HCMV Reprogramming of Infected Monocyte Survival and Differentiation: A Goldilocks Phenomenon

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Emily V. Stevenson

2014-02-01

Full Text Available The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes are also known to play a key role in viral latency and life-long persistence. However, in order to utilize infected monocytes for viral spread and persistence, HCMV must overcome a number of monocyte biological hurdles, including their naturally short lifespan and their inability to support viral gene expression and replication. Our laboratory has shown that HCMV is able to manipulate the biology of infected monocytes in order to overcome these biological hurdles by inducing the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral gene expression and replication. In this current review, we describe the unique aspects of how HCMV promotes monocyte survival and differentiation by inducing a “finely-tuned” macrophage cell type following infection. Specifically, we describe the induction of a uniquely polarized macrophage subset from infected monocytes, which we argue is the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host.

Target organs for avian pancreatic polypeptide

International Nuclear Information System (INIS)

Kimmel, J.R.; Pollock, H.G.

1981-01-01

The problem of the physiological function of pancreatic polypeptide (PP) has been approached by attempting to identify target organs. Avian PP (aPP) labeled with 125I at either the C-terminus (aPP-C) or the N-terminus (aPP-N) was injected into fasted chickens and allowed to circulate for 3-120 min. At the end of the equilibration period, the anesthetized bird was perfused first with saline, then with Buoin's solution. Samples of fixed tissue from various organs were collected, weighed, and counted. Control experiments consisted of coinjection of unlabeled aPP to compete for receptors. The rate of disappearance of aPP-N from plasma was greater than that of aPP-C. Binding of aPP-N by spleen, duodenum, ileum, pancreas, and bone marrow was markedly reduced by coinjection of unlabeled aPP. A similar but less marked reduction in binding was found in liver and proventriculus. aPP-C gave less conclusive results. The maximal competitive effect of unlabeled PP could be achieved in most cases with 30 microgram unlabeled aPP. It is concluded that pancreas, duodenum, ileum, spleen, and bone marrow, and probably liver and proventriculus, are target organs for aPP in the chicken and that the C-terminal region of aPP is involved in receptor binding

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.

Science.gov (United States)

Mele, Federico; Fornara, Chiara; Jarrossay, David; Furione, Milena; Arossa, Alessia; Spinillo, Arsenio; Lanzavecchia, Antonio; Gerna, Giuseppe; Sallusto, Federica; Lilleri, Daniele

2017-01-01

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins. Whereas, following natural infection, the majority of effector/memory CD4+ and CD8+ T cells recognized either gB or IE-1, respectively, and pp65. The pattern of T cell reactivity was comparable at early and late stages of infection and in pregnant women with primary HCMV infection transmitting or not transmitting the virus to the fetus. At an early stage of primary infection, about 50% of HCMV-reactive CD4+ T cells were long-term IL-7Rpos memory cells, while 6-12 months later, the frequency of these cells increased to 70%, approaching 100% in remote infections. In contrast, only 10-20% of HCMV-specific CD8+ T cells were long-term memory cells up to 12 months after infection onset, thereafter increasing to 70% in remote infections. Interestingly, a significantly higher frequency of HCMV-specific CD4+ T cells with a long-term IL-7Rpos memory phenotype was observed in non-transmitting compared to transmitting women. These findings indicate that immunodominance in HCMV infection is not predetermined in the naïve compartment, but is the result of virus-host interactions and suggest that prompt control of HCMV infection in pregnancy is associated with the rapid development of long-term IL-7Rpos memory HCMV-specific CD4+ T cells and a low risk of virus transmission to the fetus.

Development of a vivo rabbit ligated intestinal Loop Model for HCMV infection

OpenAIRE

Tang, Jin; Wu, Qiaoxing; Tang, Xinming; Shi, Ruihan; Suo, Jingxia; Huang, Guangping; An, Junqing; Wang, Jingyuan; Yang, Jinling; Hao, Wenzhuo; She, Ruiping; Suo, Xun

2016-01-01

Background Human Cytomegalovirus (HCMV) infections can be found throughout the body, especially in epithelial tissue. Animal model was established by inoculation of HCMV (strain AD-169) or coinoculation with Hepatitis E virus (HEV) into the ligated sacculus rotundus and vermiform appendix in living rabbits. The specimens were collected from animals sacrificed 1 and a half hours after infection. Results The virus was found to be capable of reproducing in these specimens through RT-PCR and West...

HCMV Displays a Unique Transcriptome of Immunomodulatory Genes in Primary Monocyte-Derived Cell Types.

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Ellen Van Damme

Full Text Available Human cytomegalovirus (HCMV is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs. This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages. Consequently, it has been suggested that macrophages and dendritic cells contribute to viral spread in vivo. Thus far only limited knowledge is available on the expression of HCMV genes in terminally differentiated myeloid primary cells and whether or not the virus exhibits a different set of lytic genes in primary cells compared with lytic infection in NHDF fibroblasts. To address these questions, we used Illumina next generation sequencing to determine the HCMV transcriptome in macrophages and dendritic cells during lytic infection and compared it to the transcriptome in NHDF fibroblasts. Here, we demonstrate unique expression profiles in macrophages and dendritic cells which significantly differ from the transcriptome in fibroblasts mainly by modulating the expression of viral transcripts involved in immune modulation, cell tropism and viral spread. In a head to head comparison between macrophages and dendritic cells, we observed that factors involved in viral spread and virion composition are differentially regulated suggesting that the plasticity of the virion facilitates the infection of surrounding cells. Taken together, this study provides the full transcript expression analysis of lytic HCMV genes in monocyte-derived type 1 and type 2 macrophages as well as in monocyte-derived dendritic cells. Thereby

Characterization of ppGalNAc-T18, a member of the vertebrate-specific Y subfamily of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases.

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Li, Xing; Wang, Jing; Li, Wei; Xu, Yingjiao; Shao, Dong; Xie, Yinyin; Xie, Wenxian; Kubota, Tomomi; Narimatsu, Hisashi; Zhang, Yan

2012-05-01

The first step of mucin-type O-glycosylation is catalyzed by members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T; EC 2.4.1.41) family. Each member of this family has unique substrate specificity and expression profiles. In this report, we describe a new subfamily of ppGalNAc-Ts, designated the Y subfamily. The Y subfamily consists of four members, ppGalNAc-T8, -T9, -T17 and -T18, in which the conserved YDX(5)WGGENXE sequence in the Gal/GalNAc-T motif of ppGalNAc-Ts is mutated to LDX(5)YGGENXE. Phylogenetic analysis revealed that the Y subfamily members only exist in vertebrates. All four Y subfamily members lack in vitro GalNAc-transferase activity toward classical substrates possibly because of the UDP-GalNAc-binding pocket mutants. However, ppGalNAc-T18, the newly identified defining member, was localized in the endoplasmic reticulum rather than the Golgi apparatus in lung carcinoma cells. The knockdown of ppGalNAc-T18 altered cell morphology, proliferation potential and changed cell O-glycosylation. ppGalNAc-T18 can also modulate the in vitro GalNAc-transferase activity of ppGalNAc-T2 and -T10, suggesting that it may be a chaperone-like protein. These findings suggest that the new Y subfamily of ppGalNAc-Ts plays an important role in protein glycosylation; characterizing their functions will provide new insight into the role of ppGalNAc-Ts.

PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65

Science.gov (United States)

Zhang, Tiejun; Park, Kyeong Ah; Li, Yuwen; Byun, Hee Sun; Jeon, Juhee; Lee, Yoonjung; Hong, Jang Hee; Kim, Jin Man; Huang, Song-Mei; Choi, Seung-Won; Kim, Sun-Hwan; Sohn, Kyung-Cheol; Ro, Hyunju; Lee, Ji Hoon; Lu, Tao; Stark, George R.; Shen, Han-Ming; Liu, Zheng-gang; Park, Jongsun; Hur, Gang Min

2014-01-01

Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that plant homeodomain finger protein 20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In plant homeodomain finger protein 20-overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between plant homeodomain finger protein 20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that plant homeodomain finger protein 20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies plant homeodomain finger protein 20 as a novel regulator of NF-κB activation and suggests that elevated expression of plant homeodomain finger protein 20 may drive constitutive NF-κB activation in some cancers. PMID:23797602

Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients

DEFF Research Database (Denmark)

Rasmussen, M H; Carstensen, H; List, S

1993-01-01

The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response...... is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion...

Inhibition of cyclophilin A suppresses H2O2-enhanced replication of HCMV through the p38 MAPK signaling pathway.

Science.gov (United States)

Xiao, Jun; Song, Xin; Deng, Jiang; Lv, Liping; Ma, Ping; Gao, Bo; Zhou, Xipeng; Zhang, Yanyu; Xu, Jinbo

2016-09-01

Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H2O2) stimulation, mediated by the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. However, it remains unknown whether host gene expression is involved in H2O2-upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H2O2 in a dose-dependent manner. Experiments with CyPA-specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H2O2-mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression. Furthermore, depletion or inhibition of CyPA reduced H2O2-induced p38 activation, consistent with that of H2O2-upregulated HCMV lytic replication. These results show that H2O2 is capable of activating ROS-CyPA-p38 MAPK interactions to enhance HCMV replication.

The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV Infected Glioblastoma Cells

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Melpomeni Tseliou

2016-01-01

Full Text Available Background/Aims: Rho GTPases are crucial regulators of the actin cytoskeleton, membrane trafficking and cell signaling and their importance in cell migration and invasion is well- established. The human cytomegalovirus (HCMV is a widespread pathogen responsible for generally asymptomatic and persistent infections in healthy people. Recent evidence indicates that HCMV gene products are expressed in over 90% of malignant type glioblastomas (GBM. In addition, the HCMV Immediate Early-1 protein (IE1 is expressed in >90% of tumors analyzed. Methods: RhoA, RhoB and RhoC were individually depleted in U373MG glioblastoma cells as well as U373MG cells stably expressing the HCMV IE1 protein (named U373MG-IE1 cells shRNA lentivirus vectors. Cell proliferation assays, migration as well as wound-healing assays were performed in uninfected and HCMV-infected cells. Results: The depletion of RhoA, RhoB and RhoC protein resulted in significant alterations in the morphology of the uninfected cells, which were further enhanced by the cytopathic effect caused by HCMV. Furthermore, in the absence or presence of HCMV, the knockdown of RhoB and RhoC proteins decreased the proliferation rate of the parental and the IE1-expressing glioblastoma cells, whereas the knockdown of RhoA protein in the HCMV infected cell lines restored their proliferation rate. In addition, wound healing assays in U373MG cells revealed that depletion of RhoA, RhoB and RhoC differentially reduced their migration rate, even in the presence or the absence of HCMV. Conclusion: Collectively, these data show for the first time a differential implication of Rho GTPases in morphology, proliferation rate and motility of human glioblastoma cells during HCMV infection, further supporting an oncomodulatory role of HCMV depending on the Rho isoforms' state.

Regulated expression of the human cytomegalovirus pp65 gene: Octamer sequence in the promoter is required for activation by viral gene products

International Nuclear Information System (INIS)

Depto, A.S.; Stenberg, R.M.

1989-01-01

To better understand the regulation of late gene expression in human cytomegalovirus (CMV)-infected cells, the authors examined expression of the gene that codes for the 65-kilodalton lower-matrix phosphoprotein (pp65). Analysis of RNA isolated at 72 h from cells infected with CMV Towne or ts66, a DNA-negative temperature-sensitive mutant, supported the fact that pp65 is expressed at low levels prior to viral DNA replication but maximally expressed after the initiation of viral DNA replication. To investigate promoter activation in a transient expression assay, the pp65 promoter was cloned into the indicator plasmid containing the gene for chloramphenicol acetyltransferase (CAT). Transfection of the promoter-CAT construct and subsequent superinfection with CMV resulted in activation of the promoter at early times after infection. Cotransfection with plasmids capable of expressing immediate-early (IE) proteins demonstrated that the promoter was activated by IE proteins and that both IE regions 1 and 2 were necessary. These studies suggest that interactions between IE proteins and this octamer sequence may be important for the regulation and expression of this CMV gene

Association of human cytomegalovirus viremia with human leukocyte antigens in liver transplantation recipients

Institute of Scientific and Technical Information of China (English)

Jianhua Hu; Jun Fan; Xueqin Meng; Hong Zhao; Xuan Zhang; Hainv Gao; Meifang Yang; Yadan Ma; Minhuan Li; Weihang Ma

2011-01-01

Human cytomegalovirus (HCMV) reactivation is a common complication after liver transplantation (LT).Here, we investigated whether human leukocyte antigen (HLA)-matching was related to HCMV infection and subsequent graft failure after LT for hepatitis B virus cirrhosis. This retrospective study reviewed 91 LT recipients.All the patients were grouped according to HLA-A, HLA-B, and HLA-DR locus matching. Clinical data were collected, including complete HLA-typing, HCMV viremia, graft failure, and the time of HCMV viremia.HLA typing was performed using a sequence-specific primer-polymerase chain reaction kit. HCMV was detected by pp65 antigenemia using a commercial kit.The incidence of HCMV infection post-LT was 81.32%.Graft failure was observed in 16 of 91 (17.6%) patients during the 4-year study. The incidence of HCMV viremia was 100% (5/5), 91.4% (32/35), and 72.5% (37/51) in HLA-A two locus, one locus, and zero locus compatibility,respectively. Nevertheless, the degree of the HLA-A,HLA-B, or HLA-DR match did not influence the time of HCMV viremia, graft failure, or the time of graft failure after a diagnosis of HCMV viremia (all P＞ 0.05). An interesting discovery was that the risk of HCMV viremia tended to be higher in patients with better HLA-A compatibility. Graft failure, time of HCMV viremia, and graft failure after a diagnosis of HCMV viremia appear to be independent of HLA allele compatibility.

Primary structure of pancreatic polypeptide from four species of Perissodactyla (Przewalski's horse, zebra, rhino, tapir).

Science.gov (United States)

Henry, J S; Lance, V A; Conlon, J M

1991-12-01

Pancreatic polypeptide (PP) has been purified from extracts of the pancreas of four species of odd-toed ungulates (Perissodactyla): Przewalski's horse, mountain zebra, white rhinoceros, and mountain tapir. The amino acid sequence of Przewalski's horse pancreatic polypeptide was established as Ala-Pro-Met-Glu-Pro-Val-Tyr-Pro-Gly-Asp10-Asn- Ala-Thr-Pro-Glu-Gln-Met-Ala-Gln-Tyr20-Ala-Ala-Glu-Leu-Arg-Arg-Tyr- Ile-Asn-Met30 - Leu-Thr-Arg-Pro-Arg-Tyr.NH2. Zebra PP was identical to Przewalski's horse PP, rhinoceros PP contained three substitutions relative to the horse (Ser for Ala1, Leu for Met3, and Glu for Gln16), and tapir PP contained one substitution relative to the horse (Leu for Met3). On the basis of morphological characteristics and the fossil record, the rhinocerotids are classified with the tapirids in the suborder Ceratomorpha, whereas the horse and zebra belong to a separate suborder, Hippomorpha. On the basis of structural similarity of the PP molecules, however, it would appear that the tapir is more closely related to the horse than to the rhinoceros. These observations provide a further example of the need for extreme caution when inferring taxonomic or phylogenetic relationships between species from the structures of homologous peptides.

Direct quantification of human cytomegalovirus immediate-early and late mRNA levels in blood of lung transplant recipients by competitive nucleic acid sequence-based amplification

NARCIS (Netherlands)

Greijer, AE; Verschuuren, EAM; Harmsen, MC; Dekkers, CAJ; Adriaanse, HMA; The, TH; Middeldorp, JM

The dynamics of active human cytomegalovirus (HCMV) infection was monitored by competitive nucleic acid sequence-based amplification (NASBA) assays for quantification of IE1 (UL123) and pp67 (UL65) mRNA expression levels In the blood of patients after lung transplantation. RNA was isolated from 339

Identification and HLA-Tetramer-Validation of Human CD4(+) and CD8(+) T Cell Responses against HCMV Proteins IE1 and IE2

DEFF Research Database (Denmark)

Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune Frederik Lamdahl

2014-01-01

tumor development. Both CD4(+) and CD8(+) T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8(+) T cell...

Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44

International Nuclear Information System (INIS)

Alvisi, Gualtiero; Marin, Oriano; Pari, Gregory; Mancini, Manuela; Avanzi, Simone; Loregian, Arianna; Jans, David A.; Ripalti, Alessandro

2011-01-01

The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (T427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events.

Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

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Seung-Joo Hyun

2017-11-01

Full Text Available To define whether individual human leukocyte antigen (HLA class I allotypes are used preferentially in human cytomegalovirus (CMV-specific cytotoxic T lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C present in 50 healthy Korean donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8+ T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

Selecting measures to prevent deleterious alkali-silica reaction in concrete : rationale for the AASHTO PP65 prescriptive approach.

Science.gov (United States)

2012-10-01

PP65-11 provides two approaches for selecting preventive measures: (i) a performance approach based on laboratory testing, and (ii) a prescriptive approach based on a consideration of the reactivity of the aggregate, type and size of structure, expos...

Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

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Haidar A. Shamran

2015-01-01

Full Text Available Human Cytomegalovirus (HCMV is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n=50 and from benign meningioma patients (n=30 were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG compared to 72.5% among control samples (P=0.04. These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

Intestinal mucosa is a target tissue for pancreatic polypeptide

International Nuclear Information System (INIS)

Gilbert, W.R.; Kramer, J.L.; Frank, B.H.; Gingerich, R.L.

1986-01-01

Studies were carried out to identify mammalian tissues capable of specifically binding mammalian pancreatic polypeptide (PP). Bovine PP (bPP) radiolabeled with 125 I was purified by HPLC to yield [ 125 I]iodo-(Tyr-27) bPP. The label was injected into three pairs of fasted littermate dogs and allowed to circulate for 5 min. One of the dogs was a control which received an excess of unlabeled porcine PP to provide competition for receptor binding. Unbound bPP was removed by perfusion with Krebs-Ringer bicarbonate and the tissue fixed in situ with Karnovsky's fixative. Tissue samples from various organs were removed, weighed, and counted. The entire gastrointestinal tract demonstrated high levels of 125 I after injection of the labeled peptide. The duodenum, jejunum, ileum, and colon were the only tissues to exhibit specific binding of bPP. These tissues (mucosal and muscle layers) from experimental animals exhibited 31-76% higher binding than the corresponding tissues from the control animals. Sections of the gastrointestinal tract were scraped to separate the mucosal layer from the underlying muscle layer. The mucosal layer of the duodenum, jejunum, and ileum exhibited 145-162% increases in binding compared to the control animals. The muscle layer of these tissues demonstrated no significant increase. These findings demonstrate that mucosal layer of the small intestine is a target tissue for mammalian PP

Role of pancreatic polypeptide in the regulation of pancreatic exocrine secretion in dogs

International Nuclear Information System (INIS)

Shiratori, Keiko; Lee, K.Y.; Chang, Tamin; Jo, Y.H.; Coy, D.H.; Chey, W.Y.

1988-01-01

The effect of intravenous infusion of synthetic human pancreatic polypeptide (HPP) or a rabbit anti-PP serum on pancreatic exocrine secretion was studied in 10 dogs with gastric and Thomas duodenal cannulas. The infusion of HPP, achieved a plasma PP concentration that mimicked the peak plasma concentration of PP in both interdigestive and postprandial states. This dose of HPP significantly inhibited pancreatic secretion in the interdigestive state. By contrast, immunoneutralization of circulating PP by a rabbit anti-PP serum resulted in significant increases in both interdigestive and postprandial pancreatic secretion, including water, bicarbonate, and protein. The increase in the pancreatic secretion paralleled a decrease in circulating PP level, which lasted for as long as 5 days. Furthermore, the anti-PP serum blocked the inhibitory action of exogenous HPP on pancreatic exocrine secretion. The present study indicates that endogenous PP plays a significant role in the regulation of the pancreatic exocrine secretion in both interdigestive and digestive states. Thus the authors conclude that PP is another hormone regulating pancreatic exocrine secretion in dogs

Rapid detection and quantification of cell free cytomegalovirus by a high-speed centrifugation-based microculture assay: comparison to longitudinally analyzed viral DNA load and pp67 late transcript during lactation.

Science.gov (United States)

Hamprecht, Klaus; Witzel, Simone; Maschmann, Jens; Dietz, Klaus; Baumeister, Andrea; Mikeler, Elfriede; Goelz, Rangmar; Speer, Christian P; Jahn, Gerhard

2003-12-01

Human cytomegalovirus (HCMV) is reactivated in nearly every seropositive breastfeeding mother during lactation [Lancet 357 (2001) 513]. Conventional tissue culture (TC) and low-speed centrifugation-enhanced microtiter culture methods are not able to detect HCMV from milk during all stages of lactation. Development of a sensitive and quantitative microculture technique to describe the dynamics of HCMV reactivation in different milk compartments during lactation. Milk samples were collected longitudinally from seropositive breastfeeding mothers of preterm infants. Native milk samples were separated into fraction 1 (aqueous extract of milk fat), fraction 2 (cell and fat free milk whey) and fraction 3 (milk cells). Each of these fractions was screened qualitatively (TC, nPCR, pp67 late mRNA) and quantitatively (high-speed centrifugation-based microculture, quantitative PCR). Prior to low-speed centrifugation-enhanced inoculation, virus particles were concentrated by high-speed centrifugation (60 min at 50,000 x g, 4 degrees C). Using fraction 2 we were able to describe the dynamics of viral reactivation during lactation. We present the course of the quantitative virolactia and DNAlactia and qualitative detection of HCMV pp67 late mRNA in milk whey of four mothers (three transmitters and one non-transmitter). In all these cases virolactia described an unimodal and self limited course. Peak levels of virolactia for transmitters (T1: day 44; T2: day 43; T3: day 50) were closely related the onset of viruria of the corresponding preterm infants (U1: day 39; U2a/U2b: day 44/57; U3: day 60). The courses of viral load coincidence with the courses of DNA load. We present a rapid and highly sensitive microculture method for the quantification of cell free HCMV from milk whey and aqueous extracts from milk fat. Viral reactivation during lactation describes an unimodal course. Our findings have strong implications for quality control of any virus inactivation procedure.

HCMV spread and cell tropism are determined by distinct virus populations.

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Laura Scrivano

Full Text Available Human cytomegalovirus (HCMV can infect many different cell types in vivo. Two gH/gL complexes are used for entry into cells. gH/gL/pUL(128,130,131A shows no selectivity for its host cell, whereas formation of a gH/gL/gO complex only restricts the tropism mainly to fibroblasts. Here, we describe that depending on the cell type in which virus replication takes place, virus carrying the gH/gL/pUL(128,130,131A complex is either released or retained cell-associated. We observed that virus spread in fibroblast cultures was predominantly supernatant-driven, whereas spread in endothelial cell (EC cultures was predominantly focal. This was due to properties of virus released from fibroblasts and EC. Fibroblasts released virus which could infect both fibroblasts and EC. In contrast, EC released virus which readily infected fibroblasts, but was barely able to infect EC. The EC infection capacities of virus released from fibroblasts or EC correlated with respectively high or low amounts of gH/gL/pUL(128,130,131A in virus particles. Moreover, we found that focal spread in EC cultures could be attributed to EC-tropic virus tightly associated with EC and not released into the supernatant. Preincubation of fibroblast-derived virus progeny with EC or beads coated with pUL131A-specific antibodies depleted the fraction that could infect EC, and left a fraction that could predominantly infect fibroblasts. These data strongly suggest that HCMV progeny is composed of distinct virus populations. EC specifically retain the EC-tropic population, whereas fibroblasts release EC-tropic and non EC-tropic virus. Our findings offer completely new views on how HCMV spread may be controlled by its host cells.

Pancreatic polypeptide is involved in the regulation of body weight in pima Indian male subjects

DEFF Research Database (Denmark)

Koska, Juraj; DelParigi, Angelo; de Courten, Barbora

2004-01-01

Pancreatic polypeptide (PP) is released from the pancreas in response to a meal. In humans, low-circulating PP levels have been observed in obesity, and administration of pharmacological doses of PP has been shown to decrease food intake. The aim of the present study was to investigate whether low...... circulating PP is associated with weight gain in Pima Indians. Plasma PP concentrations were measured after an overnight fast and 30 min after a standardized mixed meal in 33 nondiabetic male subjects who had a follow-up visit 4.9 +/- 2.5 years later. Cross-sectionally, fasting and postprandial PP levels were...... negatively associated with body size and adiposity. Prospectively, the change in PP response to the meal was negatively associated with the change in body weight (r = -0.53, P = 0.002). In contrast, a high fasting PP level was positively associated with change in body weight (r = 0.45, P = 0...

Catalytic and glycan-binding abilities of ppGalNAc-T2 are regulated by acetylation

DEFF Research Database (Denmark)

Zlocowski, Natacha; Sendra, Victor G; Lorenz, Virginia

2011-01-01

Post-translational acetylation is an important molecular regulatory mechanism affecting the biological activity of proteins. Polypeptide GalNAc transferases (ppGalNAc-Ts) are a family of enzymes that catalyze initiation of mucin-type O-glycosylation. All ppGalNAc-Ts in mammals are type II...

Real-time ed end-point Polymerase Chain Reaction per la quantizzazione del DNA di Citomegalovirus: confronto tra metodi e con il test per l’antigene pp65

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Tiziano Allice

2006-03-01

Full Text Available Quantitave Polymerase Chain Reaction (PCR for Cytomegalovirus (CMV DNA provides highly sensitive and specific data for detecting CMV as well as monitoring the infection and determining the appropriate antiviral strategy.To determine the clinical application of a recently introduced real-time (RT PCR assay for CMV DNA quantitation in peripheral blood leukocytes (PBLs and defining its correlation with the commercial quantitative end-point (EP PCR method COBAS AMPLICOR CMV Monitor and pp65 antigen test. Sequential PBL samples (n=158 from 32 liver transplanted patients with CMV asymptomatic infection and positive for CMV DNA by EP-PCR were retrospectively analysed with RT-PCR and studied according to pp65 antigen levels. A good correlation was found between RT-PCR and pp65 antigen test (r=0.691 and between the two PCR assays (r=0.761. RT-PCR data were significantly higher in pre-emptive treated patients (those with >20 pp65+positive cells, median value: 3.8 log10 copies/500,000 PBLs than in not-treated ones (2.9 logs.According to pp65 levels of 0, 1-10, 11-20, 21-50, 51-100 and >100 positive cells/200,000 PBLs, median CMV DNA load by RT-PCR was 2.6, 3.0, 3.6, 4.0. 4.2 and 4.8, log10 copies/ 500,000 PBLs, respectively (EP-PCR CMV DNA levels: 2. 8, 2.9, 3.8, 3.7, 3.9 and 4.0 logs. For samples with >20 pp65+cells, that is above the level at which pre-emptive therapy was started, RT-PCR values were significantly higher than in groups with less than 20 pp65+cells, whereas EP-PCR values did not significantly differ and showed a slower progression rate. Dilutions of DNA from CMV AD169 strain were used to probe RT-PCR reproducibility (between and intra-assay variability < 2% and sensitivity (100% detection rate at 10 copies/reaction, 28.5% with EP-PCR. A significant improvement is coming from the introduction of RT-PCR to the study of CMV DNA dynamics in differently CMV infected patients due to a more reliable quantitation of CMV DNA for moderate and high

Quantitative monitoring of HCMV DNAlactia in human milk by real time PCR assay: Implementation of internal control contributes to standardization and quality control.

Science.gov (United States)

Hartleif, Steffen; Göhring, Katharina; Goelz, Rangmar; Jahn, Gerhard; Hamprecht, Klaus

2016-11-01

For cytomegalovirus screening of breastfeeding mothers of preterm infants under risk, we present a rapid, quantitative real-time PCR protocol using the hybridization format of the viral gB target region. For quantification, we used an external gB fragment cloned into a vector system. For standardization, we created an internal control-plasmid by site-directed mutagenesis with an exchange of 9 nucleotides. Spiked with internal control, patient wildtype amplicons could be discriminated from internal controls by hybridization probes using two-channel fluorescence detection. Potential bias of formerly reported false nucleotide sequence data of gB-hybridization probes was excluded. Using this approach, we could demonstrate excellent analytical performance and high reproducibility of HCMV detection during lactation. This assay shows very good correlation with a commercial quantitative HCMV DNA PCR and may help to identify rapidly HCMV shedding mothers of very low birth weight preterm infants to prevent HCMV transmission. On the other hand, negative DNA amplification results allow feeding of milk samples of seropositive mothers to their preterm infants under risk (<30 weeks of gestational age, <1000g birth weight) during the onset and late stage of HCMV shedding during lactation. Copyright © 2016 Elsevier B.V. All rights reserved.

IgM-specific serodiagnosis of acute human cytomegalovirus infection using recombinant autologous fusion proteins

NARCIS (Netherlands)

Vornhagen, R; Hinderer, W; Sonneborn, HH; Bein, G; Matter, L; The, T. Hauw; Enders, G; Jahn, G; Plachter, B

Portions of three human cytomegalovirus (HCMV) polypeptides, which were shown previously to be highly reactive with patient sera, were expressed in Escherichia coli as autologous fusion proteins. Purified recombinant polypeptides were used as antigens in enzyme linked immunosorbent assay (ELISA) and

Pancreatic polypeptide: Identification of target tissues and investigation of possible physiologic significance

International Nuclear Information System (INIS)

Shetzline, M.A.

1988-01-01

Pancreatic Polypeptide (PP) is a 36 amino acid peptide with hormonal properties but whose physiologic function remains unknown. In order to determine the function of this peptide we investigated potential target tissues using an in vivo radioreceptor assay. In vitro high concentrations of unlabeled hormone competitively inhibit low concentrations of labeled hormone from binding to receptors. Our in vivo studies indicate that, in the presence of concentrated unlabeled peptide, labeled PP distributes between the plasma and interstitial fluid. When saline rather than excess unlabeled PP is injected, the labeled peptide appears to distribute in a volume exceeding the combined plasma and interstitial fluid volume of tissue. The distribution volume which exceeds the anatomic extracellular volume and which is not present with excess unlabeled peptide, is the receptor compartment. With this assay we demonstrated in the rat specific and displaceable PP binding to the ductus choledochus, duodenum, ileum, and adrenal gland. In vitro rat adrenal cell membranes showed specific I-125 labeled PP binding. Specific binding also occurred in bovine cortical and medullary membranes

Immunohistochemical localization of glucagon and pancreatic polypeptide on rat endocrine pancreas: coexistence in rat islet cells

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YH Huang

2009-08-01

Full Text Available We used immunofluorescence double staining method to investigate the cellular localization of glucagon and pancreatic polypeptide (PP in rat pancreatic islets. The results showed that both A-cells (glucagon-secreting cells and PP-cells (PPsecreting cells were located in the periphery of the islets. However, A-cells and PP-cells had a different regional distribution. Most of A-cells were located in the splenic lobe but a few of them were in the duodenal lobe of the pancreas. In contrast, the majority of PP-cells were found in the duodenal lobe and a few of them were in the splenic lobe of the pancreas. Furthermore, we found that 67.74% A-cells had PP immunoreactivity, 70.92% PP-cells contained glucagon immunoreactivity with immunofluorescence double staining. Our data support the concept of a common precursor stem cell for pancreatic hormone-producing cells.

Distribution of Pancreatic Polypeptide-secreting Endocrine Cells in Nondiabetic and Diabetic Cases.

Science.gov (United States)

Śliwińska-Mossoń, Mariola; Milnerowicz, Halina

2017-07-01

The aim of the study was to demonstrate the effects of cigarette smoking and ongoing inflammation in chronic pancreatitis on the functioning of pancreatic polypeptide (PP)-secreting cells and to determine the relationship between the occurrence of an increased number of PP cells in the pancreas, the change in their location, and the intensity of their inflammatory changes in the course of pancreatitis and diabetes. Samples of tissues from healthy persons and from patients were verified histopathologically, and then PP was localized by immunohistochemical staining using the monoclonal anti-human PP antibody. The histopathologic evaluation of the hormone expression intensity in tissue sections was carried out using the semiquantitative method and was calculated with digital image analysis. The present study showed a very strong PP expression in the pancreatic tissue (especially in the head of the pancreas) derived from smoking patients with diabetes. The increase in the percentage of cells in the PP islets, between the acinar cells in smoking patients with diabetes and a statistically significant increase in the expression of PP, indicates a pancreatic endocrine dysfunction and suggests that cigarette smoking has a negative impact on the organ's efficiency. Because of its properties, the PP appears to be a useful marker of the endocrine insufficiency of the pancreas and a specific prognostic parameter of developing diabetes due to chronic pancreatitis.

Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection.

Science.gov (United States)

Cardin, Rhonda D; Bravo, Fernando J; Pullum, Derek A; Orlinger, Klaus; Watson, Elizabeth M; Aspoeck, Andreas; Fuhrmann, Gerhard; Guirakhoo, Farshad; Monath, Thomas; Bernstein, David I

2016-04-12

Congenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine. To determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection. Female Hartley strain guinea pigs were divided into three groups: Buffer control group (n = 9), rLCMV-gB group (n = 11), and rLCMV-pp65 (n = 11). The vaccines were administered three times IM at 1.54 × 10(6)FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼ 45-55 days of gestation with 1 × 10(5)PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined. Pup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group (p = 0.044) and 26% pup mortality in the pp65 vaccine group (p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams (p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams. The rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Loss of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 3 and reduced O-glycosylation in colon carcinoma cells selected for hepatic metastasis

DEFF Research Database (Denmark)

Kato, Kentaro; Takeuchi, Hideyuki; Kanoh, Akira

2010-01-01

O-glycosylation of mucin is initiated by the attachment of N-acetyl-D-galactosamine (GalNAc) to serine or threonine residues in mucin core polypeptides by UDPGalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). It is not well understood how GalNAc attachment is regulated by multiple...... ppGalNAc-Ts in each cell. In the present study, the expression levels of murine ppGalNAc-Ts (mGalNAc-Ts), T1, T2, T3, T4, T6, and T7 were compared between mouse colon carcinoma colon 38 cells and variant SL4 cells, selected for their metastatic potentials, by using the competitive RT-PCR method....... The expression levels of mGalNAc-T1, T2, and T7 were slightly higher in the SL4 cells than in the colon 38 cells, whereas the expression level of mGalNAc-T3 in the SL4 cells was 1.5% of that in the colon 38 cells. Products of enzymatic incorporations of GalNAc residues into FITCPTTTPITTTTK peptide by the use...

Study of pp{yields}pp{eta} reaction at threshold; Etude de la reaction pp{yields}pp{eta} au seuil

Energy Technology Data Exchange (ETDEWEB)

Taleb, A

1994-11-01

The {eta} production has been studied through the pp {yields} pp{eta} reaction at threshold. Data were taken at the Synchrotron of the ``Laboratoire National Saturne``. The detection in coincidence of the two protons scattered near 0 deg and analysed with the magnetic spectrometer SPES3 allows the reconstruction of missing mass spectra for the {eta} signature. A simulation program which takes into account all the experimental set up characteristics has been realized and tested through the pp {yields} d{pi}{sup +} reaction detected simultaneously with pp {yields} pp{eta}. The generated proton momentum spectra for pp {yields} pp{eta} show a pronounced {eta} mass dependence. This characteristic, connected to the kinematical properties of pp {yields} pp{eta} at threshold, is used to extract the mass of the meson {eta}. The obtained value, m{sub {eta}} = 547.65 {+-} 0.18 MeV, is in good agreement with measurement done recently through the pd {yields} {sup H}e{eta} reaction. The total cross section {sigma}{sub t} of pp {yields} pp{eta} measured at 1260, 1265 and 1300 MeV presents a strong energy dependence. This cross section increases less with energy than the phase-space. The influence of p-p and {eta}-p final state interactions in our measurements is studied. Our results are compared with theoretical predictions and assess the dominant character of the baryonic resonance N{sup *}(1535) in the {eta} mechanism production at threshold. These experimental results give an energy dependence which is not well reproduced by the theoretical predictions. This discrepancy could be an incorrect description of the {eta}-p interaction in the models. (author). 48 refs., 60 figs., 15 tabs.

Molecular characterization of a phloem-specific gene encoding the filament protein, phloem protein 1 (PP1), from Cucurbita maxima.

Science.gov (United States)

Clark, A M; Jacobsen, K R; Bostwick, D E; Dannenhoffer, J M; Skaggs, M I; Thompson, G A

1997-07-01

Sieve elements in the phloem of most angiosperms contain proteinaceous filaments and aggregates called P-protein. In the genus Cucurbita, these filaments are composed of two major proteins: PP1, the phloem filament protein, and PP2, the phloem lactin. The gene encoding the phloem filament protein in pumpkin (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein coding sequence, with no introns, encoding an 809 amino acid polypeptide. The deduced polypeptide had characteristics of PP1 and contained a 15 amino acid sequence determined by N-terminal peptide sequence analysis of PP1. The sequence of PP1 was highly repetitive with four 200 amino acid sequence domains containing structural motifs in common with cysteine proteinase inhibitors. Expression of the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the period of rapid hypocotyl elongation after which mRNA levels declined, while protein levels remained elevated. PP1 was immunolocalized in slime plugs and P-protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in companion cells. PP1 mRNA was localized by in situ hybridization in companion cells at early stages of vascular differentiation. The developmental accumulation and localization of PP1 and its mRNA paralleled the phloem lactin, further suggesting an interaction between these phloem-specific proteins.

Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.

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Simone Thomas

2015-07-01

Full Text Available Reactivation of human cytomegalovirus (HCMV can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.

Fasting and meal-induced CCK and PP secretion following intragastric balloon treatment for obesity

NARCIS (Netherlands)

Mathus-Vliegen, Elisabeth M. H.; de Groot, Gerrit H.

2013-01-01

Satiety is centrally and peripherally mediated by gastrointestinal peptides and the vagal nerve. We aimed to investigate whether intragastric balloon treatment affects satiety through effects on fasting and meal-stimulated cholecystokinin (CCK) and pancreatic polypeptide (PP) secretion. Patients

An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2

DEFF Research Database (Denmark)

Zlocowski, Natacha; Lorenz, Virginia; Bennett, Eric Paul

2013-01-01

Abstract Polypeptide GalNAc-transferases (ppGalNAc-Ts) are a family of enzymes that catalyze the initiation of mucin-type O-glycosylation. All ppGalNAc-T family members contain a common (QXW)3 motif which is present in R-type lectin group. Acetylation site K521 is part of the QKW motif of ß......-trefoil in the lectin domain of ppGalNAc-T2. We used a combination of acetylation and site-directed mutagenesis approaches to examine the functional role of K521 in ppGalNAc-T2. Binding assays of non-acetylated and acetylated forms of the mutant ppGalNAc-T2K521Q to various naked and aGalNAc-glycosylated mucin peptides...... indicated that degree of interaction of lectin domain with aGalNAc depends on the peptide sequence of mucin. Studies of inhibitory effect of various carbohydrates on interactions of ppGalNAc-T2 with MUC1aGalNAc indicate that point K521Q mutation enhance the carbohydrate specificity of lectin domain for aGalNAc...

High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice

DEFF Research Database (Denmark)

Thieme, V; Jolly, N; Madsen, A N

2016-01-01

BACKGROUND AND PURPOSE: Human pancreatic polypeptide (hPP) is known to suppress appetite and food intake, thereby representing a potential therapeutic approach against obesity and associated metabolic disorders. The aim of this study was to improve hPP stability by covalent PEGylation with diverse...... fasting-induced food intake and bioavailability. KEY RESULTS: In human epithelia and colonic mucosal preparations, activity of the modified hPP peptides depended on the core sequence and latency of the peptides was related to PEG size. Peptides modified with a 22 kDa PEG (PEG22) remained intact in blood...... plasma and on incubation with liver homogenates for more than 96 h. Finally, hPP2-36 , [K(22) (PEG22)]hPP2-36 and [K(22) (PEG22),Q(34) ]hPP significantly reduced cumulative food intake in mice over 16 h after s.c. administration. CONCLUSIONS AND IMPLICATIONS: Modification with PEG22 at position 22...

Methods for engineering polypeptide variants via somatic hypermutation and polypeptide made thereby

Science.gov (United States)

Tsien, Roger Y; Wang, Lei

2015-01-13

Methods using somatic hypermutation (SHM) for producing polypeptide and nucleic acid variants, and nucleic acids encoding such polypeptide variants are disclosed. Such variants may have desired properties. Also disclosed are novel polypeptides, such as improved fluorescent proteins, produced by the novel methods, and nucleic acids, vectors, and host cells comprising such vectors.

Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4

International Nuclear Information System (INIS)

Tang, Juan; Zheng, Hanxi; Chen, Ling; Gao, Shangshang; Shi, Xiaorui; Liu, Jingjing; Xu, Lan

2017-01-01

The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). Our results demonstrated that the ppGalNAc-T4 was highly expressed in MC3T3-E1 cells during osteogenesis for the first time. We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. - Highlights: • ppGalNAc-T1 and T4 are highly expressed during MC3T3 cell osteogenesis. • Knockdown of ppGalNAc-T1 and -T4 decreases osteogenic differentiation and mineralization. • Expression of osteogenic factors are differentially affected by decreased ppGalNAc-T1 and -T4 expression.

Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

DEFF Research Database (Denmark)

Damholt, M B; Arlien-Soeborg, P; Hilsted, L

2006-01-01

The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed....... In this study the pancreatic polypeptide (PP) response to a mixed meal was evaluated in healthy subjects and in recently diagnosed type 1 diabetic patients....

Polypeptide N-Acetylgalactosaminyltransferase 13 Contributes to Neurogenesis via Stabilizing the Mucin-type O-Glycoprotein Podoplanin.

Science.gov (United States)

Xu, Yingjiao; Pang, Wenjie; Lu, Jishun; Shan, Aidong; Zhang, Yan

2016-11-04

Mucin-type O-glycosylation is initiated by an evolutionarily conserved family of polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). Previously, it was reported that ppGalNAc-T13 is restrictively expressed at a high level in the brain. Here we provide evidence for the critical role of ppGalNAc-T13 in neural differentiation. In detail, we show that the expression of ppGalNAc-T13 was dramatically up-regulated during early neurogenesis in mouse embryonic brains. Similar changes were also observed in cell models of neuronal differentiation by using either primary mouse cortical neural precursor cells or murine embryonal carcinoma P19 cells. Knockout of ppGalNAc-T13 in P19 cells suppressed not only neural induction but also neuronal differentiation. These effects are at least partly mediated by the mucin-type O-glycoprotein podoplanin (PDPN), as knockdown of PDPN led to a similar inhibition of neuronal differentiation and PDPN was significantly reduced at the posttranscriptional level after ppGalNAc-T13 knockout. Further data demonstrate that PDPN acts as a substrate of ppGalNAc-T13 and that the ppGalNAc-T13-mediated O-glycosylation on PDPN is important for its stability. Taken together, this study suggests that ppGalNAc-T13 contributes to neuronal differentiation through glycosylating and stabilizing PDPN, which provides insights into the regulatory roles of O-glycosylation in mammalian neural development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mosaic HIV envelope immunogenic polypeptides

Science.gov (United States)

Korber, Bette T. M.; Gnanakaran, S.; Perkins, Simon; Sodroski, Joseph; Haynes, Barton

2018-01-02

Disclosed herein are mosaic HIV envelope (Env) polypeptides that can elicit an immune response to HIV (such as cytotoxic T cell (CTL), helper T cell, and/or humoral responses). Also disclosed are sets of the disclosed mosaic Env polypeptides, which include two or more (for example, three) of the polypeptides. Also disclosed herein are methods for treating or inhibiting HIV in a subject including administering one or more of the disclosed immunogenic polypeptides or compositions to a subject infected with HIV or at risk of HIV infection. In some embodiments, the methods include inducing an immune response to HIV in a subject comprising administering to the subject at least one (such as two, three, or more) of the immunogenic polypeptides or at least one (such as two, three, or more) nucleic acids encoding at least one of the immunogenic polypeptides disclosed herein.

The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and pancreatic exocrine secretion in the anesthetized dog

International Nuclear Information System (INIS)

DeMar, A.R.; Lake, R.; Fink, A.S.

1991-01-01

Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests intermediate mechanisms of action. To examine the role of pancreatic blood flow in these inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400 pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125 ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine secretion and pancreatic blood flow during the PP or PYY hours were compared with that observed in the first and third hours of the secretin/CCK-8 infusion. PP and PYY significantly inhibited secretin/CCK-8-induced pancreatic exocrine secretion. In addition, PYY (but not PP) significantly reduced pancreatic blood flow during secretin/CCK-8 stimulation. Nevertheless, there was no correlation between pancreatic blood flow and bicarbonate or protein outputs. It is concluded that changes in pancreatic blood flow do not mediate the inhibitory effects of PP or PYY on the exocrine pancreas

Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

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Alcendor Donald J

2012-05-01

Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

Evidence that pp60/sup src/, the product of the Rous sarcoma virus src gene, undergoes autophosphorylation

International Nuclear Information System (INIS)

Purchio, A.F.

1982-01-01

pp60/sup src/, the product of the Rous sarcoma virus src gene, was purified greater than 100,000-fold by a combination of ion-exchange and immunoaffinity chromatography. Incubation of pp60/sup src/ purified in this fashion with [ 32 P-γ]ATP resulted in a single 32 P-labeled protein when analyzed by sodium dodecyl sulfate-polyacryl-amide gel electrophoresis. Staining of these gels with silver nitrate showed a predominant 60,000-dalton polypeptide which migrated with the protein labeled with 32 P in vitro. Partial digestion of this protein with V8 protease after in vitro iodination indicated that it was pp60/sup src/. These results suggest that pp60/sup src/ is able to autophosphorylate

Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas

DEFF Research Database (Denmark)

Qader, S.S.; Hakanson, R.; Lundquist, I.

2008-01-01

ghrelin, and to the 23-amino acid peptide obestatin, claimed to be a physiological opponent of acyl ghrelin. This study examines the effects of the proghrelin products, alone and in combinations, on the secretion of insulin, glucagon, pancreatic polypeptide (PP) and somatostatin from isolated islets...... times higher concentration than acyl ghrelin (corresponding to the ratio of the two peptides in circulation), desacyl ghrelin abolished the effects of acyl ghrelin but not those of obestatin. Acyl ghrelin and obestatin affected the secretion of glucagon, PP and somatostatin at physiologically relevant...

Mucin-type O-glycosylation is controlled by short- and long-range glycopeptide substrate recognition that varies among members of the polypeptide GalNAc transferase family

DEFF Research Database (Denmark)

Revoredo, Leslie; Wang, Shengjun; Bennett, Eric Paul

2016-01-01

A large family of UDP-GalNAc:polypeptide GalNAc transferases (ppGalNAc-Ts) initiates and defines sites of mucin-type Ser/Thr-O-GalNAc glycosylation. Family members have been classified into peptide- and glycopeptide-preferring subfamilies, although both families possess variable activities agains...

Short term aerobic exercise training increases postprandial pancreatic polypeptide but not peptide YY concentrations in obese individuals

OpenAIRE

Kanaley, Jill A.; Heden, Timothy D.; Liu, Ying; Whaley-Connell, Adam T.; Chockalingam, Anand; Dellsperger, Kevin C.; Fairchild, Timothy J.

2013-01-01

Objective Short-term exercise training improves glycemic control, but the effect of short-term training on postprandial satiety peptide responses or perceived satiety remains unknown. We tested the hypothesis that short-term aerobic exercise training (15 days) would alter postprandial pancreatic and gut peptide [pancreatic polypeptide (PP) and peptide YY (PYY)] responses and perceived appetite and satiety in obese individuals. Subjects Thirteen healthy obese men and women (age: 42±2 y; BMI: 3...

Aqueous cholesteric liquid crystals using uncharged rodlike polypeptides. Polypeptide vesicles by conformation-specific assembly. Ordered chiral macroporous hybrid silica-polypeptide composites

Science.gov (United States)

Bellomo, Enrico Giuseppe

2005-07-01

Aqueous cholesteric liquid crystals using uncharged rodlike polypeptides . The aqueous, lyotropic liquid-crystalline phase behavior of an alpha helical polypeptide, has been studied using optical microscopy and X-ray scattering. Solutions of optically pure polypeptide were found to form cholesteric liquid crystals at volume fractions that decreased with increasing average chain length. At very high volume fractions, the formation of a hexagonal mesophase was observed. The pitch of the cholesteric phase could be varied by a mixture of enantiomeric samples, where the pitch increased as the mixture approached equimolar. The cholesteric phases could be untwisted, using either magnetic field or shear flow, into nematic phases, which relaxed into cholesterics upon removal of field or shear. We have found that the phase diagram of this polypeptide in aqueous solution parallels that of poly(gamma-benzyl glutamate) in organic solvents, thus providing a useful system for liquid-crystal applications requiring water as solvent. Polypeptide vesicles by conformation-specific assembly. We have found that block copolymers composed of polypeptide segments provide significant advantages in controlling both the function and supramolecular structure of bioinspired self-assemblies. Incorporation of the stable chain conformations found in proteins into block copolymers was found to provide an additional element of control, beyond amphiphilicity and composition that defines self-assembled architecture. The abundance of functionality present in amino acids, and the ease by which they can be incorporated into these materials, also provides a powerful mechanism to impart block copolypeptides with function. This combination of structure and function work synergistically to enable significant advantages in the preparation of therapeutic agents as well as provide insight into design of self-assemblies beginning to approach the complexity of natural structures such as virus capsids. Ordered

Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion

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Paolo Romania

2017-07-01

Full Text Available Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 3′ UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation. Specifically, HCMV miR-UL112-5p binds the 3′ UTR of ERAP1 A variant, but not the 3′ UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant. Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly decreased HCMV seropositivity was detected among GG individuals suffering from multiple sclerosis, a disease model in which HCMV is negatively associated with adult-onset disorder. Overall, our results identify a resistance mechanism to HCMV miR-UL112-5p-based immune evasion strategy with potential implications for individual susceptibility to infection and other diseases.

Pancreatic Polypeptide Cell Proliferation in the Pancreas and Duodenum Coexisting in a Patient With Pancreatic Adenocarcinoma Treated With a GLP-1 Analog.

Science.gov (United States)

Talmon, Geoffrey A; Wren, J David; Nguyen, Christophe L; Pour, Parviz M

2017-07-01

A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells. Among the etiological factors, the possible long-lasting effects of the GLP-1 analog, with which the patient was treated, are discussed. This is the first report in the literature of both the coexistence of a pancreatic adenocarcinoma and invasive PPoma and the occurrence of PP and insulin cells in human duodenal mucosa.

Methods for using polypeptides having cellobiohydrolase activity

Science.gov (United States)

Morant, Marc D; Harris, Paul

2016-08-23

The present invention relates to isolated polypeptides having cellobiohydrolase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Polynucleotides encoding polypeptides having beta-glucosidase activity

Science.gov (United States)

Harris, Paul; Golightly, Elizabeth

2010-03-02

The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Role of pancreatic polypeptide as a market of transplanted insulin-producing fetal pig cells.

Science.gov (United States)

Tuch, B E; Tabiin, M T; Casamento, F M; Yao, M; Georges, P; Amaratunga, A; Pinto, A N

2001-01-01

Transplantation of insulin-producing fetal pancreatic tissue into diabetic recipients has been shown to normalize blood glucose levels after several months. This time period is required for the growth and maturation of the fetal tissue so insulin levels cannot be used as a marker of graft function while the beta-cell is immature. Therefore, we have examined the use of another pancreatic endocrine hormone, pancreatic polypeptide (PP), to monitor graft function. The cell that produces this hormone has been shown to be the first mature endocrine cell in the fetal pancreas. Fetal pig pancreatic tissue, both in the form of 1 mm3 explants and islet-like cell clusters (ICCs), was transplanted into immunodeficient SCID mice and the levels of PP and insulin were measured in plasma and in the graft for up to 12 weeks. PP was detected in the untransplanted explants (0.58 pmol/mg) and ICCs (0.06 pmol/ICC) and the PP to insulin ratio was 2.7% and 5.8%, respectively. PP (but not porcine C-peptide, a marker of insulin secretion) was detectable in the plasma of SCID mice from 4 days to 3 weeks after transplantation, but not thereafter. The highest values were obtained at 4 days to 1 week. In the grafted tissue PP and insulin were present at all time points and the ratio of PP to insulin was 59%, 87%, 75%, 56%, 7%, 8%, and 7% at 4 days, 1, 2, 3, 6, 9, and 12 weeks, respectively. The decline in PP levels 3 weeks after transplantation was associated with beta-cell development in the graft. PP was also secreted by fetal pig pancreatic explants transplanted into diabetic NOD/SCID mice, with plasma levels measurable in the first week after the tissue was grafted. In immunocompetent BALB/c mice transplanted with the tissue, PP was detectable in plasma for 2 days after transplantation but not at 4 days, when cellular rejection commenced, or thereafter. We conclude that plasma PP levels can be used as a marker of the viability of fetal porcine pancreatic tissue in the first 3 weeks after

Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

International Nuclear Information System (INIS)

Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.

1987-01-01

In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45 Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant

Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice.

Science.gov (United States)

Yulyaningsih, Ernie; Loh, Kim; Lin, Shu; Lau, Jackie; Zhang, Lei; Shi, Yanchuan; Berning, Britt A; Enriquez, Ronaldo; Driessler, Frank; Macia, Laurence; Khor, Ee Cheng; Qi, Yue; Baldock, Paul; Sainsbury, Amanda; Herzog, Herbert

2014-01-07

Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141.

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Jye-Lin Hsu

2015-04-01

Full Text Available Human cytomegalovirus (HCMV US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I. Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed US2 was unique in downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ and thrombomodulin. US2 recruited the cellular E3 ligase TRC8 to direct the proteasomal degradation of all its targets, reminiscent of its degradation of MHC-I. Whereas integrin α-chains were selectively degraded, their integrin β1 binding partner accumulated in the ER. Consequently integrin signaling, cell adhesion and migration were strongly suppressed. US2 was necessary and sufficient for degradation of the majority of its substrates, but remarkably, the HCMV NK cell evasion function UL141 requisitioned US2 to enhance downregulation of the NK cell ligand CD112. UL141 retained CD112 in the ER from where US2 promoted its TRC8-dependent retrotranslocation and degradation. These findings redefine US2 as a multifunctional degradation hub which, through recruitment of the cellular E3 ligase TRC8, modulates diverse immune pathways involved in antigen presentation, NK cell activation, migration and coagulation; and highlight US2's impact on HCMV pathogenesis.

Polypeptides having catalase activity and polynucleotides encoding same

Energy Technology Data Exchange (ETDEWEB)

Liu, Ye; Duan, Junxin; Zhang, Yu; Tang, Lan

2017-05-02

Provided are isolated polypeptides having catalase activity and polynucleotides encoding the polypeptides. Also provided are nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

KAUST Repository

Pahovnik, David

2015-09-01

Different synthetic approaches utilizing ring-opening polymerization of N-carboxyanhydrides for preparation of polypeptide and polypeptide-based hybrid materials with various molecular architectures are described. An overview of polymerization mechanisms using conventional (various amines) as well as some recently developed initiators (hexamethyldisilazane, N-heterocyclic persistent carbenes, etc.) is presented, and their benefits and drawbacks for preparation of polypeptides with well-defined chain lengths and chain-end functionality are discussed. Recent examples from literature are used to illustrate different possibilities for synthesis of pure polypeptide materials with different molecular architectures bearing various functional groups, which are introduced either by modification of amino acids, before they are transformed into corresponding Ncarboxyanhydrides, or by post-polymerization modifications using protective groups and/or orthogonal functional groups. Different approaches for preparation of polypeptide-based hybrid materials are discussed as well using examples from recent literature. Syntheses of simple block copolymers or copolymers with more complex molecular architectures (graft and star copolymers) as well as modifications of nanoparticles and other surfaces with polypeptides are described.

Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

Science.gov (United States)

Morant, Marc D.; Harris, Paul

2015-10-13

The present invention relates to isolated polypeptides having cellobiohydrolase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Polypeptides having xylanase activity and polynucleotides encoding same

Energy Technology Data Exchange (ETDEWEB)

Spodsberg, Nikolaj

2018-02-06

The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Measles virus polypeptides in purified virions and in infected cells

International Nuclear Information System (INIS)

Vainionpaeae, R.; Ziola, B.; Salmi, A.

1978-01-01

A wild-type measles virus was radiolabeled during growth in VERO cells and purified by two successive potassium tartrate gradient centrifugations. The virion polypeptide composition was determined by SDS-polyacrylamide gel electrophoresis employing two different buffer systems. Six virus-specific polypeptides were consistently detected. The largest (L) had a molecular weight (MW) of greater than 150,000. The second largest polypeptide, G (MW 79,000), was the only glycoprotein found. The proteins designated polypeptide 2 (MW 66 to 70,000) and nucleocapsid protein or NP (MW 61,000) were phosphorylated. The remaining virus-coded proteins were polypeptide 5 (MW 40,000) and the matrix or M protein (MW 37,000). Measles virions also contained a polypeptide (MW 42,000) thought to be actin due to co-migration with this component of uninfected cells. Analysis of in vitro 3 H-acetic anhydride radiolabeled virions confirmed the presence of these seven polypeptides. Acetic anhydride also labeled a protein designated polypeptide 4 (MW 53,000) which was not consistently radiolabeled in vivo, as well as several other minor proteins believed to be cellular in origin. Synthesis of the six virus-specific structural polypeptides was detected in lysates of infected cells by SDS-polyacrylamide slab gel electrophoresis. Virus specificity of polypeptide 4 could not be confirmed due to the similar MW of several cellular polypeptides. Two non-virion, but virus-specified polypeptides, of MW 38,000 and 18,000 were also detected. Synthesis of the virus structural proteins was in the same proportions as the polypeptides found in virions except for under production of polypeptide G and over production of polypeptide 2. (author)

HCMV gB genotypes in cervical secretion and placenta tissues in the state of Espírito Santo, Southeastearn Brazil Genótipos gB de citomegalovírus humano em secreção cervical e placenta no Espírito Santo, Sudeste do Brasil

Directory of Open Access Journals (Sweden)

Liliana Cruz Spano

2007-09-01

Full Text Available Human cytomegalovirus (HCMV displays genetic variability in several regions, supposed to be related with strain-specific tissue tropism and immunopathogenesis. Based on sequence variation in the UL55 gene that encodes gB glycoprotein, HCMV strains can be assigned to one of four genotypes. Previous studies have addressed gB genotyping mostly by investigating strains derived from immunosuppressed patients, sometimes without previous knowledge about genotype distribution in a geographic area. The present study verified the distribution of HCMV gB genotypes of strains obtained from immunocompetent women at Vitória City, Espírito Santo State, Southeastern, Brazil. The HCMV genome was extracted from their cervical secretion, fetal and maternal placenta tissues (chorionic villous and decidua from abortion cases and from white blood cells (WBCs. HCMV genotyping was performed by restriction fragment length polymorphism analyses of amplified product from the high variability site of the UL55 gene. All four genotypes were observed in both cervical secretion and placenta, whereas in WBCs a single gB1 genotype was detected. HCMV gB1 and gB2 genotypes were detected, respectively, in nine and in six of the 23 studied samples, while gB3 and gB4 were each found in four separate samples of the total. The differences in genotype frequency were not considered statistically significant. No mixed genotype infection was observed. The results indicated that the four gB HCMV genotypes had no particular tropism for placenta tissues and that all genotypes circulated within immunocompetent women at the time and in the region of study.O citomegalovírus humano (HCMV apresenta variabilidade em diversas regiões do genoma, supostamente relacionada ao tropismo tecidual e imunopatogênese viral. Baseando-se na variação de seqüência do gene UL55 que codifica a glicoproteína gB, o HCMV pode ser classificado em um dos quatro genótipos. Estudos prévios têm investigado a

Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance.

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Songyan Wang

Full Text Available We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP on insulin secretion rates (ISRs and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans.

Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

KAUST Repository

Pahovnik, David; Hadjichristidis, Nikolaos

2015-01-01

Different synthetic approaches utilizing ring-opening polymerization of N-carboxyanhydrides for preparation of polypeptide and polypeptide-based hybrid materials with various molecular architectures are described. An overview of polymerization

HCMV Infection of Human Trophoblast Progenitor Cells of the Placenta Is Neutralized by a Human Monoclonal Antibody to Glycoprotein B and Not by Antibodies to the Pentamer Complex

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Martin Zydek

2014-03-01

Full Text Available Human cytomegalovirus (HCMV is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs, the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs. Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb, TRL345, reactive with glycoprotein B (gB, but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease.

Polypeptides having xylanase activity and polynucleotides encoding same

Energy Technology Data Exchange (ETDEWEB)

Spodsberg, Nikolaj; Shaghasi, Tarana

2017-06-20

The present invention relates to polypeptides having xylanase activity, catalytic domains, and carbohydrate binding domains, and polynucleotides encoding the polypeptides, catalytic domains, and carbohydrate binding domains. The present invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains, and carbohydrate binding domains.

Phase transitions in polypeptides: analysis of energy fluctuations

DEFF Research Database (Denmark)

Yakubovich, Alexander V.; Solov'yov, Ilia; Solov'yov, Andrey V.

2009-01-01

The helix random coil transition in alanine, valine, and leucine polypeptides consisting of 30 amino acids is studied in vacuo using the Langevin molecular dynamics approach. The influence of side chain radicals on internal energy and heat capacity of the polypeptides is discussed. The heat...... of simulation time. This study provides a comparison of methods for the description of structural transitions in polypeptides....

Polypeptides having beta-glucosidase activity and polynucleotides encoding same

Science.gov (United States)

Harris, Paul; Golightly, Elizabeth

2012-11-27

The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

Science.gov (United States)

Maiyuran, Suchindra; Kramer, Randall; Harris, Paul

2013-10-29

The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Chirality-selected phase behaviour in ionic polypeptide complexes

Science.gov (United States)

Perry, Sarah L.; Leon, Lorraine; Hoffmann, Kyle Q.; Kade, Matthew J.; Priftis, Dimitrios; Black, Katie A.; Wong, Derek; Klein, Ryan A.; Pierce, Charles F.; Margossian, Khatcher O.; Whitmer, Jonathan K.; Qin, Jian; de Pablo, Juan J.; Tirrell, Matthew

2015-01-01

Polyelectrolyte complexes present new opportunities for self-assembled soft matter. Factors determining whether the phase of the complex is solid or liquid remain unclear. Ionic polypeptides enable examination of the effects of stereochemistry on complex formation. Here we demonstrate that chirality determines the state of polyelectrolyte complexes, formed from mixing dilute solutions of oppositely charged polypeptides, via a combination of electrostatic and hydrogen-bonding interactions. Fluid complexes occur when at least one of the polypeptides in the mixture is racemic, which disrupts backbone hydrogen-bonding networks. Pairs of purely chiral polypeptides, of any sense, form compact, fibrillar solids with a β-sheet structure. Analogous behaviour occurs in micelles formed from polypeptide block copolymers with polyethylene oxide, where assembly into aggregates with either solid or fluid cores, and eventually into ordered phases at high concentrations, is possible. Chirality is an exploitable tool for manipulating material properties in polyelectrolyte complexation. PMID:25586861

Vasoactive intestinal polypeptide and other preprovasoactive intestinal polypeptide-derived peptides in the female and male genital tract: localization, biosynthesis, and functional and clinical significance

DEFF Research Database (Denmark)

Ottesen, B; Fahrenkrug, J

1995-01-01

Vasoactive intestinal polypeptide, a neuropeptide with wide distribution in the central and peripheral nervous system, has a broad spectrum of biologic actions. The demonstration of vasoactive intestinal polypeptide containing nerve fibers within the female and male genital tract 17 years ago...... indicated a putative role for this peptide in the local nervous control of reproductive functions. The genes encoding the preprovasoactive intestinal polypeptide precursor molecule and the vasoactive intestinal polypeptide receptor have been identified. The gene expression has been studied by the use...... in the genital tracts (i.e., blood flow and nonvascular smooth muscle relaxation). In the ovary vasoactive intestinal polypeptide seems to play an important role as regulator and/or modulator of folliculogenesis and steroidogenesis. In the male genital tract vasoactive intestinal polypeptide seems to participate...

Study of pp→ppη reaction at threshold

International Nuclear Information System (INIS)

Taleb, A.

1994-11-01

The η production has been studied through the pp → ppη reaction at threshold. Data were taken at the Synchrotron of the ''Laboratoire National Saturne''. The detection in coincidence of the two protons scattered near 0 deg and analysed with the magnetic spectrometer SPES3 allows the reconstruction of missing mass spectra for the η signature. A simulation program which takes into account all the experimental set up characteristics has been realized and tested through the pp → dπ + reaction detected simultaneously with pp → ppη. The generated proton momentum spectra for pp → ppη show a pronounced η mass dependence. This characteristic, connected to the kinematical properties of pp → ppη at threshold, is used to extract the mass of the meson η. The obtained value, m η = 547.65 ± 0.18 MeV, is in good agreement with measurement done recently through the pd → H eη reaction. The total cross section σ t of pp → ppη measured at 1260, 1265 and 1300 MeV presents a strong energy dependence. This cross section increases less with energy than the phase-space. The influence of p-p and η-p final state interactions in our measurements is studied. Our results are compared with theoretical predictions and assess the dominant character of the baryonic resonance N * (1535) in the η mechanism production at threshold. These experimental results give an energy dependence which is not well reproduced by the theoretical predictions. This discrepancy could be an incorrect description of the η-p interaction in the models. (author). 48 refs., 60 figs., 15 tabs

[New drug developments of snake venom polypeptides and progress].

Science.gov (United States)

Fu, Sihai; Feng, Mei; Xiong, Yan

2017-11-28

The value of snake venom polypeptides in clinical application has drawn extensive attention, and the development of snake polypeptides into new drugs with anti-tumor, anti-inflammatory, antithrombotic, analgesic or antihypertensive properties has become the recent research hotspot. With the rapid development of molecular biology and biotechnology, the mechanisms of snake venom polypeptides are also gradually clarified. Numerous studies have demonstrated that snake venom polypeptides exert their pharmacological effects by regulating ion channels, cell proliferation, apoptosis, intracellular signaling pathway, and expression of cytokine as well as binding to relevant active sites or receptors.

Caffeine-water-polypeptide interaction in aqueous solution

Science.gov (United States)

Ghabi, Habib; Dhahbi, Mahmoud

1999-04-01

The interaction of caffeine monomer with the synthetic polypeptides polyasparagine (pAg) and polyaspartic acid (pAsp) was studied by UV spectrophotometry. The results show that different types of interactions are possible depending on the nature of polypeptide. The form of the complex was discussed.

A novel tetratricopeptide repeat (TPR containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Adams Brian

2001-11-01

Full Text Available Abstract Background The malarial parasite, Plasmodium falciparum (Pf, is responsible for nearly 2 million deaths worldwide. However, the mechanisms of cellular signaling in the parasite remain largely unknown. Recent discovery of a few protein kinases and phosphatases point to a thriving reversible phosphorylation system in the parasite, although their function and regulation need to be determined. Results We provide biochemical and sequence evidence for a protein serine/threonine phosphatase type PP5 in Plasmodium falciparum, and named it PfPP5. The 594-amino acid polypeptide was encoded by a 1785 nucleotide long intronless gene in the parasite. The recombinant protein, expressed in bacteria, was indistinguishable from native PfPP5. Sequencing comparison indicated that the extra-long N-terminus of PfPP5 outside the catalytic core contained four tetratricopeptide repeats (TPRs, compared to three such repeats in other PP5 phosphatases. The PfPP5 N-terminus was required for stimulation of the phosphatase activity by polyunsaturated fatty acids. Co-immunoprecipitation demonstrated an interaction between native PfPP5 and Pf heat shock protein 90 (hsp90. PfPP5 was expressed in all the asexual erythrocytic stages of the parasite, and was moderately sensitive to okadaic acid. Conclusions This is the first example of a TPR-domain protein in the Apicomplexa family of parasites. Since TPR domains play important roles in protein-protein interaction, especially relevant to the regulation of PP5 phosphatases, PfPP5 is destined to have a definitive role in parasitic growth and signaling pathways. This is exemplified by the interaction between PfPP5 and the cognate chaperone hsp90.

Polypeptides having beta-glucosidase activity and polynucleotides encoding the same

Science.gov (United States)

Brown, Kimberly; Harris, Paul

2013-12-17

The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Chimeric polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

Science.gov (United States)

Wogulis, Mark; Sweeney, Matthew; Heu, Tia

2017-06-14

The present invention relates to chimeric GH61 polypeptides having cellulolytic enhancing activity. The present invention also relates to polynucleotides encoding the chimeric GH61 polypeptides; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the chimeric GH61 polypeptides.

GLYCOSYLATED YGHJ POLYPEPTIDES FROM ENTEROTOXIGENIC ESCHERICHIA COLI (ETEC)

DEFF Research Database (Denmark)

2017-01-01

The present invention relates to glycosylated YghJ polypeptides from or derived from enterotoxigenic Escherichia coli (ETEC) that are immunogenic. In particular, the present invention relates to compositions or vaccines comprising the polypeptides and their application in immunization, vaccination...

INTERACTION BETWEEN DIFFERENT MOLECULAR FORMS OF IMMUNOGLOBULIN A AND RECOMBINANT DERIVATIVES POLYPEPTIDES OF BAC RECEPTOR PROTEINS FROM GROUP B STREPTOCOCCI

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A. S. Korzhueva

2008-01-01

Full Text Available Abstract. The article concerns interactions between immunoglobulin A and recombinant P6, P7, P8 polypeptides, designed on the basis of externally localized Bac protein of the Group B streptococci, possessing IgA-binding activity.There is a current demand for immunochemical reagents that are strictly specific for IgA, in order to develop antigenic standards for detection of IgA levels in biological fluids, as well as for affinity purification of IgA and its fragments.To analyze an opportunity of the abovementioned application ways for these proteins, a special study was performed to assay an interaction capability of recombinant P6, P7, P8 polypeptides binding to Fc regions of different IgA forms (serum IgA, secretory IgA, subclasses of serum IgA – IgA1, IgA2. Selectivity of ligand binding was specially confirmed.It was found out that, among three presented polypeptides, the structure of recombinant P6 derivative proved to be optimal for IgA-binding ability of Bac protein.Structural features of IgA-binding fragments of Bac protein, i.e., binding site position on the IgA molecule (proximity to epitopes for three monoclonal antibodies, variability of the site structure, as well as resistance of binding site for P6, P7, P8 in IgA molecule against partial disulfide bonds reduction. (Med. Immunol., vol. 10, N 4-5, pp 327-336.

Tunable drug loading and release from polypeptide multilayer nanofilms

Science.gov (United States)

Jiang, Bingbing; Li, Bingyun

2009-01-01

Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue) were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibioticloaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients. PMID:19421369

Nuclear body formation and PML body remodeling by the human cytomegalovirus protein UL35

International Nuclear Information System (INIS)

Salsman, Jayme; Wang Xueqi; Frappier, Lori

2011-01-01

The human cytomegalovirus (HCMV) UL35 gene encodes two proteins, UL35 and UL35a. Expression of UL35 in transfected cells results in the formation of UL35 nuclear bodies that associate with promyelocytic leukemia (PML) protein. PML forms the basis for PML nuclear bodies that are important for suppressing viral lytic gene expression. Given the important relationship between PML and viral infection, we have further investigated the association of UL35 with PML bodies. We demonstrate that UL35 bodies form independently of PML and subsequently recruit PML, Sp100 and Daxx. In contrast, UL35a did not form bodies; however, it could bind UL35 and inhibit the formation of UL35 bodies. The HCMV tegument protein pp71 promoted the formation of UL35 bodies and the cytoplasmic localization of UL35a. Similarly, UL35a shifted pp71 to the cytoplasm. These results indicate that the interplay between UL35, UL35a and pp71 affects their subcellular localization and likely their functions throughout infection.

pp and ̄pp elastic scattering

Directory of Open Access Journals (Sweden)

A. Donnachie

1984-01-01

Full Text Available We present an analysis of pp and ̄pp elastic scattering in terms of various exchanges. Three-gluon exchange dominates at large t, and single-pomeron exchange at small t. The dip seen in high-energy pp scattering is provided by the interference of both of these with double-pomeron exchange. We predict that this dip will not be found in high-energy ̄pp scattering. The dip that is seen in low-energy ̄pp scattering is the result of the additional presence of reggeon-pomeron exchange.

Fasting and meal-induced CCK and PP secretion following intragastric balloon treatment for obesity.

Science.gov (United States)

Mathus-Vliegen, Elisabeth M H; de Groot, Gerrit H

2013-05-01

Satiety is centrally and peripherally mediated by gastrointestinal peptides and the vagal nerve. We aimed to investigate whether intragastric balloon treatment affects satiety through effects on fasting and meal-stimulated cholecystokinin (CCK) and pancreatic polypeptide (PP) secretion. Patients referred for obesity treatment were randomised to 13 weeks of sham treatment followed by 13 weeks of balloon treatment (group 1; sham/balloon) or to twice a 13-week period of balloon treatment (group 2; balloon/balloon). Blood samples were taken for fasting and meal-stimulated CCK and PP levels at the start (T0) and after 13 (T1) and 26 (T2) weeks. Patients filled out visual analogue scales (VAS) to assess satiety. Forty-two patients (35 females, body weight 125.1 kg, BMI 43.3 kg/m(2)) participated. In group 1, basal CCK levels decreased but meal-stimulated response remained unchanged after 13 weeks of sham treatment. In group 2, basal and meal-stimulated CCK levels decreased after 13 weeks of balloon treatment. At the end of the second 13-week period, when group 1 had their first balloon treatment, they duplicated the initial 13-week results of group 2, whereas group 2 continued their balloon treatment and reduced meal-stimulated CCK release. Both groups showed reduced meal-stimulated PP secretions at T1 and T2 compared to T0. Changes in diet composition and VAS scores were similar. Improvements in glucose homeostasis partly explained the PP results. The reduced CCK and PP secretion after balloon positioning was unexpected and may reflect delayed gastric emptying induced by the balloon. Improved glucose metabolism partly explained the reduced PP secretion. Satiety and weight loss were not adversely influenced by these hormonal changes.

Star-Shaped Polypeptides: Synthesis and Opportunities for Delivery of Therapeutics.

Science.gov (United States)

Byrne, Mark; Murphy, Robert; Kapetanakis, Antonios; Ramsey, Joanne; Cryan, Sally-Ann; Heise, Andreas

2015-09-17

Significant advances in the synthesis of polypeptides by N-carboxyanhydride (NCA) polymerisation over the last decade have enabled the design of advanced polypeptide architectures such as star-shaped polypeptides. These materials combine the functionality offered by amino acids with the flexibility of creating stable nanoparticles with adjustable cargo space for therapeutic delivery. This review highlights recent advances in the synthesis of star polypeptides by NCA polymerisation followed by a critical review of the applications of this class of polymer in the delivery of therapeutic agents. This includes examples of traditional small-molecule drugs as well as the emerging class of biologics such as genetic therapeutics (gene delivery). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polypeptide profiles of human oocytes and preimplantation embryos.

Science.gov (United States)

Capmany, G; Bolton, V N

1993-11-01

The polypeptides that direct fertilization and early development until activation of the embryonic genome occurs, at the 4-8 cell stage in the human, are exclusively maternal in origin, and are either synthesized during oogenesis or translated later from maternal mRNA. Using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and silver stain, we have visualized and compared the polypeptides present in different populations of human oocytes and cleavage stage embryos obtained after superovulation and insemination in vitro. Two polypeptide patterns were resolved, differing in the region of mol. wt 69 kDa. The distribution of these patterns showed no correlation with the ability of individual oocytes to achieve fertilization and develop normally to the 8-cell stage.

Proteolytic processing of poliovirus polypeptides: antibodies to polypeptide P3-7c inhibit cleavage at glutamine-glycine pairs

International Nuclear Information System (INIS)

Hanecak, R.; Semler, B.L.; Anderson, C.W.; Wimmer, E.

1982-01-01

Proteolytic processing of poliovirus polypeptides was examined by the addition of antibodies directed against the viral proteins P3-7c and P2-X to a cell-free translation extract prepared from infected HeLa cells. Antisera to P3-7c specifically inhibited in vitro processing at Gln-Gly pairs. Partial amino acid sequence analysis revealed a second Tyr-Gly pair that is utilized in protein processing. Neither Tyr-Gly cleavage is affected by antibody to P3-7C. Anti-P3-7c antibodies react not only with P3-7c but also with P3-6a and P3-2, two viral polypeptides NH 2 -coterminal with P3-7c. Preimmune and anti-P2-X antibodies had no effect on the processing of poliovirus proteins in vitro. The authors conclude that the activity responsible for processing poliovirus polypeptides at Gln-Gly pairs resides in the primary structure of P3-7c and not in P2-X

UV cross-linking of polypeptides associated with 3'-terminal exons

International Nuclear Information System (INIS)

Stolow, D.T.; Berget, S.M.

1990-01-01

Association of nuclear proteins with chimeric vertebrate precursor RNAs containing both polyadenylation signals and an intron was examined by UV cross-linking. One major difference in cross-linking pattern was observed between this chimeric precursor RNA and precursors containing only polyadenylation or splicing signals. The heterogeneous nuclear ribonucleoprotein (hnRNP) polypeptide C cross-linked strongly to sequences downstream of the A addition site in polyadenylation precursor RNA containing only the polyadenylation signal from the simian virus 40 (SV40) late transcription unit. In contrast, the hnRNP C polypeptide cross-linked to chimeric RNA containing the same SV40 late poly(A) cassette very poorly, at a level less than 5% of that observed with the precursor RNA containing just the poly(A) site. Observation that cross-linking of the hnRNP C polypeptide to elements within the SV40 late poly(A) site was altered by the presence of an upstream intron suggests differences in the way nuclear factors associate with poly(A) sites in the presence and absence of an upstream intron. Cross-linking of C polypeptide to chimeric RNA increased with RNAs mutated for splicing or polyadenylation consensus sequences and under reaction conditions (high magnesium) that inhibited polyadenylation. Furthermore, cross-linking of hnRNP C polypeptide to precursors containing just the SV40 late poly(A) site was eliminated in the presence of competing poly(U); polyadenylation, however, was unaffected. Correlation of loss of activity with high levels of hnRNP C polypeptide cross-linking raises questions about the specificity of the interaction between the hnRNP C polypeptide and polyadenylation precursor RNAs in vitro

Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem transplantation: a single-center experience.

Science.gov (United States)

Manteiga, R; Martino, R; Sureda, A; Labeaga, R; Brunet, S; Sierra, J; Rabella, N

1998-11-01

The optimal prophylactic strategy for cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation has not yet been established. The aim of this study was to analyze our single-center experience with a uniform protocol of CMV antigenemia-guided pre-emptive treatment with ganciclovir (GCV) after allografting. Fifty-two consecutive adult patients, 48 of them transplanted from HLA-identical matched related donors were included. T cell-depleted marrow or peripheral blood were used in 21 cases. After engraftment, weekly blood samples were tested for CMV pp65 antigenemia and viremia (conventional cultures) until day +100. GCV was started if CMV antigenemia and/or CMV viremia were detected. CMV infection (CMV-I) was found in 19 patients (37%). Seven patients suffered from CMV disease (CMV-D), three colitis and four pneumonias. There was one death directly related to CMV-D and three further cases died from refractory GVHD with CMV-D. Only one patient developed CMV pneumonia without any previous positive antigenemia and/or viremia. Multivariate analysis identified grades II-IV acute GVHD (P = 0.02) and peripheral blood stem cell transplantation (P = 0.03) to be risk factors for developing CMV-I. In conclusion, this monitoring protocol allowed early treatment of CMV-I without progression to CMV-D. Pre-emptive therapy had the additional advantage of avoiding GCV administration in most of our allograft recipients.

Irradiation effect on PP/PMMA and PP/PP-g-PMMA matrices

International Nuclear Information System (INIS)

Marsongko; Soebianto, Yanti S.

1998-01-01

The effects of PMMA and PP-g-PMMA on the oxidation of polypropylene (PP) have been studied. The mixing was done in Laboplastomill at the temperature of 200 o C, and screw speed of 20 rpm, for 5 minutes. The PMMA concentrations were 1, 2, 5, and 10% by weight, and PP-g-PMMA (12% grafting) 5, 10, and 20% by weight. Mechanical properties (tensile strength (Tb) and elongation at break (Eb)( of the mixture decreased with the increase of PMMA content over 5%. The addition of PMMA over 3% produced non-transparent film. Electron beam irradiation at the dose of 5, 10, 30, and 50 kGy was carried out to accelerate the matrix oxidation is accelerated. The optimum properties of PP/PMMA blends can be achieved by addition of maximum 2% PMMA either direct as PMMA or as compatibilizer (PP-g-PMMA). (authors)

Biochemical map of polypeptides specified by foot-and-mouth disease virus.

OpenAIRE

Grubman, M J; Robertson, B H; Morgan, D O; Moore, D M; Dowbenko, D

1984-01-01

Pulse-chase labeling of foot-and-mouth disease virus-infected bovine kidney cells revealed stable and unstable viral-specific polypeptides. To identify precursor-product relationships among these polypeptides, antisera against a number of structural and nonstructural viral-specific polypeptides were used. Cell-free translations programmed with foot-and-mouth disease virion RNA or foot-and-mouth disease virus-infected bovine kidney cell lysates, which were shown to contain almost identical pol...

Polypeptide based hydrogels

OpenAIRE

Hanay, Saltuk

2018-01-01

There is a need for biocompatible, biodegradable, 3-D printable and stable hydrogels especially in the areas of tissue engineering, drug delivery, bio-sensing technologies and antimicrobial coatings. The main aim of this Ph.D. work was to fabricate polypeptide based hydrogel which may find a potential application in those fields. Focusing on tyrosine or tryptophan-containing copolypeptides prepared by NCarboxyanhydride (NCA) polymerizations, three different crosslinking strategies have been t...

Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.

Science.gov (United States)

Pyarokhil, Asadullah Hamid; Ishihara, Miyuki; Sasaki, Motoki; Kitamura, Nobuo

2012-04-10

The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle. Copyright © 2011 Elsevier B.V. All rights reserved.

Simultaneous Polymerization and Polypeptide Particle Production via Reactive Spray-Drying.

Science.gov (United States)

Glavas, Lidija; Odelius, Karin; Albertsson, Ann-Christine

2016-09-12

A method for producing polypeptide particles via in situ polymerization of N-carboxyanhydrides during spray-drying has been developed. This method was enabled by the development of a fast and robust synthetic pathway to polypeptides using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an initiator for the ring-opening polymerization of N-carboxyanhydrides. The polymerizations finished within 5 s and proved to be very tolerant toward impurities such as amino acid salts and water. The formed particles were prepared by mixing the monomer, N-carboxyanhydride of l-glutamic acid benzyl ester (NCAGlu) and the initiator (DBU) during the atomization process in the spray-dryer and were spherical with a size of ∼1 μm. This method combines two steps; making it a straightforward process that facilitates the production of polypeptide particles. Hence, it furthers the use of spray-drying and polypeptide particles in the pharmaceutical industry.

Search for Scalar Diphoton Resonances in the Mass Range $65-600$ GeV with the ATLAS Detector in $pp$ Collision Data at $\\sqrt{s}$ = 8 $TeV$

CERN Document Server

Aad, Georges; Abdallah, Jalal; Abdel Khalek, Samah; Abdinov, Ovsat; Aben, Rosemarie; Abi, Babak; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Allbrooke, Benedict; Allison, Lee John; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; 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Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cooper-Smith, Neil; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuciuc, Constantin-Mihai; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Daniells, Andrew Christopher; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davignon, Olivier; Davison, Adam; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Barros do Vale, Maria Aline; Dobos, Daniel; Doglioni, Caterina; Doherty, Tom; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudziak, Fanny; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Dwuznik, Michal; Dyndal, Mateusz; Ebke, Johannes; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Perez, Sonia; Ferrag, Samir; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franconi, Laura; Franklin, Melissa; Fraternali, Marco; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gianotti, Fabiola; Gibson, Stephen; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Glonti, George; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goeringer, Christian; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Grebenyuk, Oleg; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Groth-Jensen, Jacob; Grout, Zara Jane; Guan, Liang; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guicheney, Christophe; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Gunther, Jaroslav; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guttman, Nir; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hakobyan, Hrachya; Haleem, Mahsana; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Harrison, Paul Fraser; Hasegawa, Makoto; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hoffmann, Dirk; Hofmann, Julia Isabell; Hohlfeld, Marc; Holmes, Tova Ray; Hong, Tae Min; Hooft van Huysduynen, Loek; Hopkins, Walter; Horii, Yasuyuki; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Hurwitz, Martina; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Erik; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Khodinov, Alexander; Khoo, Teng Jian; Khoriauli, Gia; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Koll, James; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; La Rosa, Alessandro; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laier, Heiko; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Lester, Christopher Michael; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Bo; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Brian Alexander; Long, Jonathan; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Feng; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lungwitz, Matthias; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeno, Mayuko; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Mahmoud, Sara; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mandelli, Beatrice; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany Andreina; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Homero; Martinez, Mario; Martin-Haugh, Stewart; Martyniuk, Alex; Marx, Marilyn; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Mechnich, Joerg; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Meric, Nicolas; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morton, Alexander; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Thibaut; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Nanava, Gizo; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negri, Guido; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Oda, Susumu; Odaka, Shigeru; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Palmer, Jody; Pan, Yibin; Panagiotopoulou, Evgenia; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Patricelli, Sergio; Pauly, Thilo; Pearce, James; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pinamonti, Michele; Pinder, Alex; Pinfold, James; Pingel, Almut; Pinto, Belmiro; Pires, Sylvestre; Pitt, Michael; Pizio, Caterina; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poddar, Sahill; Podlyski, Fabrice; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Pohl, Martin; Polesello, Giacomo; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Portell Bueso, Xavier; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poveda, Joaquin; Pozdnyakov, Valery; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Pravahan, Rishiraj; Prell, Soeren; Price, Darren; Price, Joe; Primavera, Margherita; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Przysiezniak, Helenka; Ptacek, Elizabeth; Puddu, Daniele; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Qureshi, Anum; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Rao, Kanury; Rauscher, Felix; Rave, Tobias Christian; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reisin, Hernan; Relich, Matthew; Rembser, Christoph; Ren, Huan; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Ridel, Melissa; Rieck, Patrick; Rieger, Julia; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Rodrigues, Luis; Roe, Shaun; Røhne, Ole; Romaniouk, Anatoli; Romano, Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Matthew; Rose, Peyton; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Saddique, Asif; Sadeh, Iftach; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santoni, Claudio; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sartisohn, Georg; Sasaki, Osamu; Sasaki, Yuichi; Sauvan, Emmanuel; Savard, Pierre; Savu, Dan Octavian; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Scarfone, Valerio; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R~Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schroeder, Christian; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellers, Graham; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simoniello, Rosa; Sinervo, Pekka; Sinev, Nikolai; Siragusa, Giovanni; Sircar, Anirvan; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosebee, Mark; Soualah, Rachik; Soueid, Paul; Soukharev, Andrey; South, David; Spagnolo, Stefania; Spanò, Francesco; Spearman, William Robert; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; Spreitzer, Teresa; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Sutton, Mark; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Shuji; Tanasijczuk, Andres Jorge; Tannenwald, Benjamin Bordy; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thong, Wai Meng; Tian, Feng; Tibbetts, Mark James; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Tran, Huong Lan; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; True, Patrick; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turra, Ruggero; Turvey, Andrew John; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ugland, Maren; Uhlenbrock, Mathias; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urbaniec, Dustin; Urquijo, Phillip; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; Van Der Leeuw, Robin; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Virzi, Joseph; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Adrian; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Peter; Wagner, Wolfgang; Wahlberg, Hernan; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Walsh, Brian; Wang, Chao; Wang, Chiho; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; White, Andrew; White, Martin; White, Ryan; Whiteson, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, Alan; Wilson, John; Wingerter-Seez, Isabelle; Winklmeier, Frank; Winter, Benedict Tobias; Wittgen, Matthias; Wittig, Tobias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wright, Michael; Wu, Mengqing; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wulf, Evan; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xiao, Meng; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yakabe, Ryota; Yamada, Miho; Yamaguchi, Hiroshi; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamamura, Taiki; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Un-Ki; Yang, Yi; Yanush, Serguei; Yao, Liwen; Yao, Weiming; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yen, Andy L; Yildirim, Eda; Yilmaz, Metin; Yoosoofmiya, Reza; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Yusuff, Imran; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zaman, Aungshuman; Zambito, Stefano; Zanzi, Daniele; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Jinlong; Zhang, Lei; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Lei; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Zinonos, Zinonas; Ziolkowski, Michael; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zutshi, Vishnu; Zwalinski, Lukasz

2014-10-20

A search for scalar particles decaying via narrow resonances into two photons in the mass range $65-600$ GeV is performed using 20.3 fb$^{-1}$ of $\\sqrt{s}$ = 8 TeV $pp$ collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background. No significant evidence for an additional signal is observed. The results are presented as limits at the 95 % confidence level on the production cross-section of a scalar boson times branching ratio into two photons, in a fiducial volume where the reconstruction efficiency is approximately independent of the event topology. The upper limits set extend over a considerably wider mass range than previous searches.

Endogenous pancreatic polypeptide in different vascular beds

DEFF Research Database (Denmark)

Henriksen, J H; Schwartz, Tania; Bülow, J B

1986-01-01

a significantly higher level of circulating PP than controls (n = 10): median PP = 52 (range 21 to 352) v 20 (6 to 143) pmol/L, respectively (P less than 0.02). Circulating PP was inversely correlated to 51Cr-EDTA plasma clearance (r = -0.57, P less than 0.02, n = 14) and directly correlated to serum creatinine...... a progressively increasing rate of PP secretion in subjects with raised circulating PP. No statistically significant difference could be detected between systemic and renal venous PP or across the lung, left adrenal gland, or lower limb. Assuming steady state between secretion and biodegradation, the metabolic...

The influence of the side-chain sequence on the structure-activity correlations of immunomodulatory branched polypeptides. Synthesis and conformational analysis of new model polypeptides.

Science.gov (United States)

Mezö, G; Hudecz, F; Kajtár, J; Szókán, G; Szekerke, M

1989-10-01

New branched polypeptides were synthesized for a detailed study of the influence of the side-chain structure on the conformation and biological properties. The first subset of polypeptides were prepared by coupling of tetrapeptides to poly[L-Lys]. These polymers contain either DL-Ala3-X [poly[Lys-(X-DL-Ala3)n

Induction of protein body formation in plant leaves by elastin-like polypeptide fusions

Directory of Open Access Journals (Sweden)

Joensuu Jussi J

2009-08-01

Full Text Available Abstract Background Elastin-like polypeptides are synthetic biopolymers composed of a repeating pentapeptide 'VPGXG' sequence that are valuable for the simple non-chromatographic purification of recombinant proteins. In addition, elastin-like polypeptide fusions have been shown to enhance the accumulation of a range of different recombinant proteins in plants, thus addressing the major limitation of plant-based expression systems, which is a low production yield. This study's main objectives were to determine the general utility of elastin-like polypeptide protein fusions in various intracellular compartments and to elucidate elastin-like polypeptide's mechanism of action for increasing recombinant protein accumulation in the endoplasmic reticulum of plants. Results The effect of elastin-like polypeptide fusions on the accumulation of green fluorescent protein targeted to the cytoplasm, chloroplasts, apoplast, and endoplasmic reticulum was evaluated. The endoplasmic reticulum was the only intracellular compartment in which an elastin-like polypeptide tag was shown to significantly enhance recombinant protein accumulation. Interestingly, endoplasmic reticulum-targeted elastin-like polypeptide fusions induced the formation of a novel type of protein body, which may be responsible for elastin-like polypeptide's positive effect on recombinant protein accumulation by excluding the heterologous protein from normal physiological turnover. Although expressed in the leaves of plants, these novel protein bodies appeared similar in size and morphology to the prolamin-based protein bodies naturally found in plant seeds. The elastin-like polypeptide-induced protein bodies were highly mobile organelles, exhibiting various dynamic patterns of movement throughout the cells, which were dependent on intact actin microfilaments and a functional actomyosin motility system. Conclusion An endoplasmic reticulum-targeted elastin-like polypeptide fusion approach

Side-chain-controlled self-assembly of polystyrene-polypeptide miktoarm star copolymers

KAUST Repository

Junnila, Susanna

2012-03-27

We show how the self-assembly of miktoarm star copolymers can be controlled by modifying the side chains of their polypeptide arms, using A 2B and A 2B 2 type polymer/polypeptide hybrids (macromolecular chimeras). Initially synthesized PS 2PBLL and PS 2PBLL 2 (PS, polystyrene; PBLL, poly(ε-tert-butyloxycarbonyl-l-lysine) ) miktoarms were first deprotected to PS 2PLLHCl and PS 2PLLHCl 2 miktoarms (PLLHCl, poly(l-lysine hydrochloride)) and then complexed ionically with sodium dodecyl sulfonate (DS) to give the supramolecular complexes PS 2PLL(DS) and PS 2(PLL(DS)) 2. The solid-state self-assemblies of these six miktoarm systems were studied by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and small- and wide-angle X-ray scattering (SAXS, WAXS). The side chains of the polypeptide arms were observed to have a large effect on the solubility, polypeptide conformation, and self-assembly of the miktoarms. Three main categories were observed: (i) lamellar self-assemblies at the block copolymer length scale with packed layers of α-helices in PS 2PBLL and PS 2PBLL 2; (ii) charge-clustered polypeptide micelles with less-defined conformations in a nonordered lattice within a PS matrix in PS 2PLLHCl and PS 2PLLHCl 2; (iii) lamellar polypeptide-surfactant self-assemblies with β-sheet conformation in PS 2PLL(DS) and PS 2(PLL(DS)) 2 which dominate over the formation of block copolymer scale structures. Differences between the 3- and 4-arm systems illustrate how packing frustration between the coil-like PS arms and rigid polypeptide conformations can be relieved by the right number of arms, leading to differences in the extent of order. © 2012 American Chemical Society.

Avian leukosis virus is a versatile eukaryotic platform for polypeptide display

International Nuclear Information System (INIS)

Khare, Pranay D.; Russell, Stephen J.; Federspiel, Mark J.

2003-01-01

Display technology refers to methods of generating libraries of modularly coded biomolecules and screening them for particular properties. Retroviruses are good candidates to be a eukaryotic viral platform for the display of polypeptides synthesized in eukaryotic cells. Here we demonstrate that avian leukosis virus (ALV) provides an ideal platform for display of nonviral polyaeptides expressed in a eukaryotic cell substrate. Different sizes of polypeptides were genetically fused to the extreme N-terminus of the ALV envelope glycoprotein in an ALV infectious clone containing an alkaline phosphatase reporter gene. The chimeric envelope glycoproteins were efficiently incorporated into virions and were stably displayed on the surface of the virions through multiple virus replication cycles. The foreign polypeptides did not interfere with the attachment and entry functions of the underlying ALV envelope glycoproteins. The displayed polypeptides were fully functional and could efficiently mediate attachment of the recombinant viruses to their respective cognate receptors. This study demonstrates that ALV is an ideal display platform for the generation and selection of libraries of polypeptides where there is a need for expression, folding, and posttranslational modification in the endoplasmic reticulum of eukaryotic cells

Polypeptide synthesis in alphavirus-infected aedes albopictus cells during the establishment of persistent infection

International Nuclear Information System (INIS)

Richardson, M.A.; Boulton, R.W.; Raghow, R.S.; Dalgarno, L.

1980-01-01

Polypeptide synthesis was examined in mosquito cells during the establishment of a persistent infection with two alphaviruses, Ross River virus (RRV) and Semliki Forest virus (SFV), and in vertebrate cells cytopathically-infected with the same viruses. In Aedes albopictus cells, RRV reached peak titres at 34-48 hours p.i. At 12 hours 85 per cent of cells assayed as infected by infective centre assay; by 48 hours when persistence was established, virus production was reduced and <5 per cent of cells assayed as infected. There was not shutdown of host polypeptide synthesis during infection. Viral polypeptide synthesis was maximal between 10 and 24 hours p.i. The major viral polypeptides labelled were nucleocapsid protein and envelope protein(s).The precursor polypeptide p95 which was prominent in infected BHK cells was not detected in mosquito cells. Similar results were obtained on SFV infection. During the establishment of persistence there was a coordinate decline in the synthesis of RRV polypeptides, reaching undetectable levels by 72 hours p.i. Subculturing persistently-infected cells led to a small increase in viral polypeptide synthesis and virus titre. In contrast, during RRV growth in BHK cells host protein synthesis was severely inhibited and by 9-11 hours p.i. virus-specific polypeptide synthesis represented more than 90 per cent of total protein synthetic activity. (author)

A de novo designed 11 kDa polypeptide: model for amyloidogenic intrinsically disordered proteins.

Science.gov (United States)

Topilina, Natalya I; Ermolenkov, Vladimir V; Sikirzhytski, Vitali; Higashiya, Seiichiro; Lednev, Igor K; Welch, John T

2010-07-01

A de novo polypeptide GH(6)[(GA)(3)GY(GA)(3)GE](8)GAH(6) (YE8) has a significant number of identical weakly interacting beta-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that beta-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.

ONKALO pose experiment. Geophysical logging and imaging of drillholes ONK-PP223, ONK-PP226, ONK-PP254 and ONK-PP259...261

International Nuclear Information System (INIS)

Tarvainen, A.-M.

2011-08-01

Suomen Malmi Oy conducted geophysical drillhole logging as well as optical and acoustic imaging of shallow drillholes ONK-PP223, ONK-PP226, ONK-PP254, ONKPP259, ONK-PP260 and ONK-PP261 at ONKALO in the investigation niche ONKTKU- 3 (POSE) between December 2009 and June 2010. The survey is a part of Posiva Oy's detailed investigation program for the final disposal of spent nuclear fuel. The assignment included the field work and data processing. The report describes field operation, equipment as well as processing procedures and shows the obtained results and an analysis of their quality in the appendices. The raw and processed data are delivered digitally in WellCAD, PDF and Excel format. (orig.)

Radiolysis of polypeptide

International Nuclear Information System (INIS)

Ogura, Isao; Nakamura, Katsuichi; Tanaka, Hiroshi; Takahashi, Katsuhiro; Ozaki, Makoto

1981-01-01

Almost the same results were obtained from the additional dipeptide, Gly-DL-Ala and DL-Ala-DL-Phe, by the γ-irradiation as previous report. Tri and tetrapeptide consisted of the same amino acid signified good stability than the others. Every polypeptide composed from sulfur contained amino acid exhaled the smell of hydrogen sulfide by the irradiation. It seemed that the stability by the difference of position of amino group in amino acid increased in order α, β, γ ... amino acid and that by the existence of hydroxyl group became smaller. (author)

The Research on the Impact of Maca Polypeptide on Sport Fatigue.

Science.gov (United States)

Miao, Hua

2015-01-01

In order to study the effect of maca polypeptide on sport fatigue, this paper selected 40 male mice, and they were randomly divided into group A, B, C and D. group A, B and C were fed food with different concentrations of maca polypeptide, and group D was control group. After two weeks of feeding, measured physiological indexes of mice, including blood glucose, urea nitrogen and creatinine. At last gived the experimental results, as well as the analysis. Experimental results show that maca polypeptide can improve the ability of anti-fatigue mice, and in a certain concentration range, the higher the concentration, the better the resistance to fatigue.

Tuning Ice Nucleation with Supercharged Polypeptides

NARCIS (Netherlands)

Yang, Huige; Ma, Chao; Li, Kaiyong; Liu, Kai; Loznik, Mark; Teeuwen, Rosalie; van Hest, Jan C. M.; Zhou, Xin; Herrmann, Andreas; Wang, Jianjun

2016-01-01

Supercharged unfolded polypeptides (SUPs) are exploited for controlling ice nucleation via tuning the nature of charge and charge density of SUPs. The results show that positively charged SUPs facilitate ice nucleation, while negatively charged ones suppress it. Moreover, the charge density of the

Near infrared imaging-guided photodynamic therapy under an extremely low energy of light by galactose targeted amphiphilic polypeptide micelle encapsulating BODIPY-Br2.

Science.gov (United States)

Liu, Le; Ruan, Zheng; Li, Tuanwei; Yuan, Pan; Yan, Lifeng

2016-10-18

Near infrared (NIR) imaging-guided photodynamic therapy (PDT) is attractive, especially the utilization of one dye as both a photosensitizer and fluorescent probe, and the as-synthesized BODIPY-Br 2 molecule is a candidate. Here, a galactose targeted amphiphilic copolymer of a polypeptide was synthesized and its micelles work as nanocarriers for BODIPY for targeting the NIR imaging-guided PDT of hepatoma cancer cells. At the same time, BODIPY could light up the cytoplasm for real-time imaging and kill cancer cells when the light was switched on. In vitro tests performed on both HepG2 and HeLa cells confirmed that the as-prepared PMAGP-POEGMA-PLys-B micelles showed efficient cell suppression of the cells with galactose receptors in the presence of light under an extremely low energy density (6.5 J cm -2 ). This protocol highlights the potential of polypeptides as biodegradable carriers for NIR image-guided and confined targeting photodynamic therapy.

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

Science.gov (United States)

Rutanen, E M; Koistinen, R; Seppälä, M; Julkunen, M; Suikkari, A M; Huhtala, M L

1987-01-01

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

Ultrastructural and biochemical detection of biotin and biotinylated polypeptides in Schistosoma mansoni

Directory of Open Access Journals (Sweden)

Santos P.R.P.

1997-01-01

Full Text Available Biotinylation is proposed for the identification of surface proteins in Schistosoma mansoni using the streptavidin-HRP conjugate for the detection of labeled polypeptides. However, control samples also showed several endogenous biotinylated polypeptides. In an attempt to determine the possibility of nonspecific binding between the streptavidin-HRP conjugate and polypeptides from S. mansoni, the conjugate was blocked with biotinamidecaproate-N-hydroxysuccinimide ester (BcapNHS before biotin-streptavidin blotting. No bands were detected on the nitrocellulose sheet, demonstrating the specific recognition of biotin by the streptavidin present in the conjugate. Whole cercariae and cercarial bodies and tails showed several endogenous biotinylated polypeptides. The biotin concentration was 13 µg/190,000 cercariae. Adult worms presented less endogenous biotinylated polypeptides than cercariae. These results may be due to changes in the environment from aerobic to anaerobic conditions when cercarial bodies (schistosomula are transformed into adult worms and a decrease in CO2 production may occur. Cercariae, cercarial bodies and adult male worms were examined by transmission electron microscopy employing an avidin-colloidal gold conjugate for the detection of endogenous biotin. Gold particles were distributed mainly on the muscle fibers, but dispersed granules were observed in the tegument, mitochondria and cytosol. The discovery of endogenous biotin in S. mansoni should be investigated in order to clarify the function of this vitamin in the parasite

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

Science.gov (United States)

Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

2009-01-01

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering

[Physiology and disease of the endocrine function of the pancreas (author's transl)].

Science.gov (United States)

Stubbe, P

1980-12-01

Qualitative and quantitative immunocytochemistry, electronmicroscopy and radio-immuno-assays led to the discovery of 5 pancreatic polypeptide hormones under physiological conditions. The active endocrine cells and the produced hormones are termed A, B, D, D1, and PP cell and glucagon, insulin, somatostatin, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide (PP) respectively. Beside the physiology of secretion and action a survey of pathological conditions in the paediatric age group is given. Insulin is the most important of pancreatic hormones in childhood. Therefore diagnosis and treatment of hyperinsulinism are described in extension.

Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer

DEFF Research Database (Denmark)

Brooks, Susan A; Carter, Tracey M; Bennett, Eric P

2007-01-01

understood, may mediate the synthesis of varied glycoforms of cellular proteins with different biological activities. Disruptions in glycosylation are a common feature of cancer and may have functional significance. Immunocytochemistry with confocal scanning laser microscopy was employed to detect members...... of the ppGalNAc-T family, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell lines. The cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT 3,522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic breast cancer (ZR75-1, T47D, MCF-7, DU 4...... tightly restricted ppGalNAc-T's may result in initiation of O-linked glycosylation at normally unoccupied potential glycosylation sites leading to altered glycoforms of proteins with changed biological activity which may contribute to the pathogenesis of cancer....

Comparison between the polypeptide profile of halophilic bacteria and salt tolerant plants.

Science.gov (United States)

Muñoz, G; González, C; Flores, P; Prado, B; Campos, V

1997-12-01

Changes in the polypeptide profile induced by salt stress in halotolerant and halophilic bacteria, isolated from the Atacama desert (northern Chile), were compared with those in the cotyledons of Prosopis chilensis (Leguminoseae) seedlings, a salt tolerant plant. SDS-PAGE analyses show the presence of four predominant polypeptides, with molecular weights around 78, 70, 60 and 44 kDa respectively, both in bacteria and in cotyledons from P. chilensis seedlings raised under salt stress conditions. Moreover, the 60 and 44 kDa polypeptides seem to be salt responsive, since their concentration increases with increasing NaCl in the growth medium. Our results suggest a common mechanism for salt tolerance in prokaryotes and in eukaryotes.

The mining of toxin-like polypeptides from EST database by single residue distribution analysis.

Science.gov (United States)

Kozlov, Sergey; Grishin, Eugene

2011-01-31

Novel high throughput sequencing technologies require permanent development of bioinformatics data processing methods. Among them, rapid and reliable identification of encoded proteins plays a pivotal role. To search for particular protein families, the amino acid sequence motifs suitable for selective screening of nucleotide sequence databases may be used. In this work, we suggest a novel method for simplified representation of protein amino acid sequences named Single Residue Distribution Analysis, which is applicable both for homology search and database screening. Using the procedure developed, a search for amino acid sequence motifs in sea anemone polypeptides was performed, and 14 different motifs with broad and low specificity were discriminated. The adequacy of motifs for mining toxin-like sequences was confirmed by their ability to identify 100% toxin-like anemone polypeptides in the reference polypeptide database. The employment of novel motifs for the search of polypeptide toxins in Anemonia viridis EST dataset allowed us to identify 89 putative toxin precursors. The translated and modified ESTs were scanned using a special algorithm. In addition to direct comparison with the motifs developed, the putative signal peptides were predicted and homology with known structures was examined. The suggested method may be used to retrieve structures of interest from the EST databases using simple amino acid sequence motifs as templates. The efficiency of the procedure for directed search of polypeptides is higher than that of most currently used methods. Analysis of 39939 ESTs of sea anemone Anemonia viridis resulted in identification of five protein precursors of earlier described toxins, discovery of 43 novel polypeptide toxins, and prediction of 39 putative polypeptide toxin sequences. In addition, two precursors of novel peptides presumably displaying neuronal function were disclosed.

Processes for the production of hydroxycinnamic acids using polypeptides having tyrosine ammonia lyase activity

DEFF Research Database (Denmark)

2016-01-01

The present invention generally relates to the field of biotechnology as it applies to the production of hydroxycinnamic acids using polypeptides having tyrosine ammonia lyase activity. More particularly, the present invention pertains to polypeptides having tyrosine ammonia lyase activity and high...... substrate specificity towards tyrosine, which makes them particularly suitable in the production of p-coumaric acid and other hydroxycinnamic acids. The present invention thus provides processes for the production of p-coumaric acid and other hydroxycinnamic acids employing these polypeptides as well...

Fabrication of genetically engineered polypeptide@quantum dots hybrid nanogels for targeted imaging

Science.gov (United States)

Yang, Jie; Yao, Ming-Hao; Zhao, Dong-Hui; Zhang, Xiao-Shuai; Jin, Rui-Mei; Zhao, Yuan-Di; Liu, Bo

2017-08-01

Nanogels have been widely used as multifunctional drug delivery carriers because of high water content, biocompatibility, and high loading capability. We designed and biosynthesized two triblock artificial polypeptides PC10A and PC10ARGD as vehicles for encapsulating hydrophobic materials. These polypeptides can form nanogels by self-assembly when the concentration is below 2% ( w/ v). The physical properties of nanogels, including size, surface potential, and targeting domain, are able to be tuned. Hydrophobic materials from molecular size to nano-size can be loaded into the polypeptide nanogels to form hybrid nanogels. Hydrophobic quantum dots CdSe@ZnS below 10 nM were loaded into the polypeptide nanogels by ultrasonic treatment. Encapsulation endows hydrophobic QDs with good tunability of size, water solubility, stability, targeting, and biocompatibility. PC10ARGD nanogels and PC10ARGD@QDs hybrid nanogels showed excellent biocompatibility, which the cellular viabilities of HeLa and MCF-7 cells treated with 1% PC10ARGD nanogels and PC10ARGD@QDs hybrid nanogels contained 20 nM QDs were above 90 and 80%, respectively. PC10ARGD@QDs hybrid nanogels with an arginine-glycine-aspartic acid motif present efficient receptor-mediated endocytosis in α v β 3 overexpressing HeLa cells but not in the control MCF-7 cells as analyzed by confocal microscopy. These results demonstrate that such polypeptide nanogels as nanocarriers are expected to have great potential applications in biomedicine.

Effect of oxygen on morphogenesis and polypeptide expression by Mucor racemosus

International Nuclear Information System (INIS)

Phillips, G.J.; Borgia, P.T.

1985-01-01

The morphology of Mucor racemosus in cultures continuously sparged with nitrogen gas was investigated. When appropriate precautions were taken to prevent oxygen from entering the cultures, the morphology of the cells was uniformly yeastlike irrespective of the N 2 flow rate. When small amounts of oxygen entered the cultures the resulting microaerobic conditions evoked mycelial development. Polypeptides synthesized by aerobic mycelia, microaerobic mycelia, anaerobic yeasts, and yeasts grown in a CO 2 atmosphere were compared by two-dimensional gel electrophoresis. The results indicated that a large number of differences in polypeptide expression exist when microaerobic mycelia or anaerobic yeasts are compared with aerobic mycelia and that these alterations correlate with a change from an oxidative to a fermentative metabolic mode. The authors hypothesize that oxygen regulates the expression of polypeptides involved in both the metabolic mode and in morphogenesis

Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species.

Science.gov (United States)

Smith, Kathrine J; Petit, Chantal M; Aubart, Kelly; Smyth, Martin; McManus, Edward; Jones, Jo; Fosberry, Andrew; Lewis, Ceri; Lonetto, Michael; Christensen, Siegfried B

2003-02-01

Polypeptide deformylase (PDF) catalyzes the deformylation of polypeptide chains in bacteria. It is essential for bacterial cell viability and is a potential antibacterial drug target. Here, we report the crystal structures of polypeptide deformylase from four different species of bacteria: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Comparison of these four structures reveals significant overall differences between the two Gram-negative species (E. coli and H. influenzae) and the two Gram-positive species (S. pneumoniae and S. aureus). Despite these differences and low overall sequence identity, the S1' pocket of PDF is well conserved among the four enzymes studied. We also describe the binding of nonpeptidic inhibitor molecules SB-485345, SB-543668, and SB-505684 to both S. pneumoniae and E. coli PDF. Comparison of these structures shows similar binding interactions with both Gram-negative and Gram-positive species. Understanding the similarities and subtle differences in active site structure between species will help to design broad-spectrum polypeptide deformylase inhibitor molecules.

The mining of toxin-like polypeptides from EST database by single residue distribution analysis

Directory of Open Access Journals (Sweden)

Grishin Eugene

2011-01-01

Full Text Available Abstract Background Novel high throughput sequencing technologies require permanent development of bioinformatics data processing methods. Among them, rapid and reliable identification of encoded proteins plays a pivotal role. To search for particular protein families, the amino acid sequence motifs suitable for selective screening of nucleotide sequence databases may be used. In this work, we suggest a novel method for simplified representation of protein amino acid sequences named Single Residue Distribution Analysis, which is applicable both for homology search and database screening. Results Using the procedure developed, a search for amino acid sequence motifs in sea anemone polypeptides was performed, and 14 different motifs with broad and low specificity were discriminated. The adequacy of motifs for mining toxin-like sequences was confirmed by their ability to identify 100% toxin-like anemone polypeptides in the reference polypeptide database. The employment of novel motifs for the search of polypeptide toxins in Anemonia viridis EST dataset allowed us to identify 89 putative toxin precursors. The translated and modified ESTs were scanned using a special algorithm. In addition to direct comparison with the motifs developed, the putative signal peptides were predicted and homology with known structures was examined. Conclusions The suggested method may be used to retrieve structures of interest from the EST databases using simple amino acid sequence motifs as templates. The efficiency of the procedure for directed search of polypeptides is higher than that of most currently used methods. Analysis of 39939 ESTs of sea anemone Anemonia viridis resulted in identification of five protein precursors of earlier described toxins, discovery of 43 novel polypeptide toxins, and prediction of 39 putative polypeptide toxin sequences. In addition, two precursors of novel peptides presumably displaying neuronal function were disclosed.

Biosynthesis and characterization of typical fibroin crystalline polypeptides of silkworm Bombyx mori

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Wang Jiannan, E-mail: wangjn@suda.edu.cn [College of Material Engineering, Soochow University, Suzhou 215021 (China); Yan Shuqin [College of Material Engineering, Soochow University, Suzhou 215021 (China); Lu Changde [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Bai Lun [College of Material Engineering, Soochow University, Suzhou 215021 (China)

2009-05-05

We aimed to investigate the self-organization/self-assembly mechanisms of silkworm fibroin-based material. In the present study, for the first time, we designed and multimerized four DNA 'monomer' sequences from structurally simple fibroin crystalline peptides or analog, [GAGAGX] (X = A, S, Y and V) to encode polypeptides [GAGAGX]{sub 16} (eGA, eGS, eGY and eGV) using a 'head-to-tail' construction strategy. Multimers were cloned into pGEX-KG and fusion proteins GST-[GAGAGX]{sub 16} (KGA, KGS, KGY and KGV) were efficiently expressed in Escherichia coli. These fusion proteins were isolated and purified by GST affinity chromatography and confirmed by SDS-PAGE and Western blot analysis using antibody reactive to GST. The polypeptides were cleavaged from GST fusion proteins by digesting with thrombin enzyme. The composition of the four polypeptides was confirmed by composition analysis of amino acids, and their abilities to form {beta}-sheet structure were determined by ThT fluorescence spectral analysis. The content of {beta}-sheet among the four polypeptides followed the order: eGS > eGV > eGY > eGA.

Brachytherapy Using Elastin-Like Polypeptides with (131)I Inhibit Tumor Growth in Rabbits with VX2 Liver Tumor.

Science.gov (United States)

Liu, Xinpei; Shen, Yiming; Zhang, Xuqian; Lin, Rui; Jia, Qiang; Chang, Yixiang; Liu, Wenge; Liu, Wentian

2016-10-01

Brachytherapy is a targeted type of radiotherapy utilized in the treatment of cancers. Elastin-like polypeptides are a unique class of genetically engineered peptide polymers that have several attractive properties for brachytherapy. To explore the feasibility and application of brachytherapy for VX2 liver tumor using elastin-like polypeptides with (131)I so as to provide reliable experimental evidence for a new promising treatment of liver cancer. Elastin-like polypeptide as carrier was labeled with (131)I using the iodogen method. Ten eligible rabbits with VX2 liver tumor were randomly divided into the treatment group (n = 5) and control group (n = 5). The treatment group received brachytherapy using elastin-like polypeptide with (131)I, and in the control group, elastin-like polypeptide was injected into the VX2 liver tumor as a control. Periodic biochemical and imaging surveillances were required to assess treatment efficacy. The stability of elastin-like polypeptide with (131)I in vitro was maintained at over 96.8 % for 96 h. Biochemistry and imaging indicated brachytherapy using elastin-like polypeptide with (131)I for liver tumor can improve liver function and inhibit tumor growth (P Elastin-like polypeptide can be an ideal carrier of (131)I and have high labeling efficiency, radiochemical purity and stability. Brachytherapy using elastin-like polypeptide with (131)I for liver tumor is a useful therapy that possesses high antitumor efficacy advantages.

Moisture absorption and retention properties, and activity in alleviating skin photodamage of collagen polypeptide from marine fish skin.

Science.gov (United States)

Hou, Hu; Li, Bafang; Zhang, Zhaohui; Xue, Changhu; Yu, Guangli; Wang, Jingfeng; Bao, Yuming; Bu, Lin; Sun, Jiang; Peng, Zhe; Su, Shiwei

2012-12-01

Collagen polypeptides were prepared from cod skin. Moisture absorption and retention properties of collagen polypeptides were determined at different relative humidities. In addition, the protective effects of collagen polypeptide against UV-induced damage to mouse skin were evaluated. Collagen polypeptides had good moisture absorption and retention properties and could alleviate the damage induced by UV radiation. The action mechanisms of collagen polypeptide mainly involved enhancing immunity, reducing the loss of moisture and lipid, promoting anti-oxidative properties, inhibiting the increase of glycosaminoglycans, repairing the endogenous collagen and elastin protein fibres, and maintaining the ratio of type III to type I collagen. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polycondensation of Asparagine-comprising Dipeptides in Aqueous Media-A Simulation of Polypeptide Formation in Primordial Earth Hydrosphere

Science.gov (United States)

Munegumi, Toratane; Tanikawa, Naoya

2017-09-01

Asparagine and aspartic acid might have mutually transformed in the primordial hydrosphere of the earth, if ammonia and aspartic acid had existed in equilibrium. These amino acids seem to contribute to polypeptides, while the simple amino acids glycine and alanine easily form cyclic dipeptides and do not achieve long peptide chains. Asparagine-comprising dipeptides contribute some kinds of activation forms of dipeptides because these can polymerize faster than asparagine only. The new finding of polypeptide formation suggests a pathway of sequential polypeptides to evolve a diversity of polypeptides.

Polycondensation of Asparagine-comprising Dipeptides in Aqueous Media-A Simulation of Polypeptide Formation in Primordial Earth Hydrosphere.

Science.gov (United States)

Munegumi, Toratane; Tanikawa, Naoya

2017-09-01

Asparagine and aspartic acid might have mutually transformed in the primordial hydrosphere of the earth, if ammonia and aspartic acid had existed in equilibrium. These amino acids seem to contribute to polypeptides, while the simple amino acids glycine and alanine easily form cyclic dipeptides and do not achieve long peptide chains. Asparagine-comprising dipeptides contribute some kinds of activation forms of dipeptides because these can polymerize faster than asparagine only. The new finding of polypeptide formation suggests a pathway of sequential polypeptides to evolve a diversity of polypeptides.

Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.

Science.gov (United States)

Moreadith, R W; Cleeter, M W; Ragan, C I; Batshaw, M L; Lehninger, A L

1987-02-01

Recently, we described a patient with severe lactic acidosis due to congenital complex I (NADH-ubiquinone oxidoreductase) deficiency. We now report further enzymatic and immunological characterizations. Both NADH and ferricyanide titrations of complex I activity (measured as NADH-ferricyanide reductase) were distinctly altered in the mitochondria from the patient's tissues. In addition, antisera against complex I immunoprecipitated NADH-ferricyanide reductase from the control but not the patient's mitochondria. However, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of complex I polypeptides demonstrated that the majority of the 25 polypeptides comprising complex I were present in the affected mitochondria. A more detailed analysis using subunit selective antisera against the main polypeptides of the iron-protein fragments of complex I revealed a selective absence of the 75- and 13-kD polypeptides. These findings suggest that the underlying basis for this patient's disease was a congenital deficiency of at least two polypeptides comprising the iron-protein fragment of complex I, which resulted in the inability to correctly assemble a functional enzyme complex.

Application of Statistical Thermodynamics To Predict the Adsorption Properties of Polypeptides in Reversed-Phase HPLC.

Science.gov (United States)

Tarasova, Irina A; Goloborodko, Anton A; Perlova, Tatyana Y; Pridatchenko, Marina L; Gorshkov, Alexander V; Evreinov, Victor V; Ivanov, Alexander R; Gorshkov, Mikhail V

2015-07-07

The theory of critical chromatography for biomacromolecules (BioLCCC) describes polypeptide retention in reversed-phase HPLC using the basic principles of statistical thermodynamics. However, whether this theory correctly depicts a variety of empirical observations and laws introduced for peptide chromatography over the last decades remains to be determined. In this study, by comparing theoretical results with experimental data, we demonstrate that the BioLCCC: (1) fits the empirical dependence of the polypeptide retention on the amino acid sequence length with R(2) > 0.99 and allows in silico determination of the linear regression coefficients of the log-length correction in the additive model for arbitrary sequences and lengths and (2) predicts the distribution coefficients of polypeptides with an accuracy from 0.98 to 0.99 R(2). The latter enables direct calculation of the retention factors for given solvent compositions and modeling of the migration dynamics of polypeptides separated under isocratic or gradient conditions. The obtained results demonstrate that the suggested theory correctly relates the main aspects of polypeptide separation in reversed-phase HPLC.

Generation of polypeptide-templated gold nanoparticles using ionizing radiation.

Science.gov (United States)

Walker, Candace Rae; Pushpavanam, Karthik; Nair, Divya Geetha; Potta, Thrimoorthy; Sutiyoso, Caesario; Kodibagkar, Vikram D; Sapareto, Stephen; Chang, John; Rege, Kaushal

2013-08-13

Ionizing radiation, including γ rays and X-rays, are high-energy electromagnetic radiation with diverse applications in nuclear energy, astrophysics, and medicine. In this work, we describe the use of ionizing radiation and cysteine-containing elastin-like polypeptides (C(n)ELPs, where n = 2 or 12 cysteines in the polypeptide sequence) for the generation of gold nanoparticles. In the presence of C(n)ELPs, ionizing radiation doses higher than 175 Gy resulted in the formation of maroon-colored gold nanoparticle dispersions, with maximal absorbance at 520 nm, from colorless metal salts. Visible color changes were not observed in any of the control systems, indicating that ionizing radiation, gold salt solution, and C(n)ELPs were all required for nanoparticle formation. The hydrodynamic diameters of nanoparticles, determined using dynamic light scattering, were in the range of 80-150 nm, while TEM imaging indicated the formation of gold cores 10-20 nm in diameter. Interestingly, C2ELPs formed 1-2 nm diameter gold nanoparticles in the absence of radiation. Our results describe a facile method of nanoparticle formation in which nanoparticle size can be tailored based on radiation dose and C(n)ELP type. Further improvements in these polypeptide-based systems can lead to colorimetric detection of ionizing radiation in a variety of applications.

Effectiveness of hCMV, mEF1a and mAct promoters on driving of foreign gene expression in transgenic zebrafish

Directory of Open Access Journals (Sweden)

. Alimuddin

2007-01-01

Full Text Available Highly unsaturated fatty acids (HUFA, especially eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA have long been recognized for its beneficial effect for human health and development.   The D6 fatty acid desaturase is generally considered to be the rate-limiting factor in HUFA biosynthesis.  Here, as the first step of study, we conducted experiment to select an appropriate construct that allows higher expression levels of masu salmon (Oncorhynchus masou D6-desaturase gene in zebrafish (Danio rerio in order to increase its activity for synthesizing EPA/DHA.  Salmon D6-desaturase cDNA (sD6 was separately ligated with human cytomegalovirus (hCMV, medaka elongation factor 1a (mEF1a and medaka b-actin (mAct promoters.  The resulted construct was designated as hCMV-sD6, mEF1a-sD6 and mAct-sD6, respectively.  Each of the constructs in circular DNA form was microinjected into 1-cell stage embryos at a concentration of 30mg/ml. Transgenic individuals were identified by polymerase chain reaction (PCR and their expression levels were analyzed by reverse transcription PCR.  The first (F1 and second (F2 generation was produced by crossing the transgenic founder F0 and F1, respectively, with wild-type fish.  The results showed that the highest transient gene expression level was obtained from the mAct-D6 construct, followed respectively by EF1a-D6 and hCMV-D6 construct. The transmission rate of transgene into F1 generation was 4.2%-44.1%, and into F2 was followed the Mendellian segregation pattern.   Expression of transgene in F2 generation was varied between strains regarding as the mosaics of F0 fish.  Now, a transgenic system to study the modification of fatty acid biosynthesis pathways in fish was established.  Further investigations are to produce fish containing higher levels of EPA and DHA. Keywords: desaturase, nutraceutical fatty acid, transgenic, zebrafish, masu salmon   Abstrak Promoter merupakan regulator yang menentukan

Synthetic profiles of polypeptides of human oocytes and normal and abnormal preimplantation embryos.

Science.gov (United States)

Capmany, G; Bolton, V N

1999-09-01

There is considerable variation in the rate of development in vitro of individual preimplantation human embryos. The relationship between the rate of development and patterns of polypeptide synthesis in individual embryos was examined using SDS-PAGE and autoradiography. After incubation in [35S]methionine, 19 polypeptide bands were identified that change between fertilization and the morula stage. Although changes in two of the bands occurred in embryos that were developing normally and in ageing oocytes, and are thus independent of fertilization, the changes identified in the remaining 17 bands occurred only after fertilization. In embryos that were developing abnormally, as assessed by delayed cleavage, cleavage arrest or extensive fragmentation, the alteration in polypeptide synthetic profiles increased with increasing abnormality.

40 CFR 65.65 - Monitoring.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Monitoring. 65.65 Section 65.65 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONSOLIDATED FEDERAL AIR RULE Process Vents § 65.65 Monitoring. (a) An owner or operator of a Group 2A process vent...

Molecular diversity and hypoglycemic polypeptide-P content of Momordica charantia in different accessions and different seasons.

Science.gov (United States)

Tian, Miao; Zeng, Xiang-Qing; Song, Huan-Lei; Hu, Shan-Xin; Wang, Fu-Jun; Zhao, Jian; Hu, Zhi-Bi

2015-04-01

Momordica charantia (MC) has been used for treating diabetes mellitus from ancient times in Asia, Africa and South America. There are many MC accessions in local markets. Polypeptide-P as a main hypoglycemic component in MC was first studied in this experiment to illustrate the different contents in MC of different accessions and different harvesting times. Nineteen MC accessions collected from different regions were clustered into three groups using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) molecular markers. Content of polypeptide-P in the tested MC accessions was detected by western blot (WB) method. The WB results revealed that polypeptide-P was detected in MC accessions harvested in June and July but not in September and October. Furthermore, Polypeptide-P content corresponded well with the MC accessions. Our results suggest that the MC accessions and the harvesting times or the weather during harvest play significant roles in high content of polypeptide-P. © 2014 Society of Chemical Industry.

A comparison of pp and pp elastic scattering at 90 degrees

CERN Document Server

Eisenhandler, E F; Astbury, A; Gibson, W R; Harrison, M; Hojvat, C; Jones, D P; Kalmus, Peter I P; Kemp, M A R; Lee Chi Kwong, L; Parsons, A S L; Pritchard, T W; Range, W H; Rush, A D; Usher, E C; Williams, D T; Woulds, J N

1974-01-01

A study of low momentum antiproton-proton interactions in the momentum range 0.7 to 2.4 GeV/c has yielded differential cross sections for the elastic channel. An observation of one property of the data when compared with pp elastic scattering within the framework of quark- parton models is presented. The pp and pp systems, related by crossing symmetry, provided significant constraints on any particular model. (13 refs).

Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.

Science.gov (United States)

Lange, Karen I; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

2013-01-15

Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans

Directory of Open Access Journals (Sweden)

Karen I. Lange

2012-11-01

Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″ but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts, and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

1972, pp. 136. 76

African Journals Online (AJOL)

WERNER MASER: Adolf Hitler. legende, mythe, werkelijkheid. Uitgeverij De Arbeiders- pers, Amsterdam, 1973, pp. 531. Met aante- keninge [pp. 429 -. 506] en bibliografie. [pp. 507 - 531]. In 1945 het die skrywer van hierdie studie, op grond van 'n proefskrif oor die doelbewuste aankweek van die Hitlerlegende tot 1924,.

Cotranslational structure acquisition of nascent polypeptides monitored by NMR spectroscopy.

Science.gov (United States)

Eichmann, Cédric; Preissler, Steffen; Riek, Roland; Deuerling, Elke

2010-05-18

The folding of proteins in living cells may start during their synthesis when the polypeptides emerge gradually at the ribosomal exit tunnel. However, our current understanding of cotranslational folding processes at the atomic level is limited. We employed NMR spectroscopy to monitor the conformation of the SH3 domain from alpha-spectrin at sequential stages of elongation via in vivo ribosome-arrested (15)N,(13)C-labeled nascent polypeptides. These nascent chains exposed either the entire SH3 domain or C-terminally truncated segments thereof, thus providing snapshots of the translation process. We show that nascent SH3 polypeptides remain unstructured during elongation but fold into a compact, native-like beta-sheet assembly when the entire sequence information is available. Moreover, the ribosome neither imposes major conformational constraints nor significantly interacts with exposed unfolded nascent SH3 domain moieties. Our data provide evidence for a domainwise folding of the SH3 domain on ribosomes without significant population of folding intermediates. The domain follows a thermodynamically favorable pathway in which sequential folding units are stabilized, thus avoiding kinetic traps during the process of cotranslational folding.

Acyclovir Therapy Reduces the CD4+ T Cell Response against the Immunodominant pp65 Protein from Cytomegalovirus in Immune Competent Individuals.

Directory of Open Access Journals (Sweden)

Annette Pachnio

Full Text Available Cytomegalovirus (CMV infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

High rate of symptomatic cytomegalovirus infection in extremely low gestational age preterm infants of 22-24 weeks' gestation after transmission via breast milk.

Science.gov (United States)

Mehler, Katrin; Oberthuer, André; Lang-Roth, Ruth; Kribs, Angela

2014-01-01

Very immature preterm infants are at risk of developing symptomatic or severe infection if cytomegalovirus is transmitted via breast milk. It is still a matter of debate whether human cytomegalovirus (HCMV) infection may lead to long-term sequelae. We hypothesized that symptomatic and severe HCMV infection transmitted via breast milk affects extremely immature infants at a very high rate. In 2012, untreated breast milk was fed to extremely low birth weight infants after parental informed consent was obtained. We retrospectively analyzed data on HCMV infection of infants born in 2012 between 22 and 24 weeks of gestation. 17 infants were born to HCMV IgG-seropositive mothers. 11 (65%) of these were diagnosed with symptomatic infection. In all cases, thrombocytopenia was the reason to analyze the infant's urine. HCMV infection was diagnosed at a median time of 12 weeks after birth. In 5 (45%) infants, thrombocytopenia was the only symptom and resolved without antiviral therapy or platelet transfusion. 6 (55%) infants developed sepsis-like disease with mildly elevated CRP values and showed signs of respiratory failure. 3 (27%) were able to be stabilized on CPAP, 3 (27%) had to be intubated and mechanically ventilated. 4 children were treated with ganciclovir and/or valganciclovir. 55% failed otoacoustic emissions and/or automated auditory brainstem response testing at discharge. In very immature infants born at the border of viability and suffering from multiple preexisting problems, HCMV infection may trigger a severe deterioration of the clinical course. © 2013 S. Karger AG, Basel.

PP-O and PP-V, Monascus pigment homologues, production, and phylogenetic analysis in Penicillium purpurogenum.

Science.gov (United States)

Arai, Teppei; Kojima, Ryo; Motegi, Yoshiki; Kato, Jun; Kasumi, Takafumi; Ogihara, Jun

2015-12-01

The production of pigments as secondary metabolites by microbes is known to vary by species and by physiological conditions within a single strain. The fungus strain Penicillium purpurogenum IAM15392 has been found to produce violet pigment (PP-V) and orange pigment (PP-O),Monascus azaphilone pigment homologues, when grown under specific culture conditions. In this study, we analysed PP-V and PP-O production capability in seven strains of P. purpurogenum in addition to strain IAM15392 under specific culture conditions. The pigment production pattern of five strains cultivated in PP-V production medium was similar to that of strain IAM15392, and all violet pigments produced by these five strains were confirmed to be PP-V. Strains that did not produce pigment were also identified. In addition, two strains cultivated in PP-O production medium produced a violet pigment identified as PP-V. The ribosomal DNA (rDNA) internal transcribed spacer (ITS) region sequences from the eight P. purpurogenum strains were sequenced and used to construct a neighbor-joining phylogenetic tree. PP-O and PP-V production of P. purpurogenum was shown to be related to phylogenetic placement based on rDNA ITS sequence. Based on these results, two hypotheses for the alteration of pigment production of P. purpurogenum in evolution were proposed. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Stimuli-Triggered Sol-Gel Transitions of Polypeptides Derived from α-Amino Acid N-Carboxyanhydride (NCA) Polymerizations.

Science.gov (United States)

He, Xun; Fan, Jingwei; Wooley, Karen L

2016-02-18

The past decade has witnessed significantly increased interest in the development of smart polypeptide-based organo- and hydrogel systems with stimuli responsiveness, especially those that exhibit sol-gel phase-transition properties, with an anticipation of their utility in the construction of adaptive materials, sensor designs, and controlled release systems, among other applications. Such developments have been facilitated by dramatic progress in controlled polymerizations of α-amino acid N-carboxyanhydrides (NCAs), together with advanced orthogonal functionalization techniques, which have enabled economical and practical syntheses of well-defined polypeptides and peptide hybrid polymeric materials. One-dimensional stacking of polypeptides or peptide aggregations in the forms of certain ordered conformations, such as α helices and β sheets, in combination with further physical or chemical cross-linking, result in the construction of three-dimensional matrices of polypeptide gel systems. The macroscopic sol-gel transitions, resulting from the construction or deconstruction of gel networks and the conformational changes between secondary structures, can be triggered by external stimuli, including environmental factors, electromagnetic fields, and (bio)chemical species. Herein, the most recent advances in polypeptide gel systems are described, covering synthetic strategies, gelation mechanisms, and stimuli-triggered sol-gel transitions, with the aim of demonstrating the relationships between chemical compositions, supramolecular structures, and responsive properties of polypeptide-based organo- and hydrogels. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Finsler pp-waves

NARCIS (Netherlands)

Fuster, A.; Pabst, C.

2015-01-01

In this work we present a Finslerian version of the well-known pp-waves, which generalizes the very special relativity (VSR) line element. Our Finsler pp-waves are an exact solution of Finslerian Einstein's equations in vacuum.

Nanostructured complexes of polyelectrolytes and charged polypeptides

Czech Academy of Sciences Publication Activity Database

Müller, M.; Ouyang, W.; Bohatá, Karolína; Kessler, B.

2010-01-01

Roč. 12, Sp. Iss. 9 (2010), B519-B528 ISSN 1438-1656. [Sino-German Symposium on Advanced Biomedical Nanostructures /1./. Jena, 26.10.2009-30.10.2009] Institutional research plan: CEZ:AV0Z40500505 Keywords : situ ATR-FTIR * alpha-helical polypeptides * multilayer films Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.746, year: 2010

Gluon ladders in pp (pp-bar) collisions

International Nuclear Information System (INIS)

Machado, Magno Valerio Trindade; Ducati, Maria Beatriz Gay

2000-01-01

Full text follows: We study the contribution of a finite sum of gluon ladders to the hadronic processes showing that a reliable description is obtained using two order on perturbation theory. The pp(pp-bar) total cross sections are described with good agreement, consistent with unitarity bound. We also calculate the elastic scattering amplitude at non zero momentum transfer t, introducing two distinct Ansatz for the proton impact factor. As a by product the elastic differential cross section is obtained at small t approximation and compared with the data. (author)

GAWK, a novel human pituitary polypeptide: isolation, immunocytochemical localization and complete amino acid sequence.

Science.gov (United States)

Benjannet, S; Leduc, R; Lazure, C; Seidah, N G; Marcinkiewicz, M; Chrétien, M

1985-01-16

During the course of reverse-phase high pressure liquid chromatography (RP-HPLC) purification of a postulated big ACTH (1) from human pituitary gland extracts, a highly purified peptide bearing no resemblance to any known polypeptide was isolated. The complete sequence of this 74 amino acid polypeptide, called GAWK, has been determined. Search on a computer data bank on the possible homology to any known protein or fragment, using a mutation data matrix, failed to reveal any homology greater than 30%. An antibody produced against a synthetic fragment allowed us to detect several immunoreactive forms. The antisera also enabled us to localize the polypeptide, by immunocytochemistry, in the anterior lobe of the pituitary gland.

Biosynthesis and characterization of a non-repetitive polypeptide derived from silk fibroin heavy chain

Energy Technology Data Exchange (ETDEWEB)

Yang, Gaoqiang; Wu, Mingyang; Yi, Honggen; Wang, Jiannan, E-mail: wangjn@suda.edu.cn

2016-02-01

Silk fibroin heavy chain is the major protein component of Bombyx mori silk fibroin and is composed of 12 repetitive and 11 non-repetitive regions, with the non-repetitive domain consisting of a hydrophilic polypeptide chain. In order to determine the biomedical function of the non-repetitive domain or potentially use it to modify hydrophobic biomaterials, high-purity isolation is necessary. Previously, we cloned and extended a gene motif (f(1)) encoding the non-repetitive domain. Here, this motif and its multimers are inserted into a glutathione S-transferase (GST)-tagged fusion-protein expression vector. Motif f(1) and multimers f(4) and f(8) were expressed in Escherichia coli BL21 cells following isopropyl β-D-1-thiogalactopyranoside induction, purified by GST-affinity chromatography, and single bands of purified fusion proteins GST-F(1), GST-F(4), and GST-F(8), were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Target polypeptides F(1), F(4), and F(8), were cleaved clearly from the GST-fusion tag following thrombin digestion. Mass spectrometry results indicate that the molecular weights associated with fusion proteins GST-F(1), GST-F(4), and GST-F(8) are 31.5, 43.8, and 59.0 kDa, respectively, and with the cleaved polypeptides F(1), F(4), and F(8) are 4.8, 16.8, and 32.8 kDa, respectively. The F(1), F(4), and F(8) polypeptide chains are negatively charged with isoelectric points (pI) of 3.3, 3.2, and 3.0, respectively. The molecular weight and pI values of the polypeptide chains are consistent with the predicted values and the amino acid compositions similar to predicted sequences. FTIR and CD results show the molecular conformation of F(1) was mainly random coil, and more stable α-helix structure formed in longer molecular chain. - Highlights: • A non-repetitive domain and its multimers of silk fibroin were expressed by E. coli. • The corresponding target polypeptides F(1), F(4) and F(8) were cleaved clearly. • Their

Flow measurements and hydraulic interference tests at the Olkiluoto site in Eurajoki, drillholes OL-KR14, OL-KR30, OL-PP66, OL-PP67, OL-PP68 and OL-PP69

Energy Technology Data Exchange (ETDEWEB)

Komulainen, J. [Poeyry Finland Oy, Vantaa (Finland)

2014-08-15

The measurements described in this report are part of the infiltration experiment carried out at Olkiluoto. The emphasis of these measurements is on obtaining more detailed data on hydraulically significant fractures in the infiltration experiment area. The selected fractures or sections were pumped in turn and flow responses were observed in the other holes by the PFL DIFF-tool. The flow measurements were carried out in drillholes OL-KR14, OL-KR30, OL-PP66, OL-PP67, OL-PP68 and OL-PP69 on the Olkiluoto investigation site between January 2013 and July 2013. Two different flowmeters were used for the measurements. Posiva Flow Log, Difference flow method (PFL DIFF) was used for the determination of hydraulic conductivity and hydraulic head in fractures/fractured zones in the drillholes. PFL DIFF flow logging was conducted in all the drillholes mentioned above. Posiva Flow Log, Transverse flow method (PFL TRANS) was used to determine groundwater flow direction and flow rate across a drillhole. The transverse flow method was used in drillholes OL-KR14 and OL-PP69. PFL DIFF and PFL TRANS measurements had been carried out earlier in drillholes OL-PP66, OL-PP67, OL-PP68 and OL-PP69. The most recent measurements were conducted in 2011. Those measurements were carried out when drillhole OL-KR14 was pumped at packed-off section 13 m - 18 m. Both PFL DIFF and PFL TRANS flowmeters include an electrode for measuring single point resistance (SPR). The device has a high depth resolution and the results were used for depth synchronisation between consecutive DIFF and TRANS measurements. (orig.)

EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

Science.gov (United States)

Morales-Sánchez, A.; Pompa-Mera, E. N.; Fajardo-Gutiérrez, A.; Alvarez-Rodríguez, F. J.; Bekker-Méndez, V. C.; Flores-Chapa, J. de Diego; Flores-Lujano, J.; Jiménez-Hernández, E.; Peñaloza-González, J. G.; Rodríguez-Zepeda, M. C.; Torres-Nava, J. R.; Velázquez-Aviña, M. M.; Amador-Sánchez, R.; Alvarado-Ibarra, M.; Reyes-Zepeda, N.; Espinosa-Elizondo, R. M.; Pérez-Saldivar, M. L.; Núñez-Enríquez, J. C.; Mejía-Aranguré, J. M.; Fuentes-Pananá, E. M.

2014-01-01

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis. PMID:25309913

Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38

DEFF Research Database (Denmark)

Amin, Faisal Mohammad; Hougaard, Anders; Schytz, Henrik W

2014-01-01

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the ...

The Generation of Dehydroalanine Residues in Protonated Polypeptides: Ion/Ion Reactions for Introducing Selective Cleavages

Science.gov (United States)

Peng, Zhou; Bu, Jiexun; McLuckey, Scott A.

2017-09-01

We examine a gas-phase approach for converting a subset of amino acid residues in polypeptide cations to dehydroalanine (Dha). Subsequent activation of the modified polypeptide ions gives rise to specific cleavage N-terminal to the Dha residue. This process allows for the incorporation of selective cleavages in the structural characterization of polypeptide ions. An ion/ion reaction within the mass spectrometer between a multiply protonated polypeptide and the sulfate radical anion introduces a radical site into the multiply protonated polypeptide reactant. Subsequent collisional activation of the polypeptide radical cation gives rise to radical side chain loss from one of several particular amino acid side chains (e.g., leucine, asparagine, lysine, glutamine, and glutamic acid) to yield a Dha residue. The Dha residues facilitate preferential backbone cleavages to produce signature c- and z-ions, demonstrated with cations derived from melittin, mechano growth factor (MGF), and ubiquitin. The efficiencies for radical side chain loss and for subsequent generation of specific c- and z-ions have been examined as functions of precursor ion charge state and activation conditions using cations of ubiquitin as a model for a small protein. It is noted that these efficiencies are not strongly dependent on ion trap collisional activation conditions but are sensitive to precursor ion charge state. Moderate to low charge states show the greatest overall yields for the specific Dha cleavages, whereas small molecule losses (e.g., water/ammonia) dominate at the lowest charge states and proton catalyzed amide bond cleavages that give rise to b- and y-ions tend to dominate at high charge states. [Figure not available: see fulltext.

Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons.

Science.gov (United States)

Han, P; Lucero, M T

2005-01-01

Pituitary adenylate cyclase activating polypeptide has been shown to reduce apoptosis in neonatal cerebellar and olfactory receptor neurons, however the underlying mechanisms have not been elucidated. In addition, the neuroprotective effects of pituitary adenylate cyclase activating polypeptide have not been examined in adult tissues. To study the effects of pituitary adenylate cyclase activating polypeptide on neurons in apoptosis, we measured caspase activation in adult olfactory receptor neurons in vitro. Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50=144 microM) sensitive rapidly inactivating potassium current often referred to as A-type current. In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced. A-type current reduction by pituitary adenylate cyclase activating polypeptide was blocked by inhibiting the phospholipase C pathway, but not the adenylyl cyclase pathway. Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis. This work contributes to our growing understanding that potassium currents are involved with the activation of caspases to affect the balance between cell life and death.

PP2A-Mediated Anticancer Therapy

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Weibo Chen

2013-01-01

Full Text Available PP2A is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including protein synthesis, cellular signaling, cell cycle determination, apoptosis, metabolism, and stress responses through the negative regulation of signaling pathways initiated by protein kinases. Rapid progress is being made in the understanding of PP2A complex and its functions. Emerging studies have correlated changes in PP2A with human diseases, especially cancer. PP2A is comprised of 3 subunits: a catalytic subunit, a scaffolding subunit, and a regulatory subunit. The alternations of the subunits have been shown to be in association with many human malignancies. Therapeutic agents targeting PP2A inhibitors or activating PP2A directly have shed light on the therapy of cancers. This review focuses on PP2A structure, cancer-associated mutations, and the targeting of PP2A-related molecules to restore or reactivate PP2A in anticancer therapy, especially in digestive system cancer therapy.

Molecular cloning and protein structure of a human blood group Rh polypeptide

International Nuclear Information System (INIS)

Cherif-Zahar, B.; Bloy, C.; Le Van Kim, C.; Blanchard, D.; Bailly, P.; Hermand, P.; Salmon, C.; Cartron, J.P.; Colin, Y.

1990-01-01

cDNA clones encoding a human blood group Rh polypeptide were isolated from a human bone marrow cDNA library by using a polymerase chain reaction-amplified DNA fragment encoding the known common N-terminal region of the Rh proteins. The entire primary structure of the Rh polypeptide has been deduced from the nucleotide sequence of a 1384-base-pair-long cDNA clone. Translation of the open reading frame indicates that the Rh protein is composed of 417 amino acids, including the initiator methionine, which is removed in the mature protein, lacks a cleavable N-terminal sequence, and has no consensus site for potential N-glycosylation. The predicted molecular mass of the protein is 45,500, while that estimated for the Rh protein analyzed in NaDodSO 4 /polyacrylamide gels is in the range of 30,000-32,000. These findings suggest either that the hydrophobic Rh protein behaves abnormally on NaDodSO 4 gels or that the Rh mRNA may encode a precursor protein, which is further matured by a proteolytic cleavage of the C-terminal region of the polypeptide. Hydropathy analysis and secondary structure predictions suggest the presence of 13 membrane-spanning domains, indicating that the Rh polypeptide is highly hydrophobic and deeply buried within the phospholipid bilayer. These results suggest that the expression of the Rh gene(s) might be restricted to tissues or cell lines expressing erythroid characters

Lanthanum Containing Polymer's Modification to PP

Institute of Scientific and Technical Information of China (English)

Dai Shaojun; Zhang Ming

2004-01-01

Polypropylene (PP)'s low impact strength limits its usages. Adding some a rare earth polymer can enhance PP's tensile strength and impact strength. Acrylic lanthanum was prepared by the reaction between lanthanum oxide and acrylic acid. The IR spectrum prove that and optimum reacting conditions are that the bulk ratio of La(AA) 3 and MMA is not less than one and temperature is about 80 ℃. Lanthanum containing Polymer were added into PP. When percent of addition only was 3%, strength were enhanced 10% , and impact strength 40%. SEM shows the compatibility of rare earth polymer and PP; lanthanum containing polymer can form physical crosslinking between PP's molecules, then every particle's surface connect with several PP molecules and the PP mechanical property were enhanced.

Phase transition in polypeptides: a step towards the understanding of protein folding

DEFF Research Database (Denmark)

Yakubovich, Alexander V.; Solov'yov, Ilia; Solov'yov, Andrey V.

2006-01-01

We present a formalism which turns out to be very successful in the description of the polypeptide folding. We consider this process as a first-order phase transition and develop a theory which is free of model parameters and is based solely on fundamental physical principles. It describes...... essential thermodynamical properties of the system such as heat capacity, the phase transition temperature and others from the analysis of the polypeptide potential energy surface calculated within ab initio density functional theory and parameterized by two dihedral angles. This problem is viewed...

Nuclear trafficking of the human cytomegalovirus pp71 (ppUL82) tegument protein

International Nuclear Information System (INIS)

Shen Weiping; Westgard, Elizabeth; Huang Liqun; Ward, Michael D.; Osborn, Jodi L.; Chau, Nha H.; Collins, Lindsay; Marcum, Benjamin; Koach, Margaret A.; Bibbs, Jennifer; Semmes, O. John; Kerry, Julie A.

2008-01-01

The human cytomegalovirus tegument protein pp71 localizes to the nucleus immediately upon infection, and functions to initiate viral gene expression. Analysis of a series of random insertion mutations revealed that sequences within the mid region (MR) of pp71 are important for localization to the nucleus. Fusion of MR sequences with eGFP revealed that amino acids 94 to 300 were sufficient to target proteins to the nucleus. Random substitution mutagenesis within this domain resulted in two double substitution mutants, pp71P203T/T223M and pp71T228M/L275Q, with a predominantly cytoplasmic localization. Disruption of nuclear targeting resulted in relocalization of the fusion proteins to a distinct perinuclear region. Using tandem mass spectrometry, we determined that threonine 223 can be phosphorylated. Mutation of this residue to a phosphomimetic amino acid resulted in abrogation of nuclear targeting. These results strongly suggest that the intracellular trafficking of pp71 is regulated by phosphorylation

Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.

Science.gov (United States)

Beck, P; Nicholas, H

1975-03-01

1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as

Analysis of pp and pp-bar elastic scattering amplitudes at high energies

Energy Technology Data Exchange (ETDEWEB)

Ferreira, E.; Kodama, T.; Kohara, A.K. [Universidade Federal do Rio de Janeiro (IF/UFRJ), RJ (Brazil). Inst. de Fisica

2012-07-01

Full text: A careful analysis of high energies elastic scattering data at 7 TeV for pp, 1800 - 1950 GeV for pp-bar and 540 -541 GeV for pp-bar in terms of its amplitudes has been performed as natural extension of previous analysis for lower energies. The disentanglement of the real and imaginary parts is written consistently with constraints from dispersion relations for amplitudes and for slopes, and also satisfying the universal asymptotic behavior for large |t| values due to the three gluon Exchange process. Values for the imaginary and real slopes and for the total cross section at 7 TeV, 1800-1950 GeV and 540-541 GeV are presented, and the shape of the differential cross section at 14 TeV, with a dip/bump structure more marked and at a smaller values of |t| is predicted. It is predicted that future measurements at large |t| will be connected smoothly with the perturbative tail observed in the interval 5.5 to 14.2 GeV{sup 2} at lower energies and that a marked dip would be observed in pp-bar scattering near this tail range. It is stressed for the consistent description of elastic pp and pp-bar data and pointed out the importance of the future measurements in the Coulomb interference range and in the transition range to the perturbative tail where the perturbative and non-perturbative effects appears together. (author)

Sequence Directionality Dramatically Affects LCST Behavior of Elastin-Like Polypeptides.

Science.gov (United States)

Li, Nan K; Roberts, Stefan; Quiroz, Felipe Garcia; Chilkoti, Ashutosh; Yingling, Yaroslava G

2018-04-30

Elastin-like polypeptides (ELP) exhibit an inverse temperature transition or lower critical solution temperature (LCST) transition phase behavior in aqueous solutions. In this paper, the thermal responsive properties of the canonical ELP, poly(VPGVG), and its reverse sequence poly(VGPVG) were investigated by turbidity measurements of the cloud point behavior, circular dichroism (CD) measurements, and all-atom molecular dynamics (MD) simulations to gain a molecular understanding of mechanism that controls hysteretic phase behavior. It was shown experimentally that both poly(VPGVG) and poly(VGPVG) undergo a transition from soluble to insoluble in aqueous solution upon heating above the transition temperature ( T t ). However, poly(VPGVG) resolubilizes upon cooling below its T t , whereas the reverse sequence, poly(VGPVG), remains aggregated despite significant undercooling below the T t . The results from MD simulations indicated that a change in sequence order results in significant differences in the dynamics of the specific residues, especially valines, which lead to extensive changes in the conformations of VPGVG and VGPVG pentamers and, consequently, dissimilar propensities for secondary structure formation and overall structure of polypeptides. These changes affected the relative hydrophilicities of polypeptides above T t , where poly(VGPVG) is more hydrophilic than poly(VPGVG) with more extended conformation and larger surface area, which led to formation of strong interchain hydrogen bonds responsible for stabilization of the aggregated phase and the observed thermal hysteresis for poly(VGPVG).

Chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in rats.

Science.gov (United States)

Han, Xun; Ran, Ye; Su, Min; Liu, Yinglu; Tang, Wenjing; Dong, Zhao; Yu, Shengyuan

2017-01-01

Background Preclinical experimental studies revealed an acute alteration of pituitary adenylate cyclase-activating polypeptide in response to a single activation of the trigeminovascular system, which suggests a potential role of pituitary adenylate cyclase-activating polypeptide in the pathogenesis of migraine. However, changes in pituitary adenylate cyclase-activating polypeptide after repeated migraine-like attacks in chronic migraine are not clear. Therefore, the present study investigated chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulations in the rat. Methods A rat model of chronic migraine was established by repeated chemical dural stimulations using an inflammatory soup for a different numbers of days. The pituitary adenylate cyclase-activating polypeptide levels were quantified in plasma, the trigeminal ganglia, and the trigeminal nucleus caudalis using radioimmunoassay and Western blotting in trigeminal ganglia and trigeminal nucleus caudalis tissues. Western blot analysis and real-time polymerase chain reaction were used to measure the protein and mRNA expression of pituitary adenylate cyclase-activating polypeptide-related receptors (PAC1, VPAC1, and VPAC2) in the trigeminal ganglia and trigeminal nucleus caudalis to identify changes associated with repetitive applications of chemical dural stimulations. Results All rats exhibited significantly decreased periorbital nociceptive thresholds to repeated inflammatory soup stimulations. Radioimmunoassay and Western blot analysis demonstrated significantly decreased pituitary adenylate cyclase-activating polypeptide levels in plasma and trigeminal ganglia after repetitive chronic inflammatory soup stimulation. Protein and mRNA analyses of pituitary adenylate cyclase-activating polypeptide-related receptors demonstrated significantly increased PAC1 receptor protein and mRNA expression in the trigeminal ganglia, but not

Adhesive polypeptides of Staphylococcus aureus identified using a novel secretion library technique in Escherichia coli

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Holm Liisa

2011-05-01

Full Text Available Abstract Background Bacterial adhesive proteins, called adhesins, are frequently the decisive factor in initiation of a bacterial infection. Characterization of such molecules is crucial for the understanding of bacterial pathogenesis, design of vaccines and development of antibacterial drugs. Because adhesins are frequently difficult to express, their characterization has often been hampered. Alternative expression methods developed for the analysis of adhesins, e.g. surface display techniques, suffer from various drawbacks and reports on high-level extracellular secretion of heterologous proteins in Gram-negative bacteria are scarce. These expression techniques are currently a field of active research. The purpose of the current study was to construct a convenient, new technique for identification of unknown bacterial adhesive polypeptides directly from the growth medium of the Escherichia coli host and to identify novel proteinaceous adhesins of the model organism Staphylococcus aureus. Results Randomly fragmented chromosomal DNA of S. aureus was cloned into a unique restriction site of our expression vector, which facilitates secretion of foreign FLAG-tagged polypeptides into the growth medium of E. coli ΔfliCΔfliD, to generate a library of 1663 clones expressing FLAG-tagged polypeptides. Sequence and bioinformatics analyses showed that in our example, the library covered approximately 32% of the S. aureus proteome. Polypeptides from the growth medium of the library clones were screened for binding to a selection of S. aureus target molecules and adhesive fragments of known staphylococcal adhesins (e.g coagulase and fibronectin-binding protein A as well as polypeptides of novel function (e.g. a universal stress protein and phosphoribosylamino-imidazole carboxylase ATPase subunit were detected. The results were further validated using purified His-tagged recombinant proteins of the corresponding fragments in enzyme-linked immunoassay and

Identification of UDPG-binding polypeptides and purified (1,3)-β-glucan synthase by photoaffinity labelling with 5-azido-UDPG

International Nuclear Information System (INIS)

Frost, D.J.; Wu, A.; Read, S.M.; Wasserman, B.P.; Drake, R.R.; Haley, B.E.

1989-01-01

The photoaffinity probe 5-azido-uridine 5'-β-[ 32 P]-diphosphate glucose was used to identify the major UDPG-binding polypeptide of red beet (1,3)-β-glucan synthase. Glucan synthase was purified from plasma membranes by sequential solubilization with CHAPS followed by product entrapment. Two major polypeptides at 72 and 54 kD were labelled by probe. Labelling of both was abolished with increasing levels of cold UDPG. However, labelling of the 54 kD polypeptide was dependent upon the presence of divalent cations. These data suggest that the 54 kD polypeptide is a substrate-binding and cation-regulated component of the glucan synthase complex

Spinning, structure and properties of PP/CNTs and PP/carbon black composite fibers

Science.gov (United States)

Marcincin, A.; Hricova, M.; Ujhelyiova, A.

2014-08-01

In this paper, the effect of the compatibilisers-dispersants and other nanofillers on melt spinning of the polypropylene (PP) composites, containing carbon nanotubes (CNTs), and carbon black pigment (CBP) has been investigated. Further, the structure and selected properties of composite fibers, such as mechanical and electrical have been studied. The results revealed, that percolation threshold for PP/CBP composite fibres was situated within the concentration of 15 - 20 wt%, what is several times higher than for PP/CNTs fibers.

The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

DEFF Research Database (Denmark)

Rivas, Matilde De Las; Lira-Navarrete, Erandi; Daniel, Earnest James Paul

2017-01-01

The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- A nd/or C-terminal prior glycosylation ...

Properties of virion transactivator proteins encoded by primate cytomegaloviruses

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Barry Peter A

2009-05-01

Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

High-yield recombinant expression and purification of marginally soluble, short elastin-like polypeptides.

Science.gov (United States)

Bahniuk, Markian S; Alshememry, Abdullah K; Unsworth, Larry D

2016-12-01

The protocol described here is designed as an extension of existing techniques for creating elastin-like polypeptides. It allows for the expression and purification of elastin-like polypeptide (ELP) constructs that are poorly expressed or have very low transition temperatures. DNA concatemerization has been modified to reduce issues caused by methylation sensitivity and inefficient cloning. Linearization of the modified expression vector has been altered to greatly increase cleavage efficiency. The purification regimen is based upon using denaturing metal affinity chromatography to fully solubilize and, if necessary, pre-concentrate the target peptide before purification by inverse temperature cycling (ITC). This protocol has been used to express multiple leucine-containing elastin-like polypeptides, with final yields of 250-660 mg per liter of cells, depending on the specific construct. This was considerably greater than previously reported yields for similar ELPs. Due to the relative hydrophobicity of the tested constructs, even compared with commonly employed ELPs, conventional methods would not have been able to be purify these peptides.

ISAJET: a Monte Carlo event generator for pp and anti pp interactions

International Nuclear Information System (INIS)

Paige, F.E.; Protopopescu, S.D.

1985-01-01

ISAJET is a Monte Carlo program which simulates pp and anti pp interactions at high energy. It is based on perturbative QCD plus phenomenological models for jet and beam jet fragmentation. This article describes ISAJET Version 5.00. 21 refs., 3 figs

Induction of salivary polypeptides associated with parotid hypertrophy by gallotannins administered topically into the mouse mouth.

Science.gov (United States)

Gho, Francesca; Peña-Neira, Alvaro; López-Solís, Remigio O

2007-02-01

Isoproterenol-induced salivary polypeptides (IISP), a group of proline-rich proteins synthesized by mouse parotids, have been considered as markers for isoproterenol-induced parotid hypertrophy. Rodents fed diets containing high-tannin cereals (sorghum), also develop parotid hypertrophy. To test whether tannins are directly involved in provoking sialotrophic growth, we studied the effect of intraperitoneal and topical oral administrations of tannic acid (TA) on the induction of IISP polypeptides in endogamic mice (A/Snell). TA was characterized by HPLC chromatography and spectral analysis and shown to be composed solely of gallotannins, a complex family of glucose and gallic acid esters. IISP polypeptides were monitored in saliva by SDS-polyacrylamide gel electrophoresis during 36 h after ending TA stimulation. Single daily intraperitoneal administrations of TA for 3 consecutive days (0.033 mg/g bw/day), at variance of parallel administrations of isoproterenol (0.042 mg/g bw/day) failed to induce IISP polypeptides. However, repeated topical applications of TA into the mouse mouths (1.21 mg/g bw divided into three equal doses given at 4-h intervals within a single day) resulted in unequivocal induction of IISP polypeptides. That response was clearly intensified by increasing the stimulation frequency to eight equivalent doses given at 1.5-h intervals within a single day (corresponding to 3.23 mg/g bw) and even further by repeating this protocol for 3 days. Under these productive schemes of stimulations by TA, electrophoretic fractionation of parotid homogenates showed new polypeptide bands migrating in parallel to salivary IISP. These results suggest that topically administered gallotannins are effective inducers of trophic growth in mouse parotids.

Properties of PP/MWCNT-COOH /PP composites made by melt mixing versus solution cast /melt mixing methods

International Nuclear Information System (INIS)

Reinholds, I; Roja, Z; Zicans, J; Meri, R Merijs; Bitenieks, J

2015-01-01

An approach on improvement of the properties of polypropylene / carbon nanotube (PP/CNT) composites is reported. PP blend compositions with carboxylic acid functionalized multi-walled carbon nanotubes (MWCNT-COOH) at filler content 1.0 wt.% were researched. One part of the composites was manufactured by direct thermoplastic mixing PP with the filler, but the other one was made from solution casted masterbatch with the following thermoplastic mixing. An increase of mechanical properties (Young's modulus, storage modulus and tensile strength), compared to an increase of glass transition temperature indicated a reinforcement effect of CNTs on PP matrix, determined from the tensile tests and differential mechanical analysis (DMA), while the elongation was reduced, compared to PP matrix. By differential scanning calorimetry (DSC) analysis, the effect of nanofiller on the reorganization of PP crystallites was observed. A noticeable enhanced effect on increase of the crystallization temperature was indicated for masterbatch manufactured composite. An increase of thermal stability was also observed, compared to pristine PP and the composite made by direct thermoplastic mixing PP with the filler

Tuning the conformation of synthetic co-polypeptides of serine and glutamic acid through control over polymer composition

NARCIS (Netherlands)

Canning, A.; Pasquazi, A.; Fijten, M.; Rajput, S.; Buttery, L.; Aylott, J.W.; Zelzer, M.

2016-01-01

Ring opening polymerization (ROP) of N-carboxy anhydride (NCA) amino acids presents a rapid way to synthesize high molecular weight polypeptides with different amino acid compositions. The compositional and functional versatility of polypeptides make these materials an attractive choice for

Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism

Directory of Open Access Journals (Sweden)

Guangxin Yuan

2018-01-01

Full Text Available Our previous research revealed that Cordyceps militaris can improve the learning and memory, and although the main active ingredient should be its polypeptide complexes, the underlying mechanism of its activity remains poorly understood. In this study, we explored the mechanisms by which Cordyceps militaris improves learning and memory in a mouse model. Mice were given scopolamine hydrobromide intraperitoneally to establish a mouse model of learning and memory impairment. The effects of Cordyceps polypeptide in this model were tested using the Morris water maze test; serum superoxide dismutase activity; serum malondialdehyde levels; activities of acetyl cholinesterase, Na+-k+-ATPase, and nitric oxide synthase; and gamma aminobutyric acid and glutamate contents in brain tissue. Moreover, differentially expressed genes and the related cellular signaling pathways were screened using an mRNA expression profile chip. The results showed that the genes Pik3r5, Il-1β, and Slc18a2 were involved in the effects of Cordyceps polypeptide on the nervous system of these mice. Our findings suggest that Cordyceps polypeptide may improve learning and memory in the scopolamine-induced mouse model of learning and memory impairment by scavenging oxygen free radicals, preventing oxidative damage, and protecting the nervous system.

Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers.

Science.gov (United States)

Cho, S; Dong, S; Parent, K N; Chen, M

2016-01-01

Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers. We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs. Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells (DCs) and enhanced vaccine-induced CTL responses. A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines. It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.

GridPP returns to CERN

CERN Document Server

Neasan O'Neill

2011-01-01

In early September, GridPP, the collaboration that manages the UK’s contribution to the worldwide LHC Computing Grid (wLCG), celebrated a decade of work by holding its twenty-seventh collaboration meeting at CERN.   Officially launched in September 2001, GridPP was one of the original partners in wLCG, funding much of the early work at CERN. Over the last decade GridPP has gone from a mere proposal to almost 30,000 CPUs working for researchers scattered across the globe. Twice a year, GridPP meets to discuss the progress and future plans of the community and this year, for the first time since 2004, decamped to CERN for this biannual meeting on the theme “GridPP in the International Context”. The main meeting was held over 2 days in the IT auditorium and was the perfect opportunity to have contributions from experts based at CERN, alongside those from within GridPP. Opening with a welcome from Frederic Hemmer, Head of the IT Department at CERN, the meeting began with...

Polarization measurements in the pp → pnπ+ and pp → ppπ0 reactions at 517 and 580 MeV

International Nuclear Information System (INIS)

Bach, P.; Cantale, G.; Degli-Agosti, S.; Demierre, P.; Favier, B.; Heer, E.; Hess, R.; Lechanoine-Leluc, C.; Leo, W.; Onel, Y.; and others.

1989-01-01

The transverse polarization of the outgoing proton in the pp → pnπ + and pp → ppπ 0 reactions was investigated for the first time. The measurements were performed at SIN (now PSI) at 517 and 580 MeV on the pM1 polarized proton beam line with an average beam polarization higher than 82%, using a liquid hydrogen target. A carbon polarimeter spin-analyzed the scattered proton, 3 MWPC's tracked the recoil charged particle and a 3.84 m 2 neutron detector identified the neutral particle and measured TOF's

Kinetics of Internal-Loop Formation in Polypeptide Chains: A Simulation Study

Science.gov (United States)

Doucet, Dana; Roitberg, Adrian; Hagen, Stephen J.

2007-01-01

The speed of simple diffusional motions, such as the formation of loops in the polypeptide chain, places one physical limit on the speed of protein folding. Many experimental studies have explored the kinetics of formation of end-to-end loops in polypeptide chains; however, protein folding more often requires the formation of contacts between interior points on the chain. One expects that, for loops of fixed contour length, interior loops will form more slowly than end-to-end loops, owing to the additional excluded volume associated with the “tails”. We estimate the magnitude of this effect by generating ensembles of randomly coiled, freely jointed chains, and then using the theory of Szabo, Schulten, and Schulten to calculate the corresponding contact formation rates for these ensembles. Adding just a few residues, to convert an end-to-end loop to an internal loop, sharply decreases the contact rate. Surprisingly, the relative change in rate increases for a longer loop; sufficiently long tails, however, actually reverse the effect and accelerate loop formation slightly. Our results show that excluded volume effects in real, full-length polypeptides may cause the rates of loop formation during folding to depart significantly from the values derived from recent loop-formation experiments on short peptides. PMID:17208979

Role of Side-Chain Molecular Features in Tuning Lower Critical Solution Temperatures (LCSTs) of Oligoethylene Glycol Modified Polypeptides.

Science.gov (United States)

Gharakhanian, Eric G; Deming, Timothy J

2016-07-07

A series of thermoresponsive polypeptides has been synthesized using a methodology that allowed facile adjustment of side-chain functional groups. The lower critical solution temperature (LCST) properties of these polymers in water were then evaluated relative to systematic molecular modifications in their side-chains. It was found that in addition to the number of ethylene glycol repeats in the side-chains, terminal and linker groups also have substantial and predictable effects on cloud point temperatures (Tcp). In particular, we found that the structure of these polypeptides allowed for inclusion of polar hydroxyl groups, which significantly increased their hydrophilicity and decreased the need to use long oligoethylene glycol repeats to obtain LCSTs. The thioether linkages in these polypeptides were found to provide an additional structural feature for reversible switching of both polypeptide conformation and thermoresponsive properties.

Cytomegalovirus (CMV) Epitope-Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects.

Science.gov (United States)

Abana, Chike O; Pilkinton, Mark A; Gaudieri, Silvana; Chopra, Abha; McDonnell, Wyatt J; Wanjalla, Celestine; Barnett, Louise; Gangula, Rama; Hager, Cindy; Jung, Dae K; Engelhardt, Brian G; Jagasia, Madan H; Klenerman, Paul; Phillips, Elizabeth J; Koelle, David M; Kalams, Spyros A; Mallal, Simon A

2017-11-01

Select CMV epitopes drive life-long CD8 + T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4 + T cells specific for human CMV (HCMV) are elevated in HIV + HCMV + subjects. To determine whether HCMV epitope-specific CD4 + T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 + T cells in coinfected HLA-DR7 + long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 + T cells were inflated among these HIV + subjects compared with those from an HIV - HCMV + HLA-DR7 + cohort or with HLA-DR7-restricted CD4 + T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4 + T cells consisted of effector memory or effector memory-RA + subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell-transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX 3 CR1, CD38, or HLA-DR but less often coexpressed CD38 + and HLA-DR + The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4 + T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

DEFF Research Database (Denmark)

Durkin, M E; Wewer, U M; Chung, A E

1995-01-01

of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF......Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from lambda genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization...

CDNA encoding a polypeptide including a hevein sequence

Science.gov (United States)

Raikhel, Natasha V.; Broekaert, Willem F.; Chua, Nam-Hai; Kush, Anil

1995-03-21

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74-79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli.

Strategies to Fabricate Polypeptide-Based Structures via Ring-Opening Polymerization of N-Carboxyanhydrides

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Carmen M. González-Henríquez

2017-10-01

Full Text Available In this review, we provide a general and clear overview about the different alternatives reported to fabricate a myriad of polypeptide architectures based on the ring-opening polymerization of N-carbonyanhydrides (ROP NCAs. First of all, the strategies for the preparation of NCA monomers directly from natural occurring or from modified amino acids are analyzed. The synthetic alternatives to prepare non-functionalized and functionalized NCAs are presented. Protection/deprotection protocols, as well as other functionalization chemistries are discussed in this section. Later on, the mechanisms involved in the ROP NCA polymerization, as well as the strategies developed to reduce the eventually occurring side reactions are presented. Finally, a general overview of the synthetic strategies described in the literature to fabricate different polypeptide architectures is provided. This part of the review is organized depending on the complexity of the macromolecular topology prepared. Therefore, linear homopolypeptides, random and block copolypeptides are described first. The next sections include cyclic and branched polymers such as star polypeptides, polymer brushes and highly branched structures including arborescent or dendrigraft structures.

Differential expression of isoproterenol-induced salivary polypeptides in two mouse strains that are congenic for the H-2 histocompatibility gene complex.

Science.gov (United States)

López Solís, Remigio O; Weis, Ulrike Kemmerling; Ceballos, Alicia Ramos; Salas, Gustavo Hoecker

2003-12-01

Two inbred mouse strains, A/Snell and A.Swiss, which were produced as congenic with regard to the H-2 histocompatibility gene complex, are homozygous for two different groups of isoproterenol-induced salivary polypeptides (IISP). These polypeptides, which have been considered as markers of the hypertrophic growth of the parotid acinar cells, are members of the complex family of salivary proline-rich proteins (PRP) on the basis of both their massive accumulation in the parotid acinar cells in response to chronic isoproterenol, secretory character, high solubility in trichloroacetic acid and metachromatic staining by Coomassie blue. IISP expressed in both mouse strains were identified by unidimensional SDS-polyacrylamide electrophoresis and Coomassie blue staining both in parotid gland homogenates and in whole salivas obtained from mice repeatedly stimulated at 24-h intervals with isoproterenol. Parotid glands from 40 mice (20 A/Snell and 20 A.Swiss) and salivas from 270 mice (200 A/Snell and 70 A.Swiss) were analyzed. One of the congenic strains (A/Snell) expressed five IISP (Mr 65, 61, 51.5, 38, and 37 kDa) and the other strain (A.Swiss) expressed six IISP (Mr 59, 57, 54.5, 46, 36, and 34 kDa). No inter-individual intra-strain variations were observed, thus defining strain-associated patterns of IISP (PRP). Copyright 2003 Wiley-Liss, Inc.

Forward diffraction amplitude of pp and pp elastic scattering at accelerator energies

International Nuclear Information System (INIS)

Kawasaki, M.; Maehara, T.; Yonezawa, M.

2004-01-01

A simple relation between the total cross section and the forward exponential slope of the elastic differential cross section of pp and pp scattering is indicated. An interpretation of this relation is presented as the formation of a black-disk structure for the elastic diffraction interaction of hadron-hadron scattering at the nonasymptotic energy region

Glucose-dependent Insulinotropic Polypeptide

DEFF Research Database (Denmark)

Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

2014-01-01

CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses......: During fasting glycemia (plasma glucose ∼8 mmol/L), GIP elicited significant increments in both insulin and glucagon levels, resulting in neutral effects on plasma glucose. During insulin-induced hypoglycemia (plasma glucose ∼3 mmol/L), GIP elicited a minor early-phase insulin response and increased...... glucagon levels during the initial 30 minutes, resulting in less glucose needed to be infused to maintain the clamp (29 ± 8 vs 49 ± 12 mg × kg(-1), P glucose ∼12 mmol/L), GIP augmented insulin secretion throughout the clamp, with slightly less glucagon...

New boundaries for the “ppK−” production in p+p collisions

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Epple Eliane

2014-01-01

Full Text Available The HADES collaboration has searched for the anti-kaonic nuclear cluster “ppK−” in p+p collisions by its decay into pΛ. In the course of this analysis several cross checks had to be performed. This report discusses two examples thereof. In one test it was checked whether the presence of background events could introduce a bias on the applied partial wave analysis. The second item discussed here is the extraction of the total pK+Λ production cross section necessary to derive the absolute upper limit on the “ppK−” production cross section.

Investigation of Gelatin Polypeptides of Jellyfish (Rhopilema esculentum for Their Antioxidant Activity in vitro

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Yong-Liang Zhuang

2010-01-01

Full Text Available Jellyfish gelatin was hydrolyzed by different proteases to obtain antioxidative polypeptides. The gelatin hydrolysate obtained by progressive hydrolysis using trypsin and Properase E exhibited the highest hydrolysis degree and antioxidant activity. Three series of gelatin polypeptides (SCP1, SCP2 and SCP3 were obtained by ultrafiltrating the gelatin hydrolysate through molecular mass cut-off membranes of 10, 6 and 2 kDa, respectively. Amino acid composition analysis showed that SCP3 had the highest total hydrophobic amino acid content. The in vitro antioxidant tests demonstrated that SCP2 had the strongest hydroxyl radical and hydrogen peroxide scavenging activities and metal chelating ability, while SCP3 showed the highest reducing power, antioxidant activity in linoleic acid emulsion system and superoxide anion radical scavenging activity. The results support the feasibility of jellyfish gelatin as a natural antioxidant polypeptide provider, and enzymatic hydrolysis and ultrafiltration could be potent future processing technologies to utilize the abundant jellyfish resource.

Effects on DPPH inhibition of egg-white protein polypeptides treated by pulsed electric field technology.

Science.gov (United States)

Wang, Ke; Wang, Jia; Liu, Bolong; Lin, Songyi; Zhao, Ping; Liu, Jingbo; Jones, Gregory; Huang, Hsiang-Chi

2013-05-01

Egg-white protein polypeptides are potentially used as a functional ingredient in food products. In this study, the effects on DPPH inhibition of egg-white protein polypeptides ranging from 10 to 30 kDa treated by pulsed electric field (PEF) technology were investigated. 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) inhibition (%) was used to evaluate the antioxidant activity of polypeptides. In order to develop and optimize a pulsed electric field (PEF) mathematical model for improving the antioxidant activity, we have investigated three variables, including concentration (6, 8 and 10 mg mL(-1)), electric field intensity (10, 20 and 30 kV cm(-1)) and pulse frequency (2000, 2350 and 2700 Hz) and subsequently optimized them by response surface methodology (RSM). The concentration (8 mg mL(-1)), electric field intensity (10 kV cm(-1)) and pulse frequency (2000 Hz) were found to be the optimal conditions under which the DPPH inhibition increased 28.44%, compared to the sample without PEF treatment. Both near-infrared spectroscopy (NIR) and mid-infrared spectroscopy (MIR) were used to analyze the change of functional groups. The results showed that PEF technology could improve the antioxidant activity of antioxidant polypeptides from egg-white protein under the optimized conditions. © 2012 Society of Chemical Industry.

Polymer-Block-Polypeptides and Polymer-Conjugated Hybrid Materials as Stimuli-Responsive Nanocarriers for Biomedical Applications.

Science.gov (United States)

John, Johnson V; Johnson, Renjith P; Heo, Min Seon; Moon, Byeong Kyu; Byeon, Seong Jin; Kim, Il

2015-01-01

Stimuli-responsive nanocarriers are a class of soft materials that includes natural polymers, synthetic polymers, and polypeptides. Recently, modern synthesis tools such as atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, nitroxide-mediated radical polymerization, ring-opening polymerization of α-amino acid N-carboxyanhydrides, and various "click" chemistry strategies were simultaneously employed for the design and synthesis of nanosized drug delivery vehicles. Importantly, the research focused on the improvement of the nanocarrier targetability and the site-specific, triggered release of therapeutics with high drug loading efficiency and minimal drug leakage during the delivery to specific targets. In this context, nanocarriers responsive to common stimuli such as pH, temperature, redox potential, light, etc. have been widely used for the controlled delivery of therapeutics to pathological sites. Currently, different synthesis and self-assembly strategies improved the drug loading efficacy and targeted delivery of therapeutic agents to the desired site. In particular, polypeptide-containing hybrid materials have been developed for the controlled delivery of therapeutic agents. Therefore, stimuli-sensitive synthetic polypeptide-based materials have been extensively investigated in recent years. This review focuses on recent advances in the development of polymer-block-polypeptides and polymer-conjugated hybrid materials that have been designed and evaluated for various stimuli-responsive drug and gene delivery applications.

Smart systems related to polypeptide sequences

Directory of Open Access Journals (Sweden)

Lourdes Franco

2016-03-01

Full Text Available Increasing interest for the application of polypeptide-based smart systems in the biomedical field has developed due to the advantages given by the peptidic sequence. This is due to characteristics of these systems, which include: biocompatibility, potential control of degradation, capability to provide a rich repertoire of biologically specific interactions, feasibility to self-assemble, possibility to combine different functionalities, and capability to give an environmentally responsive behavior. Recently, applications concerning the development of these systems are receiving greater attention since a targeted and programmable release of drugs (e.g. anti-cancer agents can be achieved. Block copolymers are discussed due to their capability to render differently assembled architectures. Hybrid systems based on silica nanoparticles are also discussed. In both cases, the selected systems must be able to undergo fast changes in properties like solubility, shape, and dissociation or swelling capabilities. This review is structured in different chapters which explain the most recent advances on smart systems depending on the stimuli to which they are sensitive. Amphiphilic block copolymers based on polyanionic or polycationic peptides are, for example, typically employed for obtaining pH-responsive systems. Elastin-like polypeptides are usually used as thermoresponsive polymers, but performance can be increased by using techniques which utilize layer-by-layer electrostatic self-assembly. This approach offers a great potential to create multilayered systems, including nanocapsules, with different functionality. Recent strategies developed to get redox-, magnetic-, ultrasound-, enzyme-, light- and electric-responsive systems are extensively discussed. Finally, some indications concerning the possibilities of multi-responsive systems are discussed.

anti pp and pp elastic scattering from 10 GeV to 1000 GeV centre-of-mass energy

Energy Technology Data Exchange (ETDEWEB)

Islam, M.M. (Connecticut Univ., Storrs (USA). Dept. of Physics); Fearnley, T. (University Coll., London (UK). Dept. of Physics and Astronomy); Guillaud, J.P. (Grenoble-1 Univ., 74 - Annecy (France). Lab. de Physique des Particules)

1984-06-21

Antiproton-proton and proton-proton elastic scattering are studied simultaneously over the energy range ..sqrt..anti s approx.= (10/1000) GeV in a nucleon valence core model proposed earlier. The scattering is described as primarily due to two processes: diffraction and hard scattering. The latter originates from the scattering of a nucleon core off another core. Destructive interference between the two processes produces dips in anti pp and pp differential cross-sections. As energy increases beyond the ISR range (..sqrt..anti s = (23/62) GeV), the dips get filled up, and eventually transform into shoulders or breaks at collider energies. Differences between anti pp and pp differential cross-sections persist even at collider energies. Comparison with ISR data shows that the model provides a quantitative description of pp elastic scattering in this energy range. Predictions of anti pp and pp differential cross-sections at future collider energies ..sqrt..s = 800 and 2000 GeV are given. In order to distinguish between competing models, need for measuring the anti pp differential cross-section at the ISR and SPS collider in the vertical stroketvertical stroke-range (0.5/2.0) (GeV)/sup 2/ is stressed.

Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation

Science.gov (United States)

Fluitt, Aaron Michael

Empowered by their exquisite three-dimensional structures, or "folds," proteins carry out biological tasks with high specificity, efficiency, and fidelity. The fold that optimizes biological function represents a stable configuration of the constituent polypeptide molecule(s) under physiological conditions. Proteins and polypeptides are not static, however: battered by thermal motion, they explore a distribution of folds that is determined by the sequence of amino acids, the presence and identity of other molecules, and the thermodynamic conditions. In this dissertation, we apply molecular simulation techniques to the study of two polypeptides that have unusually diffuse distributions of folds under physiological conditions: polyglutamine (polyQ) and islet amyloid polypeptide (IAPP). Neither polyQ nor IAPP adopts a predominant fold in dilute aqueous solution, but at sufficient concentrations, both are prone to self-assemble into stable, periodic, and highly regular aggregate structures known as amyloid. The appearance of amyloid deposits of polyQ in the brain, and of IAPP in the pancreas, are associated with Huntington's disease and type 2 diabetes, respectively. A molecular view of the mechanism(s) by which polyQ and IAPP fold and self-assemble will enhance our understanding of disease pathogenesis, and it has the potential to accelerate the development of therapeutics that target early-stage aggregates. Using molecular simulations with spatial and temporal resolution on the atomic scale, we present analyses of the structural distributions of polyQ and IAPP under various conditions, both in and out of equilibrium. In particular, we examine amyloid fibers of polyQ, the IAPP dimer in solution, and single IAPP fragments at a lipid bilayer. We also benchmark the molecular models, or "force fields," available for such studies, and we introduce a novel simulation algorithm.

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector

International Nuclear Information System (INIS)

Wang, Z.; Zhou, W.; Srivastava, T.; La Rosa, C.; Mandarino, A.; Forman, S.J.; Zaia, J.A.; Britt, W.J.; Diamond, D.J.

2008-01-01

A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4 + and CD8 + T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4 + and CD8 + T cell subsets

Light Scattering Characterization of Elastin-Like Polypeptide Trimer Micelles

Science.gov (United States)

Tsuper, Ilona; Terrano, Daniel; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

The elastin-like polypeptides (ELP) nanoparticles are composed of three-armed star polypeptides connected by a negatively charged foldon. Each of the three arms extending from the foldon domain includes 20 repeats of the (GVGVP) amino acid sequence. The ELP polymer chains are soluble at room temperature and become insoluble at the transition temperature (close to 50 ° C), forming micelles. The size and shape of the micelle are dependent on the temperature and the pH of the solution, and on the concentration of the phosphate buffered saline (PBS). The depolarized dynamic light scattering (DDLS) was employed to study the structure and dynamics of micelles at 62 ° C. The solution was maintained at an approximate pH level of 7.3 - 7.5, while varying PBS concentration. At low salt concentrations (60 mM) displayed an apparent elongation of the micelles evident by a significant VH signal, along with a surge in the apparent Rh. A model of micelle growth (and potential elongation) with increase in salt concentration is considered.

Electrical conduction in (Na0⋅ 125Bi0⋅ 125 Ba0⋅ 65Ca0⋅)(Nd0 ...

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science; Volume 29; Issue 1. Electrical conduction in (Na0.125Bi0.125Ba0.65Ca0.1)(Nd0.065Ti0.87Nb0.065)O3 ceramic. Syed Mahboob G Prasad G S Kumar. Ceramics and Glasses Volume 29 Issue 1 February 2006 pp 35-41 ...

Photooxidation of HMS-PP under environment and artificial weathering conditions;Fotooxidacao do HMS-PP sob condicoes de intemperismo ambiental e artificial

Energy Technology Data Exchange (ETDEWEB)

Oliani, Washington L.; Parra, Duclerc F.; Lima, Luis Filipe C.P.; Lugao, Ademar B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2009-07-01

The linearity of the chains confers to iPP, low melt strength, which means a low strength to stretching during elongation. The increase of melt strength and the extensibility is due to the increase of the entanglement of the macromolecules chains. The HMS-PP (high melt strength polypropylene) was synthesized (based on the grains iPP) through gamma irradiation in the iPP under acetylene atmosphere followed by heat treatment for recombination and subsequent annihilation of the other free radicals. Samples of HMS-PP and iPP were subjected to environmental aging in IPEN - Sao Paulo and in the QUV chamber. The results show fractured surfaces of iPP and HMS-PP that are intensified with exposure time. The iPP degradation process has the predominance of chain scissions, with carbonyl and hydroperoxides formation which act as initiators of photo degradation mechanisms. (author)

In vitro and in vivo phosphorylation of polypeptides in plasma membrane and tonoplast-enriched fractions from barley roots

International Nuclear Information System (INIS)

Garbarino, J.E.; Hurkman, W.J.; Tanaka, C.K.; DuPont, F.M.

1991-01-01

Phosphorylation of polypeptides in membrane fractions from barley (Hordeum vulgare L. cv CM 72) roots was compared in in vitro and in vivo assays to assess the potential role of protein kinases in modification of membrane transport. Membrane fractions enriched in endoplasmic reticulum, tonoplast, and plasma membrane were isolated using sucrose gradients and the membrane polypeptides separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis. When the membrane fractions were incubated with γ[p 32 P]ATP, phosphorylation occurred almost exclusively in the plasma membrane fraction. Phosphorylation of a band at 38 kilodaltons increased as the concentration of Mg 2+ was decreased from millimolar to micromolar levels. Phosphorylation of bands at 125, 86, 58, 46 and 28 kilodaltons required millimolar Mg 2+ concentrations and was greatly enhanced by Ca 2+ . When roots of intact plants were labeled with [ 32 P]orthophosphate, polypeptides at approximately 135, 166, 90, 46 to 53, 32, 28, and 19 kilodaltons were labeled in the plasma membrane fraction and polypeptides at approximately 73, 66, and 48 kilodaltons were labeled in the tonoplast fraction. Treatment of the roots of intact plants with 150 millimolar NaCl resulted in increased phosphorylation of some polypeptides while treatment with 100 mM NaCl had no effect

Molecular mechanism of serine/threonine protein phosphatase 1 (PP1cα-PP1r7) in spermatogenesis of Toxocara canis.

Science.gov (United States)

Ma, Guang Xu; Zhou, Rong Qiong; Song, Zhen Hui; Zhu, Hong Hong; Zhou, Zuo Yong; Zeng, Yuan Qin

2015-09-01

Toxocariasis is one of the most important, but neglected, zoonoses, which is mainly caused by Toxocara canis. To better understand the role of serine/threonine protein phosphatase 1 (PP1) in reproductive processes of male adult T. canis, differential expression analysis was used to reveal the profiles of PP1 catalytic subunit α (PP1cα) gene Tc-stp-1 and PP1 regulatory subunit 7 (PP1r7) gene TcM-1309. Indirect fluorescence immunocytochemistry was carried out to determine the subcellular distribution of PP1cα. Double-stranded RNA interference (RNAi) assays were employed to illustrate the function and mechanism of PP1cα in male adult reproduction. Real-time quantitative PCR (qPCR) showed transcriptional consistency of Tc-stp-1 and TcM-1309 in sperm-producing germline tissues and localization research showed cytoplasmic distribution of PP1cα in sf9 cells, which indicated relevant involvements of PP1cα and PP1r7 in spermatogenesis. Moreover, spatiotemporal transcriptional differences of Tc-stp-1 were determined by gene knockdown analysis, which revealed abnormal morphologies and blocked meiotic divisions of spermatocytes by phenotypic aberration scanning, thereby highlighting the crucial involvement of PP1cα in spermatogenesis. These results revealed a PP1cα-PP1r7 mechanism by which PP1 regulates kinetochore-microtubule interactions in spermatogenesis and provided important clues to identify novel drug or vaccine targets for toxocariasis control. Copyright © 2015 Elsevier B.V. All rights reserved.

The Cloning and Functional Characterization of Peach CONSTANS and FLOWERING LOCUS T Homologous Genes PpCO and PpFT.

Directory of Open Access Journals (Sweden)

Xiang Zhang

Full Text Available Flowering is an essential stage of plant growth and development. The successful transition to flowering not only ensures the completion of plant life cycles, it also serves as the basis for the production of economically important seeds and fruits. CONSTANS (CO and FLOWERING LOCUS T (FT are two genes playing critical roles in flowering time control in Arabidopsis. Through homology-based cloning and rapid-amplifications of cDNA ends (RACE, we obtained full-lengths cDNA sequences of Prunus persica CO (PpCO and Prunus persica FT (PpFT from peach (Prunus persica (L. Batsch and investigated their functions in flowering time regulation. PpCO and PpFT showed high homologies to Arabidopsis CO and FT at DNA, mRNA and protein levels. We showed that PpCO and PpFT were nucleus-localized and both showed transcriptional activation activities in yeast cells, consistent with their potential roles as transcription activators. Moreover, we established that the over-expression of PpCO could restore the late flowering phenotype of the Arabidopsis co-2 mutant, and the late flowering defect of the Arabidopsis ft-1 mutant can be rescued by the over-expression of PpFT, suggesting functional conservations of CO and FT genes in peach and Arabidopsis. Our results suggest that PpCO and PpFT are homologous genes of CO and FT in peach and they may function in regulating plant flowering time.

In vivo guided vascular regeneration with a non-porous elastin-like polypeptide hydrogel tubular scaffold.

Science.gov (United States)

Mahara, Atsushi; Kiick, Kristi L; Yamaoka, Tetsuji

2017-06-01

Herein, we demonstrate a new approach for small-caliber vascular reconstruction using a non-porous elastin-like polypeptide hydrogel tubular scaffold, based on the concept of guided vascular regeneration (GVR). The scaffolds are composed of elastin-like polypeptide, (Val-Pro-Gly-Ile-Gly) n , for compliance matching and antithrombogenicity and an Arg-Gly-Asp (RGD) motif for connective tissue regeneration. When the polypeptide was mixed with an aqueous solution of β-[Tris(hydroxymethyl)phosphino]propionic acid at 37°C, the polypeptide hydrogel was rapidly formed. The elastic modulus of the hydrogel was 4.4 kPa. The hydrogel tubular scaffold was formed in a mold and reinforced with poly(lactic acid) nanofibers. When tubular scaffolds with an inner diameter of 1 mm and length of 5 mm were implanted into rat abdominal aortae, connective tissue grew along the scaffold luminal surface from the flanking native tissues, resulting in new blood vessel tissue with a thickness of 200 μm in 1 month. In contrast, rats implanted with control scaffolds without the RGD motif died. These results indicate that the non-porous hydrogel tubular scaffold containing the RGD motif effectively induced rapid tissue regeneration and that GVR is a promising strategy for the regeneration of small-diameter blood vessels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1746-1755, 2017. © 2017 Wiley Periodicals, Inc.

Membrane fractions active in poliovirus RNA replication contain VPg precursor polypeptides

International Nuclear Information System (INIS)

Takegami, T.; Semler, B.L.; Anderson, C.W.; Wimmer, E.

1983-01-01

The poliovirus specific polypeptide P3-9 is of special interest for studies of viral RNA replication because it contains a hydrophobic region and, separated by only seven amino acids from that region, the amino acid sequence of the genome-linked protein VPg. Membraneous complexes of poliovirus-infected HeLa cells that contain poliovirus RNA replicating proteins have been analyzed for the presence of P3-9 by immunoprecipitation. Incubation of a membrane fraction rich in P3-9 with proteinase leaves the C-terminal 69 amino acids of P3-9 intact, an observation suggesting that this portion is protected by its association with the cellular membrane. These studies have also revealed two hitherto undescribed viral polypeptides consisting of amino acid sequences of the P2 andf P3 regions of the polyprotein. Sequence analysis by stepwise Edman degradation show that these proteins are 3b/9 (M/sub r/77,000) and X/9 (M/sub r/50,000). 3b/9 and X/9 are membrane bound and are turned over rapidly and may be direct precursors to proteins P2-X and P3-9 of the RNA replication complex. P2-X, a polypeptide void of hydrophobic amino acid sequences but also found associated with membranes, is rapidly degraded when the membraneous complex is treated with trypsin. It is speculated that P2-X is associated with membranes by its affinity to the N-terminus of P3-9

Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

Science.gov (United States)

Perlin, Pesach; Gharakhanian, Eric G; Deming, Timothy J

2018-06-12

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions. Incorporation of GHA segments into block copolymers with poly(l-methionine), M, segments provided a means to orthogonally modify thioether side-chains different ways in separate copolypeptide domains. This approach allows preparation of functional polypeptides containing discrete domains of oxidized and alkylated thioether containing residues, where chain conformation and functionality of each domain can be independently modified.

ONKALO POSE experiment. Determination of in situ thermal properties of rocks in drillholes ONK-PP340, ONK-PP346, ONK-PP398, ONK-PP399, ONK-PP405, ONK-PP411

International Nuclear Information System (INIS)

Korpisalo, A.; Suppala, I.; Kukkonen, I.; Koskinen, T.

2014-12-01

The thermal drillhole device TERO76 (for diameter 76 mm drillholes) used in this study for determining thermal properties of rocks in situ was developed at the Geological Survey of Finland for Posiva in the early 2000's. The measurement method is based on monitoring the temperature variation of a cylindrical heating source in a drillhole. The measured data can be interpreted with full numerical 3D codes as well as with an analytical infinite line source method, a 'rapid interpretation tool', which makes it possible to calculate the first estimates of thermal properties already in the field. Both methods were applied in this study. Because of the unique measurement geometry, only the thermal conductivities can accurately be estimated using the late times of heating periods (accuracy ± 2%). The cylindrical source method cannot directly give the thermal diffusivity or volumetric heat capacity at a sufficient accuracy. Thermal diffusivities are estimated by using the average specific heat capacities and densities of the rock type at the measurement point, or the laboratory results on the general diffusivity-conductivity relationship for different Olkiluoto rock types. The latter technique was applied in this study. Thermal properties were determined in four shallow drillholes (ONK-PP398, ONK-PP399, ONK-PP405, ONK-PP411) located in the ONKALO investigation niche 3 (ONK-TKU-3620) at the access tunnel chainage of 3620 m. The measurement positions (17) were strictly selected on the grounds that approximately an equal number of in situ results would be available in both veined gneiss (VGN) and pegmatitic granite (PGR). The results from the drillholes ONK-PP340 and ONK-PP346 measured in a previous project are also presented in this report. In veined gneiss, the average conductivity determined with numerical model of the present measurements is 3.49 (2.83) Wm -1 K -1 and diffusivity 1.89 x 10 -6 (1.3 10 -6 ) m 2 s -1 . The laboratory values of Olkiluoto rocks

Salt- and pH-Triggered Helix-Coil Transition of Ionic Polypeptides under Physiology Conditions.

Science.gov (United States)

Yuan, Jingsong; Zhang, Yi; Sun, Yue; Cai, Zhicheng; Yang, Lijiang; Lu, Hua

2018-06-11

Controlling the helix-coil transition of polypeptides under physiological conditions is an attractive way toward smart functional materials. Here, we report the synthesis of a series of tertiary amine-functionalized ethylene glycol (EG x )-linked polypeptide electrolytes with their secondary structures tunable under physiological conditions. The resultant polymers, denoted as P(EG x DMA-Glu) ( x = 1, 2, and 3), show excellent aqueous solubility (>20 mg/mL) regardless of their charge states. Unlike poly-l-lysine that can form a helix only at pH above 10, P(EG x DMA-Glu) undergo a pH-dependent helix-coil switch with their transition points within the physiological range (pH ∼5.3-6.5). Meanwhile, P(EG x DMA-Glu) exhibit an unusual salt-induced helical conformation presumably owing to the unique properties of EG x linkers. Together, the current work highlights the importance of fine-tuning the linker chemistry in achieving conformation-switchable polypeptides and represents a facile approach toward stimuli-responsive biopolymers for advanced biological applications.

Comparison of short-range rapidity correlations in anti pp and pp interactions at √S = 53 GeV

International Nuclear Information System (INIS)

Breakstone, A.; Crawley, H.B.; Firestone, A.; Gorbics, M.; Lamsa, J.W.; Meyer, W.T.

1982-01-01

Measurements are presented of two-particle rapidity correlations in anti pp and pp at √S = 53 GeV. The data were recorded at the CERN-ISR using the Split Field Magnet spectrometer with a minimum bias trigger. Short range correlations in normal inelastic events with measured charged multiplicities nsub(ch) >= 4 are observed for pairs of charged particles in all charge combinations. Within the experimental errors no differences are observed between the analogous correlations in pp and anti pp interactions. (orig.)

Analysis of pp and pp-bar in forward scattering using derivative dispersion relations

International Nuclear Information System (INIS)

Kohara, A. K.; Ferreira, E.; Kodama, T.

2010-01-01

We describe the amplitudes for pp and pp-bar scattering at small momentum transfers, where Coulomb and nuclear interference occurs, with special attention to the slopes of the real and imaginary parts. The forward amplitudes are assumed to have simple exponential forms, depending on four parameters σ, ρ, B I , B R , with B I ≠ B R .

Zonadhesin D3-polypeptides vary among species but are similar in Equus species capable of interbreeding.

Science.gov (United States)

Tardif, Steve; Brady, Heidi A; Breazeale, Kelly R; Bi, Ming; Thompson, Leslie D; Bruemmer, Jason E; Bailey, Laura B; Hardy, Daniel M

2010-02-01

Zonadhesin is a rapidly evolving protein in the sperm acrosome that confers species specificity to sperm-zona pellucida adhesion. Though structural variation in zonadhesin likely contributes to its species-specific function, the protein has not previously been characterized in organisms capable of interbreeding. Here we compared properties of zonadhesin in several animals, including the horse (Equus caballus), donkey (E. asinus), and Grevy's zebra (E. grevyi) to determine if variation in zonadhesin correlates with ability of gametes to cross-fertilize. Zonadhesin localized to the apical acrosomes of spermatozoa from all three Equus species, similar to its localization in other animals. Likewise, in horse and donkey testis, zonadhesin was detected only in germ cells, first in the acrosomal granule of round spermatids and then in the developing acrosomes of elongating spermatids. Among non-Equus species, D3-domain polypeptides of mature, processed zonadhesin varied markedly in size and detergent solubility. However, zonadhesin D3-domain polypeptides in horse, donkey, and zebra spermatozoa exhibited identical electrophoretic mobility and detergent solubility. Equus zonadhesin D3-polypeptides (p110/p80 doublet) were most similar in size to porcine and bovine zonadhesin D3-polypeptides (p105). Sequence comparisons revealed that the horse zonadhesin precursor's domain content and arrangement are similar to those of zonadhesin from other large animals. Partial sequences of horse and donkey zonadhesin were much more similar to each other (>99% identity) than they were to orthologous sequences of human, pig, rabbit, and mouse zonadhesin (52%-72% identity). We conclude that conservation of zonadhesin D3-polypeptide properties correlates with ability of Equus species to interbreed.

Analysis of urine composition in type Ⅱ diabetic mice after intervention therapy using holothurian polypeptides

Science.gov (United States)

Li, Yanyan; Xu, Jiajie; Su, Xiurong

2017-07-01

Hydrolysates and peptide fractions (PF) obtained from sea cucumber with commercial enzyme were studied on the hpyerglycemic and renal protective effects on db/db rats using urine metabolomics. Compared with the control group the polypeptides from the two species could significantly reduce the urine glucose and urea. We also tried to address the compositions of highly expressed urinary proteins using a proteomics approach. They were serum albumins, AMBP proteins, negative trypsin, elastase and urinary protein, GAPDH, a receptor of urokinase-type plasminogen activator (uPAR), and Ig kappa chain C region. We used the electronic nose to quickly detect changes in the volatile substances in mice urine after holothurian polypeptides fed, and the results show it can identify the difference between treatment groups with the control group without overlapping. The protein express mechanism of holothurian polypeptides treating diabetes was discussed, and we suggested these two peptides with the hypoglycemic and renal protective activity might be utilized as nutraceuticals.

An anti-cancer WxxxE-containing azurin polypeptide inhibits Rac1-dependent STAT3 and ERK/GSK-3β signaling in breast cancer cells.

Science.gov (United States)

Zhang, Zhe; Luo, Zhiyong; Min, Wenpu; Zhang, Lin; Wu, Yaqun; Hu, Xiaopeng

2017-06-27

In our previous study, we characterized a mycoplasmal small GTPase-like polypeptide of 240 amino acids that possesses an N-terminal WVLGE sequence. The N-terminal WVLGE sequence promotes activation of Rac1 and subsequent host cancer cell proliferation. To investigate the function of the WxxxE motif in the interaction with Rac1 and host tumor progression, we synthesized a 35-amino acid WVLGE-containing polypeptide derived from a cell-penetrating peptide derived from the azurin protein. We verified that the WVLGE-containing polypeptide targeted MCF-7 cells rather than MCF-10A cells. However, the WVLGE-containing polypeptide inhibited activation of Rac1 and induced cellular phenotypes that resulted from inhibition of Rac1. In addition, the WVLGE-containing polypeptide down-regulated phosphorylation of the STAT3 and ERK/GSK-3β signaling pathways, and this effect was abolished by either stimulation or inhibition of Rac1 activity. We also found that the WVLGE-containing polypeptide has a Rac1-dependent potential to suppress breast cancer growth in vitro and in vivo. We suggest that by acting as a Rac1 inhibitor, this novel polypeptide may be useful for the treatment of breast cancer.

cDNA encoding a polypeptide including a hevein sequence

Energy Technology Data Exchange (ETDEWEB)

Raikhel, N.V.; Broekaert, W.F.; Chua, N.H.; Kush, A.

2000-07-04

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74--79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli.

cDNA encoding a polypeptide including a hevein sequence

Energy Technology Data Exchange (ETDEWEB)

Raikhel, N.V.; Broekaert, W.F.; Chua, N.H.; Kush, A.

1999-05-04

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74--79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli. 12 figs.

cDNA encoding a polypeptide including a hevein sequence

Energy Technology Data Exchange (ETDEWEB)

Raikhel, Natasha V. (Okemos, MI); Broekaert, Willem F. (Dilbeek, BE); Chua, Nam-Hai (Scarsdale, NY); Kush, Anil (New York, NY)

1999-05-04

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74-79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli.

cDNA encoding a polypeptide including a hevein sequence

Energy Technology Data Exchange (ETDEWEB)

Raikhel, N.V.; Broekaert, W.F.; Chua, N.H.; Kush, A.

1995-03-21

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1,018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74--79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli. 11 figures.

Functional polypeptides obtained by living ring opening polymerizations of N-carboxyanhydrides

NARCIS (Netherlands)

Habraken, G.J.M.

2011-01-01

N-Carboxyanhydride ring opening polymerization (NCA ROP) is a method to prepare polypeptides with a high degree of polymerization in large quantities. The living polymerization technique of NCA ROP gave the opportunity to synthesize many polymer architectures with well-defined blocks and copolymers

Side-chain-controlled self-assembly of polystyrene-polypeptide miktoarm star copolymers

KAUST Repository

Junnila, Susanna; Houbenov, Nikolay; Karatzas, A.; Hadjichristidis, Nikolaos; Hirao, Akira; Iatrou, Hermis; Ikkala, Olli T.

2012-01-01

polypeptide-surfactant self-assemblies with β-sheet conformation in PS 2PLL(DS) and PS 2(PLL(DS)) 2 which dominate over the formation of block copolymer scale structures. Differences between the 3- and 4-arm systems illustrate how packing frustration between

Study of local conformation and molecular movements of homo-polypeptides in aqueous solutions by using magnetic resonance and relaxation

International Nuclear Information System (INIS)

Perly, Bruno

1980-01-01

The objective of this research thesis is to study local conformations and mobilities of some typical homo-polypeptides by using techniques of magnetic resonance. By using these techniques, it is possible to make highly local observations of molecular elements which allows very efficient analysis of structural and dynamic properties of several biologically important compounds to be performed, and the study of their interactions. After a presentation of the general properties of the studied polypeptides, of magnetic resonance and of magnetic relaxation, the author presents some elements of macromolecular dynamics and movement models. Then, he reports the study of local conformations and structural transitions, applications of spin marking to the dynamic study of polypeptides, a dynamic study of the polypeptide skeleton under the form of statistic balls, the study of local movements of side chains by using nuclear relaxation, the study of the coupling of movements of main and side chains, and of the nuclear relaxation induced by a radical spin marker

Identification of dehydrin-like proteins responsive to chilling in floral buds of blueberry (Vaccinium, section Cyanococcus).

Science.gov (United States)

Muthalif, M M; Rowland, L J

1994-04-01

The level of three major polypeptides of 65, 60, and 14 kD increased in response to chilling unit accumulation in floral buds of a woody perennial, blueberry (Vaccinium, section Cynaococcus). The level of the polypeptides increased most dramatically within 300 h of chilling and decreased to the prechilling level with the initiation of budbreak. Cold-hardiness levels were assessed for dormant buds of Vaccinium corymbosum and Vaccinium ashei after different chilling treatments until the resumption of growth. These levels coincided with the level of the chilling-responsive polypeptides. Like some other previously described cold-induced proteins in annual plants, the level of the chilling-induced polypeptides also increased in leaves in response to cold treatment; the chilling-induced polypeptides were heat stable, resisting aggregation after incubation at 95 degrees C for 15 min. By fractionating bud proteins first by isoelectric point (pI) and then by molecular mass, the pI values of the 65- and 60-kD polypeptides were found to be 7.5 to 8.0 and the pI value of the 14-kD polypeptide was judged to be 8.5. Purification of the 65- and 60-kD polypeptides, followed by digestion with endoproteinase Lys-C and sequencing of selected fragments, revealed similarities in amino acid composition between the 65- and 60-kD polypeptides and dehydrins. Indeed, antiserum to the lysine-rich consensus sequence EKKGIMDKIKEKLPG of dehydrin proteins cross-reacted to all three of the major chilling-responsive polypeptides of blueberry, identifying these as dehydrins or dehydrin-like proteins.

Chiral power counting and pp → ppπ0 near threshold

International Nuclear Information System (INIS)

Van Kolck, U.; Miller, G.A.

1995-01-01

The pp → ppπ 0 reaction is studied near threshold using power counting arguments based on chiral perturbation theory with an explicit Δ degree of freedom. Important contributions include the so-called impulse term, rescattering via the Δ and rescattering via the (off-shell) seagull term responsible for s-wave pion-nucleon scattering. These contributions largely cancel so that their sum greatly underpredicts the total cross-section. Other mechanisms are also discussed. The inclusion of the previously proposed σ meson exchange mechanism is not sufficient to resolve the discrepancy with experiment

Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

International Nuclear Information System (INIS)

Cameron, R.S.; Cameron, P.L.; Castle, J.D.

1986-01-01

A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion

PP/clay nanocomposite films for food package; Filmes de nanocomposito PP/argila organofilica para embalagens de alimentos

Energy Technology Data Exchange (ETDEWEB)

Araujo, Arthur R.A.; Silva, Suedina M.L., E-mail: suedina@dema.ufcg.ed [Universidade Federal de Campina Grande (UAEMat/UFCG), PB (Brazil). Unidade Academica de Engenharia de Materiais; Andrade, Daniela L.A.C.S. [Universidade Federal de Campina Grande (UFCG), PB (Brazil). Programa de Pos-Graduacao em Engenharia de Processos; Mesquita, Wandemberg B [Felinto Industria e Comercio Ltda., Campina Grande, PB (Brazil)

2009-07-01

Small contents of organoclays (1 wt %) were incorporated to PP modified with maleic anhydride by melt intercalation, in order to prepare polymeric films for further applications in food package sector. The films were characterized by X-ray diffraction (XRD) and mechanical properties. The data indicates that the incorporation of organoclay to PP results in transparent films with intercalated morphology and highly. The mechanical properties of nanocomposites films were superior from those pristine films. The results evidences that the PP/PP-g-MA/organoclay nanocomposite films, prepared in this study might be promissory to the food package market and, in short time, be used like a new product by industries of this sector. (author)

Temperature-dependent morphology of hybrid nanoflowers from elastin-like polypeptides

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Koushik; Balog, Eva Rose M.; Sista, Prakash; Williams, Darrick J.; Martinez, Jennifer S., E-mail: jenm@lanl.gov, E-mail: rcrocha@lanl.gov; Rocha, Reginaldo C., E-mail: jenm@lanl.gov, E-mail: rcrocha@lanl.gov [Center for Integrated Nanotechnologies, Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Kelly, Daniel [Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2014-02-01

We report a method for creating hybrid organic-inorganic “nanoflowers” using calcium or copper ions as the inorganic component and a recombinantly expressed elastin-like polypeptide (ELP) as the organic component. Polypeptides provide binding sites for the dynamic coordination with metal ions, and then such noncovalent complexes become nucleation sites for primary crystals of metal phosphates. We have shown that the interaction between the stimuli-responsive ELP and Ca{sup 2+} or Cu{sup 2+}, in the presence of phosphate, leads to the growth of micrometer-sized particles featuring nanoscale patterns shaped like flower petals. The morphology of these flower-like composite structures is dependent upon the temperature of growth and has been characterized by scanning electron microscopy. The composition of nanoflowers has also been analyzed by energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The temperature-dependent morphologies of these hybrid nanostructures, which arise from the controllable phase transition of ELPs, hold potential for morphological control of biomaterials in emerging applications such as tissue engineering and biocatalysis.

Temperature-dependent morphology of hybrid nanoflowers from elastin-like polypeptides

Directory of Open Access Journals (Sweden)

Koushik Ghosh

2014-02-01

Full Text Available We report a method for creating hybrid organic-inorganic “nanoflowers” using calcium or copper ions as the inorganic component and a recombinantly expressed elastin-like polypeptide (ELP as the organic component. Polypeptides provide binding sites for the dynamic coordination with metal ions, and then such noncovalent complexes become nucleation sites for primary crystals of metal phosphates. We have shown that the interaction between the stimuli-responsive ELP and Ca2+ or Cu2+, in the presence of phosphate, leads to the growth of micrometer-sized particles featuring nanoscale patterns shaped like flower petals. The morphology of these flower-like composite structures is dependent upon the temperature of growth and has been characterized by scanning electron microscopy. The composition of nanoflowers has also been analyzed by energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The temperature-dependent morphologies of these hybrid nanostructures, which arise from the controllable phase transition of ELPs, hold potential for morphological control of biomaterials in emerging applications such as tissue engineering and biocatalysis.

Well-defined (co)polypeptides bearing pendant alkyne groups

KAUST Repository

Zhao, Wei

2016-03-18

A novel metal-free strategy, using hydrogen-bonding catalytic ring opening polymerization of acetylene-functionalized N-carboxy anhydrites of α-amino acids, was developed for the synthesis of well-defined polypeptides bearing pendant alkyne groups. This method provides an efficient way to synthesize novel alkyne-functionalized homopolypeptides (A) and copolypeptides, such as AB diblock (B: non-functionalized), ABA triblock and star-AB diblock, as well as linear and star random copolypeptides, precursors of a plethora complex macromolecular architectures by click chemistry.

Well-defined (co)polypeptides bearing pendant alkyne groups

KAUST Repository

Zhao, Wei; Gnanou, Yves; Hadjichristidis, Nikolaos

2016-01-01

A novel metal-free strategy, using hydrogen-bonding catalytic ring opening polymerization of acetylene-functionalized N-carboxy anhydrites of α-amino acids, was developed for the synthesis of well-defined polypeptides bearing pendant alkyne groups. This method provides an efficient way to synthesize novel alkyne-functionalized homopolypeptides (A) and copolypeptides, such as AB diblock (B: non-functionalized), ABA triblock and star-AB diblock, as well as linear and star random copolypeptides, precursors of a plethora complex macromolecular architectures by click chemistry.

Zonadhesin D3-Polypeptides Vary among Species but Are Similar in Equus Species Capable of Interbreeding1

Science.gov (United States)

Tardif, Steve; Brady, Heidi A.; Breazeale, Kelly R.; Bi, Ming; Thompson, Leslie D.; Bruemmer, Jason E.; Bailey, Laura B.; Hardy, Daniel M.

2009-01-01

Zonadhesin is a rapidly evolving protein in the sperm acrosome that confers species specificity to sperm-zona pellucida adhesion. Though structural variation in zonadhesin likely contributes to its species-specific function, the protein has not previously been characterized in organisms capable of interbreeding. Here we compared properties of zonadhesin in several animals, including the horse (Equus caballus), donkey (E. asinus), and Grevy's zebra (E. grevyi) to determine if variation in zonadhesin correlates with ability of gametes to cross-fertilize. Zonadhesin localized to the apical acrosomes of spermatozoa from all three Equus species, similar to its localization in other animals. Likewise, in horse and donkey testis, zonadhesin was detected only in germ cells, first in the acrosomal granule of round spermatids and then in the developing acrosomes of elongating spermatids. Among non-Equus species, D3-domain polypeptides of mature, processed zonadhesin varied markedly in size and detergent solubility. However, zonadhesin D3-domain polypeptides in horse, donkey, and zebra spermatozoa exhibited identical electrophoretic mobility and detergent solubility. Equus zonadhesin D3-polypeptides (p110/p80 doublet) were most similar in size to porcine and bovine zonadhesin D3-polypeptides (p105). Sequence comparisons revealed that the horse zonadhesin precursor's domain content and arrangement are similar to those of zonadhesin from other large animals. Partial sequences of horse and donkey zonadhesin were much more similar to each other (>99% identity) than they were to orthologous sequences of human, pig, rabbit, and mouse zonadhesin (52%–72% identity). We conclude that conservation of zonadhesin D3-polypeptide properties correlates with ability of Equus species to interbreed. PMID:19794156

Permanent Electric Dipole-Dipole Interactions in Lyotropic Polypeptide Liquid Crystals

OpenAIRE

MORI, Norio; Norio, MORI; Research Associate, Department of Industrial Chemistry

1981-01-01

The interaction energy between two adjacent α-helical molecules was calculated taking into account for permanent electric dipoles locating orl the helical core of a polymer mainchain in order to explain the cholesteric structure of lyotropic polypeptide liquid crystals. It was concluded that the dipole-dipole interactions were responsible for the formation of the cholesteric structure.

Pp scattering at SIN

International Nuclear Information System (INIS)

Aprile-Giboni, E.; Cantale, G.; Hausammann, R.

1983-01-01

Using the PM1 polarized proton beam at SIN and a polarized target, the elastic pp scattering as well as the inelastic channel pp → π + d have been studied between 400 and 600 MeV. For the elastic reaction, a sufficient number of spin dependent parameters has been measured in order to do a direct reconstruction of the scattering matrix between 38 0 /sub cm/ and 90 0 /sub cm/. 10 references, 6 figures

Measurement of the forward charged particle pseudorapidity density in $pp$ collisions at $\\sqrt{s} = 7$ TeV with the TOTEM experiment.

CERN Document Server

Berretti, Mirko; Scribano, Angelo

The TOTEM experiment at the LHC is dedicated to the precise measurement of the total $pp$ cross section, to the study of the elastic scattering and of the diffractive interactions. The TOTEM T2 telescope, composed of triple GEM chambers, provides the tracking of the charged particles produced by the inelastic $pp$ interactions in the pseudorapidity range 5.3$<$$|\\eta|$$<$6.5. In this thesis the offline procedures developed for the event reconstruction in the T2 telescope are reported. They include the tuning of the detector simulation, the track reconstruction algorithm and their characterisation in terms of physics performance. The detector alignment algorithms are also described and the uncertainties on the misalignment parameters are quantified. The thesis is then focused on the measurement of the charged particle pseudorapidity density ($dN_{ch}/d\\eta$) obtained in T2 for inelastic $pp$ collisions at $\\sqrt{s}=$ 7 TeV. This extends the analogous measurement performed by the other LHC experiments to...

Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines.

Science.gov (United States)

Despanie, Jordan; Dhandhukia, Jugal P; Hamm-Alvarez, Sarah F; MacKay, J Andrew

2016-10-28

Elastin-like polypeptides (ELPs) constitute a genetically engineered class of 'protein polymers' derived from human tropoelastin. They exhibit a reversible phase separation whereby samples remain soluble below a transition temperature (T t ) but form amorphous coacervates above T t . Their phase behavior has many possible applications in purification, sensing, activation, and nanoassembly. As humanized polypeptides, they are non-immunogenic, substrates for proteolytic biodegradation, and can be decorated with pharmacologically active peptides, proteins, and small molecules. Recombinant synthesis additionally allows precise control over ELP architecture and molecular weight, resulting in protein polymers with uniform physicochemical properties suited to the design of multifunctional biologics. As such, ELPs have been employed for various uses including as anti-cancer agents, ocular drug delivery vehicles, and protein trafficking modulators. This review aims to offer the reader a catalogue of ELPs, their various applications, and potential for commercialization across a broad spectrum of fields. Copyright © 2015. Published by Elsevier B.V.

ISAJET 5.30: A Monte Carlo event generator for pp and anti pp interactions

International Nuclear Information System (INIS)

Paige, F.E.; Protopopescu, S.D.

1986-09-01

ISAJET is a Monte Carlo program which simulates pp and anti pp interactions at high energy. It is based on perturbative QCD cross sections, leading order QCD radiative corrections for initial and final state partons, and phenomenological models for jet and beam jet fragmentation. This article describes ISAJET 5.30, which includes production of standard Higgs bosons and which will be released shortly

A novel peptide nanomedicine for treatment of pancreatogenic diabetes.

Science.gov (United States)

Banerjee, Amrita; Onyuksel, Hayat

2013-08-01

Pancreatogenic diabetes (PD) is a potentially fatal disease that occurs secondary to pancreatic disorders. The current anti-diabetic therapy for PD is fraught with adverse effects that can increase morbidity. Here we investigated the efficacy of novel peptide nanomedicine: pancreatic polypeptide (PP) in sterically stabilized micelles (SSM) for management of PD. PP exhibits significant anti-diabetic efficacy but its short plasma half-life curtails its therapeutic application. To prolong and improve activity of PP in vivo, we evaluated the delivery of PP in SSM. PP-SSM administered to rats with PD, significantly improved glucose tolerance, insulin sensitivity and hepatic glycogen content compared to peptide in buffer. The studies established the importance of micellar nanocarriers in protecting enzyme-labile peptides in vivo and delivering them to target site, thereby enhancing their therapeutic efficacy. In summary, this study demonstrated that PP-SSM is a promising novel anti-diabetic nanomedicine and therefore should be further developed for management of PD. Pancreatic peptide was earlier demonstrated to address pancreatogenic diabetes, but its short half-life represented major difficulties in further development for therapeutic use. PP-SSM (pancreatic polypeptide in sterically stabilized micelles) is a promising novel anti-diabetic nanomedicine that enables prolonged half-life and increased bioactivity of PP, as shown in this novel study, paving the way toward clinical studies in the near future. Copyright © 2013 Elsevier Inc. All rights reserved.

Heterogenous expression of Pyrus pyrifolia PpCAD2 and PpEXP2 in tobacco impacts lignin accumulation in transgenic plants.

Science.gov (United States)

Wang, Yuling; Zhang, Xinfu; Yang, Shaolan; Wang, Caihong; Lu, Guilong; Wang, Ran; Yang, Yingjie; Li, Dingli

2017-12-30

Lignin, a natural macromolecular compound, plays an important role in the texture and taste of fruit. Hard end is a physiological disorder of pear fruit, in which the level of lignification in fruit tissues is dramatically elevated. Cinnamyl alcohol dehydrogenase and expansin genes (PpCAD2 and PpEXP2, respectively) exhibit higher levels of expression in 'Whangkeumbae' (Pyrus pyrifolia) pear fruit exhibiting this physiological disorder, relative to control fruit without symptoms. These genes were isolated from pear fruit and subsequently expressed in tobacco (Nicotiana tabacum) to investigate their function. Histochemical staining for lignin revealed that the degree of lignification in leaf veins and stem tissues increased in plants transformed with sense constructs and decreased in plants transformed with antisense constructs of PpCAD2. The expression of native NtCADs was also inhibited in the antisense PpCAD2 transgenic tobacco. Sense and antisense PpCAD2 transgenic tobacco exhibited an 86.7% increase and a 60% decrease in CAD activity, respectively, accompanied by a complementary response in lignin content in root tissues. The basal portion of the stem in PpEXP2 transgenic tobacco was bent and highly lignified. Additionally, the level of cellulose also increased in the stem of PpEXP2 transgenic tobacco. Collectively, these results suggested that PpCAD2 and PpEXP2 genes play a significant role in lignin accumulation in transgenic tobacco plants, and it is inferred that these two genes may also participate in the increased lignification observed in hard end pear fruit. Copyright © 2017. Published by Elsevier B.V.

Characterization of mutants expressing thermostable D1 and D2 polypeptides of photosystem II in the cyanobacterium Synechococcus elongatus PCC 7942.

Science.gov (United States)

Haraguchi, Norihisa; Kaseda, Jun; Nakayama, Yasumune; Nagahama, Kazuhiro; Ogawa, Takahira; Matsuoka, Masayoshi

2018-06-08

Photosystem II complex embedded in thylakoid membrane performs oxygenic photosynthesis where the reaction center D1/D2 heterodimer accommodates all components of the electron transport chain. To express thermostable D1/D2 heterodimer in a cyanobacterium Synechococcus elongatus PCC 7942, we constructed a series of mutant strains whose psbA1 and psbD1 genes encoding, respectively, the most highly expressed D1 and D2 polypeptides were replaced with those of a thermophilic strain, Thermosynechococcus vulcanus. Because the C-terminal 16 amino acid sequences of D1 polypeptides should be processed prior to maturation but diverge from each other, we also constructed the psbA1ΔC-replaced strain expressing a thermostable D1 polypeptide devoid of the C-terminal extension. The psbA1/psbD1-replaced strain showed decreased growth rate and oxygen evolution rate, suggesting inefficient photosystem II. Immunoblot analyses for thermostable D1, D2 polypeptides revealed that the heterologous D1 protein was absent in thylakoid membrane from any mutant strains with psbA1, psbA1ΔC, and psbA1/psbD1-replacements, whereas the heterologous D2 protein was present in thylakoid membrane as well as purified photosystem II complex from the psbA1/psbD1-replaced strain. In the latter strain, the compensatory expression of psbA3 and psbD2 genes was elevated. These data suggest that heterologous D2 polypeptide could be combined with the host D1 polypeptide to form chimeric D1/D2 heterodimer, whereas heterologous D1 polypeptide even without the C-terminal extension was unable to make complex with the host D2 polypeptide. Since the heterologous D1 could not be detected even in the whole cells of psbA1/psbD1-replaced strain, the rapid degradation of unprocessed or unassembled heterologous D1 was implicated. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Relations between a novel, reliable, and rapid index of arterial compliance (PP-HDI) and well-established inidices of arterial blood pressure (ABP) in a sample of hypertensive elderly subjects.

Science.gov (United States)

Bergamini, L; Finelli, M E; Bendini, C; Ferrari, E; Veschi, M; Neviani, F; Manni, B; Pelosi, A; Rioli, G; Neri, M

2009-01-01

Hypertension is a risk factor for a long-lasting arterial wall-remodelling leading to stiffness. The rapid method measuring the pulse pressure (PP) by means of the tool of Hypertension Diagnostic Instruments (HDI) called PP-HDI, overcomes some of the problems arising with more-time consuming methods, like ambulatory blood pressure monitoring (ABPM), and give information about the elasticity of the arterial walls. We studied the relationship between the PP-HDI, the large artery compliance (LA-C) and small artery compliance (SA-C) and few well-established indices of arterial blood pressure (ABP) in a sample of 75 hypertensive subjects, aged 65 years and over. Significant correlations between LA-C and heart rate (HR), PP-ABPM and PP-HDI were found. SA-C relates with HR and systolic blood pressure (SBP) measured in lying and standing positions. Applying a stepwise regression analysis, we found that LA-C variance stems from PP-HDI and HR, while SA-C variance stems from SBP in lying position. Receiver operator characteristic (ROC) curves for thresholds of PP showed that PP-HDI reached levels of sensitivity/specificity similar to PP-ABPM. In conclusion, surveillance of ABP through hemo-dynamic indices, in particular of SBP, is essential, nevertheless the advantage of this control is not known in an elderly population where the organ damage is already evident. PP needs necessarily an instrumental measurement. The PP-HDI result is similar in reliability with respect to PPABPM, but is more rapid and well applicable in an elderly population.

Double-hydrophobic elastin-like polypeptides with added functional motifs: Self-assembly and cytocompatibility.

Science.gov (United States)

Le, Duc H T; Tsutsui, Yoko; Sugawara-Narutaki, Ayae; Yukawa, Hiroshi; Baba, Yoshinobu; Ohtsuki, Chikara

2017-09-01

We have recently developed a novel double-hydrophobic elastin-like triblock polypeptide called GPG, designed after the uneven distribution of two different hydrophobic domains found in elastin, an extracellular matrix protein providing elasticity and resilience to tissues. Upon temperature trigger, GPG undergoes a sequential self-assembling process to form flexible beaded nanofibers with high homogeneity and excellent dispersibility in water. Given that GPG might be a potential elastin-mimetic material, we sought to explore the biological activities of this block polypeptide. Besides GPG, several functionalized derivatives were also constructed by fusing functional motifs such as KAAK or KAAKGRGDS at the C-terminal of GPG. Although the added motifs affected the kinetics of fiber formation and β-sheet contents, all three GPGs assembled into beaded nanofibers at the physiological temperature. The resulting GPG nanofibers preserved their beaded structures in cell culture medium; therefore, they were coated on polystyrene substrates to study their cytocompatibility toward mouse embryonic fibroblasts, NIH-3T3. Among the three polypeptides, GPG having the cell-binding motif GRGDS derived from fibronectin showed excellent cell adhesion and cell proliferation properties compared to other conventional materials, suggesting its promising applications as extracellular matrices for mammalian cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2475-2484, 2017. © 2017 Wiley Periodicals, Inc.

Architecture effects on multivalent interactions by polypeptide-based multivalent ligands

Science.gov (United States)

Liu, Shuang

protein materials, including structural as well as functional proteins. Therefore, polypeptide-based multivalent scaffolds are used to display ligands to assess the contribution of different architectural parameters to the multivalent binding events. In this work, a family of alanine-rich alpha-helical glycopolypeptides was designed and synthesized by a combination of protein engineering and chemical coupling, to display two types of saccharide ligands for two different multivalent binding systems. The valencies, chain length and spacing between adjacent ligands of these multivalent ligands were designed in order to study architecture effects on multivalent interactions. The polypeptides and their glycoconjugates were characterized via various methods, including SDS-PAGE, NMR, HPLC, amino acid analysis (AAA), MALDI, circular dichroism (CD) and GPC. In the first multivalent binding system, cholera toxin B pentamer (CT B5) was chosen to be the protein receptor due to its well-characterized structure, lack of significant steric interference of binding to multiple binding sites, and requirement of only simple monosaccharide as ligands. Galactopyranoside was incorporated into polypeptide scaffolds through amine-carboxylic acid coupling to the side chains of glutamic acid residues. The inhibition and binding to CT B5 of these glycopolypeptide ligands were evaluated by direct enzyme-linked assay (DELA). As a complement method, weak affinity chromatography (WAC) was also used to evaluate glycopolypeptides binding to a CT B5 immobilized column. The architecture effects on CT B 5 inhibition are discussed. In the second system, cell surface receptor L-selectin was targeted by polypeptide-based multivalent ligands containing disulfated galactopyranoside ligands, due to its important roles in various immunological activities. The effects of glycopolypeptide architectural variables L-selectin shedding were evaluated via ELISA-based assays. These polypeptide-based multivalent ligands

The new ISR and collider anti p-p and p-p data and asymptotic theorems

International Nuclear Information System (INIS)

Nicolescu, B.

1982-10-01

We present a general discussion of the rigorous finite-energy effects of asymptotic theorems, with a special emphasis on the confrontation with the new ISR and collider antipp and pp total cross-section data. We point out the possible existence of a minimum in the difference between the antipp and pp total cross-sections

Photooxidation of HMS-PP under environment and artificial weathering conditions

International Nuclear Information System (INIS)

Oliani, Washington L.; Parra, Duclerc F.; Lima, Luis Filipe C.P.; Lugao, Ademar B.

2009-01-01

The linearity of the chains confers to iPP, low melt strength, which means a low strength to stretching during elongation. The increase of melt strength and the extensibility is due to the increase of the entanglement of the macromolecules chains. The HMS-PP (high melt strength polypropylene) was synthesized (based on the grains iPP) through gamma irradiation in the iPP under acetylene atmosphere followed by heat treatment for recombination and subsequent annihilation of the other free radicals. Samples of HMS-PP and iPP were subjected to environmental aging in IPEN - Sao Paulo and in the QUV chamber. The results show fractured surfaces of iPP and HMS-PP that are intensified with exposure time. The iPP degradation process has the predominance of chain scissions, with carbonyl and hydroperoxides formation which act as initiators of photo degradation mechanisms. (author)

Study of pp sup(-) → X+π- and pp sup(-) → X0#betta# reactions

International Nuclear Information System (INIS)

Alves, M.S.; Thome Filho, Z.D.

1982-01-01

Detailed calculations of the cross section of the pp sup(-) → X + π - and pp sup(-) → X 0 #betta# reactions, with the inclusion of the p meson exchange in the first reaction, are made. In the second one, the cross section is obtained taking into account the contribution of the simpler diagrams. (L.C.) [pt

Core Drilling of shallow drillholes OL-PP72...OL-PP89 at Olkiluoto, Eurajoki 2011

Energy Technology Data Exchange (ETDEWEB)

Toropainen, V. [Suomen Malmi Oy, Espoo (Finland)

2012-05-15

Suomen Malmi Oy (Smoy) core drilled eighteen drillholes to survey the ground and bedrock conditions in the encapsulation plant building site at Olkiluoto, Eurajoki 2011. Soil quality, bedrock depth and quality of near surface bedrock were investigated in this project. The drillholes were drilled between 19th of October and 8th of November 2011. The lengths of the drillholes are mostly between 7 to 9 metres, except for the drillhole OL-PP79, which is 15 metres by length. The drillholes are 76 mm by diameter, and the core diameter is 60.2 mm. The lightweight GM75 drilling rig with rubber tracks was used. The drilling water was taken from the ONKALO area research building freshwater pipeline and sodium fluorescein was added as a label agent in the drilling water. The drillholes were not left open. In addition to drilling the drillcores were logged and reported by geologist. Geological logging included the following parameters: lithology, foliation, fracture parameters, fractured zones, core loss, weathering, fracture frequency, RQD and rock quality. The average natural fracture frequencies of the drillcores range from 2.5 pc/m (OL-PP77) to 11.8 pc/m (OL-PP86). The average RQD ranges from 55.1 % (OL-PP86) to 96.4 % (OL-PP77). The penetrated soils are mostly ground fill (blast rock), but some clays and sands are lying below the fill layer. (orig.)

Core Drilling of shallow drillholes OL-PP72...OL-PP89 at Olkiluoto, Eurajoki 2011

International Nuclear Information System (INIS)

Toropainen, V.

2012-05-01

Suomen Malmi Oy (Smoy) core drilled eighteen drillholes to survey the ground and bedrock conditions in the encapsulation plant building site at Olkiluoto, Eurajoki 2011. Soil quality, bedrock depth and quality of near surface bedrock were investigated in this project. The drillholes were drilled between 19th of October and 8th of November 2011. The lengths of the drillholes are mostly between 7 to 9 metres, except for the drillhole OL-PP79, which is 15 metres by length. The drillholes are 76 mm by diameter, and the core diameter is 60.2 mm. The lightweight GM75 drilling rig with rubber tracks was used. The drilling water was taken from the ONKALO area research building freshwater pipeline and sodium fluorescein was added as a label agent in the drilling water. The drillholes were not left open. In addition to drilling the drillcores were logged and reported by geologist. Geological logging included the following parameters: lithology, foliation, fracture parameters, fractured zones, core loss, weathering, fracture frequency, RQD and rock quality. The average natural fracture frequencies of the drillcores range from 2.5 pc/m (OL-PP77) to 11.8 pc/m (OL-PP86). The average RQD ranges from 55.1 % (OL-PP86) to 96.4 % (OL-PP77). The penetrated soils are mostly ground fill (blast rock), but some clays and sands are lying below the fill layer. (orig.)

cDNA encoding a polypeptide including a hev ein sequence

Energy Technology Data Exchange (ETDEWEB)

Raikhel, Natasha V. (Okemos, MI); Broekaert, Willem F. (Dilbeek, BE); Chua, Nam-Hai (Scarsdale, NY); Kush, Anil (New York, NY)

2000-07-04

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74-79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli.

A pH- and temperature-responsive bioresorbable injectable hydrogel based on polypeptide block copolymers for the sustained delivery of proteins in vivo.

Science.gov (United States)

Turabee, Md Hasan; Thambi, Thavasyappan; Duong, Huu Thuy Trang; Jeong, Ji Hoon; Lee, Doo Sung

2018-02-27

Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive in situ-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining N-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using N-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 μg mL -1 ). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The in vivo gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel in vivo and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.

The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

DEFF Research Database (Denmark)

Gerken, Thomas A; Revoredo, Leslie; Thome, Joseph J C

2013-01-01

and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities...... relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides...

Differential cross sections of the pp -> pp pi sup 0 reaction from 310 to 425 MeV

CERN Document Server

Zlomanczuk, Yu; Brodowski, W; Calén, H; Clement, H; Dyring, J; Ekström, C; Fäldt, G; Fransson, K; Gustafsson, L; Häggström, S; Hoeistad, B; Johanson, J; Johansson, A; Johansson, T; Kilian, K; Kullander, Sven; Kupsc, A; Marciniewski, P; Morosov, B; Moertsell, A; Oelert, W; Ruber, Roger J M Y; Schuberth, U; Sundberg, P; Shwartz, B A; Stepaniak, J; Sukhanov, A; Turowiecki, A; Wagner, G J; Wilhelmi, Z; Wilkin, C; Zabierowski, J; Zernov, A

2000-01-01

Measurements of the differential cross sections of the pp -> pp pi sup 0 reaction at 310, 320, 340, 360, 400 and 425 MeV have been carried out at the CELSIUS storage ring in Uppsala. An attempt has been made to describe the distributions obtained in terms of the five partial waves Ss, Ps, Pp, Sd and Ds. The relative contributions from the different states depend significantly upon the energy. For instance, that of the Ss state drops from about 80% at 310 MeV to around 10% at 425 MeV.

PP/clay nanocomposite films for food package

International Nuclear Information System (INIS)

Araujo, Arthur R.A.; Silva, Suedina M.L.

2009-01-01

Small contents of organoclays (1 wt %) were incorporated to PP modified with maleic anhydride by melt intercalation, in order to prepare polymeric films for further applications in food package sector. The films were characterized by X-ray diffraction (XRD) and mechanical properties. The data indicates that the incorporation of organoclay to PP results in transparent films with intercalated morphology and highly. The mechanical properties of nanocomposites films were superior from those pristine films. The results evidences that the PP/PP-g-MA/organoclay nanocomposite films, prepared in this study might be promissory to the food package market and, in short time, be used like a new product by industries of this sector. (author)

Organic anion transporting polypeptide 1B transporters modulate hydroxyurea pharmacokinetics

OpenAIRE

Walker, Aisha L.; Lancaster, Cynthia S.; Finkelstein, David; Ware, Russell E.; Sparreboom, Alex

2013-01-01

Hydroxyurea is currently the only FDA-approved drug that ameliorates the pathophysiology of sickle cell anemia. Unfortunately, substantial interpatient variability in the pharmacokinetics (PK) of hydroxyurea may result in variation of the drug's efficacy. However, little is known about mechanisms that modulate hydroxyurea PK. Recent in vitro studies identifying hydroxyurea as a substrate for organic anion transporting polypeptide (OATP1B) transporters prompted the current investigation assess...

Intrapulmonary Human Cytomegalovirus Replication in Lung Transplant Recipients Is Associated With a Rise of CCL-18 and CCL-20 Chemokine Levels.

Science.gov (United States)

Weseslindtner, Lukas; Görzer, Irene; Roedl, Kevin; Küng, Erik; Jaksch, Peter; Klepetko, Walter; Puchhammer-Stöckl, Elisabeth

2017-01-01

In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNA detection in the bronchoalveolar lavage fluid (BALF) indicates HCMV replication in the pulmonary compartment. Such local HCMV replication episodes may remain asymptomatic or may lead to symptomatic HCMV disease. Here, we investigated LTRs with intrapulmonary HCMV replication for the chemokines CCL-18 and CCL-20. In particular, we analyzed whether these chemokines rise in the allograft and/or the blood and are associated with HCMV disease. CCL-18 and CCL-20 levels were quantitated by ELISA in BALF and serum samples from 60 LTRs. During the posttransplant follow-up, these LTRs displayed HCMV DNA detection in the BALF by PCR, whereas other infectious agents were undetectable. Furthermore, we investigated samples from 10 controls who did not display any HCMV replication episode during the follow-up. HCMV replication in the allograft was associated with a significant increase of CCL-18 and CCL-20 BALF levels (P Wilcoxon signed-rank test) and a significant rise of CCL-20 (P Wilcoxon signed-rank test) but not of CCL-18 in the blood. In controls, no such chemokine increase was observed. Furthermore, CCL-18 BALF levels were significantly higher in 8 LTRs who additionally developed HCMV disease, as compared with the other 52 patients in whom HCMV replication remained asymptomatic (P test). HCMV replication in the allograft causes an intrapulmonary increase of CCL-18 and CCL-20 and a systemic rise of CCL-20 serum levels. Strong intrapulmonary CCL-18 responses are associated with symptomatic HCMV disease, proposing that CCL-18 BALF levels could serve as a marker.

Relationship between compatibilizer and yield strength of PLA/PP Blend

Science.gov (United States)

Jariyakulsith, Pattanun; Puajindanetr, Somchai

2018-01-01

The aim of this research is to study the relationship between compatibilizer and yield strength of polylactic acid (PLA) and polypropylene (PP) blend. The PLA is blended with PP (PLA/PP) at the ratios of 70/30, 50/50 and 30/70. In addition, (1) polypropylene grafted maleic anhydride (PP-g-MAH) as a compatibilizer at 0.3 and 0.7 part per hundred of PLA/PP resin (phr) and (2) dicumyl peroxide (DCP) being an initiator at 0.03 and 0.07 phr are added in each composition. Yield strength is characterized to study the interaction between compatibilizer, initiator and yield strength by using experimental design of multilevel full factorial. The results show that (1) the yield strength of PLA/PP blend are increased after addition of compatibilizer. Because the adding of PP-g-MAH and DCP resulted in improving compatibility between PLA and PP. (2) there are interaction between PP-g-MAH and DCP that have affected the final properties of PLA/PP blend. The highest yield strength of 27.68 MPa is provided at the ratio of 70/30 blend by using the 0.3 phr of PP-g-MAH and 0.03 phr of DCP. Linear regression model is fitted and follow the assumptions of normal distribution.

(p)ppGpp and the bacterial cell cycle

Indian Academy of Sciences (India)

Genes of the Rel/Spo homolog (RSH) superfamily synthesize and/or hydrolyse the modified nucleotides pppGpp/ppGpp (collectively referred to as (p)ppGpp) and are prevalent across diverse bacteria and in plant chloroplasts. Bacteria accumulate (p)ppGpp in response to nutrient deprivation (generically called the stringent ...

Effects of composition and processing conditions on morphology and properties of thermoplastic elastomer blends of SEBS-PP-Oil and dynamically vulcanized EPDM-PP-Oil

NARCIS (Netherlands)

Sengupta, P.; Noordermeer, Jacobus W.M.

2004-01-01

This work presents a comparative study of the morphology and structure-related properties of thermoplastic elastomer blends based on SEBS-PP-oil and dynamically vulcanized EPDM-PP-oil prepared under identical conditions. Compositions of each blend type with three different SEBS-PP and EPDM-PP ratios

Molecular cloning, identification, and chromosomal localization of two MADS box genes in peach (Prunus persica).

Science.gov (United States)

Zhang, Lin; Xu, Yong; Ma, Rongcai

2008-06-01

MADS box proteins play an important role in floral development. To find genes involved in the floral transition of Prunus species, cDNAs for two MADS box genes, PpMADS1 and PpMADS10, were cloned using degenerate primers and 5'- and 3'-RACE based on the sequence database of P. persica and P. dulcis. The full length of PpMADS1 cDNA is 1,071 bp containing an open reading frame (ORF) of 717 bp and coding for a polypeptide of 238 amino acid residues. The full length of PpMADS10 cDNA is 937 bp containing an ORF of 633 bp and coding for a polypeptide of 210 amino acid residues. Sequence comparison revealed that PpMADS1 and PpMADS10 were highly homologous to genes AP1 and PI in Arabidopsis, respectively. Phylogenetic analysis indicated that PpMADS1 belongs to the euAP1 clade of class A, and PpMADS10 is a member of GLO/PI clade of class B. RT-PCR analysis showed that PpMADS1 was expressed in sepal, petal, carpel, and fruit, which was slightly different from the expression pattern of AP1; PpMADS10 was expressed in petal and stamen, which shared the same expression pattern as PI. Using selective mapping strategy, PpMADS1 was assigned onto the Bin1:50 on the G1 linkage group between the markers MCO44 and TSA2, and PpMADS10 onto the Bin1:73 on the same linkage group between the markers Lap-1 and FGA8. Our results provided the basis for further dissection of the two MADS box gene function.

Evolution of human cytomegalovirus-seronegative donor/-seropositive recipient high-risk combination frequency in allogeneic hematopoietic stem cell transplantations at Institute of Hematology and Blood Transfusion during 1995-2014.

Science.gov (United States)

Nemeckova, S; Sroller, V; Stastna-Markova, M

2016-04-01

Human cytomegalovirus (HCMV) establishes lifelong latent infection that can result in severe life-threatening disease in immunosuppressed patients after hematopoietic stem cell transplantation (HSCT). An HCMV-seropositive transplant recipient who receives a graft from a seronegative donor (R+/D-) is at high risk of recurrent HCMV reactivation. To assess the incidence of R+/D- combination, we retrospectively evaluated HCMV-seronegative donors for 746 allogeneic HSCT treatments carried out at our center during 1995-2014. In our cohort, 20% HCMV-seronegative HSCT recipients, 21% HCMV-seronegative related graft donors, and 52% HCMV-seronegative unrelated graft donors were included. Analyses of the HCMV serostatus of hematopoietic stem cell donors during 2 consecutive calendar periods (1995-2005 and 2006-2014) showed a significant increase in the proportion of seronegative donors (odds ratio [OR] = 1.947). In addition, the number of HSCT treatments using an unrelated donor increased (OR = 2.376). Finally, the use of grafts from countries with a very low HCMV prevalence increased. This increase in HCMV seronegativity in unrelated donors and the increased proportion of unrelated donors were responsible for the increased occurrence of the high-risk combination R+/D- (OR = 1.680). If the reduction in the rate of HCMV-seropositive graft donors continues, an increased frequency of HCMV reactivation events in our transplant recipients can be expected, because of the increasing occurrence of the high-risk R+/D- combination. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Displacement affinity chromatography of protein phosphatase one (PP1 complexes

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Gourlay Robert

2008-11-01

Full Text Available Abstract Background Protein phosphatase one (PP1 is a ubiquitously expressed, highly conserved protein phosphatase that dephosphorylates target protein serine and threonine residues. PP1 is localized to its site of action by interacting with targeting or regulatory proteins, a majority of which contains a primary docking site referred to as the RVXF/W motif. Results We demonstrate that a peptide based on the RVXF/W motif can effectively displace PP1 bound proteins from PP1 retained on the phosphatase affinity matrix microcystin-Sepharose. Subsequent co-immunoprecipitation experiments confirmed that each identified binding protein was either a direct PP1 interactor or was in a complex that contains PP1. Our results have linked PP1 to numerous new nuclear functions and proteins, including Ki-67, Rif-1, topoisomerase IIα, several nuclear helicases, NUP153 and the TRRAP complex. Conclusion This modification of the microcystin-Sepharose technique offers an effective means of purifying novel PP1 regulatory subunits and associated proteins and provides a simple method to uncover a link between PP1 and additional cellular processes.

Studies on the properties of rice-husk-filled-PP composites: effect of maleated PP

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Simone Maria Leal Rosa

2009-09-01

Full Text Available Rice husk is a by-product of rice milling process that usually finds inadequate final disposal (burning, land filling. Thermoplastics composites filled with rice husk flour are materials that offer an alternative for using this agricultural resource viewing the production of low dense materials with some specific properties. In this work composites of polypropylene (PP and rice husk flour (RHF were prepared by melt extrusion. Maleic anhydride-modified PP (MAPP was added as a coupling agent. It was verified that tensile strength decreased with filler loading. The presence of MAPP improved this property showing a strong dependence on the MAPP/RHF ratio (MAPP/RHF = 0.03 produced the best results. The density of the composites slightly increased with filler and coupling agent in comparison to pure PP. The presence of MAPP diminished more than 20% water uptake in highly-loaded composites.

Electron Spin Resonance studies on PS, PP and PS/PP blends under gamma irradiation

International Nuclear Information System (INIS)

Reyes, J.; Claro, M.; Albano, C.; Venezuela Central University, Caracas; Moronta, D.

2002-01-01

Complete text of publication follows. Electron Spin Resonance (ESR) studies on Polystyrene (PS), Polypropylene (PP) and their mixtures at compositions of 80/20 with and without a compatibilizer (SBS in block), 7.5 wt.%, irradiated with gamma rays from a Cobalt-60 source with a dose rate of 4.8 KGy/h at integral doses of radiation of 10, 25, 50, 60, 70, 400, 800 and 1300 KGy in the presence of air and at room temperature (RT) are reported. The dependence of resonance line width, Hpp; resonance line shapes K, and radical concentration, S, with the integral dose of irradiation is investigated. The nature of the free radicals after ten days of air storage is discussed. The free radical concentration, the double integral of the resonance line, S, has been estimated at room temperature, RT, for a group of single lines, characterized by the same giromagnetic, g, value by direct numerical double integration. In the samples studied no spectrum of 0 kGy of integral dose was observed. The concentration of radicals, S, observed when the integral radiation doses was increased, presents a maximum value in the PP samples at high doses (70-1300 kGy) and minimum values in the PS samples with the same doses. This shows that the PP degrades at a faster rate than the PS, owing to the presence of the bencenic ring in the latter. In the PS/PP mixtures studied with and without compatibilizer, the values of the radical concentration is found between the observed values in the homopolymers, being closer to the PS, which might imply that the presence of PS decays the degradation process of the PP in the mixture

Functional Modification of Thioether Groups in Peptides, Polypeptides, and Proteins

OpenAIRE

Deming, TJ

2017-01-01

Recent developments in the modification of methionine and other thioether-containing residues in peptides, polypeptides, and proteins are reviewed. Properties and potential applications of the resulting functionalized products are also discussed. While much of this work is focused on natural Met residues, modifications at other side-chain residues have also emerged as new thioether-containing amino acids have been incorporated into peptidic materials. Functional modification of thioether-cont...

NMR study of the cooperative behavior of thermotropic model polypeptides

Czech Academy of Sciences Publication Activity Database

Kurková, Dana; Kříž, Jaroslav; Rodríguez-Cabello, J. C.; Arias, F. J.

2007-01-01

Roč. 56, č. 2 (2007), s. 186-194 ISSN 0959-8103 R&D Projects: GA AV ČR IAA400500604 Grant - others:Spanish Ministry of Science and Culture(ES) A002/02; MAT2000-1764-C02; MAT2001-1853-C02-01; MAT2003- Institutional research plan: CEZ:AV0Z40500505 Keywords : thermotropic polymers * cooperativity * synthetic polypeptides Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.557, year: 2007

Study on GIF PR/PP evaluation methodology

Energy Technology Data Exchange (ETDEWEB)

Lee, B. H.; Kwon, E. H.; Kim, H. D. [KAERI, Daejeon (Korea, Republic of)

2012-10-15

Proliferation resistance (PR) and physical protection (PP) is one of the four technology goals of generation IV nuclear energy systems (NESs). The PR component of the goal focuses on providing strong assurance that generation IV NESs are the least desirable sources for the diversion or undeclared production of nuclear materials, whereas the PP portion of the goal ensures that generation IV NESs are robust against theft and sabotage. In 2002, the road map of the Generation IV International Forum (GIF) envisioned that the R and D program for PR and PP would have three areas: 1) safeguards and physical protection technology R and D for each GIF system; 2) formulation of PR and PP criteria and metrics; and 3) evaluation of the criteria and metrics. To cover these R and D items, the PR and PP Working Group (PRPPWG) was formed in late 2002 and has since developed a methodology for PR and PP evaluation. In a succession of revisions beginning in 2004, consensus was achieved amongst all participating GIF countries and related organizations (i.e., IAEA and EU), and Revision 6 of the methodology report was approved by GIF for open distribution in 2011. The paper describes in detail the methodology developed by the PRPPWG and discusses its applicability to the sodium-cooled fast reactor (SFR) fuel cycle with pyro processing currently under development in Korea.

Two-dimensional electrophoretic analysis of transformation-sensitive polypeptides during chemically, spontaneously, and oncogene-induced transformation of rat liver epithelial cells

DEFF Research Database (Denmark)

Wirth, P J; Luo, L D; Fujimoto, Y

1992-01-01

; AFB), spontaneously, and oncogene (v-Ha-ras, v-raf, and v-myc/v-raf)-induced transformation of RLE cells. Two-dimensional mapping of [35S]methionine-labeled whole cell lysate, cell-free in vitro translation products and [32P]orthophosphate-labeled polypeptides revealed subsets of polypeptides specific...... for each transformation modality. A search of the RLE protein database indicated the specific subcellular location for the majority of these transformation-sensitive proteins. Significant alterations in the expression of the extracellular matrix protein, fibronectin, as well as tropomyosin......- and intermediate filament-related polypeptides (vimentin, beta-tubulin, the cytokeratins, and actin) were observed among the various transformant cell lines. Immunoprecipitation and Western immunoblot analysis of tropomyosin expression in four individual AFB-, as well as four spontaneously induced, and each...

Pion interferometry and resonances in pp and AA collisions

Energy Technology Data Exchange (ETDEWEB)

Padula, S.S. (UNESP, Inst. de Fisica Teorica, Sao Paulo (Brazil)); Gyulassy, M. (Lawrence Berkeley Lab., Nuclear Science Div., CA (United States))

1992-07-20

We study the sensitivity of pion interferometry in pp and anti pp collisions at ISR energies to the resonance abundance. We show that those data are not compatible with the full resonance fractions predicted by the Lund model. The preliminary S+S and O+Au data at 200 A GeV are, however, not incompatible with the Lund predictions, although their sensitivity to resonances is significantly weaker than in the pp/anti pp case. (orig.).

Pion interferometry and resonances in pp and AA collisions

International Nuclear Information System (INIS)

Padula, S.S.; Gyulassy, M.

1992-01-01

We study the sensitivity of pion interferometry in pp and anti pp collisions at ISR energies to the resonance abundance. We show that those data are not compatible with the full resonance fractions predicted by the Lund model. The preliminary S+S and O+Au data at 200 A GeV are, however, not incompatible with the Lund predictions, although their sensitivity to resonances is significantly weaker than in the pp/anti pp case. (orig.)

Pion interferometry and resonances in pp and AA collisions

International Nuclear Information System (INIS)

Padula, S.S.

1991-01-01

We study the sensitivity of pion interferometry in bar pp and bar pp collisions at ISR energies to the resonance abundance. We show that those data are not compatible with the full resonance fractions predicted by the Lund model. The preliminary S+S and O+Au data at 200 GeV are, however, not incompatible with the Lund predictions, although their sensitivity to resonances is significantly weaker than in the pp/bar pp case

Formation of a [sup(99m)Tc]polypeptide hormone: characterization and chemical quality control by ampholyte displacement radiochromatography

International Nuclear Information System (INIS)

Sundrehagen, E.

1983-01-01

Sup(99m)Tc-complexes with the polypeptide hormone secretin in very low concentration were formed by the concentrated hydrochloric acid/vacuum evaporation/gentisic acid method. The sup(99m)Tc-secretin was characterized by a modified ampholyte radiochromatographic procedure, in addition to thin layer chromatography, gel chromatography and paper electrophoresis. High radiochemical purity and specific radioactivity were obtained. In vivo distribution studies were performed, and the conditions necessary for application of [sup(99m)Tc]polypeptides as scintigraphic agents are discussed. (author)

Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

International Nuclear Information System (INIS)

Inoue-Toyoda, Maki; Kato, Kohsuke; Nagata, Kyosuke; Yoshikawa, Hiroyuki

2015-01-01

Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX

A New in Vitro Anti-Tumor Polypeptide Isolated from Arca inflata

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Jian Xu

2013-12-01

Full Text Available A new in vitro anti-tumor polypeptide, coded as J2-C3, was isolated from Arca inflata Reeve and purified by diethyl-aminoethanol (DEAE-sepharose Fast Flow anion exchange and phenyl sepharose CL-4B hydrophobic chromatography. J2-C3 was identified to be a homogeneous compound by native polyacrylamide gel electrophoresis (Native-PAGE. The purity of J2-C3 was over 99% in reversed phase-high performance liquid chromatography (RP-HPLC. The molecular weight was determined as 20,538.0 Da by electrospray-ionization mass spectrometry (ESI-MS/MS. J2-C3 was rich in Glx (Gln + Glu, Lys, and Asx (Asp + Asn according to amino acid analysis. Four partial amino acid sequences of this peptide were determined as L/ISMEDVEESR, KNGMHSI/LDVNHDGR, AMKI/LI/LNPKKGI/LVPR and AMGAHKPPKGNEL/IGHR via MALDI-TOF/TOF-MS and de novo sequencing. Secondary structural analysis by CD spectroscopy revealed that J2-C3 had the α-helix (45.2%, β-sheet (2.9%, β-turn (26.0% and random coil (25.9%. The anti-tumor effect of J2-C3 against human tumor cells was measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, and the IC50 values of J2-C3 were 65.57, 93.33 and 122.95 µg/mL against A549, HT-29 and HepG2 cell lines, respectively. Therefore, J2-C3 might be developed as a potential anti-tumor agent.

Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding.

Science.gov (United States)

Sandikci, Arzu; Gloge, Felix; Martinez, Michael; Mayer, Matthias P; Wade, Rebecca; Bukau, Bernd; Kramer, Günter

2013-07-01

Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates with ribosomes through a charged loop that is crucial for nascent-chain processing and cell viability. MAP competes with peptide deformylase (PDF), the first enzyme to act on nascent chains, for binding sites at the ribosomal tunnel exit. PDF has extremely fast association and dissociation kinetics, which allows it to frequently sample ribosomes and ensure the processing of nascent chains after their emergence. Premature recruitment of the chaperone trigger factor, or polypeptide folding, negatively affect processing efficiency. Thus, the fast ribosome association kinetics of PDF and MAP are crucial for the temporal separation of nascent-chain processing from later maturation events, including chaperone recruitment and folding.

Effects of thermal ageing on HMS-PP crystallinity

International Nuclear Information System (INIS)

Oliani, Washington L.; Parra, Duclerc F.; Lima, Luis F.C.P.; Lugao, Ademar B.

2009-01-01

The isotactic polypropylene is a linear polymer which exhibits low melt strength. Irradiation of PP under inert atmosphere causes a combination of chain scissioning and long-chain branching, and results in a material with significant enhanced melt strength. This process, which is sometimes termed visbreaking, thus provides improvement of rheological properties. HMS-PP (High Melt Strength Polypropylene) was obtained by the irradiation in atmosphere of acetylene as crosslinker agent. It was employed doses of 12.5 and 20 kGy of gamma radiation. The objective of this study is to investigate the effects of thermal ageing on the crystallinity level and chemical structure of HMS-PP. The thermal stability of the HMS-PP was evaluated after thermal ageing of samples using a stove at temperature of 90 deg C, in presence of air at different periods of time. The samples submitted to the thermal ageing were characterized by: thermogravimetry (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Since the long-term engineering properties of HMS-PP are intrinsically linked with the polymer microstructure, there is significant interest in understanding the effects of ageing, particularly due to prolonged exposure at service temperatures. In thermo-oxidative conditions, the formation of the oxidation products essentially involves a hydrogen abstraction by the peroxyl radicals, leading to hydroperoxides as primary products and chemical degradation in the immediate crack tips. Oxidative degradation on the network of HMS-PP, created by radiation process of PP, was revealed by the analytical results showing the susceptibility of HMS-PP to thermal oxidative degradation. Yellowing of the samples surface and oxidative products of degradation among other evidences were observed. (author)

Roles of polypyrimidine tract binding proteins in major immediate-early gene expression and viral replication of human cytomegalovirus.

Science.gov (United States)

Cosme, Ruth S Cruz; Yamamura, Yasuhiro; Tang, Qiyi

2009-04-01

Human cytomegalovirus (HCMV), a member of the beta subgroup of the family Herpesviridae, causes serious health problems worldwide. HCMV gene expression in host cells is a well-defined sequential process: immediate-early (IE) gene expression, early-gene expression, DNA replication, and late-gene expression. The most abundant IE gene, major IE (MIE) gene pre-mRNA, needs to be spliced before being exported to the cytoplasm for translation. In this study, the regulation of MIE gene splicing was investigated; in so doing, we found that polypyrimidine tract binding proteins (PTBs) strongly repressed MIE gene production in cotransfection assays. In addition, we discovered that the repressive effects of PTB could be rescued by splicing factor U2AF. Taken together, the results suggest that PTBs inhibit MIE gene splicing by competing with U2AF65 for binding to the polypyrimidine tract in pre-mRNA. In intron deletion mutation assays and RNA detection experiments (reverse transcription [RT]-PCR and real-time RT-PCR), we further observed that PTBs target all the introns of the MIE gene, especially intron 2, and affect gene splicing, which was reflected in the variation in the ratio of pre-mRNA to mRNA. Using transfection assays, we demonstrated that PTB knockdown cells induce a higher degree of MIE gene splicing/expression. Consistently, HCMV can produce more viral proteins and viral particles in PTB knockdown cells after infection. We conclude that PTB inhibits HCMV replication by interfering with MIE gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

Directory of Open Access Journals (Sweden)

Lukas P. Feilen

2017-05-01

Full Text Available Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs. The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

Science.gov (United States)

Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Induction of a M/sub r/ 21,000 polypeptide in an Arthrobacter Sp. by dye-sensitized photooxidation

International Nuclear Information System (INIS)

Franzi, J.J.

1985-01-01

Irradiation of aerobic cultures of an Arthrobacter species with near-UV light and oxygen induced synthesis of a cell surface protein, M/sub r/ 21,000 polypeptide. Visible light, oxygen and a sensitizing dye were also effective in induction. Far-UV light, bleomycin and nalidixic acid, all inducers of the recA protein in Escherichia coli, were ineffective inducers of this protein. Furthermore, X-irradiation and radical-generating oxidants failed to induce synthesis of the M/sub r/ 21,000 polypeptide. DNA binding dyes proved to be capable of inducing synthesis of this protein or inhibiting dye-mediated stimulation of synthesis of this protein. For example, dGdC-specific dyes (e.g. methylene blue, neutral red, acridine orange or ethidium bromide) were efficient inducers of the M/sub r/ 21,000 polypeptide. Also methylene blue and neutral red were more efficient inducers than were acridine orange or ethidium bromide, which could be explained by the greater dGdC specificity and, possibly by the greater photoreactivity of methylene blue and neutral red. dAdT-specific dyes such as methyl green or daunomycin effectively inhibited dye-mediated induction. Rose bengal is an anionic dye which does not bind to DNA but does mediate the photooxidation of deoxyguanosine residues in DNA. It is an efficient inducer of the M/sub r/ 21,000 polypeptide. Induction with this dye is nearly eliminated when novobiocin, an inhibitor of DNA gyrase (topoisomerase II) which mediates relaxation, is added in conjunction with rose bengal

Induction of a M/sub r/ 21,000 polypeptide in an Arthrobacter Sp. by dye-sensitized photooxidation

Energy Technology Data Exchange (ETDEWEB)

Franzi, J.J.

1985-01-01

Irradiation of aerobic cultures of an Arthrobacter species with near-UV light and oxygen induced synthesis of a cell surface protein, M/sub r/ 21,000 polypeptide. Visible light, oxygen and a sensitizing dye were also effective in induction. Far-UV light, bleomycin and nalidixic acid, all inducers of the recA protein in Escherichia coli, were ineffective inducers of this protein. Furthermore, X-irradiation and radical-generating oxidants failed to induce synthesis of the M/sub r/ 21,000 polypeptide. DNA binding dyes proved to be capable of inducing synthesis of this protein or inhibiting dye-mediated stimulation of synthesis of this protein. For example, dGdC-specific dyes (e.g. methylene blue, neutral red, acridine orange or ethidium bromide) were efficient inducers of the M/sub r/ 21,000 polypeptide. Also methylene blue and neutral red were more efficient inducers than were acridine orange or ethidium bromide, which could be explained by the greater dGdC specificity and, possibly by the greater photoreactivity of methylene blue and neutral red. dAdT-specific dyes such as methyl green or daunomycin effectively inhibited dye-mediated induction. Rose bengal is an anionic dye which does not bind to DNA but does mediate the photooxidation of deoxyguanosine residues in DNA. It is an efficient inducer of the M/sub r/ 21,000 polypeptide. Induction with this dye is nearly eliminated when novobiocin, an inhibitor of DNA gyrase (topoisomerase II) which mediates relaxation, is added in conjunction with rose bengal.

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

Quantitative assessments of the distinct contributions of polypeptide backbone amides versus sidechain groups to chain expansion via chemical denaturation

Science.gov (United States)

Holehouse, Alex S.; Garai, Kanchan; Lyle, Nicholas; Vitalis, Andreas; Pappu, Rohit V.

2015-01-01

In aqueous solutions with high concentrations of chemical denaturants such as urea and guanidinium chloride (GdmCl) proteins expand to populate heterogeneous conformational ensembles. These denaturing environments are thought to be good solvents for generic protein sequences because properties of conformational distributions align with those of canonical random coils. Previous studies showed that water is a poor solvent for polypeptide backbones and therefore backbones form collapsed globular structures in aqueous solvents. Here, we ask if polypeptide backbones can intrinsically undergo the requisite chain expansion in aqueous solutions with high concentrations of urea and GdmCl. We answer this question using a combination of molecular dynamics simulations and fluorescence correlation spectroscopy. We find that the degree of backbone expansion is minimal in aqueous solutions with high concentrations denaturants. Instead, polypeptide backbones sample conformations that are denaturant-specific mixtures of coils and globules, with a persistent preference for globules. Therefore, typical denaturing environments cannot be classified as good solvents for polypeptide backbones. How then do generic protein sequences expand in denaturing environments? To answer this question, we investigated the effects of sidechains using simulations of two archetypal sequences with amino acid compositions that are mixtures of charged, hydrophobic, and polar groups. We find that sidechains lower the effective concentration of backbone amides in water leading to an intrinsic expansion of polypeptide backbones in the absence of denaturants. Additional dilution of the effective concentration of backbone amides is achieved through preferential interactions with denaturants. These effects lead to conformational statistics in denaturing environments that are congruent with those of canonical random coils. Our results highlight the role of sidechain-mediated interactions as determinants of the

Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects

DEFF Research Database (Denmark)

Jacobsen, Siv Hesse; Olesen, S C; Dirksen, C

2012-01-01

measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin......, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated...... postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after...

Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

Science.gov (United States)

Bácsi, A; Aranyosi, J; Beck, Z; Ebbesen, P; Andirkó, I; Szabó, J; Lampé, L; Kiss, J; Gergely, L; Tóth, F D

1999-10-01

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.

Biomimetic Synthesis of Gelatin Polypeptide-Assisted Noble-Metal Nanoparticles and Their Interaction Study

Science.gov (United States)

Liu, Ying; Liu, Xiaoheng; Wang, Xin

2011-12-01

Herein, the generation of gold, silver, and silver-gold (Ag-Au) bimetallic nanoparticles was carried out in collagen (gelatin) solution. It first showed that the major ingredient in gelatin polypeptide, glutamic acid, acted as reducing agent to biomimetically synthesize noble metal nanoparticles at 80°C. The size of nanoparticles can be controlled not only by the mass ratio of gelatin to gold ion but also by pH of gelatin solution. Interaction between noble-metal nanoparticles and polypeptide has been investigated by TEM, UV-visible, fluorescence spectroscopy, and HNMR. This study testified that the degradation of gelatin protein could not alter the morphology of nanoparticles, but it made nanoparticles aggregated clusters array (opposing three-dimensional α-helix folding structure) into isolated nanoparticles stabilized by gelatin residues. This is a promising merit of gelatin to apply in the synthesis of nanoparticles. Therefore, gelatin protein is an excellent template for biomimetic synthesis of noble metal/bimetallic nanoparticle growth to form nanometer-sized device.

Effect of Sequence Blockiness on the Morphologies of Surface-grafted Elastin-like Polypeptides

Science.gov (United States)

Albert, Julie; Sintavanon, Kornkanok; Mays, Robin; MacEwan, Sarah; Chilkoti, Ashutosh; Genzer, Jan

2014-03-01

The inter- and intra- molecular interactions among monomeric units of copolymers and polypeptides depend strongly on monomer sequence distribution and dictate the phase behavior of these species both in solution and on surfaces. To study the relationship between sequence and phase behavior, we have designed a series of elastin-like polypeptides (ELPs) with controlled monomer sequences that mimic copolymers with various co-monomer sequence distributions and attached them covalently to silicon substrates from buffer solutions at temperatures below and above the bulk ELPs' lower critical solution temperatures (LCSTs). The dependence of ELP grafting density on solution temperature was examined by ellipsometry and the resultant surface morphologies were examined in air and under water with atomic force microscopy. Depositions performed above the LCST resulted in higher grafting densities and greater surface roughness of ELPs relative to depositions carried out below the LCST. In addition, we are using gradient substrates to examine the effect of ELP grafting density on temperature responsiveness.

Serological Reactivity and Identification of Immunoglobulin E-Binding Polypeptides of Ganoderma applanatum Crude Spore Cytoplasmic Extract in Puerto Rican Subjects.

Science.gov (United States)

Vilá-Héreter, Frances; Rivera-Mariani, Félix E; Bolaños-Rosero, Benjamín

2017-01-01

The allergenic potential of Ganoderma applanatum basidiospores has been demonstrated previously in Puerto Rico. However, basidiomycete allergens are not available for inclusion in allergy diagnostic panels. Therefore, we sought to confirm allergic sensitization to G. applanatum crude spore cytoplasmic extract through reactivity in serological assays and detection of immunoglobulin E (IgE)-binding polypeptides. Via an indirect ELISA, serological reactivity was compared between groups of individuals with different allergic profiles. Group 1 (n = 51) consisted of individuals with sIgE to the allergens included in the diagnostic panels; group 2 (n = 14) comprised individuals with no sIgE to the allergens tested; and group 3 (n = 22) included individuals with no allergic history. To visualize IgE-binding polypeptides, group 1 sera were examined via Western blotting (WB). Polypeptide bands with the highest reactivity were analyzed by mass spectrometry (MS) for putative identification. The serological reactivity of group 1 was significantly higher than that of group 3 in an indirect ELISA (p = 0.03). Sixty-five percent of group 1 individuals showed reactivity to polypeptide bands in WB. Bands of 81 and 56 kDa had the highest reactivity proportions among the reactive sera, followed by a 45-kDa band. MS analysis of these 3 polypeptides suggests that they are basidiomycete-derived enzymes with aconitate hydratase, catalase, and enolase functions. G. applanatum spores have allergenic components recognized by Puerto Rican individuals, which could eventually be considered as markers in cases of fungal allergy and be included in diagnostic allergen panels in Puerto Rico and tropical regions. © 2017 S. Karger AG, Basel.

Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin

DEFF Research Database (Denmark)

Wang, Yin-Qiu; Qian, Ya-Ping; Yang, Su

2005-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a...

Phase separation of DMDBS from iPP, and controlled crystalline orientation

Science.gov (United States)

Sreenivas, K.; Kumaraswamy, Guruswamy; Basargekar, R. S.

2012-02-01

We report an unexpected dependence of DMDBS phase separation temperature on the molecular weight of the matrix isotactic polypropylene (iPP). DMDBS crystallizes out at lower temperatures for iPP with decreasing molecular weight (and correspondingly lower tacticity). This molecular weight dependence is unique to iPP, and is not observed for either syndiotactic PP or for random ethylene-PP copolymers. We show that thermodynamic Flory-type arguments are unable to rationalize the observed results. We also results on extrusion film casting of iPP containing DMDBS and show that flow-alignment of DMDBS networks template the orientation of PP crystals. The modulus and yield strength increase on addition of DMDBS, relative to the neat iPP. Tensile modulus and yield stress of drawn films increase with the degree of orientation, and we are able to achieve a substantial increase even at relatively low draw ratios.

Abaca fibre reinforced PP composites and comparison with jute and flax fibre PP composites

Directory of Open Access Journals (Sweden)

2007-11-01

Full Text Available Abaca fibre reinforced PP composites were fabricated with different fibre loadings (20, 30, 40, 50wt% and in some cases 35 and 45 wt%. Flax and jute fibre reinforced PP composites were also fabricated with 30 wt% fibre loading. The mechanical properties, odour emission and structure properties were investigated for those composites. Tensile, flexural and Charpy impact strengths were found to increase for fibre loadings up to 40 wt% and then decreased. Falling weight impact tests were also carried out and the same tendency was observed. Owing to the addition of coupling agent (maleated polypropylene -MAH-PP, the tensile, flexural and falling weight impact properties were found to increase in between 30 to 80% for different fibre loadings. When comparing jute and flax fibre composites with abaca fibre composites, jute fibre composites provided best tensile properties but abaca fibre polypropylene composites were shown to provide best notch Charpy and falling weight impact properties. Odours released by flax fibre composites were smaller than jute and abaca fibre composites.

The PP1 binding code: a molecular-lego strategy that governs specificity.

Science.gov (United States)

Heroes, Ewald; Lesage, Bart; Görnemann, Janina; Beullens, Monique; Van Meervelt, Luc; Bollen, Mathieu

2013-01-01

Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates. PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells. The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1. Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites. This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties. The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic. PIPs control associated PP1 by interference with substrate recruitment or access to the active site. In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1. The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo. © 2012 The Authors Journal compilation © 2012 FEBS.

Membrane polypeptide in rabbit erythrocytes associated with the inhibition of L-lactate transport by a synthetic anhydride of lactic acid

International Nuclear Information System (INIS)

Donovan, J.A.; Jennings, M.L.

1985-01-01

The synthetic lactyl anhydride isobutylcarbonyl lactyl anhydride (iBCLA), a selective and potent inhibitor of L-(+)-lactate transport in rabbit erythrocytes, reduces the chemical labeling of a 40-50-kdalton polypeptide by tritiated 4,4'-diisothiocyanato-2,2'-dihydrostilbenedisulfonate ([ 3 H]H 2 DIDS). iBCLA does so in a dose-dependent manner at concentrations that strongly inhibit lactate-lactate exchange but not chloride-phosphate exchange. These labeling experiments and inhibition reversal studies using iBCLA, p-(chloro-mercuri)benzenesulfonic acid (pCMBS), and dithiothreitol (DDT) suggest that iBCLA does not act at sulfhydryl groups but at or near an amino group that is near a disulfide linkage in the polypeptide which catalyzes lactate transport. These experiments support the association between specific monocarboxylate transport and a 40-50-kdalton membrane-bound polypeptide of the rabbit erythrocyte

Characterization of cell surface polypeptides of unfertilized, fertilized, and protease-treated zona-free mouse eggs

International Nuclear Information System (INIS)

Boldt, J.; Gunter, L.E.; Howe, A.M.

1989-01-01

The polypeptide composition of unfertilized, fertilized, and protease-treated zona-free mouse eggs was evaluated in this study. Zona-free eggs were radioiodinated by an Iodogen-catalyzed reaction. Light microscopic autoradiography of egg sections revealed that labeling was restricted to the cell surface. Labeled eggs were solubilized, and cell surface polypeptides were identified by one-dimensional SDS polyacrylamide gel electrophoresis and autoradiography. The unfertilized egg demonstrated 8-10 peptides that incorporated 125 I, with major bands observed at approximately 145-150, 94, and 23 kilodaltons (kD). Zona-free eggs fertilized in vitro and then radiolabeled demonstrated several new bands in comparison to unfertilized eggs, with a major band appearing at approximately 36 kD. Treatment of radiolabeled unfertilized eggs with either trypsin or chymotrypsin (1 mg/ml for 5-20 min) caused enzyme-specific modifications in labeled polypeptides. Trypsin (T) treatment resulted in time-dependant modification of the three major peptides at 145-150, 94, and 23 kD. Chymotrypsin (CT) treatment, in contrast, was associated with loss or modification of the 94 kD band, with no apparent effect on either the 145-150 or 23 kD band. Taken together with previous data indicating that T or CT egg treatment interferes with sperm-egg attachment and fusion, these results suggest a possible role for the 94 kD protein in sperm-egg interaction

Effect of tocopherols incorporation on physical properties of LDPE,PP and blend film of LDPE/PP

Directory of Open Access Journals (Sweden)

ZHU Xuntao

2014-12-01

Full Text Available The objectives of this study were to investigate the effects of added tocopherols and blending of different polymers on the film physical properties.Tocopherols (3 000 mg/kg were incorporate into low density polyethylene (LDPE,polypropylene (PP and a blend film of LDPE/PP (50/50 by extrusion process.Then films were evaluated to determine tocopherol recovery and physical properties.Results showed that extrusion did not significantly change film thermal properties (Tm,Tc and Tg as compared with synthetic polymer resin pellet (raw material.LDPE and PP did not seem to react with each other to form new polymers under the current extrusion conditions.Addition of tocopherol significantly changed film mechanical properties compared with control.The above results and other data seemed to support that polymer blending is a feasible approach for producing tocopherol containing packaging films.

Personalized Therapy Against Preeclampsia by Replenishing Placental Protein 13 (PP13 Targeted to Patients With Impaired PP13 Molecule or Function

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Hamutal Meiri

Full Text Available Hypertensive disorders affect about one third of all people aged 20 and above, and are treated with anti-hypertensive drugs. Preeclampsia (PE is one form of such disorders that only develops during pregnancy. It affects ten million pregnant women globally and additionally causes fetal loss and major newborn disabilities. The syndrome's origin is multifactorial, and anti-hypertensive drugs are ineffective in treating it. Biomarkers are helpful for predict its development. Generic drugs, such as low dose aspirin, were proven effective in preventing preterm PE. However, it does not cure the majority of cases and many studies are underway for fighting PE with extended use of additional generic drugs, or through new drug development programs.This review focuses on placental protein 13 (PP13. This protein is only expressed in the placenta. Impaired PP13 DNA structure and/or its reduced mRNA expression leads to lower blood PP13 level that predict a higher risk of developing PE. Two polymorphic PP13 variants have been identified: (1 The promoter PP13 variant with an “A/A” genotype in the -98 position (versus “A/C” or “C/C”. Having the “A/A” genotype is coupled to lower PP13 expression, mainly during placental syncytiotrophoblast differentiation and, if associated with obesity and history of previous preeclampsia, it accurately predicts higher risk for developing the disorder. (2 A thymidine deletion at position 221 causes a frame shift in the open reading frame, and the formation of an early stop codon resulting in the formation of DelT221, a truncated variant of PP13. In pregnant rodents, both short- and long- term replenishment of PP13 causes reversible hypotension and vasodilation of uterine vessels. Long-term exposure is also accompanied by the development of larger placentas and newborns. Also, only w/t PP13 is capable of inducing leukocyte apoptosis, providing maternal immune tolerance to pregnancy.Based on published data, we

Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors

DEFF Research Database (Denmark)

Hautmann, Matthias; Friis, Ulla G; Desch, Michael

2007-01-01

Besides of its functional role in the nervous system, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of cardiovascular function. Therefore, PACAP is a potent vasodilator in several vascular beds, including the renal vasculature. Because...

Multiplicity correlations in the forward and backward hemispheres in the center of mass in bar pp and pp interactions at 32 GeV/c

International Nuclear Information System (INIS)

Bravina, L.V.; Amelin, N.S.; Bogolyubskii, M.Y.; Bumazhnov, V.A.; Vinitskii, A.A.; Ermolov, P.F.; Zhautykov, B.O.; Zabrodin, E.E.; Kiryunin, A.E.; Klochkov, M.A.; Kotova, A.I.; Kruglov, N.A.; Levitskii, M.S.; Lukina, O.Y.; Minaenko, A.A.; Moiseev, A.M.; Murzin, V.S.; Proskuryakov, A.S.; Rizatdinova, F.K.; Sarycheva, L.I.; Smirnova, L.N.; Starchenko, E.A.; Ukhanov, M.N.; Chekulaev, S.V.

1989-01-01

A rise in the average multiplicity of particles in one hemisphere in the c.m.s. of bar pp and pp interactions with energy (s) 1/2 =7.86 GeV is observed with increase of the number of particles in the other hemisphere. The correlation parameter reaches b=0.19±0.01 and 0.10±0.02 in inelastic bar pp and pp interactions respectively. The observed correlations are reproduced in the quark-gluon string model

Exclusive channels in bar pp annihilation at rest

International Nuclear Information System (INIS)

Bluem, P.

1992-01-01

Exclusive channels in bar pp annihilation at rest provide a powerful tool for studying the meson spectrum below the bar pp threshold. The mesons can be classified in SU(3) multiplets according to their quantum numbers. The states which do not fit into this classification are candidates for new forms of hadronic matter like glueballs, hybrids, and multi-quark states. Recent results on the search for exotic states in exclusive channels of bar pp annihilation at rest are discussed. No less important is the study of the annihilation mechanism. In particular, high-statistic measurements of bar pp annihilation at rest into two-meson final states are an excellent tool for studying quark dynamics. Examples of two-body reactions are presented. 24 refs., 9 figs., 3 tabs

Texturing of polypropylene (PP) with nanosecond lasers

Science.gov (United States)

Riveiro, A.; Soto, R.; del Val, J.; Comesaña, R.; Boutinguiza, M.; Quintero, F.; Lusquiños, F.; Pou, J.

2016-06-01

Polypropylene (PP) is a biocompatible and biostable polymer, showing good mechanical properties that has been recently introduced in the biomedical field for bone repairing applications; however, its poor surface properties due to its low surface energy limit their use in biomedical applications. In this work, we have studied the topographical modification of polypropylene (PP) laser textured with Nd:YVO4 nanosecond lasers emitting at λ = 1064 nm, 532 nm, and 355 nm. First, optical response of this material under these laser wavelengths was determined. The application of an absorbing coating was also studied. The influence of the laser processing parameters on the surface modification of PP was investigated by means of statistically designed experiments. Processing maps to tailor the roughness, and wettability, the main parameters affecting cell adhesion characteristics of implants, were also determined. Microhardness measurements were performed to discern the impact of laser treatment on the final mechanical properties of PP.

Core drilling of hydco drillholes ONK-PP262 and ONK-PP274 in ONKALO at Olkiluoto 2010

Energy Technology Data Exchange (ETDEWEB)

Toropainen, V. [Suomen Malmi Oy, Espoo (Finland)

2011-10-15

Suomen Malmi Oy (Smoy) core drilled two drillholes for HYDCO-program in ONKALO at Eurajoki, Olkiluoto in 2010. The drillhole ONK-PP262 was drilled in May 2010 and the drillhole ONK-PP274 in December 2010. The lengths of the drillholes are 25.02 and 23.88 m respectively. The drillholes are 75.7 mm by diameter. The drillholes were drilled in the investigation niche 4 at the access tunnel chainage 3747. The hydraulic DE 130 drilling rig was used. The drilling water was taken from the ONKALO drilling water pipeline and premixed sodium fluorescein was used as a label agent in the drilling water. The drillholes were measured with EMS deviation survey tool. In addition to drilling the drillcores were logged and reported by geologist. Geological logging included the following parameters: lithology, foliation, fracture parameters, fractured zones, core loss, weathering, fracture frequency, RQD and rock quality. The main rock types in the drillholes are veined gneiss and pegmatitic granite. The average fracture frequencies in both drill cores are 1.4 pcs/m. The average RQD values in the drillcores are 97.2 % (ONK-PP262) and 98.6 % (ONK-PP274). (orig.)

Core drilling of hydco drillholes ONK-PP262 and ONK-PP274 in ONKALO at Olkiluoto 2010

International Nuclear Information System (INIS)

Toropainen, V.

2011-10-01

Suomen Malmi Oy (Smoy) core drilled two drillholes for HYDCO-program in ONKALO at Eurajoki, Olkiluoto in 2010. The drillhole ONK-PP262 was drilled in May 2010 and the drillhole ONK-PP274 in December 2010. The lengths of the drillholes are 25.02 and 23.88 m respectively. The drillholes are 75.7 mm by diameter. The drillholes were drilled in the investigation niche 4 at the access tunnel chainage 3747. The hydraulic DE 130 drilling rig was used. The drilling water was taken from the ONKALO drilling water pipeline and premixed sodium fluorescein was used as a label agent in the drilling water. The drillholes were measured with EMS deviation survey tool. In addition to drilling the drillcores were logged and reported by geologist. Geological logging included the following parameters: lithology, foliation, fracture parameters, fractured zones, core loss, weathering, fracture frequency, RQD and rock quality. The main rock types in the drillholes are veined gneiss and pegmatitic granite. The average fracture frequencies in both drill cores are 1.4 pcs/m. The average RQD values in the drillcores are 97.2 % (ONK-PP262) and 98.6 % (ONK-PP274). (orig.)

Preparation of Photocrosslinked Fish Elastin Polypeptide/Microfibrillated Cellulose Composite Gels with Elastic Properties for Biomaterial Applications

Directory of Open Access Journals (Sweden)

Shinya Yano

2015-01-01

Full Text Available Photocrosslinked hydrogels reinforced by microfibrillated cellulose (MFC were prepared from a methacrylate-functionalized fish elastin polypeptide and MFC dispersed in dimethylsulfoxide (DMSO. First, a water-soluble elastin peptide with a molecular weight of ca. 500 g/mol from the fish bulbus arteriosus was polymerized by N,N′-dicyclohexylcarbodiimide (DCC, a condensation reagent, and then modified with 2-isocyanatoethyl methacrylate (MOI to yield a photocrosslinkable fish elastin polypeptide. The product was dissolved in DMSO and irradiated with UV light in the presence of a radical photoinitiator. We obtained hydrogels successfully by substitution of DMSO with water. The composite gel with MFC was prepared by UV irradiation of the photocrosslinkable elastin polypeptide mixed with dispersed MFC in DMSO, followed by substitution of DMSO with water. The tensile test of the composite gels revealed that the addition of MFC improved the tensile properties, and the shape of the stress–strain curve of the composite gel became more similar to the typical shape of an elastic material with an increase of MFC content. The rheology measurement showed that the elastic modulus of the composite gel increased with an increase of MFC content. The cell proliferation test on the composite gel showed no toxicity.

Wall-associated kinase-like polypeptide mediates nutritional status perception and response

Science.gov (United States)

Yang, Zhenbiao; Karr, Stephen

2014-02-11

The disclosure relates to methods for modulating plant growth and organogenesis using dominant-negative receptor-like kinases. The disclosure further provides a method for increasing plant yield relative to corresponding wild type plants comprising modulating the expression in a plant of a nucleic acid encoding a Wall-Associated Kinase-like 14 polypeptide or a homolog thereof, and selecting for plants having increased yield or growth on a nutrient deficient substrate.

Sustained Release of Antibiotics from Injectable and Thermally Responsive Polypeptide Depots

OpenAIRE

Adams, Samuel B.; Shamji, Mohammed F.; Nettles, Dana L.; Hwang, Priscilla; Setton, Lori A.

2009-01-01

Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to u...

Evidence for CP violation in B+ → ppK+ decays.

Science.gov (United States)

Aaij, R; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, Rf; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Giani', S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lu, H; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Reichert, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

2014-10-03

Three-body B+ → ppK+ and B(+) → ppπ(+) decays are studied using a data sample corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb experiment in proton-proton collisions at center-of-mass energies of 7 and 8 TeV. Evidence of CP violation in the B(+) → ppK(+) decay is found in regions of the phase space, representing the first measurement of this kind for a final state containing baryons. Measurements of the forward-backward asymmetry of the light meson in the pp rest frame yield A(FB)(ppK(+),m(pp)m(pp) <2.85 GeV/c(2)) = -0.409 ± 0.033 (stat) ± 0.006 (syst). In addition, the branching fraction of the decay B(+) → Λ(1520)p is measured to be B(B(+) → Λ(1520)p) = (3.15 ± 0.48 (stat) ± 0.07 (syst) ± 0.26 (BF)) × 10(-7), where BF denotes the uncertainty on secondary branching fractions.

Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response

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Jun Chen

2017-12-01

Full Text Available Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β, which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI. The expression and secretion of Cyclophilin A (sCyPA, as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA.

Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor

DEFF Research Database (Denmark)

Ugleholdt, Randi; Poulsen, Marie-Louise H; Holst, Peter J

2006-01-01

The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest. Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intesti......The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest. Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage....../3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells....

76 FR 69743 - The Development and Evaluation of Human Cytomegalovirus Vaccines; Public Workshop

Science.gov (United States)

2011-11-09

... of knowledge about HCMV biology and epidemiology and on vaccine development strategies. Topics for discussion will include: (1) HCMV epidemiology and diagnosis, (2) HCMV immunology and virology, (3...

Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

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Arcangeletti, Maria-Cristina, E-mail: mariacristina.arcangeletti@unipr.it [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy); Germini, Diego; Rodighiero, Isabella [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy); Mirandola, Prisco [Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma (Italy); De Conto, Flora; Medici, Maria-Cristina [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy); Gatti, Rita [Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma (Italy); Chezzi, Carlo; Calderaro, Adriana [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy)

2013-05-25

Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promoting cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle. - Highlights: ► We studied HCMV infection impact on THP-1 macrophage cell cycle. ► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection. ► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle. ► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication. ► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.

Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection

Science.gov (United States)

Andrew Mackay, J.; Chen, Mingnan; McDaniel, Jonathan R.; Liu, Wenge; Simnick, Andrew J.; Chilkoti, Ashutosh

2009-12-01

New strategies to self-assemble biocompatible materials into nanoscale, drug-loaded packages with improved therapeutic efficacy are needed for nanomedicine. To address this need, we developed artificial recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into sub-100-nm-sized, near-monodisperse nanoparticles on conjugation of diverse hydrophobic molecules, including chemotherapeutics. These CPs consist of a biodegradable polypeptide that is attached to a short Cys-rich segment. Covalent modification of the Cys residues with a structurally diverse set of hydrophobic small molecules, including chemotherapeutics, leads to spontaneous formation of nanoparticles over a range of CP compositions and molecular weights. When used to deliver chemotherapeutics to a murine cancer model, CP nanoparticles have a fourfold higher maximum tolerated dose than free drug, and induce nearly complete tumour regression after a single dose. This simple strategy can promote co-assembly of drugs, imaging agents and targeting moieties into multifunctional nanomedicines.

Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy.

Science.gov (United States)

Ott, Wolfgang; Jobst, Markus A; Bauer, Magnus S; Durner, Ellis; Milles, Lukas F; Nash, Michael A; Gaub, Hermann E

2017-06-27

Single-molecule force spectroscopy (SMFS) is by now well established as a standard technique in biophysics and mechanobiology. In recent years, the technique has benefitted greatly from new approaches to bioconjugation of proteins to surfaces. Indeed, optimized immobilization strategies for biomolecules and refined purification schemes are being steadily adapted and improved, which in turn has enhanced data quality. In many previously reported SMFS studies, poly(ethylene glycol) (PEG) was used to anchor molecules of interest to surfaces and/or cantilever tips. The limitation, however, is that PEG exhibits a well-known trans-trans-gauche to all-trans transition, which results in marked deviation from standard polymer elasticity models such as the worm-like chain, particularly at elevated forces. As a result, the assignment of unfolding events to protein domains based on their corresponding amino acid chain lengths is significantly obscured. Here, we provide a solution to this problem by implementing unstructured elastin-like polypeptides as linkers to replace PEG. We investigate the suitability of tailored elastin-like polypeptides linkers and perform direct comparisons to PEG, focusing on attributes that are critical for single-molecule force experiments such as linker length, monodispersity, and bioorthogonal conjugation tags. Our results demonstrate that by avoiding the ambiguous elastic response of mixed PEG/peptide systems and instead building the molecular mechanical systems with only a single bond type with uniform elastic properties, we improve data quality and facilitate data analysis and interpretation in force spectroscopy experiments. The use of all-peptide linkers allows alternative approaches for precisely defining elastic properties of proteins linked to surfaces.

Invariant-mass distributions for the pp{yields}pp{eta} reaction at Q=10 MeV

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Moskal, P.; Czerwinski, E.; Klaja, J.; Klaja, P.; Krzemien, W. [Jagellonian University, Institute of Physics, Cracow (Poland); Research Center Juelich, Nuclear Physics Institute, Juelich (Germany); Czyzykiewicz, R. [Jagellonian University, Institute of Physics, Cracow (Poland); University of Silesia, Institute of Physics, Katowice (Poland); Gil, D.; Jarczyk, L.; Kamys, B.; Silarski, M.; Smyrski, J.; Zdebik, J.; Zielinski, M.J. [Jagellonian University, Institute of Physics, Cracow (Poland); Grzonka, D.; Oelert, W.; Ritman, J.; Sefzick, T.; Wuestner, P. [Research Center Juelich, Nuclear Physics Institute, Juelich (Germany); Khoukaz, A.; Taeschner, A.; Zipper, W. [Westfaelische Wilhelms-Universitaet, IKP, Muenster (Germany); Siemaszko, M. [University of Silesia, Institute of Physics, Katowice (Poland); Wolke, M. [SE-751 05 Uppsala University, Department of Physics and Astronomy, Uppsala (Sweden)

2010-02-15

Proton-proton and proton-{eta} invariant-mass distributions and the total cross-section for the pp{yields}pp{eta} reaction have been determined near the threshold at an excess energy of Q=10 MeV. The experiment has been conducted using the COSY-11 detector setup and the cooler synchrotron COSY. The determined invariant-mass spectra reveal significant enhancements in the region of low proton-proton relative momenta, similarly as observed previously at higher excess energies of Q=15.5 MeV and Q=40 MeV. (orig.)

Verwendung von Polypropylen/Polyglactin 910- (PP910- und Polypropylen/Polyglecapron 25 (PP25- Netzen bei Beckenbodenprolaps - eine retrospektive Analyse

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Schwegler Ch

2009-01-01

Full Text Available Die Entwicklung von Polypropylen- Implantaten zur Behandlung von Bauchwandhernien stellt einen Meilenstein in der Geschichte der Chirurgie dar. Mit einigen Jahren Verzug folgten die Urogynäkologen den Chirurgen und begannen, Polypropylen-Netze zur Behebung von Beckenbodenvorfällen einzusetzen. PP910-Netze (Vypro II®, Ethicon und PP25-Netze (Ultrapro®, Ethicon werden seit Langem mit gutem Erfolg bei Hernien-Operationen eingesetzt. Das Ziel dieser Studie war herauszufinden, inwieweit sich diese beiden Netze auch für den Einsatz beim Beckenbodenprolaps eignen. Hierzu wurden Fragebögen an Patientinnen versandt, denen in den Jahren 2003 und 2004 diese Netze im Beckenboden implantiert wurden. Die Hauptfragestellungen waren hierbei, inwiefern sich die Symptome des Vorfalles nach der Behandlung verändert hatten und welche Komplikationen nach der Operation aufgetreten waren. Beide Gruppen zeigten nach dem Netzeinsatz deutliche Verbesserungen der Symptomatik bei einer geringen Komplikationsquote. Beim Einsatz von PP910 zeigten sich in 6 % der Fälle Komplikationen, die auf die Implantation des Netzes zurückgeführt werden konnten. Beim Einsatz von PP25 zeigten sogar nur 1,5 % der operierten Frauen netzbedingte Komplikationen. Somit hat sich gezeigt, dass beide Netze gut für die Verwendung im Beckenboden geeignet sind. Vergleicht man die beiden Netze mit anderen Produkten, die derzeit als Implantate im Beckenboden genutzt werden, so zeigt sich ein sehr positives Ergebnis mit signifikant weniger postoperativen Komplikationen unter der Verwendung von PP25-Netzen. Im Rahmen dieser Analyse konnte festgestellt werden, dass PP25 ein sehr sicheres Netz mit ausgesprochen guten Ergebnissen für die Therapie des Beckenbodenprolaps ist.

N-terminal and C-terminal heparin-binding domain polypeptides derived from fibronectin reduce adhesion and invasion of liver cancer cells

International Nuclear Information System (INIS)

Tang, Nan-Hong; Chen, Yan-Lin; Wang, Xiao-Qian; Li, Xiu-Jin; Wu, Yong; Zou, Qi-Lian; Chen, Yuan-Zhong

2010-01-01

Fibronectin (FN) is known to be a large multifunction glycoprotein with binding sites for many substances, including N-terminal and C-terminal heparin-binding domains. We investigated the effects of highly purified rhFNHN29 and rhFNHC36 polypeptides originally cloned from the two heparin-binding domains on the adhesion and invasion of highly metastatic human hepatocellular carcinoma cells (MHCC97H) and analyzed the underlying mechanism involved. The MHCC97H cells that adhered to FN in the presence of various concentrations of rhFNHN29 and rhFNHC36 polypeptides were stained with crystal violet and measured, and the effects of rhFNHN29 and rhFNHC36 on the invasion of the MHCC97H cells were then detected using the Matrigel invasion assay as well as a lung-metastasis mouse model. The expression level of integrins and focal adhesion kinase (FAK) phosphotyrosyl protein was examined by Western blot, and the activity of matrix metalloproteinases (MMPs) and activator protein 1 (AP-1) was analyzed by gelatin zymography and the electrophoretic mobility band-shift assay (EMSA), respectively. Both of the polypeptides rhFNHN29 and rhFNHC36 inhibited adhesion and invasion of MHCC97H cells; however, rhFNHC36 exhibited inhibition at a lower dose than rhFNHN29. These inhibitory effects were mediated by integrin αvβ3 and reversed by a protein tyrosine phosphatase inhibitor. Polypeptides rhFNHN29 and rhFNHC36 abrogated the tyrosine phosphorylation of focal adhesion kinase (p-FAK) and activation of activator protein 1 (AP-1), resulting in the decrease of integrin αv, β3 and β1 expression as well as the reduction of MMP-9 activity. Polypeptides rhFNHN29 and rhFNHC36 could potentially be applicable to human liver cancer as anti-adhesive and anti-invasive agents

A role for pancreatic polypeptide in the regulation of gastric emptying and short-term metabolic control

DEFF Research Database (Denmark)

Schmidt, P T; Näslund, E; Grybäck, P

2005-01-01

of the solid meal. The change in hunger rating, satiety, desire to eat after the meal, or prospective consumption was not affected. The postprandial rise in plasma glucose was prolonged by PP. The postprandial rise in insulin was also delayed by PP. PP had no significant effect on the emptying of water...... synthetic human PP to study gastric emptying rates of a solid meal and postprandial hormone secretion and glucose disposal as well as the gastric emptying rate of water. DESIGN: This was a single-blind study. SETTING: The study was performed at a university hospital. PARTICIPANTS: Fourteen healthy adult...... subjects were studied. INTERVENTIONS: Infusion of saline or PP at 0.75 or 2.25 pmol/kg.min was given to eight subjects (gastric emptying of solid food), and infusion of saline or PP at 2.25 pmol/kg.min was given to six subjects (gastric emptying of water). MAIN OUTCOME MEASURES: The main outcome measures...

The Human Cytomegalovirus Strain DB Activates Oncogenic Pathways in Mammary Epithelial Cells

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Amit Kumar

2018-04-01

Full Text Available Background: Human cytomegalovirus (HCMV establishes a persistent life-long infection and increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. Breast milk is an important route of HCMV transmission in humans and we hypothesized that mammary epithelial cells could be one of the main cellular targets of HCMV infection. Methods: The infectivity of primary human mammary epithelial cells (HMECs was assessed following infection with the HCMV-DB strain, a clinical isolate with a marked macrophage-tropism. The impact of HCMV-DB infection on expression of p53 and retinoblastoma proteins, telomerase activity and oncogenic pathways (c-Myc, Akt, Ras, STAT3 was studied. Finally the transformation of HCMV-DB infected HMECs was evaluated using soft agar assay. CTH cells (CMV Transformed HMECs were detected in prolonged cultures of infected HMECs. Tumor formation was observed in NOD/SCID Gamma (NSG mice injected with CTH cells. Detection of long non coding RNA4.9 (lncRNA4.9 gene was assessed in CTH cells, tumors isolated from xenografted NSG mice and biopsies of patients with breast cancer using qualitative and quantitative PCR. Results: We found that HCMV, especially a clinical strain named HCMV-DB, infects HMECs in vitro. The clinical strain HCMV-DB replicates productively in HMECs as evidenced by detection of early and late viral transcripts and proteins. Following infection of HMECs with HCMV-DB, we observed the inactivation of retinoblastoma and p53 proteins, the activation of telomerase activity, the activation of the proto-oncogenes c-Myc and Ras, the activation of Akt and STAT3, and the upregulation of cyclin D1 and Ki67 antigen. Colony formation was observed in soft agar seeded with HCMV-DB-infected HMECs. Prolonged culture of infected HMECs resulted in the development of clusters of spheroid cells that we called CTH cells (CMV Transformed HMECs. CTH cells when injected in NOD/SCID Gamma (NSG mice

Measurement of the sum of WW and WZ production with W+dijet events in pp collisions at $\\sqrt{s} = 7\\ \\mbox{TeV}$

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Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Aguilo, E.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hammer, J.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Pernicka, M.; Rahbaran, B.; Rohringer, C.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Waltenberger, W.; Walzel, G.; Wulz, C. -E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Luyckx, S.; Mucibello, L.; Ochesanu, S.; Roland, B.; Rougny, R.; Selvaggi, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D’Hondt, J.; Gonzalez Suarez, R.; Kalogeropoulos, A.; Maes, M.; Olbrechts, A.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Clerbaux, B.; De Lentdecker, G.; Dero, V.; Gay, A. P. R.; Hreus, T.; Léonard, A.; Marage, P. E.; Mohammadi, A.; Reis, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Adler, V.; Beernaert, K.; Cimmino, A.; Costantini, S.; Garcia, G.; Grunewald, M.; Klein, B.; Lellouch, J.; Marinov, A.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Walsh, S.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Bruno, G.; Castello, R.; Ceard, L.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Lemaitre, V.; Liao, J.; Militaru, O.; Nuttens, C.; Pagano, D.; Pin, A.; Piotrzkowski, K.; Schul, N.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Alves, G. A.; Correa Martins Junior, M.; Martins, T.; Pol, M. E.; Souza, M. H. G.; Aldá Júnior, W. L.; Carvalho, W.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Malek, M.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Soares Jorge, L.; Sznajder, A.; Vilela Pereira, A.; Anjos, T. S.; Bernardes, C. A.; Dias, F. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Lagana, C.; Marinho, F.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Genchev, V.; Iaydjiev, P.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Trayanov, R.; Vutova, M.; Dimitrov, A.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Jiang, C. H.; Liang, D.; Liang, S.; Meng, X.; Tao, J.; Wang, J.; Wang, X.; Wang, Z.; Xiao, H.; Xu, M.; Zang, J.; Zhang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Guo, Y.; Li, W.; Liu, S.; Mao, Y.; Qian, S. J.; Teng, H.; Wang, D.; Zhang, L.; Zou, W.; Avila, C.; Gomez, J. P.; Gomez Moreno, B.; Osorio Oliveros, A. F.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Plestina, R.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Duric, S.; Kadija, K.; Luetic, J.; Mekterovic, D.; Morovic, S.; Attikis, A.; Galanti, M.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Finger, M.; Finger, M.; Assran, Y.; Elgammal, S.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Müntel, M.; Raidal, M.; Rebane, L.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Heikkinen, A.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Ungaro, D.; Wendland, L.; Banzuzi, K.; Karjalainen, A.; Korpela, A.; Tuuva, T.; Besancon, M.; Choudhury, S.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. 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A.; D’Enterria, D.; Dabrowski, A.; De Roeck, A.; Di Guida, S.; Dobson, M.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Frisch, B.; Funk, W.; Georgiou, G.; Giffels, M.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Giunta, M.; Glege, F.; Gomez-Reino Garrido, R.; Govoni, P.; Gowdy, S.; Guida, R.; Hansen, M.; Harris, P.; Hartl, C.; Harvey, J.; Hegner, B.; Hinzmann, A.; Innocente, V.; Janot, P.; Kaadze, K.; Karavakis, E.; Kousouris, K.; Lecoq, P.; Lee, Y. -J.; Lenzi, P.; Lourenço, C.; Magini, N.; Mäki, T.; Malberti, M.; Malgeri, L.; Mannelli, M.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moser, R.; Mozer, M. U.; Mulders, M.; Musella, P.; Nesvold, E.; Orimoto, T.; Orsini, L.; Palencia Cortezon, E.; Perez, E.; Perrozzi, L.; Petrilli, A.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Piparo, D.; Polese, G.; Quertenmont, L.; Racz, A.; Reece, W.; Rodrigues Antunes, J.; Rolandi, G.; Rovelli, C.; Rovere, M.; Sakulin, H.; Santanastasio, F.; Schäfer, C.; Schwick, C.; Segoni, I.; Sekmen, S.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Tsirou, A.; Veres, G. I.; Vlimant, J. R.; Wöhri, H. K.; Worm, S. D.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Gabathuler, K.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; König, S.; Kotlinski, D.; Langenegger, U.; Meier, F.; Renker, D.; Rohe, T.; Bäni, L.; Bortignon, P.; Buchmann, M. A.; Casal, B.; Chanon, N.; Deisher, A.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eugster, J.; Freudenreich, K.; Grab, C.; Hits, D.; Lecomte, P.; Lustermann, W.; Marini, A. 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W.; Olaiya, E.; Petyt, D.; Radburn-Smith, B. C.; Shepherd-Themistocleous, C. H.; Tomalin, I. R.; Womersley, W. J.; Bainbridge, R.; Ball, G.; Beuselinck, R.; Buchmuller, O.; Colling, D.; Cripps, N.; Cutajar, M.; Dauncey, P.; Davies, G.; Della Negra, M.; Ferguson, W.; Fulcher, J.; Futyan, D.; Gilbert, A.; Guneratne Bryer, A.; Hall, G.; Hatherell, Z.; Hays, J.; Iles, G.; Jarvis, M.; Karapostoli, G.; Lyons, L.; Magnan, A. -M.; Marrouche, J.; Mathias, B.; Nandi, R.; Nash, J.; Nikitenko, A.; Papageorgiou, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Pioppi, M.; Raymond, D. M.; Rogerson, S.; Rose, A.; Ryan, M. J.; Seez, C.; Sharp, P.; Sparrow, A.; Stoye, M.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Wakefield, S.; Wardle, N.; Whyntie, T.; Chadwick, M.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Martin, W.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Hatakeyama, K.; Liu, H.; Scarborough, T.; Charaf, O.; Henderson, C.; Rumerio, P.; Avetisyan, A.; Bose, T.; Fantasia, C.; Heister, A.; John, J. St.; Lawson, P.; Lazic, D.; Rohlf, J.; Sperka, D.; Sulak, L.; Alimena, J.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Jabeen, S.; Kukartsev, G.; Laird, E.; Landsberg, G.; Luk, M.; Narain, M.; Nguyen, D.; Segala, M.; Sinthuprasith, T.; Speer, T.; Breedon, R.; Breto, G.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Dolen, J.; Erbacher, R.; Gardner, M.; Houtz, R.; Ko, W.; Kopecky, A.; Lander, R.; Mall, O.; Miceli, T.; Pellett, D.; Ricci-Tam, F.; Rutherford, B.; Searle, M.; Smith, J.; Squires, M.; Tripathi, M.; Vasquez Sierra, R.; Yohay, R.; Andreev, V.; Cline, D.; Cousins, R.; Duris, J.; Erhan, S.; Everaerts, P.; Farrell, C.; Hauser, J.; Ignatenko, M.; Jarvis, C.; Rakness, G.; Schlein, P.; Traczyk, P.; Valuev, V.; Weber, M.; Babb, J.; Clare, R.; Dinardo, M. E.; Ellison, J.; Gary, J. W.; Giordano, F.; Hanson, G.; Jeng, G. Y.; Liu, H.; Long, O. R.; Luthra, A.; Nguyen, H.; Paramesvaran, S.; Sturdy, J.; Sumowidagdo, S.; Wilken, R.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; Evans, D.; Holzner, A.; Kelley, R.; Lebourgeois, M.; Letts, J.; Macneill, I.; Mangano, B.; Padhi, S.; Palmer, C.; Petrucciani, G.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Sudano, E.; Tadel, M.; Tu, Y.; Vartak, A.; Wasserbaech, S.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Bellan, R.; Campagnari, C.; D’Alfonso, M.; Danielson, T.; Flowers, K.; Geffert, P.; Golf, F.; Incandela, J.; Justus, C.; Kalavase, P.; Kovalskyi, D.; Krutelyov, V.; Lowette, S.; Mccoll, N.; Pavlunin, V.; Ribnik, J.; Richman, J.; Rossin, R.; Stuart, D.; To, W.; West, C.; Apresyan, A.; Bornheim, A.; Chen, Y.; Di Marco, E.; Duarte, J.; Gataullin, M.; Ma, Y.; Mott, A.; Newman, H. B.; Rogan, C.; Spiropulu, M.; Timciuc, V.; Veverka, J.; Wilkinson, R.; Xie, S.; Yang, Y.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carroll, R.; Ferguson, T.; Iiyama, Y.; Jang, D. W.; Liu, Y. F.; Paulini, M.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Drell, B. R.; Ford, W. T.; Gaz, A.; Luiggi Lopez, E.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Eggert, N.; Gibbons, L. K.; Heltsley, B.; Khukhunaishvili, A.; Kreis, B.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Vaughan, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Burkett, K.; Butler, J. N.; Chetluru, V.; Cheung, H. W. K.; Chlebana, F.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Green, D.; Gutsche, O.; Hanlon, J.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kunori, S.; Kwan, S.; Leonidopoulos, C.; Linacre, J.; Lincoln, D.; Lipton, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Mishra, K.; Mrenna, S.; Musienko, Y.; Newman-Holmes, C.; O’Dell, V.; Sexton-Kennedy, E.; Sharma, S.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitmore, J.; Wu, W.; Yang, F.; Yun, J. C.; Acosta, D.; Avery, P.; Bourilkov, D.; Chen, M.; Cheng, T.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Dobur, D.; Drozdetskiy, A.; Field, R. D.; Fisher, M.; Fu, Y.; Furic, I. K.; Gartner, J.; Hugon, J.; Kim, B.; Konigsberg, J.; Korytov, A.; Kropivnitskaya, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Park, M.; Remington, R.; Rinkevicius, A.; Sellers, P.; Skhirtladze, N.; Snowball, M.; Yelton, J.; Zakaria, M.; Gaultney, V.; Hewamanage, S.; Lebolo, L. M.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Chen, J.; Diamond, B.; Gleyzer, S. V.; Haas, J.; Hagopian, S.; Hagopian, V.; Jenkins, M.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Dorney, B.; Hohlmann, M.; Kalakhety, H.; Vodopiyanov, I.; Yumiceva, F.; Adams, M. R.; Anghel, I. M.; Apanasevich, L.; Bai, Y.; Bazterra, V. E.; Betts, R. R.; Bucinskaite, I.; Callner, J.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Lacroix, F.; O’Brien, C.; Silkworth, C.; Strom, D.; Turner, P.; Varelas, N.; Akgun, U.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Duru, F.; Merlo, J. -P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Newsom, C. R.; Norbeck, E.; Onel, Y.; Ozok, F.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Fehling, D.; Giurgiu, G.; Gritsan, A. V.; Guo, Z. J.; Hu, G.; Maksimovic, P.; Swartz, M.; Whitbeck, A.; Baringer, P.; Bean, A.; Benelli, G.; Kenny Iii, R. P.; Murray, M.; Noonan, D.; Sanders, S.; Stringer, R.; Tinti, G.; Wood, J. S.; Barfuss, A. F.; Bolton, T.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Shrestha, S.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Baden, A.; Calvert, B.; Eno, S. C.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kirn, M.; Kolberg, T.; Lu, Y.; Marionneau, M.; Mignerey, A. C.; Pedro, K.; Skuja, A.; Temple, J.; Tonjes, M. B.; Tonwar, S. C.; Twedt, E.; Apyan, A.; Bauer, G.; Bendavid, J.; Busza, W.; Butz, E.; Cali, I. A.; Chan, M.; Dutta, V.; Gomez Ceballos, G.; Goncharov, M.; Hahn, K. A.; Kim, Y.; Klute, M.; Krajczar, K.; Luckey, P. D.; Ma, T.; Nahn, S.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Rudolph, M.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Sung, K.; Velicanu, D.; Wenger, E. A.; Wolf, R.; Wyslouch, B.; Yang, M.; Yilmaz, Y.; Yoon, A. S.; Zanetti, M.; Zhukova, V.; Cooper, S. I.; Dahmes, B.; De Benedetti, A.; Franzoni, G.; Gude, A.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Pastika, N.; Rusack, R.; Sasseville, M.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Cremaldi, L. M.; Kroeger, R.; Perera, L.; Rahmat, R.; Sanders, D. A.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Eads, M.; Keller, J.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Snow, G. R.; Godshalk, A.; Iashvili, I.; Jain, S.; Kharchilava, A.; Krylova, K.; Kumar, A.; Rappoccio, S.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Nash, D.; Trocino, D.; Wood, D.; Zhang, J.; Anastassov, A.; Kubik, A.; Lusito, L.; Mucia, N.; Odell, N.; Ofierzynski, R. A.; Pollack, B.; Pozdnyakov, A.; Sarkar, R.; Schmitt, M.; Stoynev, S.; Velasco, M.; Won, S.; Antonelli, L.; Berry, D.; Brinkerhoff, A.; Chan, K. M.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kolb, J.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Morse, D. M.; Pearson, T.; Planer, M.; Ruchti, R.; Slaunwhite, J.; Valls, N.; Wayne, M.; Wolf, M.; Bylsma, B.; Durkin, L. S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Vuosalo, C.; Williams, G.; Winer, B. L.; Berry, E.; Elmer, P.; Halyo, V.; Hebda, P.; Hegeman, J.; Hunt, A.; Jindal, P.; Koay, S. A.; Lopes Pegna, D.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Raval, A.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zuranski, A.; Brownson, E.; Lopez, A.; Mendez, H.; Ramirez Vargas, J. E.; Alagoz, E.; Barnes, V. E.; Benedetti, D.; Bolla, G.; Bortoletto, D.; De Mattia, M.; Everett, A.; Hu, Z.; Jones, M.; Koybasi, O.; Kress, M.; Laasanen, A. T.; Leonardo, N.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Vidal Marono, M.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Guragain, S.; Parashar, N.; Adair, A.; Akgun, B.; Boulahouache, C.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Chung, Y. S.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Miner, D. C.; Vishnevskiy, D.; Zielinski, M.; Bhatti, A.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Malik, S.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Rekovic, V.; Robles, J.; Rose, K.; Salur, S.; Schnetzer, S.; Seitz, C.; Somalwar, S.; Stone, R.; Thomas, S.; Walker, M.; Cerizza, G.; Hollingsworth, M.; Spanier, S.; Yang, Z. C.; York, A.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Safonov, A.; Sakuma, T.; Sengupta, S.; Suarez, I.; Tatarinov, A.; Toback, D.; Akchurin, N.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Jeong, C.; Kovitanggoon, K.; Lee, S. W.; Libeiro, T.; Roh, Y.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Florez, C.; Greene, S.; Gurrola, A.; Johns, W.; Kurt, P.; Maguire, C.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Balazs, M.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Lin, C.; Neu, C.; Wood, J.; Gollapinni, S.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Mcgee, K.; Sakharov, A.; Siehl, K.; Anderson, M.; Belknap, D.; Borrello, L.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Friis, E.; Gray, L.; Grogg, K. S.; Grothe, M.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Klukas, J.; Lanaro, A.; Lazaridis, C.; Leonard, J.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Palmonari, F.; Pierro, G. A.; Ross, I.; Savin, A.; Smith, W. H.; Swanson, J.

2013-02-01

A measurement of the inclusive WW+WZ diboson production cross section in proton-proton collisions is reported, based on events containing a leptonically decaying W boson and exactly two jets. The data sample, collected at sqrt(s) = 7 TeV with the CMS detector at the LHC, corresponds to an integrated luminosity of 5.0 inverse femtobarns. The measured value of the sum of the inclusive WW and WZ cross sections is sigma(pp to WW+WZ) = 68.9 +/- 8.7 (stat.) +/- 9.7 (syst.) +/- 1.5 (lum.) pb, consistent with the standard model prediction of 65.6 +/- 2.2 pb. This is the first measurement of WW+WZ production in pp collisions using this signature. No evidence for anomalous triple gauge couplings is found and upper limits are set on their magnitudes.

Biocontrol of Pectobacterium carotovorum subsp. carotovorum using bacteriophage PP1.

Science.gov (United States)

Lim, Jeong-A; Jee, Samnyu; Lee, Dong Hwan; Roh, Eunjung; Jung, Kyusuk; Oh, Changsik; Heu, Sunggi

2013-08-01

Pectobacterium carotovorum subsp. carotovorum (formerly Erwinia carotovora subsp. carotovora) is a plant pathogen that causes soft rot and stem rot diseases in several crops, including Chinese cabbage, potato, and tomato. To control this bacterium, we isolated a bacteriophage, PP1, with lytic activity against P. carotovorum subsp. carotovorum. Transmission electron microscopy revealed that the PP1 phage belongs to the Podoviridae family of the order Caudovirales, which exhibit icosahedral heads and short non-contractile tails. PP1 phage showed high specificity for P. carotovorum subsp. carotovorum, and several bacteria belonging to different species and phyla were resistant to PP1. This phage showed rapid and strong lytic activity against its host bacteria in liquid medium and was stable over a broad range of pH values. Disease caused by P. carotovorum subsp. carotovorum was significantly reduced by PP1 treatment. Overall, PP1 bacteriophage effectively controls P. carotovorum subsp. carotovorum.

Search for narrow pp states in the reaction pi /sup -/p to p pi /sup - /pp at 16 GeV/c

CERN Document Server

Chung, S U; Bensinger, J; Button-Shafer, J; Dhar, S; Dowd, J; Etkin, A; Fernow, R; Foley, K; Goldman, J H; Kern, W; Kirk, H; Kopp, J; Kramer, M A; Lesnik, A; Lichti, R; Lindenbaum, S J; Love, W; Mallik, U; Morris, T; Morris, W; Ozaki, S; Platner, E; Protopopescu, S D; Saulys, A; Weygand, D P; Wheeler, C D; Willen, E; Winik, M

1980-01-01

This Letter carries out a sensitive ( approximately 5 events/nb) search for narrow pp states at the Brookhaven National Laboratory multiparticle spectrometer. No evidence is found for such states in the mass range 1900-2400 MeV/c/sup 2/ in the reaction pi /sup -/p to p pi /sup -/pp at 16 GeV/c. In particular, the pp states at 2020 and 2200 MeV/c/sup 2/ previously reported in a CERN Omega -spectrometer experiment are not observed. (7 refs).

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension.

Science.gov (United States)

Supasyndh, Ouppatham; Wang, Jian'an; Hafeez, Kudsia; Zhang, Ying; Zhang, Jack; Rakugi, Hiromi

2017-11-06

Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. Overall, 588 patients were randomized (mean age, 70.7 years; baseline msBP, 160.3/84.9 mm Hg; msPP, 75.4 mm Hg). At week 10, sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P sacubitril/valsartan. At week 14, despite more patients requiring up-titration in the olmesartan group, msBP and msPP reductions from baseline were significantly greater with sacubitril/valsartan. Both treatments were generally well-tolerated. Sacubitril/valsartan is more effective than olmesartan in reducing BP in elderly Asian patients with systolic hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

PP13, maternal ABO blood groups and the risk assessment of pregnancy complications.

Directory of Open Access Journals (Sweden)

Nandor Gabor Than

Full Text Available Placental Protein 13 (PP13, an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR. Datasets of maternal serum PP13 in Caucasian (n = 1078 and Hispanic (n = 242 women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13--blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test.

TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

NARCIS (Netherlands)

MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

1993-01-01

The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

Roles of Polypyrimidine Tract Binding Proteins in Major Immediate-Early Gene Expression and Viral Replication of Human Cytomegalovirus▿

Science.gov (United States)

Cosme, Ruth S. Cruz; Yamamura, Yasuhiro; Tang, Qiyi

2009-01-01

Human cytomegalovirus (HCMV), a member of the β subgroup of the family Herpesviridae, causes serious health problems worldwide. HCMV gene expression in host cells is a well-defined sequential process: immediate-early (IE) gene expression, early-gene expression, DNA replication, and late-gene expression. The most abundant IE gene, major IE (MIE) gene pre-mRNA, needs to be spliced before being exported to the cytoplasm for translation. In this study, the regulation of MIE gene splicing was investigated; in so doing, we found that polypyrimidine tract binding proteins (PTBs) strongly repressed MIE gene production in cotransfection assays. In addition, we discovered that the repressive effects of PTB could be rescued by splicing factor U2AF. Taken together, the results suggest that PTBs inhibit MIE gene splicing by competing with U2AF65 for binding to the polypyrimidine tract in pre-mRNA. In intron deletion mutation assays and RNA detection experiments (reverse transcription [RT]-PCR and real-time RT-PCR), we further observed that PTBs target all the introns of the MIE gene, especially intron 2, and affect gene splicing, which was reflected in the variation in the ratio of pre-mRNA to mRNA. Using transfection assays, we demonstrated that PTB knockdown cells induce a higher degree of MIE gene splicing/expression. Consistently, HCMV can produce more viral proteins and viral particles in PTB knockdown cells after infection. We conclude that PTB inhibits HCMV replication by interfering with MIE gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns. PMID:19144709

Primary structure, gene organization and polypeptide expression of poliovirus RNA

Energy Technology Data Exchange (ETDEWEB)

Kitamura, N. (State Univ. of New York, Stony Brook); Semler, B.L.; Rothberg, P.G.

1981-06-18

The primary structure of the poliovirus genome has been determined. The RNA molecule is 7433 nucleotides long, polyadenylated at the 3' terminus, and covalently linked to a small protein (VPg) at the 5' terminus. An open reading frame of 2207 consecutive triplets spans over 89% of the nucleotide sequence and codes for the viral polyprotein NCVPOO. Twelve viral polypeptides have been mapped by amino acid sequence analysis and were found to be proteolytic cleavage products of the polyprotein, cleavages occurring predominantly at Gln-Gly pairs.

PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte.

Science.gov (United States)

Tang, An; Shi, Peiliang; Song, Anying; Zou, Dayuan; Zhou, Yue; Gu, Pengyu; Huang, Zan; Wang, Qinghua; Lin, Zhaoyu; Gao, Xiang

2016-06-02

Studies using in vitro cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an in vivo model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1(st) meiotic division due to chromosome misalignment and abnormal spindle assembly. In mitosis, PP2A counteracts Aurora kinase B/C (AurkB/C) to facilitate correct kinetochore-microtubule (KT-MT) attachment. In meiosis I in oocyte, we found that PP2Ac deficiency destabilized KT-MT attachments. Chemical inhibition of AurkB/C in PP2Ac-null oocytes partly restored the formation of lateral/merotelic KT-MT attachments but not correct KT-MT attachments. Taken together, our findings demonstrate that PP2Acs are essential for chromosome alignments and regulate the formation of correct KT-MT attachments in meiosis I in oocytes.

Comparison of forward and backward pp pair knockout in 3He(e,e'pp)n

Science.gov (United States)

Baghdasaryan, H.; Weinstein, L. B.; Laget, J. M.; Adhikari, K. P.; Aghasyan, M.; Amaryan, M. J.; Anghinolfi, M.; Ball, J.; Battaglieri, M.; Biselli, A. S.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Cole, P. L.; Contalbrigo, M.; Crede, V.; D'Angelo, A.; Daniel, A.; Dashyan, N.; De Sanctis, E.; De Vita, R.; Djalali, C.; Dodge, G. E.; Doughty, D.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Fedotov, G.; Gabrielyan, M. Y.; Gevorgyan, N.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gohn, W.; Gothe, R. W.; Griffioen, K. A.; Guegan, B.; Guidal, M.; Hafidi, K.; Hicks, K.; Hyde, C. E.; Ireland, D. G.; Ishkhanov, B. S.; Jenkins, D.; Jo, H. S.; Joo, K.; Khandaker, M.; Khetarpal, P.; Kim, A.; Kim, W.; Kubarovsky, A.; Kubarovsky, V.; Kuhn, S. E.; Kuleshov, S. V.; Kvaltine, N. D.; Lu, H. Y.; MacGregor, I. J. D.; McKinnon, B.; Mirazita, M.; Mokeev, V.; Moutarde, H.; Munevar, E.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Paolone, M.; Pappalardo, L. L.; Paremuzyan, R.; Park, K.; Park, S.; Pisano, S.; Pozdniakov, S.; Procureur, S.; Raue, B. A.; Ricco, G.; Rimal, D.; Ripani, M.; Rosner, G.; Rossi, P.; Saini, M. S.; Saylor, N. A.; Schott, D.; Schumacher, R. A.; Seraydaryan, H.; Smith, E. S.; Sober, D. I.; Sokan, D.; Stepanyan, S. S.; Stepanyan, S.; Strauch, S.; Taiuti, M.; Tang, W.; Tkachenko, S.; Voskanyan, H.; Voutier, E.; Wood, M. H.; Zana, L.; Zhao, B.

2012-06-01

Measuring nucleon-nucleon short range correlations (SRCs) has been a goal of the nuclear physics community for many years. They are an important part of the nuclear wave function, accounting for almost all of the high-momentum strength. They are closely related to the EMC effect. While their overall probability has been measured, measuring their momentum distributions is more difficult. In order to determine the best configuration for studying SRC momentum distributions, we measured the 3He(e,e'pp)n reaction, looking at events with high-momentum protons (pp>0.35 GeV/c) and a low-momentum neutron (pn<0.2 GeV/c). We examined two angular configurations: either both protons emitted forward or one proton emitted forward and one backward (with respect to the momentum transfer, q⃗). The measured relative momentum distribution of the events with one forward and one backward proton was much closer to the calculated initial-state pp relative momentum distribution, indicating that this is the preferred configuration for measuring SRC.

PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

Science.gov (United States)

Than, Nandor Gabor; Romero, Roberto; Meiri, Hamutal; Erez, Offer; Xu, Yi; Tarquini, Federica; Barna, Laszlo; Szilagyi, Andras; Ackerman, Ron; Sammar, Marei; Fule, Tibor; Karaszi, Katalin; Kovalszky, Ilona; Dong, Zhong; Kim, Chong Jai; Zavodszky, Peter; Papp, Zoltan; Gonen, Ron

2011-01-01

Background Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood. Methods and Findings We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13 - blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR. Conclusions ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test. PMID:21799738

High-resolution polypeptide structure and dynamics in anisotropic environments: The gramicidin channel

Energy Technology Data Exchange (ETDEWEB)

Cross, T.A.; Lee, K.C.; Ketchem, R.R.; Hu, W.; Lazo, N.D.; Huo, S. [Florida State Univ., Tallahassee, FL (United States)

1994-12-01

To understand the details of macromolecular function, high-resolution structural and dynamic detail is essential. The polypeptide fold of the gramicidin channel has been effectively modeled for the past 20 years, yet the functional changes in conductance and channel lifetime associated with amino acid substitutions cannot be predicted. To accomplish this goal, high-resolution electrostatic modeling and the precise orientation of all dipoles are required. Furthermore, an enhanced knowledge of the complex molecular environment of this membrane-bound peptide is needed. An aqueous environment is relatively uniform and achiral. The membrane environment is very heterogenous and chiral. A knowledge of the interactions, specific and nonspecific, between peptide and lipid will aid in developing a better understanding of this environment. To accomplish this goal, it is necessary to study the peptide in an extended lipid bilayer, rather than in a vesicular or micellar form. These latter environments are likely to possess increased dynamics, increased water penetration, and distorted interactions between the polypeptide and membrane surface. To perform NMR studies on bilayer bound peptides, solid state NMR methods are required, and for specific site information, isotopic labels are incorporated using solid phase peptide synthesis.

Specific photoaffinity labeling of two plasma membrane polypeptides with an azido auxin

International Nuclear Information System (INIS)

Hicks, G.R.; Rayle, D.L.; Jones, A.M.; Lomax, T.L.

1989-01-01

Plasma membrane vesicles were isolated from zucchini (Cucurbita pepo) hypocotyl tissue by aqueous phase partitioning and assessed for homogeneity by the use of membrane-specific enzyme assays. The highly pure plasma membrane vesicles maintained a pH differential across the membrane and accumulated a tritiated azido analogue of 3-indoleacetic acid (IAA), 5-azido-[7- 3 H]IAA([ 3 H]N 3 IAA), in a manner similar to the accumulation of [ 3 H]IAA. The association of the [ 3 H]N 3 IAA with membrane vesicles was saturable and subject to competition by IAA and auxin analogues. Auxin-binding proteins were photoaffinity labeled by addition of [ 3 H]N 3 IAA to plasma membrane vesicles prior to exposure to UV light and detected by subsequent NaDodSO 4 /PAGE and fluorography. When the reaction temperature was lowered to -196 degree C, high-specific-activity labeling of a 40-kDa and a 42-kDa polypeptide was observed. Collectively, these results suggest that the radiolabeled polypeptides are auxin receptors. The covalent nature of the label should facilitate purification and further characterization of the receptors

Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.

Science.gov (United States)

Wu, Zeguang; Sinzger, Christian; Frascaroli, Giada; Reichel, Johanna; Bayer, Carina; Wang, Li; Schirmbeck, Reinhold; Mertens, Thomas

2013-07-01

Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2C(hi) CD57(hi) NK cells gated on CD3(neg) CD56(dim) cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2C(hi) CD57(hi) NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2C(hi) CD57(hi) NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2C(hi) CD57(hi) NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

The generalized model of polypeptide chain describing the helix-coil transition in biopolymers

International Nuclear Information System (INIS)

Mamasakhlisov, E.S.; Badasyan, A.V.; Tsarukyan, A.V.; Grigoryan, A.V.; Morozov, V.F.

2005-07-01

In this paper we summarize some results of our theoretical investigations of helix-coil transition both in single-strand (polypeptides) and two-strand (polynucleotides) macromolecules. The Hamiltonian of the Generalized Model of Polypeptide Chain (GMPC) is introduced to describe the system in which the conformations are correlated over some dimensional range Δ (it equals 3 for polypeptide, because one H-bond fixes three pairs of rotation, for double strand DNA it equals to one chain rigidity because of impossibility of loop formation on the scale less than Δ). The Hamiltonian does not contain any parameter designed especially for helix-coil transition and uses pure molecular microscopic parameters (the energy of hydrogen bond formation, reduced partition function of repeated unit, the number of repeated units fixed by one hydrogen bond, the energies of interaction between the repeated units and the solvent molecules). To calculate averages we evaluate the partition function using the transfer-matrix approach. The GMPC allowed to describe the influence of a number of factors, affecting the transition, basing on a unified microscopic approach. Thus we obtained, that solvents change transition temperature and interval in different ways, depending on type of solvent and on energy of solvent- macromolecule interaction; stacking on the background of H-bonding increases stability and decreases cooperativity of melting. For heterogeneous DNA we could analytically derive well known formulae for transition temperature and interval. In the framework of GMPC we calculate and show the difference of two order parameters of helix-coil transition - the helicity degree, and the average fraction of repeated units in helical conformation. Given article has the aim to review the results obtained during twenty years in the context of GMPC. (author)

Peptides and polypeptides as scaffolds for optoelectronics and biomaterials applications

Science.gov (United States)

Charati, Manoj B.

Peptides and polypeptides are emerging as a new class of biomaterials due to their unique structural, physiochemical, mechanical, and biological properties. The development of peptide and protein-based biomaterials is driven by the convergence of convenient techniques for peptide/protein engineering and its importance in applications as smart biomaterials. The thesis is divided in two parts; the first part highlights the importance of incorporation of non-natural amino acids into peptides and proteins. In particular, incorporation on p-bromophenylalanine in short alpha-helical peptide templates to control the association of chromophores is discussed. In the second part, design of a multi-component, biocompatible polypeptide with superior elasticity is discussed. Part 1. Novel peptide templates to control association of chromophores. Tailor made peptide and protein materials have many versatile applications, as both conformation and functional group position can be controlled. Such control may have intriguing applications in the development of hybrid materials for electroactive applications. A critical need in fabricating devices from organic semiconducting materials is to achieve control over the conformation and distance between two conjugated chains. Controlling chromophore spacing and orientation with required precision over nanometer length scale poses a greater challenge. Here we propose a peptide based template to control the alignment of the methylstilbene and Oxa-PPV chromophores with desired orientations and spacing. The hybrid peptides were characterized via CD, exciton coupled CD, 1H NMR and photoluminescence experiments. It is observed that slight change in the orientation of molecules has pronounced effect on the photo-physical behavior of the molecules. Characterization of the hybrid peptides via circular dichroism (CD) confirmed the helical character of the designed peptides and indicated that inclusion of non-natural amino acids has significant

Methylation-regulated decommissioning of multimeric PP2A complexes

Energy Technology Data Exchange (ETDEWEB)

Wu, Cheng-Guo; Zheng, Aiping; Jiang, Li; Rowse, Michael; Stanevich, Vitali; Chen, Hui; Li, Yitong; Satyshur, Kenneth A.; Johnson, Benjamin; Gu, Ting-Jia; Liu, Zuojia; Xing, Yongna

2017-12-01

Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivation of mutant PP2A. Strikingly, TIPRL and the latency chaperone, α4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.

Human cytomegalovirus infant infection adversely affects growth and development in maternally HIV-exposed and unexposed infants in Zambia.

Science.gov (United States)

Gompels, U A; Larke, N; Sanz-Ramos, M; Bates, M; Musonda, K; Manno, D; Siame, J; Monze, M; Filteau, S

2012-02-01

Human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) coinfections have been shown to increase infant morbidity, mortality, and AIDS progression. In HIV-endemic regions, maternal HIV-exposed but HIV-uninfected infants, which is the majority of children affected by HIV, also show poor growth and increased morbidity. Although nutrition has been examined, the effects of HCMV infection have not been evaluated. We studied the effects of HCMV infection on the growth, development, and health of maternally HIV-exposed and unexposed infants in Zambia. Infants were examined in a cohort recruited to a trial of micronutrient-fortified complementary foods. HIV-infected mothers and infants had received perinatal antiretroviral therapy to prevent mother-to-child HIV transmission. Growth, development, and morbidity were analyzed by linear regression analyses in relation to maternal HIV exposure and HCMV infection, as screened by sera DNA for viremia at 6 months of age and by antibody for infection at 18 months. All HCMV-seropositive infants had decreased length-for-age by 18 months compared with seronegative infants (standard deviation [z]-score difference: -0.44 [95% confidence interval {CI}, -.72 to -.17]; P = .002). In HIV-exposed infants, those who were HCMV positive compared with those who were negative, also had reduced head size (mean z-score difference: -0.72 [95% CI, -1.23 to -.22]; P = .01) and lower psychomotor development (Bayley test score difference: -4.1 [95% CI, -7.8 to -.5]; P = .03). HIV-exposed, HCMV-viremic infants were more commonly referred for hospital treatment than HCMV-negative infants. The effects of HCMV were unaffected by micronutrient fortification. HCMV affects child growth, development, and morbidity of African infants, particularly in those maternally exposed to HIV. HCMV is therefore a risk factor for child health in this region.

Recombinant DNA specifying the human amyloid. beta. precursor protein (ABPP) encodes a 95-kDa polypeptide

Energy Technology Data Exchange (ETDEWEB)

Mita, S; Sadlock, J; Herbert, J; Schon, E A

1988-10-11

Although the ABPP gene give rise to multiple mRNAs, the primary translation product of this gene is unknown. The longest published cDNA sequences predict a 770-aa polypeptide of 87 kDa. However, in immunoblots, ABPP migrated as a single species of >92 kDa in rat brain, and in human, as a species of 95-100 kDa in non-membrane bound form, as multiple species of 110-135 kDa in membrane-associated form and as a 130-kDa species in fibroblasts. The sizes of these larger species relative to the MW of ABPP predicted from the cDNA sequences have been attributed to postranslational modification. However, the authors have isolated a cDNA (lambdaHAP2) from a human fetal muscle lambdagt11 cDNA library encoding an 843-aa polypeptide with a deduced MW of 94,642. This cDNA contains both exons encoding an 843-aa polypeptide with a deduced MW of 94.642. This cDNA contains both exons encoding the protease inhibitor domains. Primer extension analysis indicates that the 5' terminus of this cDNA is 14 nt from a transcriptional start site. This cDNA, encoding the longest ABPP described to date, may explain some of the observations on the sizes of tissue-derived ABPP.

Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers.

Science.gov (United States)

Ahmed, Marya

2017-10-24

Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delivery therapeutics. In order to obtain multivalency and improve the gene delivery efficacies of low molecular weight cationic peptides, bioactive peptides are often incorporated into a polymeric architecture to obtain novel 'polymer-peptide hybrids' with improved gene delivery efficacies. Peptide modified polymers prepared by physical or chemical modifications exhibit enhanced endosomal escape, stimuli responsive degradation and targeting efficacies, as a function of physicochemical and biological activities of peptides attached onto a polymeric scaffold. The focus of this review is to provide comprehensive and step-wise progress in major natural and synthetic peptides, chimeric polypeptides, and peptide-polymer hybrids for nucleic acid delivery applications.

A detailed study of $(n_{ch}) vs E^{had}$ and $m_{1,2}$ at different $\\sqrt{s}_{pp}$ in (pp) interactions

CERN Document Server

Basile, M; Cesare, P D; Cifarelli, L; Contin, A; Curatolo, M; D'Ali, G; Esposito, B; Giusti, P; Massam, Thomas; Nania, R; Palmonari, F; Petrosino, A; Romeo, G C; Rossi, V; Sartorelli, G; Spinetti, M; Susinno, G; Valenti, G; Votano, L; Zichichi, A

1982-01-01

By using (pp) interactions at three different CM energies, ( \\sqrt{s})/sub pp/=30, 44, 62 GeV, it is shown that the average charged- particle multiplicity (n/sub ch/) vs. the invariant mass of the hadronic system m/sub 1,2/ has the same behaviour as it has vs. 2E/sup had/. Moreover, in both cases (n/sub ch/) is shown to be nearly independent of ( \\sqrt{s})/sub pp/ and in good agreement with the average charged-particle multiplicity measured in the (e^{+}e/sup - /) annihilation.

Tissue polypeptide antigen activity in cerebrospinal fluid

DEFF Research Database (Denmark)

Bach, F; Söletormos, Georg; Dombernowsky, P

1991-01-01

Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis......, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPp...... metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells...

Uptake and loss of dissolved zinc by the stickleback gasterosteus Aculeatus l. [Zinc 65

Energy Technology Data Exchange (ETDEWEB)

Matthiessen, P.; Brafield, A.E.

1977-01-01

Uptake and loss by sticklebacks of both stable zinc and /sup 65/Zn in hard and soft water were studied for periods up to 400 h. In calcium-free water, the zinc uptake curve is approximately asymptotic over a period of 24 h, while in hard water internal Zn levels dropped at 24 h. Over 5 h, fish in hard tapwater absorb about 3 to 5 times more Zn than those in calcium-free water. There is positive linear correlation between log Zn uptake and log wet weight of fish. Whole-body concentration factors (c.f.) at 16 h reach a maximum of 12.2 (mean = 2.9), highest concentrations of Zn being found in the gills (mean c.f. = 5.1), and lowest concentrations in the gonads (mean c.f. = 0.8). Over longer periods (400 h), internal stable zinc levels of fish exposed to 1 and 4 ppM Zn/sup +2/ remain little higher than controls (max. 28%) /sup 65/Zn efflux in zinc-free water falls to zero after 5 h, more zinc (78%) being lost after uptake in tapwater than in calcium-free water (56%).

Study of PP/Polybutene Blends Modified by Gamma Irradiation and HMS-PP/Polybutene Blends

International Nuclear Information System (INIS)

Lugao, A. B.

2006-01-01

The polypropylene (PP) has been applied to a wide range of production due to its various excellent properties such as cheapness, high stiffness, chemical resistance, no environmental pollution when incinerated, low specific density and good mechanical properties. However, PP is a linear polymer which exhibits low melt strength. One of the effective approaches to achieve high melt strength (HMS) is to add chain branches onto backbone polymers. High melt strength polypropylene (HMS-PP) has been recently developed and introduced in the market by the major international polypropylene producers. As a consequence different methods have been applied to modify polypropylenes by chain branches. The technology obtained by IPEN together with EMBRARAD and BRASKEM comprises chain branches added onto backbone species using gamma radiation, which is generated from a Co 6 0 source. Such radiation is very convenient in order to improve polymer materials by grafting, crosslinking and degradation. Another important approach to the development of polymer materials is based on the combination of different polymers into a new product having some of the desired properties of each component. In this work, gamma irradiation technique was used to induce chemical changes in commercial polypropylene (HMS-PP) that was after blended with polybutene and in polypropylene/polybutene blends. The samples were irradiated with a 60 C o source at doses of 12,5 and 20kGy in the presence of acetylene. It was investigated how the two different routes of blends processing can modify their properties. Indeed the results from melt flow, gel fraction and rheology reveal the influence of the process route in the blends properties. Effects on the elongation at break and break strength were observed by the results of mechanical tests. The results from rheology demonstrated an increase in melt strength and drawability of the blends

Natural polypeptide scaffolds: beta-sheets, beta-turns, and beta-hairpins.

Science.gov (United States)

Rotondi, Kenneth S; Gierasch, Lila M

2006-01-01

This paper provides an introduction to fundamental conformational states of polypeptides in the beta-region of phi,psi space, in which the backbone is extended near to its maximal length, and to more complex architectures in which extended segments are linked by turns and loops. There are several variants on these conformations, and they comprise versatile scaffolds for presentation of side chains and backbone amides for molecular recognition and designed catalysts. In addition, the geometry of these fundamental folds can be readily mimicked in peptidomimetics. Copyright 2005 Wiley Periodicals, Inc.

Functional Modification of Thioether Groups in Peptides, Polypeptides, and Proteins.

Science.gov (United States)

Deming, Timothy J

2017-03-15

Recent developments in the modification of methionine and other thioether-containing residues in peptides, polypeptides, and proteins are reviewed. Properties and potential applications of the resulting functionalized products are also discussed. While much of this work is focused on natural Met residues, modifications at other side-chain residues have also emerged as new thioether-containing amino acids have been incorporated into peptidic materials. Functional modification of thioether-containing amino acids has many advantages and is a complementary methodology to the widely utilized methods for modification at cysteine residues.

Role of human Cytomegalovirus in the etiology of nasopharyngeal carcinoma

Directory of Open Access Journals (Sweden)

Hussain Gadelkarim Ahmed

2018-01-01

Conclusion: The present study has shown a relatively considerable association between HCMV and NPC. The great majority of samples sheltering HCMV were also found to hide EBV, which proposes the potentiality of EBV over HCMV.

Characteristics of the groups of charged particles in bar pp,pp and K-p interactions at 32 GeV/c

International Nuclear Information System (INIS)

Bogolubsky, M.Yu.; Levitsky, M.S.; Maksimov, V.V.

1995-01-01

In the clan model, a method is developed for determining the following characteristics of the groups of charged particles: group multiplicity in an interval, particle multiplicity in a group, and width distribution of groups. Distribution densities are obtained for particles originating from clans produced at a given rapidity point with given width in bar pp, K - p, and pp interactions at 32 GeV/c. It is shown that the differences in the rate of growth of factorial moments in bar pp and K - p interactions are due to a difference in the relative contributions of small-width clans. 12 refs., 13 figs., 2 tabs

Accumulation of New Polypeptides in Ri T-DNA-Transformed Roots of Tomato (Lycopersicon esculentum) during the Development of Vesicular-Arbuscular Mycorrhizae.

Science.gov (United States)

Simoneau, P; Louisy-Louis, N; Plenchette, C; Strullu, D G

1994-06-01

Root-inducing transferred-DNA (Ri T-DNA)-transformed roots of tomato (Lycopersicon esculentum) were in vitro inoculated with surface-sterilized vesicular-arbuscular mycorrhizal leek root pieces. About 1 week after inoculation, the infection of the transformed root culture by the fungal endophyte was confirmed by photonic microscopy. Total proteins were extracted from the mycorrhizal roots and analyzed by two-dimensional polyacrylamide gel electrophoresis. Control gels were run with proteins extracted from noninoculated roots mixed with purified intraradical vesicles and extraradical hyphae. Comparison of the resulting patterns revealed the presence of two polypeptides with estimated apparent masses of 24 and 39 kDa that were detected only in infected roots. Polypeptides with similar migration parameters were not detected in roots challenged with spore extracts, suggesting that the accumulation of the polypeptides was directly linked to root colonization by the fungus rather than to induction by fungus-derived elicitors.

Two phosphoenolpyruvate carboxykinases coexist in the Crassulacean Acid Metabolism plant Ananas comosus. Isolation and characterization of the smaller 65 kDa form.

Science.gov (United States)

Martín, Mariana; Rius, Sebastián Pablo; Podestá, Florencio Esteban

2011-06-01

Two phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.49) isoforms of 74 and 65 kDa were found to coexist in vivo in pineapple leaves, a constitutive Crassulacean Acid Metabolism plant. The 65 kDa form was not the result of proteolytic cleavage of the larger form since extraction methods reported to prevent PEPCK proteolysis in other plant tissues failed to yield a single immunoreactive PEPCK polypeptide in leaf extracts. In this work, the smaller form of 65 kDa was purified to homogeneity and physically and kinetically characterized and showed parameters compatible with a fully active enzyme. The specific activity was nearly twice higher for decarboxylation of oxaloacetate when compared to carboxylation of phosphoenolpyruvate. Kinetic parameters fell within the range of those estimated for other plant PEPCKs. Its activity was affected by several metabolites, as shown by inhibition by 3-phosphoglycerate, citrate, malate, fructose-1,6-bisphosphate, l-asparagine and activation of the decarboxylating activity by succinate. A break in the Arrhenius plot at about 30°C indicates that PEPCK structure is responsive to changes in temperature. The results indicate that pineapple leaves contain two PEPCK forms. The biochemical characterization of the smaller isoform performed in this work suggests that it could participate in both carbon and nitrogen metabolism in vivo by acting as a decarboxylase. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Polypeptide composition of fraction 1 protein of the somatic hybrid between Petunia parodii and Petunia parviflora.

Science.gov (United States)

Kumar, A; Wilson, D; Cocking, E C

1981-04-01

The analysis of the subunit polypeptide composition of Fraction 1 protein provides information on the expression of both chloroplast and nuclear genomes. Fraction 1 protein, isolated from leaves of the somatic hybrid plants derived form the fusion of protoplasts of Petunia parodii and P. parviflora, was analyzed for its subunit polypeptide composition by isoelectric focusing in 8 M urea. The fraction 1 protein enzyme oligomer in the somatic hybrid plants contained small subunits resulting from the expression of both parental nuclear genomes, but probably only one of the parental large subunits, namely that of P. parodii. The relevance of such somatic hybrid material for the study of nucleocytoplasmic interrelationship is discussed, as well as the use of these fraction 1 protein isoelectric focusing patterns for the analysis of taxonomic relationships in Petunia.

Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians

DEFF Research Database (Denmark)

de Courten, Barbora; Weyer, Christian; Stefan, Norbert

2004-01-01

was administered for 120 min at the following doses: 0, 2.5, 5, and 10 micro g. kg fat-free mass (FFM)(-1). h(-1). Areas under the curve for early (AUC(0-30 min)) and total (AUC(0-120 min)) postprandial insulin and PP secretory responses were calculated. Early postprandial insulin and PP secretory responses were...

Photooxidation behaviour of HMS-PP

International Nuclear Information System (INIS)

Oliani, Washington L.; Parra, Duclerc F.; Lima, Luis F.C.P.; Lugao, Ademar B.

2009-01-01

The radiation process has played an important role to produce polymers with controlled rheological properties. The main scope of the study is to evaluate the stability of High melt strength polypropylene (HMS-PP) prepared by gamma irradiation of PP (spheres) under acetylene atmosphere followed by a heating step to terminate reactions, in different doses of 12.5 kGy and 20 kGy. The samples submitted to the natural ageing for a period of one year were characterized by: thermogravimetry (TG), differential scanning calorimetry (DSC), infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The fundamental process that is believed to be the most significant in the mechanism of photooxidative degradation is the formation of hydroperoxides. The high energy UV light is capable of initiating bond scission within the polymer backbone, which leads to further chemical modification of the bonds via scissions and chain reactions through formation of radical species. The results showed that in pristine and HMS-PP samples exposed to UV radiation, oxidation reactions occur, resulting in chain scissions. The reactions occur preferentially in the amorphous phase owing to the higher permeability of oxygen. (author)

Low energy bar pp physics

International Nuclear Information System (INIS)

Amsler, C.; Crowe, K.

1989-02-01

A detailed investigation of proton-antiproton interactions at low energy has become feasible with the commissioning of the LEAR facility in 1983. We shall shortly review the status of bar pp annihilation at rest and the physics motivations for second generation experiments with the Crystal Barrel detector. This type of detector would be adequate for the study of both Kp and bar pp interactions on an extracted beam of the KAON Factory. We shall conclude with a few remarks on the physics opportunities with bar p's at the KAON Factory which, in our opinion, will not be covered by the present LEAR facility. 11 refs., 10 figs., 2 tabs

Vasoactive intestinal polypeptide (VIP) in the pig pancreas

DEFF Research Database (Denmark)

Poulsen, Steen Seier

1984-01-01

Vasoactive intestinal polypeptide (VIP) in the pig pancreas is localized to nerves, many of which travel along the pancreatic ducts. VIP stimulates pancreatic fluid and bicarbonate secretion like secretin. Electrical vagal stimulation in the pig causes an atropine-resistant profuse secretion...... of bicarbonate-rich pancreatic juice. In an isolated perfused preparation of the pig pancreas with intact vagal nerve supply, electrical vagal stimulation caused an atropine-resistant release of VIP, which accurately parallelled the exocrine secretion of juice and bicarbonate. Perfusion of the pancreas...... with a potent VIP-antiserum inhibited the effect of vagal stimulation on the exocrine secretion. It is concluded, that VIP is responsible for (at least part of) the neurally controlled fluid and bicarbonate secretion from the pig pancreas....

The Transcriptome of the Zoanthid Protopalythoa variabilis (Cnidaria, Anthozoa) Predicts a Basal Repertoire of Toxin-like and Venom-Auxiliary Polypeptides.

Science.gov (United States)

Huang, Chen; Morlighem, Jean-Étienne Rl; Zhou, Hefeng; Lima, Érica P; Gomes, Paula B; Cai, Jing; Lou, Inchio; Pérez, Carlos D; Lee, Simon Ming; Rádis-Baptista, Gandhi

2016-10-05

Protopalythoa is a zoanthid that, together with thousands of predominantly marine species, such as hydra, jellyfish, and sea anemones, composes the oldest eumetazoan phylum, i.e., the Cnidaria. Some of these species, such as sea wasps and sea anemones, are highly venomous organisms that can produce deadly toxins for preying, for defense or for territorial disputes. Despite the fact that hundreds of organic and polypeptide toxins have been characterized from sea anemones and jellyfish, practically nothing is known about the toxin repertoire in zoanthids. Here, based on a transcriptome analysis of the zoanthid Protopalythoa variabilis, numerous predicted polypeptides with canonical venom protein features are identified. These polypeptides comprise putative proteins from different toxin families: neurotoxic peptides, hemostatic and hemorrhagic toxins, membrane-active (pore-forming) proteins, protease inhibitors, mixed-function venom enzymes, and venom auxiliary proteins. The synthesis and functional analysis of two of these predicted toxin products, one related to the ShK/Aurelin family and the other to a recently discovered anthozoan toxin, displayed potent in vivo neurotoxicity that impaired swimming in larval zebrafish. Altogether, the complex array of venom-related transcripts that are identified in P. variabilis, some of which are first reported in Cnidaria, provides novel insight into the toxin distribution among species and might contribute to the understanding of composition and evolution of venom polypeptides in toxiferous animals. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Enzymatic Properties and Mutational Studies of Chalcone Synthase from Physcomitrella patens

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Mahiran Basri

2012-08-01

Full Text Available PpCHS is a member of the type III polyketide synthase family and catalyses the synthesis of the flavonoid precursor naringenin chalcone from p-coumaroyl-CoA. Recent research reports the production of pyrone derivatives using either hexanoyl-CoA or butyryl-CoA as starter molecule. The Cys-His-Asn catalytic triad found in other plant chalcone synthase predicted polypeptides is conserved in PpCHS. Site directed mutagenesis involving these amino acids residing in the active-site cavity revealed that the cavity volume of the active-site plays a significant role in the selection of starter molecules as well as product formation. Substitutions of Cys 170 with Arg and Ser amino acids decreased the ability of the PpCHS to utilize hexanoyl-CoA as a starter molecule, which directly effected the production of pyrone derivatives (products. These substitutions are believed to have a restricted number of elongations of the growing polypeptide chain due to the smaller cavity volume of the mutant’s active site.

Characterisation and expression of a PP1 serine/threonine protein phosphatase (PfPP1 from the malaria parasite, Plasmodium falciparum: demonstration of its essential role using RNA interference

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Musiyenko Alla

2002-04-01

Full Text Available Abstract Background Reversible protein phosphorylation is relatively unexplored in the intracellular protozoa of the Apicomplexa family that includes the genus Plasmodium, to which belong the causative agents of malaria. Members of the PP1 family represent the most highly conserved protein phosphatase sequences in phylogeny and play essential regulatory roles in various cellular pathways. Previous evidence suggested a PP1-like activity in Plasmodium falciparum, not yet identified at the molecular level. Results We have identified a PP1 catalytic subunit from P. falciparum and named it PfPP1. The predicted primary structure of the 304-amino acid long protein was highly similar to PP1 sequences of other species, and showed conservation of all the signature motifs. The purified recombinant protein exhibited potent phosphatase activity in vitro. Its sensitivity to specific phosphatase inhibitors was characteristic of the PP1 class. The authenticity of the PfPP1 cDNA was further confirmed by mutational analysis of strategic amino acid residues important in catalysis. The protein was expressed in all erythrocytic stages of the parasite. Abrogation of PP1 expression by synthetic short interfering RNA (siRNA led to inhibition of parasite DNA synthesis. Conclusions The high sequence similarity of PfPP1 with other PP1 members suggests conservation of function. Phenotypic gene knockdown studies using siRNA confirmed its essential role in the parasite. Detailed studies of PfPP1 and its regulation may unravel the role of reversible protein phosphorylation in the signalling pathways of the parasite, including glucose metabolism and parasitic cell division. The use of siRNA could be an important tool in the functional analysis of Apicomplexan genes.

Elastin-like polypeptides: the power of design for smart cell encapsulation.

Science.gov (United States)

Bandiera, Antonella

2017-01-01

Cell encapsulation technology is still a challenging issue. Innovative methodologies such as additive manufacturing, and alternative bioprocesses, such as cell therapeutic delivery, where cell encapsulation is a key tool are rapidly gaining importance for their potential in regenerative medicine. Responsive materials such as elastin-based recombinant expression products have features that are particularly attractive for cell encapsulation. They can be designed and tailored to meet desired requirements. Thus, they represent promising candidates for the development of new concept-based materials that can be employed in this field. Areas covered: An overview of the design and employment of elastin-like polypeptides for cell encapsulation is given to outline the state of the art. Special attention is paid to the design of the macromolecule employed as well as to the method of matrix formation and the biological system involved. Expert opinion: As a result of recent progress in regenerative medicine there is a compelling need for materials that provide specific properties and demonstrate defined functional features. Rationally designed materials that may adapt according to applied external stimuli and that are responsive to biological systems, such as elastin-like polypeptides, belong to this class of smart material. A run through the components described to date represents a good starting point for further advancement in this area. Employment of these components in cell encapsulation application will promote its advance toward 'smart cell encapsulation technology'.

Surface treated polypropylene (PP) fibres for reinforced concrete

Energy Technology Data Exchange (ETDEWEB)

López-Buendía, Angel M., E-mail: buendia@uv.es [AIDICO Technological Institute of Construction, Benjamin Franklin 17, 46380 Paterna, Valencia (Spain); Romero-Sánchez, María Dolores [AIDICO Technological Institute of Construction, Marble Technical Unit, Camí de Castella 4, 03660 Novelda. Alicante (Spain); Climent, Verónica [Lafarge Cementos, Polígono Sepes, Isaac Newton s/n, 46500 Sagunto, Valencia (Spain); Guillem, Celia [AIDICO Technological Institute of Construction, Marble Technical Unit, Camí de Castella 4, 03660 Novelda. Alicante (Spain)

2013-12-15

Surface treatments on a polypropylene (PP) fibre have contributed to the improvement of fibre/concrete adhesion in fibre-reinforced concrete. The treatments to the PP fibre were characterized by contact angle measurements, ATR-IR and XPS to analyse chemical alterations. The surface topography and fibre/concrete interaction were analysed by several microscopic techniques, namely optical petrographic, and scanning electron microscopy. Treatment modified the surface chemistry and topography of the fibre by introducing sodium moieties and created additional fibre surface roughness. Modifications in the fibre surface led to an increase in the adhesion properties between the treated fibres and concrete and an improvement in the mechanical properties of the fibre-reinforced concrete composite as compared to the concrete containing untreated PP fibres. Compatibility with the concrete and increased roughness and mineral surface was also improved by nucleated portlandite and ettringite mineral association anchored on the alkaline PP fibre surface, which is induced during treatment.

Distribution of cytomegalovirus gN variants and associated clinical sequelae in infants.

Science.gov (United States)

Paradowska, Edyta; Jabłońska, Agnieszka; Studzińska, Mirosława; Suski, Patrycja; Kasztelewicz, Beata; Zawilińska, Barbara; Wiśniewska-Ligier, Małgorzata; Dzierżanowska-Fangrat, Katarzyna; Woźniakowska-Gęsicka, Teresa; Czech-Kowalska, Justyna; Lipka, Bożena; Kornacka, Maria; Pawlik, Dorota; Tomasik, Tomasz; Kosz-Vnenchak, Magdalena; Leśnikowski, Zbigniew J

2013-09-01

Human cytomegalovirus (HCMV) is the most widespread cause of congenital infection. The effects of various viral strains and viral loads on the infection outcome have been under debate. To determine the distribution of gN variants in HCMV strains isolated from children with congenital or postnatal infection and to establish the relationship between the viral genotype, the viral load, and the sequelae. The study population included congenitally HCMV-infected newborns and children with postnatal or unproven congenital HCMV infection. The genotyping was performed by RFLP analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. Our results demonstrated that the HCMV genotypes gN3b, gN4b, and gN4c were prevalent in the patients examined. There were no differences in the distributions of gN genotypes in the congenitally and postnatally infected children. Multiple HCMV strains were detected in both groups of children. A significant association between the HCMV gN4 genotype and the incidence of neurological disorders was observed (p=0.045). Our results suggest that the detection of the gN2 or the gN4 genotype may be indicative of serious manifestations in children. In contrast, the gN3b and the gN1 genotypes represent less pathogenic HCMV strains. The HCMV load in urine was significantly higher in children with congenital infection compared with children with postnatal infection. No correlation was found between the viral load and the genotype. Our results suggest that the gN genotype may be a virological marker of symptomatic HCMV infection in newborns. Copyright © 2013 Elsevier B.V. All rights reserved.

Bidirectional enhancing activities between human T cell leukemia-lymphoma virus type I and human cytomegalovirus in human term syncytiotrophoblast cells cultured in vitro.

Science.gov (United States)

Tóth, F D; Aboagye-Mathiesen, G; Szabó, J; Liu, X; Mosborg-Petersen, P; Kiss, J; Hager, H; Zdravkovic, M; Andirkó, I; Aranyosi, J

1995-12-01

The syncytiotrophoblast layer of the human placenta has an important role in limiting transplacental viral spread from mother to fetus. Human cytomegalovirus (HCMV) is capable of establishing a latent infection in syncytiotrophoblast cells, with restriction of gene expression to immediate-early and early proteins. We analyzed the extent of replication of human T cell leukemia-lymphoma virus type I (HTLV-I) in human term syncytiotrophoblasts infected with HTLV-I alone or coinfected with HTLV-I and HCMV. Although syncytiotrophoblasts could be infected with cell-free HTLV-I, no viral protein expression was found in the singly infected cells. On the contrary, coinfection of the cells with HTLV-I and HCMV resulted in simultaneous replication of both viruses. Bidirectional enhancing activities between HTLV-I and HCMV were mediated primarily by the Tax and immediate-early proteins, respectively. The stimulatory effect of HTLV-I Tax on HCMV replication appeared to be mediated partly by tumor necrosis factor beta and transforming growth factor beta-1. We observed formation of pseudotypes with HTLV-I nucleocapsids within HCMV envelopes, whereas HCMV was not pseudotyped by HTLV-I envelopes in dually infected syncytiotrophoblast cells. Our data suggest that in vivo dual infection of syncytiotrophoblast cells with HTLV-I and HCMV may facilitate the transplacental transmission of both viruses.

Human cytomegalovirus renders cells non-permissive for replication of herpes simplex viruses

International Nuclear Information System (INIS)

Cockley, K.D.

1988-01-01

The herpes simplex virus (HSV) genome during production infection in vitro may be subject to negative regulation which results in modification of the cascade of expression of herpes virus macromolecular synthesis leading to establishment of HSV latency. In the present study, human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of HSV type-1 (HSV-1). A delay in HSV replication of 15 hr as well as a consistent, almost 1000-fold inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 hr after superinfection were observed compared with controls infected with HSV alone. HSV type-2 (HSV-2) replication was similarly inhibited in HCMV-infected HEL cells. Prior ultraviolet-irradiation (UV) of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HCMV deoxyribonucleic acid (DNA) negative temperature-sensitive (ts) mutants inhibited HSV replications as efficiently as wild-type (wt) HCMV at the non-permissive temperature. Evidence for penetration and replication of superinfecting HSV into HCMV-infected cells was provided by blot hybridization of HSV DNA synthesized in HSV-superinfected cell cultures and by cesium chloride density gradient analysis of [ 3 H]-labeled HSV-1-superinfected cells

Evaluation of the effect of the incorporation of rubber tire waste particles on the properties of PP, HIPS and PP/HIPS matrices

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Larissa Stieven Montagna

2013-01-01

Full Text Available In recent years, the consumption of plastics has been increasing and as consequence, the waste generated has also increased. Rubber tire (RT waste is another residue which causes significant problems to society. In view of the considerable amounts of RT waste generated, this study aimed to evaluate the influence of the incorporation of RT particles into post-consumer thermoplastic matrices such as polypropylene (PP, high impact polystyrene (HIPS and PP/HIPS blends and the modification of the physical, morphological, rheological and mechanical properties. The particle sizes of the RT used were <500 and 500-1000 μm. The RT content was 10% w/w and the weight ratio for the PP/HIPS blend was 4/1, with processing by injection molding. The results showed that the smaller (500 μm particle size led to a decrease in the melt flow rate (MFR of the PP/RT composites (increased viscosity and an increase for the HIPS/RT composites. On the other hand, the larger particles (1000 μm led to a decrease in the mechanical performance of the PP/RT and HIPS/RT blends when compared with the neat polymers (PP and HIPS post-consumer. The observed decrease in the mechanical properties of these composites was due to weak filler/matrix interactions, which can be visualized in images by scanning electron microscopy (SEM of the fracture surface after tensile testing.

Injectable, Biomolecule-Responsive Polypeptide Hydrogels for Cell Encapsulation and Facile Cell Recovery through Triggered Degradation.

Science.gov (United States)

Xu, Qinghua; He, Chaoliang; Zhang, Zhen; Ren, Kaixuan; Chen, Xuesi

2016-11-16

Injectable hydrogels have been widely investigated in biomedical applications, and increasing demand has been proposed to achieve dynamic regulation of physiological properties of hydrogels. Herein, a new type of injectable and biomolecule-responsive hydrogel based on poly(l-glutamic acid) (PLG) grafted with disulfide bond-modified phloretic acid (denoted as PLG-g-CPA) was developed. The hydrogels formed in situ via enzymatic cross-linking under physiological conditions in the presence of horseradish peroxidase and hydrogen peroxide. The physiochemical properties of the hydrogels, including gelation time and the rheological property, were measured. Particularly, the triggered degradation of the hydrogel in response to a reductive biomolecule, glutathione (GSH), was investigated in detail. The mechanical strength and inner porous structure of the hydrogel were influenced by the addition of GSH. The polypeptide hydrogel was used as a three-dimensional (3D) platform for cell encapsulation, which could release the cells through triggered disruption of the hydrogel in response to the addition of GSH. The cells released from the hydrogel were found to maintain high viability. Moreover, after subcutaneous injection into rats, the PLG-g-CPA hydrogels with disulfide-containing cross-links exhibited a markedly faster degradation behavior in vivo compared to that of the PLG hydrogels without disulfide cross-links, implying an interesting accelerated degradation process of the disulfide-containing polypeptide hydrogels in the physiological environment in vivo. Overall, the injectable and biomolecule-responsive polypeptide hydrogels may serve as a potential platform for 3D cell culture and easy cell collection.

Bone-marrow-derived mesenchymal stem cells as a target for cytomegalovirus infection: Implications for hematopoiesis, self-renewal and differentiation potential

International Nuclear Information System (INIS)

Smirnov, Sergey V.; Harbacheuski, Ryhor; Lewis-Antes, Anita; Zhu Hua; Rameshwar, Pranela; Kotenko, Sergei V.

2007-01-01

Mesenchymal stem cells (MSCs) in bone marrow (BM) regulate the differentiation and proliferation of adjacent hematopoietic precursor cells and contribute to the regeneration of mesenchymal tissues, including bone, cartilage, fat and connective tissue. BM is an important site for the pathogenesis of human cytomegalovirus (HCMV) where the virus establishes latency in hematopoietic progenitors and can transmit after reactivation to neighboring cells. Here we demonstrate that BM-MSCs are permissive to productive HCMV infection, and that HCMV alters the function of MSCs: (i) by changing the repertoire of cell surface molecules in BM-MSCs, HCMV modifies the pattern of interaction between BM-MSCs and hematopoietic cells; (ii) HCMV infection of BM-MSCs undergoing adipogenic or osteogenic differentiation impaired the process of differentiation. Our results suggest that by altering BM-MSC biology, HCMV may contribute to the development of various diseases

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

DEFF Research Database (Denmark)

Fornara, O; Bartek, J; Rahbar, A

2016-01-01

Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

99mTc-HYNIC-derivatized ternary ligand complexes for 99mTc-labeled polypeptides with low in vivo protein binding

International Nuclear Information System (INIS)

Ono, Masahiro; Arano, Yasushi; Mukai, Takahiro; Fujioka, Yasushi; Ogawa, Kazuma; Uehara, Tomoya; Saga, Tsuneo; Konishi, Junji; Saji, Hideo

2001-01-01

6-Hydrazinopyridine-3-carboxylic acid (HYNIC) is a representative agent used to prepare technetium-99m ( 99m Tc)-labeled polypeptides with tricine as a coligand. However, 99m Tc-HYNIC-labeled polypeptides show delayed elimination rates of the radioactivity not only from the blood but also from nontarget tissues such as the liver and kidney. In this study, a preformed chelate of tetrafluorophenol (TFP) active ester of [ 99m Tc](HYNIC)(tricine)(benzoylpyridine: BP) ternary complex was synthesized to prepare 99m Tc-labeled polypeptides with higher stability against exchange reactions with proteins in plasma and lysosomes using the Fab fragment of a monoclonal antibody and galactosyl-neoglycoalbumin (NGA) as model polypeptides. When incubated in plasma, [ 99m Tc](HYNIC-Fab)(tricine)(BP) showed significant reduction of the radioactivity in high molecular weight fractions compared with [ 99m Tc](HYNIC-Fab)(tricine) 2. When injected into mice, [ 99m Tc](HYNIC-NGA)(tricine)(BP) was metabolized to [ 99m Tc](HYNIC-lysine)(tricine)(BP) in the liver with no radioactivity detected in protein-bound fractions in contrast to the observations with [ 99m Tc](HYNIC-NGA)(tricine) 2. In addition, [ 99m Tc](HYNIC-NGA)(tricine)(BP) showed significantly faster elimination rates of the radioactivity from the liver as compared with [ 99m Tc](HYNIC-NGA)(tricine) 2. Similar results were observed with 99m Tc-labeled Fab fragments where [ 99m Tc](HYNIC-Fab)(tricine)(BP) exhibited significantly faster elimination rates of the radioactivity not only from the blood but also from the kidney. These findings indicated that conjugation of [ 99m Tc](HYNIC)(tricine)(BP) ternary ligand complex to polypeptides accelerated elimination rates of the radioactivity from the blood and nontarget tissues due to low binding of the [ 99m Tc](HYNIC)(tricine)(BP) complex with proteins in the blood and in the lysosomes. Such characteristics would render the TFP active ester of [ 99m Tc](HYNIC)(tricine)(BP) complex

Cytomegalovirus infection in pediatric rheumatic diseases: a review

Directory of Open Access Journals (Sweden)

Wolf Dana G

2010-05-01

Full Text Available Abstract Human cytomegalovirus (HCMV is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease.

The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients

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Renata Fragelli Fonseca

2012-11-01

Full Text Available Members of the Herpesviridae family have been implicated in a number of tumours in humans. At least 75% of the human population has had contact with cytomegalovirus (HCMV. In this work, we screened 75 Brazilian glioma biopsies for the presence of HCMV DNA sequences. HCMV DNA was detected in 36% (27/75 of the biopsies. It is possible that HCMV could be a co-factor in the evolution of brain tumours.

Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia

DEFF Research Database (Denmark)

Meier, J J; Gallwitz, B; Siepmann, N

2003-01-01

AIMS/HYPOTHESIS: In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported. Therefore, we studied the effect of GIP on glucagon ...

Similarities in the induction of synthesis of a cell-surface polypeptide in Arthrobacter sp. by near-UV irradiation and photodynamic conditions

International Nuclear Information System (INIS)

Hoober, J.K.; Franzi, J.

1983-01-01

Irradiation of aerobic suspensions of Arthrobacter sp. with near-UV light (310-400 nm) induced synthesis of a 21 000 dalton, cell-surface polypeptide. Synthesis of this polypeptide also was induced by visible light in the presence of photodynamic dyes. Induction of the polypeptide in ear-UV light and with visible light plus dyes was inhibited by histidine. Hemin inhibited induction in near-UV light and in visible light with methylene blue, neutral red and acriflavin, which are cationic dyes, but failed to inhibit induction in visible light with rose bengal, an anionic dye. These results suggested that inhibition by hemin required electrostatically favored interaction between the anionic porphyrin and the sensitizer, and that the near-UV light effect was mediated by a cationic or neutral endogenous sensitizer. The similarities in the responses of the cells to near-UV irradiation and visible light plus dyes suggested that the mechanism of induction under the two conditions was the same. (author)

N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride: An immune-enhancing adjuvant for hepatitis E virus recombinant polypeptide vaccine in mice.

Science.gov (United States)

Tao, Wei; Zheng, Hai-Qun; Fu, Ting; He, Zhuo-Jing; Hong, Yan

2017-08-03

Adjuvants are essential for enhancing vaccine potency by improving the humoral and/or cell-mediated immune response to vaccine antigens. This study was performed to evaluate the immuno-enhancing characteristic of N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride (HTCC), the cationically modified chitosan, as an adjuvant for hepatitis E virus (HEV) recombinant polypeptide vaccine. Animal experiments showed that HTCC provides adjuvant activity when co-administered with HEV recombinant polypeptide vaccine by intramuscularly route. Vaccination using HTCC as an adjuvant was associated with increases of the serum HEV-specific IgG antibodies, splenocytes proliferation and the growths of CD4 + CD8 - T lymphocytes and IFN-γ-secreting T lymphocytes in peripheral blood. These findings suggested that HTCC had strong immuno-enhancing effect. Our findings are the first to demonstrate that HTCC is safe and effective in inducing a good antibody response and stimulating Th1-biased immune responses for HEV recombinant polypeptide vaccine.

High energy pp and anti-pp elastic scattering in nucleon valence core model

International Nuclear Information System (INIS)

Islam, M.M.; Fearnley, T.

1986-01-01

Connection between the valence core model and the effective QCD models of nucleon structure is pointed out. Also, implication of recent anti-pp differential cross section measurements at 53 GeV on our previous calculations is discussed

Intermittency patterns in pp collisions at 360 GeV/c

International Nuclear Information System (INIS)

Singh, J.B.; Kohli, J.M.

1991-01-01

The intermittency effect has been observed in pp collisions at 360 GeV/c and the strength decreases with the increase in multiplicity. The low multiplicity events in pp data (n ch ≤ 8), anti pp collisions (n ch ≤ 15) at Collider energy and elementary interaction (e + e - , μp) samples have almost the same strength. Most likely, few sources seem to contribute at lower multiplications. The intermittency effect is less in pp data compared to e + e - data, however it is fairly strong as compared to nucleus data. The presently used hadronization models DPM, LUND and FRITIOF do not reproduce the results fully. (orig.)

The Beads of Translation: Using Beads to Translate mRNA into a Polypeptide Bracelet

Science.gov (United States)

Dunlap, Dacey; Patrick, Patricia

2012-01-01

During this activity, by making beaded bracelets that represent the steps of translation, students simulate the creation of an amino acid chain. They are given an mRNA sequence that they translate into a corresponding polypeptide chain (beads). This activity focuses on the events and sites of translation. The activity provides students with a…

Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins

International Nuclear Information System (INIS)

Garrison, W.M.

1985-01-01

The purpose of this review is to bring together and to correlate the wide variety of experimental studies that provide information on the reaction products and reaction mechanisms involved in the radiolysis of peptides, polypeptides and proteins (including chromosomal proteins) in both aqueous and solid-state systems. The comparative radiation chemistry of these systems is developed in terms of specific reactions of the peptide main-chain and the aliphatic, aromatic-unsaturated and sulfur-containing side-chains. Information obtained with the various experimental techniques of product analysis, competition kinetics, spin-trapping, pulse radiolysis and ESR spectroscopy is included. 147 refs

Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins

Energy Technology Data Exchange (ETDEWEB)

Garrison, W.M.

1985-01-01

The purpose of this review is to bring together and to correlate the wide variety of experimental studies that provide information on the reaction products and reaction mechanisms involved in the radiolysis of peptides, polypeptides and proteins (including chromosomal proteins) in both aqueous and solid-state systems. The comparative radiation chemistry of these systems is developed in terms of specific reactions of the peptide main-chain and the aliphatic, aromatic-unsaturated and sulfur-containing side-chains. Information obtained with the various experimental techniques of product analysis, competition kinetics, spin-trapping, pulse radiolysis and ESR spectroscopy is included. 147 refs.

Analysis of Urine Composition in Type II Diabetic Mice after Intervention Therapy Using Holothurian Polypeptides

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Yanyan Li

2017-07-01

Full Text Available Hydrolysates and peptide fractions (PF obtained from sea cucumber with commercial enzyme were studied on the hyperglycemic and renal protective effects on db/db rats using urine metabolomics. Compared with the control group the polypeptides from the two species could significantly reduce the urine glucose and urea. We also tried to address the compositions of highly expressed urinary proteins using a proteomics approach. They were serum albumins, AMBP proteins, negative trypsin, elastase, and urinary protein, GAPDH, a receptor of urokinase-type plasminogen activator (uPAR, and Ig kappa chain C region. We used the electronic nose to quickly detect changes in the volatile substances in mice urine after holothurian polypeptides (HPP fed, and the results show it can identify the difference between treatment groups with the control group without overlapping. The protein express mechanism of HPP treating diabetes was discussed, and we suggested these two peptides with the hypoglycemic and renal protective activity might be utilized as nutraceuticals.

Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative Mothers in Sub-Saharan Africa.

Science.gov (United States)

Musonda, Kunda G; Nyonda, Mary; Filteau, Suzanne; Kasonka, Lackson; Monze, Mwaka; Gompels, Ursula A

2016-06-01

Breastfeeding imparts beneficial immune protection and nutrition to infants for healthy growth, but it is also a route for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. In previous studies, we showed that HCMV adversely affects infant development in Africa, particularly with maternal HIV exposure. In this study, we analyzed infants risks for acquisition of HCMV infection from breastfeeding and compared HIV-positive and HIV-negative mothers. Two cohorts were studied in Zambia. (1) Two hundred sixty-one HIV-infected and HIV-uninfected mothers were compared for HCMV deoxyribonucleic acid (DNA) loads and genotypes (glycoprotein gO) in milk from birth to 4 months postpartum. (2) Maternally HIV-exposed and HIV-unexposed infants were compared for HCMV infection risk factors. The second cohort of 460 infants, from a trial of micronutrient-fortified complementary-food to breastfeeding, were studied between 6 and 18 months of age. Human cytomegalovirus seroprevalence was assayed, and logistic regression was used to calculate risk factors for HCMV infection, including maternal HIV exposure and breastfeeding duration. Human cytomegalovirus was detected in breast milk from 3 days to 4 months postpartum, with significantly raised levels in HIV-positive women and independent of genotype. In infants, HCMV antibody seroprevalence was 83% by 18 months age. Longer breastfeeding duration increased infection risk in maternally HIV-unexposed (odds ratio [OR] = 2.69 for 18 months vs 6 months vs never; 95% CI, 3.71-111.70; P breastfeeding, which is common in Africa, increased risk of HCMV infection in infants. Both HIV-positive and HIV-negative women had extended milk HCMV secretion. Women who were HIV-positive secreted higher HCMV levels, and for longer duration, with their children at increased infection risk. Human cytomegalovirus control is required to maintain health benefits of breastfeeding. © The Author 2016. Published by Oxford University Press

Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

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Arun Kapoor

Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

Interpretation of K+¯pair production in pp collisions

Science.gov (United States)

Dzyuba, A.; Büscher, M.; Hanhart, C.; Kleber, V.; Koptev, V.; Ströher, H.; Wilkin, C.

2008-10-01

A combined analysis of the published data on the pp → dK +¯0 reaction at excess energies of 47.4MeV and 104.7MeV is presented that takes into account final-state interactions in both the K +¯0 and ¯0 d channels. The strong attraction of the antikaons with nucleons, already noted for the pp → ppK + K - reaction, leads here to very different ¯0 d and K+d distributions, with the former being dominantly in an s -wave and the latter in a p -wave. Evidence is also found from the K +¯0 distributions for the production of the a 0 +(980) scalar resonance. The inclusion of both final-state interactions improves the description of the energy dependence of the pp → dK +¯0 total cross-section.

Chemical modification as an approach for the identification of UDPG-binding polypeptides of UDPG-glucose: (1,3)-Beta-glucan synthase

International Nuclear Information System (INIS)

Mason, T.L.

1989-01-01

The lysine-reactive chemical modification reagents uridine diphosphate pyridoxal (UDP-pyridoxal) and formaldehyde (HCHO) were used to identify UDPG-binding polypeptides of UDP-glucose: (1,3)-β-D-glucan synthase (GS) from red beet storage tissue. Complete enzyme inactivation occurred after exposure to micromolar levels of UDP-pyridoxal and millimolar levels of HCHO. Divalent cations (Mg 2+ and Ca 2+ , particularly Ca 2+ ) were required by both for inactivation. Substrate (UDPG) and chelators (EDTA and EGTA) protected plasma membrane GS (PMGS) against UDP-pyridoxal and HCHO inhibition. UDPG protected CHAPS solubilized GS (CSGS) against UDP-pyridoxal inactivation, but not against HCHO. It was concluded that beet GS contains a lysine residue at the UDPG-binding site. When PMGS was directly labeled with UDP[ 3 H]-pyridoxal or [ 14 C]HCHO, random labeling occurred. Therefore, a multi-step labeling procedure was developed. Nonessential lysine residues were first blocked with HCHO while 5 mM UDPG protected the active site lysine. Background labeling was reduced 4-fold. Membranes were recovered by centrifugation and the active site lysine exposed to [ 14 C] HCHO. Major labeled polypeptides were at 200, 76, and 54 kD. Minor polypeptides were seen at 94, 82, 68, 60, and 20-25 kD. CSGS was labeled by a modified multi-step procedure. CSGS was blocked by reaction with UDP-pyridoxal in the presence of UDPG. CSGS was then recovered by product entrapment and labeled with [ 14 C]HCHO. Background labeling was reduced by 8-fold and potential UDPG-binding polypeptides narrowed to 68, 54, 25 and 22 kD

Pressure, flow and hydraulic interference measurements in ONKALO at Olkiluoto, drillholes ONK-PP262 and ONK-PP274

International Nuclear Information System (INIS)

Hurmerinta, E.; Pekkanen, J.; Komulainen, J.; Rouhiainen, P.

2012-01-01

The general purpose of these studies is to characterize the fracture network and groundwater flow properties in a volume of rock, which is representative of the rock close to deposition holes. As a part of the studies hydraulic tests and flow measurements were applied in two drillholes in hydraulically poorly conductive bedrock. This report presents the principles of the methods as well as the results of the measurements carried out in the underground facilities of ONKALO. The measurements were conducted in drillholes ONK-PP262 and ONK-PP274 between May 9, 2010 and June 9, 2011. The aim of the measurements was to obtain pressure in the closed drillholes, to detect water yielding fractures by flow measurements, to obtain transmissivity with overpressure and drawdown tests and to study hydraulic interference between the drillholes by cross-hole hydraulic tests. The PFL DIFF probe was used to detect flow within single fractures in the drillhole. Transmissive water yielding fractures were found at depths 17.9 m, 16.9 m and 16.4 m in ONK-PP262 and at depths 19.8 m and 19.5 m in ONK-PP274. The cross-hole hydraulic tests included three basic phases. Flow was measured in one drillhole when the other drillhole was open, closed or overpressurized. The cross-hole hydraulic tests were carried out to both directions in the two drillholes. (orig.)

Exploiting the yeast L-A viral capsid for the in vivo assembly of chimeric VLPs as platform in vaccine development and foreign protein expression.

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Frank Powilleit

Full Text Available A novel expression system based on engineered variants of the yeast (Saccharomyces cerevisiae dsRNA virus L-A was developed allowing the in vivo assembly of chimeric virus-like particles (VLPs as a unique platform for a wide range of applications. We show that polypeptides fused to the viral capsid protein Gag self-assemble into isometric VLP chimeras carrying their cargo inside the capsid, thereby not only effectively preventing proteolytic degradation in the host cell cytosol, but also allowing the expression of a per se cytotoxic protein. Carboxyterminal extension of Gag by T cell epitopes from human cytomegalovirus pp65 resulted in the formation of hybrid VLPs that strongly activated antigen-specific CD8(+ memory T cells ex vivo. Besides being a carrier for polypeptides inducing antigen-specific immune responses in vivo, VLP chimeras were also shown to be effective in the expression and purification of (i a heterologous model protein (GFP, (ii a per se toxic protein (K28 alpha-subunit, and (iii a particle-associated and fully recyclable biotechnologically relevant enzyme (esterase A. Thus, yeast viral Gag represents a unique platform for the in vivo assembly of chimeric VLPs, equally attractive and useful in vaccine development and recombinant protein production.

Endogenous pancreatic polypeptide in different vascular beds: relationship to release and degradation in subjects with normal and decreased kidney function

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Schwartz, T W; Bülow, J B

1986-01-01

a significantly higher level of circulating PP than controls (n = 10): median PP = 52 (range 21 to 352) v 20 (6 to 143) pmol/L, respectively (P less than 0.02). Circulating PP was inversely correlated to 51Cr-EDTA plasma clearance (r = -0.57, P less than 0.02, n = 14) and directly correlated to serum creatinine...... a progressively increasing rate of PP secretion in subjects with raised circulating PP. No statistically significant difference could be detected between systemic and renal venous PP or across the lung, left adrenal gland, or lower limb. Assuming steady state between secretion and biodegradation, the metabolic...

Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

International Nuclear Information System (INIS)

Nishiyama, Y.; Rapp, F.

1981-01-01

Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants

Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

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Leonardo D'Aiuto

Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

Fibrillar dimer formation of islet amyloid polypeptides

Energy Technology Data Exchange (ETDEWEB)

Chiu, Chi-cheng [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); de Pablo, Juan J. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

2015-05-08

Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

Fibrillar dimer formation of islet amyloid polypeptides

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Chi-cheng Chiu

2015-09-01

Full Text Available Amyloid deposits of human islet amyloid polypeptide (hIAPP, a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

Mathematical Modelling of Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide-1 following Ingestion of Glucose

DEFF Research Database (Denmark)

Røge, Rikke M; Bagger, Jonatan I; Alskär, Oskar

2017-01-01

The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play an important role in glucose homeostasis by potentiating glucose-induced insulin secretion. Furthermore, GLP-1 has been reported to play a role in glucose homeostasis by inhibiting ...

Noninvasive murine glioma detection improved following photobleaching of skin PpIX fluorescence

Science.gov (United States)

Gibbs-Strauss, Summer L.; Davis, Scott C.; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2008-02-01

Aminolevulinic Acid (ALA) is a prodrug which can be administered to cells, animals or patients after which it is transformed via the Heme synthesis pathway into the fluorescent molecule Protoporphyrin IX (PpIX). PpIX has been shown to be useful as both a photosensitizer for photodynamic therapy (PDT) and as a fluorescence imaging contrast agent. The ALA-PpIX system not only provides contrast for fluorescence imaging but also gives information about the metabolic activity of the imaged tissue and thus could be useful for monitoring cancer therapy. In the current study skin photobleaching was examined to determine if PpIX fluorescence contrast in malignant brain tumors could be better visualized noninvasively. Red light photobleaching decreased skin PpIX fluorescence and increased the ability to noninvasively quantify PpIX fluorescence in murine gliomas, as in vivo measurements of mean PpIX fluorescence more closely matched ex vivo quantification following skin photobleaching. Three doses of blue light photobleaching (4 J/cm2, 8 J/cm2 and 12 J/cm2) were tested and determined to give similar levels of skin photobleaching as well as a similar window of decreased skin PpIX fluorescence for noninvasive fluorescence imaging following the photobleaching dose administration.

Human cytomegalovirus replicates in gamma-irradiated fibroblasts

International Nuclear Information System (INIS)

Shanley, J.D.

1986-01-01

Because of the unique interdependence of human cytomegalovirus (HCMV) and the physiological state of the host cell, we evaluated the ability of human foreskin fibroblasts (HFF), exposed to gamma radiation, to support HCMV growth. Irradiation of HFF with 2,500 rADS prevented cellular proliferation and suppressed cellular DNA, but not RNA or protein synthesis. Treatment of HFF cells with 2,500 rADS 6 or 48 hours prior to infection did not alter the time course or virus yield during HCMV replication. Virus plaquing efficiency in irradiated cells was comparable to that of nonirradiated cells. As judged by thymidine incorporation and BUdR inhibition of virus replication, HCMV infection induced both thymidine kinase activity and host cell DNA synthesis in irradiated cells. In addition, virus could be recovered from HFF exposed to radiation 0-2 days after infection with HCMV. These studies indicate that the damage to cells by gamma irradiation does not alter the capacity of host cells to support HCMV replication

Core drilling of drillholes OL-PP66-69 at Olkiluoto 2008

International Nuclear Information System (INIS)

Kuusirati, J.; Tarvainen, A.-M.

2009-04-01

Suomen Malmi Oy (Smoy) core drilled four 24.88 - 25.39 m long investigation drillholes at Olkiluoto in June 2008. The identification numbers of the holes are OL-PP66, OL-PP67, OL-PP68 and OL-PP69. The drillholes are 75.7 mm by diameter. Drillholes were core drilled with the diamond drill rig Diamec 1000. The drilling water was taken from the ONKALO drilling water pipeline and premixed sodium fluorescein was used as a label agent in the drilling water. The labelled drilling water was driven to the drilling places in a tank. In addition to drilling the drill cores were logged and reported by geologist. During geological investigation the following parameters were logged: lithology, foliation, fracture parameters, fractured zones, core loss, weathering, fracture frequency, RQD and rock quality. The main rock types in the drillholes are diatexitic and veined gneisses and pegmatitic granite. The average fracture frequency in holes varied from 3.9 pcs/m to 5.8 pcs/m. The average RQD values varied from 84 % to 93 %. In the drillhole OL-PP66 two fractured zones were penetrated and in OL-PP69 one fractured zone. The drill cores OL-PP67 and OL-PP68 showed no fractured zones. Smoy also carried out optical imaging of the drillholes. The assignment included the field work and the data processing. This report describes the field operation, the equipment as well as the processing procedures and shows the obtained results and their quality. The raw and processed data are delivered digitally in WellCAD and PDF format. (orig.)

The synthesis and characterization of polypeptide-adriamycin conjugates and its complexes with adriamycin. Part I

NARCIS (Netherlands)

Heeswijk, W.A.R.; Hoes, C.J.T.; Stoffer, T.; Eenink, M.J.D.; Potman, W.; Feijen, Jan

1985-01-01

Poly(α-l-glutamic acid) (PGA) was grafted with amino acid and oligopeptide spacers up to 5 amino acids with the use of N,N'-carbonyldiimidazole and 2,3-dihydro-1,2-benz-isothiazole-3-on-1, 1-dioxide (saccharin) as an additive, and these polypeptides were characterized. The antitumor antibiotic

Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation

DEFF Research Database (Denmark)

Bellmann-Sickert, Kathrin; Elling, Christian E; Madsen, Andreas N

2011-01-01

The main disadvantages of peptide pharmaceuticals are their rapid degradation and excretion, their low hydrophilicity, and low shelf lifes. These bottlenecks can be circumvented by acylation with fatty acids (lipidation) or polyethylene glycol (PEGylation). Here, we describe the modification....... Lipidation resulted in prolonged action of the hPP analogue in respect of reducing food intake in mice after subcutaneous administration. Therefore, the lipidated hPP analogue could constitute a potential new therapeutic agent against obesity....

pp 1101–111

Indian Academy of Sciences (India)

Administrator

Electronic Supplementary Material. Graphical abstract. Preparation and characterization of monosubstituted porphyrins immobilized on nanosilica by Ebrahim Ahmadi et al (pp 1101–1112). N-(3-triethoxysilylpropyl)-4-formyl benzamide (Aldehyde (1)), that bears a Si(OEt)3 group, was anchored to silica support by controlled ...

Radiation Improved Mechanical and Thermal Property of PP/HDPE

International Nuclear Information System (INIS)

Chaisupaditsin, M.; Thammit, C.; Techakiatkul, C.

1998-01-01

The mechanical properties, thermal properties and gel contents of PP-irradiated HDPE blends were studied. HDPE was gamma irradiated in the dose range of 10-30 kGy. The ratios of polymer blends of 30PP:70HDPE was mixed by a twin screw extruder at speed of 50 rpm. Irradiated HDPE with 30 kGy showed the highest gel contents. The blends ratio of 30PP:70HDPE (30 kGy) shows better heat resistance than the blends with non-irradiated HDPE. With increasing the radiation doses, the mechanical properties of the blends were improved

pp spin correlations at high p/sub T/

International Nuclear Information System (INIS)

Auer, I.P.; Colton, E.; Ditzler, W.R.

1980-01-01

New data are presented for measurements of the spin correlation in pp reactions with longitudinally polarized beam and target. Data were obtained at 11.75 GeV/c for both elastic scattering and for π + - and π - -production at high p/sub T/ in pp reactions at 11.75 GeV/c. A comparison is made with recent predictions of quark-parton models

Inhibition of the coated vesicle proton pump and labeling of a 17,000-dalton polypeptide by N,N'-dicyclohexylcarbodiimide

International Nuclear Information System (INIS)

Arai, H.; Berne, M.; Forgac, M.

1987-01-01

N,N'-Dicyclohexylcarbodiimide (DCCD) inhibits 100% of proton transport and 80-85% of (Mg2+)-ATPase activity in clathrin-coated vesicles. Half-maximum inhibition of proton transport is observed at 10 microM DCCD after 30 min. Although treatment of the coated vesicle (H+)-ATPase with DCCD has no effect on ATP hydrolysis in the detergent-solubilized state, sensitivity of proton transport and ATPase activity to DCCD is restored following reconstitution into phospholipid vesicles. In addition, treatment of the detergent-solubilized enzyme with DCCD followed by reconstitution gives a preparation that is blocked in both proton transport and ATP hydrolysis. These results suggest that although the coated vesicle (H+)-ATPase can react with DCCD in either a membrane-bound or detergent-solubilized state, inhibition of ATPase activity is only manifested when the pump is present in sealed membrane vesicles. To identify the subunit responsible for inhibition of the coated vesicle (H+)-ATPase by DCCD, we have labeled the partially purified enzyme with [ 14 C]DCCD. A single polypeptide of molecular weight 17,000 is labeled. The extremely hydrophobic nature of this polypeptide is indicated by its extraction with chloroform:methanol. The 17,000-dalton protein can be labeled to a maximum stoichiometry of 0.99 mol of DCCD/mol of protein with 100% inhibition of proton transport occurring at a stoichiometry of 0.15-0.20 mol of DCCD/mol of protein. Amino acid analysis of the chloroform:methanol extracted 17,000-dalton polypeptide reveals a high percentage of nonpolar amino acids. The similarity in properties of this protein and the DCCD-binding subunit of the coupling factor (H+)-ATPases suggests that the 17,000-dalton polypeptide may function as part of a proton channel in the coated vesicle proton pump

Extrinsic functions of lectin domains in O-N-acetylgalactosamine glycan biosynthesis

DEFF Research Database (Denmark)

Lorenz, Virginia; Ditamo, Yanina; Cejas, Romina B

2016-01-01

during O-GalNAc glycan biosynthesis. The presence of lectin domain T3lec or T4lec during ppGalNAc-T2 and ppGalNAc-T3 catalytic reaction had a clear inhibitory effect on GalNAc-T activity. Interaction of T3lec or T4lec with ppGalNAc-T2 catalytic domain was not mediated by carbohydrate. T3lec, but not T2......Glycan biosynthesis occurs mainly in Golgi. Molecular organization and functional regulation of this process are not well understood. We evaluated the extrinsic effect of lectin domains (β-trefoil fold) of polypeptide GalNAc-transferases (ppGalNAc-Ts) on catalytic activity of glycosyltransferases...

Morphological variation of stimuli-responsive polypeptide at air–water interface

International Nuclear Information System (INIS)

Shin, Sungchul; Ahn, Sungmin; Cheng, Jie; Chang, Hyejin; Jung, Dae-Hong; Hyun, Jinho

2016-01-01

Graphical abstract: - Highlights: • It is the first report on the interfacial properties of ELP monolayers formed at the air–water interface. • ELP monolayers could be prepared with high stability at the air–water interface. • The compressive behavior of thermo-sensitive ELP monolayers was imaged. • The SERS spectra showed a change in the ELP secondary structure at different preparation conditions. - Abstract: The morphological variation of stimuli-responsive polypeptide molecules at the air–water interface as a function of temperature and compression was described. The surface pressure–area (π–A) isotherms of an elastin-like polypeptide (ELP) monolayer were obtained under variable external conditions, and Langmuir–Blodgett (LB) monolayers were deposited onto a mica substrate for characterization. As the compression of the ELP monolayer increased, the surface pressure increased gradually, indicating that the ELP monolayer could be prepared with high stability at the air–water interface. The temperature in the subphase of the ELP monolayer was critical in the preparation of LB monolayers. The change in temperature induced a shift in the π–A isotherms as well as a change in ELP secondary structures. Surprisingly, the compression of the ELP monolayer influenced the ELP secondary structure due to the reduction in the phase transition temperature with decreasing temperature. The change in the ELP secondary structure formed at the air–water interface was investigated by surface-enhanced Raman scattering. Moreover, the morphology of the ELP monolayer was subsequently imaged using atomic force microscopy. The temperature responsive behavior resulted in changes in surface morphology from relatively flat structures to rugged labyrinth structures, which suggested conformational changes in the ELP monolayers.

Biosynthesis of human sialophorins and analysis of the polypeptide core

International Nuclear Information System (INIS)

Remold-O'Donnell, E.; Kenney, D.; Rosen, F.S.

1987-01-01

Biosynthesis was examined of sialophorin (formerly called gpL115) which is altered in the inherited immunodeficiency Wiskott-Aldrich syndrome. Sialophorin is greater than 50% carbohydrate, primarily O-linked units of sialic acid, galactose, and galactosamine. Pulse-labeling with [ 35 S]methionine and chase incubation established that sialophorin is synthesized in CEM lymphoblastoid cells as an Mr 62,000 precursor which is converted within 45 min to mature glycosylated sialophorin, a long-lived molecule. Experiments with tunicamycin and endoglycosidase H demonstrated that sialophorin contains N-linked carbohydrate (approximately two units per molecule) and is therefore an N,O-glycoprotein. Pulse-labeling of tunicamycin-treated CEM cells together with immunoprecipitation provided the means to isolate the [ 35 S]-methionine-labeled polypeptide core of sialophorin and determine its molecular weight (58,000). This datum allowed us to express the previously established composition on a per molecule basis and determine that sialophorin molecules contain approximately 520 amino acid residues and greater than or equal to 100 O-linked carbohydrate units. A recent study showed that various blood cells express sialophorin and that there are two molecular forms: lymphocyte/monocyte sialophorin and platelet/neutrophil sialophorin. Biosynthesis of the two forms was compared by using sialophorin of CEM cells and sialophorin of MOLT-4 cells (another lymphoblastoid line) as models for lymphocyte/monocyte sialophorin and platelet/neutrophil sialophorin, respectively. The time course of biosynthesis and the content of N units were found to be identical for the two sialophorin species. [ 35 S]Methionine-labeled polypeptide cores of CEM sialophorin and MOLT sialophorin were isolated and compared by electrophoresis, isoelectrofocusing, and a newly developed peptide mapping technique

Morphological variation of stimuli-responsive polypeptide at air–water interface

Energy Technology Data Exchange (ETDEWEB)

Shin, Sungchul; Ahn, Sungmin; Cheng, Jie [Department of Biosystems and Biomaterials Science and Engineering, Seoul National University, Seoul 151-921 (Korea, Republic of); Chang, Hyejin; Jung, Dae-Hong [Department of Chemical Education, Seoul National University, Seoul 151-741 (Korea, Republic of); Hyun, Jinho, E-mail: jhyun@snu.ac.kr [Department of Biosystems and Biomaterials Science and Engineering, Seoul National University, Seoul 151-921 (Korea, Republic of); Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea. (Korea, Republic of)

2016-12-01

Graphical abstract: - Highlights: • It is the first report on the interfacial properties of ELP monolayers formed at the air–water interface. • ELP monolayers could be prepared with high stability at the air–water interface. • The compressive behavior of thermo-sensitive ELP monolayers was imaged. • The SERS spectra showed a change in the ELP secondary structure at different preparation conditions. - Abstract: The morphological variation of stimuli-responsive polypeptide molecules at the air–water interface as a function of temperature and compression was described. The surface pressure–area (π–A) isotherms of an elastin-like polypeptide (ELP) monolayer were obtained under variable external conditions, and Langmuir–Blodgett (LB) monolayers were deposited onto a mica substrate for characterization. As the compression of the ELP monolayer increased, the surface pressure increased gradually, indicating that the ELP monolayer could be prepared with high stability at the air–water interface. The temperature in the subphase of the ELP monolayer was critical in the preparation of LB monolayers. The change in temperature induced a shift in the π–A isotherms as well as a change in ELP secondary structures. Surprisingly, the compression of the ELP monolayer influenced the ELP secondary structure due to the reduction in the phase transition temperature with decreasing temperature. The change in the ELP secondary structure formed at the air–water interface was investigated by surface-enhanced Raman scattering. Moreover, the morphology of the ELP monolayer was subsequently imaged using atomic force microscopy. The temperature responsive behavior resulted in changes in surface morphology from relatively flat structures to rugged labyrinth structures, which suggested conformational changes in the ELP monolayers.

Effects of vasoactive intestinal polypeptide on heart rate in relation to vagal cardioacceleration in conscious dogs

NARCIS (Netherlands)

Roossien, A; Brunstig, J.R; Nijmeijer, A; Zaagsma, Hans; Zijlstra, W.G

Objective: The vagal cardiac accelerator (VCA) system takes part in the nervous control of the heart rate. In the present study we tried to adduce evidence that vasoactive intestinal polypeptide (VLP) contributes to vagally induced cardioacceleration. Methods: The effect of VIP on heart rate and

Update on the current status of cytomegalovirus vaccines.

Science.gov (United States)

Sung, Heungsup; Schleiss, Mark R

2010-11-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

Thermally Targeted Delivery of a c-Myc Inhibitory Peptide In Vivo Using Elastin-like Polypeptide

Science.gov (United States)

2009-10-01

cytoplasm. Also, in a subset of cells, Bac-ELP1⁎-H1 showed very bright nuclear staining exclusive of nucleoli (Fig. 5, lower right, arrows). 3.6. Time...localization was very bright relative to the amount of polypeptide in the cytoplasm, and it appeared to be nucleoplasmic and excluded from nucleoli . The

Difference flow and electrical conductivity measurements at the Olkiluoto site in Eurajoki, drillholes OL-PP66 - OL-PP69

International Nuclear Information System (INIS)

Poellaenen, J.

2009-04-01

The Posiva Flow Log, Difference Flow Method (PFL DIFF) uses a flowmeter that incorporates a flow guide and can be used for relatively quick determinations of hydraulic conductivity and hydraulic head in fractures/fractured zones in cored drillholes. This report presents the principles of the method and the results of measurements carried out in drillholes OL-PP66, OL-PP67, OL-PP68 and OL-PP69 at the Olkiluoto investigation site in August 2008. All the drillholes discussed in this report are ground holes. The same measuring programme was employed in all four drillholes. The section length of the flow guide was either 2 m or 0.5 m. Flow into the drillhole or from the drillhole to the bedrock was measured within the section lengths and carried out in both pumped and natural (i.e. un-pumped) conditions. Calculations of the transmissivity (T) and the hydraulic head (h) of the zones are shown in the results. The device used includes a sensor for single point resistance (SPR). SPR was measured in connection with flow measurements. The electrical conductivity (EC) of fracture-specific water was measured in chosen fractures in some of the drillholes. Fractures were selected on the basis of the measured flow from fracture to drillhole. The EC of the drillhole water was also measured. (orig.)

Hemoglobin variants as models for investigation of dissociation of intact polypeptide chains by ESI tandem mass spectrometry

International Nuclear Information System (INIS)

Light, K.J.; Loo, J.A.; Edmonds, C.G.; Smith, R.D.

1991-06-01

Electrospray ionization mass spectroscopy (ESI-MS) is rapidly becoming a practical biochemical tool for peptide and protein sequence analysis. The utility of ESI-MS is through use of Collisionally Activated Dissociation (ESI-CAD-MS). Human hemoglobin (Hb, ∼62 kDa) consists of four polypeptide chains and a prosthetic heme group. There are over 400 Hb variants, characterized by amino acid substitutions in either the alpha or beta polypeptide chains. We investigated ESI-CAD-MS as a tool for rapidly analyzing amino acid substitutions, using eight Hb beta chain variants. The approximate location of the modification can be deduced from comparison of the CAD mass spectra and observance of the mass shifts of the fragment ion containing the substitution. Fragmentation occurs preferentially at the amino terminus of proline residues. For most substitutions, differences in CAD mass spectra were not seen. 2 figs

Scalar fields nonminimally coupled to pp waves

International Nuclear Information System (INIS)

Ayon-Beato, Eloy; Hassaiene, Mokhtar

2005-01-01

Here, we report pp waves configurations of three-dimensional gravity for which a scalar field nonminimally coupled to them acts as a source. In absence of self-interaction the solutions are gravitational plane waves with a profile fixed in terms of the scalar wave. In the self-interacting case, only power-law potentials parameterized by the nonminimal coupling constant are allowed by the field equations. In contrast with the free case the self-interacting scalar field does not behave like a wave since it depends only on the wave-front coordinate. We address the same problem when gravitation is governed by topologically massive gravity and the source is a free scalar field. From the pp waves derived in this case, we obtain at the zero topological mass limit, new pp waves solutions of conformal gravity for any arbitrary value of the nonminimal coupling parameter. Finally, we extend these solutions to the self-interacting case of conformal gravity

Cancer Nano technology Using Elastin-Like Polypeptides

International Nuclear Information System (INIS)

Siti Najila Mohd Janib

2014-01-01

Despite progress in understanding cancer biology, this knowledge has not translated into comparable advances in the clinic. Two fundamental problems currently stalling the efficient treatment of cancer have been detecting cancer early enough for successful treatment and avoiding excessive toxicity to normal tissues. In view of this, cancer still remains one of the leading causes of mortality worldwide, affecting over 10 million new patients every year. Clearly the development of novel approaches for early detection and treatment of cancer is urgently needed to increase patient survival. Recently, nano technology-based systems have emerged as novel therapeutic modalities for cancer treatment. Tiny man made nanoparticles, much smaller than a virus, are being developed to package, transport, and deliver imaging and therapeutic agents. Co-inclusion of these agents, into nano carriers might be advantageous because they increase solubility of hydrophobic drugs, enhance permeability across physiological barriers, alter drug biodistribution, increase local bioavailability and reduce side effects. Initial findings have been promising and nanoparticles have been shown to deliver therapeutic agents to target cells and effect tumor growth. To this end our lab is investigating a class of biodegradable and biocompatible polymers known as elastin-like polypeptides (ELP). Elastin like polypeptide is a bio polymer derived from the structural motif found in mammalian elastin protein and has a sequence dependent transition temperature that can be used as nano carriers to treat diseases. ELPs are characterized by the pentameric repeat VPGXG, where X can be any amino acid. All functional ELPs undergo inverse phase transition whereby below its transition temperature, they exist in a solubilized form while above its transition temperature they undergo phase separation which leads to their aggregation in solution. This process is reversible. Phase transition can also be triggered by other

[Response of pancreatic polypeptide to a protein rich meal in insulin non dependent diabetes melitus and autonomic neuropathy].

Science.gov (United States)

Kostić, N; Zamaklar, M; Novaković, R; Stajić, S

1994-01-01

Parasympathetic function and plasma hPP response to a protein rich meal were evaluated in 105 insulin non-dependent diabetic patients: 20 with autonomic neuropathy (group A), diagnosed by Clonidin test; 35 patients with neurophysiological evidence of polyneuropath (group B); 30 patients with autonomic neuropathy and polineuropathy (group C), and 20 patients without any sign of neuropathy (group D). Plasma hPP levels were determined by RIA using an anti-hPP antiserum, kindly provided by Prof. S. R. Bloom (Hammersmith Hospital, London). Blood was taken at 0. 45 and 60 minutes after the beginning of the meal. In groups A and C, the meal induced hPP increase was significantly lower than in group D (p 0.001). All group B patients had a marked increase in the peptide, similar to that in diabetics without neuropathy. These result ssuggest that diabetic autonomic neuropathy is associated with dysfunction of hPP secretion, and that the evaluation of hPP response to test meal may be a sensitive and simple method for the assessment of paraympathetic impairment in diabetes.

NMR and rotational angles in solution conformation of polypeptides

Science.gov (United States)

Bystrov, V. F.

1985-01-01

Professor San-Ichiro Mizushima and Professor Yonezo Morino's classical contributions provided unique means and firm basis for understanding of conformational states and internal rotation in polypeptide molecules. Now the NMR spectroscopy is the best choice to study molecular conformation, mechanism of action and structure-functional relationships of peptide and proteins in solution under conditions approaching those of their physiological environments. Crucial details of spatial structure and interactions of these molecules in solution are revealed by using proton-proton and carbon-proton vicinal coupling constants, proton nuclear Overhauser effect and spectral perturbation techniques. The results of NMR conformational analysis are presented for valinomycin "bracelet", gramicidin A double helices, honey-bee neurotoxin apamin, scorpion insectotoxins and snake neurotoxins of long and short types.

Partial wave analysis of anti pp → anti ΛΛ

International Nuclear Information System (INIS)

Bugg, D.V.

2004-01-01

A partial wave analysis of PS185 data for anti pp → anti ΛΛ is presented. A 3 S 1 cusp is identified in the inverse process anti ΛΛ→ anti p p at threshold, using detailed balance to deduce cross sections from anti pp → anti ΛΛ. Partial wave amplitudes for anti pp 3 P 0 , 3 F 3 , 3 D 3 and 3 G 3 exhibit a behaviour very similar to resonances observed in Crystal Barrel data. With this identification, the anti pp → anti ΛΛ data then provide evidence for a new I=0, J PC =1 - resonance with mass M = 2290 ±20 MeV, Γ= 275 ±35 MeV, coupling to both 3 S 1 and 3 D 1 . (orig.)

Tailored sPP/Silica Nanocomposite for Ecofriendly Insulation of Extruded HVDC Cable

Directory of Open Access Journals (Sweden)

Bin Dang

2015-01-01

Full Text Available Cross-linked polyethylene (XLPE is a thermosetting material that cannot be recycled at the end of its lifetime. This study investigated the potential of syndiotactic polypropylene (sPP/silica as an ecofriendly extruded insulation system for HVDC cables. We investigated the morphology, Fourier transform infrared, and thermal, thermomechanical, and electrical behaviors of sPP modified with 0.5–3% nanosilica. We found that the silica/sPP nanocomposite without cross-linking offered a suitable mechanical modulus at room temperature and sufficient intensity at high temperatures, and adding nanosilica modified by a silane coupling agent to the sPP resulted in significant DC resistivity and space charge improvement. The optimal nanosilica content in the sPP was determined by balancing the mechanical and thermomechanical characteristics and the DC resistivity. The sPP/silica nanocomposite reported here shows great potential as a candidate insulation material for future ecofriendly extruded HVDC cables.

Structural changes of PP with different isotacticity induced by γ-irradiation

International Nuclear Information System (INIS)

Wang Shaofeng; Wei Genshuan; Qiao Jinliang

2000-01-01

The morphology of i-PP with different isotacticity under high absorbed dose were studied with the measurements of crystallinity, crystallite size, melting heat and melting point by x-ray diffraction and DSC methods respectively. The results indicate that the changes are not only related to the heat history but also related to the isotacticity of i-PP. In generally, the higher the isotacticity of i-PP, the less morphology changes, and the morphology of annealing samples change less than the virgin powder samples. It means that the annealed i-PP with higher isotacticity is more stable to radiation both in air and vacuum conditions. (author)

Peptide inhibition of human cytomegalovirus infection

Directory of Open Access Journals (Sweden)

Morris Cindy A

2011-02-01

Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 �

PP2A contributes to endothelial death in high glucose: inhibition by benfotiamine.

Science.gov (United States)

Du, Y; Kowluru, A; Kern, T S

2010-12-01

Endothelial death is critical in diabetic vascular diseases, but regulating factors have been only partially elucidated. Phosphatases play important regulatory roles in cell metabolism, but have not previously been implicated in hyperglycemia-induced cell death. We investigated the role of the phosphatase, type 2A protein phosphatase (PP2A), in hyperglycemia-induced changes in signaling and death in bovine aortic endothelial cells (BAEC). We explored also the influence of benfotiamine on this phosphatase. Activation of PP2A was assessed in BAEC by the extent of methylation and measurement of activity, and the enzyme was inhibited using selective pharmacological (okadaic acid, sodium fostriecin) and molecular (small interfering RNA) approaches. BAECs cultured in 30 mM glucose significantly increased PP2A methylation and activity, and PP2A inhibitors blocked these abnormalities. PP2A activity was increased also in aorta and retina from diabetic rats. NF-κB activity and cell death in BAEC were significantly increased in 30 mM glucose and inhibited by PP2A inhibition. NF-κB played a role in the hyperglycemia-induced death of BAEC, since blocking its translocation with SN50 also inhibited cell death. Inhibition of PP2A blocked the hyperglycemia-induced dephosphorylation of NF-κB and Bad, thus favoring cell survival. Incubation of benfotiamine with BAEC inhibited the high glucose-induced activation of PP2A and NF-κB and cell death, as well as several other metabolic defects, which likewise were inhibited by inhibitors of PP2A. Activation of PP2A contributes to endothelial cell death in high glucose, and beneficial actions of benfotiamine are due, at least in part, to inhibition of PP2A activation.

Comments about anti-pp collisions

International Nuclear Information System (INIS)

Jung, M.

1978-01-01

A review concerning specific properties of anti-pp collisions has been done through the summary of several theoretical and experimental papers. Some new experimental measurements are suggested towards the analysis of different already known hadronic processes

UDP-[14C]glucose-labelable polypeptides from pea: Possible components of glucan synthase I activity

International Nuclear Information System (INIS)

Ray, P.M.; Dhugga, K.S.; Gallaghar, S.R.

1989-01-01

A membrane-bound polypeptide doublet of about 40 kD can be rapidly labeled with UDP-[ 14 C]glucose under the assay conditions for glucan synthase I (GS-I). Label seems covalently bound, and chases when unlabeled UDPG is added; it might represent a covalent intermediate in polysaccharide synthesis. Labeling and GS-I activity show several common features: they co-sediment with Golgi membranes in sucrose gradients; they depend similarly on Mg 2+ or Mn 2+ (not Ca 2+ ); they decrease dramatically from stem apex to base, and are higher in epidermis than internal tissue; they show similar sensitivities to several inhibitors. But the doublet still labels after polysaccharide-synthesizing activity has been destroyed by Triton X-100. The doublet polypeptides might be glucosyl tranferases whose ability to transfer glucose units to a glucan chain is detergent-sensitive, but to accept glucose from UDPG is not; or they might be detergent-insensitive primary glucose acceptors, from which a distinct, detergent-sensitive transferase(s) move(s) these units to glucan chains

47 CFR 65.105 - Discovery.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Procedures § 65.105 Discovery. (a) Participants... evidence. (c) Discovery requests pursuant to § 65.105(b), including written interrogatories, shall be filed...

Design and synthesis of elastin-like polypeptides for an ideal nerve conduit in peripheral nerve regeneration

International Nuclear Information System (INIS)

Hsueh, Yu-Sheng; Savitha, S.; Sadhasivam, S.; Lin, Feng-Huei; Shieh, Ming-Jium

2014-01-01

The study involves design and synthesis of three different elastin like polypeptide (ELP) gene monomers namely ELP1, ELP2 and ELP3 that encode for ELP proteins. The formed ELPs were assessed as an ideal nerve conduit for peripheral nerve regeneration. ELP1 was constructed with a small elongated pentapeptide carrying VPGVG sequence to mimic the natural polypeptide ELP. The ELP2 was designed by the incorporation of 4-penta peptide chains to improve the biocompatibility and mechanical strength. Thus, the third position in unique VPGVG was replaced with alanine to VPAVG and in a similar way modified to VPGKG, VPGEG and VPGIG with the substitution of lysine, glutamic acid and isoleucine. In ELP3, fibronectin C5 domain endowed with REDV sequence was introduced to improve the cell attachment. The ELP1, ELP2 and ELP3 proteins expressed by Escherichia coli were purified by inverse transition cycling (ITC). The purified ELPs were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The Schwann cell (SC) morphology and cell adhesion were assessed by fabrication of ELP membrane cross-linked with glutaraledhyde. The Schwann cell proliferation was measured by WST-1 assay. Immunofluorostaining of Schwann cells was accomplished with SC specific phenotypic marker, S100. - Highlights: • Design and synthesis of three gene monomers of elastin like polypeptides (ELP1, 2 and 3) were reported. • Molecular weight of ITC purified ELP1, ELP2 and ELP3 was in the range of 37–38 kDa. • Schwann cell adhesion was found to be prominent in ELP3 and could be used as nerve conduit for peripheral nerve regeneration

Design and synthesis of elastin-like polypeptides for an ideal nerve conduit in peripheral nerve regeneration

Energy Technology Data Exchange (ETDEWEB)

Hsueh, Yu-Sheng [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Savitha, S. [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); Department of Biotechnology, Sree Sastha Institute of Engineering and Technology, Chennai (India); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Sadhasivam, S. [Division of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli 350, Taiwan (China); Lin, Feng-Huei, E-mail: double@ntu.edu.tw [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); Division of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli 350, Taiwan (China); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Shieh, Ming-Jium [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); College of Medicine, National Taiwan University Hospital, Taipei 100, Taiwan (China); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)

2014-05-01

The study involves design and synthesis of three different elastin like polypeptide (ELP) gene monomers namely ELP1, ELP2 and ELP3 that encode for ELP proteins. The formed ELPs were assessed as an ideal nerve conduit for peripheral nerve regeneration. ELP1 was constructed with a small elongated pentapeptide carrying VPGVG sequence to mimic the natural polypeptide ELP. The ELP2 was designed by the incorporation of 4-penta peptide chains to improve the biocompatibility and mechanical strength. Thus, the third position in unique VPGVG was replaced with alanine to VPAVG and in a similar way modified to VPGKG, VPGEG and VPGIG with the substitution of lysine, glutamic acid and isoleucine. In ELP3, fibronectin C5 domain endowed with REDV sequence was introduced to improve the cell attachment. The ELP1, ELP2 and ELP3 proteins expressed by Escherichia coli were purified by inverse transition cycling (ITC). The purified ELPs were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The Schwann cell (SC) morphology and cell adhesion were assessed by fabrication of ELP membrane cross-linked with glutaraledhyde. The Schwann cell proliferation was measured by WST-1 assay. Immunofluorostaining of Schwann cells was accomplished with SC specific phenotypic marker, S100. - Highlights: • Design and synthesis of three gene monomers of elastin like polypeptides (ELP1, 2 and 3) were reported. • Molecular weight of ITC purified ELP1, ELP2 and ELP3 was in the range of 37–38 kDa. • Schwann cell adhesion was found to be prominent in ELP3 and could be used as nerve conduit for peripheral nerve regeneration.

Universitality features in (pp), (e+e-), and deep inelastic scattering process

International Nuclear Information System (INIS)

Zichichi, A.

1985-01-01

This paper discusses the use of the correct variables in (pp), (e + e - ), and deep-inelastic scattering (DIS) processes which allow universality features to be established different ways of producing mulihadronic states. The experimental data where (pp) interactions are compared with (e + e - ) are shown. Extrapolations of collider physics are discussed and it is found that the leading effects must be subtracted and the correct variables have to be used if one wants to compare purely hadronic interactions with (e + e - ) and DIS. The new method of studying (pp) and (pp) collisions allows one to put on equal footing the multiparticle systems that are produced in purely hadronic interactions, in (e + e - ) annihilation, and in DIS processes

Vasoactive intestinal polypeptide (VIP) in cirrhosis: arteriovenous extraction in different vascular beds

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Staun-Olsen, P; Fahrenkrug, J

1980-01-01

The concentration of vasoactive intestinal polypeptide (VIP) was determined in peripheral venous plasma from 136 patients with liver cirrhosis without gastrointestinal bleeding or coma and from 112 controls. In eight patients (cirrhosis, six; fibrosis, one; steatosis, one) arteriovenous extraction...... is significantly elevated in peripheral plasma from patients with cirrhosis, probably due to porto-systemic shunting and/or compromised hepatic elimination. Hepatic elimination is still likely to account for the inactivation of most of the VIP escaping from the neurosynapses throughout the body in patients...

Mechanical and thermal properties of polypropylene (PP) composites filled with modified shell waste

Energy Technology Data Exchange (ETDEWEB)

Yao, Z.T., E-mail: sxyzt@126.com [College of Materials Science and Environmental Engineering, Hangzhou Dianzi University, Hangzhou 310018 (China); Chen, T. [Department of Ocean Science and Engineering, Zhejiang University, Hangzhou 310058 (China); Li, H.Y. [Zhoushan Ocean Research Institute, Zhejiang University, Zhoushan 316021 (China); Xia, M.S., E-mail: msxia@zju.edu.cn [Department of Ocean Science and Engineering, Zhejiang University, Hangzhou 310058 (China); Ye, Y.; Zheng, H. [Department of Ocean Science and Engineering, Zhejiang University, Hangzhou 310058 (China)

2013-11-15

Highlights: • Adding modified shell powder could significantly increase the properties of PP. • The modified shell powder could act as a nucleating agent in PP matrix. • The modified shell powder has a potential to be used as a bio-filler. -- Abstract: Shell waste, with its high content of calcium carbonate (CaCO{sub 3}) plus organic matrix, has a potential to be used as a bio-filler. In this work, shell waste was modified by furfural and then incorporated to reinforce polypropylene (PP). The shell waste and modified powder were characterized by means of X-ray diffraction (XRD), scanning electron microscopy equipped with an energy dispersive spectrometer (SEM-EDS), X-ray photoelectronic spectroscopy (XPS), and Fourier transformed infrared spectroscopy (FTIR). The mechanical and thermal properties of neat PP and PP composites were investigated as well. Thermal gravimetric (TG) analyses confirmed the reinforcing role of modified powder in PP composites. The mechanical properties studied showed that adding modified powder could significantly increase the impact strength, elongation at break point and flexural modulus of composites. The maximum incorporation content could reach 15 wt.% with a good balance between toughness and stiffness of PP composites. Differential scanning calorimetry (DSC) results showed that the modified powder could act as a nucleating agent and thus increase the crystallization temperature of PP. Polarized optical microscopy (POM) observation also indicated that the introduction of modified powder could promote the heterogeneous nucleation of PP matrix.

UV stability of HMS-PP (High Melt Strength Polypropylene) obtained by radiation process

International Nuclear Information System (INIS)

Oliani, W.L.; Parra, Duclerc F.; Lugao, Ademar B.

2006-01-01

HMS-PP in grains was synthesized by the gamma irradiation of PP under a crosslinking atmosphere of acetylene, followed by thermal treatment for radical recombination and thermal treatment for annihilation of the remaining radicals. The UV stability of the material was evaluated in reference to grains. Accelerated weathering test of HMS-PP samples were performed in artificial ultraviolet light and condensation chamber apparatus Comexim (C-UV type) in aging conditions of exposure for 120 hours and 240 hours. The results were compared to the deterioration caused by sunlight and dew under natural exposition. This work investigated changes in mechanical proprieties (elongation and rupture strength) behavior, Infrared Spectroscopy (FTIR), Optical Microscopy (MO), Scanning Electronic Microscopy (SEM) and Rheological properties of HMS-PP. The HMS-PP is more fragile than PP and undergoes predominately chain scission in aggressive environment degradation conditions. (author)

2 pi production in pp collisions close to threshold

CERN Document Server

Bilger, R; Calén, H; Clement, H; Dyring, J; Ekström, C; Fransson, K; Gustafsson, L; Häggström, S; Hoeistad, B; Johanson, J; Johansson, A; Johansson, T; Khoukaz, A; Kilian, K; Kullander, K; Kupsc, A; Marciniewski, P; Morosov, B; Moertsell, A; Oelert, W; Paetzold, J; Ruber, Roger J M Y; Schepkin, M G; Stepaniak, J; Sukhanov, A; Sundberg, P; Turowiecki, A; Wagner, G J; Wilhelmi, Z; Zabierowski, J; Zernov, A; Zlomanczuk, Yu

2000-01-01

The reaction pp -> NN pi pi has been measured close to threshold in the energy range from 650 to 775 MeV using the PROMICE/WASA setup at CELSIUS. These data constitute the first exclusive high-statistics measurements of this reaction on a pure hydrogen target, supplying both differential and integral cross sections. The obtained total cross sections are an order of magnitude below previously published bubble-chamber results. Differential spectra for pp -> pp pi sup -pi sup + are close to phase space predictions identifying the production via N*(1440) -> N(pi pi) sub I sub = sub L sub = sub 0 as the dominant process. Possible contributions from dibaryon resonances are discussed.

High pT jet production in pp collisions

International Nuclear Information System (INIS)

Eskola, K.J.; Wang, X.N.

1995-01-01

Production rates of large p T jets in pp collisions at RHIC and LHC energies are studied using the next-to-leading order calculation of S. D. Ellis, Z. Zunszt and D. Soper. The computed inclusive one-jet cross sections are compared against the CERN and Fermilab jet data from p bar p and pp collisions. The dependence of the results on the choice of the parton distributions and renormalization/factorization scales is investigated

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

Science.gov (United States)

Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

2015-10-13

Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. Copyright © 2015, American Association for the Advancement of Science.

The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

Energy Technology Data Exchange (ETDEWEB)

Peng, Yi; Zhou, Yajuan [Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071 (China); Cheng, Long [Department of Interventional Radiology, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215001 (China); Hu, Desheng; Zhou, Xiaoyi; Wang, Zhaohua [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071 (China); Xie, Conghua, E-mail: chxie_65@hotmail.com [Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhou, Fuxiang, E-mail: ZhouFuxiangwuhan@126.com [Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

2015-09-11

Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.

cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells.

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Jennifer Paijo

2016-04-01

Full Text Available Human cytomegalovirus (HCMV infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING and thus induces antiviral type I interferon (IFN-I responses. We found that plasmacytoid dendritic cells (pDC as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages.

Herpesviruses in asymptomatic apical periodontitis lesions: an immunohistochemical approach.

Science.gov (United States)

Saboia-Dantas, C J; Coutrin de Toledo, L F; Sampaio-Filho, H R; Siqueira, J F

2007-10-01

Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have been recently detected in samples from apical periodontitis lesions by means of molecular biology techniques and a role in the pathogenesis of this disease has been suggested. The present study was designed to survey asymptomatic primary apical periodontitis lesions for the presence of HCMV- and/or EBV-infected cells by means of immunohistochemistry. Apical periodontitis lesions were obtained from 35 patients [26 human immunodeficiency virus (HIV) -seronegative patients and nine HIV-seropositive patients] after tooth extraction and subjected to immunohistochemical analysis using monoclonal antibodies specific for HCMV and EBV. Fifteen of the 35 apical periodontitis lesions were positive for the target herpesviruses. Overall, EBV was found in 31% of the samples and HCMV in 23%, with 14% of the lesions showing EBV and HCMV dual infection. No association was found between HCMV or EBV with any particular histopathological type of apical periodontitis (P > 0.05). HCMV was significantly more frequent in apical periodontitis lesions from HIV-positive patients (67%) than in lesions from HIV-negative patients (8%) (P = 0.001). EBV was detected in 44% of lesions from HIV-positive patients and in 27% of lesions from HIV-negative patients, but this difference was not significant (P = 0.91). Our results showed that cells infected by HCMV and EBV can be found in apical periodontitis lesions, with a higher prevalence in HIV-positive patients. The specific role that these viruses play in the pathogenesis of apical periodontitis remains to be described.

Gauge theory description of compactified pp-waves

International Nuclear Information System (INIS)

Bertolini, Matteo; Boer, Jan de; Harmark, Troels; Imeroni, Emiliano; Obers, Niels A.

2003-01-01

We find a new Penrose limit of AdS 5 xS 5 that gives the maximally symmetric pp-wave background of type-IIB string theory in a coordinate system that has a manifest space-like isometry. This induces a new pp-wave/gauge-theory duality which on the gauge theory side involves a novel scaling limit of N=4 SYM theory. The new Penrose limit, when applied to AdS 5 xS 5 /Z M , yields a pp-wave with a space-like circle. The dual gauge theory description involves a triple scaling limit of an N=2 quiver gauge theory. We present in detail the map between gauge theory operators and string theory states including winding states, and verify agreement between the energy eigenvalues obtained from string theory and those computed in gauge theory, at least to one-loop order in the planar limit. We furthermore consider other related new Penrose limits and explain how these limits can be understood as part of a more general framework. (author)

The spectroscopy analyses of PpIX by ultrasound irradiation and its sonotoxicity in vitro.

Science.gov (United States)

Wang, Pan; Wang, Xiaobing; Zhang, Kun; Gao, Kaili; Song, Ming; Liu, Quanhong

2013-07-01

Protoporphyrin IX (PpIX) has been used as a sensitizer in photodynamic therapy (PDT) as well as in sonodynamic therapy (SDT). The photo-bleaching of PpIX has been well investigated in many experimental systems and some photo-products have also been identified in PDT. But until now, little information has been reported about the sono-damage of PpIX in SDT. So, the present study was to investigate changes of PpIX properties before and after different ultrasound treatment, and the potential interactions between PpIX, ultrasound and the irradiated cells. In cell-free system, the absorption and fluorescence spectra of PpIX in different solutions were measured by ultraviolet spectrometer and fluorescence spectrophotometer, respectively. The terephthalic acid dosimetry was applied to evaluate the efficiency of ultrasound cavitation by monitoring hydroxyl radical (OH) production on the thermolysis of H2O in the ultrasound field. In in vitro study, confocal microscopy was applied to detect the sub-cellular localization of PpIX in S180 cells before and after ultrasound exposure. Flow cytometry was used to detect the reactive oxygen species (ROS) generation during PpIX-SDT. MTT assay was performed to evaluate the cell viability of S180 cells after SDT treatment with or without ROS scavengers. The results show that PpIX displayed different spectral patterns in different solutions. PpIX was decomposed by ultrasound exposure as measured by the decreased absorption and fluorescence peak values in RPMI-1640 medium. In addition, the decomposition of PpIX was found to be simultaneously accompanied by OH production with increasing output power from ultrasound generator. PpIX at 1μg/ml significantly enhanced the ultrasound induced cavitation as measured by OH generation, and which was greatly eliminated by NaN3, histidine, mannitol, EDTA and catalase, but not by SOD. The in vitro study indicates more PpIX entered into S180 cells after ultrasound exposure. And, the extra-cellular Pp

Conformational energy calculations on polypeptides and proteins: use of a statistical mechanical procedure for evaluating structure and properties.

Science.gov (United States)

Scheraga, H A; Paine, G H

1986-01-01

We are using a variety of theoretical and computational techniques to study protein structure, protein folding, and higher-order structures. Our earlier work involved treatments of liquid water and aqueous solutions of nonpolar and polar solutes, computations of the stabilities of the fundamental structures of proteins and their packing arrangements, conformations of small cyclic and open-chain peptides, structures of fibrous proteins (collagen), structures of homologous globular proteins, introduction of special procedures as constraints during energy minimization of globular proteins, and structures of enzyme-substrate complexes. Recently, we presented a new methodology for predicting polypeptide structure (described here); the method is based on the calculation of the probable and average conformation of a polypeptide chain by the application of equilibrium statistical mechanics in conjunction with an adaptive, importance sampling Monte Carlo algorithm. As a test, it was applied to Met-enkephalin.

p-p, p-$\\Lambda$ and $\\Lambda$-$\\Lambda$ correlations studied via femtoscopy in pp reactions at $\\sqrt{s}$ = 7 TeV

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Naik, Bharati; Nair, Rahul; Nandi, Basanta Kumar; Nania, Rosario; Nappi, Eugenio; Narayan, Amrendra; Naru, Muhammad Umair; Nassirpour, Adrian Fereydon; Ferreira Natal Da Luz, Pedro Hugo; Nattrass, Christine; Rosado Navarro, Sebastian; Nayak, Kishora; Nayak, Ranjit; Nayak, Tapan Kumar; Nazarenko, Sergey; Negrao De Oliveira, Renato Aparecido; Nellen, Lukas; Nesbo, Simon Voigt; Neskovic, Gvozden; Ng, Fabian; Nicassio, Maria; Niedziela, Jeremi; Nielsen, Borge Svane; Nikolaev, Sergey; Nikulin, Sergey; Nikulin, Vladimir; Noferini, Francesco; Nomokonov, Petr; Nooren, Gerardus; Cabanillas Noris, Juan Carlos; Norman, Jaime; Nyanin, Alexander; Nystrand, Joakim Ingemar; Oh, Hoonjung; Ohlson, Alice Elisabeth; Oleniacz, Janusz; Oliveira Da Silva, Antonio Carlos; Oliver, Michael Henry; Onderwaater, Jacobus; Oppedisano, Chiara; Orava, Risto; Oravec, Matej; Ortiz Velasquez, Antonio; Oskarsson, Anders Nils Erik; Otwinowski, Jacek Tomasz; Oyama, Ken; Pachmayer, Yvonne Chiara; Pacik, Vojtech; Pagano, Davide; Paic, Guy; Palni, Prabhakar; Pan, Jinjin; Pandey, Ashutosh Kumar; Panebianco, Stefano; Papikyan, Vardanush; Pareek, Pooja; Park, Jonghan; Parkkila, Jasper Elias; Parmar, Sonia; Passfeld, Annika; Pathak, Surya Prakash; Patra, Rajendra Nath; Paul, Biswarup; Pei, Hua; Peitzmann, Thomas; Peng, Xinye; Pereira, Luis Gustavo; Pereira Da Costa, Hugo Denis Antonio; Peresunko, Dmitry Yurevich; Perez Lezama, Edgar; Peskov, Vladimir; Pestov, Yury; Petracek, Vojtech; Petrovici, Mihai; Petta, Catia; Peretti Pezzi, Rafael; Piano, Stefano; Pikna, Miroslav; Pillot, Philippe; Ozelin De Lima Pimentel, Lais; Pinazza, Ombretta; Pinsky, Lawrence; Pisano, Silvia; Piyarathna, Danthasinghe; Ploskon, Mateusz Andrzej; Planinic, Mirko; Pliquett, Fabian; Pluta, Jan Marian; Pochybova, Sona; Podesta Lerma, Pedro Luis Manuel; Poghosyan, Martin; Polishchuk, Boris; Poljak, Nikola; Poonsawat, Wanchaloem; Pop, Amalia; Poppenborg, Hendrik; Porteboeuf, Sarah Julie; Pozdniakov, Valeriy; Prasad, Sidharth Kumar; Preghenella, Roberto; Prino, Francesco; Pruneau, Claude Andre; Pshenichnov, Igor; Puccio, Maximiliano; Punin, Valery; Putschke, Jorn Henning; Raha, Sibaji; Rajput, Sonia; Rak, Jan; Rakotozafindrabe, Andry Malala; Ramello, Luciano; Rami, Fouad; Raniwala, Rashmi; Raniwala, Sudhir; Rasanen, Sami Sakari; Rascanu, Bogdan Theodor; Rath, Rutuparna; Ratza, Viktor; Ravasenga, Ivan; Read, Kenneth Francis; Redlich, Krzysztof; Rehman, Attiq Ur; Reichelt, Patrick Simon; Reidt, Felix; Ren, Xiaowen; Renfordt, Rainer Arno Ernst; Reshetin, Andrey; Revol, Jean-pierre; Reygers, Klaus Johannes; Riabov, Viktor; Richert, Tuva Ora Herenui; Richter, Matthias Rudolph; Riedler, Petra; Riegler, Werner; Riggi, Francesco; Ristea, Catalin-lucian; Rode, Sudhir Pandurang; Rodriguez Cahuantzi, Mario; Roeed, Ketil; Rogalev, Roman; Rogochaya, Elena; Rohr, David Michael; Roehrich, Dieter; Rokita, Przemyslaw Stefan; Ronchetti, Federico; Dominguez Rosas, Edgar; Roslon, Krystian; Rosnet, Philippe; Rossi, Andrea; Rotondi, Alberto; Roukoutakis, Filimon; Roy, Christelle Sophie; Roy, Pradip Kumar; Vazquez Rueda, Omar; Rui, Rinaldo; Rumyantsev, Boris; Rustamov, Anar; Ryabinkin, Evgeny; Ryabov, Yury; Rybicki, Andrzej; Saarinen, Sampo; Sadhu, Samrangy; Sadovskiy, Sergey; Safarik, Karel; Saha, Sumit Kumar; Sahoo, Baidyanath; Sahoo, Pragati; Sahoo, Raghunath; Sahoo, Sarita; Sahu, Pradip Kumar; Saini, Jogender; Sakai, Shingo; Saleh, Mohammad Ahmad; Sambyal, Sanjeev Singh; Samsonov, Vladimir; Sandoval, Andres; Sarkar, Amal; Sarkar, Debojit; Sarkar, Nachiketa; Sarma, Pranjal; Sas, Mike Henry Petrus; Scapparone, Eugenio; Scarlassara, Fernando; Schaefer, Brennan; Scheid, Horst Sebastian; Schiaua, Claudiu Cornel; Schicker, Rainer Martin; Schmidt, Christian Joachim; Schmidt, Hans Rudolf; Schmidt, Marten Ole; Schmidt, Martin; Schmidt, Nicolas Vincent; Schukraft, Jurgen; Schutz, Yves Roland; Schwarz, Kilian Eberhard; Schweda, Kai Oliver; Scioli, Gilda; Scomparin, Enrico; Sefcik, Michal; Seger, Janet Elizabeth; Sekiguchi, Yuko; Sekihata, Daiki; Selyuzhenkov, Ilya; Senyukov, Serhiy; Serradilla Rodriguez, Eulogio; Sett, Priyanka; Sevcenco, Adrian; Shabanov, Arseniy; Shabetai, Alexandre; Shahoyan, Ruben; Shaikh, Wadut; Shangaraev, Artem; Sharma, Anjali; Sharma, Ankita; Sharma, Meenakshi; Sharma, Natasha; Sheikh, Ashik Ikbal; Shigaki, Kenta; Shimomura, Maya; Shirinkin, Sergey; Shou, Qiye; Shtejer Diaz, Katherin; Sibiryak, Yury; Siddhanta, Sabyasachi; Sielewicz, Krzysztof Marek; Siemiarczuk, Teodor; Silvermyr, David Olle Rickard; Simatovic, Goran; Simonetti, Giuseppe; Singaraju, Rama Narayana; Singh, Ranbir; Singh, Randhir; Singhal, Vikas; Sarkar - Sinha, Tinku; Sitar, Branislav; Sitta, Mario; Skaali, Bernhard; Slupecki, Maciej; Smirnov, Nikolai; Snellings, Raimond; Snellman, Tomas Wilhelm; Sochan, Jaroslav; Soncco Meza, Carlos; Song, Jihye; Soramel, Francesca; Sorensen, Soren Pontoppidan; Sozzi, Federica; Sputowska, Iwona Anna; Stachel, Johanna; Stan, Ionel; Stankus, Paul; Stenlund, Evert Anders; Stocco, Diego; Storetvedt, Maksim Melnik; Strmen, Peter; Alarcon Do Passo Suaide, Alexandre; Sugitate, Toru; Suire, Christophe Pierre; Suleymanov, Mais Kazim Oglu; Suljic, Miljenko; Sultanov, Rishat; Sumbera, Michal; Sumowidagdo, Suharyo; Suzuki, Ken; Swain, Sagarika; Szabo, Alexander; Szarka, Imrich; Tabassam, Uzma; Takahashi, Jun; Tambave, Ganesh Jagannath; Tanaka, Naoto; Tarhini, Mohamad; Tariq, Mohammad; Tarzila, Madalina-gabriela; Tauro, Arturo; Tejeda Munoz, Guillermo; Telesca, Adriana; Terrevoli, Cristina; Teyssier, Boris; Thakur, Dhananjaya; Thakur, Sanchari; Thomas, Deepa; Thoresen, Freja; Tieulent, Raphael Noel; Tikhonov, Anatoly; Timmins, Anthony Robert; Toia, Alberica; Topilskaya, Nataliya; Toppi, Marco; Rojas Torres, Solangel; Tripathy, Sushanta; Trogolo, Stefano; Trombetta, Giuseppe; Tropp, Lukas; Trubnikov, Victor; Trzaska, Wladyslaw Henryk; Trzcinski, Tomasz Piotr; Trzeciak, Barbara Antonina; Tsuji, Tomoya; Tumkin, Alexandr; Turrisi, Rosario; Tveter, Trine Spedstad; Ullaland, Kjetil; Umaka, Ejiro Naomi; Uras, Antonio; Usai, Gianluca; Utrobicic, Antonija; Vala, Martin; Van Hoorne, Jacobus Willem; Van Leeuwen, Marco; Vande Vyvre, Pierre; Varga, Dezso; Diozcora Vargas Trevino, Aurora; Vargyas, Marton; Varma, Raghava; Vasileiou, Maria; Vasiliev, Andrey; Vauthier, Astrid; Vazquez Doce, Oton; Vechernin, Vladimir; Veen, Annelies Marianne; Vercellin, Ermanno; Vergara Limon, Sergio; Vermunt, Luuk; Vernet, Renaud; Vertesi, Robert; Vickovic, Linda; Viinikainen, Jussi Samuli; Vilakazi, Zabulon; Villalobos Baillie, Orlando; Villatoro Tello, Abraham; Vinogradov, Alexander; Virgili, Tiziano; Vislavicius, Vytautas; Vodopyanov, Alexander; Volkl, Martin Andreas; Voloshin, Kirill; Voloshin, Sergey; Volpe, Giacomo; Von Haller, Barthelemy; Vorobyev, Ivan; Voscek, Dominik; Vranic, Danilo; Vrlakova, Janka; Wagner, Boris; Wang, Hongkai; Wang, Mengliang; Watanabe, Yosuke; Weber, Michael; Weber, Steffen Georg; Wegrzynek, Adam; Weiser, Dennis Franz; Wenzel, Sandro Christian; Wessels, Johannes Peter; Westerhoff, Uwe; Whitehead, Andile Mothegi; Wiechula, Jens; Wikne, Jon; Wilk, Grzegorz Andrzej; Wilkinson, Jeremy John; Willems, Guido Alexander; Williams, Crispin; Willsher, Emily; Windelband, Bernd Stefan; Witt, William Edward; Xu, Ran; Yalcin, Serpil; Yamakawa, Kosei; Yano, Satoshi; Yin, Zhongbao; Yokoyama, Hiroki; Yoo, In-kwon; Yoon, Jin Hee; Yurchenko, Volodymyr; Zaccolo, Valentina; Zaman, Ali; Zampolli, Chiara; Correa Zanoli, Henrique Jose; Zardoshti, Nima; Zarochentsev, Andrey; Zavada, Petr; Zavyalov, Nikolay; Zbroszczyk, Hanna Paulina; Zhalov, Mikhail; Zhang, Xiaoming; Zhang, Yonghong; Zhang, Zuman; Zhao, Chengxin; Zherebchevskii, Vladimir; Zhigareva, Natalia; Zhou, Daicui; Zhou, You; Zhou, Zhuo; Zhu, Hongsheng; Zhu, Jianhui; Zhu, Ya; Zichichi, Antonino; Zimmermann, Markus Bernhard; Zinovjev, Gennady; Zmeskal, Johann; Zou, Shuguang

2018-01-01

We report on the first femtoscopic measurement of baryon pairs, such as p-p, p-$\\Lambda$ and $\\Lambda$-$\\Lambda$, measured by ALICE at the Large Hadron Collider (LHC) in proton-proton collisions at $\\sqrt{s}$ = 7 TeV This study demonstrates the feasibility of such measurements in pp collisions at ultrarelativistic energies. The femtoscopy method is employed to constrain the hyperon-nucleon and hyperon-hyperon interactions, which are still rather poorly understood. A new method to evaluate the influence of residual correlations induced by the decays of resonances and experimental impurities is hereby presented. The p-p, p-$\\Lambda$ and $\\Lambda$-$\\Lambda$ correlation functions were fitted simultaneously with the help of a new tool developed specifically for the femtoscopy analysis in small colliding systems “Correlation Analysis Tool using the Schrödinger Equation” (CATS). Within the assumption that in collisions the three particle pairs originate from a common source, its radius is found to be equal to...

Viral and cellular subnuclear structures in human cytomegalovirus-infected cells.

Science.gov (United States)

Strang, Blair L

2015-02-01

In human cytomegalovirus (HCMV)-infected cells, a dramatic remodelling of the nuclear architecture is linked to the creation, utilization and manipulation of subnuclear structures. This review outlines the involvement of several viral and cellular subnuclear structures in areas of HCMV replication and virus-host interaction that include viral transcription, viral DNA synthesis and the production of DNA-filled viral capsids. The structures discussed include those that promote or impede HCMV replication (such as viral replication compartments and promyelocytic leukaemia nuclear bodies, respectively) and those whose role in the infected cell is unclear (for example, nucleoli and nuclear speckles). Viral and cellular proteins associated with subnuclear structures are also discussed. The data reviewed here highlight advances in our understanding of HCMV biology and emphasize the complexity of HCMV replication and virus-host interactions in the nucleus. © 2015 The Authors.

AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis.

Science.gov (United States)

Xu, Feng; Previti, Mary Lou; Nieman, Marvin T; Davis, Judianne; Schmaier, Alvin H; Van Nostrand, William E

2009-04-29

The amyloid beta-protein precursor (AbetaPP) is best recognized as the precursor to the Abeta peptide that accumulates in the brains of patients with Alzheimer's disease, but less is known about its physiological functions. Isoforms of AbetaPP that contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed in brain and, outside the CNS, in circulating blood platelets. Recently, we showed that KPI-containing forms of AbetaPP regulates cerebral thrombosis in vivo (Xu et al., 2005, 2007). Amyloid precursor like protein-2 (APLP2), a closely related homolog to AbetaPP, also possesses a highly conserved KPI domain. Virtually nothing is known of its function. Here, we show that APLP2 also regulates cerebral thrombosis risk. Recombinant purified KPI domains of AbetaPP and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery thrombosis model, both AbetaPP(-/-) and APLP2(-/-) mice exhibit similar significantly shorter times to vessel occlusion compared with wild-type mice indicating a prothrombotic phenotype. Similarly, in an experimental model of intracerebral hemorrhage, both AbetaPP(-/-) and APLP2(-/-) mice produce significantly smaller hematomas with reduced brain hemoglobin content compared with wild-type mice. Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury.

Characterization of Human Cytomegalovirus Genome Diversity in Immunocompromised Hosts by Whole-Genome Sequencing Directly From Clinical Specimens.

Science.gov (United States)

Hage, Elias; Wilkie, Gavin S; Linnenweber-Held, Silvia; Dhingra, Akshay; Suárez, Nicolás M; Schmidt, Julius J; Kay-Fedorov, Penelope C; Mischak-Weissinger, Eva; Heim, Albert; Schwarz, Anke; Schulz, Thomas F; Davison, Andrew J; Ganzenmueller, Tina

2017-06-01

Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals. Next-generation sequencing was performed on target enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast milk, respiratory samples, biopsies, and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients, and congenitally infected children). De novo-assembled HCMV genome sequences were obtained for 57 of 68 sequenced samples. Analysis of longitudinal or compartmental HCMV diversity revealed various patterns: no major differences were detected among longitudinal, intraindividual blood samples from 9 of 15 patients and in most of the patients with compartmental samples, whereas a switch of the major HCMV population was observed in 6 individuals with sequential blood samples and upon compartmental analysis of 1 patient with HCMV retinitis. Variant analysis revealed additional aspects of minor virus population dynamics and antiviral-resistance mutations. In immunosuppressed patients, HCMV can remain relatively stable or undergo drastic genomic changes that are suggestive of the emergence of minor resident strains or de novo infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

A fluorescence-based method for direct measurement of submicrosecond intramolecular contact formation in biopolymers: an exploratory study with polypeptides.

Science.gov (United States)

Hudgins, Robert R; Huang, Fang; Gramlich, Gabriela; Nau, Werner M

2002-01-30

A fluorescent amino acid derivative (Fmoc-DBO) has been synthesized, which contains 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as a small, hydrophilic fluorophore with an extremely long fluorescence lifetime (325 ns in H2O and 505 ns in D2O under air). Polypeptides containing both the DBO residue and an efficient fluorescence quencher allow the measurement of rate constants for intramolecular end-to-end contact formation. Bimolecular quenching experiments indicated that Trp, Cys, Met, and Tyr are efficient quenchers of DBO (k(q) = 20, 5.1, 4.5, and 3.6 x 10(8) M(-1) x s(-1) in D2O), while the other amino acids are inefficient. The quenching by Trp, which was selected as an intrinsic quencher, is presumed to involve exciplex-induced deactivation. Flexible, structureless polypeptides, Trp-(Gly-Ser)n-DBO-NH2, were prepared by standard solid-phase synthesis, and the rates of contact formation were measured through the intramolecular fluorescence quenching of DBO by Trp with time-correlated single-photon counting, laser flash photolysis, and steady-state fluorometry. Rate constants of 4.1, 6.8, 4.9, 3.1, 2.0, and 1.1 x 10(7) s(-1) for n = 0, 1, 2, 4, 6, and 10 were obtained. Noteworthy was the relatively slow quenching for the shortest peptide (n = 0). The kinetic data are in agreement with recent transient absorption studies of triplet probes for related peptides, but the rate constants are significantly larger. In contrast to the flexible structureless Gly-Ser polypeptides, the polyproline Trp-Pro4-DBO-NH2 showed insignificant fluorescence quenching, suggesting that a high polypeptide flexibility and the possibility of probe-quencher contact is essential to induce quenching. Advantages of the new fluorescence-based method for measuring contact formation rates in biopolymers include high accuracy, fast time range (100 ps-1 micros), and the possibility to perform measurements in water under air.

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

Science.gov (United States)

Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

2017-04-11

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

Polarization in pp → p(baryon)

International Nuclear Information System (INIS)

Castillo-Vallejo, Victor M.; Felix, Julian

2003-01-01

It's introduced a calculation, which is based on symmetries followed by high energy hadronic interactions, of resonance polarization and specific angular momentum state polarization created in pp → p(baryon)

Characterization of dispersion of a nano composites PP/TiO{sub 2} non modified; Caracterizacao da dispersao dos nanocompositos de PP/TiO{sub 2} nao modificados

Energy Technology Data Exchange (ETDEWEB)

Soares, Igor L.; Tavares, Maria I.B.; Silva, Vanessa A. da; Legramanti, Cintia, E-mail: igorl@ima.ufrj.br [Universidade Federal do Rio de Janeiro - UFRJ, Instituto de Macromoleculas - IMA (Brazil); Luetkmeyer, Leandro [Universidades Federais do Mato Grosso - UFMT, Escritorio de Inovacao Tecnologica - EIT (Brazil)

2011-07-01

Polymeric nano composites are composite materials where an inorganic particle, which has a dimension in the nanometer range, is dispersed in a polymer matrix. Nano composites, using polypropylene (PP) as matrix polymer and titanium dioxide (TiO{sub 2}) as filler, have great versatility in marketing applications, this factor is inherent in the PP and the inherent ability photo degraded TiO{sub 2} particles. This combination can lead to a widely used material and a degradation time after discharge reduced, there by becoming, a residue of low environmental impact. This study aimed to evaluate the dispersion and particle distribution of TiO{sub 2}, non modified, in PP matrix, using the process of preparation by melt extrusion pathway and characterization of the materials obtained: on the molecular dynamics, using low field NMR solid state, measures the relaxation time spin-network (T{sub 1}H); morphology using XRD technique, and thermal analysis technique with the TGA of pure PP and nano composites PP/TiO{sub 2}. (author)

Konfirmasi spesifitas GAD65 terhadap anti-GAD65 pada tikus DM dan pasien DM tipe 1

Directory of Open Access Journals (Sweden)

Aulanni’a Aulanni’a

2012-02-01

Full Text Available The use of glutamic acid decarboxylase (GAD65 from bovine brain has been studied to obtain basic knowledge and diagnosis and prediction of Type 1 Diabetes Mellitus (DM patients. The importance of GAD65 in DM diagnosis based on its patogenesis. One of the autoimmune marker that can be used to detect beta-pancreas destruction in Diabetes Type I is the antibody to glutamic acid decarboxylase (GAD65. Most of the pre-diabetic patients indicate the reactive autoantibody to GAD65. For early detection of anti-GAD65 in the serum of the patient, human recombinat GAD65 has been succeed to be used. However this is not economical, therefore, it is necessary to find the alternative source of cheaper GAD65. The aim of this research is to develop an early detection kit of Type 1 DM based on antibody- GAD65, since the longest patient suffering from DM has higher probability to be complicated, especially for uncured patients. The anti- GAD65 antibodies induced by anti-GAD65 synthetized and labelled by alkaline phosphatase can be used as reagent detection early DM patients. The ten patients of DM as samples (positive of anti-GAD65 and five rats of DM were positive with western blott technique using reagents as result of this research. It can be concluded, GAD65 enzyme isolated from bovine brain induced anti-GAD65 production and have possibilities to be packaged in a diagnostic kit for patient pre DM.

The lectin domain of UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-T4 directs its glycopeptide specificities

DEFF Research Database (Denmark)

Hassan, H; Reis, C A; Bennett, E P

2000-01-01

The initiation step of mucin-type O-glycosylation is controlled by a large family of homologous UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Differences in kinetic properties, substrate specificities, and expression patterns of these isoenzymes provide for diff...

New KF-PP-SVM classification method for EEG in brain-computer interfaces.

Science.gov (United States)

Yang, Banghua; Han, Zhijun; Zan, Peng; Wang, Qian

2014-01-01

Classification methods are a crucial direction in the current study of brain-computer interfaces (BCIs). To improve the classification accuracy for electroencephalogram (EEG) signals, a novel KF-PP-SVM (kernel fisher, posterior probability, and support vector machine) classification method is developed. Its detailed process entails the use of common spatial patterns to obtain features, based on which the within-class scatter is calculated. Then the scatter is added into the kernel function of a radial basis function to construct a new kernel function. This new kernel is integrated into the SVM to obtain a new classification model. Finally, the output of SVM is calculated based on posterior probability and the final recognition result is obtained. To evaluate the effectiveness of the proposed KF-PP-SVM method, EEG data collected from laboratory are processed with four different classification schemes (KF-PP-SVM, KF-SVM, PP-SVM, and SVM). The results showed that the overall average improvements arising from the use of the KF-PP-SVM scheme as opposed to KF-SVM, PP-SVM and SVM schemes are 2.49%, 5.83 % and 6.49 % respectively.

Operational reliability of the GPK and the 4PP-2 heading machines

Energy Technology Data Exchange (ETDEWEB)

Ivanov, N.A.; Demchenko, N.T.

1985-09-01

Reliability of the GPK and 4PP-2 heading machines used in 98 development workings in 40 coal mines is analyzed. Failure analysis was based on records of 199 heading machines after overhauls. The mean-time-between-failures of the GPK and the 4PP-2 was 270 min (93 t) and 155 min (35 t), availability coefficient was 0.83 and 0.77 respectively. Reliability of the GPK on the average was higher than that of the 4PP-2. The mean-time-to-overhaul of the GPK was 17.7 months (54,000 t), of the 4PP-2 - 18 months (59,000 t). Time between overhauls in the case of the GPK was 14 months (47,200 t), in the case of the 4PP-2 it was 14.5 months (38,300 t). During the 17.7 months between overhauls the GPK failed 580 times, the repair operations lasted 530 h. During the 18 month time to overhaul the 4PP-2 failed 1600 times, the repair operations lasted 1300 h. Reliability of major elements of the 2 heading machines is analyzed: cutters, materials handling equipment, electrical equipment, hydraulic systems, dust suppression systems, etc.

Binding Properties of Streptococcus gordonii SspA and SspB (Antigen I/II Family) Polypeptides Expressed on the Cell Surface of Lactococcus lactis MG1363

OpenAIRE

Holmes, Ann R.; Gilbert, Christophe; Wells, Jeremy M.; Jenkinson, Howard F.

1998-01-01

The oral bacterium Streptococcus gordonii expresses two cell wall-associated polypeptides, designated SspA (1,542 amino acid residues) and SspB (1,462 amino acid residues), that have 70% sequence identity. These polypeptides are members of the antigen I/II family of oral streptococcal adhesins and mediate the binding of streptococci to salivary glycoproteins, collagen, and other oral microorganisms such as Actinomyces naeslundii. To determine if SspA and SspB have differential binding propert...

Rapid measurement of 3J(H N-H alpha) and 3J(N-H beta) coupling constants in polypeptides.

Science.gov (United States)

Barnwal, Ravi Pratap; Rout, Ashok K; Chary, Kandala V R; Atreya, Hanudatta S

2007-12-01

We present two NMR experiments, (3,2)D HNHA and (3,2)D HNHB, for rapid and accurate measurement of 3J(H N-H alpha) and 3J(N-H beta) coupling constants in polypeptides based on the principle of G-matrix Fourier transform NMR spectroscopy and quantitative J-correlation. These experiments, which facilitate fast acquisition of three-dimensional data with high spectral/digital resolution and chemical shift dispersion, will provide renewed opportunities to utilize them for sequence specific resonance assignments, estimation/characterization of secondary structure with/without prior knowledge of resonance assignments, stereospecific assignment of prochiral groups and 3D structure determination, refinement and validation. Taken together, these experiments have a wide range of applications from structural genomics projects to studying structure and folding in polypeptides.

Associated strangeness production in pp collisions near threshold

International Nuclear Information System (INIS)

Winter, P.

2004-01-01

Motivated by the ongoing discussion concerning the nature of the scalar resonances f0(980) and a0(980), the COSY-11 collaboration has taken exclusive data on the pp → ppK+K- reaction near the production threshold. A first total cross section σ = (1.80 ± 0.27 -0.35 +0.28 ) nb for the excess energy Q = 17 MeV has been determined. In contrary to the η, ω, and η' single meson production studies which clearly show the strong pp final state interaction (FSI), the cross section values obtained at COSY-11 and DISTO can be both described by a fit with a four-body phase space including the proton-proton final state interaction as well as with one-meson exchange calculations neglecting FSI effects. Therefore, one might think about a compensation of the strong pp interaction through a pK-FSI effect or an additional degree of freedom caused by the four-body final state. In the latter case, strong FSI effects can be expected at Q-values very close to the K+K- production threshold. Such a motivation triggered - in combination with the investigation of the KK-bar interaction being relevant to the structure of the f0 (980) - further measurements at the excess energies Q = 10 and Q 28 MeV at COSY-11

New horizons for (p)ppGpp in bacterial and plant physiology.

Science.gov (United States)

Braeken, Kristien; Moris, Martine; Daniels, Ruth; Vanderleyden, Jos; Michiels, Jan

2006-01-01

A hyperphosphorylated guanosine nucleotide, (p)ppGpp, was initially identified as the effector molecule responsible for the stringent response in Escherichia coli. However, a rapidly growing number of reports proves that (p)ppGpp-mediated regulation is conserved in many bacteria and even in plants. It is now clear that (p)ppGpp acts as a global regulator during physiological adaptation of the organism to a plethora of environmental conditions. Adaptation is not only essential for surviving periods of stress and nutrient exhaustion but also for the interaction of bacteria with their eukaryotic host, as observed during pathogenesis and symbiosis, and for bacterial multicellular behaviour. Recently, there have been several new discoveries about the effects of (p)ppGpp levels, balanced by RelA-SpoT homologue proteins, in diverse organisms.

High Reproducibility of ELISPOT Counts from Nine Different Laboratories

Directory of Open Access Journals (Sweden)

Srividya Sundararaman

2015-01-01

Full Text Available The primary goal of immune monitoring with ELISPOT is to measure the number of T cells, specific for any antigen, accurately and reproducibly between different laboratories. In ELISPOT assays, antigen-specific T cells secrete cytokines, forming spots of different sizes on a membrane with variable background intensities. Due to the subjective nature of judging maximal and minimal spot sizes, different investigators come up with different numbers. This study aims to determine whether statistics-based, automated size-gating can harmonize the number of spot counts calculated between different laboratories. We plated PBMC at four different concentrations, 24 replicates each, in an IFN-γ ELISPOT assay with HCMV pp65 antigen. The ELISPOT plate, and an image file of the plate was counted in nine different laboratories using ImmunoSpot® Analyzers by (A Basic Count™ relying on subjective counting parameters set by the respective investigators and (B SmartCount™, an automated counting protocol by the ImmunoSpot® Software that uses statistics-based spot size auto-gating with spot intensity auto-thresholding. The average coefficient of variation (CV for the mean values between independent laboratories was 26.7% when counting with Basic Count™, and 6.7% when counting with SmartCount™. Our data indicates that SmartCount™ allows harmonization of counting ELISPOT results between different laboratories and investigators.

Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

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Wynn, Katherine K.; Fulton, Zara; Cooper, Leanne; Silins, Sharon L.; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Miles, John J.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

2008-04-29

CD8{sup +} T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8{sup +} T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more 'featureless' landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

Comparative magnitude and kinetics of human cytomegalovirus-specific CD4⁺ and CD8⁺ T-cell responses in pregnant women with primary versus remote infection and in transmitting versus non-transmitting mothers: Its utility for dating primary infection in pregnancy.

Science.gov (United States)

Fornara, Chiara; Furione, Milena; Arossa, Alessia; Gerna, Giuseppe; Lilleri, Daniele

2016-07-01

To discriminate between primary (PI) and remote (RI) human cytomegalovirus (HCMV) infection, several immunological parameters were monitored for a 2-year period in 53 pregnant women with PI, and 33 pregnant women experiencing HCMV PI at least 5 years prior. Cytokine (IFN-γ and IL-2) production by and phenotype (effector/memory CD45RA(+)) of HCMV-specific CD4(+) and CD8(+) T-cells as well as the lymphoproliferative responses (LPR) were evaluated, with special reference to the comparison between a group of women transmitting (T) and a group of non-transmitting (NT) the infection to fetus. While HCMV-specific CD4(+) T-cells reached at 90 days post-infection (p.i.) values comparable to RI, CD8(+) T-cells reached at 60 days p.i. levels significantly higher and persisting throughout the entire follow-up. Instead, IL-2 production and lymphoproliferative responses were lower in PI than RI for the entire follow-up period. Effector memory CD45RA(+) CD4(+) and CD8(+) HCMV-specific T-cells increased until 90 days p.i., reaching and maintaining levels higher than RI. The comparison between T and NT women showed that, at 30 days p.i., in NT women there was a significantly higher IL-2 production by HCMV-specific CD4(+) T-cells, and at 60 days p.i. a significantly higher frequency of both specific CD4(+) and CD8(+) CD45RA(+) T-cells. HCMV T-cell response appears to correlate with virus transmission to fetus and some parameters (CD4(+) lymphoproliferation, and frequency of HCMV-specific CD8(+) IL2(+) T-cells) may help in dating PI during pregnancy. © 2015 Wiley Periodicals, Inc.

HPLC of the Polypeptides in a Hydrolyzate of Egg-White Lysozyme. An Experiment for the Undergraduate Biochemistry Laboratory.

Science.gov (United States)

Richardson, W. S., III; Burns, L.

1988-01-01

Describes a simple high-performance liquid chromatography experiment for undergraduate biochemistry laboratories. The experiment illustrates the separation of polypeptides by a step gradient elution using a single pump instrument with no gradient attachments. Discusses instrumentation, analysis, a sample preparation, and results. (CW)

Human cytomegalovirus antigens in malignant gliomas as targets for adoptive cellular therapy

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Daniel eLandi

2014-11-01

Full Text Available Malignant gliomas are the most common primary brain tumor in adults, with over 12,000 new cases diagnosed in the United States each year. Over the last decade, investigators have reliably identified human cytomegalovirus (HCMV proteins, nucleic acids, and virions in most high-grade gliomas, including glioblastoma (GBM. This discovery is significant because human cytomegalovirus gene products can be targeted by immune-based therapies.In this review, we describe the current level of understanding regarding the presence and role in pathogenesis of HCMV in GBM. We describe our success detecting and expanding HCMV-specific cytotoxic T lymphocytes to kill GBM cells and explain how these cells can be used as a platform for enhanced cellular therapies. We discuss alternative approaches that capitalize on HCMV infection to treat patients with HCMV-positive tumors. Adoptive cellular therapy for HCMV-positive GBM has been tried in a small number of patients with some benefit, but we reason why, to date, these approaches generally fail to generate long-term remission or cure. We conjecture how cellular therapy for GBM can be improved and describe the barriers that must be overcome to cure these patients.

A radioimmunoassay of gastric inhibitory polypeptide in human plasma

International Nuclear Information System (INIS)

Sarson, D.L.; Bryant, M.G.; Bloom, S.R.

1980-01-01

A sensitive radioimmunoassay for the measurement of human gastric inhibitory polypeptide (GIP), using pure porcine GIP, has been developed. Cross-reactivity of the antiserum with all available mammalian gut peptide preparations was negligible with the exception of glucagon when it was approximately 1%. Two major molecular forms of GIP were detectable in plasma and tissue extracts, one of large molecular size and the other corresponding to the elution coefficient of pure porcine standard. Concentrations of GIP in plasma from 50 normal subjects after overnight fasting were 9+-1.0(S.E.M.) pmol/1 rising to a peak of 34+-2.8 pmol/1 following the ingestion of a small mixed test meal. Ingestion of glucose or fat resulted in a similar rise of plasma GIP, whereas no change was observed after the ingestion of protein. (author)

EPR Study of the Activation of Antioxidants in PP Irradiated with Gamma Rays

International Nuclear Information System (INIS)

Silva, P.

2006-01-01

The behavior of different formulations of Polypropylene (PP) with stabilizers such as buthyl-hydroxy-toluene (BHT), Chimasorb 944 (Hals) (CHIM), both from Ciba, and a copolymer of styrene-butadiene-styrene (SBS) were studied using electron paramagnetic resonance (EPR). In all the cases but the sample of PP-Hals, a characteristic specta for PP irradiated in air in the recently-irradiated condition was obtained. The lineshape of the signal was changed to that of a pure PP EPR signal as time elapsed and the alkyl radical concentration decreased up to its total disappearance. At that stage, the polyenil radical signal could be visualized better. The total free radical concentration decayed until approximately 800 hours in the PP-Hals and until around 2000 hours in all other cases. At those points, the total free radical concentrations began to increase in all the cases, except in the PP-BHT case. The lineshape was transformed into the lineshape of the Chimasorb radical in all the cases, except for the PP-BHT. In this last case, the EPR signal was not detectable. The BHT and the SBS diluted the free radical concentrations, being them smaller when they are present. The observed behavior in all the samples is consistent with the activation of the Chimasorb radical by gamma radiation

Placental Protein 13 (PP13 – a placental immunoregulatory galectin protecting pregnancy

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Nandor Gabor Than

2014-08-01

Full Text Available Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13. It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing