became a critic of ‘formal’ theory, exemplified by mathematical economics, that failed to engage with real-world facts and data, and of econometric modeling that presumed more knowledge of economic structure than Friedm...

  12. Multistage bioassociation of uranium onto an extremely halophilic archaeon revealed by a unique combination of spectroscopic and microscopic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Bader, Miriam; Müller, Katharina; Foerstendorf, Harald; Drobot, Björn [Helmholtz-Zentrum Dresden – Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden (Germany); Schmidt, Matthias; Musat, Niculina [Helmholtz Centre for Environmental Research–UFZ, Department of Isotope Biogeochemistry, Permoserstraße 15, 04318 Leipzig (Germany); Swanson, Juliet S.; Reed, Donald T. [Los Alamos National Laboratory, Repository Science and Operations, 1400 University Drive, Carlsbad, NM, 88220 (United States); Stumpf, Thorsten [Helmholtz-Zentrum Dresden – Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden (Germany); Cherkouk, Andrea, E-mail: a.cherkouk@hzdr.de [Helmholtz-Zentrum Dresden – Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden (Germany)

    2017-04-05

    Highlights: • First prolonged kinetics study of uranium to halophilic archaea was performed. • An atypical time-dependent bioassociation behavior of uranium was observed. • Unique combination of spectroscopic and microscopic methods was used. • In situ ATR FT-IR showed association of U(VI) to phosphoryl and carboxylate groups. • Time-dependent changes of U(VI) localization could be monitored by SEM/EDX. - Abstract: The interactions of two extremely halophilic archaea with uranium were investigated at high ionic strength as a function of time, pH and uranium concentration. Halobacterium noricense DSM-15987 and Halobacterium sp. putatively noricense, isolated from the Waste Isolation Pilot Plant repository, were used for these investigations. The kinetics of U(VI) bioassociation with both strains showed an atypical multistage behavior, meaning that after an initial phase of U(VI) sorption, an unexpected interim period of U(VI) release was observed, followed by a slow reassociation of uranium with the cells. By applying in situ attenuated total reflection Fourier-transform infrared spectroscopy, the involvement of phosphoryl and carboxylate groups in U(VI) complexation during the first biosorption phase was shown. Differences in cell morphology and uranium localization become visible at different stages of the bioassociation process, as shown with scanning electron microscopy in combination with energy dispersive X-ray spectroscopy. Our results demonstrate for the first time that association of uranium with the extremely halophilic archaeon is a multistage process, beginning with sorption and followed by another process, probably biomineralization.

  13. Multistage bioassociation of uranium onto an extremely halophilic archaeon revealed by a unique combination of spectroscopic and microscopic techniques

    International Nuclear Information System (INIS)

    Bader, Miriam; Müller, Katharina; Foerstendorf, Harald; Drobot, Björn; Schmidt, Matthias; Musat, Niculina; Swanson, Juliet S.; Reed, Donald T.; Stumpf, Thorsten; Cherkouk, Andrea

    2017-01-01

    Highlights: • First prolonged kinetics study of uranium to halophilic archaea was performed. • An atypical time-dependent bioassociation behavior of uranium was observed. • Unique combination of spectroscopic and microscopic methods was used. • In situ ATR FT-IR showed association of U(VI) to phosphoryl and carboxylate groups. • Time-dependent changes of U(VI) localization could be monitored by SEM/EDX. - Abstract: The interactions of two extremely halophilic archaea with uranium were investigated at high ionic strength as a function of time, pH and uranium concentration. Halobacterium noricense DSM-15987 and Halobacterium sp. putatively noricense, isolated from the Waste Isolation Pilot Plant repository, were used for these investigations. The kinetics of U(VI) bioassociation with both strains showed an atypical multistage behavior, meaning that after an initial phase of U(VI) sorption, an unexpected interim period of U(VI) release was observed, followed by a slow reassociation of uranium with the cells. By applying in situ attenuated total reflection Fourier-transform infrared spectroscopy, the involvement of phosphoryl and carboxylate groups in U(VI) complexation during the first biosorption phase was shown. Differences in cell morphology and uranium localization become visible at different stages of the bioassociation process, as shown with scanning electron microscopy in combination with energy dispersive X-ray spectroscopy. Our results demonstrate for the first time that association of uranium with the extremely halophilic archaeon is a multistage process, beginning with sorption and followed by another process, probably biomineralization.

  14. High Blood Pressure: Unique to Older Adults

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z High Blood Pressure Hypertension Unique to Older Adults This section provides ... Pressure Targets are Different for Very Old Adults High blood pressure (also called hypertension) increases your chance of having ...

  15. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin

    Directory of Open Access Journals (Sweden)

    Fang Zhao

    2016-02-01

    Full Text Available Voltage-gated sodium channels (VGSCs are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1–Nav1.9, Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR membrane potential (FMP blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  16. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin.

    Science.gov (United States)

    Zhao, Fang; Li, Xichun; Jin, Liang; Zhang, Fan; Inoue, Masayuki; Yu, Boyang; Cao, Zhengyu

    2016-02-16

    Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  17. Introducing COSS: A new and unique oil spill research facility

    International Nuclear Information System (INIS)

    Kitchen, R. B.; Bonner, J. S.; Autenrieth, R. L.; Donnelly, K. C.; Ernest, A. N. S.

    1997-01-01

    A new oil spill research facility in Corpus Christi, Texas began operation in April 1997 to address the appropriate use, application and effectiveness of chemical, physical and biological oil spill response agents. The Coastal Oil Spill Simulation (COSS) facility consists of nine meso scale wave tanks and will offer to science and industry a unique opportunity to spill oil in a controlled environment and to study fate, transport and remediation of oil releases in simulated coastal, intertidal, lagunal, channel and porous media. 1 ref

  18. Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry

    Directory of Open Access Journals (Sweden)

    Fogarty Keir H

    2010-09-01

    Full Text Available Abstract Background Human T-lymphotropic virus type 1 (HTLV-1 is an important human retrovirus that is a cause of adult T-cell leukemia/lymphoma. While an important human pathogen, the details regarding virus replication cycle, including the nature of HTLV-1 particles, remain largely unknown due to the difficulties in propagating the virus in tissue culture. In this study, we created a codon-optimized HTLV-1 Gag fused to an EYFP reporter as a model system to quantitatively analyze HTLV-1 particles released from producer cells. Results The codon-optimized Gag led to a dramatic and highly robust level of Gag expression as well as virus-like particle (VLP production. The robust level of particle production overcomes previous technical difficulties with authentic particles and allowed for detailed analysis of particle architecture using two novel methodologies. We quantitatively measured the diameter and morphology of HTLV-1 VLPs in their native, hydrated state using cryo-transmission electron microscopy (cryo-TEM. Furthermore, we were able to determine HTLV-1 Gag stoichiometry as well as particle size with the novel biophysical technique of fluorescence fluctuation spectroscopy (FFS. The average HTLV-1 particle diameter determined by cryo-TEM and FFS was 71 ± 20 nm and 75 ± 4 nm, respectively. These values are significantly smaller than previous estimates made of HTLV-1 particles by negative staining TEM. Furthermore, cryo-TEM reveals that the majority of HTLV-1 VLPs lacks an ordered structure of the Gag lattice, suggesting that the HTLV-1 Gag shell is very likely to be organized differently compared to that observed with HIV-1 Gag in immature particles. This conclusion is supported by our observation that the average copy number of HTLV-1 Gag per particle is estimated to be 510 based on FFS, which is significantly lower than that found for HIV-1 immature virions. Conclusions In summary, our studies represent the first quantitative biophysical

  19. Astronomers Reveal Extinct Extra-Terrestrial Fusion Reactor

    Science.gov (United States)

    2004-06-01

    An international team of astronomers, studying the left-over remnants of stars like our own Sun, have found a remarkable object where the nuclear reactor that once powered it has only just shut down. This star, the hottest known white dwarf, H1504+65, seems to have been stripped of its entire outer regions during its death throes leaving behind the core that formed its power plant. Scientists from the United Kingdom, Germany and the USA focused two of NASA's space telescopes, the Chandra X-ray Observatory and the Far Ultraviolet Spectroscopic Explorer (FUSE), onto H1504+65 to probe its composition and measure its temperature. The data revealed that the stellar surface is extremely hot, 200,000 degrees, and is virtually free of hydrogen and helium, something never before observed in any star. Instead, the surface is composed mainly of carbon and oxygen, the 'ashes' of the fusion of helium in a nuclear reactor. An important question we must answer is why has this unique star lost the hydrogen and helium, which usually hide the stellar interior from our view? Professor Martin Barstow (University of Leicester) said. 'Studying the nature of the ashes of dead stars give us important clues as to how stars like the Sun live their lives and eventually die. The nuclear waste of carbon and oxygen produced in the process are essential elements for life and are eventually recycled into interstellar space to form new stars, planets and, possibly, living beings.' Professor Klaus Werner (University of Tübingen) said. 'We realized that this star has, on astronomical time scales, only very recently shut down nuclear fusion (about a hundred years ago). We clearly see the bare, now extinct reactor that once powered a bright giant star.' Dr Jeffrey Kruk (Johns Hopkins University) said: 'Astronomers have long predicted that many stars would have carbon-oxygen cores near the end of their lives, but I never expected we would actually be able to see one. This is a wonderful opportunity to

  20. Combining complexity measures of EEG data: multiplying measures reveal previously hidden information.

    Science.gov (United States)

    Burns, Thomas; Rajan, Ramesh

    2015-01-01

    Many studies have noted significant differences among human electroencephalograph (EEG) results when participants or patients are exposed to different stimuli, undertaking different tasks, or being affected by conditions such as epilepsy or Alzheimer's disease. Such studies often use only one or two measures of complexity and do not regularly justify their choice of measure beyond the fact that it has been used in previous studies. If more measures were added to such studies, however, more complete information might be found about these reported differences. Such information might be useful in confirming the existence or extent of such differences, or in understanding their physiological bases. In this study we analysed publically-available EEG data using a range of complexity measures to determine how well the measures correlated with one another. The complexity measures did not all significantly correlate, suggesting that different measures were measuring unique features of the EEG signals and thus revealing information which other measures were unable to detect. Therefore, the results from this analysis suggests that combinations of complexity measures reveal unique information which is in addition to the information captured by other measures of complexity in EEG data. For this reason, researchers using individual complexity measures for EEG data should consider using combinations of measures to more completely account for any differences they observe and to ensure the robustness of any relationships identified.

  1. Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer; Iversen, Line V

    2013-01-01

    To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.......To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases....

  2. Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein

    Directory of Open Access Journals (Sweden)

    Barbara Mojsa

    2014-05-01

    Full Text Available Mcl-1 is an anti-apoptotic protein of the Bcl-2 family that is essential for the survival of multiple cell lineages and that is highly amplified in human cancer. Under physiological conditions, Mcl-1 expression is tightly regulated at multiple levels, involving transcriptional, post-transcriptional and post-translational processes. Ubiquitination of Mcl-1, that targets it for proteasomal degradation, allows for rapid elimination of the protein and triggering of cell death, in response to various cellular events. In the last decade, a number of studies have elucidated different pathways controlling Mcl-1 ubiquitination and degradation. Four different E3 ubiquitin-ligases (e.g., Mule, SCFβ-TrCP, SCFFbw7 and Trim17 and one deubiquitinase (e.g., USP9X, that respectively mediate and oppose Mcl-1 ubiquitination, have been formerly identified. The interaction between Mule and Mcl-1 can be modulated by other Bcl-2 family proteins, while recognition of Mcl-1 by the other E3 ubiquitin-ligases and deubiquitinase is influenced by phosphorylation of specific residues in Mcl-1. The protein kinases and E3 ubiquitin-ligases that are involved in the regulation of Mcl-1 stability vary depending on the cellular context, highlighting the complexity and pivotal role of Mcl-1 regulation. In this review, we attempt to recapitulate progress in understanding Mcl-1 regulation by the ubiquitin-proteasome system.

  3. Addressing Unison and Uniqueness of Reliability and Safety for Better Integration

    Science.gov (United States)

    Huang, Zhaofeng; Safie, Fayssal

    2015-01-01

    For a long time, both in theory and in practice, safety and reliability have not been clearly differentiated, which leads to confusion, inefficiency, and sometime counter-productive practices in executing each of these two disciplines. It is imperative to address the uniqueness and the unison of these two disciplines to help both disciplines become more effective and to promote a better integration of the two for enhancing safety and reliability in our products as an overall objective. There are two purposes of this paper. First, it will investigate the uniqueness and unison of each discipline and discuss the interrelationship between the two for awareness and clarification. Second, after clearly understanding the unique roles and interrelationship between the two in a product design and development life cycle, we offer suggestions to enhance the disciplines with distinguished and focused roles, to better integrate the two, and to improve unique sets of skills and tools of reliability and safety processes. From the uniqueness aspect, the paper identifies and discusses the respective uniqueness of reliability and safety from their roles, accountability, nature of requirements, technical scopes, detailed technical approaches, and analysis boundaries. It is misleading to equate unreliable to unsafe, since a safety hazard may or may not be related to the component, sub-system, or system functions, which are primarily what reliability addresses. Similarly, failing-to-function may or may not lead to hazard events. Examples will be given in the paper from aerospace, defense, and consumer products to illustrate the uniqueness and differences between reliability and safety. From the unison aspect, the paper discusses what the commonalities between reliability and safety are, and how these two disciplines are linked, integrated, and supplemented with each other to accomplish the customer requirements and product goals. In addition to understanding the uniqueness in

  4. Haplotype structure around Bru1 reveals a narrow genetic basis for brown rust resistance in modern sugarcane cultivars.

    Science.gov (United States)

    Costet, L; Le Cunff, L; Royaert, S; Raboin, L-M; Hervouet, C; Toubi, L; Telismart, H; Garsmeur, O; Rousselle, Y; Pauquet, J; Nibouche, S; Glaszmann, J-C; Hoarau, J-Y; D'Hont, A

    2012-09-01

    Modern sugarcane cultivars (Saccharum spp., 2n = 100-130) are high polyploid, aneuploid and of interspecific origin. A major gene (Bru1) conferring resistance to brown rust, caused by the fungus Puccinia melanocephala, has been identified in cultivar R570. We analyzed 380 modern cultivars and breeding materials covering the worldwide diversity with 22 molecular markers genetically linked to Bru1 in R570 within a 8.2 cM segment. Our results revealed a strong LD in the Bru1 region and strong associations between most of the markers and rust resistance. Two PCR markers, that flank the Bru1-bearing segment, were found completely associated with one another and only in resistant clones representing efficient molecular diagnostic for Bru1. On this basis, Bru1 was inferred in 86 % of the 194 resistant sugarcane accessions, revealing that it constitutes the main source of brown rust resistance in modern cultivars. Bru1 PCR diagnostic markers should be particularly useful to identify cultivars with potentially alternative sources of resistance to diversify the basis of brown rust resistance in breeding programs.

  5. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis.

    Science.gov (United States)

    Wen, Chengping; Zheng, Zhijun; Shao, Tiejuan; Liu, Lin; Xie, Zhijun; Le Chatelier, Emmanuelle; He, Zhixing; Zhong, Wendi; Fan, Yongsheng; Zhang, Linshuang; Li, Haichang; Wu, Chunyan; Hu, Changfeng; Xu, Qian; Zhou, Jia; Cai, Shunfeng; Wang, Dawei; Huang, Yun; Breban, Maxime; Qin, Nan; Ehrlich, Stanislav Dusko

    2017-07-27

    The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers. Alterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.

  6. “Clavicular duplication causing thoracic outlet obstruction”: Unique ...

    African Journals Online (AJOL)

    A 22‑year‑old female student reported with features of neurogenic thoracic outlet syndrome mainly involving C8‑T1 components of the brachial plexus, seemingly originating from involvement in costo‑clavicular space. Radiograph of the shoulder revealed clavicular duplication. Neuro‑physiological studies corroborated the ...

  7. Arm coordination in octopus crawling involves unique motor control strategies.

    Science.gov (United States)

    Levy, Guy; Flash, Tamar; Hochner, Binyamin

    2015-05-04

    To cope with the exceptional computational complexity that is involved in the control of its hyper-redundant arms [1], the octopus has adopted unique motor control strategies in which the central brain activates rather autonomous motor programs in the elaborated peripheral nervous system of the arms [2, 3]. How octopuses coordinate their eight long and flexible arms in locomotion is still unknown. Here, we present the first detailed kinematic analysis of octopus arm coordination in crawling. The results are surprising in several respects: (1) despite its bilaterally symmetrical body, the octopus can crawl in any direction relative to its body orientation; (2) body and crawling orientation are monotonically and independently controlled; and (3) contrasting known animal locomotion, octopus crawling lacks any apparent rhythmical patterns in limb coordination, suggesting a unique non-rhythmical output of the octopus central controller. We show that this uncommon maneuverability is derived from the radial symmetry of the arms around the body and the simple pushing-by-elongation mechanism by which the arms create the crawling thrust. These two together enable a mechanism whereby the central controller chooses in a moment-to-moment fashion which arms to recruit for pushing the body in an instantaneous direction. Our findings suggest that the soft molluscan body has affected in an embodied way [4, 5] the emergence of the adaptive motor behavior of the octopus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Word from the CSO - CERN’s unique scientific breadth

    CERN Multimedia

    2008-01-01

    Whilst we are all clearly focused on completion of the LHC and the detectors around it and look forward to a successful start of operations later this year, we should not forget that CERN has yet more to offer in addition to this highest priority programme ‘at the energy frontier’. Indeed, CERN also attracts a large scientific community seizing the opportunities offered by its other facilities. Sometimes I wonder whether we are not too modest and should not emphasize more CERN’s unique scientific breadth. ISOLDE, at the PS Booster, relies on innovative techniques to produce results at the forefront of nuclear physics very cost-effectively. nTOF has provided unique measurements of interest to nuclear technology, nuclear astrophysics and basic nuclear physics, and still has an ambitious programme ahead of it after refurbishment of the target. Another unique facility is the Antiproton Decelerator, at which the study of antimatter is being pursued with ingenious experiment...

  9. TDRSS S-shuttle unique receiver equipment

    Science.gov (United States)

    Weinberg, A.; Schwartz, J. J.; Spearing, R.

    1985-01-01

    Beginning with STS-9, the Tracking and Date Relay Satellite system (TDRSS) will start providing S- and Ku-band communications and tracking support to the Space Shuttle and its payloads. The most significant element of this support takes place at the TDRSS White Sands Ground Terminal, which processes the Shuttle return link S- and Ku-band signals. While Ku-band hardware available to other TDRSS users is also applied to Ku-Shuttle, stringent S-Shuttle link margins have precluded the application of the standard TDRSS S-band processing equipment to S-Shuttle. It was therfore found necessary to develop a unique S-Shuttle Receiver that embodies state-of-the-art digital technology and processing techniques. This receiver, developed by Motorola, Inc., enhances link margins by 1.5 dB relative to the standard S-band equipment and its bit error rate performance is within a few tenths of a dB of theory. An overview description of the Space Shuttle Receiver Equipment (SSRE) is presented which includes the presentation of block diagrams and salient design features. Selected, measured performance results are also presented.

  10. Duality based direct resolution of unique profiles using zero concentration region information.

    Science.gov (United States)

    Tavakkoli, Elnaz; Rajkó, Róbert; Abdollahi, Hamid

    2018-07-01

    Self Modeling Curve Resolution (SMCR) is a class of techniques concerned with estimating pure profiles underlying a set of measurements on chemical systems. In general, the estimated profiles are ambiguous (non-unique) except if some special conditions fulfilled. Implementing the adequate information can reduce the so-called rotational ambiguity effectively, and in the most desirable cases lead to the unique solution. Therefore, studies on circumstances resulting in unique solution are of particular importance. The conditions of unique solution can particularly be studied based on duality principle. In bilinear chemical (e.g., spectroscopic) data matrix, there is a natural duality between its row and column vector spaces using minimal constraints (non-negativity of concentrations and absorbances). In this article, the conditions of the unique solution according to duality concept and using zero concentration region information is intended to show. A simulated dataset of three components and an experimental system with synthetic mixtures containing three amino acids tyrosine, phenylalanine and tryptophan are analyzed. It is shown that in the presence of sufficient information, the reliable unique solution is obtained that is valuable in analytical qualification and for quantitative verification analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Quantitative Proteomics Reveals the Regulatory Networks of Circular RNA CDR1as in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Yang, Xue; Xiong, Qian; Wu, Ying; Li, Siting; Ge, Feng

    2017-10-06

    Circular RNAs (circRNAs), a class of widespread endogenous RNAs, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Cerebellar-degeneration-related protein 1 antisense RNA (CDR1as), an oncogenic circRNA, is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CDR1as functions in HCC remain unclear. Here we explored the functions of CDR1as and searched for CDR1as-regulated proteins in HCC cells. A quantitative proteomics strategy was employed to globally identify CDR1as-regulated proteins in HCC cells. In total, we identified 330 differentially expressed proteins (DEPs) upon enhanced CDR1as expression in HepG2 cells, indicating that they could be proteins regulated by CDR1as. Bioinformatic analysis revealed that many DEPs were involved in cell proliferation and the cell cycle. Further functional studies of epidermal growth factor receptor (EGFR) found that CDR1as exerts its effects on cell proliferation at least in part through the regulation of EGFR expression. We further confirmed that CDR1as could inhibit the expression of microRNA-7 (miR-7). EGFR is a validated target of miR-7; therefore, CDR1as may exert its function by regulating EGFR expression via targeting miR-7 in HCC cells. Taken together, we revealed novel functions and underlying mechanisms of CDR1as in HCC cells. This study serves as the first proteome-wide analysis of a circRNA-regulated protein in cells and provides a reliable and highly efficient method for globally identifying circRNA-regulated proteins.

  12. In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway

    Science.gov (United States)

    Ning, Jiying; Erdemci-Tandogan, Gonca; Yufenyuy, Ernest L.; Wagner, Jef; Himes, Benjamin A.; Zhao, Gongpu; Aiken, Christopher; Zandi, Roya; Zhang, Peijun

    2016-12-01

    HIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. There are two competing models for the process of forming the mature HIV-1 core: the disassembly and de novo reassembly model and the non-diffusional displacive model. To study the maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature particles and assembled virus-like particles with recombinant HIV-1 protease and monitor the process with biochemical assays and cryoEM structural analysis in parallel. Processing of Gag in vitro is accurate and efficient and results in both soluble capsid protein and conical or tubular capsid assemblies, seemingly converted from immature Gag particles. Computer simulations further reveal probable assembly pathways of HIV-1 capsid formation. Combining the experimental data and computer simulations, our results suggest a sequential combination of both displacive and disassembly/reassembly processes for HIV-1 maturation.

  13. Probing the Unique Role of Gallium in Amorphous Oxide Semiconductors through Structure-Property Relationships

    Energy Technology Data Exchange (ETDEWEB)

    Moffitt, Stephanie L.; Zhu, Qimin; Ma, Qing; Falduto, Allison F.; Buchholz, D. Bruce; Chang, Robert P.H.; Mason, Thomas O.; Medvedeva, Julia E.; Marks, Tobin J.; Bedzyk, Michael J. (NWU); (MUST)

    2017-09-01

    This study explores the unique role of Ga in amorphous (a-) In[BOND]Ga[BOND]O oxide semiconductors through combined theory and experiment. It reveals substitutional effects that have not previously been attributed to Ga, and that are investigated by examining how Ga influences structure–property relationships in a series of pulsed laser deposited a-In[BOND]Ga[BOND]O thin films. Element-specific structural studies (X-ray absorption and anomalous scattering) show good agreement with the results of ab initio molecular dynamics simulations. This structural knowledge is used to understand the results of air-annealing and Hall effect electrical measurements. The crystallization temperature of a-IO is shown to increase by as much as 325 °C on substituting Ga for In. This increased thermal stability is understood on the basis of the large changes in local structure that Ga undergoes, as compared to In, during crystallization. Hall measurements reveal an initial sharp drop in both carrier concentration and mobility with increasing Ga incorporation, which moderates at >20 at% Ga content. This decline in both the carrier concentration and mobility with increasing Ga is attributed to dilution of the charge-carrying In[BOND]O matrix and to increased structural disorder. The latter effect saturates at high at% Ga.

  14. The end of the unique myocardial band

    DEFF Research Database (Denmark)

    MacIver, David H; Partridge, John B; Agger, Peter

    2018-01-01

    Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

  15. Solitary intraosseous neurofibroma: Report of a unique case

    Directory of Open Access Journals (Sweden)

    Sagar Satish Jangam

    2014-01-01

    Full Text Available Neural tumors located centrally in jaw bones are relatively rare compared with soft tissue neurofibromas. Less than 50 cases have been reported in the literature with a predilection for mandible. This article aims to elucidate a unique case of intraosseous neurofibroma of mandible in a 62-year-old edentulous female patient associated with facial asymmetry due to the swelling extending from the right body of mandible to left body of mandible. The uniqueness of this case is related to the age and extensiveness of this lesion. A review of clinical, radiographic, histological, and immunohistochemical features, and the surgical management pertaining to this case are discussed along with a review of the literature.

  16. Probing the Unique Contributions of Self-Concept, Task Values, and Their Interactions Using Multiple Value Facets and Multiple Academic Outcomes

    Directory of Open Access Journals (Sweden)

    Jiesi Guo

    2016-01-01

    Full Text Available Drawing on expectancy-value theory, the present study examined the unique contributions of the four major value beliefs and self-concept on achievement, self-reported effort, and teacher-rated behavioral engagement in mathematics. In particular, we examined the multiplicative effects of self-concept and task values on educational outcomes using the latent moderated structural equation approach. Participants were 1,868 German ninth-grade students. The data analyses relied on a higher-order structure of value beliefs, which is suited to parsing the differential patterns of predictive relations for different value beliefs. The findings revealed that (a self-concept was more predictive of achievement, whereas value beliefs were more predictive of self-rated effort; (b self-concept and value beliefs emerged as equally important predictors of teacher-reported engagement; (c among the four value beliefs, achievement was more associated with low cost, whereas effort was more associated with attainment value; and (d latent interactions between self-concept and value beliefs predicted the three outcomes synergistically.

  17. Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland.

    Science.gov (United States)

    Shilaih, Mohaned; Marzel, Alex; Yang, Wan Lin; Scherrer, Alexandra U; Schüpbach, Jörg; Böni, Jürg; Yerly, Sabine; Hirsch, Hans H; Aubert, Vincent; Cavassini, Matthias; Klimkait, Thomas; Vernazza, Pietro L; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F; Kouyos, Roger

    2016-06-14

    Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8-2.1), female gender (OR: 1.6; 95% CI: 1.4-1.7), black ethnicity (OR: 1.9; 95% CI: 1.7-2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6-2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS'. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance.

  18. Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria

    NARCIS (Netherlands)

    Salzman, NH; de Jong, H; Paterson, Y; Harmsen, HJM; Welling, GW; Bos, NA

    2002-01-01

    Total genomic DNA from samples of intact mouse small intestine, large intestine, caecum and faeces was used as template for PCR amplification of 16S rRNA gene sequences with conserved bacterial primers. Phylogenetic analysis of the amplification products revealed 40 unique 16S rDNA sequences. Of

  19. Antiproliferative Effects of Bacillus coagulans Unique IS2 in Colon Cancer Cells.

    Science.gov (United States)

    Madempudi, Ratna Sudha; Kalle, Arunasree M

    2017-10-01

    In the present study, the in vitro anticancer (antiproliferative) effects of Bacillus coagulans Unique IS2 were evaluated on human colon cancer (COLO 205), cervical cancer (HeLa), and chronic myeloid leukemia (K562) cell lines with a human embryonic kidney cell line (HEK 293T) as noncancerous control cells. The Cytotoxicity assay (MTT) clearly demonstrated a 22%, 31.7%, and 19.5% decrease in cell proliferation of COLO 205, HeLa, and K562 cells, respectively, when compared to the noncancerous HEK 293T cells. Normal phase-contrast microscopic images clearly suggested that the mechanism of cell death is by apoptosis. To further confirm the induction of apoptosis by Unique IS2, the sub-G0-G1 peak of the cell cycle was quantified using a flow cytometer and the data indicated 40% of the apoptotic cells in Unique IS2-treated COLO cells when compared with their untreated control cells. The Western blot analysis showed an increase in pro-apoptotic protein BAX, decrease in antiapoptotic protein, Bcl2, decrease in mitochondrial membrane potential, increase in cytochrome c release, increase in Caspase 3 activity, and cleavage of poly(ADP-ribose) polymerase. The present study suggests that the heat-killed culture supernatant of B. coagulans can be more effective in inducing apoptosis of colon cancer cells and that can be considered for adjuvant therapy in the treatment of colon carcinoma.

  20. Unique double concentric ring organization of light harvesting complexes in Gemmatimonas phototrophica.

    Directory of Open Access Journals (Sweden)

    Marko Dachev

    2017-12-01

    Full Text Available The majority of life on Earth depends directly or indirectly on the sun as a source of energy. The initial step of photosynthesis is facilitated by light-harvesting complexes, which capture and transfer light energy into the reaction centers (RCs. Here, we analyzed the organization of photosynthetic (PS complexes in the bacterium G. phototrophica, which so far is the only phototrophic representative of the bacterial phylum Gemmatimonadetes. The isolated complex has a molecular weight of about 800 ± 100 kDa, which is approximately 2 times larger than the core complex of Rhodospirillum rubrum. The complex contains 62.4 ± 4.7 bacteriochlorophyll (BChl a molecules absorbing in 2 distinct infrared absorption bands with maxima at 816 and 868 nm. Using femtosecond transient absorption spectroscopy, we determined the energy transfer time between these spectral bands as 2 ps. Single particle analyses of the purified complexes showed that they were circular structures with an outer diameter of approximately 18 nm and a thickness of 7 nm. Based on the obtained, we propose that the light-harvesting complexes in G. phototrophica form 2 concentric rings surrounding the type 2 RC. The inner ring (corresponding to the B868 absorption band is composed of 15 subunits and is analogous to the inner light-harvesting complex 1 (LH1 in purple bacteria. The outer ring is composed of 15 more distant BChl dimers with no or slow energy transfer between them, resulting in the B816 absorption band. This completely unique and elegant organization offers good structural stability, as well as high efficiency of light harvesting. Our results reveal that while the PS apparatus of Gemmatimonadetes was acquired via horizontal gene transfer from purple bacteria, it later evolved along its own pathway, devising a new arrangement of its light harvesting complexes.

  1. Unique Features of Halophilic Proteins.

    Science.gov (United States)

    Arakawa, Tsutomu; Yamaguchi, Rui; Tokunaga, Hiroko; Tokunaga, Masao

    2017-01-01

    Proteins from moderate and extreme halophiles have unique characteristics. They are highly acidic and hydrophilic, similar to intrinsically disordered proteins. These characteristics make the halophilic proteins soluble in water and fold reversibly. In addition to reversible folding, the rate of refolding of halophilic proteins from denatured structure is generally slow, often taking several days, for example, for extremely halophilic proteins. This slow folding rate makes the halophilic proteins a novel model system for folding mechanism analysis. High solubility and reversible folding also make the halophilic proteins excellent fusion partners for soluble expression of recombinant proteins.

  2. The unique relationship between fear of cognitive dyscontrol and self-reports of problematic drinking.

    Science.gov (United States)

    Koven, Nancy S; Heller, Wendy; Miller, Gregory A

    2005-03-01

    Research has established positive associations between anxiety sensitivity (AS) and problematic drinking in clinical samples. The present study confirmed this relationship in a nonclinical sample (N=162) and investigated which AS dimension best predicts self-reports of problematic drinking. Only one AS facet, fear of cognitive dyscontrol (FCC), was associated with symptoms of alcohol dependence, severity of drinking problems, and alcohol-related expectations of global, positive changes, sexual enhancement, and tension reduction. The possible role of depression in these relationships was also evaluated. A series of hierarchical regressions revealed that, when trait anxiety, anxious arousal, and anxious apprehension were statistically removed, depression did not contribute significant variance beyond the effects of FMC and other anxiety measures. Results suggest that FCC is uniquely associated with self-reports of problematic drinking behaviors and attitudes. Implications for tension-reduction models of alcohol are discussed.

  3. Rare events in earth history include the LB1 human skeleton from Flores, Indonesia, as a developmental singularity, not a unique taxon

    Science.gov (United States)

    Eckhardt, Robert B.; Henneberg, Maciej; Weller, Alex S.; Hsü, Kenneth J.

    2014-08-01

    The original centrally defining features of "Homo floresiensis" are based on bones represented only in the single specimen LB1. Initial published values of 380-mL endocranial volume and 1.06-m stature are markedly lower than later attempts to confirm them, and facial asymmetry originally unreported, then denied, has been established by our group and later confirmed independently. Of nearly 200 syndromes in which microcephaly is one sign, more than half include asymmetry as another sign and more than one-fourth also explicitly include short stature. The original diagnosis of the putative new species noted and dismissed just three developmental abnormalities. Subsequent independent attempts at diagnosis (Laron Syndrome, Majewski osteodysplastic primordial dwarfism type II, cretinism) have been hampered a priori by selectively restricted access to specimens, and disparaged a posteriori using data previously unpublished, without acknowledging that all of the independent diagnoses corroborate the patent abnormal singularity of LB1. In this report we establish in detail that even in the absence of a particular syndromic diagnosis, the originally defining features of LB1 do not establish either the uniqueness or normality necessary to meet the formal criteria for a type specimen of a new species. In a companion paper we present a new syndromic diagnosis for LB1.

  4. Esperanto: A Unique Model for General Linguistics.

    Science.gov (United States)

    Dulichenko, Aleksandr D.

    1988-01-01

    Esperanto presents a unique model for linguistic research by allowing the study of language development from project to fully functioning language. Esperanto provides insight into the growth of polysemy and redundancy, as well as into language universals and the phenomenon of social control. (Author/CB)

  5. Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

    Directory of Open Access Journals (Sweden)

    Matthew W Parker

    Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

  6. The glossyhead1 allele of acc1 reveals a principal role for multidomain acetyl-coenzyme a carboxylase in the biosynthesis of cuticular waxes by Arabidopsis

    KAUST Repository

    Lu, Shiyou

    2011-09-23

    A novel mutant of Arabidopsis (Arabidopsis thaliana), having highly glossy inflorescence stems, postgenital fusion in floral organs, and reduced fertility, was isolated from an ethyl methanesulfonate-mutagenized population and designated glossyhead1 (gsd1). The gsd1 locus was mapped to chromosome 1, and the causal gene was identified as a new allele of Acetyl-Coenzyme A Carboxylase1 (ACC1), a gene encoding the main enzyme in cytosolic malonyl-coenzyme A synthesis. This, to our knowledge, is the first mutant allele of ACC1 that does not cause lethality at the seed or early germination stage, allowing for the first time a detailed analysis of ACC1 function in mature tissues. Broad lipid profiling of mature gsd1 organs revealed a primary role for ACC1 in the biosynthesis of the very-long-chain fatty acids (C 20:0 or longer) associated with cuticular waxes and triacylglycerols. Unexpectedly, transcriptome analysis revealed that gsd1 has limited impact on any lipid metabolic networks but instead has a large effect on environmental stress-responsive pathways, especially senescence and ethylene synthesis determinants, indicating a possible role for the cytosolic malonyl-coenzyme A-derived lipids in stress response signaling. © 2011 American Society of Plant Biologists. All Rights Reserved.

  7. Interspecific introgression in cetaceans: DNA markers reveal post-F1 status of a pilot whale.

    Directory of Open Access Journals (Sweden)

    Laura Miralles

    Full Text Available Visual species identification of cetacean strandings is difficult, especially when dead specimens are degraded and/or species are morphologically similar. The two recognised pilot whale species (Globicephala melas and Globicephala macrorhynchus are sympatric in the North Atlantic Ocean. These species are very similar in external appearance and their morphometric characteristics partially overlap; thus visual identification is not always reliable. Genetic species identification ensures correct identification of specimens. Here we have employed one mitochondrial (D-Loop region and eight nuclear loci (microsatellites as genetic markers to identify six stranded pilot whales found in Galicia (Northwest Spain, one of them of ambiguous phenotype. DNA analyses yielded positive amplification of all loci and enabled species identification. Nuclear microsatellite DNA genotypes revealed mixed ancestry for one individual, identified as a post-F1 interspecific hybrid employing two different Bayesian methods. From the mitochondrial sequence the maternal species was Globicephala melas. This is the first hybrid documented between Globicephala melas and G. macrorhynchus, and the first post-F1 hybrid genetically identified between cetaceans, revealing interspecific genetic introgression in marine mammals. We propose to add nuclear loci to genetic databases for cetacean species identification in order to detect hybrid individuals.

  8. Genetic characterization of Toxoplasma gondii isolates from Portugal, Austria and Israel reveals higher genetic variability within the type II lineage.

    Science.gov (United States)

    Verma, S K; Ajzenberg, D; Rivera-Sanchez, A; Su, C; Dubey, J P

    2015-06-01

    This study compared genetic diversity of Toxoplasma gondii isolates from Portugal, Austria and Israel. For this, we genotyped 90 T. gondii isolates (16 from Portugal, 67 from Austria and 7 from Israel) using 10 nested PCR-restriction length polymorphism (RFLP) genetic markers and 15 microsatellite (MS) markers. By PCR-RFLP typing, 7 isolates from Portugal chickens were identified as type II (ToxoDB #1 or #3), 4 were type III (ToxoDB #2) and the remaining 4 isolates have unique genotype pattern were designated as ToxoDB #254. One mouse virulent isolate from a bovine fetus (Bos taurus) in Portugal was type I (ToxoDB #10) at all loci and designated as TgCowPr1. All 67 isolates from Austria and 7 from Israel were type II (ToxoDB #1 or #3). By MS typing, many additional genetic variations were revealed among the type II and type III isolates. Phylogenetic analysis showed that isolates from the same geographical locations tend to cluster together, and there is little overlapping of genotypes among different locations. This study demonstrated that the MS markers can provide higher discriminatory power to reveal association of genotypes with geographical locations. Future studies of the type II strains in Europe by these MS markers will be useful to reveal transmission patterns of the parasite.

  9. The limit distribution in the q-CLT for q\\,\\geqslant \\,1 is unique and can not have a compact support

    Science.gov (United States)

    Umarov, Sabir; Tsallis, Constantino

    2016-10-01

    In a paper by Umarov et al (2008 Milan J. Math. 76 307-28), a generalization of the Fourier transform, called the q-Fourier transform, was introduced and applied for the proof of a q-generalized central limit theorem (q-CLT). Subsequently, Hilhorst illustrated (2009 Braz. J. Phys. 39 371-9 2010 J. Stat. Mech. P10023) that the q-Fourier transform for q\\gt 1, is not invertible in the space of density functions. Indeed, using an invariance principle, he constructed a family of densities with the same q-Fourier transform and noted that ‘as a consequence, the q-CLT falls short of achieving its stated goal’. The distributions constructed there have compact support. We prove now that the limit distribution in the q-CLT is unique and can not have a compact support. This result excludes all the possible counterexamples which can be constructed using the invariance principle and fills the gap mentioned by Hilhorst.

  10. Multilocus Sequence Analysis of Nectar Pseudomonads Reveals High Genetic Diversity and Contrasting Recombination Patterns

    Science.gov (United States)

    Álvarez-Pérez, Sergio; de Vega, Clara; Herrera, Carlos M.

    2013-01-01

    The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas ‘sensu stricto’ isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA) of four core housekeeping genes (rrs, gyrB, rpoB and rpoD). A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs) 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1); P. fluorescens, P. lutea and P. syringae (NG 2); and P. rhizosphaerae (NG 3). Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria. PMID:24116076

  11. Multilocus sequence analysis of nectar pseudomonads reveals high genetic diversity and contrasting recombination patterns.

    Science.gov (United States)

    Alvarez-Pérez, Sergio; de Vega, Clara; Herrera, Carlos M

    2013-01-01

    The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas 'sensu stricto' isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA) of four core housekeeping genes (rrs, gyrB, rpoB and rpoD). A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs) 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1); P. fluorescens, P. lutea and P. syringae (NG 2); and P. rhizosphaerae (NG 3). Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria.

  12. Unique hyper-thermal composting process in Kagoshima City forms distinct bacterial community structures.

    Science.gov (United States)

    Tashiro, Yukihiro; Tabata, Hanae; Itahara, Asuka; Shimizu, Natsuki; Tashiro, Kosuke; Sakai, Kenji

    2016-11-01

    A unique compost, Satsuma soil, is produced from three types of wastewater sludge using hyper-thermal processes at temperatures much higher than that of general thermophilic processes in Kagoshima City, Japan. We analyzed the bacterial community structures of this hyper-thermal compost sample and other sludges and composts by a high-throughput barcoded pyrosequencing method targeting the 16S rRNA gene. In total, 621,076 reads were derived from 17 samples and filtered. Artificial sequences were deleted and the reads were clustered based on the operational taxonomic units (OTUs) at 97% similarity. Phylum-level analysis of the hyper-thermal compost revealed drastic changes of the sludge structures (each relative abundance) from Firmicutes (average 47.8%), Proteobacteria (average 22.3%), and Bacteroidetes (average 10.1%) to two main phyla including Firmicutes (73.6%) and Actinobacteria (25.0%) with less Proteobacteria (∼0.3%) and Bacteroidetes (∼0.1%). Furthermore, we determined the predominant species (each relative abundance) of the hyper-thermal compost including Firmicutes related to Staphylococcus cohnii (13.8%), Jeotgalicoccus coquinae (8.01%), and Staphylococcus lentus (5.96%), and Actinobacteria related to Corynebacterium stationis (6.41%), and found that these species were not predominant in wastewater sludge. In contrast, we did not observe any common structures among eight other composts produced, using the hyper-thermal composts as the inoculums, under thermophilic conditions from different materials. Principle coordinate analysis of the hyper-thermal compost indicated a large difference in bacterial community structures from material sludge and other composts. These results suggested that a distinct bacterial community structure was formed by hyper-thermal composting. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. Unique Rhizosphere Micro-characteristics Facilitate Phytoextraction of Multiple Metals in Soil by the Hyperaccumulating Plant Sedum alfredii.

    Science.gov (United States)

    Hou, Dandi; Wang, Kai; Liu, Ting; Wang, Haixin; Lin, Zhi; Qian, Jie; Lu, Lingli; Tian, Shengke

    2017-05-16

    Understanding the strategies that the roots of hyperaccumulating plants use to extract heavy metals from soils is important for optimizing phytoremediation. The rhizosphere characteristics of Sedum alfredii, a hyperaccumulator, were investigated 6 months after it had been planted in weathered field soils contaminated with 5.8 μg of Cd g -1 , 1985.1 μg of Zn g -1 , 667.5 μg of Pb g -1 , and 698.8 μg of Cu g -1 . In contrast with the non-hyperaccumulating ecotype (NHE), the hyperaccumulating ecotype (HE) of S. alfredii was more tolerant to the metals, and higher levels of Cd and Zn accumulated. The HE was characterized by a unique rhizosphere, including extensive root systems, a reduced soil pH, a higher metal bioavailability, and increased rhizomicrobial activity. The bioavailability of metals was significantly correlated with the HE's unique bacterial communities (P heavy metal phytoextraction.

  14. A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells.

    Science.gov (United States)

    Hadland, Brandon K; Varnum-Finney, Barbara; Mandal, Pankaj K; Rossi, Derrick J; Poulos, Michael G; Butler, Jason M; Rafii, Shahin; Yoder, Mervin C; Yoshimoto, Momoko; Bernstein, Irwin D

    2017-06-06

    Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Existence and uniqueness of solution for a system of equations of ...

    African Journals Online (AJOL)

    The existence and uniqueness of solution for a system of equations of microwave heating of biologic issue is discussed. Using the Green function approach we establish the existence and uniqueness of solution. Journal of the Nigerian Association of Mathematical Physics Vol. 8 2004: pp. 177-180 ...

  16. Structure of the hDmc1-ssDNA filament reveals the principles of its architecture.

    Directory of Open Access Journals (Sweden)

    Andrei L Okorokov

    Full Text Available In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1, a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active and compressed (inactive. However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds DNA nucleoprotein filaments, the extended (active state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers

  17. Case Report: Exome sequencing reveals recurrent RETSAT mutations and a loss-of-function POLDIP2 mutation in a rare undifferentiated tongue sarcoma [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jason Y. K. Chan

    2018-04-01

    Full Text Available Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV-positive head and neck cancer. Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93% of a gene for DNA replication and repair, namely POLDIP2 (DNA polymerase delta interacting protein 2, and two recurrent mutations of the adipogenesis and adipocyte differentiation gene RETSAT (retinol saturase, were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations to POLDIP2, may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 and NOTCH1 germline mutations of the patient’s blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue.

  18. Unique organizational and functional features of the cytochrome c maturation system in Shewanella oneidensis.

    Directory of Open Access Journals (Sweden)

    Miao Jin

    Full Text Available Shewanella are renowned for their ability to respire on a wide range of electron acceptors, which has been partially accredited to the presence of a large number of the c-type cytochromes. In the model species S. oneidensis MR-1, at least 41 genes encode c-type cytochromes that are predicted to be intact, thereby likely functional. Previously, in-frame deletion mutants for 36 of these genes were obtained and characterized. In this study, first we completed the construction of an entire set of c-type cytochrome mutants utilizing a newly developed att-based mutagenesis approach, which is more effective and efficient than the approach used previously by circumventing the conventional cloning. Second, we investigated the cytochrome c maturation (Ccm system in S. oneidensis. There are two loci predicted to encode components of the Ccm system, SO0259-SO0269 and SO0476-SO0478. The former is proven essential for cytochrome c maturation whereas the latter is dispensable. Unlike the single operon organization observed in other γ-proteobacteria, genes at the SO0259-SO0269 locus are uniquely organized into four operons, ccmABCDE, scyA, SO0265, and ccmFGH-SO0269. Functional analysis revealed that the SO0265 gene rather than the scyA and SO0269 genes are relevant to cytochrome c maturation.

  19. Functional Crosstalk between the PP2A and SUMO Pathways Revealed by Analysis of STUbL Suppressor, razor 1-1.

    Directory of Open Access Journals (Sweden)

    Minghua Nie

    2016-07-01

    Full Text Available Posttranslational modifications (PTMs provide dynamic regulation of the cellular proteome, which is critical for both normal cell growth and for orchestrating rapid responses to environmental stresses, e.g. genotoxins. Key PTMs include ubiquitin, the Small Ubiquitin-like MOdifier SUMO, and phosphorylation. Recently, SUMO-targeted ubiquitin ligases (STUbLs were found to integrate signaling through the SUMO and ubiquitin pathways. In general, STUbLs are recruited to target proteins decorated with poly-SUMO chains to ubiquitinate them and drive either their extraction from protein complexes, and/or their degradation at the proteasome. In fission yeast, reducing or preventing the formation of SUMO chains can circumvent the essential and DNA damage response functions of STUbL. This result indicates that whilst some STUbL "targets" have been identified, the crucial function of STUbL is to antagonize SUMO chain formation. Herein, by screening for additional STUbL suppressors, we reveal crosstalk between the serine/threonine phosphatase PP2A-Pab1B55 and the SUMO pathway. A hypomorphic Pab1B55 mutant not only suppresses STUbL dysfunction, but also mitigates the phenotypes associated with deletion of the SUMO protease Ulp2, or mutation of the STUbL cofactor Rad60. Together, our results reveal a novel role for PP2A-Pab1B55 in modulating SUMO pathway output, acting in parallel to known critical regulators of SUMOylation homeostasis. Given the broad evolutionary functional conservation of the PP2A and SUMO pathways, our results could be relevant to the ongoing attempts to therapeutically target these factors.

  20. The structural pathway of interleukin 1 (IL-1 initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer.

    Directory of Open Access Journals (Sweden)

    Saliha Ece Acuner Ozbabacan

    2014-02-01

    Full Text Available Interleukin-1 (IL-1 is a large cytokine family closely related to innate immunity and inflammation. IL-1 proteins are key players in signaling pathways such as apoptosis, TLR, MAPK, NLR and NF-κB. The IL-1 pathway is also associated with cancer, and chronic inflammation increases the risk of tumor development via oncogenic mutations. Here we illustrate that the structures of interfaces between proteins in this pathway bearing the mutations may reveal how. Proteins are frequently regulated via their interactions, which can turn them ON or OFF. We show that oncogenic mutations are significantly at or adjoining interface regions, and can abolish (or enhance the protein-protein interaction, making the protein constitutively active (or inactive, if it is a repressor. We combine known structures of protein-protein complexes and those that we have predicted for the IL-1 pathway, and integrate them with literature information. In the reconstructed pathway there are 104 interactions between proteins whose three dimensional structures are experimentally identified; only 15 have experimentally-determined structures of the interacting complexes. By predicting the protein-protein complexes throughout the pathway via the PRISM algorithm, the structural coverage increases from 15% to 71%. In silico mutagenesis and comparison of the predicted binding energies reveal the mechanisms of how oncogenic and single nucleotide polymorphism (SNP mutations can abrogate the interactions or increase the binding affinity of the mutant to the native partner. Computational mapping of mutations on the interface of the predicted complexes may constitute a powerful strategy to explain the mechanisms of activation/inhibition. It can also help explain how an oncogenic mutation or SNP works.

  1. Family members' unique perspectives of the family: examining their scope, size, and relations to individual adjustment.

    Science.gov (United States)

    Jager, Justin; Bornstein, Marc H; Putnick, Diane L; Hendricks, Charlene

    2012-06-01

    Using the McMaster Family Assessment Device (Epstein, Baldwin, & Bishop, 1983) and incorporating the perspectives of adolescent, mother, and father, this study examined each family member's "unique perspective" or nonshared, idiosyncratic view of the family. We used a modified multitrait-multimethod confirmatory factor analysis that (a) isolated for each family member's 6 reports of family dysfunction the nonshared variance (a combination of variance idiosyncratic to the individual and measurement error) from variance shared by 1 or more family members and (b) extracted common variance across each family member's set of nonshared variances. The sample included 128 families from a U.S. East Coast metropolitan area. Each family member's unique perspective generalized across his or her different reports of family dysfunction and accounted for a sizable proportion of his or her own variance in reports of family dysfunction. In addition, after holding level of dysfunction constant across families and controlling for a family's shared variance (agreement regarding family dysfunction), each family member's unique perspective was associated with his or her own adjustment. Future applications and competing alternatives for what these "unique perspectives" reflect about the family are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  2. Family Members' Unique Perspectives of the Family: Examining their Scope, Size, and Relations to Individual Adjustment

    Science.gov (United States)

    Jager, Justin; Bornstein, Marc H.; Diane, L. Putnick; Hendricks, Charlene

    2012-01-01

    Using the Family Assessment Device (FAD; Epstein, Baldwin, & Bishop, 1983) and incorporating the perspectives of adolescent, mother, and father, this study examined each family member's “unique perspective” or non-shared, idiosyncratic view of the family. To do so we used a modified multitrait-multimethod confirmatory factor analysis that (1) isolated for each family member's six reports of family dysfunction the non-shared variance (a combination of variance idiosyncratic to the individual and measurement error) from variance shared by one or more family members and (2) extracted common variance across each family member's set of non-shared variances. The sample included 128 families from a U.S. East Coast metropolitan area. Each family member's unique perspective generalized across his or her different reports of family dysfunction and accounted for a sizable proportion of his or her own variance in reports of family dysfunction. Additionally, after holding level of dysfunction constant across families and controlling for a family's shared variance (agreement regarding family dysfunction), each family member's unique perspective was associated with his or her own adjustment. Future applications and competing alternatives for what these “unique perspectives” reflect about the family are discussed. PMID:22545933

  3. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  4. Uniqueness of the gauge invariant action for cosmological perturbations

    International Nuclear Information System (INIS)

    Prokopec, Tomislav; Weenink, Jan

    2012-01-01

    In second order perturbation theory different definitions are known of gauge invariant perturbations in single field inflationary models. Consequently the corresponding gauge invariant cubic actions do not have the same form. Here we show that the cubic action for one choice of gauge invariant variables is unique in the following sense: the action for any other, non-linearly related variable can be brought to the same bulk action, plus additional boundary terms. These boundary terms correspond to the choice of hypersurface and generate extra, disconnected contributions to the bispectrum. We also discuss uniqueness of the action with respect to conformal frames. When expressed in terms of the gauge invariant curvature perturbation on uniform field hypersurfaces the action for cosmological perturbations has a unique form, independent of the original Einstein or Jordan frame. Crucial is that the gauge invariant comoving curvature perturbation is frame independent, which makes it extremely helpful in showing the quantum equivalence of the two frames, and therefore in calculating quantum effects in nonminimally coupled theories such as Higgs inflation

  5. Uniqueness of Gibbs states and global Markov property for Euclidean fields

    International Nuclear Information System (INIS)

    Albeverio, S.; Hoeegh-Krohn, R.

    1981-01-01

    The authors briefly discuss the proof of the uniqueness of solutions of the DLR equations (uniqueness of Gibbs states) in the class of regular generalized random fields (in the sense of having second moments bounded by those of some Euclidean field), for the Euclidean fields with trigonometric interaction. (Auth.)

  6. Unique aspects of impulsive traits in substance use and overeating: specific contributions of common assessments of impulsivity.

    Science.gov (United States)

    Beaton, Derek; Abdi, Hervé; Filbey, Francesca M

    2014-11-01

    Abstract Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Identify unique impulsivity traits specific to substance use and overeating. Impulsive Sensation Seeking (ImpSS) and Barratt's Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n = 37). A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm Overeating: lacks focus, but plans (short and long term). Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories - instead of categories - of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies.

  7. Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin

    Science.gov (United States)

    Jankowitsch, Frank; Schwarz, Julia; Rückert, Christian; Gust, Bertolt; Szczepanowski, Rafael; Blom, Jochen; Pelzer, Stefan; Kalinowski, Jörn

    2012-01-01

    Streptomyces davawensis JCM 4913 synthesizes the antibiotic roseoflavin, a structural riboflavin (vitamin B2) analog. Here, we report the 9,466,619-bp linear chromosome of S. davawensis JCM 4913 and a 89,331-bp linear plasmid. The sequence has an average G+C content of 70.58% and contains six rRNA operons (16S-23S-5S) and 69 tRNA genes. The 8,616 predicted protein-coding sequences include 32 clusters coding for secondary metabolites, several of which are unique to S. davawensis. The chromosome contains long terminal inverted repeats of 33,255 bp each and atypical telomeres. Sequence analysis with regard to riboflavin biosynthesis revealed three different patterns of gene organization in Streptomyces species. Heterologous expression of a set of genes present on a subgenomic fragment of S. davawensis resulted in the production of roseoflavin by the host Streptomyces coelicolor M1152. Phylogenetic analysis revealed that S. davawensis is a close relative of Streptomyces cinnabarinus, and much to our surprise, we found that the latter bacterium is a roseoflavin producer as well. PMID:23043000

  8. Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells

    Directory of Open Access Journals (Sweden)

    Chad M. Toledo

    2015-12-01

    Full Text Available To identify therapeutic targets for glioblastoma (GBM, we performed genome-wide CRISPR-Cas9 knockout (KO screens in patient-derived GBM stem-like cells (GSCs and human neural stem/progenitors (NSCs, non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers. In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, most likely as a result of oncogenic signaling, causing GBM-specific lethality.

  9. Marketing the Uniqueness of Small Towns. Revised.

    Science.gov (United States)

    Dunn, Douglas; Hogg, David H.

    The key to marketing a town is determining and promoting the town's "differential advantage" or uniqueness that would make people want to visit or live there. Exercises to help communities gain important insights into the town's competitive edge include a brainstorming session with knowledgeable community members, a visitor…

  10. Efficient Serial and Parallel Algorithms for Selection of Unique Oligos in EST Databases.

    Science.gov (United States)

    Mata-Montero, Manrique; Shalaby, Nabil; Sheppard, Bradley

    2013-01-01

    Obtaining unique oligos from an EST database is a problem of great importance in bioinformatics, particularly in the discovery of new genes and the mapping of the human genome. Many algorithms have been developed to find unique oligos, many of which are much less time consuming than the traditional brute force approach. An algorithm was presented by Zheng et al. (2004) which finds the solution of the unique oligos search problem efficiently. We implement this algorithm as well as several new algorithms based on some theorems included in this paper. We demonstrate how, with these new algorithms, we can obtain unique oligos much faster than with previous ones. We parallelize these new algorithms to further improve the time of finding unique oligos. All algorithms are run on ESTs obtained from a Barley EST database.

  11. A unique Fock quantization for fields in non-stationary spacetimes

    International Nuclear Information System (INIS)

    Cortez, Jerónimo; Marugán, Guillermo A. Mena; Olmedo, Javier; Velhinho, José M.

    2010-01-01

    In curved spacetimes, the lack of criteria for the construction of a unique quantization is a fundamental problem undermining the significance of the predictions of quantum field theory. Inequivalent quantizations lead to different physics. Recently, however, some uniqueness results have been obtained for fields in non-stationary settings. In particular, for vacua that are invariant under the background symmetries, a unitary implementation of the classical evolution suffices to pick up a unique Fock quantization in the case of Klein-Gordon fields with time-dependent mass, propagating in a static spacetime whose spatial sections are three-spheres. In fact, the field equation can be reinterpreted as describing the propagation in a Friedmann-Robertson-Walker spacetime after a suitable scaling of the field by a function of time. For this class of fields, we prove here an even stronger result about the Fock quantization: the uniqueness persists when one allows for linear time-dependent transformations of the field in order to account for a scaling by background functions. In total, paying attention to the dynamics, there exists a preferred choice of quantum field, and only one SO(4)-invariant Fock representation for it that respects the standard probabilistic interpretation along the evolution. The result has relevant implications e.g. in cosmology

  12. F-Type Lectins: A Highly Diversified Family of Fucose-Binding Proteins with a Unique Sequence Motif and Structural Fold, Involved in Self/Non-Self-Recognition

    Directory of Open Access Journals (Sweden)

    Gerardo R. Vasta

    2017-11-01

    Full Text Available The F-type lectin (FTL family is one of the most recent to be identified and structurally characterized. Members of the FTL family are characterized by a fucose recognition domain [F-type lectin domain (FTLD] that displays a novel jellyroll fold (“F-type” fold and unique carbohydrate- and calcium-binding sequence motifs. This novel lectin family comprises widely distributed proteins exhibiting single, double, or greater multiples of the FTLD, either tandemly arrayed or combined with other structurally and functionally distinct domains, yielding lectin subunits of pleiotropic properties even within a single species. Furthermore, the extraordinary variability of FTL sequences (isoforms that are expressed in a single individual has revealed genetic mechanisms of diversification in ligand recognition that are unique to FTLs. Functions of FTLs in self/non-self-recognition include innate immunity, fertilization, microbial adhesion, and pathogenesis, among others. In addition, although the F-type fold is distinctive for FTLs, a structure-based search revealed apparently unrelated proteins with minor sequence similarity to FTLs that displayed the FTLD fold. In general, the phylogenetic analysis of FTLD sequences from viruses to mammals reveals clades that are consistent with the currently accepted taxonomy of extant species. However, the surprisingly discontinuous distribution of FTLDs within each taxonomic category suggests not only an extensive structural/functional diversification of the FTLs along evolutionary lineages but also that this intriguing lectin family has been subject to frequent gene duplication, secondary loss, lateral transfer, and functional co-option.

  13. The unique karyotype of Henochilus wheatlandii, a critically endangered fish living in a fast-developing region in Minas Gerais State, Brazil.

    Directory of Open Access Journals (Sweden)

    Priscilla C Silva

    Full Text Available Henochilus wheatlandii, the only species of this genus, is critically endangered and was considered extinct for over a century. The rediscovery of this fish in 1996 made it possible to study its phylogenetic relationships with other species in the subfamily Bryconinae. The aim of this study was to characterise the karyotype of H. wheatlandii. Standard staining, C-positive heterochromatin and nucleolar organiser region (NOR banding, chromomycin A(3 staining, and fluorescent in situ hybridisation (FISH using 5S rDNA and 18S rDNA probes were conducted on nineteen specimens collected in the Santo Antonio River, a sub-basin of the Doce River in Ferros municipality, Minas Gerais State, Brazil. Henochilus wheatlandii shared the same diploid number and chromosome morphology as other species of Bryconinae. However, its heterochromatin distribution patterns, NOR localisation, and FISH patterns revealed a cytogenetic profile unique among Neotropical Bryconinae, emphasizing the evolutionary uniqueness of this threatened species.

  14. Unique players in the BMP pathway: Small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling

    Science.gov (United States)

    Knockaert, Marie; Sapkota, Gopal; Alarcón, Claudio; Massagué, Joan; Brivanlou, Ali H.

    2006-01-01

    Smad transcription factors are key signal transducers for the TGF-β/bone morphogenetic protein (BMP) family of cytokines and morphogens. C-terminal serine phosphorylation by TGF-β and BMP membrane receptors drives Smads into the nucleus as transcriptional regulators. Dephosphorylation and recycling of activated Smads is an integral part of this process, which is critical for agonist sensing by the cell. However, the nuclear phosphatases involved have remained unknown. Here we provide functional, biochemical, and embryological evidence identifying the SCP (small C-terminal domain phosphatase) family of nuclear phosphatases as mediators of Smad1 dephosphorylation in the BMP signaling pathway in vertebrates. Xenopus SCP2/Os4 inhibits BMP activity in the presumptive ectoderm and leads to neuralization. In Xenopus embryos, SCP2/Os4 and human SCP1, 2, and 3 cause selective dephosphorylation of Smad1 compared with Smad2, inhibiting BMP- and Smad1-dependent transcription and leading to the induction of the secondary dorsal axis. In human cells, RNAi-mediated depletion of SCP1 and SCP2 increases the extent and duration of Smad1 phosphorylation in response to BMP, the transcriptional action of Smad1, and the strength of endogenous BMP gene responses. The present identification of the SCP family as Smad C-terminal phosphatases sheds light on the events that attenuate Smad signaling and reveals unexpected links to the essential phosphatases that control RNA polymerase II in eukaryotes. PMID:16882717

  15. A unique tripartite collision tumor of the esophagus

    Science.gov (United States)

    Schizas, Dimitrios; Michalinos, Adamantios; Alexandrou, Paraskevi; Moris, Demetrios; Baliou, Evangelia; Tsilimigras, Diamantis; Throupis, Theodore; Liakakos, Theodore

    2017-01-01

    Abstract Rationale: We report a unique case of a tripartite esophageal collision tumor consisting of three separate histologic types. Patients concerns: Therapeutic dilemmas on the proper treatment of those rare neoplasms remain unanswered considering both proper surgical therapy and adjuvant therapy. Diagnose: In this paper, we report a unique case of a patient with a tripartite esophageal collision tumor consisting of a small cell carcinoma, an adenocarcinoma of medium differentiation and a signet ring cell carcinoma. Diagnosis is difficult as clinical presentation of the patient was undistinguishable from other, commoner tumor types. Interventions: The patient's diagnostic and therapeutic course along with available data on the collisions tumor's biological behavior and treatment are briefly discussed. Outcomes: Esophagectomy is the best treatment options for these patients. Unique nature of this tumor demands aggresive oncologic treatment. Lessons: Collision tumors are rare neoplasms consisting of distinct cell populations developing in juxtaposition to one another without any areas of intermingling. Various cell types can be found. However, collision neoplasms of the esophagus combining adenomatous and neuroendocrine components are exceedingly rare, with only 5 cases described to date in the literature. Given their rarity, limited information is available on their tumorigenesis, biological behavior and clinical course. In general, these tumors are aggressive neoplasms and significantly affect patient treatment and prognosis. PMID:29245236

  16. A unique gesture of sharing

    International Nuclear Information System (INIS)

    Mustafa, T.

    1985-01-01

    The Atoms for Peace program was a unique gesture of sharing on the part of the leading industrialized nation, and has very few parallels in modern history. The author says one of the major advantages of the program for developing nations was the much needed stimulation of their indigenous science and technology efforts and the awakening of their governments to the multifaceted benefits of atomic energy. The author discusses how the program benefited Pakistan in the production of electrical energy and in the application of nuclear techniques in the fields of agriculture and medicine, which help to alleviate hunger and combat disease

  17. Clinical Study of Bacillus coagulans Unique IS-2 (ATCC PTA-11748) in the Treatment of Patients with Bacterial Vaginosis.

    Science.gov (United States)

    Ratna Sudha, M; Yelikar, Kanan A; Deshpande, Sonali

    2012-09-01

    Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by reduction of native lactobacilli. Antimicrobial therapy used to cure the disease is often found to be ineffective. We postulate that Bacillus coagulans Unique IS-2 (Unique Biotech Limited, India) might provide an appendage to antimicrobial treatment and improve curing rate. In the present study 40 Indian women diagnosed with BV by the presence of symptoms including white discharge, pH greater than 4.7, burning micturation, itching, soreness and redness at vulva. The subjects were divided in 2 groups probiotic (n = 20) and control (n = 20) based on age (control group, 33 ± 3 years and probiotic group, 32.5 ± 3 years), history of previous vaginosis (control group, 75% or 15/20 and probiotic group, 75% or 15/20) and severity of current vaginosis infection (burning micturation and itching, 35% in each group). Probiotic group subjects were assigned to receive a dose of antibiotic therapy [Ofloxacin-Ornidazole with strength of 200-500 mg per capsule/day for 5 days along with vaginal peccaries (co-kimaxazol) for 3 days] simultaneously with two probiotic capsules (10(9) CFUs of Bacillus coagulans Unique IS-2 per capsule). The control group received only antibiotic therapy. At the end of the treatment the 80% of probiotic group subjects showed significant positive response as revealed by reduction of vaginosis symptoms compared to the control group which exhibited reduction in 45% subjects only. Thus, the results of present study indicate that strain Bacillus coagulans Unique IS-2 can provide benefits to women being treated with antibiotics to cure an infectious condition.

  18. mRNA-seq analysis of the Gossypium arboreum transcriptome reveals tissue selective signaling in response to water stress during seedling stage.

    Directory of Open Access Journals (Sweden)

    Xueyan Zhang

    Full Text Available The cotton diploid species, Gossypium arboreum, shows important properties of stress tolerance and good genetic stability. In this study, through mRNA-seq, we de novo assembled the unigenes of multiple samples with 3h H(2O, NaCl, or PEG treatments in leaf, stem and root tissues and successfully obtained 123,579 transcripts of G. arboreum, 89,128 of which were with hits through BLAST against known cotton ESTs and draft genome of G. raimondii. About 36,961 transcripts (including 1,958 possible transcription factor members were identified with differential expression under water stresses. Principal component analysis of differential expression levels in multiple samples suggested tissue selective signalling responding to water stresses. Venn diagram analysis showed the specificity and intersection of transcripts' response to NaCl and PEG treatments in different tissues. Self-organized mapping and hierarchical cluster analysis of the data also revealed strong tissue selectivity of transcripts under salt and osmotic stresses. In addition, the enriched gene ontology (GO terms for the selected tissue groups were differed, including some unique enriched GO terms such as photosynthesis and tetrapyrrole binding only in leaf tissues, while the stem-specific genes showed unique GO terms related to plant-type cell wall biogenesis, and root-specific genes showed unique GO terms such as monooxygenase activity. Furthermore, there were multiple hormone cross-talks in response to osmotic and salt stress. In summary, our multidimensional mRNA sequencing revealed tissue selective signalling and hormone crosstalk in response to salt and osmotic stresses in G. arboreum. To our knowledge, this is the first such report of spatial resolution of transcriptome analysis in G. arboreum. Our study will potentially advance understanding of possible transcriptional networks associated with water stress in cotton and other crop species.

  19. A unique metal-semiconductor interface and resultant electron transfer phenomenon

    OpenAIRE

    Taft, S. L.

    2012-01-01

    An unusual electron transfer phenomenon has been identified from an n-type semiconductor to Schottky metal particles, the result of a unique metal semiconductor interface that results when the metal particles are grown from the semiconductor substrate. The unique interface acts as a one-way (rectifying) open gateway and was first identified in reduced rutile polycrystalline titanium dioxide (an n-type semiconductor) to Group VIII (noble) metal particles. The interface significantly affects th...

  20. Supergravity p-branes reexamined: Extra parameters, uniqueness, and topological censorship

    International Nuclear Information System (INIS)

    Gal'tsov, Dmitri V.; Lemos, Jose P.S.; Clement, Gerard

    2004-01-01

    We perform a complete integration of the Einstein-dilaton-antisymmetric form action describing black p-branes in arbitrary dimensions assuming the transverse space to be homogeneous and possessing spherical, toroidal, or hyperbolic topology. The generic solution contains eight parameters satisfying one constraint. Asymptotically flat solutions form a five-parametric subspace, while conditions of regularity of the nondegenerate event horizon further restrict this number to 3, which can be related to the mass and charge densities and the asymptotic value of the dilaton. In the case of a degenerate horizon, this number is reduced by 1. Our derivation constitutes a constructive proof of the uniqueness theorem for p-branes with the homogeneous transverse space. No asymptotically flat solutions with toroidal or hyperbolic transverse space within the considered class are shown to exist, which result can be viewed as a demonstration of the topological censorship for p-branes. From our considerations it follows, in particular, that some previously discussed p-brane-like solutions with extra parameters do not satisfy the standard conditions of asymptotic flatness and absence of naked singularities. We also explore the same system in presence of a cosmological constant and derive a complete analytic solution for higher-dimensional charged topological black holes, thus proving their uniqueness

  1. Identification of Bombyx mori bidensovirus VD1-ORF4 reveals a novel protein associated with viral structural component.

    Science.gov (United States)

    Li, Guohui; Hu, Zhaoyang; Guo, Xuli; Li, Guangtian; Tang, Qi; Wang, Peng; Chen, Keping; Yao, Qin

    2013-06-01

    Bombyx mori bidensovirus (BmBDV) VD1-ORF4 (open reading frame 4, ORF4) consists of 3,318 nucleotides, which codes for a predicted 1,105-amino acid protein containing a conserved DNA polymerase motif. However, its functions in viral propagation remain unknown. In the current study, the transcription of VD1-ORF4 was examined from 6 to 96 h postinfection (p.i.) by RT-PCR, 5'-RACE revealed the transcription initiation site of BmBDV ORF4 to be -16 nucleotides upstream from the start codon, and 3'-RACE revealed the transcription termination site of VD1-ORF4 to be +7 nucleotides downstream from termination codon. Three different proteins were examined in the extracts of BmBDV-infected silkworms midguts by Western blot using raised antibodies against VD1-ORF4 deduced amino acid, and a specific protein band about 53 kDa was further detected in purified virions using the same antibodies. Taken together, BmBDV VD1-ORF4 codes for three or more proteins during the viral life cycle, one of which is a 53 kDa protein and confirmed to be a component of BmBDV virion.

  2. Increased expression of MERTK is associated with a unique form of canine retinopathy.

    Directory of Open Access Journals (Sweden)

    Saija J Ahonen

    Full Text Available Progressive retinal degenerations are among the most common causes of blindness both in human and in dogs. Canine progressive retinal atrophy (PRA resembles human retinitis pigmentosa (RP and is typically characterized by a progressive loss of rod photoreceptors followed by a loss of cone function. The disease gradually progress from the loss of night and day vision to a complete blindness. We have recently described a unique form of retinopathy characterized by the multifocal gray/brown discoloration and thinning of the retina in the Swedish Vallhund (SV breed. We aimed to identify the genetic cause by performing a genome wide association analysis in a cohort of 18 affected and 10 healthy control dogs using Illumina's canine 22k SNP array. We mapped the disease to canine chromosome 17 (p = 7.7×10(-5 and found a 6.1 Mb shared homozygous region in the affected dogs. A combined analysis of the GWAS and replication data with additional 60 dogs confirmed the association (p = 4.3×10(-8, OR = 11.2 for homozygosity. A targeted resequencing of the entire associated region in four cases and four controls with opposite risk haplotypes identified several variants in the coding region of functional candidate genes, such as a known retinopathy gene, MERTK. However, none of the identified coding variants followed a compelling case- or breed-specific segregation pattern. The expression analyses of four candidate genes in the region, MERTK, NPHP1, ANAPC1 and KRCC1, revealed specific upregulation of MERTK in the retina of the affected dogs. Collectively, these results indicate that the retinopathy is associated with overexpression of MERTK, however further investigation is needed to discover the regulatory mutation for the better understanding of the disease pathogenesis. Our study establishes a novel gain-of-function model for the MERTK biology and provides a therapy model for retinopathy MERTK inhibitors. Meanwhile, a marker-based genetic

  3. Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

    Science.gov (United States)

    Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

    2018-04-20

    Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0% to 96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Copyright © 2018. Published by Elsevier B.V.

  4. The MTP1 promoters from Arabidopsis halleri reveal cis-regulating elements for the evolution of metal tolerance.

    Science.gov (United States)

    Fasani, Elisa; DalCorso, Giovanni; Varotto, Claudio; Li, Mingai; Visioli, Giovanna; Mattarozzi, Monica; Furini, Antonella

    2017-06-01

    In the hyperaccumulator Arabidopsis halleri, the zinc (Zn) vacuolar transporter MTP1 is a key component of hypertolerance. Because protein sequences and functions are highly conserved between A. halleri and Arabidopsis thaliana, Zn tolerance in A. halleri may reflect the constitutively higher MTP1 expression compared with A. thaliana, based on copy number expansion and different cis regulation. Three MTP1 promoters were characterized in A. halleri ecotype I16. The comparison with the A. thaliana MTP1 promoter revealed different expression profiles correlated with specific cis-acting regulatory elements. The MTP1 5' untranslated region, highly conserved among A. thaliana, Arabidopsis lyrata and A. halleri, contains a dimer of MYB-binding motifs in the A. halleri promoters absent in the A. thaliana and A. lyrata sequences. Site-directed mutagenesis of these motifs revealed their role for expression in trichomes. A. thaliana mtp1 transgenic lines expressing AtMTP1 controlled by the native A. halleri promoter were more Zn-tolerant than lines carrying mutations on MYB-binding motifs. Differences in Zn tolerance were associated with different distribution of Zn among plant organs and in trichomes. The different cis-acting elements in the MTP1 promoters of A. halleri, particularly the MYB-binding sites, are probably involved in the evolution of Zn tolerance. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  5. A unique theory of all forces

    International Nuclear Information System (INIS)

    Di Vecchia, Paolo

    1997-01-01

    In discussing the construction of a consistent theory of quantum gravity unified with the gauge interactions we are naturally led to a string theory. We review its properties and the five consistent supersymmetric string theories in ten dimensions. We finally discuss the evidence that these theories are actually special limits of a unique 11-dimensional theory, called M-theory, and a recent conjecture for its explicit formulation as a supersymmetric Matrix theory

  6. Temporal information partitioning: Characterizing synergy, uniqueness, and redundancy in interacting environmental variables

    Science.gov (United States)

    Goodwell, Allison E.; Kumar, Praveen

    2017-07-01

    Information theoretic measures can be used to identify nonlinear interactions between source and target variables through reductions in uncertainty. In information partitioning, multivariate mutual information is decomposed into synergistic, unique, and redundant components. Synergy is information shared only when sources influence a target together, uniqueness is information only provided by one source, and redundancy is overlapping shared information from multiple sources. While this partitioning has been applied to provide insights into complex dependencies, several proposed partitioning methods overestimate redundant information and omit a component of unique information because they do not account for source dependencies. Additionally, information partitioning has only been applied to time-series data in a limited context, using basic pdf estimation techniques or a Gaussian assumption. We develop a Rescaled Redundancy measure (Rs) to solve the source dependency issue, and present Gaussian, autoregressive, and chaotic test cases to demonstrate its advantages over existing techniques in the presence of noise, various source correlations, and different types of interactions. This study constitutes the first rigorous application of information partitioning to environmental time-series data, and addresses how noise, pdf estimation technique, or source dependencies can influence detected measures. We illustrate how our techniques can unravel the complex nature of forcing and feedback within an ecohydrologic system with an application to 1 min environmental signals of air temperature, relative humidity, and windspeed. The methods presented here are applicable to the study of a broad range of complex systems composed of interacting variables.

  7. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types

    Science.gov (United States)

    Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D’Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

    2016-01-01

    In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

  8. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

    Science.gov (United States)

    Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

    2010-10-13

    Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Msx-1 (p Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

  9. Is Self-Assessment in Religious Education Unique?

    Science.gov (United States)

    Brooks, Val; Fancourt, Nigel

    2012-01-01

    This paper addresses the question: is self-assessment in religious education unique? It first presents an overview of some challenges for assessment from subject differences, and then reviews the generic literature on self-assessment. It builds on earlier empirical research on self-assessment in religious education, carried out in an English state…

  10. A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.

    Directory of Open Access Journals (Sweden)

    Akiko Nakanishi

    Full Text Available Transposable elements, including short interspersed repetitive elements (SINEs, comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs, which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8. Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer.

  11. Protein Profiling Reveals Novel Proteins in Pollen and Pistil of W22 (ga1; Ga1 in Maize

    Directory of Open Access Journals (Sweden)

    Jin Yu

    2014-05-01

    Full Text Available Gametophytic factors mediate pollen-pistil interactions in maize (Zea mays L. and play active roles in limiting gene flow among maize populations and between maize and teosinte. This study was carried out to identify proteins and investigate the mechanism of gametophytic factors using protein analysis. W22 (ga1; which did not carry a gametophytic factor and W22 (Ga1, a near iso-genic line, were used for the proteome investigation. SDS-PAGE was executed to investigate proteins in the pollen and pistil of W22 (ga1 and W22 (Ga1. A total of 44 differentially expressed proteins were identified in the pollen and pistil on SDS-PAGE using LTQ-FTICR MS. Among the 44 proteins, a total of 24 proteins were identified in the pollen of W22 (ga1 and W22 (Ga1 whereas 20 differentially expressed proteins were identified from the pistil of W22 (ga1 and W22 (Ga1. However, in pollen, 2 proteins were identified only in the W22 (ga1 and 12 proteins only in the W22 (Ga1 whereas 10 proteins were confirmed from the both of W22 (ga1 and W22 (Ga1. In contrary, 10 proteins were appeared only in the pistil of W22 (ga1 and 7 proteins from W22 (Ga1 while 3 proteins confirmed in the both of W22 (ga1 and W22 (Ga1. Moreover, the identified proteins were generally involved in hydrolase activity, nucleic acid binding and nucleotide binding. These results help to reveal the mechanism of gametophytic factors and provide a valuable clue for the pollen and pistil research in maize.

  12. Novel phage group infecting Lactobacillus delbrueckii subsp. lactis, as revealed by genomic and proteomic analysis of bacteriophage Ldl1.

    Science.gov (United States)

    Casey, Eoghan; Mahony, Jennifer; Neve, Horst; Noben, Jean-Paul; Dal Bello, Fabio; van Sinderen, Douwe

    2015-02-01

    Ldl1 is a virulent phage infecting the dairy starter Lactobacillus delbrueckii subsp. lactis LdlS. Electron microscopy analysis revealed that this phage exhibits a large head and a long tail and bears little resemblance to other characterized phages infecting Lactobacillus delbrueckii. In vitro propagation of this phage revealed a latent period of 30 to 40 min and a burst size of 59.9 +/- 1.9 phage particles. Comparative genomic and proteomic analyses showed remarkable similarity between the genome of Ldl1 and that of Lactobacillus plantarum phage ATCC 8014-B2. The genomic and proteomic characteristics of Ldl1 demonstrate that this phage does not belong to any of the four previously recognized L. delbrueckii phage groups, necessitating the creation of a new group, called group e, thus adding to the knowledge on the diversity of phages targeting strains of this industrially important lactic acid bacterial species.

  13. Unique Three-Dimensional InP Nanopore Arrays for Improved Photoelectrochemical Hydrogen Production.

    Science.gov (United States)

    Li, Qiang; Zheng, Maojun; Ma, Liguo; Zhong, Miao; Zhu, Changqing; Zhang, Bin; Wang, Faze; Song, Jingnan; Ma, Li; Shen, Wenzhong

    2016-08-31

    Ordered three-dimensional (3D) nanostructure arrays hold promise for high-performance energy harvesting and storage devices. Here, we report the fabrication of InP nanopore arrays (NPs) in unique 3D architectures with excellent light trapping characteristic and large surface areas for use as highly active photoelectrodes in photoelectrochemical (PEC) hydrogen evolution devices. The ordered 3D NPs were scalably synthesized by a facile two-step etching process of (1) anodic etching of InP in neutral 3 M NaCl electrolytes to realize nanoporous structures and (2) wet chemical etching in HCl/H3PO4 (volume ratio of 1:3) solutions for removing the remaining top irregular layer. Importantly, we demonstrated that the use of neutral electrolyte of NaCl instead of other solutions, such as HCl, in anodic etching of InP can significantly passivate the surface states of 3D NPs. As a result, the maximum photoconversion efficiency obtained with ∼15.7 μm thick 3D NPs was 0.95%, which was 7.3 and 1.4 times higher than that of planar and 2D NPs. Electrochemical impedance spectroscopy and photoluminescence analyses further clarified that the improved PEC performance was attributed to the enhanced charge transfer across 3D NPs/electrolyte interfaces, the improved charge separation at 3D NPs/electrolyte junction, and the increased PEC active surface areas with our unique 3D NP arrays.

  14. Botulinum neurotoxin: unique folding of enzyme domain of the most-poisonous poison.

    Science.gov (United States)

    Kumar, Raj; Kukreja, Roshan V; Li, Li; Zhmurov, Artem; Kononova, Olga; Cai, Shuowei; Ahmed, Syed A; Barsegov, Valeri; Singh, Bal Ram

    2014-01-01

    Botulinum neurotoxin (BoNT), the most toxic substance known to mankind, is the first example of the fully active molten globule state. To understand its folding mechanism, we performed urea denaturation experiments and theoretical modeling using BoNT serotype A (BoNT/A). We found that the extent of BoNT/A denaturation from the native state (N) shows a nonmonotonic dependence on urea concentration indicating a unique multistep denaturation process, N → I1 [Formula: see text] I2 [Formula: see text] U, with two intermediate states I1 and I2. BoNT/A loses almost all its secondary structure in 3.75 M urea (I1), yet it displays a native-like secondary structure in 5 M urea (I2). This agrees with the results of theoretical modeling, which helped to determine the molecular basis of unique behavior of BoNT/A in solution. Except for I2, all the states revert back to full enzymatic activity for SNAP-25 including the unfolded state U stable in 7 M urea. Our results stress the importance of structural flexibility in the toxin's mechanism of survival and action, an unmatched evolutionary trait from billion-year-old bacteria, which also correlates with the long-lasting enzymatic activity of BoNT inside neuronal cells. BoNT/A provides a rich model to explore protein folding in relation to functional activity.

  15. Structure of Stenotrophomonas maltophilia FeoA complexed with zinc: a unique prokaryotic SH3-domain protein that possibly acts as a bacterial ferrous iron-transport activating factor

    International Nuclear Information System (INIS)

    Su, Yi-Che; Chin, Ko-Hsin; Hung, Hui-Chih; Shen, Gwan-Han; Wang, Andrew H.-J.; Chou, Shan-Ho

    2010-01-01

    The crystal structure of FeoA from Stenotrophomonas maltophilia has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach and revealed a unique dimer cross-linked by two zinc ions and six chloride ions. Iron is vital to the majority of prokaryotes, with ferrous iron believed to be the preferred form for iron uptake owing to its much better solubility. The major route for bacterial ferrous iron uptake is found to be via an Feo (ferrous iron-transport) system comprising the three proteins FeoA, FeoB and FeoC. Although the structure and function of FeoB have received much attention recently, the roles played by FeoA and FeoC have been little investigated to date. Here, the tertiary structure of FeoA from Stenotrophomonas maltophilia (Sm), a vital opportunistic pathogen in immunodepressed hosts, is reported. The crystal structure of SmFeoA has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach. Although SmFeoA bears low sequence identity to eukaryotic proteins, its structure is found to adopt a eukaryotic SH3-domain-like fold. It also bears weak similarity to the C-terminal SH3 domain of bacterial DtxR (diphtheria toxin regulator), with some unique characteristics. Intriguingly, SmFeoA is found to adopt a unique dimer cross-linked by two zinc ions and six anions (chloride ions). Since FeoB has been found to contain a G-protein-like domain with low GTPase activity, FeoA may interact with FeoB through the SH3–G-protein domain interaction to act as a ferrous iron-transport activating factor

  16. Why are predictions of general relativity theory for gravitational effects non-unique?

    International Nuclear Information System (INIS)

    Loskutov, Yu.M.

    1990-01-01

    Reasons of non-uniqueness of predictions of the general relativity theory (GRT) for gravitational effects are analyzed in detail. To authors' opinion, the absence of comparison mechanism of curved and plane metrics is the reason of non-uniqueness

  17. Hierarchical domain structure of lead-free piezoelectric (Na{sub 1/2} Bi{sub 1/2})TiO{sub 3}-(K{sub 1/2} Bi{sub 1/2})TiO{sub 3} single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chengtao, E-mail: lchentao@vt.edu; Wang, Yaojin; Ge, Wenwei; Li, Jiefang; Viehland, Dwight [Materials Science and Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Delaire, Olivier [Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Li, Xiaobin; Luo, Haosu [Shanghai Institute of Ceramics, Chinese Academy of Sciences, 215 Chengbei Road, Jiading, Shanghai 201800 (China)

    2016-05-07

    We report a unique hierarchical domain structure in single crystals of (Na{sub 1/2}Bi{sub 1/2})TiO{sub 3}-xat. %(K{sub 1/2}Bi{sub 1/2})TiO{sub 3} for x = 5 and 8 by transmission electron microscopy (TEM). A high density of polar nano-domains with a lamellar morphology was found, which were self-assembled into a quadrant-like configuration, which then assembled into conventional ferroelectric macro-domains. Studies by high resolution TEM revealed that the polar lamellar regions contained a coexistence of in-phase and anti-phase oxygen octahedral tilt regions of a few nanometers in size. Domain frustration over multiple length scales may play an important role in the stabilization of the hierarchy, and in reducing the piezoelectric response of this Pb-free piezoelectric solid solution.

  18. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

    Directory of Open Access Journals (Sweden)

    Schwend Tyler

    2009-11-01

    Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

  19. Uniqueness of flat spherically symmetric spacelike hypersurfaces admitted by spherically symmetric static spacetimes

    Science.gov (United States)

    Beig, Robert; Siddiqui, Azad A.

    2007-11-01

    It is known that spherically symmetric static spacetimes admit a foliation by flat hypersurfaces. Such foliations have explicitly been constructed for some spacetimes, using different approaches, but none of them have proved or even discussed the uniqueness of these foliations. The issue of uniqueness becomes more important due to suitability of flat foliations for studying black hole physics. Here, flat spherically symmetric spacelike hypersurfaces are obtained by a direct method. It is found that spherically symmetric static spacetimes admit flat spherically symmetric hypersurfaces, and that these hypersurfaces are unique up to translation under the timelike Killing vector. This result guarantees the uniqueness of flat spherically symmetric foliations for such spacetimes.

  20. Young children's preference for unique owned objects.

    Science.gov (United States)

    Gelman, Susan A; Davidson, Natalie S

    2016-10-01

    An important aspect of human thought is the value we place on unique individuals. Adults place higher value on authentic works of art than exact replicas, and young children at times value their original possessions over exact duplicates. What is the scope of this preference in early childhood, and when do children understand its subjective nature? On a series of trials, we asked three-year-olds (N=36) to choose between two toys for either themselves or the researcher: an old (visibly used) toy vs. a new (more attractive) toy matched in type and appearance (e.g., old vs. brand-new blanket). Focal pairs contrasted the child's own toy with a matched new object; Control pairs contrasted toys the child had never seen before. Children preferred the old toys for Focal pairs only, and treated their own preferences as not shared by the researcher. By 3years of age, young children place special value on unique individuals, and understand the subjective nature of that value. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Event segmentation ability uniquely predicts event memory.

    Science.gov (United States)

    Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

    2013-11-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Revealing1 Programmed Ribosomal Frameshifting Mechanisms by Single-Molecule Techniques and Computational Methods

    Directory of Open Access Journals (Sweden)

    Kai-Chun Chang

    2012-01-01

    Full Text Available Programmed ribosomal frameshifting (PRF serves as an intrinsic translational regulation mechanism employed by some viruses to control the ratio between structural and enzymatic proteins. Most viral mRNAs which use PRF adapt an H-type pseudoknot to stimulate −1 PRF. The relationship between the thermodynamic stability and the frameshifting efficiency of pseudoknots has not been fully understood. Recently, single-molecule force spectroscopy has revealed that the frequency of −1 PRF correlates with the unwinding forces required for disrupting pseudoknots, and that some of the unwinding work dissipates irreversibly due to the torsional restraint of pseudoknots. Complementary to single-molecule techniques, computational modeling provides insights into global motions of the ribosome, whose structural transitions during frameshifting have not yet been elucidated in atomic detail. Taken together, recent advances in biophysical tools may help to develop antiviral therapies that target the ubiquitous −1 PRF mechanism among viruses.

  3. Modularity, comparative cognition and human uniqueness

    OpenAIRE

    Shettleworth, Sara J.

    2012-01-01

    Darwin's claim ‘that the difference in mind between man and the higher animals … is certainly one of degree and not of kind’ is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference ...

  4. Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain

    Science.gov (United States)

    Zeidan, F.; Grant, J.A.; Brown, C.A.; McHaffie, J.G.; Coghill, R.C.

    2013-01-01

    The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain. PMID:22487846

  5. Unique rheological behavior of chitosan-modified nanoclay at highly hydrated state.

    Science.gov (United States)

    Liang, Songmiao; Liu, Linshu; Huang, Qingrong; Yam, Kit L

    2009-04-30

    This work attempts to explore the dynamic and steady-state rheological properties of chitosan modified clay (CMCs) at highly hydrated state. CMCs with different initial chitosan/clay weight ratios (s) were prepared from pre-exfoliated clay via electrostatic adsorption process. Thermogravimetric analysis and optical microscopy were used to determine the adsorbed content of chitosan (m) in CMCs and the microstructure of CMCs at highly hydrated state, respectively. Dynamic rheological results indicate that both stress-strain behavior and moduli of CMCs exhibit strong dependence on m. Shear-thinning behavior for all of CMCs is observed and further confirmed by steady-state shear test. Interestingly, two unique transitions, denoted as a small peak region of the shear viscosity for CMCs with m > 2.1% and a sharp drop region of the shear viscosity for CMCs with m 1), respectively. Further, analysis on the recovery of CMCs at rest after underwent a preshearing process was performed with an emphasis to explain the presence of these unique transitions. Thixotropic effect was observed in CMCs and showed strong dependence on m and the preshearing history. Failure to Cox-Merz rule of the rheological behavior of CMCs suggests that some preferential orientation of the initial quiescent random arrangement of CMCs particles or their tactoids occurs under the applied shearing.

  6. A note on unique solvability of the absolute value equation

    Directory of Open Access Journals (Sweden)

    Taher Lotfi

    2014-05-01

    Full Text Available It is proved that applying sufficient regularity conditions to the interval matrix $[A-|B|,A+|B|]$‎, ‎we can create a new unique solvability condition for the absolute value equation $Ax+B|x|=b$‎, ‎since regularity of interval matrices implies unique solvability of their corresponding absolute value equation‎. ‎This condition is formulated in terms of positive definiteness of a certain point matrix‎. ‎Special case $B=-I$ is verified too as an application.

  7. Synthetic Biology of Cyanobacteria: Unique Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Bertram M Berla

    2013-08-01

    Full Text Available Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria’s potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as ‘chassis’ strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a ‘green E. coli’. In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

  8. Non-unique monopole oscillations of harmonically confined Yukawa systems

    Science.gov (United States)

    Ducatman, Samuel; Henning, Christian; Kaehlert, Hanno; Bonitz, Michael

    2008-11-01

    Recently it was shown that the Breathing Mode (BM), the mode of uniform radial expansion and contraction, which is well known from harmonically confined Coulomb systems [1], does not exist in general for other systems [2]. As a consequence the monopole oscillation (MO), the radial collective excitation, is not unique, but there are several MO with different frequencies. Within this work we show simulation results of those monopole oscillations of 2-dimensional harmonically confined Yukawa systems, which are known from, e.g., dusty plasma crystals [3,4]. We present the corresponding spectrum of the particle motion, including analysis of the frequencies found, and compare with theoretical investigations.[1] D.H.E. Dubin and J.P. Schiffer, Phys. Rev. E 53, 5249 (1996)[2] C. Henning at al., accepted for publication in Phys. Rev. Lett. (2008)[3] A. Melzer et al., Phys. Rev. Lett. 87, 115002 (2001)[4] M. Bonitz et al., Phys. Rev. Lett. 96, 075001 (2006)

  9. Uniqueness: skews bit occurrence frequencies in randomly generated fingerprint libraries.

    Science.gov (United States)

    Chen, Nelson G

    2016-08-01

    Requiring that randomly generated chemical fingerprint libraries have unique fingerprints such that no two fingerprints are identical causes a systematic skew in bit occurrence frequencies, the proportion at which specified bits are set. Observed frequencies (O) at which each bit is set within the resulting libraries systematically differ from frequencies at which bits are set at fingerprint generation (E). Observed frequencies systematically skew toward 0.5, with the effect being more pronounced as library size approaches the compound space, which is the total number of unique possible fingerprints given the number of bit positions each fingerprint contains. The effect is quantified for varying library sizes as a fraction of the overall compound space, and for changes in the specified frequency E. The cause and implications for this systematic skew are subsequently discussed. When generating random libraries of chemical fingerprints, the imposition of a uniqueness requirement should either be avoided or taken into account.

  10. Is subjective social status a unique correlate of physical health? A meta-analysis.

    Science.gov (United States)

    Cundiff, Jenny M; Matthews, Karen A

    2017-12-01

    Both social stratification (e.g., social rank) as well as economic resources (e.g., income) are thought to contribute to socioeconomic health disparities. It has been proposed that subjective socioeconomic status (an individual's perception of his or her hierarchical rank) provides increased predictive utility for physical health over and above more traditional, well-researched socioeconomic constructs such as education, occupation, and income. PsycINFO and PubMed databases were systematically searched for studies examining the association of subjective socioeconomic status (SES) and physical health adjusting for at least 1 measure of objective SES. The final sample included 31 studies and 99 unique effects. Meta-analyses were performed to: (a) estimate the overlap among subjective and objective indicators of SES and (b) estimate the cumulative association of subjective SES with physical health adjusting for objective SES. Potential moderators such as race and type of health indicator assessed (global self-reports vs. more specific and biologically based indicators) were also examined. Across samples, subjective SES shows moderate overlap with objective indicators of SES, but associations are much stronger in Whites than Blacks. Subjective SES evidenced a unique cumulative association with physical health in adults, above and beyond traditional objective indicators of SES (Z = .07, SE = .01, p Subjective SES may provide unique information relevant to understanding disparities in health, especially self-rated health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Feeling fat in eating disorders: Testing the unique relationships between feeling fat and measures of disordered eating in anorexia nervosa and bulimia nervosa.

    Science.gov (United States)

    Linardon, Jake; Phillipou, Andrea; Castle, David; Newton, Richard; Harrison, Philippa; Cistullo, Leonardo L; Griffiths, Scott; Hindle, Annemarie; Brennan, Leah

    2018-06-01

    Although widely discussed in theories of eating disorders, the experience of "feeling fat" in this population has received little research attention. This study tested the unique relationships between feeling fat and measures of problematic eating behaviours and attitudes. Data were analysed from individuals with anorexia nervosa (AN; n = 123) and bulimia nervosa (BN; n = 51). Correlations revealed considerable unshared variance between feeling fat and shape and weight over-evaluation and depressive symptoms. Moreover, when over-evaluation and depressive symptoms were controlled, feeling fat predicted unique variance in restraint and eating concerns. Findings offer some support for the idea that feeling fat is a distinct and important component of body image concerns in eating disorders. Further research that develops a standardized measure of feeling fat is required. Further research that examines whether feeling fat is an important treatment mechanism is also needed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions.

    Directory of Open Access Journals (Sweden)

    Zuchra Zakirova

    2018-01-01

    Full Text Available Dystonia is characterized by involuntary muscle contractions. Its many forms are genetically, phenotypically and etiologically diverse and it is unknown whether their pathogenesis converges on shared pathways. Mutations in THAP1 [THAP (Thanatos-associated protein domain containing, apoptosis associated protein 1], a ubiquitously expressed transcription factor with DNA binding and protein-interaction domains, cause dystonia, DYT6. There is a unique, neuronal 50-kDa Thap1-like immunoreactive species, and Thap1 levels are auto-regulated on the mRNA level. However, THAP1 downstream targets in neurons, and the mechanism via which it causes dystonia are largely unknown. We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1 C54Y or ΔExon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum. Enriched pathways and gene ontology terms include eIF2α Signaling, Mitochondrial Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and Synaptic LongTerm Depression, which are dysregulated in a genotype and tissue-dependent manner. Electrophysiological and neurite outgrowth assays were consistent with those enrichments, and the plasticity defects were partially corrected by salubrinal. Notably, several of these pathways were recently implicated in other forms of inherited dystonia, including DYT1. We conclude that dysfunction of these pathways may represent a point of convergence in the pathophysiology of several forms of inherited dystonia.

  13. Gratitude uniquely predicts lower depression in chronic illness populations: A longitudinal study of inflammatory bowel disease and arthritis.

    Science.gov (United States)

    Sirois, Fuschia M; Wood, Alex M

    2017-02-01

    Although gratitude has been identified as a key clinically relevant trait for improving well-being, it is understudied within medical populations. The current study addressed this gap and extended previous and limited cross-sectional research by examining the longitudinal associations of gratitude to depression in 2 chronic illness samples, arthritis and inflammatory bowel disease (IBD). Two chronic illness samples, arthritis (N = 423) and IBD (N = 427), completed online surveys at Time 1 (T1). One hundred sixty-three people with arthritis and 144 people with IBD completed the 6-month follow-up survey (T2). Depression, gratitude, illness cognitions, perceived stress, social support, and disease-related variables were assessed at T1 and T2. At T2, 57.2% of the arthritis sample and 53.4% of the IBD sample met the cut off scores for significant depression. T1 gratitude was negatively associated with depressive symptoms at T1 and T2 in both samples (rs from -.43 to -.50). Regression analyses revealed that T1 gratitude remained a significant and unique predictor of lower T2 depression after controlling for T1 depression, relevant demographic variables, illness cognitions, changes in illness-relevant variables, and another positive psychological construct, thriving, in both samples. As the first investigation of the longitudinal associations of gratitude to psychological well-being in the context of chronic illness, the current study provides important evidence for the relevance of gratitude for health-related clinical populations. Further intervention-based research is warranted to more fully understand the potential benefits of gratitude for adjustment to chronic illness. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. A Content Analysis of Unique Selling Propositions of Tobacco Print Ads.

    Science.gov (United States)

    Johnson Shen, Megan; Banerjee, Smita C; Greene, Kathryn; Carpenter, Amanda; Ostroff, Jamie S

    2017-03-01

    We describe the unique selling propositions (USPs) (propositions used to convince customers to use a particular brand/product by focusing on the unique benefit) of print tobacco ads. A qualitative content analysis was conducted of print tobacco ads (N = 171) selected from August 2012 to August 2013 for cigarettes, moist snuff, e-cigarettes, cigars, and snus to determine the content and themes of USPs for tobacco ads. Cigarette ad USP themes focused on portraying the product as attractive; moist snuff ads focused on portraying product as masculine; cigar ads focused on selling a "high end product;" and new and emerging tobacco products (e-cigarette, snus) focused on directly comparing these products to cigarettes. Whereas traditional tobacco product ads used USPs focused on themes of enjoyment and pleasure (eg, attractive for cigarettes, "high end product" for cigars), new and emerging tobacco product ads offered the unique benefit (USP) of their product being a better and "safer" alternative to traditional tobacco products. Snuff's USPs focused nearly exclusively on the masculinity of their products. Our results provide targets for potential tobacco regulatory actions that could be implemented to reduce demand for tobacco products by reducing their perceived unique benefits.

  15. Edges and vertices in a unique signed circle in a signed graph

    Directory of Open Access Journals (Sweden)

    Richard Behr

    2017-12-01

    Full Text Available We examine the conditions under which a signed graph contains an edge or a vertex that is contained in a unique negative circle or a unique positive circle. For an edge in a unique signed circle, the positive and negative case require the same structure on the underlying graph, but the requirements on the signature are different. We characterize the structure of the underlying graph necessary to support such an edge in terms of bridges of a circle. We then use the results from the edge version of the problem to help solve the vertex version.

  16. High-throughput screening reveals alsterpaullone, 2-cyanoethyl as a potent p27Kip1 transcriptional inhibitor.

    Directory of Open Access Journals (Sweden)

    Brandon J Walters

    Full Text Available p27Kip1 is a cell cycle inhibitor that prevents cyclin dependent kinase (CDK/cyclin complexes from phosphorylating their targets. p27Kip1 is a known tumor suppressor, as the germline loss of p27Kip1 results in sporadic pituitary formation in aged rodents, and its presence in human cancers is indicative of a poor prognosis. In addition to its role in cancer, loss of p27Kip1 results in regenerative phenotypes in some tissues and maintenance of stem cell pluripotency, suggesting that p27Kip1 inhibitors could be beneficial for tissue regeneration. Because p27Kip1 is an intrinsically disordered protein, identifying direct inhibitors of the p27Kip1 protein is difficult. Therefore, we pursued a high-throughput screening strategy to identify novel p27Kip1 transcriptional inhibitors. We utilized a luciferase reporter plasmid driven by the p27Kip1 promoter to transiently transfect HeLa cells and used cyclohexamide as a positive control for non-specific inhibition. We screened a "bioactive" library consisting of 8,904 (4,359 unique compounds, of which 830 are Food and Drug Administration (FDA approved. From this screen, we successfully identified 111 primary hits with inhibitory effect against the promoter of p27Kip1. These hits were further refined using a battery of secondary screens. Here we report four novel p27Kip1 transcriptional inhibitors, and further demonstrate that our most potent hit compound (IC50 = 200 nM Alsterpaullone 2-cyanoethyl, inhibits p27Kip1 transcription by preventing FoxO3a from binding to the p27Kip1 promoter. This screen represents one of the first attempts to identify inhibitors of p27Kip1 and may prove useful for future tissue regeneration studies.

  17. The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby (Michigan)

    2014-10-02

    {alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

  18. The unique hemoglobin system of Pleuragramma antarcticum, an antarctic migratory teleost. Structure and function of the three components.

    Science.gov (United States)

    Tamburrini, M; D'Avino, R; Fago, A; Carratore, V; Kunzmann, A; Prisco, G

    1996-09-27

    Pleuragramma antarcticum (suborder Notothenioidei, family Nototheniidae) is the most abundant fish in the antarctic shelf. This pelagic species has a circum-antarctic distribution and is characterized by spawning migration. This species displays the highest multiplicity of major hemoglobins (three); the other notothenioids have a single one (except one species, having two) with relatively low oxygen affinity regulated by pH and organophosphates. The hemoglobins of P. antarcticum display strong Bohr and Root effects; however, they reveal important functional differences in subunit cooperativity and organophosphate regulation and, above all, in the response of oxygenation to temperature. Despite the substitution ValbetaE11 --> Ile found in Hb 2, which decreases the affinity in human mutants, the hemoglobins have similar oxygen affinity, higher than that of the other notothenioids. Hb 1 has the alpha chain in common with Hb 2 and the beta in common with Hb 3. The amino acid sequence of all four chains has been established. Thus the hematological features of P. antarcticum differ remarkably from those of antarctic notothenioids. This unique and sophisticated oxygen transport system may adequately meet the requirements of the unusual mode of life of this fish.

  19. On the Existence and Uniqueness of the Scientific Method.

    Science.gov (United States)

    Wagensberg, Jorge

    2014-01-01

    The ultimate utility of science is widely agreed upon: the comprehension of reality. But there is much controversy about what scientific understanding actually means, and how we should proceed in order to gain new scientific understanding. Is there a method for acquiring new scientific knowledge? Is this method unique and universal? There has been no shortage of proposals, but neither has there been a shortage of skeptics about these proposals. This article proffers for discussion a potential scientific method that aspires to be unique and universal and is rooted in the recent and ancient history of scientific thinking. Curiously, conclusions can be inferred from this scientific method that also concern education and the transmission of science to others.

  20. Uniqueness of KMS states for continuous fermion systems

    International Nuclear Information System (INIS)

    Jaekel, C.D.

    1993-01-01

    In 1989 Prof H. Narnhofer and Prof. W. Thirring established a (nonlocal) model of fermions with pair interactions. The existence of equilibrium states and the appearance of mixing properties was proofed. If this model reflects the basic facts of nature, one has to expect and to require that at high temperatures there is a unique equilibrium state and at low temperatures there are many different equilibrium states. Uniqueness of the equilibrium state at high temperatures is the topic of this dissertation. One may be astonished, that the proof of the uniqueness requires such a huge machinery, while the existence of KMS-states followes from fairly general conditions. Two states differ, if they can be distinguished by experiment. If one considers now that we have to show that two KMS-states at high temperatures result into the same value in all experiments one can think of, one might get an idea how unhandy this problem is. Even a conscious numeration of all experiments was a problem. Surprisingly only a few principal ideas of the treatment of spin-models survive. The temperature is the leading parameter and therefore it is a good idea to make a high temperature perturbation expansion for the KMS-condition, which fixes an equilibrium state in mathematical terms. But when we choose a generating vector for the perturbation expansion the similarities end. We better use physical considerations: at high temperatures we expect that chemical bounds will be broken up and the interacting equilibrium state will differ only slightly from the equilibrium state for the free time evolution. Roughly spoken, one can expect that high-energetic particles neglect interactions and fly in a straight line. In chapter 2.4 the whole machinery is presented in an easy-to-survey manner on a simple interaction. But in the case of pair interactions every particle interacts with each other and so the author was not able to find an easily accessible form of the developed method for this case

  1. Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

    Science.gov (United States)

    Chiu, Chun-Ching; Shi, Ya-Fang; Yang, Jiann-Jou; Hsiao, Yuan-Chao; Tzang, Bor-Show; Hsu, Tsai-Ching

    2014-01-01

    As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity. PMID:25268969

  2. Unique nest architecture in the North African osmiine bee Hoplitis (Hoplitis mucida (Hymenoptera, Megachilidae

    Directory of Open Access Journals (Sweden)

    Andreas Müller

    2017-10-01

    Full Text Available The osmiine bee species Hoplitis mucida is considered to consist of two subspecies with H. mucida mucida (Dours, 1873 ranging from northwestern Africa to Israel and Jordan and H. mucida stecki (Frey-Gessner, 1908 occurring in southwestern Europe and Sicily. The discovery of nests of H. mucida in Morocco and Tunisia revealed striking differences in the nesting biology of the two subspecies. In North Africa, females construct fully exposed, cake-like nests of mud on the flat surface of rocks and stones containing 8–12 vertically oriented brood cells, rendering these nests unique among osmiine bees regarding both nesting site and nest architecture. In contrast, in Europe females build their few-celled mud nests inside small rock cavities. This discrepancy in the nesting biology is paralleled by considerable morphological differences between the two subspecies suggestive of a long geographical isolation. Due to these biological and morphological differences, we propose to elevate the European subspecies H. mucida stecki to species rank.

  3. BAC and RNA sequencing reveal the brown planthopper resistance gene BPH15 in a recombination cold spot that mediates a unique defense mechanism.

    Science.gov (United States)

    Lv, Wentang; Du, Ba; Shangguan, Xinxin; Zhao, Yan; Pan, Yufang; Zhu, Lili; He, Yuqing; He, Guangcun

    2014-08-11

    Brown planthopper (BPH, Nilaparvata lugens Stål), is the most destructive phloem-feeding insect pest of rice (Oryza sativa). The BPH-resistance gene BPH15 has been proved to be effective in controlling the pest and widely applied in rice breeding programs. Nevertheless, molecular mechanism of the resistance remain unclear. In this study, we narrowed down the position of BPH15 on chromosome 4 and investigated the transcriptome of BPH15 rice after BPH attacked. We analyzed 13,000 BC2F2 plants of cross between susceptible rice TN1 and the recombinant inbred line RI93 that carrying the BPH15 gene from original resistant donor B5. BPH15 was mapped to a 0.0269 cM region on chromosome 4, which is 210-kb in the reference genome of Nipponbare. Sequencing bacterial artificial chromosome (BAC) clones that span the BPH15 region revealed that the physical size of BPH15 region in resistant rice B5 is 580-kb, much bigger than the corresponding region in the reference genome of Nipponbare. There were 87 predicted genes in the BPH15 region in resistant rice. The expression profiles of predicted genes were analyzed. Four jacalin-related lectin proteins genes and one LRR protein gene were found constitutively expressed in resistant parent and considered the candidate genes of BPH15. The transcriptomes of resistant BPH15 introgression line and the susceptible recipient line were analyzed using high-throughput RNA sequencing. In total, 2,914 differentially expressed genes (DEGs) were identified. BPH-responsive transcript profiles were distinct between resistant and susceptible plants and between the early stage (6 h after infestation, HAI) and late stage (48 HAI). The key defense mechanism was related to jasmonate signaling, ethylene signaling, receptor kinase, MAPK cascades, Ca(2+) signaling, PR genes, transcription factors, and protein posttranslational modifications. Our work combined BAC and RNA sequencing to identify candidate genes of BPH15 and revealed the resistance mechanism

  4. The Relations of Family Members’ Unique and Shared Perspectives of Family Dysfunction to Dyad Adjustment

    Science.gov (United States)

    Jager, Justin; Yuen, Cynthia X.; Bornstein, Marc H.; Putnick, Diane L.; Hendricks, Charlene

    2017-01-01

    Among a community sample of families (N = 128), this study examined how family members’ shared and unique perspectives of family dysfunction relate to dyad members’ shared views of dyad adjustment within adolescent-mother, adolescent-father, and mother-father dyads. Independent of a family’s family perspective (shared perspective of family dysfunction), the adolescent’s unique perspective was associated with lower security and higher conflict with both mother and father, the father’s unique perspective was associated with lower security and higher conflict with the adolescent as well as lower marital quality with mother, and the mother unique perspective was associated with lower marital quality with the father. Moreover, for adolescent-parent dyads, compared to the parent unique perspective, the adolescent unique perspective was more strongly associated with dyad adjustment. These findings indicate that both shared and unique views of the family system – the adolescent’s unique view in particular - independently relate to the health of family subsystems. They also suggest that research as well as therapeutic interventions that focus on just the shared view of the family may miss important elements of family dysfunction. PMID:24884682

  5. Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques

    International Nuclear Information System (INIS)

    Noda, Akihiro; Fushiki, Hiroshi; Murakami, Yoshihiro; Sasaki, Hiroshi; Miyoshi, Sosuke; Kakuta, Hirotoshi; Nishimura, Shintaro

    2012-01-01

    Introduction: Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT 1 ) receptor (AT 1 R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using 11 C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Methods: Three male rhesus macaques were bolus intravenously administered [ 11 C]telmisartan either alone or as a mixture with unlabeled telmisartan (1 mg/kg). Dynamic PET images were acquired for 95 min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Results: Telmisartan penetrated into the brain little but enough to block AT 1 R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90 min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT 1 R distribution was noted over the entire brain, even on tracer alone dosing. Conclusions: Telmisartan penetrated into the brain enough to block AT 1 R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs.

  6. Establishment and characterization of a new epithelial cell line, KC-1, from koala (Phascolarctos cinereus) conjunctiva.

    Science.gov (United States)

    Girjes, Adeeb A; Lee, Kristen E; Carrick, Frank N

    2003-01-01

    A novel, untransformed koala cell line (KC-1) was established by culturing koala conjunctival tissue in growth medium, which has permitted the study of the cell biology of this unique system. After the establishment of the KC-1 cell line, the cells were characterized by light microscopy, doubling time, and Western blot analysis. Light microscopy revealed that the cells have an epithelial morphology. Doubling times were significantly different (P koala cell line was adapted to grow continuously in Dulbecco modified Eagle medium containing 10% FCS for at least 30 passages. This unique cell line is an ideal tool for further investigation on koala cell biology and cytogenetics and for exploration of the pathophysiological mechanism of eye infections caused by different pathogens in koalas.

  7. The phosphoproteome of Aspergillus nidulans reveals functional association with cellular processes involved in morphology and secretion.

    Science.gov (United States)

    Ramsubramaniam, Nikhil; Harris, Steven D; Marten, Mark R

    2014-11-01

    We describe the first phosphoproteome of the model filamentous fungus Aspergillus nidulans. Phosphopeptides were enriched using titanium dioxide, separated using a convenient ultra-long reverse phase gradient, and identified using a "high-high" strategy (high mass accuracy on the parent and fragment ions) with higher-energy collisional dissociation. Using this approach 1801 phosphosites, from 1637 unique phosphopeptides, were identified. Functional classification revealed phosphoproteins were overrepresented under GO categories related to fungal morphogenesis: "sites of polar growth," "vesicle mediated transport," and "cytoskeleton organization." In these same GO categories, kinase-substrate analysis of phosphoproteins revealed the majority were target substrates of CDK and CK2 kinase families, indicating these kinase families play a prominent role in fungal morphogenesis. Kinase-substrate analysis also identified 57 substrates for kinases known to regulate secretion of hydrolytic enzymes (e.g. PkaA, SchA, and An-Snf1). Altogether this data will serve as a benchmark that can be used to elucidate regulatory networks functionally associated with fungal morphogenesis and secretion. All MS data have been deposited in the ProteomeXchange with identifier PXD000715 (http://proteomecentral.proteomexchange.org/dataset/PXD000715). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

    Science.gov (United States)

    Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

    2005-09-01

    We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

  9. The neXtProt peptide uniqueness checker: a tool for the proteomics community.

    Science.gov (United States)

    Schaeffer, Mathieu; Gateau, Alain; Teixeira, Daniel; Michel, Pierre-André; Zahn-Zabal, Monique; Lane, Lydie

    2017-11-01

    The neXtProt peptide uniqueness checker allows scientists to define which peptides can be used to validate the existence of human proteins, i.e. map uniquely versus multiply to human protein sequences taking into account isobaric substitutions, alternative splicing and single amino acid variants. The pepx program is available at https://github.com/calipho-sib/pepx and can be launched from the command line or through a cgi web interface. Indexing requires a sequence file in FASTA format. The peptide uniqueness checker tool is freely available on the web at https://www.nextprot.org/tools/peptide-uniqueness-checker and from the neXtProt API at https://api.nextprot.org/. lydie.lane@sib.swiss. © The Author(s) 2017. Published by Oxford University Press.

  10. On uniqueness in diffuse optical tomography

    International Nuclear Information System (INIS)

    Harrach, Bastian

    2009-01-01

    A prominent result of Arridge and Lionheart (1998 Opt. Lett. 23 882–4) demonstrates that it is in general not possible to simultaneously recover both the diffusion (aka scattering) and the absorption coefficient in steady-state (dc) diffusion-based optical tomography. In this work we show that it suffices to restrict ourselves to piecewise constant diffusion and piecewise analytic absorption coefficients to regain uniqueness. Under this condition both parameters can simultaneously be determined from complete measurement data on an arbitrarily small part of the boundary

  11. Assessment of labour market returns in the case of gender unique human capital

    OpenAIRE

    Paas, Tiiu; Tverdostup, Maryna

    2016-01-01

    Maryna Tverdostup, Tiiu Paas, ERSA 2016: The paper focuses on the identification of the unique, non-reached by the opposite gender human capital and the analysis of its effect on the earning profiles of unique human capital holders. The overwhelming research aim is to better understand the possible reasons behind gender wage disparities, focusing on the unique features of male and female human capital and their returns. When assessing the gender pay disparities, variation of human capital cha...

  12. Curcumolide, a unique sesquiterpenoid with anti-inflammatory properties from Curcuma wenyujin.

    Science.gov (United States)

    Dong, Jianyong; Shao, Weiwei; Yan, Pengcheng; Cai, Xiaoqing; Fang, Lianglian; Zhao, Xiaowei; Lin, Weiwei; Cai, Yuan

    2015-01-15

    Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. The structure and absolute configuration were elucidated by extensive NMR, ECD data analysis, and a single-crystal X-ray study. This molecule exhibited significant anti-inflammatory effects in LPS-induced RAW 264.7 macrophages. It suppressed LPS-induced NF-κB activation, including the nuclear translocation and DNA binding activity of NF-κB, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitric oxide (NO) and reactive oxygen species (ROS) production. Therefore, Curcumolide may have therapeutic potential for treating inflammatory diseases by inhibiting NF-κB activation and pro-inflammatory mediator production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition

    Science.gov (United States)

    Limou, Sophie; Delaneau, Olivier; van Manen, Daniëlle; An, Ping; Sezgin, Efe; Le Clerc, Sigrid; Coulonges, Cédric; Troyer, Jennifer L.; Veldink, Jan H.; van den Berg, Leonard H.; Spadoni, Jean-Louis; Taing, Lieng; Labib, Taoufik; Montes, Matthieu; Delfraissy, Jean-François; Schachter, François; O’Brien, Stephen J.; Buchbinder, Susan; van Natta, Mark L.; Jabs, Douglas A.; Froguel, Philippe; Schuitemaker, Hanneke; Winkler, Cheryl A.

    2012-01-01

    Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10−5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10−8. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation. PMID:22362864

  14. Extensive genomic plasticity in Pseudomonas aeruginosa revealed by identification and distribution studies of novel genes among clinical isolates.

    Science.gov (United States)

    Shen, Kai; Sayeed, Sameera; Antalis, Patricia; Gladitz, John; Ahmed, Azad; Dice, Bethany; Janto, Benjamin; Dopico, Richard; Keefe, Randy; Hayes, Jay; Johnson, Sandra; Yu, Sujun; Ehrlich, Nathan; Jocz, Jennifer; Kropp, Laura; Wong, Ray; Wadowsky, Robert M; Slifkin, Malcolm; Preston, Robert A; Erdos, Geza; Post, J Christopher; Ehrlich, Garth D; Hu, Fen Z

    2006-09-01

    The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.

  15. Evaluation of unique identifiers used for citation linking [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Heidi Holst Madsen

    2016-06-01

    Full Text Available Unique identifiers (UID are seen as an effective tool to create links between identical publications in databases or identify duplicates in a database. The purpose of the present study is to investigate how well UIDs work for citation linking. We have two objectives: Explore the coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match key.   Illustrate how publication sets formed by using UIDs as the match key may affect the bibliometric indicators: Number of publications, number of citations and the average number of citations per publication.   The objectives are addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI, incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition.   The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication.   The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of UIDs may become critical for the inclusion of a publication or a database in a bibliometric analysis.

  16. Three Unique Implementations of Processes for PyCSP

    DEFF Research Database (Denmark)

    Friborg, Rune Møllegaard; Bjørndalen, John Markus; Vinter, Brian

    2009-01-01

    In this work we motivate and describe three unique implementations of processes for PyCSP: process, thread and greenlet based. The overall purpose is to demonstrate the feasibility of Communicating Sequential Processes as a framework for different application types and target platforms. The result...

  17. Differentiating Performance Approach Goals and Their Unique Effects

    Science.gov (United States)

    Edwards, Ordene V.

    2014-01-01

    The study differentiates between two types of performance approach goals (competence demonstration performance approach goal and normative performance approach goal) by examining their unique effects on self-efficacy, interest, and fear of failure. Seventy-nine students completed questionnaires that measure performance approach goals,…

  18. Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry.

    Science.gov (United States)

    Asara, John M; Schweitzer, Mary H; Freimark, Lisa M; Phillips, Matthew; Cantley, Lewis C

    2007-04-13

    Fossilized bones from extinct taxa harbor the potential for obtaining protein or DNA sequences that could reveal evolutionary links to extant species. We used mass spectrometry to obtain protein sequences from bones of a 160,000- to 600,000-year-old extinct mastodon (Mammut americanum) and a 68-million-year-old dinosaur (Tyrannosaurus rex). The presence of T. rex sequences indicates that their peptide bonds were remarkably stable. Mass spectrometry can thus be used to determine unique sequences from ancient organisms from peptide fragmentation patterns, a valuable tool to study the evolution and adaptation of ancient taxa from which genomic sequences are unlikely to be obtained.

  19. Clinical EPR: Unique Opportunities and Some Challenges

    Science.gov (United States)

    Swartz, Harold M.; Williams, Benjamin B.; Zaki, Bassem I.; Hartford, Alan C.; Jarvis, Lesley A.; Chen, Eunice; Comi, Richard J.; Ernstoff, Marc S.; Hou, Huagang; Khan, Nadeem; Swarts, Steven G.; Flood, Ann B.; Kuppusamy, Periannan

    2014-01-01

    Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe and regulatory constraints. This paper describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry), and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease, by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice. PMID:24439333

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